medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2024-529medsovet-8785Research ArticleХИМИОТЕРАПИЯCHEMOTHERAPYНерешенные вопросы периоперационной химиотерапии рака желудкаOutstanding issues in perioperative chemotherapy for gastric cancerhttps://orcid.org/0000-0002-3371-7548ДешкинаТ. И.DeshkinaT. I.

Дешкина Татьяна Игоревна, к.м.н., старший научный сотрудник отделения химиотерапии

125284, Москва, 2-й Боткинский проезд, д. 3

Tatiana I. Deshkina, Cand. Sci. (Med.), Senior Researcher of the Department of Chemotherapy

3, 2nd Botkinskiy Proezd, Moscow, 125284

rew9@yandex.ruhttps://orcid.org/0000-0003-4879-2687БолотинаЛ. В.BolotinaL. V.

Болотина Лариса Владимировна, д.м.н., профессор, заведующая отделением химиотерапии

125284, Москва, 2-й Боткинский проезд, д. 3 

LarisaV. Bolotina, Dr. Sci. (Med.), Head of the Department of Chemotherapy

3, 2nd Botkinskiy Proezd, Moscow, 125284

lbolotina@yandex.ruhttps://orcid.org/0000-0003-3532-6476ГолубевП. В.GolubevP. V.

Голубев Павел Вячеславович, к.м.н., врач-онколог химиотерапевтического отделения №2  Онкологического центра №1

115446, Москва, Коломенский проезд, д. 4

Pavel V. Golubev, Cand. Sci. (Med.), Oncologist, Chemotherapy Department No. 2, Oncology Center No. 1

4, Kolomenskiy Proezd, Moscow, 115446

golubev194@gmail.comhttps://orcid.org/0000-0003-0092-0459КорниецкаяА. Л.KornietskayaA. L.

Корниецкая Анна Леонидовна, к.м.н., ведущий научный сотрудник отдела лекарственного лечения опухолей

125284, Москва, 2-й Боткинский проезд, д. 3

Anna L. Kornietskaya, Cand. Sci. (Med.), Leading Researcher of the Department of Drug Treatment of Tumors

3, 2nd Botkinskiy Proezd, Moscow, 125284

kornietskaya@mail.ruhttps://orcid.org/0000-0002-4008-9180РубанМ. С.RubanM. S.

Рубан Максим Сергеевич, аспирант отделения химиотерапии

125284, Москва, 2-й Боткинский проезд, д. 3

Maksim S. Ruban, Postgraduate Student of the Department of Chemotherapy

3, 2nd Botkinskiy Proezd, Moscow, 125284

ruban.m.s@yandex.ruhttps://orcid.org/0000-0003-4927-5585ФеденкоА. А.FedenkoA. A.

Феденко Александр Александрович, д.м.н., профессор РАН, руководитель отдела лекарственного лечения опухолей

125284, Москва, 2-й Боткинский проезд, д. 3

Alexander A. Fedenko, Dr. Sci. (Med.), Professor RAS, Head of the Department of Drug Treatment of Tumors

3, 2nd Botkinskiy Proezd, Moscow, 125284

fedenko@eesg.ruМосковский научно-исследовательский онкологический институт имени П.А. Герцена – филиал Национального медицинского исследовательского центра радиологииРоссияHertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological CenterRussian FederationГородская клиническая больница имени С.С. ЮдинаРоссияMoscow City Hospital named after S.S. YudinRussian Federation2024221220240217075Copyright © Дешкина Т.И., Болотина Л.В., Голубев П.В., Корниецкая А.Л., Рубан М.С., Феденко А.А., 20242024Дешкина Т.И., Болотина Л.В., Голубев П.В., Корниецкая А.Л., Рубан М.С., Феденко А.А.Deshkina T.I., Bolotina L.V., Golubev P.V., Kornietskaya A.L., Ruban M.S., Fedenko A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/8785

Рак желудка является важной медико-социальной проблемой во всем мире. Агрессивность течения данного заболевания отражают высокие цифры одногодичной летальности, что обусловлено как высокой запущенностью на момент постановки диагноза, так и неудовлетворительными результатами хирургического лечения даже локализованного опухолевого процесса, что с биологической точки зрения ставит под сомнение возможность выполнения «радикальной» операции при данном типе злокачественного новообразования. В настоящее время «золотым стандартом» стало проведение периоперационной химиотерапии по схеме FLOT при местнораспространенных стадиях рака желудка, пищеводно-желудочного перехода и нижней трети пищевода. Дальнейшим перспективным направлением по совершенствованию периоперационной химиотерапии является изучение ингибиторов контрольных точек иммунного ответа (пембролизумаба, атезолизумаба и дурвалумаба) в комбинации с цитостатиками. Сегодня же сохраняется еще целый ряд нерешенных вопросов, в т. ч. остается неясной необходимость продолжения столь агрессивного лечения в послеоперационном периоде при неудовлетворительном патоморфологическом ответе со стороны опухоли. Выполнение всего объема химиотерапии является сложной задачей, что обусловлено токсичностью данного вида лечения и ослабленным состоянием больного после обширного хирургического вмешательства. Значимость патоморфологического регресса опухоли после проведения неоадъювантной химиотерапии также не ясна. Только 10–15% пациентов достигают полного патоморфологического ответа со стороны опухоли. Стандартной послеоперационной практикой является проведение того же предоперационного режима химиотерапии вне зависимости от чувствительности к нему. Поиск прогностических маркеров поможет индивидуализировать стратегию лечения подобных пациентов и оградить больных от избыточной токсичности при необоснованном продолжении химиотерапии.

Gastric cancer is an important medical and social problem all over the world. The aggressiveness of the course of this disease is reflected by the high figures of one-year mortality, which is due to both high neglect at the time of diagnosis and unsatisfactory results of surgical treatment of even a localized tumor process, which from a biological point of view casts doubt on the possibility of performing a “radical” operation for this type of malignant tumor. Currently, the “gold standard” has become the conduct of perioperative chemotherapy according to the FLOT scheme for locally advanced stages of gastric cancer, esophagogastric junction and esophagogastric junction and lower esophagus. A further promising direction for improving perioperative chemotherapy is the investigation of immune checkpoint inhibitors (pembrolizumab, atezolizumab and durvalumab) in combination with cytostatics. Today, there are still a number of unresolved issues, including the need to continue such aggressive treatment in the postoperative period with an unsatisfactory pathomorphological response from the tumor. Performing the entire volume of chemotherapy is a difficult task, due to the toxicity of this type of treatment and the weakened condition of the patient after extensive surgery. The significance of the pathomorphological regression of the tumor after neoadjuvant chemotherapy is also unclear. Only 10–15% of patients achieve a complete pathomorphological response. The standard postoperative practice is to carry out the same preoperative chemotherapy regimen, regardless of sensitivity to it. The search for prognostic markers will help to individualize the treatment strategy of such patients and protect patients from excessive toxicity with unjustified continuation of chemotherapy.

рак желудкарак пищеводно-желудочного перехода и нижней трети пищеводааденокарциномапериоперационная химиотерапияпатоморфологический ответ опухолипостнеоадъювантная терапияиндивидуализация леченияgastric cancercancer of the esophagogastric junction and lower esophagusadenocarcinomaperioperative chemotherapypathomorphological responsepostneoadjuvant treatmentindividualization of treatmentReferencesFerlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L et al. Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer; 2024. Available at: https://gco.iarc.who.int/today.Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L et al. Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer; 2024. Available at: https://gco.iarc.who.int/today.Каприн АД, Старинский ВВ, Шахзадова ГВ (ред.). Состояние онкологической помощи в России в 2019 году. М.: МНИОИ им. П.А. Герцена - филиал ФГБУ «НМИРЦ» Минздрава России; 2020. 239 с. Режим доступа: https://glavonco.ru/cancer_register/Помощь%202019.pdf.Каприн АД, Старинский ВВ, Шахзадова ГВ (ред.). Состояние онкологической помощи в России в 2019 году. М.: МНИОИ им. П.А. Герцена - филиал ФГБУ «НМИРЦ» Минздрава России; 2020. 239 с. Режим доступа: https://glavonco.ru/cancer_register/Помощь%202019.pdf.D’Angelica M, Gonen M, Brennan MF, Turnbull AD, Bains M, Karpeh MS. Patterns of initial recurrence in completely resected gastric adenocarcinoma. Ann Surg. 2004;240(5):808-816. https://doi.org/10.1097/01.sla.0000143245.28656.15.D’Angelica M, Gonen M, Brennan MF, Turnbull AD, Bains M, Karpeh MS. Patterns of initial recurrence in completely resected gastric adenocarcinoma. Ann Surg. 2004;240(5):808-816. https://doi.org/10.1097/01.sla.0000143245.28656.15.Yoo CH, Noh SH, Shin DW, Choi SH, Min JS. Recurrence following curative resection for gastric carcinoma. Br J Surg. 2000;87(2):236-242. https://doi.org/10.1046/j.1365-2168.2000.01360.x.Yoo CH, Noh SH, Shin DW, Choi SH, Min JS. Recurrence following curative resection for gastric carcinoma. Br J Surg. 2000;87(2):236-242. https://doi.org/10.1046/j.1365-2168.2000.01360.x.Mamon H, Enzinger PC. Adjuvant and neoadjuvant treatment of gastric cancer. UpToDate; 2024. Available at: https://www.uptodate.com/contents/adjuvant-and-neoadjuvant-treatment-of-gastric-cancer?search=perioperative%20gastric%20cancer&source=search_result&selectedTitle=1%7E150&usage_type=default&display_rank=1#H3313275765.Mamon H, Enzinger PC. Adjuvant and neoadjuvant treatment of gastric cancer. UpToDate; 2024. Available at: https://www.uptodate.com/contents/adjuvant-and-neoadjuvant-treatment-of-gastric-cancer?search=perioperative%20gastric%20cancer&source=search_result&selectedTitle=1%7E150&usage_type=default&display_rank=1#H3313275765.Jácome AA, Sankarankutty AK, dos Santos JS. Adjuvant therapy for gastric cancer: what have we learned since INT0116? World J Gastroenterol. 2015;21(13):3850-3859. https://doi.org/10.3748/wjg.v21.i13.3850.Jácome AA, Sankarankutty AK, dos Santos JS. Adjuvant therapy for gastric cancer: what have we learned since INT0116? World J Gastroenterol. 2015;21(13):3850-3859. https://doi.org/10.3748/wjg.v21.i13.3850.Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345(10):725-730. https://doi.org/10.1056/NEJMoa010187.Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345(10):725-730. https://doi.org/10.1056/NEJMoa010187.Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol. 2010;11(5):439-449. https://doi.org/10.1016/S1470-2045(10)70070-X.Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol. 2010;11(5):439-449. https://doi.org/10.1016/S1470-2045(10)70070-X.Paoletti X, Oba K, Burzykowski T, Michiels S, Ohashi Y, Pignon JP et al. Benefit of adjuvant chemotherapy for resectable gastric cancer: a meta-analysis. JAMA. 2010;303(17):1729-1737. https://doi.org/10.1001/jama.2010.534.Paoletti X, Oba K, Burzykowski T, Michiels S, Ohashi Y, Pignon JP et al. Benefit of adjuvant chemotherapy for resectable gastric cancer: a meta-analysis. JAMA. 2010;303(17):1729-1737. https://doi.org/10.1001/jama.2010.534.Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357(18):1810-1820. https://doi.org/10.1056/NEJMoa072252.Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357(18):1810-1820. https://doi.org/10.1056/NEJMoa072252.Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T et al. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011;29(33):4387-4393. https://doi.org/10.1200/JCO.2011.36.5908.Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T et al. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011;29(33):4387-4393. https://doi.org/10.1200/JCO.2011.36.5908.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):315-321. https://doi.org/10.1016/S0140-6736(11)61873-4.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):315-321. https://doi.org/10.1016/S0140-6736(11)61873-4.Oba K, Paoletti X, Alberts S, Bang YJ, Benedetti J, Bleiberg H et al. Diseasefree survival as a surrogate for overall survival in adjuvant trials of gastric cancer: a meta-analysis. J Natl Cancer Inst. 2013;105(21):1600-1607. https://doi.org/10.1093/jnci/djt270.Oba K, Paoletti X, Alberts S, Bang YJ, Benedetti J, Bleiberg H et al. Diseasefree survival as a surrogate for overall survival in adjuvant trials of gastric cancer: a meta-analysis. J Natl Cancer Inst. 2013;105(21):1600-1607. https://doi.org/10.1093/jnci/djt270.Cunningham D, Allum WH, Stenning SP, Thompson JN, Vande Velde CJ, Nicolson M et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11-20. https://doi.org/10.1056/NEJMoa055531.Cunningham D, Allum WH, Stenning SP, Thompson JN, Vande Velde CJ, Nicolson M et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11-20. https://doi.org/10.1056/NEJMoa055531.Ychou M, Boige V, Pignon JP, Conroy T, Bouché 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):1715-1721. https://doi.org/10.1200/JCO.2010.33.0597.Ychou M, Boige V, Pignon JP, Conroy T, Bouché 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):1715-1721. https://doi.org/10.1200/JCO.2010.33.0597.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):1697-1708. https://doi.org/10.1016/S1470-2045(16)30531-9.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):1697-1708. https://doi.org/10.1016/S1470-2045(16)30531-9.Al-Batran SE, Homann N, Pauligk C, Illerhaus G, Martens UM, Stoehlmacher J et al. Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The AIO-FLOT3 Trial. JAMA Oncol. 2017;3(9):1237-1244. https://doi.org/10.1001/jamaoncol.2017.0515.Al-Batran SE, Homann N, Pauligk C, Illerhaus G, Martens UM, Stoehlmacher J et al. Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The AIO-FLOT3 Trial. JAMA Oncol. 2017;3(9):1237-1244. https://doi.org/10.1001/jamaoncol.2017.0515.Shitara K, Rha SY, Wyrwicz LS, Oshima T, Karaseva N, Osipov M et al. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): an interim analysis of the multicentre, double-blind, randomised phase 3 study. Lancet Oncol. 2024;25(2):212-224. https://doi.org/10.1016/S1470-2045(23)00541-7.Shitara K, Rha SY, Wyrwicz LS, Oshima T, Karaseva N, Osipov M et al. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): an interim analysis of the multicentre, double-blind, randomised phase 3 study. Lancet Oncol. 2024;25(2):212-224. https://doi.org/10.1016/S1470-2045(23)00541-7.Chalabi M, Verschoor YL, Van De Haar J, van den Berg J, Kodach L, van Sandick J et al. Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction (G/GEJ) adenocarcinoma: The PANDA study. Ann Oncol. 2022;33(7):S1106. https://doi.org/10.1016/j.annonc.2022.07.1337.Chalabi M, Verschoor YL, Van De Haar J, van den Berg J, Kodach L, van Sandick J et al. Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction (G/GEJ) adenocarcinoma: The PANDA study. Ann Oncol. 2022;33(7):S1106. https://doi.org/10.1016/j.annonc.2022.07.1337.Janjigian YY, Van Cutsem E, Muro K, Wainberg Z, Al-Batran SE, Hyung WJ et al. MATTERHORN: phase III study of durvalumab plus FLOT chemotherapy in resectable gastric/gastroesophageal junction cancer. Future Oncol. 2022;18(20):2465-2473. https://doi.org/10.2217/fon-2022-0093.Janjigian YY, Van Cutsem E, Muro K, Wainberg Z, Al-Batran SE, Hyung WJ et al. MATTERHORN: phase III study of durvalumab plus FLOT chemotherapy in resectable gastric/gastroesophageal junction cancer. Future Oncol. 2022;18(20):2465-2473. https://doi.org/10.2217/fon-2022-0093.Conforti F, Pala L, Sala I, Oriecuia C, De Pas T, Specchia C et al. Evaluation of pathological complete response as surrogate endpoint in neoadjuvant randomised clinical trials of early stage breast cancer: systematic review and meta-analysis. BMJ. 2021;375:e066381. https://doi.org/10.1136/bmj2021-066381.Conforti F, Pala L, Sala I, Oriecuia C, De Pas T, Specchia C et al. Evaluation of pathological complete response as surrogate endpoint in neoadjuvant randomised clinical trials of early stage breast cancer: systematic review and meta-analysis. BMJ. 2021;375:e066381. https://doi.org/10.1136/bmj2021-066381.Kang WZ, Wang BZ, Li DF, Jiang ZC, Xiong JP, Li Y et al. Can Gastric Cancer Patients with High Mandard Score Benefit from Neoadjuvant Chemotherapy? Can J Gastroenterol Hepatol. 2022;2022:8178184. https://doi.org/10.1155/2022/8178184.Kang WZ, Wang BZ, Li DF, Jiang ZC, Xiong JP, Li Y et al. Can Gastric Cancer Patients with High Mandard Score Benefit from Neoadjuvant Chemotherapy? Can J Gastroenterol Hepatol. 2022;2022:8178184. https://doi.org/10.1155/2022/8178184.Saunders JH, Bowman CR, Reece-Smith AM, Pang V, Dorrington MS, Mumtaz E et al. The role of adjuvant platinum-based chemotherapy in esophagogastric cancer patients who received neoadjuvant chemotherapy prior to definitive surgery. J Surg Oncol. 2017;115(7):821-829. https://doi.org/10.1002/jso.24601.Saunders JH, Bowman CR, Reece-Smith AM, Pang V, Dorrington MS, Mumtaz E et al. The role of adjuvant platinum-based chemotherapy in esophagogastric cancer patients who received neoadjuvant chemotherapy prior to definitive surgery. J Surg Oncol. 2017;115(7):821-829. https://doi.org/10.1002/jso.24601.Lin JX, Tang YH, Lin GJ, Ma YB, Desiderio J, Li P et al. Association of Adjuvant Chemotherapy With Overall Survival Among Patients With Locally Advanced Gastric Cancer After Neoadjuvant Chemotherapy. JAMA Netw Open. 2022;5(4):e225557. https://doi.org/10.1001/jamanetworkopen.2022.5557.Lin JX, Tang YH, Lin GJ, Ma YB, Desiderio J, Li P et al. Association of Adjuvant Chemotherapy With Overall Survival Among Patients With Locally Advanced Gastric Cancer After Neoadjuvant Chemotherapy. JAMA Netw Open. 2022;5(4):e225557. https://doi.org/10.1001/jamanetworkopen.2022.5557.Deng L, Groman A, Jiang C, Perimbeti S, Gabriel E, Kukar M, Mukherjee S. Association of Preoperative Chemosensitivity With Postoperative Survival in Patients With Resected Gastric Adenocarcinoma. JAMA Netw Open. 2021;4(11):e2135340. https://doi.org/10.1001/jamanetworkopen.2021.35340.Deng L, Groman A, Jiang C, Perimbeti S, Gabriel E, Kukar M, Mukherjee S. Association of Preoperative Chemosensitivity With Postoperative Survival in Patients With Resected Gastric Adenocarcinoma. JAMA Netw Open. 2021;4(11):e2135340. https://doi.org/10.1001/jamanetworkopen.2021.35340.von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019;380(7):617-628. https://doi.org/10.1056/NEJMoa1814017.von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019;380(7):617-628. https://doi.org/10.1056/NEJMoa1814017.Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med. 2017;376(22):2147-2159. https://doi.org/10.1056/NEJMoa1612645.Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med. 2017;376(22):2147-2159. https://doi.org/10.1056/NEJMoa1612645.Liu Z, Wang Y, Shan F, Ying X, Zhang Y, Li S et al. Treatment Switch in Poor Responders with Locally Advanced Gastric Cancer After Neoadjuvant Chemotherapy. Ann Surg Oncol. 2021;28(13):8892–8907. https://doi.org/10.1245/s10434-021-10087-x..Liu Z, Wang Y, Shan F, Ying X, Zhang Y, Li S et al. Treatment Switch in Poor Responders with Locally Advanced Gastric Cancer After Neoadjuvant Chemotherapy. Ann Surg Oncol. 2021;28(13):8892–8907. https://doi.org/10.1245/s10434-021-10087-x..

The authors declare that there are no conflicts of interest present.