FACTORS PREDICTING RESPONSE TO NEOADJUVANT CHEMOTHERAPY IN LOCALLY ADVANCED GASTRIC CANCER

Year 2022, Volume: 85 Issue: 1, 41 - 50, 25.01.2022

Emine Yıldırım , Sibel Bektaş , Sabin Goktas Aydın , Ahmet Muzaffer Er İrem Yanık , Perihan Özkan Gümüşkaya , Barbaros Utku Yılmaz , Ahmet Bilici , Mustafa Oncel

https://doi.org/10.26650/IUITFD.950751

Abstract

Objective: In the treatment of local advanced gastric cancer (LAGC), it is recommended to start with neoadjuvant chemotherapy (NAC). Although the benefits of NAC have been shown, it is still not fully understood which patients respond better. The aim of this study was to investigate the effect of hematological and histopathological parameters on the response to chemotherapy. Material and Method: A retrospective examination was made of 38 patients who underwent surgery for LAGC after receiving NAC. Evaluations were made by comparing the demographic characteristics, histopathological characteristics in an endoscopic biopsy of the tumor, preoperative hemoglobin levels, and neutrophil-lymphocyte ratios with the postoperative pathological response to determine which tumor characteristics gave a better response. Results: In the postoperative histopathological evaluation, there was a pathological complete response to chemotherapy in two patients (6%), grade 1 in 9 patients (24%), grade 2 in 13 patients (34%), and grade 3 in 14 patients (36%). A statistically significant relationship was determined between the histopathological absence of perineural invasion and pathological complete response (p=0.023). Conclusion: A relationship between perineural invasion and poor response to chemotherapy was determined. Although not at a statistically significant level, there was also observed to be a poor response to chemotherapy in the presence of low grade and lymphovascular invasion.

Keywords

Local advanced gastric cancer, neoadjuvant chemotherapy response, pathological complete response, perineural invasion

LOKAL İLERİ MİDE KANSERİNDE NEOADJUVAN KEMOTERAPİYE YANITI ÖNGÖREN FAKTÖRLER

Abstract

Amaç: Lokal ileri mide kanserinde (LİMK) tedaviye neoadjuvan kemoterapi (NAK) ile başlanması önerilir. Ancak NAK’nin faydaları gösterilmiş olsa da hangi hasta gurubunun tedaviye daha iyi yanıt verdiği tam olarak anlaşılamamıştır. Çalışmamızda hematolojik ve histopatolojik parametrelerin kemoterapi yanıtı üzerine etkisi araştırılmıştır. Yöntem ve Gereç: Bu çalışmada lokal ileri evre mide kanseri nedeni ile neoadjuvan kemoterapi görüp sonrasında ameliyat edilen 38 hasta retrospektif olarak incelendi. Ameliyat sonrası patolojik yanıt ile hastanın demografik özellikleri, tümörün endoskopik biyopsideki histopatolojik özellikleri, preoperatif hemoglobin seviyesi, nötrofil lenfosit oranı karşılaştırılıp hangi özellikteki tümörlerin daha iyi yanıt verdiği değerlendirildi. Bulgular: Ameliyat sonrası yapılan histopatolojik değerlendirmede 2 (%6) hastada patolojik tam yanıt, 9 (%24) hastada grade 1 yanıt, 13 (%34) hastada grade 2 yanıt ve 14 hastada (%36) grade 3 yanıt mevcuttu. Patolojik tam yanıt ile histopatolojik olarak perinöral invazyon olmaması istatistiksel olarak anlamlı ilişki gösterdi (p=0.023). Sonuç: Çalışmamızda NAK alan LİMK’li hastalarda perinöral invazyon varlığının kemoterapiye kötü yanıt ile ilişkisi olduğu görülmüştür. Ayrıca lenfovaskular invazyon ve düşük grade mevcudiyetinde istatistiksel olarak anlamlı olmasa da kemoterapiye kötü yanıt gözlenmiştir.

Keywords

Lokal ileri mide kanseri, neoadjuvan kemoterapi yanıtı, patolojik tam yanıt, perinöral invazyon

References

• 1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68(6):394-424. [CrossRef]
• 2. Kikuchi S, Katada N, Sakuramoto S, Kobayashi N, Shimao H, Watanabe M, et al. Survival after surgical treatment of early gastric cancer: surgical techniques and long-term survival. Langenbecks Arch Surg 2004;389(2):69-74. [CrossRef]
• 3. Lu J, Huang CM, Zheng CH, Li P, Xie JW, Wang JB, et al. Consideration of tumor size improves the accuracy of TNM predictions in patients with gastric cancer after curative gastrectomy. Surg Oncol 2013;22(3):167-71. [CrossRef] 4. Gee DW, Rattner DW. Management of gastroesophageal tumors. Oncologist 2007;12(2):175-85. [CrossRef]
• 5. Ajani JA, D’Amico TA, Almhanna K, Bentrem DJ, Chao J, Das P, et al. Gastric Cancer, Version 3.2016, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2016;14(10):1286-312. [CrossRef]
• 6. Stewart C, Chao J, Chen YJ, Lin J, Sullivan MJ, Melstrom L, et al. Multimodality management of locally advanced gastric cancer-the timing and extent of surgery. Transl Gastroenterol Hepatol 2019;4:42. [CrossRef]
• 7. Wang XZ, Zeng ZY, Ye X, Sun J, Zhang ZM, Kang WM. Interpretation of the development of neoadjuvant therapy for gastric cancer based on the vicissitudes of the NCCN guidelines. World J Gastrointest Oncol 2020;12(1):37-53. [CrossRef]
• 8. Cao LL, Lu J, Li P, Xie JW, Wang JB, Lin JX, et al. Evaluation of the Eighth Edition of the American Joint Committee on Cancer TNM Staging System for Gastric Cancer: An Analysis of 7371 Patients in the SEER Database. Gastroenterol Res Pract 2019;2019:6294382. [CrossRef]
• 9. Yamamura Y, Nakajima T, Ohta K, Nashimoto A, Arai K, Hiratsuka M, et al. Determining prognostic factors for gastric cancer using the regression tree method. Gastric Cancer 2002;5(4):201-7. [CrossRef]
• 10. Yokota T, Ishiyama S, Saito T, Teshima S, Narushima Y, Murata K, et al. Lymph node metastasis as a significant prognostic factor in gastric cancer: a multiple logistic regression analysis. Scand J Gastroenterol 2004;39(4):380-4. [CrossRef]
• 11. Bu Z, Zheng Z, Li Z, Zhang L, Wu A, Wu X, et al. Lymphatic vascular invasion is an independent correlated factor for lymph node metastasis and the prognosis of resectable T2 gastric cancer patients. Tumour Biol 2013;34(2):1005-12. [CrossRef]
• 12. Li Z, Shan F, Wang Y, Zhang Y, Zhang L, Li S, et al. Correlation of pathological complete response with survival after neoadjuvant chemotherapy in gastric or gastroesophageal junction cancer treated with radical surgery: A metaanalysis. PLoS One. 2018;13(1):e0189294. [CrossRef]
• 13. Cho H, Nakamura J, Asaumi Y, Yabusaki H, Sakon M, Takasu N, et al. Long-term survival outcomes of advanced gastric cancer patients who achieved a pathological complete response with neoadjuvant chemotherapy: a systematic review of the literature. Ann Surg Oncol 2015;22(3):787-92. [CrossRef]
• 14. Ajani JA, Winter K, Okawara GS, Donohue JH, Pisters PW, Crane CH, et al. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol 2006;24(24):3953-8. [CrossRef]
• 15. Ajani JA, Mansfield PF, Janjan N, Morris J, Pisters PW, Lynch PM, et al. Multi-institutional trial of preoperative chemoradiotherapy in patients with potentially resectable gastric carcinoma. J Clin Oncol 2004;22(14):2774-80. [CrossRef]
• 16. Kurokawa Y, Shibata T, Sasako M, Sano T, Tsuburaya A, Iwasaki Y, et al. Validity of response assessment criteria in neoadjuvant chemotherapy for gastric cancer (JCOG0507-A). Gastric Cancer 2014;17(3):514-21. [CrossRef]
• 17. Valenti V, Hernandez-Lizoain JL, Beorlegui MC, Diaz- Gonzalez JA, Regueira FM, Rodriguez JJ, et al. Morbidity, mortality, and pathological response in patients with gastric cancer preoperatively treated with chemotherapy or chemoradiotherapy. J Surg Oncol 2011;104(2):124-9. [CrossRef]
• 18. Zhu Y, Sun Y, Hu S, Jiang Y, Yue J, Xue X, et al. Comparison of five tumor regression grading systems for gastric adenocarcinoma after neoadjuvant chemotherapy: a retrospective study of 192 cases from National Cancer Center in China. BMC Gastroenterol 2017;17(1):41. [CrossRef]
• 19. Lauren P. The Two Histological Main Types of Gastric Carcinoma: Diffuse and So-Called Intestinal-Type Carcinoma. An Attempt at a Histo-Clinical Classification. Acta Pathol Microbiol Scand 1965;64:31-49. [CrossRef]
• 20. Kushima R, Lauwers GY, Rugge M. Gastric Dysplasia. In: WHO Classification of Tumours: Digestive Systemic Tumours, 5th, WHO Classification of Tumours Editorial Board (Ed), International Agency for Research on Cancer, Lyon 2019. p.71
• 21. Bartley AN, Washington MK, Ventura CB, Ismaila N, Colasacco C, Benson AB, 3rd, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology. Arch Pathol Lab Med 2016;140(12):1345-63. [CrossRef]
• 22. Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol 2016;17(12):1697-708. [CrossRef]
• 23. Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet 2012;379(9813):315-21. [CrossRef]
• 24. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2018 (5th edition). Gastric Cancer 2021;24(1):1-21. [CrossRef]
• 25. Shi C, Berlin J, Branton PA, Burgart LJ, Carter DK, Compton CC, et al. Protocol for the examination of specimens from patients with carcinoma of the stomach. In: Cancer Protocol Templates. Northfield, IL: College of American Pathologists; 2017. (Available from: URL: http://www.cap.org)
• 26. Sanchez de Molina ML, Diaz Del Arco C, Vorwald P, Garcia-Olmo D, Estrada L, Fernandez-Acenero MJ. Histopathological factors predicting response to neoadjuvant therapy in gastric carcinoma. Clin Transl Oncol 2018;20(2):253-7. [CrossRef]
• 27. Russell MC. Comparison of neoadjuvant versus a surgery first approach for gastric and esophagogastric cancer. J Surg Oncol 2016;114(3):296-303. [CrossRef]
• 28. Ajani JA, Mansfield PF, Lynch PM, Pisters PW, Feig B, Dumas P, et al. Enhanced staging and all chemotherapy preoperatively in patients with potentially resectable gastric carcinoma. J Clin Oncol 1999;17(8):2403-11. [CrossRef]
• 29. Brenner B, Shah MA, Karpeh MS, Gonen M, Brennan MF, Coit DG, et al. A phase II trial of neoadjuvant cisplatinfluorouracil followed by postoperative intraperitoneal floxuridine-leucovorin in patients with locally advanced gastric cancer. Ann Oncol 2006;17(9):1404-11. [CrossRef]
• 30. Koh YW, Park YS, Ryu MH, Ryoo BY, Park HJ, Yook JH, et al. Postoperative nodal status and diffuse-type histology are independent prognostic factors in resectable advanced gastric carcinomas after preoperative chemotherapy. Am J Surg Pathol 2013;37(7):1022-9. [CrossRef]
• 31. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006;355(1):11-20. [CrossRef]
• 32. Ychou M, Boige V, Pignon JP, Conroy T, Bouche O, Lebreton G, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 2011;29(13):1715-21. [CrossRef]
• 33. Li S, Li J, Liu Z, Zhang Z, Zhang W, Yang H, et al. [Predictive value of P53, Ki-67, HER2 protein detection in neoadjuvant chemotherapy for adenocarcinoma of gastroesophageal junction). Zhonghua Wei Chang Wai Ke Za Zhi 2015;18(9):901-4.
• 34. Qu JJ, Shi YR, Hao FY. [Clinical study of the predictors to neoadjuvant chemotherapy in patients with advanced gastric cancer). Zhonghua Wei Chang Wai Ke Za Zhi 2013;16(3):276-80.
• 35. Wang LB, Teng RY, Jiang ZN, Hu WX, Dong MJ, Yuan XM, et al. Clinicopathologic variables predicting tumor response to neoadjuvant chemotherapy in patients with locally advanced gastric cancer. J Surg Oncol 2012;105(3):293-6. [CrossRef]
• 36. Shivakumar L, Ansell S. Targeting B-lymphocyte stimulator/ B-cell activating factor and a proliferation-inducing ligand in hematologic malignancies. Clin Lymphoma Myeloma 2006;7(2):106-8. [CrossRef]
• 37. Yao Y, Yuan D, Liu H, Gu X, Song Y. Pretreatment neutrophil to lymphocyte ratio is associated with response to therapy and prognosis of advanced non-small cell lung cancer patients treated with first-line platinum-based chemotherapy. Cancer Immunol Immunother 2013;62(3):471-9. [CrossRef]
• 38. Kishi Y, Kopetz S, Chun YS, Palavecino M, Abdalla EK, Vauthey JN. Blood neutrophil-to-lymphocyte ratio predicts survival in patients with colorectal liver metastases treated with systemic chemotherapy. Ann Surg Oncol 2009;16(3):614-22. [CrossRef]
• 39. Aizawa M, Gotohda N, Takahashi S, Konishi M, Kinoshita T. Predictive value of baseline neutrophil/lymphocyte ratio for T4 disease in wall-penetrating gastric cancer. World J Surg 2011;35(12):2717-22. [CrossRef]
• 40. Chen Y, Chen K, Xiao X, Nie Y, Qu S, Gong C, et al. Pretreatment neutrophil-to-lymphocyte ratio is correlated with response to neoadjuvant chemotherapy as an independent prognostic indicator in breast cancer patients: a retrospective study. BMC Cancer 2016;16:320. [CrossRef]