1
|
Judson I, Jones RL, Wong NACS, Dileo P, Bulusu R, Smith M, Almond M. Gastrointestinal stromal tumour (GIST): British Sarcoma Group clinical practice guidelines. Br J Cancer 2025; 132:1-10. [PMID: 38840030 PMCID: PMC11723931 DOI: 10.1038/s41416-024-02672-0] [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: 01/09/2024] [Revised: 03/21/2024] [Accepted: 03/25/2024] [Indexed: 06/07/2024] Open
Abstract
BACKGROUND British Sarcoma Group guidelines for the management of GIST were initially informed by those published by the European Society of Clinical Oncology. This update was written by a group of experts to includes a discussion of the highlight improvements in our knowledge of the disease and recent treatment developments. The guidelines include sections on Incidence, Aetiology, Diagnosis, including risk assessment, Treatment and Follow-up. METHODS A careful review of the literature was performed to ensure that wherever possible recommendations are supported by the results of clinical trials or substantive retrospective reports. Areas of uncertainty are indicated appropriately. CONCLUSION Guidelines represent a consensus view of current best clinical practice. Where appropriate, key recommendations are given and the levels of evidence and strength of recommendation gradings are those used by the European Society for Medical Oncology (ESMO).
Collapse
Affiliation(s)
- Ian Judson
- The Institute of Cancer Research, London, UK.
| | | | | | | | | | - Myles Smith
- Royal Marsden NHS Foundation Trust, London, UK
| | - Max Almond
- Birmingham University Hospitals, Birmingham, UK
| |
Collapse
|
2
|
Hirota S, Tateishi U, Nakamoto Y, Yamamoto H, Sakurai S, Kikuchi H, Kanda T, Kurokawa Y, Cho H, Nishida T, Sawaki A, Ozaka M, Komatsu Y, Naito Y, Honma Y, Takahashi F, Hashimoto H, Udo M, Araki M, Nishidate S. English version of Japanese Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST) issued by the Japan Society of Clinical Oncology. Int J Clin Oncol 2024; 29:647-680. [PMID: 38609732 PMCID: PMC11130037 DOI: 10.1007/s10147-024-02488-1] [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: 12/27/2023] [Accepted: 02/12/2024] [Indexed: 04/14/2024]
Abstract
The Japan Society of Clinical Oncology Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST) have been published in accordance with the Minds Manual for Guideline Development 2014 and 2017. A specialized team independent of the working group for the revision performed a systematic review. Since GIST is a rare type of tumor, clinical evidence is not sufficient to answer several clinical and background questions. Thus, in these guidelines, we considered that consensus among the experts who manage GIST, the balance between benefits and harms, patients' wishes, medical economic perspective, etc. are important considerations in addition to the evidence. Although guidelines for the treatment of GIST have also been published by the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO), there are some differences between the treatments proposed in those guidelines and the treatments in the present guidelines because of the differences in health insurance systems among countries.
Collapse
Affiliation(s)
- Seiichi Hirota
- Department of Surgical Pathology, Hyogo Medical University School of Medicine, Nishinomiya, Japan.
| | - Ukihide Tateishi
- Department of Diagnostic Radiology and Nuclear Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yuji Nakamoto
- Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hidetaka Yamamoto
- Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Shinji Sakurai
- Department of Diagnostic Pathology, Japan Community Healthcare Organization Gunma Central Hospital, Maebashi, Japan
| | - Hirotoshi Kikuchi
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Tatsuo Kanda
- Department of Gastroenterology, Southern TOHOKU General Hospital, Koriyama, Japan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Haruhiko Cho
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Toshirou Nishida
- Department of Surgery, Japan Community Healthcare Organization Osaka Hospital, Osaka, Japan
| | - Akira Sawaki
- Department of Medical Oncology, Shonan Kamakura General Hospital, Kamakura, Japan
| | - Masato Ozaka
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yoshito Komatsu
- Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Sapporo, Japan
| | - Yoichi Naito
- Department of General Internal Medicine, National Cancer Center Hospital East, Kashiwa, Japan
| | - Yoshitaka Honma
- Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Fumiaki Takahashi
- Department of Information Science, Iwate Medical University, Morioka, Japan
| | | | - Midori Udo
- Nursing Department, Osaka Police Hospital, Osaka, Japan
| | - Minako Araki
- Association of Chubu GIST Patients and Their Families, Nagoya, Japan
| | | |
Collapse
|
3
|
Hompland I, Boye K, Wiedswang AM, Papakonstantinou A, Røsok B, Joensuu H, Bruland Ø. Discontinuation of imatinib in patients with oligometastatic gastrointestinal stromal tumour who are in complete radiological remission: a prospective multicentre phase II study. Acta Oncol 2024; 63:288-293. [PMID: 38712513 PMCID: PMC11332466 DOI: 10.2340/1651-226x.2024.39851] [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: 01/17/2024] [Accepted: 03/16/2024] [Indexed: 05/08/2024]
Abstract
INTRODUCTION Metastatic gastrointestinal stromal tumour (GIST) is considered incurable, and life-long treatment with tyrosine kinase inhibitors is recommended. We investigated whether selected patients with metastatic GIST may remain in durable remission despite imatinib discontinuation. PATIENTS In this 1-group, prospective, multicentre phase II trial selected patients with oligometastatic (≤3 metastases) GIST discontinued imatinib treatment. Eligible patients had been treated with imatinib >5 years without progression and had no radiologically detectable metastases after metastasectomy, radiofrequency ablation (RFA) or complete response to imatinib. The primary endpoint was progression-free survival (PFS) 3-years after stopping imatinib. Overall survival (OS) and quality of life (QoL) were secondary endpoints. RESULTS The trial closed prematurely due to slow accrual. Between January 5, 2017, and June 5, 2019, 13 patients were enrolled, of whom 12 discontinued imatinib. The median follow-up time was 55 months (range, 36 to 69) after study entry. Five (42%) of the 12 eligible patients remained progression free, and seven (58%) progressed with a median time to progression 10 months. Median PFS was 23 months and the estimated 3-year PFS 41%. Six of the seven patients who progressed restarted imatinib, and all six responded. Three-year OS was 100%, and all patients were alive at the time of the study analysis. QoL measured 5 and 11 months after discontinuation of imatinib demonstrated improvement compared to the baseline. INTERPRETATION A substantial proportion of selected patients with oligometastatic GIST treated with imatinib and metastasis surgery/RFA may remain disease-free for ≥3 years with improved QoL after stopping of imatinib.
Collapse
Affiliation(s)
- Ivar Hompland
- Department of Oncology, Oslo University Hospital, Oslo, Norway.
| | - Kjetil Boye
- Department of Oncology, Oslo University Hospital, Oslo, Norway
| | | | - Andri Papakonstantinou
- Department of Breast Cancer, Endocrine Tumors and Sarcoma, Karolinska University Hospital, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden
| | - Bård Røsok
- Department of Hepato-Pancreatic-Biliary Surgery, Oslo University Hospital, Oslo, Norway
| | - Heikki Joensuu
- Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Øyvind Bruland
- Department of Oncology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| |
Collapse
|
4
|
De Luca I, Miliziano D, Guerra G, Colombo R, Morosi C, Sposito C, Fiore M, Venturelli E, Sangalli C, Casali PG, Cavalleri A, Fumagalli E. Hemodialysis and imatinib: Plasma levels, efficacy and tolerability in a patient with metastatic GIST - Case report. Heliyon 2024; 10:e28494. [PMID: 38596050 PMCID: PMC11002597 DOI: 10.1016/j.heliyon.2024.e28494] [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: 11/26/2023] [Revised: 03/13/2024] [Accepted: 03/20/2024] [Indexed: 04/11/2024] Open
Abstract
Purpose To study plasma levels, efficacy and tolerability of imatinib in a patient affected by metastatic GIST treated with oral Imatinib and undergoing hemodialysis. Patients and methods The patient suffered from metastatic GIST to the liver having a mutation of exon 9 of KIT. He was on hemodialysis and received first-line treatment with imatinib 400 mg/day. Results The overall mean plasma level of imatinib was 1875,4 ng/ml pre-dialysis, 1553,0 ng/ml post-dialysis and 1998,1 ng/ml post-24h. In red blood cells the overall mean level of imatinib was 619,5 ng/ml pre-dialysis, 484,9 ng/ml post-dialysis and 663,1 ng/ml post-24h. The plasma level of nor-imatinib/imatinib was 16,2% pre-dialysis, 15,6% post-dialysis and 16,4% post-24h. Comparing our findings regarding levels of imatinib in plasma and RBC, we found a statistically significant difference between pre-dialysis and post-dialysis (respectively p < 0,001 and p = 0,002), post-dialysis and post-24h (both p < 0,001), pre-dialysis and post-24h (respectively p = 0.035 and p = 0,042). Ultimately, regarding nor-imatinib/imatinib in plasma, we did not find any statistically significant difference between pre-dialysis and post-dialysis (p = 0,091), post-dialysis and post-24h (p = 0,091), pre-dialysis and post-24h (p = 0.903). Currently the patient is receiving oral imatinib 400 mg/day with radiological evidence of response. Conclusion In this case, hemodialysis did not affect significantly imatinib plasma levels. The statistically significant difference between pre- and post-dialysis can be explained by the fact that dialysis may likely contribute to a small portion of the normal metabolism of imatinib. The evaluation of imatinib levels in RBC and of its main metabolite in plasma also suggests that hemodialysis did not affect other aspects of the elimination of the drug.
Collapse
Affiliation(s)
- Ida De Luca
- Fondazione IRCCS Istituto Nazionale dei Tumori, Oncologia medica 2 Tumori mesenchimali dell'adulto, Milan, Italy
| | - Daniela Miliziano
- Fondazione IRCCS Istituto Nazionale dei Tumori, Oncologia medica 2 Tumori mesenchimali dell'adulto, Milan, Italy
| | - Giulia Guerra
- Fondazione IRCCS Istituto Nazionale dei Tumori, s.c. Epidemiologia e Prevenzione, Milan, Italy
| | | | - Carlo Morosi
- Fondazione IRCCS Istituto Nazionale dei Tumori, Radiologia diagnostica ed interventistica, Milan, Italy
| | - Carlo Sposito
- Fondazione IRCCS Istituto Nazionale dei Tumori, Chirurgia dell'apparato digerente e Trapianto di Fegato, Milan, Italy
| | - Marco Fiore
- Fondazione IRCCS Istituto Nazionale dei Tumori, Dipartimento di Chirurgia, Milan, Italy
| | - Elisabetta Venturelli
- Fondazione IRCCS Istituto Nazionale dei Tumori, s.s.d. Ricerca Nutrizionale e Metabolomica, Milan, Italy
| | - Claudia Sangalli
- Fondazione IRCCS Istituto Nazionale dei Tumori, Radioterapia, Milan, Italy
| | - Paolo G. Casali
- Fondazione IRCCS Istituto Nazionale dei Tumori & University of Milan, Milan, Italy
| | - Adalberto Cavalleri
- Fondazione IRCCS Istituto Nazionale dei Tumori, s.c. Epidemiologia e Prevenzione, Milan, Italy
| | - Elena Fumagalli
- Fondazione IRCCS Istituto Nazionale dei Tumori, Oncologia medica 2 Tumori mesenchimali dell'adulto, Milan, Italy
| |
Collapse
|
5
|
Musa J, Kochendoerfer SM, Willis F, Sauerteig C, Harnoss JM, Rompen IF, Grünewald TGP, Al-Saeedi M, Schneider M, Harnoss JC. The GIST of it all: management of gastrointestinal stromal tumors (GIST) from the first steps to tailored therapy. A bibliometric analysis. Langenbecks Arch Surg 2024; 409:95. [PMID: 38480587 PMCID: PMC10937785 DOI: 10.1007/s00423-024-03271-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 02/24/2024] [Indexed: 03/17/2024]
Abstract
PURPOSE Improvement of patient care is associated with increasing publication numbers in biomedical research. However, such increasing numbers of publications make it challenging for physicians and scientists to screen and process the literature of their respective fields. In this study, we present a comprehensive bibliometric analysis of the evolution of gastrointestinal stromal tumor (GIST) research, analyzing the current state of the field and identifying key open questions going beyond the recent advantages for future studies to assess. METHODS Using the Web of Science Core Collection, 5040 GIST-associated publications in the years 1984-2022 were identified and analyzed regarding key bibliometric variables using the Bibliometrix R package and VOSviewer software. RESULTS GIST-associated publication numbers substantially increased over time, accentuated from year 2000 onwards, and being characterized by multinational collaborations. The main topic clusters comprise surgical management, tyrosine kinase inhibitor (TKI) development/treatment, diagnostic workup, and molecular pathophysiology. Within all main topic clusters, a significant progress is reflected by the literature over the years. This progress ranges from conventional open surgical techniques over minimally invasive, including robotic and endoscopic, resection techniques to increasing identification of specific functional genetic aberrations sensitizing for newly developed TKIs being extensively investigated in clinical studies and implemented in GIST treatment guidelines. However, especially in locally advanced, recurrent, and metastatic disease stages, surgery-related questions and certain specific questions concerning (further-line) TKI treatment resistance were infrequently addressed. CONCLUSION Increasing GIST-related publication numbers reflect a continuous progress in the major topic clusters of the GIST research field. Especially in advanced disease stages, questions related to the interplay between surgical approaches and TKI treatment sensitivity should be addressed in future studies.
Collapse
Affiliation(s)
- Julian Musa
- Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
- Department of General, Visceral, Thoracic, and Transplantation Surgery, University Hospital Giessen and Marburg, Giessen, Germany
- Division of Translational Pediatric Sarcoma Research (B410), German Cancer Research Center (DKFZ), Heidelberg, Germany
- Hopp-Children's Cancer Center (KiTZ), Heidelberg, Germany
| | - Sarah M Kochendoerfer
- Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
| | - Franziska Willis
- Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
- Department of General, Visceral, Thoracic, and Transplantation Surgery, University Hospital Giessen and Marburg, Giessen, Germany
| | - Christine Sauerteig
- Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
| | - Jonathan M Harnoss
- Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
- Department of General, Visceral, Thoracic, and Transplantation Surgery, University Hospital Giessen and Marburg, Giessen, Germany
| | - Ingmar F Rompen
- Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
| | - Thomas G P Grünewald
- Division of Translational Pediatric Sarcoma Research (B410), German Cancer Research Center (DKFZ), Heidelberg, Germany
- Hopp-Children's Cancer Center (KiTZ), Heidelberg, Germany
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | - Mohammed Al-Saeedi
- Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
| | - Martin Schneider
- Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
- Department of General, Visceral, Thoracic, and Transplantation Surgery, University Hospital Giessen and Marburg, Giessen, Germany
| | - Julian-C Harnoss
- Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany.
| |
Collapse
|
6
|
D’Ambrosio L, Fumagalli E, De Pas TM, Nannini M, Bertuzzi A, Carpano S, Boglione A, Buonadonna A, Comandini D, Gasperoni S, Vincenzi B, Brunello A, Badalamenti G, Maccaroni E, Baldi GG, Merlini A, Mogavero A, Ligorio F, Pennacchioli E, Conforti F, Manessi G, Aliberti S, Tolomeo F, Fiore M, Sbaraglia M, Dei Tos AP, Stacchiotti S, Pantaleo MA, Gronchi A, Grignani G. Guideline-Based Follow-Up Outcomes in Patients With Gastrointestinal Stromal Tumor With Low Risk of Recurrence: A Report From the Italian Sarcoma Group. JAMA Netw Open 2023; 6:e2341522. [PMID: 37930700 PMCID: PMC10628737 DOI: 10.1001/jamanetworkopen.2023.41522] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 09/25/2023] [Indexed: 11/07/2023] Open
Abstract
Importance Gastrointestinal stromal tumor (GIST) follow-up is recommended by international guidelines, but data on the role of follow-up in patients with low relapse risk are missing. For these patients, the potential benefit of anticipating recurrence detection should be weighed against psychological burden and radiologic examination loads in terms of costs and radiation exposure. Objective To evaluate the outcomes of guideline-based follow-up in low-risk GIST. Design, Setting, and Participants This multi-institutional retrospective cohort study involving Italian Sarcoma Group reference institutions evaluated patients with GIST who underwent surgery between January 2001 and June 2019. Median follow-up time was 69.2 months. Data analysis was performed from December 15, 2022, to March 20, 2023. Patients with GIST at low risk according to Armed Forces Institute of Pathology criteria were included provided adequate clinical information was available: primary site, size, mitotic index, surgical margins, and 2 or more years of follow-up. Exposures All patients underwent follow-up according to European Society for Medical Oncology (ESMO) guidelines. Main Outcomes and Measures The primary outcome was the number of tests needed to identify a relapse according to ESMO guidelines follow-up plan. Secondary outcomes included relapse rate, relapse timing, disease-free survival (DFS), overall survival (OS), GIST-specific survival (GIST-SS), postrelapse OS, secondary tumor rates, and theoretical ionizing radiation exposure. An exploratory end point, new follow-up schedule proposal for patients with low-risk GIST according to the observed results, was also assessed. Results A total of 737 patients (377 men [51.2%]; median age at diagnosis, 63 [range, 18-86] years) with low-risk GIST were included. Estimated 5-year survival rates were 95.5% for DFS, 99.8% for GIST-SS, and 96.1% for OS. Estimated 10-year survival rates were 93.4% for DFS, 98.1% for GIST-SS, and 91.0% for OS. Forty-two patients (5.7%) experienced disease relapse during follow-up (9 local, 31 distant, 2 both), of which 9 were detected after 10 or more years. This translated into approximately 1 relapse detected for every 170 computed tomography scans performed, with a median radiation exposure of 80 (IQR, 32-112) mSv per patient. Nongastric primary tumor (hazard ratio [HR], 2.09; 95% CI, 1.14-3.83; P = .02), and KIT mutation (HR, 2.77; 95% CI, 1.05-7.27; P = .04) were associated with a higher risk of relapse. Second tumors affected 187 of 737 patients (25%), of which 56 were detected during follow-up and represented the primary cause of death in these patients. Conclusions and Relevance In this cohort study on patients affected by low-risk GISTs, the risk of relapse was low despite a follow-up across 10 or more years. These data suggest the need to revise follow-up schedules to reduce the anxiety, costs, and radiation exposure of currently recommended follow-up strategy.
Collapse
Affiliation(s)
- Lorenzo D’Ambrosio
- Department of Medical Oncology, University of Turin, Turin, Italy
- San Luigi Gonzaga University Hospital, Orbassano, Italy
| | - Elena Fumagalli
- Medical Oncology Unit 2, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
| | - Tommaso Martino De Pas
- Medical Oncology Division, Cliniche Humanitas Gavazzeni, Bergamo, Italy
- Previously at Unit of Sarcomas and Thymomas, European Institute of Oncology, Milan, Italy
| | - Margherita Nannini
- Oncology Unit. Department of Medical and Surgical Sciences, University of Bologna, 40138, Bologna, Italy
| | - Alexia Bertuzzi
- Medical Oncology, Humanitas Cancer Center, Rozzano (MI), Italy
| | - Silvia Carpano
- Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | | | - Angela Buonadonna
- Sarcoma and gastrointestinal tumors Unit, Centro di Riferimento Oncologico, Aviano, Italy
| | - Danila Comandini
- Medical Oncology 1, Ospedale Policlinico San Martino, University of Genova, Genova, Italy
| | - Silvia Gasperoni
- Clinical Oncology Unit, Oncology Department and Robotic Surgery, AOU Careggi, Florence, Italy
| | - Bruno Vincenzi
- Medical Oncology, Università Campus Bio-Medico, Rome, Italy
| | | | - Giuseppe Badalamenti
- Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy
| | - Elena Maccaroni
- Department of Oncology, Azienda Ospedaliero-Universitaria delle Marche, 60126 Ancona, Italy
| | | | - Alessandra Merlini
- Department of Medical Oncology, University of Turin, Turin, Italy
- Sarcoma Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo (TO), Italy
| | - Andrea Mogavero
- Department of Medical Oncology, University of Turin, Turin, Italy
- Sarcoma Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo (TO), Italy
| | - Francesca Ligorio
- Medical Oncology Unit 2, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
| | | | - Fabio Conforti
- Medical Oncology Division, Cliniche Humanitas Gavazzeni, Bergamo, Italy
- Previously at Unit of Sarcomas and Thymomas, European Institute of Oncology, Milan, Italy
| | - Giulia Manessi
- Department of Medical Oncology, University of Turin, Turin, Italy
- Sarcoma Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo (TO), Italy
| | - Sandra Aliberti
- Sarcoma Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo (TO), Italy
| | - Francesco Tolomeo
- Sarcoma Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo (TO), Italy
| | - Marco Fiore
- Sarcoma Service, Surgical Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
| | - Marta Sbaraglia
- Department of Medicine, University of Padua School of Medicine, Padua, Italy
| | | | | | - Maria Abbondanza Pantaleo
- Oncology Unit. Department of Medical and Surgical Sciences, University of Bologna, 40138, Bologna, Italy
| | - Alessandro Gronchi
- Sarcoma Service, Surgical Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
| | - Giovanni Grignani
- Sarcoma Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo (TO), Italy
- Medical Oncology 2, AOU Città della Salute e della Scienza di Torino, Turin, Italy
| |
Collapse
|
7
|
Brink P, Kalisvaart GM, Schrage YM, Mohammadi M, Ijzerman NS, Bleckman RF, Wal T, de Geus-Oei LF, Hartgrink HH, Grunhagen DJ, Verhoef C, Sleijfer S, Oosten AW, Been LB, van Ginkel RJ, Reyners AKL, Bonenkamp HJ, Desar IME, Gelderblom H, van Houdt WJ, Steeghs N, Fiocco M, van der Hage JA. Local treatment in metastatic GIST patients: A multicentre analysis from the Dutch GIST Registry. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:106942. [PMID: 37246093 DOI: 10.1016/j.ejso.2023.05.017] [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: 03/07/2023] [Revised: 05/12/2023] [Accepted: 05/22/2023] [Indexed: 05/30/2023]
Abstract
BACKGROUND The added value of local treatment in selected metastatic GIST patients is unclear. This study aims to provide insight into the usefulness of local treatment in metastatic GIST by use of a survey study and retrospective analyses in a clinical database. METHODS A survey study was conducted among clinical specialists to select most relevant characteristics of metastatic GIST patients considered for local treatment, defined as elective surgery or ablation. Patients were selected from the Dutch GIST Registry. A multivariate Cox-regression model for overall survival since time of diagnosis of metastatic disease was estimated with local treatment as a time-dependent variable. An additional model was estimated to assess prognostic factors since local treatment. RESULTS The survey's response rate was 14/16. Performance status, response to TKIs, location of active disease, number of lesions, mutation status, and time between primary diagnosis and metastases, were regarded the 6 most important characteristics. Of 457 included patients, 123 underwent local treatment, which was associated with better survival after diagnosis of metastases (HR = 0.558, 95%CI = 0.336-0.928). Progressive disease during systemic treatment (HR = 3.885, 95%CI = 1.195-12.627) and disease confined to the liver (HR = 0.269, 95%CI = 0.082-0.880) were associated with worse and better survival after local treatment, respectively. CONCLUSION Local treatment is associated with better survival in selected patients with metastatic GIST. Locally treated patients with response to TKIs and disease confined to the liver have good clinical outcome. These results might be considered for tailoring treatment, but should be interpreted with care because only specific patients are provided with local treatment in this retrospective study.
Collapse
Affiliation(s)
- Pien Brink
- Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
| | | | - Yvonne M Schrage
- Department of Surgery, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Mahmoud Mohammadi
- Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands
| | - Nikki S Ijzerman
- Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Roos F Bleckman
- Department of Medical Oncology, University Medical Centre Groningen, Groningen, the Netherlands
| | - Tom Wal
- Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Lioe-Fee de Geus-Oei
- Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands; Biomedical Photonic Imaging Group, University of Twente, Enschede, the Netherlands
| | - Henk H Hartgrink
- Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
| | - Dirk J Grunhagen
- Department of Surgery, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Cornelis Verhoef
- Department of Surgery, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Stefan Sleijfer
- Department of Medical Oncology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Astrid W Oosten
- Department of Medical Oncology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Lukas B Been
- Department of Surgery, University Medical Centre Groningen, Groningen, the Netherlands
| | - Robert J van Ginkel
- Department of Surgery, University Medical Centre Groningen, Groningen, the Netherlands
| | - An K L Reyners
- Department of Medical Oncology, University Medical Centre Groningen, Groningen, the Netherlands
| | - Han J Bonenkamp
- Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Ingrid M E Desar
- Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Hans Gelderblom
- Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands
| | - Winan J van Houdt
- Department of Surgery, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Neeltje Steeghs
- Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Marta Fiocco
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands; Mathematical Institute, Leiden University, Leiden, the Netherlands
| | - Jos A van der Hage
- Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
| |
Collapse
|
8
|
Efthymiou E, Charalampopoulos G, Velonakis G, Grigoriadis S, Kelekis A, Kelekis N, Filippiadis D. Ablative Techniques for Sarcoma Metastatic Disease: Current Role and Clinical Applications. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:485. [PMID: 36984486 PMCID: PMC10054887 DOI: 10.3390/medicina59030485] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 02/13/2023] [Accepted: 02/21/2023] [Indexed: 03/06/2023]
Abstract
Sarcomas are heterogenous mesenchymal neoplasms with more than 80 different histologic subtypes. Lung followed by liver and bone are the most common sites of sarcoma metastatic disease. Ablative techniques have been recently added as an additional alternative curative or palliative therapeutic tool in sarcoma metastatic disease. When compared to surgery, ablative techniques are less invasive therapies which can be performed even in non-surgical candidates and are related to decreased recovery time as well as preservation of the treated organ's long-term function. Literature data upon ablative techniques for sarcoma metastatic disease are quite heterogeneous and variable regarding the size and the number of the treated lesions and the different histologic subtypes of the original soft tissue or bone sarcoma. The present study focuses upon the current role of minimal invasive thermal ablative techniques for the management of metastatic sarcoma disease. The purpose of this review is to present the current minimally invasive ablative techniques in the treatment of metastatic soft tissue and bone sarcoma, including local control and survival rates.
Collapse
Affiliation(s)
| | | | | | | | | | | | - Dimitrios Filippiadis
- 2nd Department of Radiology, University General Hospital “ATTIKON”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece
| |
Collapse
|
9
|
Surgical Options for Peritoneal Surface Metastases from Digestive Malignancies-A Comprehensive Review. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59020255. [PMID: 36837456 PMCID: PMC9960111 DOI: 10.3390/medicina59020255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/25/2023] [Accepted: 01/25/2023] [Indexed: 01/31/2023]
Abstract
The peritoneum is a common site for the dissemination of digestive malignancies, particularly gastric, colorectal, appendix, or pancreatic cancer. Other tumors such as cholangiocarcinomas, digestive neuroendocrine tumors, or gastrointestinal stromal tumors (GIST) may also associate with peritoneal surface metastases (PSM). Peritoneal dissemination is proven to worsen the prognosis of these patients. Cytoreductive surgery (CRS), along with systemic chemotherapy, have been shown to constitute a survival benefit in selected patients with PSM. Furthermore, the association of CRS with hyperthermic intraperitoneal chemotherapy (HIPEC) seems to significantly improve the prognosis of patients with certain types of digestive malignancies associated with PSM. However, the benefit of CRS with HIPEC is still controversial, especially due to the significant morbidity associated with this procedure. According to the results of the PRODIGE 7 trial, CRS for PSM from colorectal cancer (CRC) achieved overall survival (OS) rates higher than 40 months, but the addition of oxaliplatin-based HIPEC failed to improve the long-term outcomes. Furthermore, the PROPHYLOCHIP and COLOPEC trials failed to demonstrate the effectiveness of oxaliplatin-based HIPEC for preventing peritoneal metastases development in high-risk patients operated for CRC. In this review, we discuss the limitations of these studies and the reasons why these results are not sufficient to refute this technique, until future well-designed trials evaluate the impact of different HIPEC regimens. In contrast, in pseudomyxoma peritonei, CRS plus HIPEC represents the gold standard therapy, which is able to achieve 10-year OS rates ranging between 70 and 80%. For patients with PSM from gastric carcinoma, CRS plus HIPEC achieved median OS rates higher than 40 months after complete cytoreduction in patients with a peritoneal cancer index (PCI) ≤6. However, the data have not yet been validated in randomized clinical trials. In this review, we discuss the controversies regarding the most efficient drugs that should be used for HIPEC and the duration of the procedure. We also discuss the current evidence and controversies related to the benefit of CRS (and HIPEC) in patients with PSM from other digestive malignancies. Although it is a palliative treatment, pressurized intraperitoneal aerosolized chemotherapy (PIPAC) significantly increases OS in patients with unresectable PSM from gastric cancer and represents a promising approach for patients with PSM from other digestive cancers.
Collapse
|
10
|
Yue L, Sun Y, Hu M, Hu W. Might Patients with Metastatic Gastrointestinal Stromal Tumors Benefit from Operative Management? A Population-Based Retrospective Study. BIOMED RESEARCH INTERNATIONAL 2022; 2022:9432410. [PMID: 36119927 PMCID: PMC9473875 DOI: 10.1155/2022/9432410] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 08/02/2022] [Accepted: 08/08/2022] [Indexed: 11/29/2022]
Abstract
Background With respect to effect of surgery on the therapy of patients with metastatic gastrointestinal stromal tumors (mGISTs), still no consensus has been reached. This research designed to investigate the effect of surgical treatment on prognosis in patients with mGISTs. Methods The population-based study consisted of 6282 GIST patients diagnosed between 2001 and 2016, from the Surveillance, Epidemiology, and End Results (SEER) database registry. The Kaplan-Meier method and Cox model were employed for the exploration of the effect of surgery on overall survival (OS) and GIST-specific survival (GSS). Results In total, 6282 patients were diagnosed with GISTs, including 1238 (19.7%) mGIST patients and 5044 (80.3%) non-mGIST patients. Compared with the patients with non-mGISTs, metastatic patients assumed relatively lower proportion of surgical management (756 [61.1%] vs. 4666 [92.5%], P < 0.001). Based on unadjusted analysis, mGIST patients with operative management presented higher five years OS together with GSS in comparison with those without operative management (OS: 58.3% vs. 33.1%, P < 0.001; GSS: 61.6% vs. 36.7%, P < 0.001). Multivariable analysis found that no surgery was correlated to more than 2-fold increased death risk (OS, adjusted HR = 2.27, 95% CI: 1.90-2.71; GSS, adjusted HR = 2.42, 95% CI: 2.00-2.93). Conclusion Metastatic GIST patients could potentially benefit from operative management with improved GSS and OS.
Collapse
Affiliation(s)
- Lei Yue
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou, China
| | - Yingchao Sun
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou, China
| | - Mengjia Hu
- Department of Gastroenterology, The First Hospital of Jiaxing, Zhejiang, China
| | - Weiling Hu
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou, China
- Institute of Gastroenterology, Zhejiang University (IGZJU), Hangzhou, China
| |
Collapse
|
11
|
Intraoperative Near-Infrared Fluorescence Imaging with Indocyanine Green for Identification of Gastrointestinal Stromal Tumors (GISTs), a Feasibility Study. Cancers (Basel) 2022; 14:cancers14061572. [PMID: 35326721 PMCID: PMC8946640 DOI: 10.3390/cancers14061572] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 03/14/2022] [Accepted: 03/14/2022] [Indexed: 02/04/2023] Open
Abstract
Simple Summary Surgical resection plays a pivotal role in the treatment of GIST patients. The current study aims to explore the use of near-infrared fluorescence imaging to optimize the intraoperative tumor identification of GISTs. For this purpose, the potential and limitations of the widely used, and non-specific, tracer indocyanine green were assessed in a multicenter study including 10 patients. Our results show that GISTs typically have similar fluorescence intensity to the surrounding tissue, within several minutes after the intravenous administration of indocyanine green. These findings justify future research into specific fluorescent tracers for GISTs, and set a reference for future intraoperative imaging trials. Abstract Background: Optimal intraoperative tumor identification of gastrointestinal stromal tumors (GISTs) is important for the quality of surgical resections. This study aims to assess the potential of near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) to improve intraoperative tumor identification. Methods: Ten GIST patients, planned to undergo resection, were included. During surgery, 10 mg of ICG was intravenously administered, and NIRF imaging was performed at 5, 10, and 15 min after the injection. The tumor fluorescence intensity was visually assessed, and tumor-to-background ratios (TBRs) were calculated for exophytic lesions. Results: Eleven GIST lesions were imaged. The fluorescence intensity of the tumor was visually synchronous and similar to the background in five lesions. In one lesion, the tumor fluorescence was more intense than in the surrounding tissue. Almost no fluorescence was observed in both the tumor and healthy peritoneal tissue in two patients with GIST lesions adjacent to the liver. In three GISTs without exophytic growth, no fluorescence of the tumor was observed. The median TBRs at 5, 10, and 15 min were 1.0 (0.4–1.2), 1.0 (0.5–1.9), and 0.9 (0.7–1.2), respectively. Conclusion: GISTs typically show similar fluorescence intensity to the surrounding tissue in NIRF imaging after intraoperative ICG administration. Therefore, intraoperatively administered ICG is currently not applicable for adequate tumor identification, and further research should focus on the development of tumor-specific fluorescent tracers for GISTs.
Collapse
|
12
|
Casali PG, Blay JY, Abecassis N, Bajpai J, Bauer S, Biagini R, Bielack S, Bonvalot S, Boukovinas I, Bovee JVMG, Boye K, Brodowicz T, Buonadonna A, De Álava E, Dei Tos AP, Del Muro XG, Dufresne A, Eriksson M, Fedenko A, Ferraresi V, Ferrari A, Frezza AM, Gasperoni S, Gelderblom H, Gouin F, Grignani G, Haas R, Hassan AB, Hindi N, Hohenberger P, Joensuu H, Jones RL, Jungels C, Jutte P, Kasper B, Kawai A, Kopeckova K, Krákorová DA, Le Cesne A, Le Grange F, Legius E, Leithner A, Lopez-Pousa A, Martin-Broto J, Merimsky O, Messiou C, Miah AB, Mir O, Montemurro M, Morosi C, Palmerini E, Pantaleo MA, Piana R, Piperno-Neumann S, Reichardt P, Rutkowski P, Safwat AA, Sangalli C, Sbaraglia M, Scheipl S, Schöffski P, Sleijfer S, Strauss D, Strauss SJ, Hall KS, Trama A, Unk M, van de Sande MAJ, van der Graaf WTA, van Houdt WJ, Frebourg T, Gronchi A, Stacchiotti S. Gastrointestinal stromal tumours: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2022; 33:20-33. [PMID: 34560242 DOI: 10.1016/j.annonc.2021.09.005] [Citation(s) in RCA: 260] [Impact Index Per Article: 86.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 09/01/2021] [Accepted: 09/04/2021] [Indexed: 02/06/2023] Open
Affiliation(s)
- P G Casali
- Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; Department of Oncology and Hemato-oncology University of Milan, Milan, Italy
| | - J Y Blay
- Centre Leon Berard and UCBL1, Lyon, France
| | - N Abecassis
- Instituto Portugues de Oncologia de Lisboa Francisco Gentil, EPE, Lisbon, Portugal
| | - J Bajpai
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - S Bauer
- Department of Medical Oncology, Interdisciplinary Sarcoma Center, West German Cancer Center, University of Duisburg-Essen, Essen, Germany
| | - R Biagini
- Department of Oncological Orthopedics, Musculoskeletal Tissue Bank, IFO, Regina Elena National Cancer Institute, Rome, Italy
| | - S Bielack
- Klinikum Stuttgart-Olgahospital, Stuttgart, Germany
| | - S Bonvalot
- Department of Surgery, Institut Curie, Paris, France
| | | | - J V M G Bovee
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
| | - K Boye
- Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway
| | - T Brodowicz
- Vienna General Hospital (AKH), Medizinische Universität Wien, Vienna, Austria
| | - A Buonadonna
- Centro di Riferimento Oncologico di Aviano, Aviano, Italy
| | - E De Álava
- Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Seville, Spain; Department of Normal and Pathological Cytology and Histology, School of Medicine, University of Seville, Seville, Spain
| | - A P Dei Tos
- Department of Pathology, Azienda Ospedale Università Padova, Padova, Italy
| | - X G Del Muro
- Integrated Unit ICO Hospitalet, HUB, Barcelona, Spain
| | - A Dufresne
- Département d'Oncologie Médicale, Centre Leon Berard, Lyon, France
| | - M Eriksson
- Skane University Hospital-Lund, Lund, Sweden
| | - A Fedenko
- P. A. Herzen Cancer Research Institute, Moscow, Russian Federation
| | - V Ferraresi
- Sarcomas and Rare Tumors Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - A Ferrari
- Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - A M Frezza
- Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - S Gasperoni
- Department of Oncology and Robotic Surgery, Azienda Ospedaliera Universitaria Careggi, Florence, Italy
| | - H Gelderblom
- Department of Medical Oncology, Leiden University Medical Centre, Leiden, The Netherlands
| | - F Gouin
- Centre Leon-Berard Lyon, Lyon, France
| | - G Grignani
- Candiolo Cancer Institute, FPO - IRCCS, Candiolo, Italy
| | - R Haas
- Department of Radiotherapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Radiotherapy, Leiden University Medical Centre, Leiden, The Netherlands
| | - A B Hassan
- Oxford University Hospitals NHS Foundation Trust and University of Oxford, Oxford, UK
| | - N Hindi
- Department of Medical Oncology, Fundación Jimenez Diaz, University Hospital, Advanced Therapies in Sarcoma Lab, Madrid, Spain
| | - P Hohenberger
- Mannheim University Medical Center, Mannheim, Germany
| | - H Joensuu
- Helsinki University Hospital (HUH) and University of Helsinki, Helsinki, Finland
| | - R L Jones
- Sarcoma Unit, Royal Marsden Hospital and Institute of Cancer Research, London, UK
| | - C Jungels
- Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - P Jutte
- University Medical Center Groningen, Groningen, The Netherlands
| | - B Kasper
- Mannheim University Medical Center, Mannheim, Germany
| | - A Kawai
- Department of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - K Kopeckova
- University Hospital Motol, Prague, Czech Republic
| | - D A Krákorová
- Masaryk Memorial Cancer Institute, Brno, Czech Republic
| | - A Le Cesne
- Department of Cancer Medicine, Gustave Roussy, Villejuif, France
| | - F Le Grange
- Department of Oncology, University College London Hospitals NHS Foundation Trust (UCLH), London, UK
| | - E Legius
- Department for Human Genetics, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - A Leithner
- Department of Orthopaedics and Trauma, Medical University of Graz, Graz, Austria
| | - A Lopez-Pousa
- Medical Oncology Department, Hospital Universitario Santa Creu i Sant Pau, Barcelona, Spain
| | - J Martin-Broto
- Department of Medical Oncology, Fundación Jimenez Diaz, University Hospital, Advanced Therapies in Sarcoma Lab, Madrid, Spain
| | - O Merimsky
- Aviv Sourasky Medical Center (Ichilov), Tel Aviv, Israel
| | - C Messiou
- Department of Radiology, Royal Marsden Hospital and Institute of Cancer Research, London, UK
| | - A B Miah
- Department of Oncology, Royal Marsden Hospital and Institute of Cancer Research, London, UK
| | - O Mir
- Department of Ambulatory Cancer Care, Gustave Roussy, Villejuif, France
| | - M Montemurro
- Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
| | - C Morosi
- Department of Radiology, IRCCS Foundation National Cancer Institute, Milan, Italy
| | - E Palmerini
- Department of Osteoncology, Bone and Soft Tissue Sarcomas and Innovative Therapies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - M A Pantaleo
- Division of Oncology, IRCCS Azienda Ospedaliero-Universitaria, di Bologna, Bologna, Italy
| | - R Piana
- Azienda Ospedaliero, Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | | | - P Reichardt
- Helios Klinikum Berlin Buch, Berlin, Germany
| | - P Rutkowski
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - A A Safwat
- Aarhus University Hospital, Aarhus, Denmark
| | - C Sangalli
- Department of Radiotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - M Sbaraglia
- Department of Pathology, Azienda Ospedale Università Padova, Padova, Italy
| | - S Scheipl
- Department of Orthopaedics and Trauma, Medical University of Graz, Graz, Austria
| | - P Schöffski
- Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium
| | - S Sleijfer
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - D Strauss
- Department of Surgery, Royal Marsden Hospital, London, UK
| | - S J Strauss
- Department of Oncology, University College London Hospitals NHS Foundation Trust (UCLH), London, UK
| | - K Sundby Hall
- Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway
| | - A Trama
- Department of Research, Evaluative Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - M Unk
- Institute of Oncology of Ljubljana, Ljubljana, Slovenia
| | - M A J van de Sande
- Department of Orthopedic Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - W T A van der Graaf
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands; Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - W J van Houdt
- Department of Surgical Oncology, the Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - T Frebourg
- Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Normandie University, UNIROUEN, Inserm U1245 and Rouen University Hospital, Rouen, France
| | - A Gronchi
- Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Milan, Italy
| | - S Stacchiotti
- Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| |
Collapse
|
13
|
Surgical Management of Metastatic Gastrointestinal Stromal Tumors. Curr Treat Options Oncol 2021; 22:37. [PMID: 33743084 DOI: 10.1007/s11864-021-00837-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/18/2021] [Indexed: 02/08/2023]
Abstract
OPINION STATEMENT Treatment with the tyrosine kinase inhibitor (TKI), imatinib is the standard first-line treatment for metastatic gastrointestinal stromal tumors (GISTs). Unfortunately, acquired c-kit mutations cause secondary resistance to imatinib in a median of 18-24 months. Sunitinib and regorafenib are multi-kinase inhibitors that can be used as second-line or third-line therapy in imatinib-resistant or -intolerant GISTs, respectively. Ripretinib (a switch-control tyrosine kinase inhibitor) has recently been approved for fourth-line treatment in metastatic GIST. The TKI avapritinib has been approved for metastatic GIST harboring the imatinib-resistant PDGFRA exon 18 mutation. Although TKI therapies have revolutionized the treatment of metastatic GISTs, they cannot cure metastatic GISTs. Therefore, cytoreductive surgery is of considerable interest and has been accordingly investigated. Retrospective non-randomized studies demonstrated the feasibility and safety of continuous TKI therapy and surgical resection. Most studies demonstrate response to TKI therapy, completeness of resection, extent of disease, and surgical complexity as predictors of outcomes. Most TKIs can be stopped shortly before surgery and restarted shortly after. There is no known survival benefit from debulking operations or R2 resections and this should not be considered. However, debulking/palliative surgery may be necessary for patients with complications of hemorrhage, pain, or intestinal obstruction. SDH-deficient GISTs have an indolent natural history despite metastatic disease and may be another uncommon subgroup that would benefit from surgical debulking (R2 resection). At the time of operation, care should be taken to avoid tumor rupture. After surgical resection, patients should resume tyrosine kinase inhibitor (TKI) therapy as soon as possible and be monitored for disease progression. In all patients with metastatic GIST, the decision to pursue metastasectomy for GIST should be made in a multidisciplinary setting and be individualized according to patient age, comorbidities, functional status, symptoms, mutation status, extent of disease, completeness of resection, TKI response, and goals of the patient.
Collapse
|
14
|
Wada N, Takahashi T, Kurokawa Y, Nakajima K, Nishida T, Koh M, Akamaru Y, Motoori M, Kimura Y, Tanaka K, Miyazaki Y, Makino T, Yamasaki M, Eguchi H, Doki Y. Clinical significance of surgical intervention for imatinib-resistant gastrointestinal stromal tumors in the era of multiple tyrosine kinase inhibitors. Surg Today 2021; 51:1506-1512. [PMID: 33570662 DOI: 10.1007/s00595-021-02241-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Accepted: 01/11/2021] [Indexed: 11/29/2022]
Abstract
PURPOSE Imatinib is the standard treatment for unresectable and metastatic GIST. In the late stages, patients undergoing imatinib show drug resistance. Surgical intervention has been occasionally performed for resistant lesions. However, the clinical significance of such intervention remains unclear. METHODS Between 2006 and 2015, 37 patients were diagnosed with imatinib-resistant GISTs. We performed surgical intervention only for localized resistant lesions. We retrospectively investigated the background characteristics, data on surgical intervention and subsequent treatment, progression-free survival (PFS), and overall survival (OS). RESULTS Eighteen patients diagnosed with localized resistance received surgical intervention (S-group) and 19 patients diagnosed with generalized resistance were received other TKIs (M-group). In S-group, no serious complications occurred, and all patients restarted imatinib after resection. The median PFS was 14.5 months. Five patients underwent surgical intervention multiple times followed by the continuation of imatinib, and the median duration of imatinib continuation was 22.2 months. Second-line TKIs were administered to 93% of the patients and the dose-intensity and outcome were similar in both groups. The median OS was 47.2 months after surgery. CONCLUSIONS Surgical intervention could be performed safely and therefore could be followed by the continuation of TKI therapy. Surgical intervention based on the appropriate criteria of resistance might thus be useful for imatinib-resistant GISTs.
Collapse
Affiliation(s)
- Noriko Wada
- Department of Gastroenterological Surgery, Ikeda City Hospital, Osaka, Japan.,Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Tsuyoshi Takahashi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Kiyokazu Nakajima
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Toshirou Nishida
- Department of Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Masahiro Koh
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yusuke Akamaru
- Department of Gastroenterological Surgery, Ikeda City Hospital, Osaka, Japan
| | - Masaaki Motoori
- Department of Surgery, Osaka General Medical Center, Osaka, Japan
| | - Yutaka Kimura
- Department of Surgery, Faculty of Medicine, Kinki University, Osaka, Japan
| | - Koji Tanaka
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yasuhiro Miyazaki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Tomoki Makino
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Makoto Yamasaki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| |
Collapse
|
15
|
Shou C, Gao Q, Yang W, Zhang Q, Liu X, Yu J. Surgery Combined with Long-Term Imatinib Treatment for Patients with Recurrent or Metastatic Gastrointestinal Stromal Tumors. Indian J Surg 2021. [DOI: 10.1007/s12262-020-02261-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
|
16
|
Zhao S, Zhu H, Jiao R, Wu X, Zhang X, Ji G. Primary Tumor Resection Improves Survival in Patients With Metastatic Gastrointestinal Stromal Tumors: A Preliminary Population-Based Analysis. Front Oncol 2020; 10:1440. [PMID: 32974163 PMCID: PMC7466430 DOI: 10.3389/fonc.2020.01440] [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: 03/23/2020] [Accepted: 07/08/2020] [Indexed: 01/17/2023] Open
Abstract
Background: Surgery has been the primary treatment in patients with localized gastrointestinal stromal tumors (GISTs) for many decades, whereas it remains controversial regarding the efficacy of primary tumor resection for metastatic GISTs treated with chemotherapy, and likewise it is unclear who would benefit from the surgical resection. Methods: GISTs patients with distant metastases were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. Cox proportional hazards regression models were used to identify prognostic factors of overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier analyses and log-rank tests were conducted to assess the effectiveness of surgery on survival. Results: In total, of 455 patients with metastatic GISTs, 235 patients (51.6%) underwent primary tumor resection and 220 patients (48.4%) did not. Median survival of patients in resection group was 72 (95% CI: 62.90–81.10) months vs. 40 (95% CI: 29.53–50.47) months for those in non-resection group (p < 0.001). Similarly, surgery in conjunction with chemotherapy led to a favorable impact on survival than chemotherapy alone (OS: 72 vs. 40 months, p < 0.001; CSS: 74 vs. 44 months, p < 0.001). Multivariable analysis showed that both OS (HR: 0.581, 95% CI: 0.386–0.874, p = 0.009) and CSS (HR: 0.663, 95% CI: 0.439–0.912, p = 0.042] were dramatically improved in patients with surgical removal of primary site, as well as primary tumor size between 5 and 10 cm, while increasing age was predictive of poorer survival. Stratified analysis revealed that patients with tumor locations in the stomach demonstrated a prolonged survival after surgery, with no significant differential surgical effect between the stomach and small intestine. Conclusions: Our study preliminarily suggests that carefully selected patients with metastatic GISTs might prolong survival after treatment of surgery, especially those with a primary tumor between 5 and 10 cm and a tumor located in the stomach.
Collapse
Affiliation(s)
- Si Zhao
- Medical Centre for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Hanlong Zhu
- Medical Centre for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Ruonan Jiao
- Medical Centre for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Xueru Wu
- Medical Centre for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Xiuhua Zhang
- Medical Centre for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Guozhong Ji
- Medical Centre for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
| |
Collapse
|
17
|
Keung EZ, Raut CP, Rutkowski P. The Landmark Series: Systemic Therapy for Resectable Gastrointestinal Stromal Tumors. Ann Surg Oncol 2020; 27:3659-3671. [PMID: 32734368 PMCID: PMC7471171 DOI: 10.1245/s10434-020-08869-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Accepted: 07/04/2020] [Indexed: 12/16/2022]
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Complete resection is the only potentially curative treatment, although recurrence is common, occurring in approximately 40–50% of patients. The introduction of effective molecularly targeted therapies for GISTs has dramatically changed the clinical management paradigms for, and prognosis of, patients with intermediate- and high-risk GISTs, as well as those with locally advanced and metastatic disease. In this article, we review landmark studies that evaluated the use and efficacy of the tyrosine kinase inhibitors imatinib and sunitinib in the adjuvant and neoadjuvant settings for resectable primary and limited resectable metastatic GISTs.
Collapse
Affiliation(s)
- Emily Z Keung
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Chandrajit P Raut
- Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Piotr Rutkowski
- Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
| |
Collapse
|
18
|
Yang DP, Zhuang BW, Wang YZ, Lin MX, Xu M, Kuang M, Lei YY, Xie XY, Xie XH. Thermal ablation versus hepatic resection for the treatment of liver metastases from gastrointestinal stromal tumors: a retrospective study. Int J Hyperthermia 2020; 37:592-599. [PMID: 32484012 DOI: 10.1080/02656736.2020.1772513] [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: 10/24/2022] Open
Abstract
Objective: The study aimed to compare effectiveness and safety of thermal ablation and hepatic resection in patients with liver metastases of gastrointestinal stromal tumors (GISTs).Method: A total of 55 patients (27 in the ablation group and 28 in the surgery group) with liver metastases were included. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier's survival estimate curves. Univariate and multivariate regression analyses were carried out to identify potential prognostic factors.Results: The median OS was 102.0 months in the ablation group and 117.0 months in the surgery group (p = .875). The 1-, 3- and 5-year OS rates were 100%, 88.9% and 74.1% in the ablation group and 92.8%, 82.1% and 78.6% in the surgery group, respectively. The 1-, 3- and 5-year PFS rates were 48.1%, 25.9% and 18.5% in the ablation group and 67.8%, 64.3% and 64.3% in the surgery group, respectively. Multivariate analysis showed that preoperative tyrosine kinase inhibitor (TKI) treatment (progressive disease, PD) (HR, 13.985; 95% CI, 1.791-109.187; p = .012) was the only significant independent prognostic factor for OS. Tumor number (HR, 1.318; 95% CI, 1.021-1.702; p = .034) was identified as an independent predictor for PFS in multivariate analysis. There were fewer postoperative complications (18.5% vs. 78.6%, p = .001) and shorter lengths of hospital stay (8.0 vs. 16.5 days, p = .001) in the ablation group.Conclusion: Compared with resection, thermal ablation offered comparable OS for liver metastases of GISTs. Furthermore, thermal ablation had the advantages of fewer complications and shorter lengths of hospital stay.
Collapse
Affiliation(s)
- Dao-Peng Yang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Bo-Wen Zhuang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yu-Zhao Wang
- Sun Yat-Sen University School of Medicine, Guangzhou, China
| | - Man-Xia Lin
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Ming Xu
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Ming Kuang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yang-Yang Lei
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xiao-Yan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xiao-Hua Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| |
Collapse
|
19
|
Wang J, Yin Y, Shen C, Yin X, Cai Z, Pu L, Fu W, Wang Y, Zhang B. Preoperative imatinib treatment in patients with locally advanced and metastatic/recurrent gastrointestinal stromal tumors: A single-center analysis. Medicine (Baltimore) 2020; 99:e19275. [PMID: 32118738 PMCID: PMC7478449 DOI: 10.1097/md.0000000000019275] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The advent of imatinib mesylate (IM) has dramatically revolutionized the prognosis of advanced and metastatic/recurrent gastrointestinal stromal tumors (GISTs). The objective of this retrospective study is to investigate the safety and efficacy of combination of surgery following IM treatment in the management of advanced and metastatic/recurrent GISTs. We further explore the long-term clinical outcomes in these who underwent therapy of preoperative IM.Eligible patients with GISTs before the onset of the IM therapy and were periodically followed up in the outpatient clinic were included in this study. Detailed clinical and pathologic characteristics were obtained from the medical records of our institution. Univariate and multivariate regression analyses were performed to use for the evaluation of potential prognostic factors.A total of 51 patients were included in the study, of these patients, 36 patients underwent surgery and median duration of preoperative IM is 8.2months (range 3.5-85 months). Significant median tumor shrinkage rate was 29.27% (95% confidence interval 21.00%-34.00%) observed in these patients who responded to IM, and partial response and stable disease were achieved in 24 patients (47.06%) and 23 patients (45.10%), respectively, in light of the RECIST guideline (version 1.1). After the median follow-up of 43.70 months (range 14.2-131.1 months), 1- and 3-year overall survival (OS) were estimated to be 96.1% and 94.0%, respectively, and there was a significant improvement in OS for patients who received surgical intervention versus those who did not.Our study consolidates that patients were received preoperative IM therapy could shrink the size of tumors and facilitate organ-function preservation. The long-term analysis on this study supports that surgical intervention following IM therapy benefits for patients with primary advanced and recurrent or metastatic GISTs on long-term prognosis.
Collapse
|
20
|
|
21
|
Cho H, Ryu MH, Lee Y, Park YS, Kim KH, Kim JH, Park Y, Lee SM, Kim CW, Kim BS, Yoo MW, Kang YK. Role of Resection Following Focal Progression with Standard Doses of Imatinib in Patients with Advanced Gastrointestinal Stromal Tumors: Results of Propensity Score Analyses. Oncologist 2019; 24:e1443-e1449. [PMID: 31315961 PMCID: PMC6975948 DOI: 10.1634/theoncologist.2019-0009] [Citation(s) in RCA: 3] [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: 01/04/2019] [Accepted: 06/12/2019] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND There are limited data on the clinical benefits of adding surgical resection in patients with focally progressive gastrointestinal stromal tumor (GIST). This study aims to compare the clinical outcomes of resection plus imatinib dose escalation or maintenance (S group) with imatinib dose escalation alone (NS group) in patients with advanced GIST following focal progression (FP) with standard doses of imatinib. MATERIALS AND METHODS A total of 90 patients with advanced GISTs who experienced FP with standard doses of imatinib were included in this retrospective analysis. The primary endpoints were time to imatinib treatment failure (TTF) and overall survival (OS). RESULTS Compared with the NS group (n = 52), patients in the S group (n = 38) had a higher proportion of primary tumor site involvement and lower tumor burden at FP. With a median follow-up duration of 31.0 months, patients in the S group had significantly better TTF and OS than patients in the NS group (median TTF: 24.2 vs. 6.5 months, p < .01; median OS: 53.2 vs. 35.1 months, p = .009). Multivariate analysis showed that S group independently demonstrated better TTF (hazard ratio [HR], 0.29; p < .01) and OS (HR, 0.47; p = .01). Even after applying inverse probability of treatment-weighting adjustments, S group demonstrated significantly better TTF (HR, 0.36; p < .01) and OS (HR, 0.58; p = .049). CONCLUSION Our results suggested that resection following FP with standard doses of imatinib in patients with advanced GIST provides additional benefits over imatinib dose escalation alone. IMPLICATIONS FOR PRACTICE This is the first study to compare the clinical outcomes of resection plus imatinib dose escalation or maintenance (S group) with imatinib dose escalation alone (NS group) in patients with advanced gastrointestinal stromal tumor (GIST) following focal progression (FP) with standard doses of imatinib. These findings suggest that resection can be safely performed following FP, and the addition of surgical resection provides further clinical benefit over imatinib dose escalation alone. Based on these results, the authors recommend resection following FP in patients with advanced GIST provided that an experienced multidisciplinary team is involved in the patient's treatment.
Collapse
Affiliation(s)
- Hyungwoo Cho
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Min-Hee Ryu
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Yongjune Lee
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Young Soo Park
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Ki-Hun Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jwa Hoon Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Yangsoon Park
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sun Mi Lee
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Chan Wook Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Beom Soo Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Moon-Won Yoo
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Yoon-Koo Kang
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| |
Collapse
|
22
|
Guo Y, Liu J, Wang F, Wang Q, Zheng G, Liu S, Lian X, Zhang H, Feng F. The Role of Surgical Resection Following Tyrosine Kinase Inhibitors Treatment in Patients with Advanced Gastrointestinal Stromal Tumors: A Systematic Review and Meta-analysis. J Cancer 2019; 10:5785-5792. [PMID: 31737115 PMCID: PMC6843877 DOI: 10.7150/jca.30040] [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] [Received: 06/03/2019] [Accepted: 08/16/2019] [Indexed: 01/17/2023] Open
Abstract
Background The benefit of surgical resection for advanced gastrointestinal stromal tumors (GISTs) following tyrosine kinase inhibitors (TKIs) treatment was still under debate. The present meta-analysis was designed to assess the value of surgical resection for the prognosis of patients with metastatic, recurrence and unresectable GISTs. Methods A systematic search of PubMed Central, PubMed, EMBASE and the Cochrane Library database was performed. Relevant studies of the role of surgery in advanced GISTs published before 1 May 2019 were identified. The quality of studies was assessed by the Newcastle-Ottawa Quality Assessment Scale. The progression-free survival (PFS) and overall survival (OS) were assessed through software Stata 15.0. Results A total of 6 retrospective studies including 655 patients were analyzed. The pooled result revealed that surgical resection group was associated with better PFS (HR = 2.08; 95% CI: 1.58 to 2.76; P<0.001) and better OS (HR = 2.13; 95% CI: 1.59 to 2.85; P<0.001) compared with TKIs treatment alone group. Conclusions Surgical resection following TKIs treatment could significantly improve the prognosis of patients with advanced GISTs.
Collapse
Affiliation(s)
- Yinghao Guo
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, 127 West Changle Road, 710032, Xi'an, Shaanxi, China
- Health company, 92667 Army of PLA, 39 East Zaoshan Road, 266100, Qingdao, Shandong, China
| | - Jinqiang Liu
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, 127 West Changle Road, 710032, Xi'an, Shaanxi, China
- Cadre' s sanitarium, 62101 Army of PLA, 67 Nahu Road, 464000, Xinyang, Henan, China
| | - Fei Wang
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, 127 West Changle Road, 710032, Xi'an, Shaanxi, China
- Department of General Surgery, No. 534 Hospital of PLA, West Lichun Road, 471000, Luoyang, Henan, China
| | - Qiao Wang
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, 127 West Changle Road, 710032, Xi'an, Shaanxi, China
- Department of General Surgery, No. 91 Hospital of PLA, 239 Gongye Road, 454000, Jiaozuo, Henan, China
| | - Gaozan Zheng
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, 127 West Changle Road, 710032, Xi'an, Shaanxi, China
| | - Shushang Liu
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, 127 West Changle Road, 710032, Xi'an, Shaanxi, China
| | - Xiao Lian
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, 127 West Changle Road, 710032, Xi'an, Shaanxi, China
| | - Hongwei Zhang
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, 127 West Changle Road, 710032, Xi'an, Shaanxi, China
| | - Fan Feng
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, 127 West Changle Road, 710032, Xi'an, Shaanxi, China
| |
Collapse
|
23
|
Hamacher R, Falkenhorst J, Treckmann J, Bauer S. [Imatinib and beyond-what is important for surgery?]. Chirurg 2019; 90:462-469. [PMID: 30903227 DOI: 10.1007/s00104-019-0934-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The treatment of gastrointestinal stromal tumors (GIST) has dramatically improved since the introduction of small molecule KIT proto-oncogene receptor tyrosine kinase inhibitors. Nevertheless, the cure of patients is still based on surgical treatment of the primary tumor. The chance of long-term tumor control by tyrosine kinase inhibitors (TKI) even in the metastatic setting also appears to be improved after achieving a surgical complete resection. The decision on which patients will most likely profit from multimodal treatment approaches is increasingly based on complex molecular predictors in addition to clinical factors and also a profound understanding of the biology of GIST that requires discussion in a multidisciplinary, highly experienced treatment team. Novel, more potent inhibitors enable a response to treatment in so far treatment-refractory GIST subtypes, such as the platelet-derived growth factor receptor (PDGFR) D842V mutated GIST subtype and also appear to show treatment benefits even in KIT mutated GIST after the failure of all approved treatments. These treatments are expected to profoundly change treatment algorithms in the near future.
Collapse
Affiliation(s)
- R Hamacher
- Innere Klinik (Tumorforschung), Sarkomzentrum am Westdeutschen Tumorzentrum, Universitätsklinik Essen, Universität Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Deutschland
| | - J Falkenhorst
- Innere Klinik (Tumorforschung), Sarkomzentrum am Westdeutschen Tumorzentrum, Universitätsklinik Essen, Universität Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Deutschland
| | - J Treckmann
- Sektion Viszerale/retroperitoneale Sarkome und GIST, Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Sarkomzentrum am Westdeutschen Tumorzentrum, Universitätsklinik Essen, Universität Duisburg-Essen, Essen, Deutschland
| | - S Bauer
- Innere Klinik (Tumorforschung), Sarkomzentrum am Westdeutschen Tumorzentrum, Universitätsklinik Essen, Universität Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Deutschland.
| |
Collapse
|
24
|
Kim BJ, Milgrom DP, Feizpour C, Kays JK, Koniaris LG. Role for targeted resection in the multidisciplinary treatment of metastatic gastrointestinal stromal tumor. Transl Gastroenterol Hepatol 2019; 4:26. [PMID: 31143847 DOI: 10.21037/tgh.2019.04.02] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Accepted: 03/27/2019] [Indexed: 01/13/2023] Open
Abstract
The management of advanced gastrointestinal stromal tumors (GISTs) has evolved in the modern era due to the discovery of c-kit mutations and the development of tyrosine kinase inhibitors (TKIs). Until the advent of TKIs such as imatinib, the median survival reported for patients with advanced GIST was 19 months. Although surgery is the treatment of choice for resectable primary GIST, its role in cases of recurrence and metastasis remains to be unclear. This review outlines the potential beneficial role of repeat surgical resection in the multidisciplinary treatment of advanced GIST in the era of TKIs.
Collapse
Affiliation(s)
- Bradford J Kim
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Daniel P Milgrom
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Cyrus Feizpour
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Joshua K Kays
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Leonidas G Koniaris
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| |
Collapse
|
25
|
Tjhoi WE, Li K, Shou CH, Yang WL, Yu JR. Long-term adjuvant imatinib treatment for a patient who underwent complete resection of a localized recurrent gastrointestinal stromal tumor after preoperative imatinib treatment: A case report. Medicine (Baltimore) 2019; 98:e14477. [PMID: 30732216 PMCID: PMC6380822 DOI: 10.1097/md.0000000000014477] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
RATIONALE The efficiency and tolerance of long-term adjuvant imatinib treatment for patient who underwent complete resection of a localized recurrent gastrointestinal stromal tumor (GIST) was unknown. PATIENT CONCERNS A 45-year-old man underwent complete resection of an intestinal GIST in August 2001. Four years later, a giant (11 × 8 × 6 cm) recurrent GIST located in the retroperitoneum was detected. DIAGNOSIS The recurrent tumor was positive for CD117 by immunohistochemistry. INTERVENTIONS The recurrent tumor was completely resected after 4 months of effective imatinib treatment (400 mg/day), and the patient continued imatinib treatment postoperatively. In June 2011, imatinib treatment was stopped for 3 weeks because of hepatitis B infection, and resumed with a reduced dose level of 300 mg/day when liver function recovered. In March 2017, imatinib treatment was interrupted again for 12 days because the patient underwent cholecystectomy. OUTCOMES In December 2017, a computed tomography scan showed no signs of tumor recurrence. To date, the patient has been under adjuvant imatinib treatment for >12 years without severe side effects. The plasma concentration of imatinib (detected in February 2018) was trough concentration (Cmin) 1015.7 ng/mL and peak concentration (Cmax) 1550.5 ng/mL. LESSONS This case report highlights the active role of long-term (>12 years) imatinib treatment after complete resection of localized recurrent GIST.
Collapse
|
26
|
Kim JH, Ryu MH, Yoo C, Chae H, Na H, Beck M, Kim BS, Yoo MW, Yook JH, Kim BS, Kim KH, Kim CW, Kang YK. Long-term survival outcome with tyrosine kinase inhibitors and surgical intervention in patients with metastatic or recurrent gastrointestinal stromal tumors: A 14-year, single-center experience. Cancer Med 2019; 8:1034-1043. [PMID: 30693663 PMCID: PMC6434201 DOI: 10.1002/cam4.1994] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Revised: 12/11/2018] [Accepted: 01/08/2019] [Indexed: 12/17/2022] Open
Abstract
The long‐term effects of tyrosine kinase inhibitors (TKIs), including imatinib, and surgical intervention on advanced gastrointestinal stromal tumor (GIST) were evaluated. All 379 patients had metastatic or recurrent GIST and started 400 mg/d imatinib at the Asan Medical Center in periods 1 and 2 [2001‐2007 (33.2%) and 2008‐2014 (66.8%), respectively]. Men constituted 60.4%; median patient age and tumor size at the initiation of imatinib were 58.6 (14.6‐85.5) years and 51 (0‐324) mm, respectively, without differences between periods except for older age and less preimatinib surgery in period 2. Response and disease control rates with imatinib in measurable GIST were 63.1% and 94.3%, respectively, without differences between periods. More patients in period 2 underwent surgical resection for TKI‐responsive diseases within the first 2 years (24.9%, P = 0.006). With a median follow‐up of 6.1 years (2.5‐16.0) in survivors, median progression‐free survival (PFS) was 5.4 years [95% confidence interval (CI), 4.0‐6.9]. Subsequent sunitinib (P = 0.066) and regorafenib (P = 0.003) were more commonly administered in period 2. Median overall survival (OS) was 8.8 years (95% CI, 7.8‐9.7). PFS with imatinib (P = 0.002) and OS (P = 0.019) were significantly longer in period 2. Young age, smaller tumor size at the initiation of imatinib, KIT exon 11 mutation, surgical intervention, and period 2 were favorable factors for PFS and OS. Patients with advanced GIST showed better prognosis with the optimal use of imatinib, along with active surgical intervention and more common use of subsequent TKIs in period 2.
Collapse
Affiliation(s)
- Jwa Hoon Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Min-Hee Ryu
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Changhoon Yoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Heejung Chae
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hana Na
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Moyoul Beck
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Beom Su Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Moon-Won Yoo
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong Hwan Yook
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Byung Sik Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ki-Hun Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chan Wook Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yoon-Koo Kang
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| |
Collapse
|
27
|
Yan LH, Chen ZN, Li CJ, Chen J, Qin YZ, Chen JS, Tang WZ. Prolonging Gastrointestinal-Stromal-Tumor-free life, an optimal suggestion of imatinib intervention ahead of operation. J Cancer 2018; 9:3850-3857. [PMID: 30410587 PMCID: PMC6218762 DOI: 10.7150/jca.25263] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Accepted: 04/14/2018] [Indexed: 01/16/2023] Open
Abstract
Background: Imatinib has been regarded as the first successful synthetic small molecule targeting at blocking tyrosine kinase. Its high efficacy stabilized disease in above 80% of chronic myeloid leukemia (CML) patients over 10 years survival. Due to the similar canceration of gastrointestinal stromal tumor (GIST) as to CML, imatinib has been approved to be used as first-line treatment. Study design: Our retrospective study was proposed to enroll 191 GIST patients with larger tumor size (≥8 cm) who preoperative accepted imatinib from those with direct operation. Analysis included demographics, cancer specific survival and relationship of their risk factors. Results: Male patients and gastrointestinal (GI) tract location took higher proportion in total cases, detection of KIT mutant took 89.7% among all traceable genetic testing. Patients with preoperative imatinib can achieve higher cancer specific survival (CSS) after both in 1 year and 3 years duration than their counterpart. Tumor size above its threshold of 8 cm would be a hazardous factor for poor prognosis. Conclusion: In conclusion, as for regressing tumor progression and creating operative chance, preoperative imatinib should be considered for the patients with high risk, although the precise duration of this intervention needs further validation.
Collapse
Affiliation(s)
- Lin-Hai Yan
- Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Zhi-Ning Chen
- Department of Pathology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Chun-Jun Li
- Department of Pathology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jia Chen
- Department of Medical Image Center, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Yu-Zhou Qin
- Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jian-Si Chen
- Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Wei-Zhong Tang
- Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| |
Collapse
|
28
|
Casali PG, Abecassis N, Aro HT, Bauer S, Biagini R, Bielack S, Bonvalot S, Boukovinas I, Bovee JVMG, Brodowicz T, Broto JM, Buonadonna A, De Álava E, Dei Tos AP, Del Muro XG, Dileo P, Eriksson M, Fedenko A, Ferraresi V, Ferrari A, Ferrari S, Frezza AM, Gasperoni S, Gelderblom H, Gil T, Grignani G, Gronchi A, Haas RL, Hassan B, Hohenberger P, Issels R, Joensuu H, Jones RL, Judson I, Jutte P, Kaal S, Kasper B, Kopeckova K, Krákorová DA, Le Cesne A, Lugowska I, Merimsky O, Montemurro M, Pantaleo MA, Piana R, Picci P, Piperno-Neumann S, Pousa AL, Reichardt P, Robinson MH, Rutkowski P, Safwat AA, Schöffski P, Sleijfer S, Stacchiotti S, Sundby Hall K, Unk M, Van Coevorden F, van der Graaf WTA, Whelan J, Wardelmann E, Zaikova O, Blay JY. Gastrointestinal stromal tumours: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2018; 29:iv68-iv78. [PMID: 29846513 DOI: 10.1093/annonc/mdy095] [Citation(s) in RCA: 281] [Impact Index Per Article: 40.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/08/2023] Open
Affiliation(s)
- P G Casali
- Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Milan, Italy
| | - N Abecassis
- Instituto Portugues de Oncologia de Lisboa Francisco Gentil, EPE, Lisbon, Portugal
| | - H T Aro
- Turku University Hospital (Turun Yliopistollinen Keskussairaala), Turlu, Finland
| | - S Bauer
- University Hospital Essen, Essen Germany
| | - R Biagini
- Department of Oncological Orthopedics, Musculoskeletal Tissue Bank, IFO, Regina Elena National Cancer Institute, Rome, Italy
| | - S Bielack
- Klinikum Stuttgart-Olgahospital, Stuttgart, Germany
| | | | | | - J V M G Bovee
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
| | - T Brodowicz
- Vienna General Hospital (AKH), Medizinische Universität Wien, Vienna, Austria
| | - J M Broto
- Hospital Universitario Virgen del Rocio-CIBERONC, Seville, Spain
| | - A Buonadonna
- Centro di Riferimento Oncologico di Aviano, Aviano
| | - E De Álava
- Hospital Universitario Virgen del Rocio-CIBERONC, Seville, Spain
| | - A P Dei Tos
- Ospedale Regionale di Treviso 'S.Maria di Cà Foncello', Treviso, Italy
| | - X G Del Muro
- Integrated Unit ICO Hospitalet, HUB, Barcelona, Spain
| | - P Dileo
- Sarcoma Unit, University College London Hospitals, London, UK
| | - M Eriksson
- Skane University Hospital-Lund, Lund, Sweden
| | - A Fedenko
- N. N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation
| | - V Ferraresi
- Institute of Scientific Hospital Care (IRCCS), Regina Elena National Cancer Institute, Rome
| | - A Ferrari
- Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan
| | - S Ferrari
- Istituto Ortopedico Rizzoli, Bologna
| | - A M Frezza
- Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Milan, Italy
| | - S Gasperoni
- Azienda Ospedaliera Universitaria Careggi Firenze, Florence, Italy
| | - H Gelderblom
- Department of Medical Oncology, Leiden University Medical Centre, Leiden, The Netherlands
| | - T Gil
- Institut Jules Bordet, Brussels, Belgium
| | - G Grignani
- Candiolo Cancer Institute, FPO IRCCS, Candiolo, Italy
| | - A Gronchi
- Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Milan, Italy
| | - R L Haas
- Department of Radiotherapy, The Netherlands Cancer Institute, Amsterdam and Department of Radiotherapy, Leiden University Medical Centre, Leiden, The Netherlands
| | - B Hassan
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | | | - R Issels
- Department of Medicine III, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany
| | - H Joensuu
- Helsinki University Central Hospital (HUCH), Helsinki, Finland
| | | | - I Judson
- The Institute of Cancer Research, London, UK
| | - P Jutte
- University Medical Center Groningen, Groningen
| | - S Kaal
- Radboud University Medical Center, Nijmegen, The Netherlands
| | - B Kasper
- Mannheim University Medical Center, Mannheim
| | | | - D A Krákorová
- Masaryk Memorial Cancer Institute, Brno, Czech Republic
| | - A Le Cesne
- Gustave Roussy Cancer Campus, Villejuif, France
| | - I Lugowska
- Maria Sklodowska Curie Institute, Oncology Centre, Warsaw, Poland
| | - O Merimsky
- Tel Aviv Sourasky Medical Center (Ichilov), Tel Aviv, Israel
| | - M Montemurro
- Medical Oncology, University Hospital of Lausanne, Lausanne, Switzerland
| | - M A Pantaleo
- Azienda Ospedaliera, Universitaria, Policlinico S Orsola-Malpighi Università di Bologna, Bologna
| | - R Piana
- Azienda Ospedaliero, Universitaria Cita della Salute e della Scienza di Torino, Turin, Italy
| | - P Picci
- Istituto Ortopedico Rizzoli, Bologna
| | | | - A L Pousa
- Fundacio de Gestio Sanitaria de L'hospital de la Santa Creu I Sant Pau, Barcelona, Spain
| | - P Reichardt
- Helios Klinikum Berlin Buch, Berlin, Germany
| | - M H Robinson
- YCRC Department of Clinical Oncology, Weston Park Hospital NHS Trust, Sheffield, UK
| | - P Rutkowski
- Maria Sklodowska Curie Institute, Oncology Centre, Warsaw, Poland
| | - A A Safwat
- Aarhus University Hospital, Aarhus, Finland
| | | | - S Sleijfer
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - S Stacchiotti
- Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan, Italy
| | - K Sundby Hall
- Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway
| | - M Unk
- Institute of Oncology of Ljubljana, Ljubljana, Slovenia
| | - F Van Coevorden
- Netherlands Cancer Institute Antoni van Leeuwenhoek, Amsterdam, The Netherlands
| | | | - J Whelan
- University College Hospital, London, UK
| | - E Wardelmann
- Gerhard-Domagk-Institut für Pathologie, Universitätsklinikum Münster, Münster, Germany
| | - O Zaikova
- Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway
| | - J Y Blay
- Centre Leon Bernard and UCBL1, Lyon, France
| |
Collapse
|
29
|
Jakob J, Hohenberger P. Neoadjuvant Therapy to Downstage the Extent of Resection of Gastrointestinal Stromal Tumors. Visc Med 2018; 34:359-365. [PMID: 30498703 PMCID: PMC6257203 DOI: 10.1159/000493405] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
INTRODUCTION Gastrointestinal stromal tumors (GIST) are rare malignant tumors in terms of incidence, and they are not linked to specific symptoms. Often, primary tumors, particularly of the stomach, rectum, or rectovaginal space, are quite large when detected, and multivisceral resection seems to be the treatment of choice as the mainstay of therapy is complete tumor removal. If a gain-of-function mutation in the KIT gene is present, drug therapy with receptor tyrosine kinase inhibitors (RTKIs) might significantly downstage primary GIST tumors. METHODS A review of the literature was performed to identify the current evidence for preoperative treatment of GIST regarding toxicity, efficacy, and oncological outcome, including mutational data from our own database. RESULTS Four phase II as well as several cohort studies showed acceptable toxicity and no increased perioperative morbidity of preoperative imatinib. Progressive disease during preoperative treatment was a rare event, and partial response was achieved in 40-80% of all patients. For methodological reasons, the trials cannot prove an oncological long-term superiority of preoperative treatment. CONCLUSION Preoperative therapy with imatinib is safe and recommended for patients with locally advanced GIST. Neoadjuvant imatinib therapy may enable less invasive and organ-sparing surgery, avoid tumor rupture during extensive resectional procedures, and improve the quality of perioperative RTKI treatment.
Collapse
Affiliation(s)
- Jens Jakob
- Division of Surgical Oncology and Thoracic Surgery, Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
- Department of General, Visceral and Pediatric Surgery, University Medical Center, Göttingen, Germany
| | - Peter Hohenberger
- Division of Surgical Oncology and Thoracic Surgery, Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| |
Collapse
|
30
|
Ronellenfitsch U, Hohenberger P. Surgery for Gastrointestinal Stromal Tumors: State of the Art of Laparoscopic Resection and Surgery for M1 Tumors. Visc Med 2018; 34:367-374. [PMID: 30498704 PMCID: PMC6257156 DOI: 10.1159/000491799] [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: 02/05/2023] Open
Abstract
BACKGROUND The principles of surgery for primary gastrointestinal stromal tumor (GIST) are resection with clear margins without lymphadenectomy, thus enabling organ-preserving resection in many cases. Tumor rupture needs to be avoided, because it entails peritoneal sarcomatosis. Given these preconditions, there is a rationale for laparoscopic resection of primary GIST. In metastatic GIST, surgery cannot achieve cure, but constitutes an important cornerstone of treatment. Resection can be performed either for residual lesions in responding patients, for focally progressive lesions, or as palliative measure in generalized progression. METHODS Selective literature review. RESULTS There is ample evidence on laparoscopic resection of gastric GIST, but none from randomized trials. The studies show favorable perioperative outcomes and suggest adequate oncological results; however, a direct comparison to open resection is difficult. For surgery in M1 stages, survival outcomes are better for resection in generalized response than in focal progression. Perioperative morbidity is acceptable. Surgery in generalized progression does not prolong survival and bears relevant morbidity risks. CONCLUSION Laparoscopy seems an adequate surgical approach for primary gastric GIST, as long as the surgical principles relevant for this entity are respected. For other tumor sites, there is no sufficient evidence available. In M1 stages, selected patients may benefit from surgery. Survival differences between resection at different stages probably mirror the biology of the disease rather than the effect of the timing of the operation.
Collapse
Affiliation(s)
- Ulrich Ronellenfitsch
- Department of Vascular and Endovascular Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Peter Hohenberger
- Division of Surgical Oncology and Thoracic Surgery, Department of Surgery, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany
| |
Collapse
|
31
|
Schrage Y, Hartgrink H, Smith M, Fiore M, Rutkowski P, Tzanis D, Messiou C, Servois V, Bonvalot S, van der Hage J. Surgical management of metastatic gastrointestinal stromal tumour. Eur J Surg Oncol 2018; 44:1295-1300. [DOI: 10.1016/j.ejso.2018.06.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Accepted: 06/04/2018] [Indexed: 12/12/2022] Open
|
32
|
Zhang X, Zhou Y, Wu X, Nie M, Zhang B, Zhou Y, Sun L, Liu Z, Liu X, Kou Y, Wang Y, Zhang Y, Hao C, Shen L, Li J. Cytoreductive surgery for metastatic gastrointestinal stromal tumors followed by sunitinib compared to followed by imatinib-a multi-center cohort study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2018; 45:318-323. [PMID: 30145000 DOI: 10.1016/j.ejso.2018.08.001] [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] [Received: 07/09/2018] [Revised: 07/24/2018] [Accepted: 08/02/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND The progression-free survival (PFS) is not optimal when imatinib was recommended for treatment of gastrointestinal stromal tumor (GIST) undergoing surgery after tumor local or multifocal progression. METHODS We evaluate PFS of patients undergoing R0 resection or optimal cytoreductive surgery followed by sunitinib therapy compared with imatinib after tumor unifocal or multifocal progression. RESULTS From January 2006 to June 2017, ninety-seven patients from thirteen medical centers were enrolled. Fifty-six patients continued imatinib therapy and 41 patients switched sunitinib treatment directly after R0 resection or optimal cytoreductive surgery. The PFS of sunitinib group was longer than that of imatinib group (30.0 months vs 12.0 months, p = 0.009). In subgroup analysis, the PFS of the sunitinib and imatinib groups were 25.5 months and 12.0 months in patients with tumor multifocal progression (p = 0.008), and 39.0 months and 13.0 months in patients with unifocal progression (p = 0.156), respectively. PFS of postoperative sunitinib group was also superior to the total PFS of postoperative imatinib group (PFS of postoperative imatinib plus PFS of subsequent sunitinib therapy (30.0 months vs 21.0 months, p = 0.012). The overall survival in the sunitinib and imatinib groups were 37.0 months and 33.0 months, respectively (p = 0.794). CONCLUSIONS Surgery followed by sunitinib in GIST patients with unifocal or multifocal progression on imatinib may improve PFS, compared with surgery followed by imatinib.
Collapse
Affiliation(s)
- Xinhua Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangdong, China
| | - Ye Zhou
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Xin Wu
- General Surgery, The General Hospital of the People's Liberation Army, Beijing, China
| | - Mingming Nie
- Department of Gastrointestinal Surgery, Shanghai Changhai Hospital, Navy Military Medical University, Shanghai, China
| | - Bo Zhang
- Gastrointestinal Surgery, West China Hospital, Sichuan University, Sichuan, China
| | - Yongjian Zhou
- Department of Gastric Surgery, Union Hospital of Fujian Medical University, Fujian, China
| | - Lifeng Sun
- Department of Surgical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang, China
| | - Zimin Liu
- Department of Oncology, The Affiliated Hospital of Qingdao University, Shandong, China
| | - Xiufeng Liu
- People's Liberation Army Cancer Center, Bayi Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangsu, China
| | - Youwei Kou
- Department of Gastrointestinal and Nutriology Surgery, Shengjing Hospital of China Medical University, Liaoning, China
| | - Yongpeng Wang
- Department of Colorectal Surgery, Liaoning Cancer Hospital and Institute, Liaoning, China
| | - Yefan Zhang
- Department of Hepatobiliary Surgery, National Cancer Center/cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chunyi Hao
- Department of Hepatobiliary Surgery, Laboratory of Carcinogenesis and Translational Research of the Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing, China
| | - Lin Shen
- Department of GI Oncology, Laboratory of Carcinogenesis and Translational Research of the Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing, China.
| | - Jian Li
- Department of GI Oncology, Laboratory of Carcinogenesis and Translational Research of the Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing, China.
| |
Collapse
|
33
|
Cai Z, Yin Y, Shen C, Tang S, Yin X, Chen Z, Zhang B. Role of surgical resection for patients with recurrent or metastatic gastrointestinal stromal tumors: A systematic review and meta-analysis. Int J Surg 2018; 56:108-114. [PMID: 29920339 DOI: 10.1016/j.ijsu.2018.06.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Revised: 04/24/2018] [Accepted: 06/10/2018] [Indexed: 01/11/2023]
|
34
|
Gaitanidis A, Alevizakos M, Tsaroucha A, Pitiakoudis M. Outcomes After Surgical Resection Differ by Primary Tumor Location for Metastatic Gastrointestinal Stromal Tumors (GISTs): a Propensity Score Matching Population Study. J Gastrointest Cancer 2018; 50:750-758. [PMID: 30033508 DOI: 10.1007/s12029-018-0137-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
PURPOSE Primary tumor location has been identified as an important prognostic factor among patients with gastrointestinal stromal tumors (GISTs). The purpose of this study is to identify how primary tumor location may affect outcomes after resection for patients with metastatic GISTs. METHODS Patients with GISTs and distant metastases at diagnosis were identified in the Surveillance Epidemiology and End Results (SEER) database. Patients that underwent surgery were matched to patients that did not undergo surgery using propensity score matching (PSM) analysis. RESULTS After PSM, 570 patients were identified (males 334 [58.6%], females 236 [41.4%], age 62 ± 13.9 years). Gastric tumors constituted the majority (325 [57%]), followed by small intestinal (136 [23.9%]), colorectal (19 [3.3%]), and retroperitoneal/peritoneal tumors (23 [4%]). Median follow-up was 25.5 months (95% CI 23-29 months). Undergoing surgery was associated with improved disease-specific survival (DSS) on both univariate (median not reached vs. 51 months, p < 0.001) and multivariate analyses (HR 4.98, 95% CI 2.23-11.12, p < 0.001). A sub-analysis of patients with gastric GISTs showed that undergoing surgery was the only significant factor associated with improved DSS (median not reached vs. 39 months, p < 0.001, HR 2.95, 95% CI 1.92-4.53). In contrast, undergoing surgery was not associated with improved survival for small intestinal, colorectal, or retroperitoneal/peritoneal tumors. CONCLUSIONS Surgery for gastric metastatic GISTs is associated with improved survival. No discernible benefit after surgical resection was identified for patients with small intestinal, colorectal, retroperitoneal, or peritoneal metastatic GISTs.
Collapse
Affiliation(s)
- Apostolos Gaitanidis
- Second Department of Surgery, University General Hospital of Alexandroupoli, Democritus University of Thrace Medical School, 68100, Alexandroupoli, Greece.
| | - Michail Alevizakos
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Alexandra Tsaroucha
- Second Department of Surgery, University General Hospital of Alexandroupoli, Democritus University of Thrace Medical School, 68100, Alexandroupoli, Greece
| | - Michail Pitiakoudis
- Second Department of Surgery, University General Hospital of Alexandroupoli, Democritus University of Thrace Medical School, 68100, Alexandroupoli, Greece
| |
Collapse
|
35
|
de Baere T, Tselikas L, Gravel G, Hakime A, Deschamps F, Honoré C, Mir O, Lecesne A. Interventional radiology: Role in the treatment of sarcomas. Eur J Cancer 2018; 94:148-155. [DOI: 10.1016/j.ejca.2018.02.017] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Accepted: 02/08/2018] [Indexed: 02/06/2023]
|
36
|
Roland CL, Bednarski BK, Watson K, Torres KE, Cormier JN, Wang WL, Lazar A, Somaiah N, Hunt KK, Feig BW. Identification of preoperative factors associated with outcomes following surgical management of intra-abdominal recurrent or metastatic GIST following neoadjuvant tyrosine kinase inhibitor therapy. J Surg Oncol 2018; 117:879-885. [PMID: 29448300 PMCID: PMC5992050 DOI: 10.1002/jso.24988] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 12/20/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND The role of surgical resection in the treatment of patients with metastatic/recurrent gastrointestinal stromal tumors (GIST) is unclear. The aim of this study was to identify preoperative factors associated with oncologic outcomes for recurrent/metastatic GIST after tyrosine kinase inhibitor (TKI) therapy. METHODS We identified 107 patients with metastatic or recurrent GIST treated with TKIs and surgical resection (2002-2012). Patients that underwent palliative or incomplete resection were excluded. Complete resection was achieved in 87 patients which comprise the analytic cohort. Univariate and multivariate analyses were conducted to identify risk factors for GIST-specific survival (DSS) and time-to-recurrence (TTR). RESULTS At a median follow-up of 51 months (91 months for survivors), median DSS was 74 months and TTR was 21 months. By univariate analysis, unifocal disease, duration of TKI < 365 days, and no evidence of radiographic progression were associated with improved TTR and DSS. Multivariate Cox regression demonstrated that evidence of radiographic progression was associated with shorter DSS (HR 2.53, 95%CI = 1.27-5.06, P = 0.008) and increased risk of recurrence (HR 3.33, 95%CI = 1.91-5.82, P < 0.001). CONCLUSIONS Patients with unifocal disease and radiographic evidence of response to TKI therapy may achieve improved oncologic outcomes when complete surgical resection is achieved following treatment with TKI.
Collapse
Affiliation(s)
- Christina L. Roland
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Brian K. Bednarski
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Kelsey Watson
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Keila E. Torres
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Janice N. Cormier
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Wei-Lien Wang
- Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Alexander Lazar
- Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Neeta Somaiah
- Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Kelly K. Hunt
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Barry W. Feig
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| |
Collapse
|
37
|
Kikuchi H, Hiramatsu Y, Kamiya K, Morita Y, Sakaguchi T, Konno H, Takeuchi H. Surgery for metastatic gastrointestinal stromal tumor: to whom and how to? Transl Gastroenterol Hepatol 2018; 3:14. [PMID: 29682621 DOI: 10.21037/tgh.2018.02.02] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Accepted: 02/25/2018] [Indexed: 12/20/2022] Open
Abstract
Although imatinib is a standard treatment for metastatic or recurrent gastrointestinal stromal tumors (GISTs), acquired c-kit mutations reportedly cause secondary resistance to imatinib. Sunitinib is a tyrosine kinase inhibitor (TKI) that can be used as second-line therapy in imatinib-resistant or -intolerant GISTs. For sunitinib-resistant or -intolerant GISTs, regorafenib is a standard third-line treatment. Although TKI therapies have revolutionized the treatment of recurrent or metastatic GISTs, they cannot cure GISTs. Therefore, in the era of TKIs, role of cytoreductive surgery for recurrent or metastatic GISTs has been discussed. Retrospective studies of treatment strategies with front-line surgery prior to imatinib have shown that initial cytoreduction confers no benefit in cases of advanced or recurrent GIST, and administering imatinib is the principle treatment. Most retrospective studies report cytoreductive surgery to be feasible in patients with metastatic GIST whose disease is stable or responsive to imatinib. Cytoreductive surgery may be indicated in limited disease progression refractory to imatinib when complete resection is possible, but case selection is critical. Cytoreductive surgery for metastatic GIST treated with sunitinib seems less feasible because of high rates of incomplete resections and complications. The role of cytoreductive surgery for metastatic GISTs would be difficult to establish in a prospective study; individualized treatments need to be carefully designed based on c-kit and platelet-derived growth factor receptor alpha (PDGFRA) mutations and other factors.
Collapse
Affiliation(s)
| | | | | | | | | | - Hiroyuki Konno
- Hamamatsu University School of Medicine, Hamamatsu, Japan
| | | |
Collapse
|
38
|
Ishikawa T, Kanda T, Kameyama H, Wakai T. Neoadjuvant therapy for gastrointestinal stromal tumor. Transl Gastroenterol Hepatol 2018; 3:3. [PMID: 29441368 DOI: 10.21037/tgh.2018.01.01] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Accepted: 12/27/2017] [Indexed: 12/21/2022] Open
Abstract
Molecular-targeting therapy using tyrosine kinase inhibitor imatinib mesylate is effective for metastasis/recurrent gastrointestinal stromal tumors (GISTs). Likewise, imatinib would be effective in the neoadjuvant therapy for high-risk GIST. Neoadjuvant therapy may have the potential to increase the complete resection rate and to avoid the surgical rupture by decreasing the tumor size. Thereby, it is expected that improvement of recurrence rate and survival rate can be obtained by neoadjuvant therapy. Neoadjuvant therapy is also expected to be favored from the viewpoint of organ/function preservation by tumor shrinkage. The existing results of clinical trials established the feasibility of neoadjuvant imatinib therapy. However, proof of the survival effectiveness of neoadjuvant imatinib therapy has not been sufficiently demonstrated. The aim of this article is to introduce previous evidence and strategies regarding neoadjuvant therapy for GIST.
Collapse
Affiliation(s)
- Takashi Ishikawa
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Tatsuo Kanda
- Department of Surgery, Sanjo General Hospital, Niigata, Japan
| | - Hitoshi Kameyama
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| |
Collapse
|
39
|
Qiu HB, Zhou ZG, Feng XY, Liu XC, Guo J, Ma MZ, Chen YB, Sun XW, Zhou ZW. Advanced gastrointestinal stromal tumor patients benefit from palliative surgery after tyrosine kinase inhibitors therapy. Medicine (Baltimore) 2018; 97:e9097. [PMID: 29480823 PMCID: PMC5943843 DOI: 10.1097/md.0000000000009097] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
The role of palliative surgery is controversial in advanced gastrointestinal stromal tumors (GIST) after tyrosine kinase inhibitors (TKIs) therapy.We evaluated safety and clinical outcomes in a single institution series of advanced GIST patients from January 2002 to December 2008.One hundred and fifty-six patients had been recruited, including 87 patients underwent surgical resection and 69 patients kept on TKIs treatment. Four patients had major surgical complications. Median follow-up was 38.3 months, the overall survival (OS) and progression-free survival (PFS) of the patients in surgical group were longer than the nonsurgical group, PFS: 46.1 versus 33.8 months (P < .01), OS: 54.8 versus 40.4 months. In the subgroup analysis for the patients received surgery, the median PFS for patients with progression disease, stable disease, and partial response was 33.3, 51.5, and 83.0 months, respectively (P < .01). Median OS was 68.0 months in those with only liver or peritoneal metastases, and 45.3 months in those with both metastases. Median PFS of patients underwent R0/R1 resection was 73.6 months compared with 35.8 months in R2 resection patients (P < .01).Patients with advanced GISTs have prolonged OS after debulking procedures. Surgery for patients who have responsive disease after TKIs treatment should be considered.
Collapse
Affiliation(s)
- Hai-Bo Qiu
- Department of Gastric and Pancreatic Surgery
| | - Zhong-Guo Zhou
- State Key Laboratory of Southern China, Department of Hepatobilliary Oncology, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine
| | - Xing-Yu Feng
- Department of General Surgery, Guangdong General Hospital, Guangzhou, Guangdong, China
| | | | - Jing Guo
- Department of Gastric and Pancreatic Surgery
| | - Ming-Zhe Ma
- Department of Gastric and Pancreatic Surgery
| | | | | | | |
Collapse
|
40
|
Fero KE, Coe TM, Fanta PT, Tang CM, Murphy JD, Sicklick JK. Surgical Management of Adolescents and Young Adults With Gastrointestinal Stromal Tumors: A US Population-Based Analysis. JAMA Surg 2017; 152:443-451. [PMID: 28114506 DOI: 10.1001/jamasurg.2016.5047] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Importance There is a dearth of population-based evidence regarding outcomes of the adolescent and young adult (AYA) population with gastrointestinal stromal tumors (GISTs). Objectives To describe a large cohort of AYA patients with GISTs and investigate the effect of surgery on GIST-specific survival (GSS) and overall survival (OS). Design, Setting, and Participants This retrospective cohort study of 392 AYA patients and 5373 older adult (OA) patients in the Surveillance, Epidemiology, and End Results (SEER) database with GISTs histologically diagnosed from January 1, 2001, through December 31, 2013, with follow-up through December 31, 2015, compared the baseline characteristics of AYA (13-39 years old) and OA (≥40 years old) patients and among AYA patients stratified by operative management. Kaplan-Meier estimates were used for OS analyses. Cumulative incidence functions were used for GSS analysis. The effect of surgery on survival was evaluated with a multivariable Fine-Gray regression model. Exposure Tumor resection. Main Outcomes and Measures GIST-specific survival and OS. Results This study included 392 AYA and 5373 OA patients diagnosed with GISTs (207 [52.8%] male AYA patients, 2767 [51.5%] male OA patients, 277 [70.7%] white AYA patients, and 3661 [68.1%] white OA patients). Compared with the OA patients, more AYA patients had small-intestine GISTs (139 [35.5%] vs 1465 [27.3%], P = .008) and were managed operatively (332 [84.7%] vs 4212 [78.4%], P = .003). Multivariable analysis of AYA patients found that nonoperative management was associated with a more than 2-fold increased risk of death from GISTs (subdistribution hazard ratio, 2.27; 95% CI, 1.21-2.25; P = .01). On subset analysis of 349 AYA patients with tumors of the stomach and small intestine, small-intestine location was associated with improved survival (OS: 91.1% vs 77.2%, P = .01; GSS: 91.8% vs 78.0%, P = .008). On subset analysis of 91 AYA patients with metastatic disease, operative management was associated with improved survival (OS: 69.5% vs 53.7%, P = .04; GSS: 71.5% vs 56.7%, P = .03). Conclusions and Relevance This study found that AYA patients are more likely to undergo surgical management than OA patients. Operative management is associated with improved OS and GSS in AYA patients, including those with metastatic disease.
Collapse
Affiliation(s)
- Katherine E Fero
- School of Medicine, University of California, San Diego, La Jolla
| | - Taylor M Coe
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston
| | - Paul T Fanta
- School of Medicine, University of California, San Diego, La Jolla3Moores Cancer Center, Division of Medical Oncology, Department of Medicine, University of California, San Diego, La Jolla
| | - Chih-Min Tang
- Moores Cancer Center, Division of Surgical Oncology, Department of Surgery, University of California, San Diego, La Jolla
| | - James D Murphy
- School of Medicine, University of California, San Diego, La Jolla5Moores Cancer Center, Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla
| | - Jason K Sicklick
- School of Medicine, University of California, San Diego, La Jolla4Moores Cancer Center, Division of Surgical Oncology, Department of Surgery, University of California, San Diego, La Jolla
| |
Collapse
|
41
|
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract. The stomach is the most common site of origin. Management of GISTs changed after the introduction of molecularly targeted therapies. Although the only potentially curative treatment of resectable primary GISTs is surgery, recurrence is common. Patients with primary GISTs at intermediate or high risk of recurrence should receive imatinib postoperatively. Imatinib is also first-line therapy for advanced disease. Cytoreductive surgery might be considered in advanced GIST for patients with stable/responding disease or limited focal progression on tyrosine kinase inhibitor therapy. GIST requires multidisciplinary management.
Collapse
Affiliation(s)
- Emily Z Keung
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Unit 1484, Houston, TX 77030, USA
| | - Chandrajit P Raut
- Department of Surgery, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA; Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02115, USA.
| |
Collapse
|
42
|
D'Ambrosio L, Palesandro E, Boccone P, Tolomeo F, Miano S, Galizia D, Manca A, Chiara G, Bertotto I, Russo F, Campanella D, Venesio T, Sangiolo D, Pignochino Y, Siatis D, De Simone M, Ferrero A, Pisacane A, Dei Tos AP, Aliberti S, Aglietta M, Grignani G. Impact of a risk-based follow-up in patients affected by gastrointestinal stromal tumour. Eur J Cancer 2017; 78:122-132. [PMID: 28448856 DOI: 10.1016/j.ejca.2017.03.025] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2016] [Revised: 02/16/2017] [Accepted: 03/24/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND Follow-up aims to precociously identify recurrences, metastases or treatment-related adverse events so as to undertake the appropriate therapy. Guidelines admit lack of knowledge on optimal surveillance schedule, but suggest follow-up based on experts' opinion and risk stratification. To identify the impact, if any, of regular follow-up, we interrogated our prospectively collected database whether early detection of recurrences affected both clinical management and, likely, the outcome. PATIENTS AND METHODS We required information to be available on primary surgery and ≥3°years of follow-up for non-recurring patients. We analysed recurrence characteristics (asymptomatic versus symptomatic, low- versus high tumour burden) and computed tomography (CT) scan counts to detect one recurrence. Kaplan-Meier method estimated recurrence-free survival (RFS), post-recurrence progression-free survival (PR-PFS), and disease-specific overall survival (OS). Comparisons used Hazard ratios (HR) with 95% confidence intervals (CIs). Multivariate analyses employed the Cox proportional hazards model. All tests were two-sided. RESULTS Between 01/2001 and 12/2012 we found 233 study-eligible patients. Estimated 5- and 10-year RFS were 61.8% and 50.4%, respectively. After a 68-month median follow-up, we observed 94 (40.3%) recurrences [73/94 (77.7%) asymptomatic versus 21/94 (22.3%) symptomatic and 45/94 (47.9%) low- versus 49/94 (52.1%) high tumour burden]. Multivariate analysis revealed that symptomatic and high tumour burden recurrences were highly predictive of both worse PR-PFS (HR:3.19, P < 0.001; HR:2.80, P = 0.003, respectively) and OS (HR:3.65, P < 0.001; HR:2.38, P = 0.026, respectively). Finally, 29 second (primary) cancers were detected during follow-up. CONCLUSIONS Regular follow-up detects recurrences at an earlier stage and may be associated with a better PR-PFS and OS for these patients. In the absence of randomised trials, these evidences support follow-up effort and cost.
Collapse
Affiliation(s)
- Lorenzo D'Ambrosio
- Sarcoma Unit, Division of Medical Oncology Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy; University of Torino, Department of Oncology, Regione Gonzole, 10, 10043 Orbassano, TO, Italy
| | - Erica Palesandro
- Sarcoma Unit, Division of Medical Oncology Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy; University of Torino, Department of Oncology, Regione Gonzole, 10, 10043 Orbassano, TO, Italy
| | - Paola Boccone
- Sarcoma Unit, Division of Medical Oncology Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy; University of Torino, Department of Oncology, Regione Gonzole, 10, 10043 Orbassano, TO, Italy
| | - Francesco Tolomeo
- Sarcoma Unit, Division of Medical Oncology Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy; University of Torino, Department of Oncology, Regione Gonzole, 10, 10043 Orbassano, TO, Italy
| | - Sara Miano
- Sarcoma Unit, Division of Medical Oncology Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy; University of Torino, Department of Oncology, Regione Gonzole, 10, 10043 Orbassano, TO, Italy
| | - Danilo Galizia
- Sarcoma Unit, Division of Medical Oncology Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy; University of Torino, Department of Oncology, Regione Gonzole, 10, 10043 Orbassano, TO, Italy
| | - Antonio Manca
- Radiology Unit, Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy
| | - Gabriele Chiara
- Radiology Unit, Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy
| | - Ilaria Bertotto
- Radiology Unit, Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy
| | - Filippo Russo
- Radiology Unit, Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy
| | - Delia Campanella
- Radiology Unit, Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy
| | - Tiziana Venesio
- Pathology Unit, Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy
| | - Dario Sangiolo
- Sarcoma Unit, Division of Medical Oncology Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy; University of Torino, Department of Oncology, Regione Gonzole, 10, 10043 Orbassano, TO, Italy
| | - Ymera Pignochino
- Sarcoma Unit, Division of Medical Oncology Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy; University of Torino, Department of Oncology, Regione Gonzole, 10, 10043 Orbassano, TO, Italy
| | - Dimitrios Siatis
- Surgical Oncology Unit, Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy
| | - Michele De Simone
- Surgical Oncology Unit, Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy
| | - Alessandro Ferrero
- Department of General and Oncological Surgery, Ospedale Mauriziano "Umberto I", Via Magellano 1, 10128 Torino, TO, Italy
| | - Alberto Pisacane
- Pathology Unit, Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy
| | - Angelo Paolo Dei Tos
- Department of Pathology and Molecular Genetics, Treviso General Hospital, Piazza Ospedale 23, 31100 Treviso, TV, Italy; University of Padova, Department of Medicine, Via 8 febbraio 2, 35122 Padova, PD, Italy
| | - Sandra Aliberti
- Sarcoma Unit, Division of Medical Oncology Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy
| | - Massimo Aglietta
- Sarcoma Unit, Division of Medical Oncology Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy; University of Torino, Department of Oncology, Regione Gonzole, 10, 10043 Orbassano, TO, Italy
| | - Giovanni Grignani
- Sarcoma Unit, Division of Medical Oncology Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy; University of Torino, Department of Oncology, Regione Gonzole, 10, 10043 Orbassano, TO, Italy.
| |
Collapse
|
43
|
Judson I, Bulusu R, Seddon B, Dangoor A, Wong N, Mudan S. UK clinical practice guidelines for the management of gastrointestinal stromal tumours (GIST). Clin Sarcoma Res 2017; 7:6. [PMID: 28465823 PMCID: PMC5408425 DOI: 10.1186/s13569-017-0072-8] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Accepted: 04/06/2017] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Soft tissue sarcomas (STS) are rare tumours arising in mesenchymal tissues. Gastrointestinal stromal tumour (GIST) is the commonest STS and arises within the wall of the gastrointestinal (GI) tract. While most GISTs occur in the stomach they do occur in all parts of the GI tract. As with other STS, it is important that GISTs are managed by expert teams, to ensure consistent and optimal treatment, as well as recruitment to clinical trials, and the ongoing accumulation of further knowledge of the disease. The development of appropriate guidance, by an experienced panel referring to the evidence available, is therefore a useful foundation on which to build progress in the field. METHODOLOGY British Sarcoma Group guidelines for the management of GIST were initially developed by a panel of physicians experienced in the management of GIST. This current version has been updated and amended with reference to other European and US guidance. We have received input from representatives of all diagnostic and treatment disciplines as well as patient representatives. Levels of evidence and strength of recommendation gradings are those used by ESMO adapted from those published by the Infectious Disease Society of America. CONCLUSIONS The guidelines cover aetiology, genetics and underlying molecular mechanisms, diagnosis and initial investigations, staging and risk stratification, surgery, neoadjuvant and adjuvant therapy, the management of advanced disease and follow-up. The importance of mutational analysis in guiding treatment is highlighted, since this can indicate the most effective treatment and avoid administration of ineffective drugs, emphasising the need for management in specialist centres.
Collapse
Affiliation(s)
- Ian Judson
- The Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Fulham Road, London, SW3 6JJ UK
| | - Ramesh Bulusu
- Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, UK
| | - Beatrice Seddon
- University College Hospital, University College London Hospitals NHS Foundation Trust, London, UK
| | - Adam Dangoor
- Bristol Cancer Institute, University Hospitals, Bristol NHS Trust, Bristol, UK
| | - Newton Wong
- Southmead Hospital, North Bristol NHS Trust, Bristol, UK
| | | |
Collapse
|
44
|
Kawamura N, Kamiyama T, Yokoo H, Kakisaka T, Orimo T, Wakayama K, Tsuruga Y, Kamachi H, Hatanaka K, Taketomi A. Hepatectomy for liver metastasis from gastrointestinal stromal tumor in the era of imatinib mesylate: a case series study. Int Cancer Conf J 2017; 6:121-125. [PMID: 31149485 DOI: 10.1007/s13691-017-0289-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Accepted: 03/23/2017] [Indexed: 10/19/2022] Open
Abstract
The prognosis of metastatic gastrointestinal stromal tumor (GIST) has improved since the introduction of imatinib mesylate; however, acquired resistance has been reported, so alternative treatment option is needed. We evaluated the efficacy of hepatectomy for metastatic GIST. Six patients with liver metastases from GIST underwent hepatectomy. Four were treated with imatinib mesylate before hepatectomy, and all the patients were treated with imatinib mesylate after hepatectomy. Patients were followed-up for a mean duration of 113.5 months after hepatectomy. Complete resection was accomplished in four patients, with incomplete resection performed in the remaining two patients due to peritoneal dissemination. One patient with incomplete resection died 10 months after surgery. One patient with complete resection has survived without disease progression since initial hepatectomy. The remaining four patients with progressive disease during imatinib mesylate treatment developed tumor recurrence and three of them underwent a second hepatectomy. These three patients underwent complete resection during repeat surgery. In total, three patients died during the follow-up period, all of whom had tumors of small intestine origin. Primary tumor site (small intestine vs. others) was identified as a risk factor of mortality (P = 0.02). Although not statistically significant, there was a trend toward better outcomes in patients with exon 11 mutations. Surgical resection for metastatic GIST was shown to be effective and needed to achieve a better prognosis. Repeat hepatectomy demonstrated efficacy in selected patients. Hepatectomy should be considered based on tumor characteristics such as primary tumor site and c-KIT mutation status.
Collapse
Affiliation(s)
- Norio Kawamura
- 1Gastroenterological Surgery 1, Hokkaido University Hospital, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8648 Japan
| | - Toshiya Kamiyama
- 1Gastroenterological Surgery 1, Hokkaido University Hospital, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8648 Japan
| | - Hideki Yokoo
- 1Gastroenterological Surgery 1, Hokkaido University Hospital, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8648 Japan
| | - Tatsuhiko Kakisaka
- 1Gastroenterological Surgery 1, Hokkaido University Hospital, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8648 Japan
| | - Tatsuya Orimo
- 1Gastroenterological Surgery 1, Hokkaido University Hospital, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8648 Japan
| | - Kenji Wakayama
- 1Gastroenterological Surgery 1, Hokkaido University Hospital, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8648 Japan
| | - Yosuke Tsuruga
- 1Gastroenterological Surgery 1, Hokkaido University Hospital, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8648 Japan
| | - Hirofumi Kamachi
- 1Gastroenterological Surgery 1, Hokkaido University Hospital, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8648 Japan
| | - Kanako Hatanaka
- 2Department of Surgical Pathology, Hokkaido University Hospital, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8648 Japan
| | - Akinobu Taketomi
- 1Gastroenterological Surgery 1, Hokkaido University Hospital, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8648 Japan
| |
Collapse
|
45
|
Kubo N, Takeuchi N. Gastrointestinal stromal tumor of the stomach with axillary lymph node metastasis: A case report. World J Gastroenterol 2017; 23:1720-1724. [PMID: 28321172 PMCID: PMC5340823 DOI: 10.3748/wjg.v23.i9.1720] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Revised: 01/05/2017] [Accepted: 01/17/2017] [Indexed: 02/07/2023] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common type of gastrointestinal mesenchymal tumors, although metastasis to the perigastric lymph nodes is relatively rare, compared with liver or peritoneal metastasis. In this report, we describe a case of stomach GIST with a solitary simultaneous metastasis in the left axillary lymph node. A 68-year-old man was diagnosed with a large upper-stomach GIST, and computed tomography and positron emission tomography revealed masses in the left axilla and right mediastinum. We did not detect evidence of metastases to the liver, or other sites including the perigastric lymph nodes, although findings from the surgically resected axillary lymph nodes were compatible with GIST metastasis. Treatment using imatinib markedly reduced the gastric and mediastinal lesions, and this response persisted for 3 years. The patient subsequently experienced rapid growth of the gastric lesion without mediastinal or axilla recurrence, which required palliative surgery. Despite continuing medical treatment (sunitinib and regorafenib), the patient died of liver metastases 23 mo after the surgery. Based on our findings, it appears that the axillary lymph nodes can be a potential metastatic site for GIST metastasis.
Collapse
|
46
|
Sugase T, Takahashi T, Ishikawa T, Ichikawa H, Kanda T, Hirota S, Nakajima K, Tanaka K, Miyazaki Y, Makino T, Kurokawa Y, Yamasaki M, Takiguchi S, Wakai T, Mori M, Doki Y. Surgical resection of recurrent gastrointestinal stromal tumor after interruption of long-term nilotinib therapy. Surg Case Rep 2016; 2:137. [PMID: 27864817 PMCID: PMC5116018 DOI: 10.1186/s40792-016-0266-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Accepted: 11/15/2016] [Indexed: 01/01/2023] Open
Abstract
Background Nilotinib inhibits the tyrosine kinase activities of ABL1/BCR-ABL1, KIT, and platelet-derived growth factor receptors (PDGFRs). The results of a phase III clinical trial indicated that nilotinib could not be recommended for broad use as first-line therapy for gastrointestinal stromal tumor (GIST). However, some clinical studies have reported the effectiveness of nilotinib. We report here the cases of two patients who underwent surgical resections of nilotinib-resistant lesions after long-term nilotinib administration. Case presentation Two Japanese female patients, aged 66 and 70 years, experienced peritoneal recurrence of intestinal GIST several years after surgery. Both were registered in the ENESTg1 trial and received nilotinib therapy. Although they continued nilotinib administration with a partial response according to the protocol, nilotinib-resistant lesions, which were diagnosed as focally progressive disease, developed and complete surgical resection was performed. Pathological examination revealed that the tumors were composed of viable KIT-positive spindle cells, and the recurrent tumors were diagnosed as nilotinib-resistant GIST. In gene mutation analysis, a secondary KIT gene mutation was detected in one case. Both patients have survived more than 5 years after the first surgery. Conclusions Of patients who were registered in this trial, we have encountered two patients with long-term effects after nilotinib administration. Moreover, secondary mutations in the KIT gene, similar to those involved in resistance to imatinib, might be involved in resistance to nilotinib.
Collapse
Affiliation(s)
- Takahito Sugase
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Tsuyoshi Takahashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
| | - Takashi Ishikawa
- Division of Digestive and General Surgery, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Hiroshi Ichikawa
- Division of Digestive and General Surgery, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Tatsuo Kanda
- Department of Surgery, Sanjo General Hospital, Niigata, Japan
| | - Seiichi Hirota
- Department of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Kiyokazu Nakajima
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Koji Tanaka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yasuhiro Miyazaki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Tomoki Makino
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Makoto Yamasaki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Shuji Takiguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Masaki Mori
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| |
Collapse
|
47
|
Preoperative imatinib treatment in patients with advanced gastrointestinal stromal tumors: patient experiences and systematic review of 563 patients. Int Surg 2016; 100:860-9. [PMID: 26011207 DOI: 10.9738/intsurg-d-14-00178.1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Preoperative IM therapy for GIST is now a research focus. Due to the low incidence of the disease, there are few RCTs on the preoperative treatment for advanced GIST, let alone relevant meta-analysis. Efficacy of this therapy and targeting population are still undetermined. Therefore, the first part of this article is composed of a controlled retrospective study and demonstrates that preoperative therapy with IM can significantly improve the outcome of advanced GIST. In the second part of the paper, we further investigated what portion of advanced GIST patients benefit more from the therapy, based on a meta-analysis. As the disease is relatively rare, we involved 563 cases in the meta-analysis, much higher than in the controlled clinical studies (51 cases). The objective of this paper is to investigate effects of surgical resection on imatinib-treated advanced GIST. Twenty-two consecutive advanced GIST patients (Group A) with preoperative IM treatment were compared to 29 patients (Group B) who underwent initial tumor resection during the same period. Subsequently, a systematic review of 563 patients was applied to identify the benefit of the advanced GIST patients receiving imatinib before surgery. Compared with Group B, less patients in Group A underwent multivisceral resection (18.2% versus 48.3%, P = 0.026) or suffered tumor rupture at time of surgery (0% versus 17.2%, P = 0.04). The 3-year estimated progression-free survival of Group A (94.4%) was also superior to that of Group B (61.4%; P = 0.045). Subsequent meta-analysis indicated that primarily unresectable patients had higher complete resection and 2-year PFS rates than recurrent/metastasis patients (P = 0.005 and 0.20, respectively); (b) stable disease (SD) patients had better outcome in resection including resectability rate (P < 0.0001), PFS (P < 0.00001) and OS (P = 0.0008) than progressive disease (PD) patients; (c) in recurrent/metastatic PD patients, surgery played a minor role, because they had a higher bulky residual disease rate (P = 0.0005) and higher progression risk (P < 0.00001) within 2 years after surgery. Preoperative IM treatment improves prognosis of advanced GISTs. Among recurrent/metastatic patients, postimatinib surgery may benefit those who have SD after IM treatment but not those resistant to IM.
Collapse
|
48
|
Abstract
OPINION STATEMENT Gastrointestinal stromal tumors (GISTs) are the most common sarcomas and mesenchymal neoplasms of the gastrointestinal tract. Macroscopically complete (R0/R1) resection is the standard treatment for localized resectable GIST with adjuvant imatinib therapy recommended for patients with intermediate or high-risk disease. In patients with advanced unresectable or metastatic GIST, imatinib has significantly improved outcomes. However, while most patients achieve partial response (PR) or stable disease (SD) on imatinib (with maximal response typically seen by 6 months on treatment), approximately half will develop secondary resistance by 2 years. Available data suggest that cytoreductive surgery may be considered in patients with metastatic GIST who respond to imatinib, particularly if a R0/R1 resection is achieved. The benefit of surgery in patients with focal tumor progression on imatinib is unclear, but may be considered. Patients with multifocal progression undergoing surgery generally have poor outcomes. Thus, surgery should be considered in patients with metastatic GIST whose disease responds to imatinib with a goal of performing R0/R1 resection. Optimal timing of surgery is unclear but should be considered between 6 months and 2 years after starting imatinib. Although surgery in patients with metastatic GIST treated with sunitinib is feasible, incomplete resections are common, complication rates are high, and survival benefit is unclear. Therefore, a careful multidisciplinary consultation is required to determine optimal treatment options on a case-by-case basis. Finally, patients with metastatic GIST should resume tyrosine kinase inhibitor treatment postoperatively.
Collapse
|
49
|
Abstract
Radical surgery is the mainstay of therapy for primary resectable, localized gastrointestinal stromal tumors (GIST). Nevertheless, approximately 40% to 50% of patients with potentially curative resections develop recurrent or metastatic disease. The introduction of imatinib mesylate has revolutionized the therapy of advanced (inoperable and/or metastatic) GIST and has become the standard of care in treatment of patients with advanced GIST. This article discusses the proper selection of candidates for adjuvant and neoadjuvant treatment in locally advanced GIST, exploring the available evidence behind the combination of preoperative imatinib and surgery.
Collapse
Affiliation(s)
- Piotr Rutkowski
- Department of Soft Tissue, Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center, Institute of Oncology, Roentgena 5, Warsaw 02-781, Poland.
| | - Daphne Hompes
- Department of Surgical Oncology, University Hospitals Gasthuisberg Leuven, Herestraat 49, Leuven 3000, Belgium
| |
Collapse
|
50
|
Ford SJ, Gronchi A. Indications for surgery in advanced/metastatic GIST. Eur J Cancer 2016; 63:154-67. [PMID: 27318456 DOI: 10.1016/j.ejca.2016.05.019] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2015] [Revised: 05/05/2016] [Accepted: 05/17/2016] [Indexed: 01/14/2023]
Abstract
Gastrointestinal stromal tumours (GISTs) are a relatively rare entity and often present as a locally advanced tumour or with metastatic disease. Complete surgical resection is the only means of cure in localised disease; however, imatinib therapy has greatly advanced the management of GIST and is established as both an adjunct to surgery in high-risk cases and as principle therapy in metastatic disease. Surgery in advanced GIST has undergone a renaissance in recent years with the potential for a combined treatment approach with either neoadjuvant imatinib in locally advanced primary disease or as an adjunct to imatinib in those with metastases or recurrent disease. Neoadjuvant imatinib can render a locally advanced primary GIST resectable, allow less invasive procedures or promote preservation of function, especially if the tumour is located in an anatomically difficult position. The role of surgery in metastatic or recurrent disease is more controversial and case selection is critical. The potential benefit is difficult to quantify, although surgery may have a limited favourable impact on progression-free survival and overall survival for those patients whose disease is responding to imatinib or those with limited focal progression. Patients with imatinib resistant disease should not be offered surgery unless as an emergency where palliative intervention may be justified.
Collapse
Affiliation(s)
- Samuel J Ford
- Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Surgery, The Queen Elizabeth Hospital, Birmingham, United Kingdom
| | - Alessandro Gronchi
- Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
| |
Collapse
|