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Russell M, Gild ML, Wirth LJ, Robinson B, Karcioglu AS, Iwata A, Athni TS, Abdelhamid Ahmed AH, Randolph GW. Neoadjuvant therapy to improve resectability of advanced thyroid cancer: A real-world experience. Head Neck 2024; 46:2496-2507. [PMID: 38488238 DOI: 10.1002/hed.27735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 02/27/2024] [Accepted: 03/04/2024] [Indexed: 03/21/2024] Open
Abstract
BACKGROUND Experience with targeted neoadjuvant treatment for locoregionally advanced thyroid cancer is nascent. METHODS Multicenter retrospective case series examining targeted neoadjuvant treatment for locoregionally advanced thyroid cancer. The primary outcome was change in surgical morbidity as measured by two metrics developed for use in clinical trials to characterize surgical complexity and morbidity. Secondary outcomes included percentage of patients proceeding to surgery and percentage receiving an R0/R1 resection. RESULTS Seventeen patients with varied molecular alterations, pathologies, and treatment regimens were included. Mean surgical complexity scores decreased between time points for baseline and postneoadjuvant treatment, postneoadjuvant treatment and surgery, and between baseline and surgery. Eleven patients (64.7%) underwent surgical resection, with 10 (58.8%) receiving an R0/R1 resection. CONCLUSIONS Neoadjuvant treatment of advanced thyroid cancer improves resectability and decreases the morbidity of required surgical procedures. However, treatment is not uniformly effective.
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Affiliation(s)
- Marika Russell
- Division of Thyroid and Parathyroid Endocrine Surgery, Harvard Medical School, Boston, Massachusetts, USA
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA
| | - Matti L Gild
- Department of Endocrinology and Diabetes, Royal North Shore Hospital, Sydney, Australia
- Cancer Genetics Laboratory, Kolling Institute of Medical Research, Sydney, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, Australia
| | - Lori J Wirth
- Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Bruce Robinson
- Department of Endocrinology and Diabetes, Royal North Shore Hospital, Sydney, Australia
- Cancer Genetics Laboratory, Kolling Institute of Medical Research, Sydney, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, Australia
| | - Amanda Silver Karcioglu
- Division of Thyroid and Parathyroid Endocrine Surgery, Harvard Medical School, Boston, Massachusetts, USA
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA
- Division of Otolaryngology-Head and Neck Surgery, North Shore University HealthSystem, Evanston, Illinois, USA
- Department of Surgery, North Shore University HealthSystem, Evanston, Illinois, USA
- The University of Chicago, Pritzker School of Medicine, Chicago, Illinois, USA
| | - Ayaka Iwata
- Division of Thyroid and Parathyroid Endocrine Surgery, Harvard Medical School, Boston, Massachusetts, USA
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA
- Department of Otolaryngology-Head and Neck Surgery, Kaiser Permanente Santa Clara Medical Center, Santa Clara, California, USA
| | | | - Amr H Abdelhamid Ahmed
- Division of Thyroid and Parathyroid Endocrine Surgery, Harvard Medical School, Boston, Massachusetts, USA
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA
| | - Gregory W Randolph
- Division of Thyroid and Parathyroid Endocrine Surgery, Harvard Medical School, Boston, Massachusetts, USA
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
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Patel PS, Rodgers M, Kulasegaran S. Gastric cardia submucosal tumours - histopathological diagnosis and challenges in management. ANZ J Surg 2024; 94:1869-1870. [PMID: 39286950 DOI: 10.1111/ans.19233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 08/22/2024] [Accepted: 09/05/2024] [Indexed: 09/19/2024]
Affiliation(s)
- Preekesh Suresh Patel
- Upper Gastrointestinal Unit, Department of General Surgery, Te Whatu Ora - Waitemata, Waitemata, New Zealand
- Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Michael Rodgers
- Upper Gastrointestinal Unit, Department of General Surgery, Te Whatu Ora - Waitemata, Waitemata, New Zealand
| | - Suheelan Kulasegaran
- Upper Gastrointestinal Unit, Department of General Surgery, Te Whatu Ora - Waitemata, Waitemata, New Zealand
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Wu C, Wen F, Lin F, Zeng Y, Lin X, Hu X, Zhang X, Zhang X, Wang X. Predictive performance of [ 18F]F-fibroblast activation protein inhibitor (FAPI)-42 positron emission tomography/computed tomography (PET/CT) in evaluating response of recurrent or metastatic gastrointestinal stromal tumors: complementary or alternative to [ 18F]fluorodeoxyglucose (FDG) PET/CT? Quant Imaging Med Surg 2024; 14:5333-5345. [PMID: 39144061 PMCID: PMC11320500 DOI: 10.21037/qims-24-192] [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: 01/30/2024] [Accepted: 05/22/2024] [Indexed: 08/16/2024]
Abstract
Background Accurately and promptly predicting the response of gastrointestinal stromal tumors (GISTs) to targeted therapy is essential for optimizing treatment strategies. However, some fractions of recurrent or metastatic GISTs present as non-FDG-avid lesions, limiting the value of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) in treatment evaluation. This study evaluated the efficacy of [18F]F-fibroblast activation protein inhibitor (FAPI)-42 [18F]FAPI-42) PET/CT for assessing the treatment response in recurrent or metastatic GISTs, in comparison to [18F]FDG PET/CT and explores a model integrating PET/CT imaging and clinical parameters to optimize the clinical use of these diagnostic tools. Methods Our retrospective analysis included 27 patients with recurrent or metastatic GISTs who underwent [18F]FAPI-42 PET/CT and [18F]FDG PET/CT at baseline before switching targeted therapy. Treatment response status was divided into a progression group (PG) and a non-progression group (NPG) based on the Response Criteria in Solid Tumors (RECIST) 1.1, according to the contrast-enhanced computed tomography (CT) scan at six months. [18F]FAPI-42 and [18F]FDG PET/CT parameters including the mean standardized uptake value (SUVmean), the standard uptake value corrected for lean body mass (SULpeak), the maximum standardized uptake value (SUVmax), tumor-to-blood pool SUV ratio (TBR), tumor-to-liver SUV ratio (TLR), metabolic tumor volume (MTV)/FAPI-positive tumor volume (GTV-FAPI), total lesion glycolysis (TLG)/FAPI-positive total lesion accumulation (TLF) were correlated with the response status to identify indicative of treatment response. The predictive performance of them was quantified by generating receiver operating characteristic curves (ROC), calibration curves, and cross-validation. Results A total of 110 lesions were identified in 27 patients. Compared with PG, NPG was associated with lower levels of TBR and SUVmean in FDG PET/CT (TBR-FDG, SUVmean-FDG; P=0.033 and P=0.038, respectively), with higher SULpeak and TLF in FAPI PET/CT (SULpeak-FAPI, TLF-FAPI; P=0.10 and P=0.049, respectively). The predictive power of a composite-parameter model, including TBR-FDG, SULpeak-FAPI, gene mutation, and type of targeted therapy [area under the curve (AUC) =0.865], was superior to the few-parameter models incorporating TBR-FDG (AUC =0.637, P<0.001), SULpeak-FAPI (AUC =0.665, P<0.001) or both (AUC =0.721, P<0.001). Conclusions Both [18F]FAPI-42 PET/CT and [18F]FDG PET/CT have value in predicting the treatment response of recurrent or metastatic GISTs. And [18F]FAPI-42 PET/CT offers synergistic value when used in combination with [18F]FDG PET/CT. Notably, the nomogram generated from the model incorporating [18F]FAPI-42 PET/CT, [18F]FDG PET/CT parameters, gene mutation, and type of targeted therapy could yield more precise predictions of the response of recurrent metastatic GISTs.
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Affiliation(s)
- Chunhui Wu
- Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Fang Wen
- Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Fangzeng Lin
- Department of Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yu Zeng
- Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiaojie Lin
- Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xin Hu
- Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiangsong Zhang
- Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xinhua Zhang
- Center of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiaoyan Wang
- Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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4
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Mirovic M, Stojanovic MD, Jovanovic M, Stankovic V, Milosev D, Zdravkovic N, Milosevic B, Cvetkovic A, Spasic M, Vekic B, Jovanovic I, Stojanovic BS, Petrovic M, Bogut A, Peulic M, Stojanovic B. Exploring Perforated Jejunal GIST: A Rare Case Report and Review of Molecular and Clinical Literature. Curr Issues Mol Biol 2024; 46:1192-1207. [PMID: 38392194 PMCID: PMC10887764 DOI: 10.3390/cimb46020076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 01/13/2024] [Accepted: 01/24/2024] [Indexed: 02/24/2024] Open
Abstract
This case report details a rare instance of a perforated jejunal gastrointestinal stromal tumor (GIST) in a 76-year-old female patient. The patient presented with acute abdominal pain and distension without any changes in bowel habits or episodes of nausea and vomiting. Initial diagnostics, including abdominal plain radiography and ultrasonography, were inconclusive; however, a computed tomography (CT) scan revealed pneumoperitoneum and an irregular fluid collection suggestive of small intestine perforations. Surgical intervention uncovered a 35 mm jejunal GIST with a 10 mm perforation. Histopathological examination confirmed a mixed cell type GIST with high malignancy potential, further substantiated by immunohistochemistry markers CD117, DOG1, and vimentin. Molecular analysis illuminated the role of key oncogenes, primarily KIT and PDGFRA mutations, emphasizing the importance of molecular diagnostics in GIST management. Despite the severity of the presentation, the patient's postoperative recovery was favorable, highlighting the effectiveness of prompt surgical and multidisciplinary approaches in managing complex GIST cases.
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Affiliation(s)
- Milos Mirovic
- Department of General Surgery, Clinical Hospital Center Kotor, 85330 Kotor, Montenegro
| | - Milica Dimitrijevic Stojanovic
- Department of Pathology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
- Department of Pathology, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia
| | - Marina Jovanovic
- Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
| | - Vesna Stankovic
- Department of Pathology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
- Department of Pathology, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia
| | - Danijela Milosev
- Department of Pathology, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia
| | - Natasa Zdravkovic
- Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
| | - Bojan Milosevic
- Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
| | - Aleksandar Cvetkovic
- Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
| | - Marko Spasic
- Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
| | - Berislav Vekic
- Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
| | - Ivan Jovanovic
- Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
| | - Bojana S Stojanovic
- Department of Pathophysiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
| | - Marko Petrovic
- Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
| | - Ana Bogut
- City Medical Emergency Department, 11000 Belgrade, Serbia
| | - Miodrag Peulic
- Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
| | - Bojan Stojanovic
- Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
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Berndsen M, Renberg S, Hølmebakk T, Hancke E, Puls F, Karlsson F, Stoldt S, Bjerkehagen B, Haglund de Flon F, Muth A, Papakonstantinou A, Boye K, Lindskog S. Long-term outcome after surgical resection of non-high-risk gastrointestinal stromal tumours without adjuvant therapy. Br J Surg 2023; 110:1857-1862. [PMID: 37758514 PMCID: PMC10638541 DOI: 10.1093/bjs/znad309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 08/04/2023] [Accepted: 09/08/2023] [Indexed: 10/03/2023]
Abstract
BACKGROUND Gastrointestinal stromal tumour (GIST) is the most common intra-abdominal sarcoma. Risk classification systems, commonly the modified National Institutes of Health consensus criteria, identify tumour properties relating to patient outcomes. However, owing to limited long-term evidence, most guidelines recommend up to 10-year follow-up for all risk groups except very low-risk GIST. METHODS This retrospective multicentre study included patients who had complete resection of primary, non-metastatic GIST from three Scandinavian sarcoma centres: Gothenburg (2004-2020), Stockholm (2000-2019), and Oslo (2000-2017). Medical records were reviewed for clinical details regarding diagnosis, treatment, and follow-up, and recurrence-free and disease-specific survival evaluated. RESULTS The total cohort consisted of 1213 patients with GIST. High-risk patients and those treated with tyrosine kinase inhibitors were excluded. The remaining 649 patients were included in the present analysis: 118 with very low-, 381 with low-, and 150 with intermediate-risk GISTs. Five-year recurrence-free survival rates were 100, 98.5, and 100 per cent for the intermediate-, low-, and very low-risk groups respectively (P = 0.246). Disease-specific survival rates 10 years after surgery were 100, 98.4, and 100 per cent for the intermediate-, low-, and very low-risk groups respectively (P = 0.262). CONCLUSION Patients with completely resected non-high-risk GISTs have an excellent long-term outcome, irrespective of risk group. Follow-up programmes to detect disease recurrences in these patients are probably not indicated.
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Affiliation(s)
- Marta Berndsen
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Section of Endocrine and Sarcoma Surgery, Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Sara Renberg
- Department of Head, Neck, Lung and Skin Tumours, Karolinska University Hospital, Stockholm, Sweden
| | - Toto Hølmebakk
- Department of Abdominal and Paediatric Surgery, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway
| | - Emma Hancke
- Section of Endocrine and Sarcoma Surgery, Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Florian Puls
- Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Fredrik Karlsson
- Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
- Department of Breast Cancer, Endocrine Tumours and Sarcoma, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden
| | - Stephan Stoldt
- Department of Abdominal and Paediatric Surgery, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway
| | - Bodil Bjerkehagen
- Department of Pathology, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Felix Haglund de Flon
- Department of Oncology–Pathology, Karolinska Institutet, Stockholm, Sweden
- Department of Pathology and Cancer diagnostics, Karolinska University Hospital, Stockholm, Sweden
| | - Andreas Muth
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Section of Endocrine and Sarcoma Surgery, Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Andri Papakonstantinou
- Department of Breast Cancer, Endocrine Tumours and Sarcoma, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden
- Department of Oncology–Pathology, Karolinska Institutet, Stockholm, Sweden
| | - Kjetil Boye
- Department of Oncology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway
| | - Stefan Lindskog
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Section of Endocrine and Sarcoma Surgery, Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Surgery, Halland Hospital, Varberg, Sweden
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Ling J, Shi L, Cheng X, Fu Y, Lin Z, Zhao Y, Li Z, Zhang J, Hu H, Cai Y, Deng Y. Neoadjuvant versus adjuvant imatinib in primary localized gastrointestinal stromal tumor. J Gastrointest Oncol 2023; 14:73-84. [PMID: 36915468 PMCID: PMC10007957 DOI: 10.21037/jgo-22-931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 11/27/2022] [Indexed: 01/12/2023] Open
Abstract
Background The effect of neoadjuvant therapy (NAT) with imatinib versus upfront resection (UR) followed by adjuvant therapy (AT) with imatinib on the outcomes of gastrointestinal stromal tumors (GIST) is unknown. Methods This is a retrospective study at a high-volume center. All the patients with primary localized GIST were identified in a hospital database from 2007 to 2021. The endpoints included local recurrence-free survival (LRFS), distance recurrence-free survival (DRFS), and overall survival (OS). Cox regression was used to perform multivariate survival analyses. The sensitivity analysis was conducted with the inverse probability of treatment weighting (IPTW) method. Results A total of 211 patients were included (Group A: UR + AT, n=140; Group B: NAT + resection + AT, n=71). In the entire cohort, 5-year DRFS, LRFS, and OS were 85.6%, 90.7%, and 92.5%, respectively. In the multivariate analysis, better DRFS was linked to NAT, tumor size of 5 cm, and AT. Sixteen patients (11.4%) in Group A and 1 (1.4%) in Group B had distant recurrences after AT discontinuation. The sensitivity analysis by IPTW provided approximately similar results. An interaction effect was observed between NAT and tumor location on DRFS. In non-gastric GISTs, NAT was associated with better DRFS [hazard ratio =0.131, 95% confidence interval (CI): 0.017-0.989, P=0.049], which was not the case in gastric GIST (P=0.08). NAT was not independently associated with LRFS or OS. Conclusions When compared to UR + AT, NAT + resection + AT may reduce the risk of distant recurrence in localized GIST and may be especially beneficial for patients with non-gastric GISTs.
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Affiliation(s)
- Jiayu Ling
- Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lishuo Shi
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Center for Clinical Research, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xingyu Cheng
- Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yang Fu
- Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Ziqin Lin
- Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yandong Zhao
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Department of Pathology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zheqing Li
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Department of Data Management, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jianwei Zhang
- Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Huabin Hu
- Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yue Cai
- Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yanhong Deng
- Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Ran P, Zhou H, Li J, Tan T, Yang H, Li J, Zhang J. Improving Outcomes in the Advanced Gastrointestinal Stromal Tumors: The Role of the Multidisciplinary Team Discussion Intervention. J Pers Med 2023; 13:jpm13030417. [PMID: 36983599 PMCID: PMC10057951 DOI: 10.3390/jpm13030417] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 02/16/2023] [Accepted: 02/25/2023] [Indexed: 03/02/2023] Open
Abstract
Objectives: There is disagreement over the prognostic value of multidisciplinary team (MDT) discussion for advanced gastrointestinal stromal tumors (GISTs). This study examined how an MDT affected patients with advanced GISTs in terms of their overall survival (OS) and whether it may enhance their performance status (PS). Methods: A retrospective data analysis was conducted on patients with advanced GISTs between 2000 and 2022. Depending on whether they had received the MDT discussion intervention, the patients were split into two groups. The OS between the two groups was compared using the Kaplan–Meier method. A multivariate Cox regression analysis was used to analyze the prognostic variables for advanced GIST. Fisher’s test was used to investigate the relationship between an MDT and PS. Results: There were 122 patients with an MDT and 117 patients without an MDT in this study. In comparison to the non-MDT group, the MDT group showed a higher survival rate (5-year OS, 42.62% vs. 28.21%, p < 0.05). MDT was an independent prognostic factor for OS in univariate and multivariate Cox regression analyses (p < 0.05). Fisher’s test revealed that there were variations in PS between the two groups (p < 0.05). Conclusions: The effectiveness of an MDT in the treatment of advanced GIST was examined for the first time in this study. MDT discussion intervention is an effective measure for improving the outcomes of patients with advanced GISTs.
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Affiliation(s)
- Pan Ran
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Hui Zhou
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Jinjin Li
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Tao Tan
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Hao Yang
- Department of Internal Medicine, Chongqing Key Laboratory of Translation Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Juan Li
- Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
- Correspondence: (J.L.); (J.Z.)
| | - Jun Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
- Correspondence: (J.L.); (J.Z.)
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8
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Malignant diagnosis and prognostic analysis of 89 GIST patients using preoperative FDG-PET. Sci Rep 2023; 13:2266. [PMID: 36755154 PMCID: PMC9908908 DOI: 10.1038/s41598-023-29038-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Accepted: 01/30/2023] [Indexed: 02/10/2023] Open
Abstract
There is no preoperative imaging accurately diagnose malignancy of gastrointestinal stromal tumor (GIST). To evaluate the usefulness of preoperative [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the malignant diagnosis and prognostic analysis of GIST. Eighty-nine consecutive patients with GIST who underwent curative surgery were reviewed retrospectively. PET scan was performed within 2-3 weeks before surgery and maximum standardized uptake values (SUVmax) were assessed for GIST. The relationship between prognostic factors and prognosis of GIST and SUVmax were evaluated. Tumor size, mitotic count, and Ki-67 index showed significant positive correlations with the SUVmax. When the cutoff value was set as SUVmax 5.68, the accuracy was 86.5% for the high-risk group, 76.4% for the recurrence group, and 73.0% for the death group. The group with SUVmax ≥ 5.68 demonstrated a significantly lower 10-year relapse-free survival than the group with SUVmax < 5.68 (55.2% vs. 98.2%, P < 0.001), while the group with SUVmax ≥ 5.68 demonstrated a significantly lower 10-year overall survival than the group with SUVmax < 5.68 (68.0% vs. 97.6%, P < 0.001). In GISTs, FDG-PET is a very useful imaging marker for the diagnosis of malignant GISTs, such as those in high-risk and poor-prognosis groups.
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9
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Wu C, Zhang X, Zeng Y, Wu R, Ding L, Xia Y, Chen Z, Zhang X, Wang X. [ 18F]FAPI-42 PET/CT versus [ 18F]FDG PET/CT for imaging of recurrent or metastatic gastrointestinal stromal tumors. Eur J Nucl Med Mol Imaging 2022; 50:194-204. [PMID: 36040490 DOI: 10.1007/s00259-022-05955-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Accepted: 08/23/2022] [Indexed: 11/29/2022]
Abstract
PURPOSE PET has been important for monitoring recurrence and metastasis of Gastrointestinal Stromal Tumors (GISTs) and the selection of therapeutic strategies. A significant portion of GISTs lesions show negative FDG uptake and therefore calls for more tumor-specific imaging biomarkers. This study compared the imaging performance of [18F]FAPI-42 PET/CT and [18F]FDG PET/CT in recurrent or metastatic gastrointestinal stromal tumors (R/M GISTs). METHODS This study retrospectively included 35 patients with R/M GISTs who underwent both FAPI PET/CT and FDG PET/CT. The definite diagnosis was confirmed by pathology or follow-up drug treatment effects. The differences in detection rates and tumor-to-background SUVmax ratio (SUVTBR) of different locations between dual-tracer PET/CT were compared. Factors including tumor size, degree of enhancement, type of gene mutation, and targeted treatment potentially influencing the uptake of both tracers were assessed. The excised lesions (n = 3) underwent immunohistochemical staining to verify FAP expression in the tissue. RESULTS A total of 106 lesions in 35 patients were identified, out of which 38/106 (35.8%) lesions (FAPI + /FDG -) were additionally detected by FAPI PET/CT as compared to that by FDG, including 26 liver metastases, ten peritoneal metastases, one gastrointestinal recurrence, and one bone metastasis. The positive detection rate of FAPI PET/CT for recurrent or metastatic GISTs was higher than that of FDG (80.2% vs. 53.8%, P< 0.001), especially in liver metastases (87.5% vs. 33.3%, P< 0.001). Moreover, the SUVTBR of liver metastases of GISTs in FAPI PET/CT was higher than that in FDG [2.4 (0.3 to 11.2) vs. 0.9 (0.3 to 6.5), P< 0.001]. The longest diameter of tumors in the FDG-positive group was higher than that of the FDG-negative group (P= 0.005); still, it did not differ between the FAPI-positive group and the FAPI-negative group. No difference in the degree of enhancement was observed between both tracers' positive and negative groups. Besides, the SUVTBR of FDG but not FAPI differed significantly among various gene mutations (P< 0.001) as well as the targeted therapy and no targeted therapy groups (P= 0.001). FAP was expressed in R/M GISTs, and the uptake of FAPI corresponded to the level of FAP expression. CONCLUSION In conclusion, FAPI for imaging of R/M GISTs could be superior to FDG, specifically for liver metastases. The uptake of FAPI could reflect the level of FAP expression, and it was independent of tumor size, degree of enhancement, type of gene mutation, and targeted therapy as compared to FDG.
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Affiliation(s)
- Chunhui Wu
- Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-Sen University, 58 2nd Zhongshan Road, Guangzhou, 510080, Guangdong Province, China
| | - Xinhua Zhang
- Center of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou , Guangdong Province, China
| | - Yu Zeng
- Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-Sen University, 58 2nd Zhongshan Road, Guangzhou, 510080, Guangdong Province, China
| | - Renbo Wu
- Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-Sen University, 58 2nd Zhongshan Road, Guangzhou, 510080, Guangdong Province, China
| | - Li Ding
- Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou , Guangdong Province, China
| | - Yanzhe Xia
- Department of Pharmacy, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou , Guangdong Province, China
| | - Zhifeng Chen
- Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-Sen University, 58 2nd Zhongshan Road, Guangzhou, 510080, Guangdong Province, China
| | - Xiangsong Zhang
- Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-Sen University, 58 2nd Zhongshan Road, Guangzhou, 510080, Guangdong Province, China.
| | - Xiaoyan Wang
- Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-Sen University, 58 2nd Zhongshan Road, Guangzhou, 510080, Guangdong Province, China.
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10
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Saito H, Kotake M, Ogawa J, Hashimoto M, Sawada K, Oshima M, Hada M, Kato Y, Oyama K, Hara T, Inaki N. Laparoscopic resection of a gastrointestinal stromal tumor that recurred more than 15 years after surgery using lighted ureteral catheters: A case report. Asian J Endosc Surg 2022; 15:397-400. [PMID: 34874113 DOI: 10.1111/ases.13018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 10/29/2021] [Accepted: 11/15/2021] [Indexed: 11/29/2022]
Abstract
A 69-year-old woman underwent abdominoperineal resection for a gastrointestinal stromal tumor (GIST) of the rectum 15 years ago. She received adjuvant chemotherapy for 8 years. Seven years later, abdominal computed tomography revealed a soft-tissue shadow in the left lower abdomen, and fluorodeoxyglucose uptake was observed at the same site on positron emission tomography. The recurrence of GIST was suspected, and laparoscopic resection was performed. Laparoscopy showed that the tumor was located at the retroperitoneum near to the descending colon and invaded the left ovarian vessels. It also made contact with the left ureter; however, lighted ureteral catheters enabled us to identify and preserve the left ureter. An immunohistochemical examination revealed the recurrence of GIST. Recurrence may become apparent 15 years or more after GIST surgery, and, thus, a long-term follow-up is required. Lighted ureteral catheters were useful for identifying the ureter and preventing ureteral injury in a recurrent case suspected of invading the ureter.
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Affiliation(s)
- Hiroshi Saito
- Department of Surgery, Koseiren Takaoka Hospital, Takaoka, Japan
| | - Masanori Kotake
- Department of Surgery, Koseiren Takaoka Hospital, Takaoka, Japan
| | - Jyunichi Ogawa
- Department of Surgery, Koseiren Takaoka Hospital, Takaoka, Japan
| | | | - Koichiro Sawada
- Department of Surgery, Koseiren Takaoka Hospital, Takaoka, Japan
| | - Masahiro Oshima
- Department of Surgery, Koseiren Takaoka Hospital, Takaoka, Japan
| | - Masahiro Hada
- Department of Surgery, Koseiren Takaoka Hospital, Takaoka, Japan
| | - Yosuke Kato
- Department of Surgery, Koseiren Takaoka Hospital, Takaoka, Japan
| | - Kaeko Oyama
- Department of Surgery, Koseiren Takaoka Hospital, Takaoka, Japan
| | - Takuo Hara
- Department of Surgery, Koseiren Takaoka Hospital, Takaoka, Japan
| | - Noriyuki Inaki
- Department of Gastrointestinal Surgery/Breast Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
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11
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Yang H, Shen C, Yin X, Cai Z, Wang Q, Zhang B. Clinicopathological features, clinical efficacy on 101 cases of rectal gastrointestinal stromal tumors, and the significance of neoadjuvant therapy. BMC Surg 2021; 21:400. [PMID: 34798856 PMCID: PMC8603575 DOI: 10.1186/s12893-021-01397-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 11/04/2021] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE To investigate the clinicopathological features and clinical efficacy among 101 cases of rectal gastrointestinal stromal tumors (GISTs) and to investigate the significance of imatinib mesylate (IM) neoadjuvant therapy. METHODS The clinicopathological features, treatment methods, perioperative data, and prognosis of the patients were summarized and analysed in 101 patients with rectal GISTs who received treatment in the Gastrointestinal Surgery of West China Hospital of Sichuan University and the Affiliated Hospital of Guizhou Medical University from August 2002 to November 2020 in China. RESULTS A total of 101 patients, including 64 males and 37 females, were aged from 22 to 79 years (55.4 ± 12.2 years). Among the 70 patients who underwent direct surgery, 8 were very low risk cases, 10 were low risk cases, 7 were intermediate risk cases, and 45 were high risk cases. Cox regression analysis showed that postoperative IM adjuvant treatment improved the disease-free survival (DFS) and overall survival (OS) of 52 intermediate and high risk patients. Among the 31 patients who received neoadjuvant therapy, the objective response rate (ORR) was 83.9% (26/31), and the disease control rate (DCR) reached 96.8% (30/31). Subgroup analysis was also conducted based on the tumour diameter. (1) Among the 36 patients with a diameter ≤ 5 cm, two patients received IM neoadjuvant therapy, while 34 patients received direct surgery. Neither univariate nor Cox regression analysis found that neoadjuvant therapy affected DFS and OS. (2) Among the 65 patients with a diameter > 5 cm, 29 received IM neoadjuvant therapy, and 36 received direct surgery. Patients who underwent neoadjuvant therapy had less blood loss (P = 0.022), shorter postoperative hospital stay (P = 0.001), increased anal retention rate (93.1% vs. 72.2%, P = 0.031), and decreased enterostomy rate (10.3% vs. 33.3%, P = 0.037) than those who underwent direct surgery. Cox regression analysis suggested that neoadjuvant therapy and postoperative IM adjuvant therapy improved DFS. CONCLUSION Rectal GISTs are relatively rare and highly malignant tumors. Postoperative oral IM therapy can improve the DFS and OS of intermediate and high risk patients. In patients with rectal GISTs with diameters > 5 cm, IM neoadjuvant therapy can improve anal retention rate, preserve the structure and function of the organs, reduce enterostomy rate, and improve prognosis.
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Affiliation(s)
- Hongxin Yang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China
| | - Chaoyong Shen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Xiaonan Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Zhaolun Cai
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Qian Wang
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China
| | - Bo Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
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In Vivo Biodistribution and Efficacy Evaluation of NeoB, a Radiotracer Targeted to GRPR, in Mice Bearing Gastrointestinal Stromal Tumor. Cancers (Basel) 2021; 13:cancers13051051. [PMID: 33801382 PMCID: PMC7958597 DOI: 10.3390/cancers13051051] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 02/22/2021] [Accepted: 02/24/2021] [Indexed: 12/11/2022] Open
Abstract
Simple Summary NeoB is undergoing evaluation as a novel theragnostic agent—that is, that it can be employed either for the diagnosis of tumor expressing gastrin-releasing peptide receptor (GRPR) using nuclear imaging, or for the therapy of such GRPR positive tumors using internal radiotherapy. The switch from diagnosis to therapy simply rely on the choice of the radioisotope that is coupled to NeoB. The aim of our study was to investigate—for the first time—the potency of NeoB for tumor therapy once labeled with the beta- emitter Lu-177. This study has been conducted in mice bearing human Gastrointestinal Stromal Tumors (GIST). [177Lu]Lu-NeoB was found to accumulate in the tumor, with only minimal retention in off-target organs. Consequently, mice treated with therapeutic doses of [177Lu]Lu-NeoB (37MBq/week for three weeks) exhibited tumor regression and therefore long term survival in comparison to the control untreated mice. Abstract NeoB is a radiotracer targeting the gastrin-releasing peptide receptor (GRPR), a G-protein–coupled receptor expressed in various cancers. The aim of the present study was to evaluate the biodistribution and efficacy of this new therapeutic agent in Gastrointestinal Stromal Tumors (GIST). Eighty-two SCID mice bearing GIST-882 tumors were employed. [177Lu]Lu-NeoB biodistribution was evaluated up to seven days by organ sampling (200 pmol/0.8 MBq, i.v.). For efficacy evaluation, mice received either saline, 400 pmol or 800 pmol of [177Lu]Lu-NeoB (37MBq, 1/w, 3 w, i.v.). SPECT/CT imaging was performed at 24 h, and tumor volume was determined up to 100 days. Elevated and specific [177Lu]Lu-NeoB uptake was found in the GIST tumor, as demonstrated by in vivo competition (19.1 ± 3.9 %ID/g vs. 0.3 ± 0.1 %ID/g at 4h). [177Lu]Lu-NeoB tumor retention (half-life of 40.2 h) resulted in elevated tumor-to-background ratios. Tumor volumes were significantly reduced in both treated groups (p < 0.01), even leading to complete tumor regression at the 400 pmol dose. [177Lu]Lu-NeoB exhibited excellent pharmacokinetics with elevated and prolonged tumor uptake and low uptake in non-target organs such as pancreas. The potential of this new theragnostic agent in different indications, including GIST, is under evaluation in the FIH [177Lu]Lu-NeoB clinical trial.
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13
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Enhancer of zeste homolog 2-mediated paired box 8 methylation promotes gastrointestinal stromal tumor progression through Wnt4 downregulation. Cancer Gene Ther 2021; 28:1162-1174. [PMID: 33479444 DOI: 10.1038/s41417-020-00266-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Accepted: 11/17/2020] [Indexed: 01/03/2023]
Abstract
Gastrointestinal stromal tumor (GIST) is a refractory malignant tumor without satisfactory therapy. In recent years, aberrant gene methylation has been highlighted as an inducer for tumor progression. In this study, we explored whether enhancer of zeste homolog 2 (EZH2)-mediated paired box 8 (PAX8) methylation affects GIST development through regulation of Wnt4. A total of 50 cases of GIST tissues were collected and the human GIST cell lines were cultured. PAX8 methylation was examined using MS-PCR. Following loss- and gain-function approaches, GIST cell proliferation, migration, invasion, and apoptosis were examined by CCK-8 assay, Transwell assay and flow cytometry. The expression of proliferation related factors and apoptosis related factors was determined. Finally, xenograft tumors in nude mice were observed to examine in vivo tumorigenicity of GIST cells. Downregulated PAX8 and upregulated EZH2 expression was found in GIST tissues. Overexpression of PAX8 or suppression of PAX8 methylation using DNA methyltransferase inhibitor 5-Aza-dC inhibited the proliferation, migration, and invasion of GIST cells while promoting their apoptosis (diminished PCNA, Ki67 and Bcl-2, elevated Bax, and cleaved caspase-3). EZH2 promoted PAX8 methylation to inhibit its expression. Downregulated PAX8 decreased Wnt4 expression to accelerate GIST progression both in vitro and in vivo. Collectively, EZH2 inhibits PAX8 expression by promoting its methylation, which thus downregulates Wnt4 expression, thereby promoting the development of GIST.
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14
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Rutkowski P, Ziętek M, Cybulska-Stopa B, Streb J, Głuszek S, Jankowski M, Łopacka-Szatan K, Las-Jankowska M, Hudziec P, Klimczak A, Olesiński T, Świtaj T, Koseła-Paterczyk H, Bylina E, Osuch C. The analysis of 3-year adjuvant therapy with imatinib in patients with high-risk molecular profiled gastrointestinal stromal tumors (GIST) treated in routine practice. Eur J Surg Oncol 2020; 47:1191-1195. [PMID: 32826113 DOI: 10.1016/j.ejso.2020.08.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Revised: 07/29/2020] [Accepted: 08/06/2020] [Indexed: 12/18/2022] Open
Abstract
INTRODUCTION The real-world data on adjuvant imatinib therapy in high-risk primary GIST are scarce. METHODS We have analysed the data of 107 consecutive patients with gastrointestinal stromal tumour (GIST) after resection treated with adjuvant imatinib (for planned 3 years with initial dose 400 mg daily, started not later than 4 months after operation) in 6 oncological centres in 2013-2018. All patients were required to have high risk of recurrence (at least 50% according to NCCN/AFIP criteria), known mutational status to exclude PDGFRA D842V mutants and KIT/PDGFRA-wild type cases from therapy without any further selection. Median follow-up time was 27 months. RESULTS The most common primary localization of GIST was small bowel (63 patients; 59%), followed by the stomach (40 patients; 37%). The majority of GIST cases harboured exon 11 KIT mutations (88 cases, 82%), 11 cases had exon 9 KIT mutations (10%), 8 had other KIT/PDGFRA mutations potentially sensitive to imatinib. Forty patients (37%) finished 3-year adjuvant imatinib therapy as planned, 48 (45%) still continue therapy, 5 (4.5%) patients had finished adjuvant therapy prematurely due to toxicity, 6 (6%) due to disease progression on treatment and 8 (7.5%) due to other reasons. The disease relapse was detected in 19 patients, of them in 5 cases in exon 9 KIT mutants (45%), and 14 cases in patients with exon 11 KIT mutations (11%) [p < 0.01]. Estimated 4-year relapse-free survival (RFS) rate is 78%. CONCLUSIONS The early results of adjuvant therapy with imatinib in routine practice outside clinical trials in high-risk mutation-driven GIST patients only confirm high efficacy of this therapy with better tolerability than in clinical trials. We found overrepresentation of exon 9 KIT mutants and ruptured tumors in a group of patients with disease relapse.
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Affiliation(s)
- Piotr Rutkowski
- Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
| | | | - Bożena Cybulska-Stopa
- Maria Sklodowska-Curie National Research Institute of Oncology, Cracow Branch, Cracow, Poland
| | | | | | | | | | | | | | - Anna Klimczak
- Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Tomasz Olesiński
- Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Tomasz Świtaj
- Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | | | - Elżbieta Bylina
- Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
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Ahmed M. Recent advances in the management of gastrointestinal stromal tumor. World J Clin Cases 2020; 8:3142-3155. [PMID: 32874969 PMCID: PMC7441252 DOI: 10.12998/wjcc.v8.i15.3142] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 05/26/2020] [Accepted: 07/14/2020] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal stromal tumor (GIST) is a rare but an important clinical entity seen in our clinical practice. It is the most common mesenchymal tumor of the gastrointestinal tract and most common malignancy of the small intestine. Although the exact prevalence of GIST is not known, the incidence of GIST has been increasing. GISTs arise from interstitial cells of Cajal. Most of the GISTs occur due to mutation in c-kit gene or platelet derived growth factor receptor alpha gene. 15% of GISTs do not have these mutations and they are called wild-type GISTs. Almost all GISTs express KIT receptor tyrosine kinase. Histologically, GISTs look like spindle cell tumors most of the time but they can be epitheloid or mixed type. The median size of GISTs varies from 2.7 cm to 8.9 cm. Clinically, patients with small GISTs remain asymptomatic but as the GIST size increases, patients present with various symptoms depending on the location of the GIST. Most of GISTs are located in the stomach or small bowel. Diagnosis is suspected on imaging and endoscopic studies, and confirmed by tissue acquisition with immunohistochemical staining. The aggressiveness of GISTs depends on the size, mitotic index and location. Surgical resection is the treatment of choice. But various endoscopic modalities of resection are increasingly being tried. Tyrosine kinase inhibitors are extremely useful in the management of large GISTs, unresectable GISTs and metastatic GISTs. Treatment options for metastatic GISTs also include radiotherapy, chemotherapy, hepatic artery embolization, chemoembolization and radiofrequency ablation.
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Affiliation(s)
- Monjur Ahmed
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Thomas Jefferson University, Philadelphia, PA 19107, United States
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Pagliuca F, Ronchi A, Cozzolino I, Montella M, Zito Marino F, Franco R. Mesenchymal neoplasms: Is it time for cytology? New perspectives for the pre-operative diagnosis of soft tissue tumors in the molecular era. Pathol Res Pract 2020; 216:152923. [PMID: 32303388 DOI: 10.1016/j.prp.2020.152923] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Revised: 03/08/2020] [Accepted: 03/14/2020] [Indexed: 12/26/2022]
Abstract
Soft tissue tumors comprise a great variety of common and rare entities with overlapping features. Their diagnosis is based on the evaluation of several histological parameters which are difficult to assess on small incisional biopsies. Useful diagnostic markers in the field of soft tissue tumors include: 1) molecular biomarkers detecting pathogenetically relevant, distinctive alterations; 2) immunohistochemical surrogate biomarkers of pathogenetically relevant, distinctive molecular alterations; 3) highly specific immunohistochemical biomarkers indicating tumor differentiation. Their introduction in clinical practice has revolutionized the pre-operative diagnosis of soft tissue tumors. Cytology has long been considered inadequate as a first-line approach in this setting. However, since the implementation of new immunohistochemical and molecular tests with high diagnostic specificity, fine needle aspiration cytology (FNAC) is starting to gain acceptance for the pre-operative assessment of soft tissue tumors. FNAC represents a versatile, poorly expensive and well-tolerated diagnostic strategy with relevant advantages over histological biopsies. Moreover, evidences suggest that, in expert hands, FNAC can also aim at a definite diagnosis, especially if a cell block is prepared, allowing the application of multiple ancillary techniques.
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Affiliation(s)
- Francesca Pagliuca
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Andrea Ronchi
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Immacolata Cozzolino
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Marco Montella
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Federica Zito Marino
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Renato Franco
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.
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Kosmidis CS, Alexandrou V, Koimtzis GD, Mantalovas S, Varsamis NC, Koulouris C, Taraboulous D, Leptopoulou A, Georgakoudi E, Sevva CD, Sapalidis K, Lypiridou S, Karayannopoulou G, Kesisoglou II. Treatment of a Gastrointestinal Stromal Tumor (GIST) Adherent to the Spleen and the Tail of the Pancreas: A Case Report. AMERICAN JOURNAL OF CASE REPORTS 2020; 21:e918278. [PMID: 32231176 PMCID: PMC7161921 DOI: 10.12659/ajcr.918278] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2019] [Revised: 02/17/2020] [Accepted: 12/16/2019] [Indexed: 12/24/2022]
Abstract
BACKGROUND Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal gastrointestinal tumors (GIT). Usually, they appear in patients ages 55-65 years, with no apparent difference between males and females. Their annual incidence is about 11-14 per 10⁶. They generally do not present with any prominent symptoms, appearing with the atypical symptoms of abdominal pain, weight loss, early satiety, and occasionally bleeding. Adequate surgical treatment involves sphenoid resection of the tumor within clear margins. If adjacent organs are involved, en bloc resection is the procedure of choice. CASE REPORT A 62-year-old male patient presented to the Emergency Department complaining of melena for 1 week. He underwent gastroscopy, colonoscopy and abdominal computed tomography scan, which revealed a large, exophytic, lobular mass (12.6×9.7×12 cm) of the greater curvature of the stomach. The patient underwent en bloc sphenoid gastrectomy, splenectomy, and caudal pancreatectomy. The histopathologic examination revealed findings compatible with a gastrointestinal stromal tumor located at the stomach, with low-grade malignancy (G1) and T4N0 according to TNM classification. He was discharged from the hospital on the 7th postoperative day. CONCLUSIONS GISTs are uncommon tumors of the gastrointestinal system that usually do not invade neighboring organs or develop distant metastases; therefore, local resection is usually the treatment of choice. However, in cases of large GISTs that are adherent to neighboring organs, en bloc resection and resection of adjacent organs may be inevitable.
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Affiliation(s)
| | - Vyron Alexandrou
- 3 Surgical Department, University Hospital of Thessaloniki AHEPA, Thessaloniki, Greece
| | - Georgios D. Koimtzis
- 3 Surgical Department, University Hospital of Thessaloniki AHEPA, Thessaloniki, Greece
| | - Stylianos Mantalovas
- 3 Surgical Department, University Hospital of Thessaloniki AHEPA, Thessaloniki, Greece
| | - Nikolaos C. Varsamis
- 3 Surgical Department, University Hospital of Thessaloniki AHEPA, Thessaloniki, Greece
| | - Charilaos Koulouris
- 3 Surgical Department, University Hospital of Thessaloniki AHEPA, Thessaloniki, Greece
| | | | - Ariadne Leptopoulou
- University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Eleni Georgakoudi
- University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Christina D. Sevva
- University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | | | - Sophia Lypiridou
- Department of Pathology, University Hospital of Thessaloniki AHEPA, Thessaloniki, Greece
| | | | - Isaac I. Kesisoglou
- 3 Surgical Department, University Hospital of Thessaloniki AHEPA, Thessaloniki, Greece
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Yasuda T, Eto K, Yoshida N, Iwagami S, Hiyoshi Y, Nagai Y, Iwatsuki M, Ishimoto T, Baba Y, Miyamoto Y, Shiota T, Mikami Y, Baba H. Multiple heterochronic gastrointestinal stromal tumors in the stomach detected 6 years after resection: a case report. Surg Case Rep 2020; 6:48. [PMID: 32146688 PMCID: PMC7060937 DOI: 10.1186/s40792-020-00812-1] [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: 01/11/2020] [Accepted: 02/26/2020] [Indexed: 11/16/2022] Open
Abstract
Background To date, only a few cases of multiple GISTs with different clones in different organs have been published. However, a case of multiple GISTs with different clones occurring in a single organ has never been reported. Case presentation A 41-year-old patient underwent laparoscopic partial gastrectomy for gastric gastrointestinal stromal tumor (GIST) in 2012. The pathological findings showed high-risk characteristics for recurrence, so he received adjuvant therapy with imatinib for 3 years. In 2018, 3 years after completing the adjuvant therapy, tumor lesions at residual gastric cardia were incidentally identified by follow-up computed tomography (CT). The pathological findings of the tumor biopsy revealed gastric GIST. He underwent secondary laparoscopic partial gastrectomy and was diagnosed with high-risk GIST. Adjuvant therapy with imatinib was restarted immediately. The two gastric GISTs had the same exon 11 mutations in the c-kit gene, but they had different missense mutations. This molecular heterogeneity suggested that they were derived from different origins. Conclusion We reported a multiple heterochronic GIST in the stomach detected 6 years after resection. There may be a possibility that another heterochronic GIST will occur in the remnant stomach in the future, so close follow-up will be needed.
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Affiliation(s)
- Tadahito Yasuda
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Kojiro Eto
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Naoya Yoshida
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Shiro Iwagami
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yukiharu Hiyoshi
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Youhei Nagai
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Masaaki Iwatsuki
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Takatsugu Ishimoto
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yoshifumi Baba
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yuji Miyamoto
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Takuya Shiota
- Department of Diagnostic Pathology, Kumamoto University Hospital, Kumamoto, Japan, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yoshiki Mikami
- Department of Diagnostic Pathology, Kumamoto University Hospital, Kumamoto, Japan, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Hideo Baba
- Department of Gastroenterology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
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Fernández JA, Frutos MD, Ruiz-Manzanera JJ, Navarro A, Torres G, Soria T. Gastrointestinal Stromal Tumors After Laparoscopic Gastric Bypass for Morbid Obesity: a Diagnostic and Therapeutic Challenge. Obes Surg 2019; 29:2618-2621. [DOI: 10.1007/s11695-019-03944-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
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