Современные подходы к оценке ответа рака прямой кишки на неоадъювантное лечение

1. Kapiteijn E, Marijnen CA, Nagtegaal ID, et al.; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345(9):638-46. DOI:10.1056/NEJMoa010580
2. MacFarlane JK, Ryall RD, Heald RJ. Mesorectal excision for rectal cancer. Lancet. 1993;341(8843):457-60. DOI:10.1016/0140-6736(93)90207-w
3. Gérard JP, André T, Bibeau F, et al.; Société Française de Chirurgie Digestive (SFCD), Société Française d’Endoscopie Digestive (SFED0), Société Française de Radiothérapie Oncologique (SFRO). Rectal cancer: French Intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO). Dig Liver Dis. 2017;49(4):359-67. DOI:10.1016/j.dld.2017.01.152
4. Sauer R, Liersch T, Merkel S, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30(16):1926-33. DOI:10.1200/JCO.2011.40.1836
5. Bosset JF, Calais G, Daban A, et al.; EORTC Radiotherapy Group. Preoperative chemoradiotherapy versus preoperative radiotherapy in rectal cancer patients: assessment of acute toxicity and treatment compliance. Report of the 22921 randomised trial conducted by the EORTC Radiotherapy Group. Eur J Cancer. 2004;40(2):219-24. DOI:10.1016/j.ejca.2003.09.032
6. Bahadoer RR, Dijkstra EA, van Etten B, et al.; RAPIDO collaborative investigators. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(1):29-42. DOI:10.1016/S1470-2045(20)30555-6. Erratum in: Lancet Oncol. 2021;22(2):e42. DOI:10.1016/S1470-2045(20)30781-6
7. Conroy T, Bosset J-F, Etienne P-L, et al. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22:702-15.
8. Habr-Gama A, Perez RO, Nadalin W, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy. Trans Meeting Am Surg Assocs. 2004;CXXII:309-16.
9. Rullier E, Perez RO. Surgery or a watch-and-wait approach for rectal cancer? Lancet Oncol. 2019;20:189-90.
10. Gani C, Bonomo P, Zwirner K, et al. Organ preservation in rectal cancer – challenges and future strategies. Clin Transl Radiat Oncol. 2017;3:9-15.
11. Glynne-Jones R, Hughes R. Critical appraisal of the ‘wait and see’ approach in rectal cancer for clinical complete responders after chemoradiation. Br J Surg. 2012;99:897-909.
12. Paun BC, Cassie S, MacLean AR, et al. Postoperative complications following surgery for rectal cancer. Ann Surg. 2010;251:807-18.
13. Peeters KCMJ. Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients – a Dutch colorectal cancer group study. J Clin Oncol. 2005;23:6199-206.
14. Arezzo A, Lo Secco G, Passera R, et al. Individual participant data pooled-analysis of risk factors for recurrence after neoadjuvant radiotherapy and transanal local excision of rectal cancer: the PARTTLE study. Tech Coloproctol. 2019;23:831-42.
15. Habr-Gama A, Gama-Rodrigues J, São Julião GP, et al. Local recurrence after complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradiation: impact of salvage therapy on local disease control. Int J Radiat Oncol Biol Phys. 2014;88:822-8.
16. Fernandez LM, São Julião GP, Renehan AG, et al. The Risk of distant metastases in patients with clinical complete response managed by watch and wait after neoadjuvant therapy for rectal cancer: the infuence of local regrowth in the International Watch and Wait Database. Dis Colon Rectum. 2023;66:41-9.
17. Rullier E, Rouanet P, Tuech J-J, et al. Organ preservation for rectal cancer (GRECCAR 2): a prospective, randomised, open-label, multicentre, phase 3 trial. Lancet. 2017;390:469-79.
18. Dossa F, Chesney TR, Acuna SA, et al. A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2017;2:501-13.
19. Chadi SA, Malcomson L, Ensor J, et al. Factors affecting local regrowth after watch and wait for patients with a clinical complete response following chemoradiotherapy in rectal cancer (InterCoRe consortium): an individual participant data meta-analysis. Lancet Gastroenterol Hepatol. 2018;3(12):825-36. DOI:10.1016/S2468-1253(18)30301-7
20. Habr-Gama A, Perez RO, Wynn G, et al. Complete clinical response after neoadjuvant chemoradiation therapy for distal rectal cancer: characterization of clinical and endoscopic fndings for standardization. Dis Colon Rectum. 2010;53(12):1692-8. DOI:10.1007/DCR.0b013e3181f42b89
21. Tjalma JJJ, Koller M, Linssen MD, et al. Quantitative fluorescence endoscopy: an innovative endoscopy approach to evaluate neoadjuvant treatment response in locally advanced rectal cancer. Gut. 2020;69(3):406-10. DOI:10.1136/gutjnl-2019-319755
22. Bujko K, Kepka L, Michalski W, et al. Does rectal cancer shrinkage induced by preoperative radio(chemo)therapy increase the likelihood of anterior resection? A systematic review of randomised trials. Radiother Oncol. 2006;80:4-12.
23. Patel UB, Brown G, Rutten H, et al. Comparison of magnetic resonance imaging and histopathological response to chemoradiotherapy in locally advanced rectal cancer. Ann Surg Oncol. 2012;19(9):2842-52. DOI:10.1245/s10434-012-2309-3
24. Perez RO, Habr-Gama A, Gama-Rodrigues J, et al. Accuracy of positron emission tomography/computed tomography and clinical assessment in the detection of complete rectal tumor regression after neoadjuvant chemoradiation. Cancer. 2011;118:3501-11.
25. Cascini GL, Avallone A, Delrio P, et al. 18F-FDG PET is an early predictor of pathologic tumor response to preoperative radiochemotherapy in locally advanced rectal cancer. J Nucl Med. 2006;47:1241-8.
26. 2017 European Society of Coloproctology (ESCP) collaborating group. Evaluating the incidence of pathological complete response in current international rectal cancer practice: the barriers to widespread safe deferral of surgery. Colorectal Dis. 2018;20(Suppl. 6):58-68. DOI:10.1111/codi.14361
27. Lee JH, Kim SH, Jang HS, et al. Preoperative elevation of carcinoembryonic antigen predicts poor tumor response and frequent distant recurrence for patients with rectal cancer who receive preoperative chemoradiotherapy and total mesorectal excision: a multi-institutional analysis in an Asian population. Int J Colorectal Dis. 2013;28:511-7.
28. Park JW, Lim S-B, Kim DY, et al. Carcinoembryonic antigen as a predictor of pathologic response and a prognostic factor in locally advanced rectal cancer patients treated with preoperative chemoradiotherapy and surgery. Int J Radiat Oncol Biol Phys. 2009;74:810-7.
29. Lee JH, Hyun JH, Kim DY, et al. The role of fbrinogen as a predictor in preoperative chemoradiation for rectal cancer. Ann Surg Oncol. 2015;22:209-15.
30. Policicchio A, Mercier J, Digklia A, et al. Platelet and neutrophil counts as predictive markers of neoadjuvant therapy effcacy in rectal cancer. J Gastrointest Cancer. 2019;50:894-900.
31. Diefenhardt M, Hofheinz R-D, Martin D, et al. Leukocytosis and neutrophilia as independent prognostic immunological biomarkers for clinical outcome in the CAO/ARO/AIO-04 randomized phase 3 rectal cancer trial. Int J Cancer. 2019;145:2282-91.
32. Dudani S, Marginean H, Tang PA, et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictive and prognostic markers in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation. BMC Cancer. 2019;19(1):664. DOI:10.1186/s12885-019-5892-x
33. Cabel L, Proudhon C, Gortais H, et al. Circulating tumor cells: clinical validity and utility. Int J Clin Oncol. 2017;22:421-30.
34. Sun W, Li G, Wan J, et al. Circulating tumor cells: a promising marker of predicting tumor response in rectal cancer patients receiving neoadjuvant chemo-radiation therapy. Oncotarget. 2016;7:69507-17.
35. Pan R-J, Hong H-J, Sun J, et al. Detection and clinical value of circulating tumor cells as an assisted prognostic marker in colorectal cancer patients. CMAR. 2021;13:4567-78.
36. Hasan S, Renz P, Wegner RE, et al. Microsatellite instability (MSI) as an independent predictor of pathologic complete response (PCR) in locally advanced rectal cancer: a National Cancer Database (NCDB) Analysis. Ann Surg. 2020;271:716-23.
37. Mi M, Ye C, Yuan Y. Neoadjuvant PD-1 blockade: a promising nonoperative strategy for mismatch repair-deficient, locally advanced rectal cancer. Signal Transduct Target Ther. 2022;7(1):361. DOI:10.1038/s41392-022-01216-3
38. Tie J, Cohen JD, Wang Y, et al. Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study. Gut. 2019;68:663-71.
39. Vidal J, Casadevall D, Bellosillo B, et al. Clinical impact of presurgery circulating tumor DNA after total neoadjuvant treatment in locally advanced rectal cancer: a biomarker study from the GEMCAD 1402 trial. Clin Cancer Res. 2021;27:2890-8.
40. Saw RPM, Morgan M, Koorey D, et al. p53, deleted in colorectal cancer gene, and thymidylate synthase as predictors of histopathologic response and survival in low, locally advanced rectal cancer treated with preoperative adjuvant therapy. Dis Colon Rectum. 2003;46(2):192-202. DOI:10.1007/s10350-004-6524-2
41. Chen MB, Wu XY, Yu R, et al. P53 status as a predictive biomarker for patients receiving neoadjuvant radiation-based treatment: a meta-analysis in rectal cancer. PLoS One. 2012;7(9):e45388. DOI:10.1371/journal.pone.0045388
42. Sclafani F, Wilson SH, Cunningham D, et al. Analysis of KRAS, NRAS, BRAF, PIK3CA and TP53 mutations in a large prospective series of locally advanced rectal cancer patients. Int J Cancer. 2020;146:94-102.
43. Oh CR, Kim JE, Kang J, et al. Prognostic Value of the Microsatellite Instability Status in Patients With Stage II/III Rectal Cancer Following Upfront Surgery. Clin Colorectal Cancer. 2018;17(4):e679-85. DOI:10.1016/j.clcc.2018.07.003
44. Cercek A, Lumish M, Sinopoli J, et al. PD-1 blockade in mismatch repair-defcient, locally advanced rectal cancer. N Engl J Med. 2022;386(25):2363-76. DOI:10.1056/NEJMoa2201445
45. Zeitoun G, Sissy CE, Kirilovsky A, et al. The Immunoscore in the clinical practice of patients with colon and rectal cancers. Chirurgia (Bucur). 2019;114:152-61.
46. El Sissy C, Kirilovsky A, Van den Eynde M, et al. A diagnostic biopsy-adapted Immunoscore predicts response to neoadjuvant treatment and selects patients with rectal cancer eligible for a watch-and-wait strategy. Clin Cancer Res. 2020;26:5198-207.

________________________________________________

1. Kapiteijn E, Marijnen CA, Nagtegaal ID, et al.; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345(9):638-46. DOI:10.1056/NEJMoa010580
2. MacFarlane JK, Ryall RD, Heald RJ. Mesorectal excision for rectal cancer. Lancet. 1993;341(8843):457-60. DOI:10.1016/0140-6736(93)90207-w
3. Gérard JP, André T, Bibeau F, et al.; Société Française de Chirurgie Digestive (SFCD), Société Française d’Endoscopie Digestive (SFED0), Société Française de Radiothérapie Oncologique (SFRO). Rectal cancer: French Intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO). Dig Liver Dis. 2017;49(4):359-67. DOI:10.1016/j.dld.2017.01.152
4. Sauer R, Liersch T, Merkel S, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30(16):1926-33. DOI:10.1200/JCO.2011.40.1836
5. Bosset JF, Calais G, Daban A, et al.; EORTC Radiotherapy Group. Preoperative chemoradiotherapy versus preoperative radiotherapy in rectal cancer patients: assessment of acute toxicity and treatment compliance. Report of the 22921 randomised trial conducted by the EORTC Radiotherapy Group. Eur J Cancer. 2004;40(2):219-24. DOI:10.1016/j.ejca.2003.09.032
6. Bahadoer RR, Dijkstra EA, van Etten B, et al.; RAPIDO collaborative investigators. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(1):29-42. DOI:10.1016/S1470-2045(20)30555-6. Erratum in: Lancet Oncol. 2021;22(2):e42. DOI:10.1016/S1470-2045(20)30781-6
7. Conroy T, Bosset J-F, Etienne P-L, et al. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22:702-15.
8. Habr-Gama A, Perez RO, Nadalin W, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy. Trans Meeting Am Surg Assocs. 2004;CXXII:309-16.
9. Rullier E, Perez RO. Surgery or a watch-and-wait approach for rectal cancer? Lancet Oncol. 2019;20:189-90.
10. Gani C, Bonomo P, Zwirner K, et al. Organ preservation in rectal cancer – challenges and future strategies. Clin Transl Radiat Oncol. 2017;3:9-15.
11. Glynne-Jones R, Hughes R. Critical appraisal of the ‘wait and see’ approach in rectal cancer for clinical complete responders after chemoradiation. Br J Surg. 2012;99:897-909.
12. Paun BC, Cassie S, MacLean AR, et al. Postoperative complications following surgery for rectal cancer. Ann Surg. 2010;251:807-18.
13. Peeters KCMJ. Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients – a Dutch colorectal cancer group study. J Clin Oncol. 2005;23:6199-206.
14. Arezzo A, Lo Secco G, Passera R, et al. Individual participant data pooled-analysis of risk factors for recurrence after neoadjuvant radiotherapy and transanal local excision of rectal cancer: the PARTTLE study. Tech Coloproctol. 2019;23:831-42.
15. Habr-Gama A, Gama-Rodrigues J, São Julião GP, et al. Local recurrence after complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradiation: impact of salvage therapy on local disease control. Int J Radiat Oncol Biol Phys. 2014;88:822-8.
16. Fernandez LM, São Julião GP, Renehan AG, et al. The Risk of distant metastases in patients with clinical complete response managed by watch and wait after neoadjuvant therapy for rectal cancer: the infuence of local regrowth in the International Watch and Wait Database. Dis Colon Rectum. 2023;66:41-9.
17. Rullier E, Rouanet P, Tuech J-J, et al. Organ preservation for rectal cancer (GRECCAR 2): a prospective, randomised, open-label, multicentre, phase 3 trial. Lancet. 2017;390:469-79.
18. Dossa F, Chesney TR, Acuna SA, et al. A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2017;2:501-13.
19. Chadi SA, Malcomson L, Ensor J, et al. Factors affecting local regrowth after watch and wait for patients with a clinical complete response following chemoradiotherapy in rectal cancer (InterCoRe consortium): an individual participant data meta-analysis. Lancet Gastroenterol Hepatol. 2018;3(12):825-36. DOI:10.1016/S2468-1253(18)30301-7
20. Habr-Gama A, Perez RO, Wynn G, et al. Complete clinical response after neoadjuvant chemoradiation therapy for distal rectal cancer: characterization of clinical and endoscopic fndings for standardization. Dis Colon Rectum. 2010;53(12):1692-8. DOI:10.1007/DCR.0b013e3181f42b89
21. Tjalma JJJ, Koller M, Linssen MD, et al. Quantitative fluorescence endoscopy: an innovative endoscopy approach to evaluate neoadjuvant treatment response in locally advanced rectal cancer. Gut. 2020;69(3):406-10. DOI:10.1136/gutjnl-2019-319755
22. Bujko K, Kepka L, Michalski W, et al. Does rectal cancer shrinkage induced by preoperative radio(chemo)therapy increase the likelihood of anterior resection? A systematic review of randomised trials. Radiother Oncol. 2006;80:4-12.
23. Patel UB, Brown G, Rutten H, et al. Comparison of magnetic resonance imaging and histopathological response to chemoradiotherapy in locally advanced rectal cancer. Ann Surg Oncol. 2012;19(9):2842-52. DOI:10.1245/s10434-012-2309-3
24. Perez RO, Habr-Gama A, Gama-Rodrigues J, et al. Accuracy of positron emission tomography/computed tomography and clinical assessment in the detection of complete rectal tumor regression after neoadjuvant chemoradiation. Cancer. 2011;118:3501-11.
25. Cascini GL, Avallone A, Delrio P, et al. 18F-FDG PET is an early predictor of pathologic tumor response to preoperative radiochemotherapy in locally advanced rectal cancer. J Nucl Med. 2006;47:1241-8.
26. 2017 European Society of Coloproctology (ESCP) collaborating group. Evaluating the incidence of pathological complete response in current international rectal cancer practice: the barriers to widespread safe deferral of surgery. Colorectal Dis. 2018;20(Suppl. 6):58-68. DOI:10.1111/codi.14361
27. Lee JH, Kim SH, Jang HS, et al. Preoperative elevation of carcinoembryonic antigen predicts poor tumor response and frequent distant recurrence for patients with rectal cancer who receive preoperative chemoradiotherapy and total mesorectal excision: a multi-institutional analysis in an Asian population. Int J Colorectal Dis. 2013;28:511-7.
28. Park JW, Lim S-B, Kim DY, et al. Carcinoembryonic antigen as a predictor of pathologic response and a prognostic factor in locally advanced rectal cancer patients treated with preoperative chemoradiotherapy and surgery. Int J Radiat Oncol Biol Phys. 2009;74:810-7.
29. Lee JH, Hyun JH, Kim DY, et al. The role of fbrinogen as a predictor in preoperative chemoradiation for rectal cancer. Ann Surg Oncol. 2015;22:209-15.
30. Policicchio A, Mercier J, Digklia A, et al. Platelet and neutrophil counts as predictive markers of neoadjuvant therapy effcacy in rectal cancer. J Gastrointest Cancer. 2019;50:894-900.
31. Diefenhardt M, Hofheinz R-D, Martin D, et al. Leukocytosis and neutrophilia as independent prognostic immunological biomarkers for clinical outcome in the CAO/ARO/AIO-04 randomized phase 3 rectal cancer trial. Int J Cancer. 2019;145:2282-91.
32. Dudani S, Marginean H, Tang PA, et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictive and prognostic markers in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation. BMC Cancer. 2019;19(1):664. DOI:10.1186/s12885-019-5892-x
33. Cabel L, Proudhon C, Gortais H, et al. Circulating tumor cells: clinical validity and utility. Int J Clin Oncol. 2017;22:421-30.
34. Sun W, Li G, Wan J, et al. Circulating tumor cells: a promising marker of predicting tumor response in rectal cancer patients receiving neoadjuvant chemo-radiation therapy. Oncotarget. 2016;7:69507-17.
35. Pan R-J, Hong H-J, Sun J, et al. Detection and clinical value of circulating tumor cells as an assisted prognostic marker in colorectal cancer patients. CMAR. 2021;13:4567-78.
36. Hasan S, Renz P, Wegner RE, et al. Microsatellite instability (MSI) as an independent predictor of pathologic complete response (PCR) in locally advanced rectal cancer: a National Cancer Database (NCDB) Analysis. Ann Surg. 2020;271:716-23.
37. Mi M, Ye C, Yuan Y. Neoadjuvant PD-1 blockade: a promising nonoperative strategy for mismatch repair-deficient, locally advanced rectal cancer. Signal Transduct Target Ther. 2022;7(1):361. DOI:10.1038/s41392-022-01216-3
38. Tie J, Cohen JD, Wang Y, et al. Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study. Gut. 2019;68:663-71.
39. Vidal J, Casadevall D, Bellosillo B, et al. Clinical impact of presurgery circulating tumor DNA after total neoadjuvant treatment in locally advanced rectal cancer: a biomarker study from the GEMCAD 1402 trial. Clin Cancer Res. 2021;27:2890-8.
40. Saw RPM, Morgan M, Koorey D, et al. p53, deleted in colorectal cancer gene, and thymidylate synthase as predictors of histopathologic response and survival in low, locally advanced rectal cancer treated with preoperative adjuvant therapy. Dis Colon Rectum. 2003;46(2):192-202. DOI:10.1007/s10350-004-6524-2
41. Chen MB, Wu XY, Yu R, et al. P53 status as a predictive biomarker for patients receiving neoadjuvant radiation-based treatment: a meta-analysis in rectal cancer. PLoS One. 2012;7(9):e45388. DOI:10.1371/journal.pone.0045388
42. Sclafani F, Wilson SH, Cunningham D, et al. Analysis of KRAS, NRAS, BRAF, PIK3CA and TP53 mutations in a large prospective series of locally advanced rectal cancer patients. Int J Cancer. 2020;146:94-102.
43. Oh CR, Kim JE, Kang J, et al. Prognostic Value of the Microsatellite Instability Status in Patients With Stage II/III Rectal Cancer Following Upfront Surgery. Clin Colorectal Cancer. 2018;17(4):e679-85. DOI:10.1016/j.clcc.2018.07.003
44. Cercek A, Lumish M, Sinopoli J, et al. PD-1 blockade in mismatch repair-defcient, locally advanced rectal cancer. N Engl J Med. 2022;386(25):2363-76. DOI:10.1056/NEJMoa2201445
45. Zeitoun G, Sissy CE, Kirilovsky A, et al. The Immunoscore in the clinical practice of patients with colon and rectal cancers. Chirurgia (Bucur). 2019;114:152-61.
46. El Sissy C, Kirilovsky A, Van den Eynde M, et al. A diagnostic biopsy-adapted Immunoscore predicts response to neoadjuvant treatment and selects patients with rectal cancer eligible for a watch-and-wait strategy. Clin Cancer Res. 2020;26:5198-207.

А.Е. Орлов^1,2, О.И. Каганов^1,2, С.А. Фролов*^1,2, Н.В. Блинов¹, Н.Б. Окулевич<sup>1

1</sup>ГБУЗ «Самарский областной клинический онкологический диспансер», Самара, Россия;
²ФГБОУ ВО «Самарский государственный медицинский университет» Минздрава России, Самара, Россия
*frol_ser@mail.ru

________________________________________________

Andrey E. Orlov^1,2, Oleg I. Kaganov^1,2, Sergey A. Frolov*^1,2, Nikita V. Blinov¹, Nikita B. Okulevich<sup>1

1</sup>Samara Regional Clinical Oncologic Dispensary, Samara, Russia;
²Samara State Medical University, Samara, Russia
*frol_ser@mail.ru