Advancements and challenges in understanding gastrointestinal stromal tumors: A comprehensive review

Atash Raut; Supriya Meshram; Preeti Raut; Avinash Thakre

doi:10.31893/multirev.2024263

Keywords:

gist in immunosuppressed

intestinal gist

sigmoid gist

gastrointestinal tumor (gist)

gastric gist

colon gist

Abstract

The most common mesenchymal tumor affecting the gastrointestinal system is gastrointestinal stromal tumor (GIST). Although GISTs are a relatively new type of tumor, the under understanding of these tumors has increased quickly. Nevertheless, there is a dearth of research on this illness in India, and the majority of treatment plans are based on studies performed on populations outside of the nation. Since the 1990s, considerable progress has been made in our knowledge of the lineage of origin of the GIST domain. According to recent research, multipotent mesenchymal stem cells are the source of GISTs, which are thought to occur in 10-20 cases per million people annually. With the overexpression of the tyrosine kinase receptor KIT in intestinal Cajal cells, GISTs are the most prevalent malignant subepithelial lesions (SELs) in the digestive tract. GISTs can have a variety of morphologies, such as rhabdomyosarcoma, angiosarcoma, or undifferentiated pleomorphic sarcoma, which makes diagnosis difficult. However, new developments in molecular targeted therapy have transformed solid tumor oncology and provided exciting new avenues for treatment. To differentiate dedifferentiated GISTs from other gastrointestinal malignancies, this review paper will address current immunohistochemical markers and provide an outline of the morphologic and molecular features of these tumors. The findings also emphasize the importance of GIST genetic testing, progressive surgical approaches, adjuvant and neoadjuvant therapy for localized disorders, and metastatic condition-addressing methodologies. This article's major body explores the impact of imatinib therapy, the rarity of GISTs in pediatric patients, imaging methods for staging and monitoring, and difficulties with treating anorectal GISTs. This study highlights how crucial it is to pinpoint particular molecular subtypes to inform therapeutic choices for adjuvant and metastatic therapies.
References
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2. Al-Maghrabi, H., Alahmadi, S., & Falemban, A. H. (2020). Primary Gastrointestinal Stromal Tumor of the Prostate: Unexpected Guest. Cureus, 12(9), e10244. https://doi.org/10.7759/cureus.10244
3. Altini, C., Mammucci, P., Pisani, A. R., D’Alò, C., Sardaro, A., Rubini, D., Ferrari, C., & Rubini, G. (2021). 18F-FDG PET/CT in GIST treatment response evaluation beyond Imatinib. Hellenic Journal of Nuclear Medicine, 24(3), 239–246. https://doi.org/10.1967/s002449912407
4. Amato, A. (2010a). Colorectal gastrointestinal stromal tumor. Techniques in Coloproctology, 14 Suppl 1, S91-95. https://doi.org/10.1007/s10151-010-0631-y
5. Amato, A. (2010b). Colorectal gastrointestinal stromal tumor. Techniques in Coloproctology, 14 Suppl 1, S91-95. https://doi.org/10.1007/s10151-010-0631-y
6. Beham, A. W., Schaefer, I.-M., Schüler, P., Cameron, S., & Ghadimi, B. M. (2012). Gastrointestinal stromal tumors. International Journal of Colorectal Disease, 27(6), 689–700. https://doi.org/10.1007/s00384-011-1353-y
7. Dhillon, S. (2020). Ripretinib: First Approval. Drugs, 80(11), 1133–1138. https://doi.org/10.1007/s40265-020-01348-2
8. Dudzisz-Śledź, M., Bylina, E., Teterycz, P., & Rutkowski, P. (2021). Treatment of Metastatic Gastrointestinal Stromal Tumors (GIST): A Focus on Older Patients. Drugs & Aging, 38(5), 375–396. https://doi.org/10.1007/s40266-021-00841-x
9. Eisenberg, B. L., & Pipas, J. M. (2012). Gastrointestinal stromal tumor—Background, pathology, treatment. Hematology/Oncology Clinics of North America, 26(6), 1239–1259. https://doi.org/10.1016/j.hoc.2012.08.003
10. Goggin, C., Stansfeld, A., Mahalingam, P., Thway, K., Smith, M. J., Huang, P., Jones, R. L., & Napolitano, A. (2022). Ripretinib in advanced gastrointestinal stromal tumors: An overview of current evidence and drug approval. Future Oncology (London, England), 18(26), 2967–2978. https://doi.org/10.2217/fon-2022-0226
11. Gupta, A. (2019). Gallbladder GIST: A review of literature. Polski Przeglad Chirurgiczny, 92(1), 34–37. https://doi.org/10.5604/01.3001.0013.5550
12. Herzberg, M., Beer, M., Anupindi, S., Vollert, K., & Kröncke, T. (2018). Imaging pediatric gastrointestinal stromal tumor (GIST). Journal of Pediatric Surgery, 53(9), 1862–1870. https://doi.org/10.1016/j.jpedsurg.2018.03.022
13. Huang, W.-K., Wu, C.-E., Wang, S.-Y., Chang, C.-F., Chou, W.-C., Chen, J.-S., & Yeh, C.-N. (2022). Systemic Therapy for Gastrointestinal Stromal Tumor: Current Standards and Emerging Challenges. Current Treatment Options in Oncology, 23(9), 1303–1319. https://doi.org/10.1007/s11864-022-00996-8
14. Iorio, N., Sawaya, R. A., & Friedenberg, F. K. (2014). Review article: The biology, diagnosis and management of gastrointestinal stromal tumours. Alimentary Pharmacology & Therapeutics, 39(12), 1376–1386. https://doi.org/10.1111/apt.12761
15. Joensuu, H. (2013). Gastrointestinal stromal tumors: Risk assessment and adjuvant therapy. Hematology/Oncology Clinics of North America, 27(5), 889–904. https://doi.org/10.1016/j.hoc.2013.07.004
16. Khan, S. I., O’Sullivan, N. J., Temperley, H. C., Rausa, E., Mehigan, B. J., McCormick, P., Larkin, J. O., Kavanagh, D. O., & Kelly, M. E. (2023). Gastrointestinal Stromal Tumours (GIST) of the Rectum: A Systematic Review and Meta-Analysis. Current Oncology, 30(1), Article 1. https://doi.org/10.3390/curroncol30010034
17. Lamba, G., Ambrale, S., Lee, B., Gupta, R., Rafiyath, S. M., & Liu, D. (2012). Recent advances and novel agents for gastrointestinal stromal tumor (GIST). Journal of Hematology & Oncology, 5, 21. https://doi.org/10.1186/1756-8722-5-21
18. Liu, Z., Wu, S., Gou, S., Li, Y., Wu, H., & Li, Y. (2019). A Population-Based Study of the Incidence and Survival of Anorectal Gastrointestinal Stromal Tumor. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, 25, 5408–5417. https://doi.org/10.12659/MSM.915967
19. Mantese, G. (2019). Gastrointestinal stromal tumor: Epidemiology, diagnosis, and treatment. Current Opinion in Gastroenterology, 35(6), 555–559. https://doi.org/10.1097/MOG.0000000000000584
20. Minhas, S., Bhalla, S., Jauhri, M., Ganvir, M., & Aggarwal, S. (2019). Clinico-Pathological Characteristics and Mutational Analysis of Gastrointestinal Stromal Tumors from India: A Single Institution Experience. Asian Pacific Journal of Cancer Prevention : APJCP, 20(10), 3051–3055. https://doi.org/10.31557/APJCP.2019.20.10.3051
21. Nannini, M., Rizzo, A., Indio, V., Schipani, A., Astolfi, A., & Pantaleo, M. A. (2021). Targeted therapy in SDH-deficient GIST. Therapeutic Advances in Medical Oncology, 13, 17588359211023278. https://doi.org/10.1177/17588359211023278
22. Park, J.-J. (2016). Long-Term Outcomes after Endoscopic Treatment of Gastric Gastrointestinal Stromal Tumor. Clinical Endoscopy, 49(3), 232–234. https://doi.org/10.5946/ce.2016.052
23. Reid, T. (2013). Reintroduction of imatinib in GIST. Journal of Gastrointestinal Cancer, 44(4), 385–392. https://doi.org/10.1007/s12029-013-9532-4
24. Schaefer, I.-M., DeMatteo, R. P., & Serrano, C. (2022). The GIST of Advances in Treatment of Advanced Gastrointestinal Stromal Tumor. American Society of Clinical Oncology Educational Book. American Society of Clinical Oncology. Annual Meeting, 42, 1–15. https://doi.org/10.1200/EDBK_351231
25. Sciot, R., & Debiec-Rychter, M. (2006). GIST under imatinib therapy. Seminars in Diagnostic Pathology, 23(2), 84–90. https://doi.org/10.1053/j.semdp.2006.08.005
26. Senchak, J., Ahr, K., & von Mehren, M. (2022). Gastrointestinal Stromal Tumors: What Is the Best Sequence of TKIs? Current Treatment Options in Oncology, 23(5), 749–761. https://doi.org/10.1007/s11864-022-00958-0
27. Serrano, C., & Bauer, S. (2022). New Tyrosine Kinase Inhibitors for the Treatment of Gastrointestinal Stromal Tumors. Current Oncology Reports, 24(2), 151–159. https://doi.org/10.1007/s11912-021-01165-0
28. Stamatakos, M., Douzinas, E., Stefanaki, C., Safioleas, P., Polyzou, E., Levidou, G., & Safioleas, M. (2009). Gastrointestinal stromal tumor. World Journal of Surgical Oncology, 7, 61. https://doi.org/10.1186/1477-7819-7-61
29. Swalchick, W., Shamekh, R., & Bui, M. M. (2015). Is DOG1 Immunoreactivity Specific to Gastrointestinal Stromal Tumor? Cancer Control: Journal of the Moffitt Cancer Center, 22(4), 498–504. https://doi.org/10.1177/107327481502200416
30. Valadão, M., & Linhares, E. (2009). The role of the surgeon in the management of GIST. Revista Do Colegio Brasileiro De Cirurgioes, 36(3), 261–265.
31. Willobee, B. A., Quiroz, H. J., Sussman, M. S., Thorson, C. M., Sola, J. E., & Perez, E. A. (2018). Current treatment strategies in pediatric gastrointestinal stromal cell tumor. Translational Gastroenterology and Hepatology, 3, 53. https://doi.org/10.21037/tgh.2018.07.09
32. Xue, F., Wang, W., Shi, N., Ma, X.-B., & Liu, C.-X. (2019). Endoscopic resection of giant gastrointestinal stromal tumor at the esophagogastric junction: A case report. BMC Gastroenterology, 19(1), 227. https://doi.org/10.1186/s12876-019-1151-5

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

How to cite

Raut, A., Meshram, S., Raut, P., & Thakre, A. (2024). Advancements and challenges in understanding gastrointestinal stromal tumors: A comprehensive review. Multidisciplinary Reviews, 7(11), 2024263. https://doi.org/10.31893/multirev.2024263

[1] Akahoshi, K., Oya, M., Koga, T., & Shiratsuchi, Y. (2018). Current clinical management of gastrointestinal stromal tumor. World Journal of Gastroenterology, 24(26), 2806–2817. https://doi.org/10.3748/wjg.v24.i26.2806

[2] Al-Maghrabi, H., Alahmadi, S., & Falemban, A. H. (2020). Primary Gastrointestinal Stromal Tumor of the Prostate: Unexpected Guest. Cureus, 12(9), e10244. https://doi.org/10.7759/cureus.10244

[3] Altini, C., Mammucci, P., Pisani, A. R., D’Alò, C., Sardaro, A., Rubini, D., Ferrari, C., & Rubini, G. (2021). 18F-FDG PET/CT in GIST treatment response evaluation beyond Imatinib. Hellenic Journal of Nuclear Medicine, 24(3), 239–246. https://doi.org/10.1967/s002449912407

[4] Amato, A. (2010a). Colorectal gastrointestinal stromal tumor. Techniques in Coloproctology, 14 Suppl 1, S91-95. https://doi.org/10.1007/s10151-010-0631-y

[5] Amato, A. (2010b). Colorectal gastrointestinal stromal tumor. Techniques in Coloproctology, 14 Suppl 1, S91-95. https://doi.org/10.1007/s10151-010-0631-y

[6] Beham, A. W., Schaefer, I.-M., Schüler, P., Cameron, S., & Ghadimi, B. M. (2012). Gastrointestinal stromal tumors. International Journal of Colorectal Disease, 27(6), 689–700. https://doi.org/10.1007/s00384-011-1353-y

[7] Dhillon, S. (2020). Ripretinib: First Approval. Drugs, 80(11), 1133–1138. https://doi.org/10.1007/s40265-020-01348-2

[8] Dudzisz-Śledź, M., Bylina, E., Teterycz, P., & Rutkowski, P. (2021). Treatment of Metastatic Gastrointestinal Stromal Tumors (GIST): A Focus on Older Patients. Drugs & Aging, 38(5), 375–396. https://doi.org/10.1007/s40266-021-00841-x

[9] Eisenberg, B. L., & Pipas, J. M. (2012). Gastrointestinal stromal tumor—Background, pathology, treatment. Hematology/Oncology Clinics of North America, 26(6), 1239–1259. https://doi.org/10.1016/j.hoc.2012.08.003

[10] Goggin, C., Stansfeld, A., Mahalingam, P., Thway, K., Smith, M. J., Huang, P., Jones, R. L., & Napolitano, A. (2022). Ripretinib in advanced gastrointestinal stromal tumors: An overview of current evidence and drug approval. Future Oncology (London, England), 18(26), 2967–2978. https://doi.org/10.2217/fon-2022-0226

[11] Gupta, A. (2019). Gallbladder GIST: A review of literature. Polski Przeglad Chirurgiczny, 92(1), 34–37. https://doi.org/10.5604/01.3001.0013.5550

[12] Herzberg, M., Beer, M., Anupindi, S., Vollert, K., & Kröncke, T. (2018). Imaging pediatric gastrointestinal stromal tumor (GIST). Journal of Pediatric Surgery, 53(9), 1862–1870. https://doi.org/10.1016/j.jpedsurg.2018.03.022

[13] Huang, W.-K., Wu, C.-E., Wang, S.-Y., Chang, C.-F., Chou, W.-C., Chen, J.-S., & Yeh, C.-N. (2022). Systemic Therapy for Gastrointestinal Stromal Tumor: Current Standards and Emerging Challenges. Current Treatment Options in Oncology, 23(9), 1303–1319. https://doi.org/10.1007/s11864-022-00996-8

[14] Iorio, N., Sawaya, R. A., & Friedenberg, F. K. (2014). Review article: The biology, diagnosis and management of gastrointestinal stromal tumours. Alimentary Pharmacology & Therapeutics, 39(12), 1376–1386. https://doi.org/10.1111/apt.12761

[15] Joensuu, H. (2013). Gastrointestinal stromal tumors: Risk assessment and adjuvant therapy. Hematology/Oncology Clinics of North America, 27(5), 889–904. https://doi.org/10.1016/j.hoc.2013.07.004

[16] Khan, S. I., O’Sullivan, N. J., Temperley, H. C., Rausa, E., Mehigan, B. J., McCormick, P., Larkin, J. O., Kavanagh, D. O., & Kelly, M. E. (2023). Gastrointestinal Stromal Tumours (GIST) of the Rectum: A Systematic Review and Meta-Analysis. Current Oncology, 30(1), Article 1. https://doi.org/10.3390/curroncol30010034

[17] Lamba, G., Ambrale, S., Lee, B., Gupta, R., Rafiyath, S. M., & Liu, D. (2012). Recent advances and novel agents for gastrointestinal stromal tumor (GIST). Journal of Hematology & Oncology, 5, 21. https://doi.org/10.1186/1756-8722-5-21

[18] Liu, Z., Wu, S., Gou, S., Li, Y., Wu, H., & Li, Y. (2019). A Population-Based Study of the Incidence and Survival of Anorectal Gastrointestinal Stromal Tumor. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, 25, 5408–5417. https://doi.org/10.12659/MSM.915967

[19] Mantese, G. (2019). Gastrointestinal stromal tumor: Epidemiology, diagnosis, and treatment. Current Opinion in Gastroenterology, 35(6), 555–559. https://doi.org/10.1097/MOG.0000000000000584

[20] Minhas, S., Bhalla, S., Jauhri, M., Ganvir, M., & Aggarwal, S. (2019). Clinico-Pathological Characteristics and Mutational Analysis of Gastrointestinal Stromal Tumors from India: A Single Institution Experience. Asian Pacific Journal of Cancer Prevention : APJCP, 20(10), 3051–3055. https://doi.org/10.31557/APJCP.2019.20.10.3051

[21] Nannini, M., Rizzo, A., Indio, V., Schipani, A., Astolfi, A., & Pantaleo, M. A. (2021). Targeted therapy in SDH-deficient GIST. Therapeutic Advances in Medical Oncology, 13, 17588359211023278. https://doi.org/10.1177/17588359211023278

[22] Park, J.-J. (2016). Long-Term Outcomes after Endoscopic Treatment of Gastric Gastrointestinal Stromal Tumor. Clinical Endoscopy, 49(3), 232–234. https://doi.org/10.5946/ce.2016.052

[23] Reid, T. (2013). Reintroduction of imatinib in GIST. Journal of Gastrointestinal Cancer, 44(4), 385–392. https://doi.org/10.1007/s12029-013-9532-4

[24] Schaefer, I.-M., DeMatteo, R. P., & Serrano, C. (2022). The GIST of Advances in Treatment of Advanced Gastrointestinal Stromal Tumor. American Society of Clinical Oncology Educational Book. American Society of Clinical Oncology. Annual Meeting, 42, 1–15. https://doi.org/10.1200/EDBK_351231

[25] Sciot, R., & Debiec-Rychter, M. (2006). GIST under imatinib therapy. Seminars in Diagnostic Pathology, 23(2), 84–90. https://doi.org/10.1053/j.semdp.2006.08.005

[26] Senchak, J., Ahr, K., & von Mehren, M. (2022). Gastrointestinal Stromal Tumors: What Is the Best Sequence of TKIs? Current Treatment Options in Oncology, 23(5), 749–761. https://doi.org/10.1007/s11864-022-00958-0

[27] Serrano, C., & Bauer, S. (2022). New Tyrosine Kinase Inhibitors for the Treatment of Gastrointestinal Stromal Tumors. Current Oncology Reports, 24(2), 151–159. https://doi.org/10.1007/s11912-021-01165-0

[28] Stamatakos, M., Douzinas, E., Stefanaki, C., Safioleas, P., Polyzou, E., Levidou, G., & Safioleas, M. (2009). Gastrointestinal stromal tumor. World Journal of Surgical Oncology, 7, 61. https://doi.org/10.1186/1477-7819-7-61

[29] Swalchick, W., Shamekh, R., & Bui, M. M. (2015). Is DOG1 Immunoreactivity Specific to Gastrointestinal Stromal Tumor? Cancer Control: Journal of the Moffitt Cancer Center, 22(4), 498–504. https://doi.org/10.1177/107327481502200416

[30] Valadão, M., & Linhares, E. (2009). The role of the surgeon in the management of GIST. Revista Do Colegio Brasileiro De Cirurgioes, 36(3), 261–265.

[31] Willobee, B. A., Quiroz, H. J., Sussman, M. S., Thorson, C. M., Sola, J. E., & Perez, E. A. (2018). Current treatment strategies in pediatric gastrointestinal stromal cell tumor. Translational Gastroenterology and Hepatology, 3, 53. https://doi.org/10.21037/tgh.2018.07.09

[32] Xue, F., Wang, W., Shi, N., Ma, X.-B., & Liu, C.-X. (2019). Endoscopic resection of giant gastrointestinal stromal tumor at the esophagogastric junction: A case report. BMC Gastroenterology, 19(1), 227. https://doi.org/10.1186/s12876-019-1151-5

Abstract

References

How to cite