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Papakonstantinou M, Fantakis A, Torzilli G, Donadon M, Chatzikomnitsa P, Giakoustidis D, Papadopoulos VN, Giakoustidis A. A Systematic Review of Disappearing Colorectal Liver Metastases: Resection or No Resection? J Clin Med 2025; 14:1147. [PMID: 40004679 PMCID: PMC11856073 DOI: 10.3390/jcm14041147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2025] [Revised: 01/29/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
Background: Colorectal cancer is the second most common type of cancer and a leading cause of cancer-related deaths worldwide. Approximately 15% of the patients with colorectal cancer will already have liver metastases (CRLMs) at diagnosis. Luckily, the advances in chemotherapy regimens during the past few decades have led to increased rates of disease regression that could even render an originally unresectable disease resectable. In certain patients with CRLMs, the hepatic lesions are missing on preoperative imaging after neoadjuvant chemotherapy. These patients can undergo surgery with or without resection of the sites of the disappearing liver metastases (DLMs). In this systematic review, we assess the recurrence rate of the DLMs that were left unresected as well as the complete pathologic response of those resected. Methods: A literature search was conducted in PubMed for studies including patients with CRLMs who received neoadjuvant chemotherapy and had DLMs in preoperative imaging. Two independent reviewers completed the search according to the PRISMA checklist. Results: Three hundred and twenty-six patients with 1134 DLMs were included in our review. A total of 47 out of 480 DLMs (72.29%) that were removed had viable tumor cells in postoperative histology. One hundred and forty-five tumors could not be identified intraoperatively and were removed based on previous imaging, with thirty (20.69%) of them presenting viable cancer cells. Four hundred and sixty-five lesions could not be identified and were left in place. Of them, 152 (32.69%) developed local recurrence within 5 years. Of note, 34 DLMs could not be categorized as viable or non-viable tumors. Finally, DLMs that were identifiable intraoperatively had a higher possibility of viable tumors compared to non-identifiable ones (72.29% vs. 20.69%, respectively). Conclusions: Disappearing liver metastases that are left unresected have an increased possibility of recurrence. Patients receiving neoadjuvant treatment for CRLMs may have better survival chances after resecting all the DLM sites, either identifiable intraoperatively or not.
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Affiliation(s)
- Menelaos Papakonstantinou
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Antonios Fantakis
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Guido Torzilli
- Department of Surgery, Division of Hepatobiliary Surgery & General Surgery, Humanitas Research Hospital, 20089 Rozzano, Italy;
| | - Matteo Donadon
- Surgical Oncology Program, University Maggiore Hospital, University of Piemonte Orientale, 28100 Novara, Italy;
| | - Paraskevi Chatzikomnitsa
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Dimitrios Giakoustidis
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Vasileios N. Papadopoulos
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Alexandros Giakoustidis
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
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Baron T, Laroche S, Wagner M, Lim C, Renaud F, Charlotte F, Scatton O, Goumard C. On-site recurrence risk after parenchymal R1 liver resection for colorectal metastases. Surgery 2025; 181:109137. [PMID: 39879880 DOI: 10.1016/j.surg.2024.109137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 12/18/2024] [Accepted: 12/30/2024] [Indexed: 01/31/2025]
Abstract
BACKGROUND Histologic microscopic positive resection margin is a debated prognostic factor in patients resected for colorectal liver metastases. This study aimed to assess whether patients with R1 resection experience recurrence at the site of the resection (on-site recurrence) and to identify predictive factors for recurrence profiles in patients with R1 margins after resection of colorectal liver metastases. METHODS All surgical colorectal liver metastasis resection cases with R1 parenchymal margin from September 2014 to March 2020 in our center were retrospectively included. Imaging was reviewed for each metastasis. All the analyses were performed per metastasis. Recurrence location was examined for each metastasis according to the site of the R1 margin and defined as on-site when recurrence was at the same place of the resected lesion. Prognostic factors for recurrence type were assessed using logistic regression. RESULTS Of 700 patients who underwent liver resection for colorectal liver metastases, 105 (15%) had at least 1 metastasis with R1 resection margin, representing 6.8% per metastasis. The median follow-up was 34 months. Overall recurrence occurred in 130 metastases (83.3%) with intrahepatic recurrence in 106 metastases (80.9%). On-site recurrence was observed for 49 metastases (31.4%) and isolated (without an additional recurrence site) for 20 metastases (12.8%). The on-site recurrence did not impact overall survival. Three predictive factors for on-site recurrence were found in the multivariate logistic regression: synchronous metastases, nonanatomic resection, and pathologic response tumor regression grade 4-5. CONCLUSION Intrahepatic localization of recurrence is more frequent than on-site recurrence after R1 parenchymal resection. Synchronous metastases, nonanatomic resection, and tumor regression grade 4-5 may impact the risk of on-site recurrence.
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Affiliation(s)
- Thomas Baron
- Hepatobiliary Surgery and Liver Transplantation Department, Sorbonne University, Pitié Salpêtrière Hospital, Paris, France
| | - Sophie Laroche
- Hepatobiliary Surgery and Liver Transplantation Department, Sorbonne University, Pitié Salpêtrière Hospital, Paris, France
| | - Mathilde Wagner
- Radiology Department, Sorbonne University, Pitié Salpêtrière Hospital, Paris, France
| | - Chetana Lim
- Hepatobiliary Surgery and Liver Transplantation Department, Sorbonne University, Pitié Salpêtrière Hospital, Paris, France
| | - Florence Renaud
- Pathology Department, Sorbonne University, Pitié Salpêtrière Hospital, Paris, France
| | - Frederic Charlotte
- Pathology Department, Sorbonne University, Pitié Salpêtrière Hospital, Paris, France
| | - Olivier Scatton
- Hepatobiliary Surgery and Liver Transplantation Department, Sorbonne University, Pitié Salpêtrière Hospital, Paris, France.
| | - Claire Goumard
- Hepatobiliary Surgery and Liver Transplantation Department, Sorbonne University, Pitié Salpêtrière Hospital, Paris, France
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Miyamoto Y, Nakaura T, Ohuchi M, Ogawa K, Kato R, Maeda Y, Eto K, Iwatsuki M, Baba Y, Hirai T, Baba H. Radiomics-based Machine Learning Approach to Predict Chemotherapy Responses in Colorectal Liver Metastases. J Anus Rectum Colon 2025; 9:117-126. [PMID: 39882217 PMCID: PMC11772800 DOI: 10.23922/jarc.2024-077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 10/15/2024] [Indexed: 01/31/2025] Open
Abstract
Objectives This study explored the clinical utility of CT radiomics-driven machine learning as a predictive marker for chemotherapy response in colorectal liver metastasis (CRLM) patients. Methods We included 150 CRLM patients who underwent first-line doublet chemotherapy, dividing them into a training cohort (n=112) and a test cohort (n=38). We manually delineated three-dimensional tumor volumes, selecting the largest liver metastasis for measurement, using pretreatment portal-phase CT images and extracted 107 radiomics features. Treatment response was classified as responder (complete or partial response) or non-responder (stable or progressive disease), based on the best overall response according to RECIST criteria, version 1.1. Employing Random Forest and Boruta algorithms, we identified significant features for responder-non-responder differentiation. Radiomics signatures were developed and validated in the training cohort using five-fold cross-validation, and performance was assessed using the area under the curve (AUC). Results Among the patients, 91 (61%) were responders and 59 (39%) were non-responders. Variable selection with Boruta revealed three key parameters ("DependenceVariance," "ClusterShade," and "RunVariance"). In the training cohort, individual CT texture parameter AUCs ranged from 0.4 to 0.65, while the machine learning analysis incorporating all valid parameters exhibited a significantly higher AUC of 0.94 (p<0.01). The validation cohort also demonstrated strong predictive accuracy, with an AUC of 0.87 for treatment response. Conclusions This study highlights the potential of CT radiomics-driven machine learning in predicting chemotherapy responses among CRLM patients.
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Affiliation(s)
- Yuji Miyamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Takeshi Nakaura
- Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Mayuko Ohuchi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Katsuhiro Ogawa
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Rikako Kato
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yuto Maeda
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Kojiro Eto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Masaaki Iwatsuki
- Division of Translational Research and Advanced Treatment Against Gastrointestinal Cancer, Kumamoto University, Kumamoto, Japan
| | - Yoshifumi Baba
- Department of Next-Generation Surgical Therapy Development, Kumamoto University, Kumamoto, Japan
| | - Toshinori Hirai
- Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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Zeng ZX, Wu JY, Wu JY, Zhang ZB, Wang K, Zhuang SW, Li B, Zhou JY, Lin ZT, Li SQ, Li YN, Fu YK, Yan ML. Prognostic Value of Pathological Response for Patients with Unresectable Hepatocellular Carcinoma Undergoing Conversion Surgery. Liver Cancer 2024; 13:498-508. [PMID: 39435272 PMCID: PMC11493390 DOI: 10.1159/000536376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 01/17/2024] [Indexed: 10/23/2024] Open
Abstract
Introduction Transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor (triple therapy) has displayed encouraging clinical outcomes for unresectable hepatocellular carcinoma (uHCC). We aimed to explore the prognostic value of pathological response (PR) in patients with initially uHCC who underwent conversion surgery following triple therapy and identify predictors of major pathological response (MPR). Methods A total of 76 patients with initially uHCC who underwent conversion surgery following triple therapy were retrospectively analyzed. PR was calculated as the proportion of nonviable tumor cell surface area of the whole tumor bed surface area. MPR was identified when PR was ≥90%. Pathological complete response (pCR) was defined as the absence of viable tumor cells. Results MPR and pCR were identified in 53 (69.7%) and 25 (32.9%) patients, respectively. The 1- and 2-year overall survival in patients with MPR were significantly higher than in those without MPR (100.0% and 91.3% vs. 67.7% and 19.4%; p < 0.001). The corresponding recurrence-free survival was also improved in patients with MPR compared to those without (75.9% and 50.8% vs. 22.3% and 11.2%; p < 0.001). Similar results were observed among patients with pCR and those without. Patients who achieved MPR without pCR exhibited survival rates comparable to those of patients who achieved pCR. Baseline neutrophil-to-lymphocyte ratio ≥2.6 (p = 0.016) and preoperative alpha-fetoprotein level ≥400 ng/mL (p = 0.015) were independent predictors of MPR. Conclusion The presence of MPR or pCR could improve prognosis in patients with initially uHCC who underwent conversion surgery following triple therapy. The PR may become a surrogate marker for predicting the prognosis of these patients.
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Affiliation(s)
- Zhen-Xin Zeng
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Jia-Yi Wu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Jun-Yi Wu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Zhi-Bo Zhang
- Department of Hepatopancreatobiliary Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Kai Wang
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Shao-Wu Zhuang
- Department of Interventional Radiology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Bin Li
- Department of Hepato-Biliary-Pancreatic and Vascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Jian-Yin Zhou
- Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China
| | - Zhong-Tai Lin
- Department of General Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Shu-Qun Li
- Department of Hepatobiliary Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Yi-Nan Li
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Yang-Kai Fu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Mao-Lin Yan
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
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Shimamaki Y, Hosokawa I, Takayashiki T, Takano S, Sonoda I, Ohtsuka M. Pathological complete response following neoadjuvant chemotherapy for locally advanced intrahepatic cholangiocarcinoma. Surg Case Rep 2024; 10:35. [PMID: 38332333 PMCID: PMC10853132 DOI: 10.1186/s40792-024-01832-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 01/28/2024] [Indexed: 02/10/2024] Open
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer. Cases when found are often advanced with vascular invasion, and radical resection is often difficult. Despite curative resection, the postoperative recurrence rate of patients with histological lymph node metastasis is high, and their prognosis is poor. Therefore, there is an urgent need to establish multidisciplinary treatment that combines chemotherapy and surgical resection. The efficacy of neoadjuvant chemotherapy (NAC) for locally advanced ICC is unclear. In this report, a case of locally advanced ICC in which pathological complete response (pCR) was achieved after NAC is described. CASE PRESENTATION A 79-year-old woman was admitted to a local hospital with appetite loss. Computed tomography showed a 100 × 90 mm low-contrast tumor in the left hepatic lobe and segment 1 with invasion to the inferior vena cava (IVC), and several lymph nodes along the left gastric artery and lesser curvature were enlarged. Therefore, she was treated with a combined chemotherapy regimen of gemcitabine and cisplatin. After four courses, the tumor size decreased to 30 × 60 mm without invasion to the IVC. Left hepatectomy extending to segment 1 with bile duct resection combined with middle hepatic vein resection (H1234-B-MHV), dissection of regional lymph nodes and pyloroplasty were performed. After radical resection, pCR was achieved. She is alive with no evidence of disease, 2 years after surgery. CONCLUSIONS In this case, a patient with locally advanced ICC achieved pCR to NAC. NAC may be effective for ICC. Patients who achieve pCR may have a better prognosis.
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Affiliation(s)
- Yoshitaka Shimamaki
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-0856, Japan
| | - Isamu Hosokawa
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-0856, Japan
| | - Tsukasa Takayashiki
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-0856, Japan
| | - Shigetsugu Takano
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-0856, Japan
| | - Itaru Sonoda
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-0856, Japan
| | - Masayuki Ohtsuka
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-0856, Japan.
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Dijkstra M, Kuiper BI, Schulz HH, van der Lei S, Puijk RS, Vos DJW, Timmer FEF, Scheffer HJ, Buffart TE, van den Tol MP, Lissenberg-Witte BI, Swijnenburg RJ, Versteeg KS, Meijerink MR. Recurrent Colorectal Liver Metastases: Upfront Local Treatment versus Neoadjuvant Systemic Therapy Followed by Local Treatment (COLLISION RELAPSE): Study Protocol of a Phase III Prospective Randomized Controlled Trial. Cardiovasc Intervent Radiol 2024; 47:253-262. [PMID: 37943351 PMCID: PMC10844349 DOI: 10.1007/s00270-023-03602-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Accepted: 10/17/2023] [Indexed: 11/10/2023]
Abstract
PURPOSE The objective of the COLLISION RELAPSE trial is to prove or disprove superiority of neoadjuvant systemic therapy followed by repeat local treatment (either thermal ablation and/or surgical resection), compared to repeat local treatment alone, in patients with at least one recurrent locally treatable CRLM within one year and no extrahepatic disease. METHODS A total of 360 patients will be included in this phase III, multicentre randomized controlled trial. The primary endpoint is overall survival. Secondary endpoints are distant progression-free survival, local tumour progression-free survival analysed per patient and per tumour, systemic therapy-related toxicity, procedural morbidity and mortality, length of hospital stay, pain assessment and quality of life, cost-effectiveness ratio and quality-adjusted life years. DISCUSSION If the addition of neoadjuvant systemic therapy to repeat local treatment of CRLM proves to be superior compared to repeat local treatment alone, this may lead to a prolonged life expectancy and increased disease-free survival at the cost of possible systemic therapy-related side effects. LEVEL OF EVIDENCE Level 1, phase III randomized controlled trial. TRIAL REGISTRATION NCT05861505. May 17, 2023.
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Affiliation(s)
- Madelon Dijkstra
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location VUmc, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
| | - Babette I Kuiper
- Department of Surgery, Amsterdam UMC, Location VUmc, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Hannah H Schulz
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location VUmc, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Susan van der Lei
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location VUmc, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Robbert S Puijk
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location VUmc, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Danielle J W Vos
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location VUmc, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Florentine E F Timmer
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location VUmc, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Hester J Scheffer
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location VUmc, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
- Department of Radiology and Nuclear Medicine, Noordwest Ziekenhuisgroep, Alkmaar, the Netherlands
| | - Tineke E Buffart
- Department of Medical Oncology, Amsterdam UMC, Location VUmc, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | | | - Birgit I Lissenberg-Witte
- Department of Epidemiology and Data Science, Amsterdam University Medical Centers, Location VUmc, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Rutger-Jan Swijnenburg
- Department of Surgery, Amsterdam UMC, Location VUmc, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Kathelijn S Versteeg
- Department of Medical Oncology, Amsterdam UMC, Location VUmc, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Martijn R Meijerink
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location VUmc, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
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Marolleau P, Tougeron D, Allignet B, Cohen R, Sefrioui D, Gallet B, Dumont F, Guimbaud R, Alouani E, Passot G, Desolneux G, Ghiringhelli F, Marchal F, Mourthadhoi F, Coriat R, Desgrippes R, Locher C, Goujon G, Des Guetz G, Aparicio T, Paubelle E, Dupré A, de la Fouchardière C. Complete pathological response after chemotherapy or immune checkpoint inhibitors in deficient MMR metastatic colorectal cancer: Results of a retrospective multicenter study. Int J Cancer 2023; 153:1376-1385. [PMID: 37403609 DOI: 10.1002/ijc.34636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 03/31/2023] [Accepted: 05/03/2023] [Indexed: 07/06/2023]
Abstract
About 5% of the patients with metastatic colorectal cancers (mCRC) present microsatellite instability (MSI)/deficient mismatch repair system (dMMR). While metastasectomy is known to improve overall and progression-free survival in mCRC, specific results in selected patients with dMMR/MSI mCRC are lacking. Our study aimed to describe metastasectomy results, characterize histological response and evaluate pathological complete response (pCR) rate in patients with dMMR/MSI mCRC. We retrospectively reviewed data from all consecutive patients with dMMR/MSI mCRC who underwent surgical metastasectomy between January 2010 and June 2021 in 17 French centers. Primary outcome was to assess the pCR rate defined by tumor regression grade (TRG) 0. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), and explored TRG as predictive factor for RFS and OS. Among the 88 patients operated, 109 metastasectomies were performed in 81 patients after neoadjuvant treatment [chemotherapy ± targeted therapy (CTT): 69, 85.2%; immunotherapy (ICI): 12, 14.8%], and pCR was achieved in 13 (16.1%) patients. Among the latter, pCR rate were 10.2% in the patients having received CTT (N = 7) and 50.0% in the patients treated with ICI (N = 6). Radiological response did not predict TRG. With a median follow-up of 57.9 (IQR 34.2-81.6) months, median RFS was 20.2 (15.4-not reached) months, median OS was not reached. Major pathological responses (TRG0 + TRG1) were significantly associated with longer RFS (HR 0.12, 95% CI 0.03-0.55; P = .006). The pCR rate of 16.1% achieved with neoadjuvant treatment in patients with dMMR/MSI mCRC is consistent with previously reported rates in pMMR/MSS mCRC. Immunotherapy showed better pCR rate than chemotherapy ± targeted therapy. Further prospective trials are needed to validate immunotherapy as neoadjuvant treatment in resectable/potentially resectable dMMR/MSI mCRC and identify predictive factors for pCR.
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Affiliation(s)
| | - David Tougeron
- Gastroenterology and Hepatology Department, Poitiers University Hospital, University of Poitiers, Poitiers, France
| | - Benoit Allignet
- Department of Radiation Oncology, Leon Berard Center, Lyon, France
| | - Romain Cohen
- Department of Medical Oncology, Saint-Antoine Hospital, Sorbonne Université, AP-HP, and INSERM, Unité Mixte de Recherche Scientifique 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, France
| | - David Sefrioui
- Normandy Centre for Genomic and Personalized Medicine and Department of Hepatogastroenterology, Normandie Univ, UNIROUEN, Inserm U1245, IRON group, Rouen University Hospital, Rouen, France
| | - Blandine Gallet
- Department of Medical Oncology, Val d'Aurelle Center, Montpellier, France
| | - Frédéric Dumont
- Department of Surgical Oncology, Comprehensive Cancer Center, Institut de Cancérologie de l'Ouest, France
| | - Rosine Guimbaud
- Digestive Oncology Department, Rangueil Hospital, University Hospital of Toulouse, France
| | - Emily Alouani
- Digestive Oncology Department, Rangueil Hospital, University Hospital of Toulouse, France
| | - Guillaume Passot
- Department of General Surgery and Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France
| | | | | | - Frédéric Marchal
- Department of Surgical Oncology, Lorraine Cancer Center, Vandoeuvre les Nancy, France
| | - Farouk Mourthadhoi
- Department of General Surgery, Saint Etienne University Hospital, Jean Monnet University, Saint Etienne, France
| | - Romain Coriat
- Gastroenterology Department, Cochin University Hospital, Université de Paris, APHP, Paris, France
| | - Romain Desgrippes
- Gastroenterology Department, Saint Malo General Hospital, Saint Malo, France
| | - Christophe Locher
- Gastroenterology and Digestive Oncology Department, Meaux Hospital, Meaux, France
| | - Gaël Goujon
- Gastroenterology Department, Bichat Hospital, Paris, France
| | | | - Thomas Aparicio
- Gastroenterology Department, Saint Louis Hospital, Paris, France
| | - Etienne Paubelle
- Hematology Department, Amiens University Hospital, Amiens, France
| | | | - Christelle de la Fouchardière
- Medical Oncology Department, Leon Berard Center, Lyon, France
- Medical Oncology Department, Institut Paoli-Calmettes, Marseille, France
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Kuhlmann KF, Tufo A, Kok NF, Gordon-Weeks A, Poston GJ, Diaz Nieto R, Jones R, Fenwick SW, Malik HZ. Disappearing colorectal liver metastases in the era of state-of-the-art triple-modality diagnostic imaging. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:1016-1022. [PMID: 36702715 DOI: 10.1016/j.ejso.2023.01.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 12/19/2022] [Accepted: 01/11/2023] [Indexed: 01/13/2023]
Abstract
INTRODUCTION Systemic therapy can result in disappearance of colorectal liver metastases in up to 40% of patients. This might be an overestimation caused by suboptimal imaging modalities. The aim of this study was to investigate the use of imaging modalities and the incidence, management and outcome of patients with disappearing liver metastases (DLMs). METHODS This was a retrospective study of consecutive patients treated for colorectal liver metastases at a high volume hepatobiliary centre between January 2013 and January 2015 after receiving induction or neoadjuvant systemic therapy. Main outcomes were use of imaging modalities, incidence, management and longterm outcome of patients with DLMs. RESULTS Of 158 patients included, 32 (20%) had 110 DLMs. Most patients (88%) had initial diagnostic imaging with contrast enhanced-CT, primovist-MR and FDG-PET and 94% of patients with DLMs were restaged using primovist-MR. Patients with DLMs had significantly smaller metastases and the median initial size of DLMs was 10 mm (range 5-61). In the per lesion analysis, recurrence after "watch & wait" for DLMs occurred in 36%, while in 19 of 20 resected DLMs no viable tumour cells were found. Median overall (51 vs. 28 months, p < 0.05) and progression free survival (10 vs. 3 months, p = 0.003) were significantly longer for patients with DLMs. CONCLUSION Even state-of-the-art imaging and restaging cannot solve problems associated with DLMs. Regrowth of these lesions occurs in approximately a third of the lesions. Patients with DLMs have better survival.
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Affiliation(s)
- K F Kuhlmann
- Department of Surgical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, the Netherlands; Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - A Tufo
- Department of General Surgery, Ospedale del Mare, Via Enrico Russo, 80147, Naples, Italy; Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - N F Kok
- Department of Surgical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, the Netherlands
| | - A Gordon-Weeks
- Nuffield Department of Surgical Sciences, University of Oxford, Old Road, OX3 7BN, United Kingdom
| | - G J Poston
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - R Diaz Nieto
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - R Jones
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - S W Fenwick
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - H Z Malik
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom.
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9
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Weilert H, Sadeghi D, Lipp M, Oldhafer KJ, Donati M, Stang A. Potential for cure and predictors of long-term survival after radiofrequency ablation for colorectal liver metastases: A 20-years single-center experience. Eur J Surg Oncol 2022; 48:2487-2494. [PMID: 35718675 DOI: 10.1016/j.ejso.2022.06.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 05/16/2022] [Accepted: 06/07/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Additional radiofrequency ablation (RFA) of liver-limited colorectal liver metastases (CRLM) improves overall (OS) and recurrence-free survival (RFS) over systemic therapy alone. We aimed to assess the potential and predictive factors of long-term survival and cure to optimize patient selection for RFA application. METHODS Retrospective review of a prospectively maintained single-center database of consecutive patients undergoing RFA for liver-limited CRLM after systemic therapy between 2002 and 2020. Clinicopathologic characteristics and KRAS/BRAF-genotype data (tested routinely since 2010) were correlated to RFS and OS. Cure was defined as ≥10-years RFS (long-term survival as ≥5-years OS) following RFA. RESULTS For the entire cohort of 158 patients (median follow-up 13.6 years), co-occurrence of three factors, RECIST-defined response, number of ≤3 CRLM, and ≤3 cm maximum size determined a survival plateau that distinguished cured from non-cured patients (10-years RFS: 15.5% vs 0%, p < 0.0001). Among 59 patients (37.3%) being tested, 4(6.8%) were BRAF-mt, 15(25.4%) KRAS-mt, and 40(67.8%) KRAS/BRAF-wt. OS (median follow-up 8.3 years) was estimated to be higher with KRAS/BRAF-wt compared to a mutant KRAS or BRAF status (5-years OS: 22.8% vs 3.4%, p = 0.0018). CONCLUSION This study indicates about 15% chance of cure following RFA of low-volume liver-limited CRLM after downsizing by systemic therapy and a negative effect of KRAS or BRAF mutation on long-term survival after CRLM ablation. These findings may improve clinical decision-making in patients potentially candidate to RFA of CRLM and encourage further investigations on molecular factors determining an oligometastatic state of CRLM curable with focal ablative therapy.
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Affiliation(s)
- Hauke Weilert
- Department of Hematology and Oncology, Asklepios Hospital Barmbek, Hamburg, Germany; Asklepios Campus Hamburg, Semmelweis University, Budapest, Hungary
| | - Darja Sadeghi
- Asklepios Campus Hamburg, Semmelweis University, Budapest, Hungary
| | - Michael Lipp
- Asklepios Campus Hamburg, Semmelweis University, Budapest, Hungary; Department of General and Abdominal Surgery, Asklepios Hospital Barmbek, Hamburg, Germany
| | - Karl Jürgen Oldhafer
- Asklepios Campus Hamburg, Semmelweis University, Budapest, Hungary; Department of General and Abdominal Surgery, Asklepios Hospital Barmbek, Hamburg, Germany
| | - Marcello Donati
- Surgical Clinic Unit, Department of Surgery and Medical Surgical Specialties, University of Catania, Italy
| | - Axel Stang
- Department of Hematology and Oncology, Asklepios Hospital Barmbek, Hamburg, Germany; Asklepios Campus Hamburg, Semmelweis University, Budapest, Hungary.
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10
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Anselmo A, Cascone C, Siragusa L, Sensi B, Materazzo M, Riccetti C, Bacchiocchi G, Ielpo B, Rosso E, Tisone G. Disappearing Colorectal Liver Metastases: Do We Really Need a Ghostbuster? Healthcare (Basel) 2022; 10:healthcare10101898. [PMID: 36292345 PMCID: PMC9602313 DOI: 10.3390/healthcare10101898] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 09/06/2022] [Accepted: 09/22/2022] [Indexed: 11/24/2022] Open
Abstract
The development of new systemic treatment strategies has resulted in a significant increase in the response rates of colorectal liver metastases (CRLM) in the last few years. Although the radiological response is a favorable prognostic factor, complete shrinkage of CRLM, known as disappearing liver metastases (DLM), presents a therapeutic dilemma, and proper management is still debated in the literature. In fact, DLM is not necessarily equal to cure, and when resected, pathological examination reveals in more than 80% of patients a variable percentage of the tumor as residual disease or early recurrence in situ. Moreover, while a higher incidence of intrahepatic recurrence is documented in small series when surgery is avoided, its clinical significance for long-term OS is still under investigation. In light of this, a multidisciplinary approach and, in particular, radiologists’ role is needed to assist the surgeon in the management of DLM, thanks to emerging technology and strategy. Therefore, the aim of this review is to provide an overview of the DLM phenomenon and current management.
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Affiliation(s)
- Alessandro Anselmo
- Department of Surgical Science, University of Rome “Tor Vergata”, 00133 Roma, Italy
| | - Chiara Cascone
- Department of Surgery, University Campus Bio-Medico di Roma, 00128 Roma, Italy
- Correspondence: ; Tel.: +39-348-445-7000
| | - Leandro Siragusa
- Department of Surgical Science, University of Rome “Tor Vergata”, 00133 Roma, Italy
| | - Bruno Sensi
- Department of Surgical Science, University of Rome “Tor Vergata”, 00133 Roma, Italy
| | - Marco Materazzo
- Department of Surgical Science, University of Rome “Tor Vergata”, 00133 Roma, Italy
| | - Camilla Riccetti
- Department of Surgical Science, University of Rome “Tor Vergata”, 00133 Roma, Italy
| | - Giulia Bacchiocchi
- Department of Surgical Science, University of Rome “Tor Vergata”, 00133 Roma, Italy
| | - Benedetto Ielpo
- Hepatobiliary and Pancreatic Surgery Unit, Hospital del Mar. Universitat Pompeu Fabra Barcelona, 08003 Barcelona, Spain
| | - Edoardo Rosso
- Unité des Maladies de l’Appareil Digestif et Endocrine, Centre Hospitalier de Luxembourg, 1210 Luxembourg, Luxembourg
| | - Giuseppe Tisone
- Department of Surgical Science, University of Rome “Tor Vergata”, 00133 Roma, Italy
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11
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Xu Y, He J, Li W, Zhang W, Liu S, He J, Pan Z, Lu Z, Peng J, Lin J. The Pathologic Complete Response Ratio of Liver Metastases Represents a Valuable Prognostic Indicator. Pathol Oncol Res 2022; 28:1610663. [PMID: 36147656 PMCID: PMC9485473 DOI: 10.3389/pore.2022.1610663] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 08/17/2022] [Indexed: 11/13/2022]
Abstract
Background and Objectives: The aim of this study was to evaluate the role of the pathologic complete response ratio of liver metastases (PCRRLM) in predicting the prognosis and recurrence of colorectal cancer liver metastases (CRLM). Methods: A total of 305 CRLM patients who underwent preoperative chemotherapy followed by hepatectomy were included. PCRRLM was defined as the number of liver metastases exhibiting pathologic complete response (PCR) divided by the number of total resected liver metastases. The Kaplan–Meier method was used to calculate survival, and differences were examined by the log-rank test. Univariate and multivariate analyses were performed to identify the predictors of PCRRLM, recurrence-free survival (RFS) and overall survival (OS). Results: Among the 305 included patients, 44 (14.4%) achieved a PCRRLM ≥0.50 (including PCRRLM = 1), and 261 (85.6%) achieved a PCRRLM <0.50 (including PCRRLM = 0). Patients of an older age (≥55 years old) and those with higher carcinoembryonic antigen (CEA) levels (≥5 ng/ml) were less likely to achieve a PCRRLM ≥0.50. In the multivariate analysis, PCRRLM≥ 0.50 (vs. < 0.50, HR [95% CI]: 0.67 [0.46–0.99], p = 0.043) was associated with better RFS. Positive lymph node status (vs. negative, HR [95% CI]: 1.46 [1.04–2.05], p = 0.028) and TBS ≥5 (vs. < 5, HR [95% CI]: 1.44 [1.02–2.04], p = 0.038) were associated with worse RFS. Conclusion: PCRRLM was significantly associated with long-term RFS after preoperative chemotherapy and CRLM resection. Thus, it may be a valuable indicator of recurrence in CRLM patients.
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12
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Mason MC, Krasnodebski M, Hester CA, Kothari AN, Barker C, Nishioka Y, Chiang YJ, Newhook TE, Tzeng CWD, Chun YS, Vauthey JN, Tran Cao HS. Outcomes of Mixed Pathologic Response in Patients with Multiple Colorectal Liver Metastases Treated with Neoadjuvant Chemotherapy and Liver Resection. Ann Surg Oncol 2022; 29:5156-5164. [DOI: 10.1245/s10434-022-11683-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 02/08/2022] [Indexed: 11/18/2022]
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13
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Frosio F, Cervantes B, Nassar A, Faermark N, Sanou Y, Bonnet S, Lefevre M, Louvet C, Gayet B, Fuks D. Prognostic role of infracentimetric colorectal liver metastases. Langenbecks Arch Surg 2022; 407:1971-1980. [DOI: 10.1007/s00423-022-02499-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Accepted: 03/19/2022] [Indexed: 10/18/2022]
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14
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Eriksson S, Bengtsson J, Torén W, Lätt J, Andersson R, Sturesson C. Changes in apparent diffusion coefficient and pathological response in colorectal liver metastases after preoperative chemotherapy. Acta Radiol 2022; 64:51-57. [PMID: 35084232 DOI: 10.1177/02841851221074496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND The pathological response to preoperative chemotherapy of colorectal liver metastases (CRLMs) is predictive of long-term prognosis after liver resection. Accurate preoperative assessment of chemotherapy response could enable treatment optimization. PURPOSE To investigate whether changes in lesion-apparent diffusion coefficient (ADC) measured with diffusion-weighted magnetic resonance imaging (MRI) can be used to assess pathological treatment response in patients with CRLMs undergoing preoperative chemotherapy. MATERIAL AND METHODS Patients who underwent liver resection for CRLMs after preoperative chemotherapy between January 2011 and December 2019 were retrospectively included if they had undergone MRI before and after preoperative chemotherapy on the same 1.5-T MRI scanner with diffusion-weighted imaging with b-values 50, 400, and 800 s/mm2. The pathological chemotherapy response was assessed using the tumor regression grade (TRG) by AJCC/CAP. Lesions were divided into two groups: pathological responding (TRG 0-2) and non-responding (TRG 3). The change in lesion ADC after preoperative chemotherapy was compared between responding and non-responding lesions. RESULTS A total of 27 patients with 49 CRLMs were included, and 24/49 lesions showed a pathological chemotherapy response. After chemotherapy, ADC increased in both pathological responding (pretreatment ADC: 1.26 [95% confidence interval (CI)=1.06-1.37] vs. post-treatment ADC: 1.33 [95% CI=1.13-1.56] × 10-3 mm2/s; P = 0.026) and non-responding lesions (1.12 [95% CI=0.980-1.21] vs. 1.20 [95% CI=1.09-1.43] × 10-3 mm2/s; P = 0.018). There was no difference in median relative difference in ADC after chemotherapy between pathological responding and non-responding lesions (15.8 [95% CI=1.42-26.3] vs. 7.17 [95% CI=-4.31 to 31.2]%; P = 0.795). CONCLUSION Changes in CRLM ADCs did not differ between pathological responding and non-responding lesions.
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Affiliation(s)
- Sam Eriksson
- Surgery, Department of Clinical Sciences Lund, Lund University, Skane University Hospital, Lund, Sweden
- Center for Medical Imaging and Physiology, Skane University Hospital, Lund, Sweden
| | - Johan Bengtsson
- Center for Medical Imaging and Physiology, Skane University Hospital, Lund, Sweden
- Diagnostic Radiology, Department of Clinical Sciences Lund, Lund University, Skane University Hospital, Lund, Sweden
| | - William Torén
- Surgery, Department of Clinical Sciences Lund, Lund University, Skane University Hospital, Lund, Sweden
| | - Jimmy Lätt
- Center for Medical Imaging and Physiology, Skane University Hospital, Lund, Sweden
| | - Roland Andersson
- Surgery, Department of Clinical Sciences Lund, Lund University, Skane University Hospital, Lund, Sweden
| | - Christian Sturesson
- Surgery, Department of Clinical Sciences Lund, Lund University, Skane University Hospital, Lund, Sweden
- Division of Surgery, Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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15
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Al Jazzar RI, Algarni M, Al-Maiman S, Alzahrani N. OUP accepted manuscript. J Surg Case Rep 2022; 2022:rjac041. [PMID: 35198145 PMCID: PMC8858422 DOI: 10.1093/jscr/rjac041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 01/21/2022] [Indexed: 11/13/2022] Open
Abstract
Treatment of metastatic colorectal cancer has evolved throughout the years and various methods have been proposed to reach a pathological complete response state. We report a case of a 73-year-old male presented with a sigmoid adenocarcinoma with two synchronous liver metastases. The patient received five cycles of FOLFOX neoadjuvant chemotherapy, 41% reduction of tumor size was noted upon reassessment. Therefore, a low anterior resection of the rectum and synchronous resection of segment 5 and 8 of the liver was done along with right-sided diaphragmatic stripping. A pathological complete response was achieved in both primary and secondary tumors that are considered rare and challenging in metastatic colorectal cancer. Neoadjuvant chemotherapy showed promising findings in advanced colorectal cancer.
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Affiliation(s)
- Ragad I Al Jazzar
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- Correspondence address. College of Medicine, King Saud bin Abdulaziz University for Health Sciences, P.O.Box: 7489, Riyadh, Saudi Arabia. Tel: 00 966 583251192; E-mail:
| | - Mohammed Algarni
- King Saud bin Abdulaziz University for Health Sciences, Oncology Department, Ministry of National Guard—Health Affairs, Saudi Arabia, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
| | - Sarah Al-Maiman
- Consultant Anatomic Pathology, GI, Pancreatobillary and Liver Pathology, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Nayef Alzahrani
- Department of Surgery, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
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16
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Herman P, Fonseca GM, Coelho FF, Kruger JAP, Makdissi FF, Jeismann VB, Carrilho FJ, D'Albuquerque LAC, Nahas SC. Two decades of liver resection with a multidisciplinary approach in a single institution: What has changed? Analysis of 1409 cases. Clinics (Sao Paulo) 2022; 77:100088. [PMID: 35901605 PMCID: PMC9326330 DOI: 10.1016/j.clinsp.2022.100088] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 03/19/2022] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVES To evaluate results of patients undergoing liver resection in a single center over the past two decades with a particular look at Colorectal Liver Metastasis (CRLM) and Hepatocellular Carcinoma (HCC). METHOD Patients were divided into two eras, from 2000 to 2010 (Era 1) and 2011 to 2020 (Era 2). The most frequent diagnosis was CRLM and HCC, with 738 (52.4%) and 227 (16.1%) cases respectively. An evaluation of all liver resection cases and a subgroup analysis of both CRLM and HCC were performed. Preoperative and per operative variables and long-term outcomes were evaluated. RESULTS 1409 liver resections were performed. In Era 2 the authors observed higher BMI, more: minimally invasive surgeries, Pringle maneuvers, and minor liver resections; and less transfusion, less ICU necessity, and shorter length of hospital stay. Severe complications were observed in 14.7% of patients, and 90-day mortality was 4.2%. Morbidity and mortality between eras were not different. From 738 CRLM resections, in Era 2 there were significantly more patients submitted to neoadjuvant chemotherapy, bilateral metastases, and smaller sizes with significantly less transfusion, the necessity of ICU, and shorter length of hospital stay. More pedicle clamping, minimally invasive surgeries, and minor resections were also observed. From 227 HCC resections, in Era 2 significantly more minimally invasive surgeries, fewer transfusions, less necessity of ICU, and shorter length of hospital stay were observed. OS was not different between eras for CRLM and HCC. CONCLUSIONS Surgical resection in a multidisciplinary environment remains the cornerstone for the curative treatment of primary and metastatic liver tumors.
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Affiliation(s)
- Paulo Herman
- Serviço de Cirurgia do Fígado, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil.
| | - Gilton Marques Fonseca
- Serviço de Cirurgia do Fígado, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Fabricio Ferreira Coelho
- Serviço de Cirurgia do Fígado, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Jaime Arthur Pirola Kruger
- Serviço de Cirurgia do Fígado, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Fabio Ferrari Makdissi
- Serviço de Cirurgia do Fígado, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Vagner Birk Jeismann
- Serviço de Cirurgia do Fígado, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Flair José Carrilho
- Serviço de Cirurgia do Fígado, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Luiz Augusto Carneiro D'Albuquerque
- Serviço de Cirurgia do Fígado, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Sergio Carlos Nahas
- Serviço de Cirurgia do Fígado, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
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17
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Moslim MA, Jeyarajah DR. Narrative review of the role of yttrium-90 selective internal radiation therapy in the surgical management of colorectal liver metastases. J Gastrointest Oncol 2021; 12:2438-2446. [PMID: 34790404 DOI: 10.21037/jgo-21-96] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 06/08/2021] [Indexed: 11/06/2022] Open
Abstract
The management of colorectal liver metastasis (CRLM) is complicated and benefits from a multidisciplinary team approach. Liver-directed therapy has been emerging as a modality for better progression-free control. In its early years, selective internal radiation therapy (SIRT) with yttrium-90 (Y-90) was confined as an end-of-line therapy. However, literature has supported other roles including: a first-line treatment for CRLM alone or in combination with systemic chemotherapy; an adjunct to second or third-line chemotherapy; and a salvage treatment for chemo-refractory disease. Although future liver remnant (FLR) hypertrophy may take 3-12 months, the SIRT effect on loco-regional disease control has rendered it to be a useful tool in some pathologies with certain strategic goals. This paper reviews the use of SIRT with Y-90 in a surgical treatment pathway. This includes: (I) an element of multidisciplinary treatment of low-volume CRLMs, (II) convert an R1 to R0 resection by sterilizing the margins of tumor near critical structures, and (III) radiation lobectomy to induce contralateral hypertrophy in order to aid in a safer resection. There are many opportunities to validate the role of SIRT as a first-line therapy along with surgical resection including an umbrella clinical trial design.
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18
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Repeat Local Treatment of Recurrent Colorectal Liver Metastases, the Role of Neoadjuvant Chemotherapy: An Amsterdam Colorectal Liver Met Registry (AmCORE) Based Study. Cancers (Basel) 2021; 13:cancers13194997. [PMID: 34638481 PMCID: PMC8507904 DOI: 10.3390/cancers13194997] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 10/02/2021] [Accepted: 10/03/2021] [Indexed: 01/10/2023] Open
Abstract
This cohort study aimed to evaluate efficacy, safety, and survival outcomes of neoadjuvant chemotherapy (NAC) followed by repeat local treatment compared to upfront repeat local treatment of recurrent colorectal liver metastases (CRLM). A total of 152 patients with 267 tumors from the prospective Amsterdam Colorectal Liver Met Registry (AmCORE) met the inclusion criteria. Two cohorts of patients with recurrent CRLM were compared: patients who received chemotherapy prior to repeat local treatment (32 patients) versus upfront repeat local treatment (120 patients). Data from May 2002 to December 2020 were collected. Results on the primary endpoint overall survival (OS) and secondary endpoints local tumor progression-free survival (LTPFS) and distant progression-free survival (DPFS) were reviewed using the Kaplan-Meier method. Subsequently, uni- and multivariable Cox proportional hazard regression models, accounting for potential confounders, were estimated. Additionally, subgroup analyses, according to patient, initial and repeat local treatment characteristics, were conducted. Procedure-related complications and length of hospital stay were compared using chi-square test and Fisher's exact test. The 1-, 3-, and 5-year OS from date of diagnosis of recurrent disease was 98.6%, 72.5%, and 47.7% for both cohorts combined. The crude survival analysis did not reveal a significant difference in OS between the two cohorts (p = 0.834), with 1-, 3-, and 5-year OS of 100.0%, 73.2%, and 57.5% for the NAC group and 98.2%, 72.3%, and 45.3% for the upfront repeat local treatment group, respectively. After adjusting for two confounders, comorbidities (p = 0.010) and primary tumor location (p = 0.023), the corrected HR in multivariable analysis was 0.839 (95% CI, 0.416-1.691; p = 0.624). No differences between the two cohorts were found with regards to LTPFS (HR = 0.662; 95% CI, 0.249-1.756; p = 0.407) and DPFS (HR = 0.798; 95% CI, 0.483-1.318; p = 0.378). No heterogeneous treatment effects were detected in subgroup analyses according to patient, disease, and treatment characteristics. No significant difference was found in periprocedural complications (p = 0.843) and median length of hospital stay (p = 0.600) between the two cohorts. Chemotherapy-related toxicity was reported in 46.7% of patients. Adding NAC prior to repeat local treatment did not improve OS, LTPFS, or DPFS, nor did it affect periprocedural morbidity or length of hospital stay. The results of this comparative assessment do not substantiate the routine use of NAC prior to repeat local treatment of CRLM. Because the exact role of NAC (in different subgroups) remains inconclusive, we are currently designing a phase III randomized controlled trial (RCT), COLLISION RELAPSE trial, directly comparing upfront repeat local treatment (control) to neoadjuvant systemic therapy followed by repeat local treatment (intervention).
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19
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Missing colorectal liver metastases: the surgical challenge. Langenbecks Arch Surg 2021; 406:2163-2175. [PMID: 34590190 DOI: 10.1007/s00423-021-02297-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 08/04/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND New chemotherapy schemes have allowed for a better radiological response of unresectable colorectal liver metastases, leading to an interesting scenario known as a complete radiological response. The aim of this study was to review the current management of missing liver metastases (MLM) from the liver surgeon's point of view. METHODS A systematic search was conducted on all publications of PubMed and Embase between 2003 and 2018. Meta-analysis was performed on MLM resected/unresected. Residual tumor or regrowth and relapse-free survival were used as evaluation indices. RESULTS After literature search, 18 original articles were included for analysis. The predictive factors for MLM are type and duration of chemotherapy and size and number of lesions. Magnetic resonance is the most sensitive preoperative technique. Regarding clinical management, liver surgery is deemed the fundamental pillar in the therapeutic strategy of these patients. Meta-analysis due to data heterogeneity was inconclusive. CONCLUSIONS Depending on the clinical context, MLM monitoring appears to be a valid therapeutic alternative. Nevertheless, prospective randomized clinical studies are needed.
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Xu D, Wang YY, Yan XL, Li J, Wang K, Xing BC. Development of a model to predict pathologic response to chemotherapy in patients with colorectal liver metastases. J Gastrointest Oncol 2021; 12:1498-1508. [PMID: 34532105 DOI: 10.21037/jgo-21-82] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 06/08/2021] [Indexed: 11/09/2022] Open
Abstract
Background Preoperative chemotherapy has widely been used in colorectal cancer liver metastasis (CRLM). Pathological response to chemotherapy is very important in evaluating tumor biology. However, there is still a lack of a non-invasive and accurate method to evaluate pathological response before surgery. Methods We retrospectively analyzed the clinicopathologic data of patients with CRLM who underwent liver resection after preoperative chemotherapy between January 2006 and December 2018. Pathological responses were defined as minor when there are ≥50% remnant viable cells and as major when 0-49% remnant viable cells exist. Results A total of 482 patients were included and randomly divided into training (n=241) and validation (n=241) cohorts. The proportion of major pathologic response was similar between the two groups (51.5% and 48.5%). Multivariate analysis determined the disease-free interval (DFI), tumor size, tumor number, and RAS status as independent predictors of major pathologic response to preoperative chemotherapy. The nomogram incorporating these variables showed good concordance statistics in the training cohort (0.746, 95% CI: 0.685-0.807) and validation cohort (0.764, 95% CI: 0.704-0.823). In addition, the nomogram showed good applicability in patients with different characteristics. Conclusions The established nomogram model performed well in predicting pathological response in patients with CRLM.
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Affiliation(s)
- Da Xu
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China
| | - Yan-Yan Wang
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China
| | - Xiao-Luan Yan
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China
| | - Juan Li
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China
| | - Kun Wang
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China
| | - Bao-Cai Xing
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China
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21
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Dai Y, Zhang Y, He W, Peng C, Qiu J, Zheng N, Li H, Liu W, Zheng Y, Li B, Yuan Y, Zou R. Long-term outcome for colorectal liver metastases: combining hepatectomy with intraoperative ultrasound guided open microwave ablation versus hepatectomy alone. Int J Hyperthermia 2021; 38:372-381. [PMID: 33657952 DOI: 10.1080/02656736.2021.1892835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
Abstract
OBJECTIVE To compare the long-term outcome of combining hepatectomy with intraoperative ultrasound (IOUS)-guided open microwave ablation (MWA) versus hepatectomy alone in patients with colorectal cancer liver metastases (CRLM). METHOD A retrospective analysis of patients with CRLM who underwent hepatectomy alone (HT group; 380 patients) or hepatectomy combined with IOUS-guided open MWA (HT + MWA group; 57 patients) from April 2002 to September 2018 was conducted at our center. A propensity score-matched (PSM) analysis was used to reduce data bias between the two groups. RESULTS The overall survival (OS) and disease-free survival (DFS) were not significantly different between the two groups after matching. Although intrahepatic recurrence was more frequent in the HT + MWA group in both the whole and matched cohort, the two groups exhibited similar rates of extrahepatic recurrence as well as concomitant intra- and extrahepatic recurrence. A higher number of CRLM (>3), larger maximum-size and absence of response to induction chemotherapy were independent risk factors for OS. CONCLUSION The oncological outcomes of hepatectomy combined with intraoperative open ablation was not significantly different to hepatectomy alone and should be considered as a safe and fair option for patients with difficultly resectable CRLM.
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Affiliation(s)
- Yunzhu Dai
- Department of Ultrasound, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Yuanping Zhang
- Department of Hepatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Wei He
- Department of Hepatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Chuan Peng
- Department of Ultrasound, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Jiliang Qiu
- Department of Hepatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Nan Zheng
- Department of Ultrasound, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Huifang Li
- Department of Ultrasound, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Wenwu Liu
- Department of Hepatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Yun Zheng
- Department of Hepatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Binkui Li
- Department of Hepatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Yunfei Yuan
- Department of Hepatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Ruhai Zou
- Department of Ultrasound, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, PR China
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22
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Jácome AA, Oliveira FA, Lino F, Lima JPSN. Effect of Adding Bevacizumab to Chemotherapy on Pathologic Response to Preoperative Systemic Therapy for Resectable Colorectal Liver Metastases: A Systematic Review and Meta-analysis. Clin Colorectal Cancer 2021; 20:265-272. [PMID: 34158251 DOI: 10.1016/j.clcc.2021.05.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 05/04/2021] [Accepted: 05/17/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Liver-limited metastatic colorectal cancer is a potentially curable disease. Pathologic response (pR) to preoperative chemotherapy (CT) for colorectal liver metastases (CLM) is a surrogate endpoint for overall survival (OS). We conducted the first meta-analysis of observational studies to estimate the overall effect of bevacizumab on pR in preoperative systemic therapy for CLM. METHODS We systematically searched PubMed, Cochrane Library, CINAHL, Web of Science, Embase, and LILACS for studies published between January 2004 and August 2019 that compared the pR of CT plus bevacizumab to CT alone as preoperative therapy for CLM. The primary endpoint was pathologic complete response (pCR). Secondary endpoints were pathologic major (pMaR) and minor (pMiR) response. Overall effects were expressed by odds ratios (ORs) and 95% confidence intervals (CIs) using a random-effects model. RESULTS Of the 1,452 studies yielded by the search, 9 were eligible, totaling 1,202 patients (516 CT plus bevacizumab and 686 CT alone). The addition of bevacizumab to CT increased the pCR rate without reaching statistical significance (OR: 1.24, 95% CI 0.81 to 1.92, P = .32). However, pMaR was significantly higher (OR: 2.45, 95% CI 1.85 to 3.25, P < .001), and pMiR was significantly lower (OR: 0.41, 95% CI 0.31 to 0.54, P < .001), in the bevacizumab group. The analyses showed a low level of heterogeneity (I2 = 0% to 6%). Publication bias was not found. CONCLUSIONS This meta-analysis demonstrates that bevacizumab plus preoperative CT is associated with higher rates of pR in CLM. Antiangiogenics might improve the OS of CLM patients and should be evaluated in randomized clinical trials. MICROABSTRACT The benefit of perioperative chemotherapy for colorectal liver metastases (CLM) is uncertain, but pathologic response (pR) to preoperative chemotherapy is a strong prognostic factor. Our meta-analysis of observational studies compared the pR of bevacizumab plus chemotherapy to chemotherapy alone as preoperative systemic therapy in the management of CLM. The addition of bevacizumab was associated with significantly higher rates of pR.
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Affiliation(s)
- Alexandre A Jácome
- Department of Gastrointestinal Medical Oncology, Oncoclinicas, Belo Horizonte, Brazil.
| | | | - Flora Lino
- Department of Gastrointestinal Medical Oncology, Oncoclinicas, Rio de Janeiro, Brazil
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Histopathological and Immune Prognostic Factors in Colo-Rectal Liver Metastases. Cancers (Basel) 2021; 13:cancers13051075. [PMID: 33802446 PMCID: PMC7959473 DOI: 10.3390/cancers13051075] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 02/23/2021] [Accepted: 02/24/2021] [Indexed: 12/16/2022] Open
Abstract
Simple Summary Clinical management of colo-rectal liver metastasis would benefit from a refined stratification of patients in prognostic groups, in order to identify the best therapeutic option. Efforts are ongoing in the definition of parameters associated with clinical behaviors, which could help classifying patients in clinically relevant groups. Here we aimed at discussing the recent advances in this field, and we introduced current and new promising candidates, such as morphological tumor features and immune components, which have been showing significant association with survival. Some of these parameters are slowly reaching the clinic and further efforts are ongoing in the attempt to combine them in multiparametric scores. Abstract Prognostic studies are increasingly providing new tools to stratify colo-rectal liver metastasis patients into clinical subgroups, with remarkable implications in terms of clinical management and therapeutic choice. Here, the strengths and hurdles of current prognostic tools in colo-rectal liver metastasis are discussed. Alongside more classic histopathological parameters, which capture features related to the tumor component, such as tumor invasion, tumor growth pattern and regression score, we will discuss immune mediators, which are starting to be considered important features. Their objective quantification has shown significant results in prognostication studies, with most of the work focused on adaptive immune cells, namely T cells. As for macrophages, they are only starting to be appreciated and we will present recent advances in evaluation of macrophage morphological features. Deeper knowledge acquired by multiparametric analyses is rapidly uncovering the variety of immune players that should be assessed. The future projection is to implement deep-learning histopathological tools and to integrate histopathological and immune metrics in multiparametric scores, with the ultimate objective to achieve a deeper resolution of the tumor features and their relevance for colo-rectal liver metastasis.
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24
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Anaya DA, Dogra P, Wang Z, Haider M, Ehab J, Jeong DK, Ghayouri M, Lauwers GY, Thomas K, Kim R, Butner JD, Nizzero S, Ramírez JR, Plodinec M, Sidman RL, Cavenee WK, Pasqualini R, Arap W, Fleming JB, Cristini V. A Mathematical Model to Estimate Chemotherapy Concentration at the Tumor-Site and Predict Therapy Response in Colorectal Cancer Patients with Liver Metastases. Cancers (Basel) 2021; 13:cancers13030444. [PMID: 33503971 PMCID: PMC7866038 DOI: 10.3390/cancers13030444] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 01/21/2021] [Indexed: 12/22/2022] Open
Abstract
Simple Summary It is known that drug transport barriers in the tumor determine drug concentration at the tumor site, causing disparity from the systemic (plasma) drug concentration. However, current clinical standard of care still bases dosage and treatment optimization on the systemic concentration of drugs. Here, we present a proof of concept observational cohort study to accurately estimate drug concentration at the tumor site from mathematical modeling using biologic, clinical, and imaging/perfusion data, and correlate it with outcome in colorectal cancer liver metastases. We demonstrate that drug concentration at the tumor site, not in systemic circulation, can be used as a credible biomarker for predicting chemotherapy outcome, and thus our mathematical modeling approach can be applied prospectively in the clinic to personalize treatment design to optimize outcome. Abstract Chemotherapy remains a primary treatment for metastatic cancer, with tumor response being the benchmark outcome marker. However, therapeutic response in cancer is unpredictable due to heterogeneity in drug delivery from systemic circulation to solid tumors. In this proof-of-concept study, we evaluated chemotherapy concentration at the tumor-site and its association with therapy response by applying a mathematical model. By using pre-treatment imaging, clinical and biologic variables, and chemotherapy regimen to inform the model, we estimated tumor-site chemotherapy concentration in patients with colorectal cancer liver metastases, who received treatment prior to surgical hepatic resection with curative-intent. The differential response to therapy in resected specimens, measured with the gold-standard Tumor Regression Grade (TRG; from 1, complete response to 5, no response) was examined, relative to the model predicted systemic and tumor-site chemotherapy concentrations. We found that the average calculated plasma concentration of the cytotoxic drug was essentially equivalent across patients exhibiting different TRGs, while the estimated tumor-site chemotherapeutic concentration (eTSCC) showed a quadratic decline from TRG = 1 to TRG = 5 (p < 0.001). The eTSCC was significantly lower than the observed plasma concentration and dropped by a factor of ~5 between patients with complete response (TRG = 1) and those with no response (TRG = 5), while the plasma concentration remained stable across TRG groups. TRG variations were driven and predicted by differences in tumor perfusion and eTSCC. If confirmed in carefully planned prospective studies, these findings will form the basis of a paradigm shift in the care of patients with potentially curable colorectal cancer and liver metastases.
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Affiliation(s)
- Daniel A. Anaya
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA; (M.H.); (J.E.); (R.K.); (J.B.F.)
- Correspondence: (D.A.A.); (V.C.); Tel.: +1-813-745-1432 (D.A.A.); +1-505-934-1813 (V.C.); Fax: +1-813-745-7229 (D.A.A.)
| | - Prashant Dogra
- Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, TX 77030, USA; (P.D.); (Z.W.); (J.D.B.); (S.N.); (J.R.R.)
| | - Zhihui Wang
- Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, TX 77030, USA; (P.D.); (Z.W.); (J.D.B.); (S.N.); (J.R.R.)
| | - Mintallah Haider
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA; (M.H.); (J.E.); (R.K.); (J.B.F.)
| | - Jasmina Ehab
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA; (M.H.); (J.E.); (R.K.); (J.B.F.)
| | - Daniel K. Jeong
- Department of Diagnostic Imaging and Interventional Radiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA; (D.K.J.); (M.G.); (G.Y.L.); (K.T.)
| | - Masoumeh Ghayouri
- Department of Diagnostic Imaging and Interventional Radiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA; (D.K.J.); (M.G.); (G.Y.L.); (K.T.)
| | - Gregory Y. Lauwers
- Department of Diagnostic Imaging and Interventional Radiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA; (D.K.J.); (M.G.); (G.Y.L.); (K.T.)
| | - Kerry Thomas
- Department of Diagnostic Imaging and Interventional Radiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA; (D.K.J.); (M.G.); (G.Y.L.); (K.T.)
| | - Richard Kim
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA; (M.H.); (J.E.); (R.K.); (J.B.F.)
| | - Joseph D. Butner
- Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, TX 77030, USA; (P.D.); (Z.W.); (J.D.B.); (S.N.); (J.R.R.)
| | - Sara Nizzero
- Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, TX 77030, USA; (P.D.); (Z.W.); (J.D.B.); (S.N.); (J.R.R.)
| | - Javier Ruiz Ramírez
- Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, TX 77030, USA; (P.D.); (Z.W.); (J.D.B.); (S.N.); (J.R.R.)
| | - Marija Plodinec
- Biozentrum and the Swiss Nanoscience Institute & ARTIDIS AG, University of Basel, 4056 Basel, Switzerland;
| | - Richard L. Sidman
- Department of Neurology, Harvard Medical School, Boston, MA 02115, USA;
| | - Webster K. Cavenee
- Ludwig Institute for Cancer Research, University of California-San Diego, La Jolla, CA 92093, USA;
| | - Renata Pasqualini
- Rutgers Cancer Institute of New Jersey & Division of Cancer Biology, Department of Radiation Oncology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA;
| | - Wadih Arap
- Rutgers Cancer Institute of New Jersey & Division of Hematology/Oncology, Department of Medicine Rutgers New Jersey Medical School, Newark, NJ 07103, USA;
| | - Jason B. Fleming
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA; (M.H.); (J.E.); (R.K.); (J.B.F.)
| | - Vittorio Cristini
- Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, TX 77030, USA; (P.D.); (Z.W.); (J.D.B.); (S.N.); (J.R.R.)
- Correspondence: (D.A.A.); (V.C.); Tel.: +1-813-745-1432 (D.A.A.); +1-505-934-1813 (V.C.); Fax: +1-813-745-7229 (D.A.A.)
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Azam F, Vazquez A. Trends in Phase II Trials for Cancer Therapies. Cancers (Basel) 2021; 13:E178. [PMID: 33430223 PMCID: PMC7825663 DOI: 10.3390/cancers13020178] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 12/27/2020] [Accepted: 01/05/2021] [Indexed: 12/15/2022] Open
Abstract
Background: Drug combinations are the standard of care in cancer treatment. Identifying effective cancer drug combinations has become more challenging because of the increasing number of drugs. However, a substantial number of cancer drugs stumble at Phase III clinical trials despite exhibiting favourable efficacy in the earlier Phase. Methods: We analysed recent Phase II cancer trials comprising 2165 response rates to uncover trends in cancer therapies and used a null model of non-interacting agents to infer synergistic and antagonistic drug combinations. We compared our latest efficacy dataset with a previous dataset to assess the progress of cancer therapy. Results: Targeted therapies reach higher response rates when used in combination with cytotoxic drugs. We identify four synergistic and 10 antagonistic combinations based on the observed and expected response rates. We demonstrate that recent targeted agents have not significantly increased the response rates. Conclusions: We conclude that either we are not making progress or response rate measured by tumour shrinkage is not a reliable surrogate endpoint for the targeted agents.
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Affiliation(s)
- Faruque Azam
- Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, UK;
| | - Alexei Vazquez
- Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, UK;
- Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK
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26
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Martin J, Petrillo A, Smyth EC, Shaida N, Khwaja S, Cheow HK, Duckworth A, Heister P, Praseedom R, Jah A, Balakrishnan A, Harper S, Liau S, Kosmoliaptsis V, Huguet E. Colorectal liver metastases: Current management and future perspectives. World J Clin Oncol 2020; 11:761-808. [PMID: 33200074 PMCID: PMC7643190 DOI: 10.5306/wjco.v11.i10.761] [Citation(s) in RCA: 120] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 05/14/2020] [Accepted: 08/31/2020] [Indexed: 02/06/2023] Open
Abstract
The liver is the commonest site of metastatic disease for patients with colorectal cancer, with at least 25% developing colorectal liver metastases (CRLM) during the course of their illness. The management of CRLM has evolved into a complex field requiring input from experienced members of a multi-disciplinary team involving radiology (cross sectional, nuclear medicine and interventional), Oncology, Liver surgery, Colorectal surgery, and Histopathology. Patient management is based on assessment of sophisticated clinical, radiological and biomarker information. Despite incomplete evidence in this very heterogeneous patient group, maximising resection of CRLM using all available techniques remains a key objective and provides the best chance of long-term survival and cure. To this end, liver resection is maximised by the use of downsizing chemotherapy, optimisation of liver remnant by portal vein embolization, associating liver partition and portal vein ligation for staged hepatectomy, and combining resection with ablation, in the context of improvements in the functional assessment of the future remnant liver. Liver resection may safely be carried out laparoscopically or open, and synchronously with, or before, colorectal surgery in selected patients. For unresectable patients, treatment options including systemic chemotherapy, targeted biological agents, intra-arterial infusion or bead delivered chemotherapy, tumour ablation, stereotactic radiotherapy, and selective internal radiotherapy contribute to improve survival and may convert initially unresectable patients to operability. Currently evolving areas include biomarker characterisation of tumours, the development of novel systemic agents targeting specific oncogenic pathways, and the potential re-emergence of radical surgical options such as liver transplantation.
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Affiliation(s)
- Jack Martin
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Angelica Petrillo
- Department of Precision Medicine, Division of Medical Oncology, University of Campania "L. Vanvitelli", Napoli 80131, Italy, & Medical Oncology Unit, Ospedale del Mare, 80147 Napoli Italy
| | - Elizabeth C Smyth
- Department of Oncology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Nadeem Shaida
- Department of Radiology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB22 0QQ, United Kingdom
| | - Samir Khwaja
- Department of Radiology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB22 0QQ, United Kingdom
| | - HK Cheow
- Department of Nuclear Medicine, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Adam Duckworth
- Department of Pathology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Paula Heister
- Department of Pathology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Raaj Praseedom
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Asif Jah
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Anita Balakrishnan
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Simon Harper
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Siong Liau
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Vasilis Kosmoliaptsis
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Emmanuel Huguet
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
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27
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Xu D, Yan XL, Liu JM, Li J, Xing BC. The characteristics and long-term survival of patients with colorectal liver metastases with pathological complete response after chemotherapy. J Cancer 2020; 11:6256-6263. [PMID: 33033509 PMCID: PMC7532511 DOI: 10.7150/jca.47911] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 08/13/2020] [Indexed: 01/05/2023] Open
Abstract
Purpose: Preoperative chemotherapy is widely used for colorectal liver metastasis (CRLM). Pathological complete response (PCR) after chemotherapy indicates complete tumor regression and an extremely favorable prognosis. This study aimed to explore the characteristics and long-term survival of CRLM patients with pCR, who underwent surgery after preoperative chemotherapy. Methods: We retrospectively analyzed the clinical data of 494 CRLM patients who underwent hepatectomy after preoperative chemotherapy between January 2006 and January 2019. pCR was defined as the absence of any cancer cells on pathological examination. Results: Thirty (6.07%) patients achieved pCR after preoperative chemotherapy; 70% patients who achieved pCR did not experience recurrence and were cured after hepatectomy. The long-term prognosis of patients with pCR was extremely favorable, with 10-year overall and disease-free survivals of 85.2% and 73.7%, respectively; these were significantly better than those of patients without pCR (31.3% and 15.2%, respectively). Liver metastases <3 cm, preoperative carcinoembryonic antigen level ≤20 ng/mL, primary T stage 1-2, and right-sided primary tumors were independent predictors for pCR. Conclusion: pCR occurred in 6% of patients with CRLM after preoperative chemotherapy. Patients with a smaller tumor burden are more likely to benefit from chemotherapy and achieve pCR.
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Affiliation(s)
- Da Xu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Hepatopancreatobiliary Surgery Department I, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Xiao-Luan Yan
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Hepatopancreatobiliary Surgery Department I, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Jia-Ming Liu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Hepatopancreatobiliary Surgery Department I, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Juan Li
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Hepatopancreatobiliary Surgery Department I, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Bao-Cai Xing
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Hepatopancreatobiliary Surgery Department I, Peking University Cancer Hospital & Institute, Beijing 100142, China
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28
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Hepatic metastases resection after cetuximab: are we missing something? Lancet Oncol 2020; 21:e228. [PMID: 32359493 DOI: 10.1016/s1470-2045(20)30144-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 02/19/2020] [Indexed: 11/21/2022]
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Golan T, Barenboim A, Lahat G, Nachmany I, Goykhman Y, Shacham-Shmueli E, Halpern N, Brazowski E, Geva R, Wolf I, Goldes Y, Ben-Haim M, Klausner JM, Lubezky N. Increased Rate of Complete Pathologic Response After Neoadjuvant FOLFIRINOX for BRCA Mutation Carriers with Borderline Resectable Pancreatic Cancer. Ann Surg Oncol 2020; 27:3963-3970. [PMID: 32314163 DOI: 10.1245/s10434-020-08469-8] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND Neoadjuvant FOLFIRINOX is a standard-of-care treatment for BRPC patients. Patients with gBRCAm who have demonstrated improved response to platinum-based chemotherapy may have impaired homologous repair deficiency. This study aimed to describe the pathologic complete response rate and long-term survival for patients with germline BRCA1 or BRCA2 mutation (gBRCAm) and borderline resectable pancreatic cancer (BRPC) treated with neoadjuvant FOLFIRINOX. METHODS A dual-center retrospective analysis was performed. Patients who had BRPC treated with neoadjuvant FOLFIRINOX followed by curative resection were identified from clinical databases. Pathologic complete response was defined as no viable tumor cells present in the specimen. Common founder Jewish germline BRCA1 or BRCA2 mutation was determined for available patients. RESULTS The 61 BRPC patients in this study underwent resection after neoadjuvant FOLFIRINOX. Analysis of BRCA mutation was performed for 39 patients, and 9 patients were found to be BRCA2 germline mutation carriers. The pathologic complete response rate was 44.4% for the gBRCAm patients and 10% for the BRCA non-carriers (p = 0.009). The median disease-free survival was not reached for the gBRCAm patients and was 7 months for the BRCA non-carriers (p = 0.03). The median overall survival was not reached for the gBRCAm patients and was 32 months for the BRCA non-carriers (p = 0.2). After a mean follow-up period of 33.7 months, all eight patients with pathologic complete response were disease-free. CONCLUSIONS The study showed that gBRCAm patients with BRPC have an increased chance for pathologic complete response and prolonged survival after neoadjuvant FOLFIRINOX. The results support the benefit of exposing gBRCAm patients to platinum-based chemotherapy early in the course of the disease. Neoadjuvant FOLFIRINOX should be considered for BRCA carriers who have resectable pancreatic cancer.
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Affiliation(s)
- Talia Golan
- Institute of Oncology, Sheba Medical Center, Tel Hashomer, Israel
| | - Alex Barenboim
- Liver Surgery Unit, Department of Surgery, Tel-Aviv Medical Center, Tel Aviv, Israel
| | - Guy Lahat
- Liver Surgery Unit, Department of Surgery, Tel-Aviv Medical Center, Tel Aviv, Israel
| | - Ido Nachmany
- Liver Surgery Unit, Department of Surgery, Tel-Aviv Medical Center, Tel Aviv, Israel
| | - Yacov Goykhman
- Liver Surgery Unit, Department of Surgery, Tel-Aviv Medical Center, Tel Aviv, Israel
| | | | - Naama Halpern
- Institute of Oncology, Sheba Medical Center, Tel Hashomer, Israel
| | - Eli Brazowski
- Institute of Pathology, Tel-Aviv Medical Center, Tel Aviv, Israel
| | - Ravit Geva
- Institute of Oncology, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Ido Wolf
- Institute of Oncology, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Yuri Goldes
- Department of Surgery, Sheba Medical Center, The Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Menahem Ben-Haim
- Department of Surgery, Shaarey Zedek Medical Center, Jerusalem, Israel
| | - Joseph M Klausner
- Liver Surgery Unit, Department of Surgery, Tel-Aviv Medical Center, Tel Aviv, Israel
| | - Nir Lubezky
- Liver Surgery Unit, Department of Surgery, Tel-Aviv Medical Center, Tel Aviv, Israel.
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Miura S, Ito K, Takemura N, Mihara F, Kiyomatsu T, Kokudo N. Complete remission of multiple liver metastases with only partial response of the primary rectal cancer after neoadjuvant chemotherapy. Surg Case Rep 2020; 6:46. [PMID: 32107670 PMCID: PMC7046888 DOI: 10.1186/s40792-020-00807-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 02/17/2020] [Indexed: 11/12/2022] Open
Abstract
Background Colorectal cancer is commonly diagnosed among the Japanese population, and various strategies in treating the colorectal liver metastasis have been introduced over the years. Here, we present a case of colorectal liver metastases in which we devised a multidisciplinary treatment plan for a better prognosis. Case presentation We report a case of a 44-year-old female who developed rectal cancer with advanced synchronous liver metastases and was treated by a liver-first surgical approach following neoadjuvant chemotherapy. At diagnosis, there were 12 bilobular lesions in the liver, and the primary rectal cancer was asymptomatic and unprogressive. We adopted a liver-first strategy because the control of the liver metastases was considered the key prognostic factor. Furthermore, because the lesions were highly progressive, we planned neoadjuvant systemic chemotherapy first to provide an observational period to identify potential new metastatic lesions that were refractory to systemic chemotherapy or contraindicative for surgical resection. We administered two courses of S-1 + oxaliplatin (SOX)+ bevacizumab (BV) and an additional course of SOX without BV as neoadjuvant chemotherapy in preparation for surgery. This resulted in a prominent minimalization of colorectal liver metastases, and no other remote metastasis was observed. Then, surgical resection of the colorectal liver metastases was performed safely, and the pathological result revealed complete remission of all tumors by neoadjuvant chemotherapy. The primary tumor in the colon was successfully resected 2 months after the hepatectomy. Although the patient experienced a recurrence in two different sites in the lungs 10 months after resection of the primary rectal lesion, these metastases were successfully resected after diagnosis. The patient is alive with no signs of recurrence 3 years after the diagnosis of colorectal cancer with synchronous liver metastases. Conclusions The combination of a liver-first strategy and neoadjuvant chemotherapy is a possible treatment of choice to cure colorectal cancer with simultaneous advanced colorectal liver metastases.
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Affiliation(s)
- Satomi Miura
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
| | - Kyoji Ito
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
| | - Nobuyuki Takemura
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
| | - Fuminori Mihara
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
| | - Tomomichi Kiyomatsu
- Colorectal Surgery Division, Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
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31
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Aykan NF, Özatlı T. Objective response rate assessment in oncology: Current situation and future expectations. World J Clin Oncol 2020; 11:53-73. [PMID: 32133275 PMCID: PMC7046919 DOI: 10.5306/wjco.v11.i2.53] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Revised: 11/05/2019] [Accepted: 11/29/2019] [Indexed: 02/06/2023] Open
Abstract
The tumor objective response rate (ORR) is an important parameter to demonstrate the efficacy of a treatment in oncology. The ORR is valuable for clinical decision making in routine practice and a significant end-point for reporting the results of clinical trials. World Health Organization and Response Evaluation Criteria in Solid Tumors (RECIST) are anatomic response criteria developed mainly for cytotoxic chemotherapy. These criteria are based on the visual assessment of tumor size in morphological images provided by computed tomography (CT) or magnetic resonance imaging. Anatomic response criteria may not be optimal for biologic agents, some disease sites, and some regional therapies. Consequently, modifications of RECIST, Choi criteria and Morphologic response criteria were developed based on the concept of the evaluation of viable tumors. Despite its limitations, RECIST v1.1 is validated in prospective studies, is widely accepted by regulatory agencies and has recently shown good performance for targeted cancer agents. Finally, some alternatives of RECIST were developed as immune-specific response criteria for checkpoint inhibitors. Immune RECIST criteria are based essentially on defining true progressive disease after a confirmatory imaging. Some graphical methods may be useful to show longitudinal change in the tumor burden over time. Tumor tissue is a tridimensional heterogenous mass, and tumor shrinkage is not always symmetrical; thus, metabolic response assessments using positron emission tomography (PET) or PET/CT may reflect the viability of cancer cells or functional changes evolving after anticancer treatments. The metabolic response can show the benefit of a treatment earlier than anatomic shrinkage, possibly preventing delays in drug approval. Computer-assisted automated volumetric assessments, quantitative multimodality imaging in radiology, new tracers in nuclear medicine and finally artificial intelligence have great potential in future evaluations.
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Affiliation(s)
- Nuri Faruk Aykan
- Department of Medical Oncology, Istinye University Medical School, Bahcesehir Liv Hospital, Istanbul 34510, Turkey
| | - Tahsin Özatlı
- Department of Medical Oncology, Istinye University Medical School, Bahcesehir Liv Hospital, Istanbul 34510, Turkey
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Hashiguchi Y, Muro K, Saito Y, Ito Y, Ajioka Y, Hamaguchi T, Hasegawa K, Hotta K, Ishida H, Ishiguro M, Ishihara S, Kanemitsu Y, Kinugasa Y, Murofushi K, Nakajima TE, Oka S, Tanaka T, Taniguchi H, Tsuji A, Uehara K, Ueno H, Yamanaka T, Yamazaki K, Yoshida M, Yoshino T, Itabashi M, Sakamaki K, Sano K, Shimada Y, Tanaka S, Uetake H, Yamaguchi S, Yamaguchi N, Kobayashi H, Matsuda K, Kotake K, Sugihara K. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol 2020; 25:1-42. [PMID: 31203527 PMCID: PMC6946738 DOI: 10.1007/s10147-019-01485-z] [Citation(s) in RCA: 1209] [Impact Index Per Article: 241.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 05/29/2019] [Indexed: 02/06/2023]
Abstract
The number of deaths from colorectal cancer in Japan continues to increase. Colorectal cancer deaths exceeded 50,000 in 2016. In the 2019 edition, revision of all aspects of treatments was performed, with corrections and additions made based on knowledge acquired since the 2016 version (drug therapy) and the 2014 version (other treatments). The Japanese Society for Cancer of the Colon and Rectum guidelines 2019 for the treatment of colorectal cancer (JSCCR guidelines 2019) have been prepared to show standard treatment strategies for colorectal cancer, to eliminate disparities among institutions in terms of treatment, to eliminate unnecessary treatment and insufficient treatment and to deepen mutual understanding between healthcare professionals and patients by making these guidelines available to the general public. These guidelines have been prepared by consensuses reached by the JSCCR Guideline Committee, based on a careful review of the evidence retrieved by literature searches and in view of the medical health insurance system and actual clinical practice settings in Japan. Therefore, these guidelines can be used as a tool for treating colorectal cancer in actual clinical practice settings. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. Controversial issues were selected as clinical questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here, we present the English version of the JSCCR guidelines 2019.
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Affiliation(s)
- Yojiro Hashiguchi
- Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8606, Japan.
| | - Kei Muro
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yutaka Saito
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Yoshinori Ito
- Department of Radiation Oncology, Showa University School of Medicine, Tokyo, Japan
| | - Yoichi Ajioka
- Division of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Tetsuya Hamaguchi
- Department of Gastroenterological Oncology, Saitama Medical University International Medical Center, Saitama, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kinichi Hotta
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Hideyuki Ishida
- Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan
| | - Megumi Ishiguro
- Department of Chemotherapy and Oncosurgery, Tokyo Medical and Dental University Medical Hospital, Tokyo, Japan
| | - Soichiro Ishihara
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yukihide Kanemitsu
- Department of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Yusuke Kinugasa
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Keiko Murofushi
- Department of Radiation Oncology, faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Takako Eguchi Nakajima
- Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Shiro Oka
- Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan
| | - Toshiaki Tanaka
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroya Taniguchi
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan
| | - Akihito Tsuji
- Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Keisuke Uehara
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Hideki Ueno
- Department of Surgery, National Defense Medical College, Saitama, Japan
| | - Takeharu Yamanaka
- Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Japan
| | - Kentaro Yamazaki
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Masahiro Yoshida
- Department of Hepato-Biliary-Pancreatic and Gastrointestinal Surgery, School of Medicine, International University of Health and Welfare, Narita, Japan
| | - Takayuki Yoshino
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan
| | - Michio Itabashi
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Kentaro Sakamaki
- Center for Data Science, Yokohama City University, Yokohama, Japan
| | - Keiji Sano
- Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8606, Japan
| | - Yasuhiro Shimada
- Division of Clinical Oncology, Kochi Health Sciences Center, Kochi, Japan
| | - Shinji Tanaka
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Hiroyuki Uetake
- Department of Specialized Surgeries, Tokyo Medical and Dental University, Tokyo, Japan
| | - Shigeki Yamaguchi
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Hidaka, Japan
| | | | - Hirotoshi Kobayashi
- Department of Surgery, Mizonokuchi Hospital, Teikyo University School of Medicine, Kanagawa, Japan
| | - Keiji Matsuda
- Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8606, Japan
| | - Kenjiro Kotake
- Department of Surgery, Sano City Hospital, Tochigi, Japan
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Araujo RLC, Milani JM, Armentano DP, Moreira RB, Pinto GSF, de Castro LA, Lucchesi FR. Disappearing colorectal liver metastases: Strategies for the management of patients achieving a radiographic complete response after systemic chemotherapy. J Surg Oncol 2019; 121:848-856. [PMID: 31773747 DOI: 10.1002/jso.25784] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Accepted: 11/14/2019] [Indexed: 12/12/2022]
Abstract
The mainstays of treatment for colorectal liver metastases (CRLMs) are surgery and chemotherapy. Chemotherapeutic benefits of tumor shrinkage and systemic control of micrometastases are in part counterbalanced by chemotoxicity that can modify the liver parenchyma, jeopardizing the detection of CRLM. This review addresses the clinical decision-making process in the context of radiographic and pathologic responses, the preoperative imaging workup, and the approaches to the liver for CRLM, which disappear after systemic chemotherapy.
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Affiliation(s)
- Raphael L C Araujo
- Department of Digestive Surgery, Escola Paulista de Medicina - UNIFESP, São Paulo, Brazil.,Department of Oncology, Americas Medical Service/Brazil, United Health Group, São Paulo, Brazil.,Hospital Israelita Albert Einstein, São Paulo, Brazil.,Post-Graduation Program, Barretos Cancer Hospital, Barretos, Brazil
| | - Jean Michel Milani
- Department of Digestive Surgery, Escola Paulista de Medicina - UNIFESP, São Paulo, Brazil
| | | | - Raphael Brandão Moreira
- Department of Oncology, Americas Medical Service/Brazil, United Health Group, São Paulo, Brazil
| | - Gustavo S F Pinto
- Department of Clinical Oncology, Barretos Cancer Hospital, Barretos, Brazil
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Cai Y, Lu X, Zhu X, Ju H, Sun W, Wu W. Histological tumor response assessment in colorectal liver metastases after neoadjuvant chemotherapy: impact of the variation in tumor regression grading and peritumoral lymphocytic infiltration. J Cancer 2019; 10:5852-5861. [PMID: 31737121 PMCID: PMC6843876 DOI: 10.7150/jca.31493] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Accepted: 08/14/2019] [Indexed: 12/29/2022] Open
Abstract
Background: The objective of this study was to evaluate the prognostic value of the variation in tumor regression grade (TRG) and peritumoral lymphocytic infiltration of colorectal liver metastases (CRLMs) after neoadjuvant chemotherapy (NACT). Methods: A retrospective review was performed in 98 patients with CRLMs who underwent NACT between 2010 and 2016. The TRG scores and counts of TILs at the tumor-normal interface were assessed in all 176 resected liver metastases to determine their association with prognosis. According to the variation in TRG scores, 40 patients with more than one liver metastasis were divided into a decreased TRG group and a stable TRG group. An additional independent cohort of 64 patients with 106 resected liver specimens was established to validate our main findings. Results: In the derivation cohort of 98 patients, 41.8% patients had a favourable pathological response to NACT (TRG 1-3), which were significantly associated with improved prognosis. Seventeen patients (42.5%) showed decreased TRG scores, and the remaining patients had stable scores. The multivariate analysis indicated that patients with decreased TRG scores had a better recurrence-free survival (RFS) compared with those with stable TRG scores (HR=0.42, P=0.034), and a similar trend was observed in the validation cohort (P=0.068). Dense TILs surrounding the metastases were present in 55.1% of the derivation cohort and associated with pathological response (P=0.008). Among patients with a pathological response to NACT, those with dense TILs had a superior RFS compared to those with weak TILs in both cohorts (derivation: HR=0.36, P=0.035; validation: HR=0.34, P=0.016). Conclusions: Variation in TRG scores and peritumoral lymphocytic infiltration may be proposed as secondary pathological parameters to evaluate the pathological response to NACT and predict the risk of recurrence after liver surgery.
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Affiliation(s)
- Yibo Cai
- Department of Colorectal Surgery, Institute of Cancer and Basic Medicine (ICBM) of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China
| | - Xingang Lu
- Department of Colorectal Surgery, Institute of Cancer and Basic Medicine (ICBM) of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China
| | - Xiu Zhu
- Department of Pathology, Institute of Cancer and Basic Medicine (ICBM) of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China
| | - Haixing Ju
- Department of Colorectal Surgery, Institute of Cancer and Basic Medicine (ICBM) of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China
| | - Wenyong Sun
- Department of Pathology, Institute of Cancer and Basic Medicine (ICBM) of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China
| | - Wei Wu
- Department of Pathology, Institute of Cancer and Basic Medicine (ICBM) of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China
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Barresi V, Fioravanzo A, Pecori S, Tomezzoli A, Reggiani Bonetti L. The histopathologic report of surgically resected colorectal liver metastases: What is clinically relevant? Pathol Res Pract 2019; 215:152547. [PMID: 31371210 DOI: 10.1016/j.prp.2019.152547] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 07/12/2019] [Accepted: 07/17/2019] [Indexed: 02/08/2023]
Abstract
Colorectal carcinoma (CRC) is one of the most common malignancies and a major cause of cancer-related death worldwide. The liver is the most frequent site of metastatic spread, so that about half of the patients with CRC have or develop liver metastases (LM) during the clinical course of the disease. Colorectal LM can potentially be cured by surgery, but most patients still experience disease progression and recurrence after the surgical treatment. Prediction of a patient's post-surgical clinical course is mainly based on clinical parameters or the histopathological features of the primary tumor, while little attention is given to the pathological characteristics of the LM. In this paper, we review the prognostic relevance of the gross and microscopic pathological features observed in surgically resected LM and propose which information should be included in the histopathological report to guide surgeons and oncologists for the subsequent therapeutic management.
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Affiliation(s)
- Valeria Barresi
- Department of Diagnostics and Public Health, Polyclinic G.B. Rossi, P.le L.A. Scuro, 1, 37134, Verona, Italy.
| | - Adele Fioravanzo
- Department of Diagnostics and Public Health, Polyclinic G.B. Rossi, P.le L.A. Scuro, 1, 37134, Verona, Italy
| | - Sara Pecori
- Department of Diagnostics and Public Health, Polyclinic G.B. Rossi, P.le L.A. Scuro, 1, 37134, Verona, Italy
| | - Anna Tomezzoli
- Department of Diagnostics and Public Health, Polyclinic G.B. Rossi, P.le L.A. Scuro, 1, 37134, Verona, Italy
| | - Luca Reggiani Bonetti
- Department of Laboratory Integrated Activities, Anatomic Pathology and Legal Medicine, University of Modena and Reggio Emilia, Modena, Italy
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Impact of Genetics on Neoadjuvant Therapy with Complete Pathological Response in Metastatic Colorectal Cancer: Case Report and Review of the Literature. Balkan J Med Genet 2019; 22:75-80. [PMID: 31523624 PMCID: PMC6714337 DOI: 10.2478/bjmg-2019-0004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Treatment of colorectal metastatic cancer is still challenging, despite recent improvements in chemotherapy. A genetic cancer profile, such as the KRAS (Kirsten rat sarcoma) gene status, plays a key role in individualized tailored therapy. Molecular targeted therapy added to neo-adjuvant chemotherapy can achieve a better pathological response and prolong survival. Pathological complete response of colorectal cancer stage IV is rare. A 47-year-old female patient presented with rectal adenocarcinoma and three liver metastases (cT3d/4, N2, Ml). After seven cycles of Bevacizumab and CAPOX in neoadjuvant setting, we noted more than 70.0% regression of metastases and complete regression of the primary tumor. We performed low anterior resection of rectum and synchronous subsegmental resection of S3, because the other two lesions were not detectable. Pathology revealed complete response of the primary and also secondary tumors. After 8 months, diagnostic tests did not show any sign of recurrence and the remaining liver lesions disappeared. Colorectal cancer is a heterogeneous disease and it is necessary to identify patients who are at-risk of recurrence and suitable for neoadjuvant therapy. Genetic biomarkers play an important role in metastatic colorectal cancer treatment. Because of the mutated KRAS gene, Bevacizumab was added to cytotoxic therapy achieving a complete pathological response of primary tumor and metastasis. This case is unique because all reported cases with similar results, described staged surgery and one of reverse staged surgery, but with similar results. This neoadjuvant therapy has extraordinary results for colorectal cancer stage IV and can help disease-free and long-term survival.
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Matos I, Noguerido A, Ros J, Mulet N, Argilés G, Elez É, Tabernero J. Triple-drug chemotherapy regimens in combination with an anti-EGFR agent in metastatic colorectal cancer - prospects from phase II clinical trials. Expert Opin Investig Drugs 2019; 28:463-471. [PMID: 30905200 DOI: 10.1080/13543784.2019.1599860] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
INTRODUCTION The addition of monoclonal antibody (mAb) epidermal growth factor receptor (EGFR) inhibitors to classic chemotherapy doublet backbones has improved survival of metastatic colorectal cancer (mCRC). However, the role of triple-drug chemotherapy regimens in combination with an anti-EGFR mAb inhibitor is not yet clear. AREAS COVERED The activity of triple-drug chemotherapy regimens when combined with an anti-EGFR mAb in mCRC patients is examined. We describe the overall safety and tolerability profiles based on a literature review of all published phase I and II clinical trials in this setting. Drug exposure, tumor mutational status, and metastases resectability are discussed. A review of PubMed and abstracts of major oncology congresses from 2009 to 2018, with MeSH and full-text search terms for clinical trials of anti-EGFR for 'metastatic' or 'advanced' 'colorectal cancer/adenocarcinoma' was implemented. Only English language publications were included. EXPERT OPINION Efficacy data from phase II trials are promising, but the safety profiles are not as encouraging; the development of severe diarrhea and acneiform rash limit the drug exposure that is critical for improved outcomes. Phase II studies of these triplet chemotherapy/anti-EGFR mAb combinations have focused on conversion therapy in liver-limited disease or in the first-line setting in advanced disease. The identification of biomarkers of response and toxicity may support the use of personalized medicine and more precise design of phase III trials.
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Affiliation(s)
- Ignacio Matos
- a Department of Medical Oncology , Vall D'Hebron University Hospital Barcelona/Universitat Autònoma de Barcelona , Barcelona , Spain.,b Department of Medical Oncology , Vall d'Hebron Institute of Oncology (VHIO) , Barcelona , Spain
| | - Alba Noguerido
- a Department of Medical Oncology , Vall D'Hebron University Hospital Barcelona/Universitat Autònoma de Barcelona , Barcelona , Spain.,b Department of Medical Oncology , Vall d'Hebron Institute of Oncology (VHIO) , Barcelona , Spain
| | - Javier Ros
- a Department of Medical Oncology , Vall D'Hebron University Hospital Barcelona/Universitat Autònoma de Barcelona , Barcelona , Spain.,b Department of Medical Oncology , Vall d'Hebron Institute of Oncology (VHIO) , Barcelona , Spain
| | - Nuria Mulet
- a Department of Medical Oncology , Vall D'Hebron University Hospital Barcelona/Universitat Autònoma de Barcelona , Barcelona , Spain.,c Department of Medical Oncology, Institut Català d'Oncologia-IDIBELL , Universitat de Barcelona , Barcelona , Spain
| | - Guillem Argilés
- a Department of Medical Oncology , Vall D'Hebron University Hospital Barcelona/Universitat Autònoma de Barcelona , Barcelona , Spain.,b Department of Medical Oncology , Vall d'Hebron Institute of Oncology (VHIO) , Barcelona , Spain
| | - Élena Elez
- a Department of Medical Oncology , Vall D'Hebron University Hospital Barcelona/Universitat Autònoma de Barcelona , Barcelona , Spain.,b Department of Medical Oncology , Vall d'Hebron Institute of Oncology (VHIO) , Barcelona , Spain
| | - Josep Tabernero
- a Department of Medical Oncology , Vall D'Hebron University Hospital Barcelona/Universitat Autònoma de Barcelona , Barcelona , Spain.,b Department of Medical Oncology , Vall d'Hebron Institute of Oncology (VHIO) , Barcelona , Spain
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Larsen FO, Jensen BV, Nørgaard HH, Hermann HK, Larsen PN, Markussen A, Hogdall E, Nielsen D. Intrahepatic Oxaliplatin and Systemic 5-FU +/- Cetuximab in Chemo-Naïve Patients with Liver Metastases from Colorectal Cancer. Oncology 2019; 96:299-308. [PMID: 30999314 DOI: 10.1159/000499314] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Accepted: 02/28/2019] [Indexed: 01/26/2023]
Abstract
BACKGROUND In case of response to chemotherapy, unresectable liver metastases from colorectal cancer can be converted to resectable and thereby obtain a chance of cure. The primary aim of this trial was to evaluate the response rate with intrahepatic oxaliplatin in combination with systemic 5-FU +/- cetuximab. Secondary aims were to evaluate the conversion rate from unresectable to resectable liver metastases, median progression-free survival, median overall survival, and toxicity. METHODS Forty-five chemo-naïve patients with liver metastases from colorectal cancer were treated in a prospective phase II trial. Calcium folinate and 5-FU were delivered systemically while oxaliplatin was delivered alternating between systemic and intrahepatic administration. When oxaliplatin was delivered intrahepatic-ally, infusion time was reduced to 10 min followed by embolic material. In patients with KRAS wild-type tumors, cetuximab was added. RESULTS The treatment was well tolerated and only pain in the liver and a mild increase in liver enzymes were observed after intrahepatic oxaliplatin. The patients obtained a response rate of 82%. Further, 58% converted from having unresectable to resectable liver metastases. The median overall survival and progression-free survival were 38.7 months (95% confidence interval [CI] 33.0-44.3) and 12.9 months (95% CI 10.2-15.6), respectively. CONCLUSIONS Intrahepatic infusion of oxaliplatin in 10 min with systemic 5-FU to patients with chemo-naïve colorectal cancer is feasible and with low toxicity. A high response rate and long median overall survival were obtained.
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Affiliation(s)
- Finn Ole Larsen
- Department of Oncology, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark,
| | - Benny V Jensen
- Department of Oncology, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark
| | - Hans Henrik Nørgaard
- Department of Radiology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Bispebjerg and Frederiksberg, Denmark
| | - Helle Kirstine Hermann
- Department of Radiology, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark
| | - Peter N Larsen
- Department of Liver Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Alice Markussen
- Department of Oncology, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark
| | - Estrid Hogdall
- Department of Pathology, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark
| | - Dorte Nielsen
- Department of Oncology, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark
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Utility of Image Guidance in the Localization of Disappearing Colorectal Liver Metastases. J Gastrointest Surg 2019; 23:760-767. [PMID: 30680630 PMCID: PMC6717434 DOI: 10.1007/s11605-019-04106-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Accepted: 01/01/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Colorectal liver metastases that demonstrate a complete radiographic response during chemotherapy are increasingly common with advances in chemotherapy regimens and are described as disappearing liver metastases (DLMs). However, these DLMs often continue to harbor residual viable tumor. If these tumors are found in the operating room with ultrasound (US), they should be treated. The intraoperative sonographic visualization of these lesions, however, can be hindered by chemotherapy-associated liver parenchyma changes. The objective of this study was to evaluate the use of an intraoperative image guidance system, Explorer (Analogic Corporation, Peabody, MA), to aid surgeons in the identification of DLMs initially undetected by US alone. STUDY DESIGN In a single-arm prospective trial, patients with colorectal liver metastases undergoing liver resection and/or ablation with one or more DLMs during neoadjuvant chemotherapy were enrolled. Intraoperatively, DLMs were localized with conventional US. Any DLM not found by conventional US was re-evaluated with the image guidance system. The primary outcome was the proportion of sonographically occult DLMs subsequently located by image-guided US. RESULTS Between April 2016 and November 2017, 25 patients with 61 DLMs were enrolled. Thirty-eight DLMs (62%) in 14 patients (56%) were not identified with US alone. Six (16%) DLMs in five patients (36%) were subsequently located with assistance of the image guidance system. The image guidance changed the intraoperative surgical plan in four of these patients. CONCLUSIONS Image guidance can aid surgeons in the identification of initially sonographically occult DLMs and facilitate the complete surgical clearance of all sites of liver disease.
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Quénet F, Pissas MH, Gil H, Roca L, Carrère S, Sgarbura O, Rouanet P, de Forges H, Khellaf L, Deshayes E, Ychou M, Bibeau F. Two-stage hepatectomy for colorectal liver metastases: Pathologic response to preoperative chemotherapy is associated with second-stage completion and longer survival. Surgery 2019; 165:703-711. [DOI: 10.1016/j.surg.2018.10.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 09/21/2018] [Accepted: 10/09/2018] [Indexed: 12/17/2022]
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Perioperative Bevacizumab-based Triplet Chemotherapy in Patients With Potentially Resectable Colorectal Cancer Liver Metastases. Clin Colorectal Cancer 2019; 18:34-43.e6. [DOI: 10.1016/j.clcc.2018.11.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Revised: 08/10/2018] [Accepted: 11/19/2018] [Indexed: 01/14/2023]
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Chow FCL, Chok KSH. Colorectal liver metastases: An update on multidisciplinary approach. World J Hepatol 2019; 11:150-172. [PMID: 30820266 PMCID: PMC6393711 DOI: 10.4254/wjh.v11.i2.150] [Citation(s) in RCA: 137] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Revised: 11/24/2018] [Accepted: 12/05/2018] [Indexed: 02/06/2023] Open
Abstract
Liver metastasis is the commonest form of distant metastasis in colorectal cancer. Selection criteria for surgery and liver-directed therapies have recently been extended. However, resectability remains poorly defined. Tumour biology is increasingly recognized as an important prognostic factor; hence molecular profiling has a growing role in risk stratification and management planning. Surgical resection is the only treatment modality for curative intent. The most appropriate surgical approach is yet to be established. The primary cancer and the hepatic metastasis can be removed simultaneously or in a two-step approach; these two strategies have comparable long-term outcomes. For patients with a limited future liver remnant, portal vein embolization, combined ablation and resection, and associating liver partition and portal vein ligation for staged hepatectomy have been advocated, and each has their pros and cons. The role of neoadjuvant and adjuvant chemotherapy is still debated. Targeted biological agents and loco-regional therapies (thermal ablation, intra-arterial chemo- or radio-embolization, and stereotactic radiotherapy) further improve the already favourable results. The recent debate about offering liver transplantation to highly selected patients needs validation from large clinical trials. Evidence-based protocols are missing, and therefore optimal management of hepatic metastasis should be personalized and determined by a multi-disciplinary team.
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Affiliation(s)
| | - Kenneth Siu-Ho Chok
- Department of Surgery and State Key Laboratory for Liver Research, the University of Hong Kong, Hong Kong, China
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Kepenekian V, Muller A, Valette PJ, Rousset P, Chauvenet M, Phelip G, Walter T, Adham M, Glehen O, Passot G. Evaluation of a strategy using pretherapeutic fiducial marker placement to avoid missing liver metastases. BJS Open 2019; 3:344-353. [PMID: 31183451 PMCID: PMC6551408 DOI: 10.1002/bjs5.50140] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Accepted: 12/06/2018] [Indexed: 12/19/2022] Open
Abstract
Background Hepatic surgery is appropriate for selected patients with colorectal liver metastases (CRLM). Advances in chemotherapy have led to modification of management, particularly when metastases disappear. Treatment should address all initial CRLM sites based on pretherapeutic cross-sectional imaging. This study aimed to evaluate pretherapeutic fiducial marker placement to optimize CRLM treatment. Methods This pilot investigation included patients with CRLM who were considered for potentially curative treatment between 2009 and 2016. According to a multidisciplinary team decision, lesions smaller than 25 mm in diameter that were more than 10 mm deep in the hepatic parenchyma and located outside the field of a planned resection were marked. Complication rates and clinicopathological data were analysed. Results Some 76 metastases were marked in 43 patients among 217 patients with CRLM treated with curative intent. Of these, 23 marked CRLM (30 per cent), with a mean(s.d.) size of 11·0(3·4) mm, disappeared with preoperative chemotherapy. There were four complications associated with marking: two intrahepatic haematomas, one fiducial migration and one misplacement. After a median follow-up of 47·7 (range 18·1-144·9) months, no needle-track seeding was noted. Of four disappearing CRLM that were marked and resected, two presented with persistent active disease. Other missing lesions were treated with thermoablation. Conclusion Pretherapeutic fiducial marker placement appears useful for the curative management of CRLM.
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Affiliation(s)
- V Kepenekian
- Department of Digestive Surgery Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Lyon France
| | - A Muller
- Department of Radiology Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Lyon France
| | - P J Valette
- Department of Radiology Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Lyon France
| | - P Rousset
- Department of Radiology Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Lyon France
| | - M Chauvenet
- Department of Digestive Oncology Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Lyon France
| | - G Phelip
- Department of Digestive Oncology Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Lyon France
| | - T Walter
- Department of Medical Oncology Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon 1 University Lyon France
| | - M Adham
- Department of Digestive Surgery Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon 1 University Lyon France
| | - O Glehen
- Department of Digestive Surgery Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Lyon France
| | - G Passot
- Department of Digestive Surgery Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Lyon France
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Tsilimigras DI, Ntanasis-Stathopoulos I, Paredes AZ, Moris D, Gavriatopoulou M, Cloyd JM, Pawlik TM. Disappearing liver metastases: A systematic review of the current evidence. Surg Oncol 2019; 29:7-13. [PMID: 31196496 DOI: 10.1016/j.suronc.2019.02.005] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Accepted: 02/10/2019] [Indexed: 12/14/2022]
Abstract
Advances in systemic chemotherapy have resulted in a significant increase in the reported response rates of colorectal liver metastases (CRLM) over time. Although radiologic response is usually prognostic of favorable outcomes, complete shrinkage of CRLM after chemotherapy, namely "disappearing liver metastases" (DLMs) poses significant therapeutic dilemmas. A systematic review of the literature was conducted to evaluate the existing evidence on the imaging and management of patients with DLMs using the PubMed (Medline), Embase and Cochrane library through December 21st, 2018. The following algorithm was used: "(disappearing OR vanishing OR missing OR (residual tiny)) AND ((liver OR hepatic) AND (metastasis OR metastases OR metastatic OR secondary))." From the 225 records retrieved, 15 studies were finally deemed eligible. A total of 479 patients with DLMs with a median age of 59.5 years (range, 30-83) were identified. Median number of DLM per patient ranged from 1 to 8.8. Median size of LMs prior to chemotherapy was 1.07 cm (range 0.3-3.5). The systemic treatment used to achieve DLMs included systemic chemotherapy alone (only 2 studies) or in combination with targeted agents (11 studies). The median number of chemotherapy cycles in the included studies was 7.8 (range 6-12). Identified factors predisposing to the development of DLM were small size (<2 cm), increased number of treatment cycles, oxaliplatin-based therapy, increased number of CRLM (≥3) and synchronous CRLM. Baseline and preoperative MRI with iv contrast showed the highest sensitivity for DLM detection. Fiducial placement facilitated pre- and intra-operative identification of DLM. Although resection of DLM decreased the local recurrence risk, there was no clearly demonstrated survival benefit after resecting all sites of disappearing lesions. Future randomized clinical trials are highly encouraged to provide strict, evidence-based recommendations for the treatment of patients with DLM.
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Affiliation(s)
- Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Ioannis Ntanasis-Stathopoulos
- Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece
| | - Anghela Z Paredes
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Dimitrios Moris
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Maria Gavriatopoulou
- Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece
| | - Jordan M Cloyd
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA.
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Kaganov OI, Kozlov SV, Orlov AE, Blinov NV. The Results of the Combine Treatment of Patients with Liver Bilobar Metastases from Colorectal Cancer Using Radiofrequency Ablation. Indian J Surg Oncol 2018; 9:175-180. [PMID: 29887697 PMCID: PMC5984858 DOI: 10.1007/s13193-018-0740-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Accepted: 03/28/2018] [Indexed: 10/17/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide. The mortality from CRC remains very high. The main cause of such a high mortality is a disseminate process with the appearance of distant metastases. In this regard, the treatment of metastatic lesions is recognized as an important trend in modern oncology. The program of study included 176 patients with colorectal cancer after primary tumor removal with the malignant progression-multiple (more than 4) bilobar liver metastases. The research was organized in Samara Regional Oncology Centre from 2001 to 2014. By the treatment method, patients were divided into two groups. Main group got the combined (chemotherapy + radiofrequency ablation (RFA)) treatment (n = 98). In control group, only chemotherapy was applied (n = 78). One-, two-, and three-year OS were 73.5, 25.1, and 7.2% in the main group and 39.6, 6.3, and 2.1% in the control group. The RFA application allowed us to reach the index of 4-year survival 1.8% in the main group, while we received only 2.1 of 3-year survival in the control group. The OS median reached 18 months in the main group and 11 months in the control group. So, the OS curves in two comparing groups were significantly different according to statistics (log-rank test 3.77, р = 0.000). The application of RFA in combination with chemotherapy in the treatment of bilobar metastasis colorectal cancer allows to improve the performance of disease-free survival and overall survival significantly, compared with the group of patients who received only chemotherapy.
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Baimas-George M, Baker E, Kamionek M, Salmon JS, Sastry A, Levi D, Vrochides D. A Complete Pathological Response to Pembrolizumab following ex vivo Liver Resection in a Patient with Colorectal Liver Metastases. Chemotherapy 2018; 63:90-94. [PMID: 29621772 DOI: 10.1159/000487814] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Accepted: 02/16/2018] [Indexed: 02/28/2024]
Abstract
Advances in the systemic treatment of stage IV colorectal cancer with liver metastases has offered improved survival rates for patients who otherwise face a dismal prognosis. However, a pathologically complete response (PCR) to chemotherapy for colorectal liver metastases is still rare, and its significance is not fully understood. In this case report, we describe a patient who achieved PCR after neoadjuvant immunotherapy with pembrolizumab and a left hepatectomy using an ex vivo resection technique.
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Affiliation(s)
- Maria Baimas-George
- Department of General Surgery, Carolinas Medical Center, Carolinas Healthcare Systems, Charlotte, North Carolina, USA
| | - Erin Baker
- Department of Hepatopancreatobiliary Surgery, Carolinas Medical Center, Carolinas Healthcare Systems, Charlotte, North Carolina, USA
| | - Michal Kamionek
- Department of Pathology, Carolinas Medical Center, Carolinas Healthcare Systems, Charlotte, North Carolina, USA
| | - J Stuart Salmon
- Department of Medical Oncology, Carolinas Medical Center, Carolinas Healthcare Systems, Charlotte, North Carolina, USA
| | - Amit Sastry
- Department of Hepatopancreatobiliary Surgery, Carolinas Medical Center, Carolinas Healthcare Systems, Charlotte, North Carolina, USA
| | - David Levi
- Department of Transplant Surgery, Carolinas Medical Center, Carolinas Healthcare Systems, Charlotte, North Carolina, USA
| | - Dionisios Vrochides
- Department of Hepatopancreatobiliary Surgery, Carolinas Medical Center, Carolinas Healthcare Systems, Charlotte, North Carolina, USA
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Cremolini C, Milione M, Marmorino F, Morano F, Zucchelli G, Mennitto A, Prisciandaro M, Lonardi S, Pellegrinelli A, Rossini D, Bergamo F, Aprile G, Urbani L, Morelli L, Schirripa M, Cardellino GG, Fassan M, Fontanini G, de Braud F, Mazzaferro V, Falcone A, Pietrantonio F. Differential histopathologic parameters in colorectal cancer liver metastases resected after triplets plus bevacizumab or cetuximab: a pooled analysis of five prospective trials. Br J Cancer 2018; 118:955-965. [PMID: 29531324 PMCID: PMC5931102 DOI: 10.1038/s41416-018-0015-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Revised: 01/10/2018] [Accepted: 01/10/2018] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Many factors, including histopathologic parameters, seem to influence the prognosis of patients undergoing resection of colorectal cancer liver metastases (CRCLM), although their relative weight is unclear. Histopathologic growth patterns (HGPs) of CRCLM may affect sensitivity to antiangiogenics. We aimed at evaluating differences in histopathologic parameters of response according to the use of bevacizumab or cetuximab as first-line targeted agents, and at exploring the prognostic and predictive role of HGPs. METHODS We performed a comprehensive histopathologic characterisation of CRCLM from 159 patients who underwent secondary resection, after receiving triplets FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) or COI (capecitabine, oxaliplatin, and irinotecan) plus bevacizumab (N = 103) vs cetuximab (N = 56) in five first-line no-profit clinical trials. RESULTS Both major histopathologic response (tumour regression grade TRG1-2, 32 vs 14%, p = 0.013) and infarct-like necrosis (80 vs 64%, p = 0.035) were significantly higher in the bevacizumab than in the cetuximab group. Achieving major response positively affected relapse-free survival (RFS) (p = 0.012) and overall survival (OS) (p = 0.045), also in multivariable models (RFS, p = 0.008; OS, p = 0.033). In the desmoplastic HGP (N = 28), a higher percentage of major response was reported (57 vs 17% in pushing and 22% in replacement HGP, p < 0.001) and an unsignificant advantage from cetuximab vs bevacizumab was evident in RFS (p = 0.116). In the pushing HGP (N = 66), a significant benefit from bevacizumab vs cetuximab (p = 0.017) was observed. No difference was described in the replacement HGP (N = 65, p = 0.615). CONCLUSIONS The histopathologic response is the only independent determinant of survival in patients resected after triplets plus a biologic. When associated with triplet chemotherapy, bevacizumab induces a higher histopathologic response rate than cetuximab. The assessment of HGPs should be further explored as a predictor of benefit from available targeted agents.
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Affiliation(s)
- Chiara Cremolini
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, 56126, Italy
| | - Massimo Milione
- Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori - Via Venezian, 20100, Milano, Italy.
| | - Federica Marmorino
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, 56126, Italy
| | - Federica Morano
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori - Via Venezian, 1, 20100, Milano, Italy
| | - Gemma Zucchelli
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, 56126, Italy
| | - Alessia Mennitto
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori - Via Venezian, 1, 20100, Milano, Italy
| | - Michele Prisciandaro
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori - Via Venezian, 1, 20100, Milano, Italy
| | - Sara Lonardi
- Unit of Medical Oncology 1, Department of Clinical and Experimental Oncology, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua, 35128, Padova, Italy
| | - Alessio Pellegrinelli
- Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori - Via Venezian, 20100, Milano, Italy
| | - Daniele Rossini
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, 56126, Italy
| | - Francesca Bergamo
- Unit of Medical Oncology 1, Department of Clinical and Experimental Oncology, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua, 35128, Padova, Italy
| | - Giuseppe Aprile
- Department of Oncology, University & General Hospital, Udine - Pz.le S. Maria della Misericordia 15, 33100, Udine, Italy
- General Hospital, ULSS8 Berica - East District, 36100, Vicenza, Italy
| | - Lucio Urbani
- General Surgery Unit, Azienda Ospedaliero-Universitaria Pisana, Ospedale Nuovo Santa Chiara, Cisanello, 56124, Pisa, Italy
| | - Luca Morelli
- 1st General Surgery Unit, Azienda Ospedaliero-Universitaria Pisana, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124, Pisa, Italy
| | - Marta Schirripa
- Unit of Medical Oncology 1, Department of Clinical and Experimental Oncology, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua, 35128, Padova, Italy
| | - Giovanni Gerardo Cardellino
- Department of Oncology, University & General Hospital, Udine - Pz.le S. Maria della Misericordia 15, 33100, Udine, Italy
| | - Matteo Fassan
- Surgical Pathology Unit, Department of Medicine University of Padua, Padua, via Giustiniani 2, 56126, Padova, Italy
| | - Gabriella Fontanini
- Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa - Via Roma, 67 56126, Pisa, Italy
| | - Filippo de Braud
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori - Via Venezian, 1, 20100, Milano, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Vincenzo Mazzaferro
- General Surgery and Liver Surgery, Transplantation and Gastroenterology, University of Milan, IRCCS Istituto Nazionale Tumori Fondazione, 20100, Milan, Italy
| | - Alfredo Falcone
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, 56126, Italy
| | - Filippo Pietrantonio
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori - Via Venezian, 1, 20100, Milano, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
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Pai RK, Pai RK. Pathologic assessment of gastrointestinal tract and pancreatic carcinoma after neoadjuvant therapy. Mod Pathol 2018; 31:4-23. [PMID: 28776577 DOI: 10.1038/modpathol.2017.87] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Revised: 05/31/2017] [Accepted: 06/18/2017] [Indexed: 12/17/2022]
Abstract
Neoadjuvant therapy is increasingly used to treat patients with a wide variety of malignancies. Histologic evaluation of treated specimens provides important prognostic information and may guide subsequent chemotherapy. Neoadjuvant therapy is commonly employed in the treatment of locally advanced rectal adenocarcinoma, hepatic colorectal metastases, esophageal/esophagogastric junction carcinoma, and pancreatic ductal adenocarcinoma. Numerous tumor regression schemes have been used in these tumors and standardized approaches to evaluate these specimens are needed. In this review, the various tumor regression scoring systems that have been used in these organs are described and their associations with clinical outcomes are discussed. Recommendations regarding how to handle and report the histologic findings in these resections specimens are provided.
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Affiliation(s)
- Reetesh K Pai
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Rish K Pai
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ, USA
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Preoperative tumor restaging and resectability assessment of gastric cancers after chemotherapy: diagnostic accuracy of MDCT using new staging criteria. Abdom Radiol (NY) 2017. [PMID: 28643135 DOI: 10.1007/s00261-017-1224-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
PURPOSE To evaluate the diagnostic performance of preoperative MDCT for tumor restaging and determination of resectability in gastric cancers after chemotherapy using new staging criteria. METHODS This retrospective study was approved by our institutional review board and the requirement for informed consent was waived. Thirty-seven patients with initially unresectable gastric cancers who had received chemotherapy followed by surgery were included. Two independent radiologists reviewed preoperative MDCT images to determine the TNM staging and rate the overall likelihood of resectability using a 5-point scale (5: definitely unresectable, 1: definitely resectable). New post-chemotherapy MDCT criteria do not use non-enhancing perigastric infiltrations, non-enhancing lymph nodes (LNs), and subtle remaining infiltrations after marked decrease in the size of distant metastases for T, N, and M upstaging, respectively. Discrepancies in TNM staging were resolved by a third reviewer. The diagnostic performances of MDCT were assessed using pathologic results or operation records as reference standards. RESULTS For predicting resectability, the areas under the ROC curve were 0.885 and 0.882 (95% CIs 0.737-0.966 and 0.733-0.964) in reviewers 1 and 2, respectively, with substantial inter-reader agreement (weighted κ = 0.689). Sensitivities and specificities of MDCT for tumor restaging on a consensus review were 80.0% (4/5) and 100% (29/29) for T4b, 35.3% (6/17) and 81.3% (13/16) for N-positive, and 63.6% (7/11) and 100% (26/26) for M1, respectively. CONCLUSIONS For gastric cancers after chemotherapy, new MDCT criteria demonstrated high specificities for T4b and M-staging and good performances to predict resectability before conversion surgery.
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Nielsen K, Scheffer HJ, Volders JH, van der Vorst MJDL, van Tilborg AAJM, Comans EF, de Lange-de Klerk ESM, Sietses C, Meijer S, Meijerink MR, van den Tol MP. Radiofrequency Ablation to Improve Survival After Conversion Chemotherapy for Colorectal Liver Metastases. World J Surg 2017; 40:1951-8. [PMID: 27220509 DOI: 10.1007/s00268-016-3554-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
INTRODUCTION Systemic chemotherapy is able to convert colorectal liver metastases (CRLM) that are initially unsuitable for local treatment into locally treatable disease. Surgical resection further improves survival in these patients. Our aim was to evaluate disease-free survival (DFS), overall survival, and morbidity for patients with CRLM treated with RFA following effective downstaging by chemotherapy, and to identify factors associated with recurrence and survival. MATERIALS AND METHODS Included patients had liver-dominant CRLM initially unsuitable for local treatment but eligible for RFA or RFA with resection after downstaging by systemic chemotherapy. Chemotherapeutic regimens consisted predominantly of CapOx, with or without bevacizumab. Follow-up was conducted with PET-CT or thoraco-pelvic CT. RESULTS Fifty-one patients had a total of 325 CRLM (median = 7). Following chemotherapy, 183 lesions were still visible on CT (median = 3). Twenty-six patients were treated with RFA combined with resection. During surgery, 309 CRLM were retrieved on intraoperative ultrasound (median = 5). Median survival was 49 months and was associated with extrahepatic disease at time of presentation and recurrences after treatment. Estimated cumulative survival at 1, 3 and 4 years was 90, 63 and 45 %, respectively. Median DFS was 6 months. Twelve patients remained free of recurrence after a mean follow-up of 32.6 months. CONCLUSION RFA of CRLM after conversion chemotherapy provides potential local control and a good overall survival. To prevent undertreatment, the involvement of a multidisciplinary team in follow-up imaging and assessment of local treatment possibilities after palliative chemotherapy for liver-dominant CRLM should always be considered.
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Affiliation(s)
- Karin Nielsen
- Department of Surgery, VU University Medical Center, Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
| | - Hester J Scheffer
- Department of Radiology and Nuclear Medicine, VU University Medical Center, Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - José H Volders
- Department of Surgery, Gelderse Vallei Hospital, Postbus 9025, 6716 RP, Ede, The Netherlands
| | - Maurice J D L van der Vorst
- Department of Medical Oncology, VU University Medical Center, Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
- Department of Medical Oncology, Rijnstate Hospital, Marga Klompélaan 6, 6836 TA, Arnhem, The Netherlands
| | - Aukje A J M van Tilborg
- Department of Radiology and Nuclear Medicine, VU University Medical Center, Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Emile Fi Comans
- Department of Radiology and Nuclear Medicine, VU University Medical Center, Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - E S M de Lange-de Klerk
- Department of Epidemiology and Biostatistics, VU University Medical Center, Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Colin Sietses
- Department of Surgery, Gelderse Vallei Hospital, Postbus 9025, 6716 RP, Ede, The Netherlands
| | - Sybren Meijer
- Department of Surgery, VU University Medical Center, Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Martijn R Meijerink
- Department of Radiology and Nuclear Medicine, VU University Medical Center, Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - M Petrousjka van den Tol
- Department of Surgery, VU University Medical Center, Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
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