employee
Moscow, Russian Federation
employee
Moscow, Russian Federation
employee
employee
Moscow, Russian Federation
graduate student
Moscow, Russian Federation
employee
GRNTI 76.33 Гигиена и эпидемиология
GRNTI 76.03 Медико-биологические дисциплины
OKSO 31.06.2001 Клиническая медицина
OKSO 31.08.08 Радиология
OKSO 32.08.12 Эпидемиология
OKSO 14.04.02 Ядерные физика и технологии
BBK 534 Общая диагностика
BBK 51 Социальная гигиена и организация здравоохранения. Гигиена. Эпидемиология
TBK 5712 Медицинская биология. Гистология
TBK 5734 Медицинская радиология и рентгенология
TBK 6212 Радиоактивные элементы и изотопы. Радиохимия
TBK 5708 Гигиена и санитария. Эпидемиология. Медицинская экология
Purpose: To improve the effectiveness of treatment of patients with locally advanced rectal cancer (LARC) stage T3(MRF+)-4N0-2M0 by developing a new strategy of therapy. Material and methods: The study included 414 patients with LARC. Control group I included 89 patients who underwent neoadjuvant CRT 52–56 Gy with capecitabine. Control group II included 160 patients, underwent neoadjuvant CRT 52–56 Gy with capecitabine and oxaliplatin once a week, during the course of RT. Study group III - 165 patients. This group combined neoadjuvant CRT 52–56 Gy with capecitabine and additional consecutive courses of chemotherapy (CT) in the CapOx mode. This group, depending on the variant of chemotherapy, was divided into 2 subgroups: subgroup IIIa included 106 patients with consolidating CT (after CRT); subgroup IIIb included 59 patients who underwent "sandwich" treatment. Therapy consists of conducting 1 or 2 courses of induction CT (up to CRT) in the CapOx mode and 1 or 2 courses of consolidating CT in the CapOx mode with an interval of 7 days. In the interval between the courses of drug therapy, prolonged CRT was performed. According to the results of the control examination, further treatment tactics were determined. Results: IComplete therapeutic pathomorphosis in the tumor was significantly more frequently registered in patients in the study group III (17.5 %; p=0.021) compared to the control groups: in I – 8.0 % and II – 8.3 %. In total, relapses in the study were registered in 34 (8.3 %) of 410 patients. A comparative analysis of patients in the control groups (I and II) of treatment did not determine significant differences in the development of relapses (11.4 % vs. 10.8 %, respectively; p=0.884). When analyzing the subgroups (IIIa and IIIb) of the study group, there were also no significant differences in the development of relapses (4.8 % vs. 3.4 %; p=0.676). In the present study, long-term metastases at various times after treatment were diagnosed in 100 (24.4 %) of 410 patients. All metastases occurred at a median follow-up of 20.9 months (4 to 46 months). Metastases were significantly less frequent in patients in group III (18.3 %) compared to group I (31.8 %; p=0.015) and II (26.6 %; p=0.037). There were no significant differences between patients in group I and II (p=0.382). The analysis of the treatment subgroups of the study group (IIIa and IIIb) did not determine significant differences in the development of metastases (19.1 % vs. 17.0 %; p=0.456). The overall five-year survival rate in patients in group III was 90.5 %, in group I – 71.8% and in group II – 78.3%. Five-year relapse-free survival in patients in the study groups was: III – 71.5%, I – 56.9% and II – 65.6%, respectively. Conclusion: The shift in the focus on strengthening the neoadjuvant effect on the tumor and the improvement of approaches to drug therapy regimens allowed to significantly increase the relapse-free survival in this category of patients.
locally advanced rectal cancer, chemo radiotherapy, induction chemotherapy, consolidation chemotherapy, sandwich therapy
1. Jung K., Kim H., Park J., et al. Adjuvant Chemotherapy after Neoadjuvant Chemoradiation and Curative Resection for Rectal Cancer: is it Necessary for All Patients? // J. Surgical Oncology. 2015. V.111, No. 4. P. 439-444.
2. Bosset J.-F., Calais G., Mineur L., et al. Fluorouracil-Based Adjuvant Chemotherapy after Preoperative Chemoradiotherapy in Rectal Cancer: Long-Term Results of the EORTC 22921 Randomised Study // Lancet Oncol. 2014. V.15, No. 2. P. 184-190.
3. Sainato A., Cernusco Luna Nunzia V., Valentini V., et al. No Benefit of Adjuvant Fluorouracil Leucovorin Chemotherapy after Neoadjuvant Chemoradiotherapy in Locally Advanced Cancer of the Rectum (LARC): Long Term Results of a Randomized Trial (I-CNR-RT) // Radiother Oncol. 2014. V.113, No. 2. P. 223-229.
4. Rödel C., Graeven U., Fietkau R., et al. Oxaliplatin Added to Fluorouracil-Based Preoperative Chemoradiotherapy and Postoperative Chemotherapy of Locally Advanced Rectal Cancer (the German CAO/ARO/AIO-04 Study): Final Results of the Multicentre, Open-Label, Randomised, Phase 3 Trial // Lancet Oncol. 2015. V.16, No. 8. P. 979-989.
5. Hong Y.S., Nam B.-H., Kim K.-P., et al. Oxaliplatin, Fluorouracil, and Leucov-Orin Versus Fluorouracil and Leucovorin as Adjuvant Chemotherapy for Locally Advanced Rectal Cancer after Preoperative Chemoradiotherapy (ADORE): an Open-Label, Multicentre, Phase 2, Randomised Controlled Trial // Lancet Oncol. 2014. V.15, No. 11. P. 1245-1253.
6. Schmoll H.J., Stein A., Hofheinz R.D., et al. Preoperative Chemoradiotherapy and Postoperative Chemotherapy with Capecitabine and Oxaliplatin vs. Capecitabine Alone in Locally Advanced Rectal Cancer: Final Analyses // Ann. Oncol. 2016. V.27 (suppl 6). Available at: https://academic.oup.com /annonc/article/ 27/suppl _ 6/467PD/2799263 Last Accessed November 21, 2019.
7. Hu X., Li Y.-Q., Li Q.-G., Ma Y.-L., Peng J.-J., Cai S.-J. Adjuvant Chemotherapy Seemed not to Have Survival Benefit in Rectal Cancer Patients with YpTis-2N0 after Preoperative Radiotherapy and Surgery from a Population-Based Propensity Score Analysis // Oncologist. 2019. V.24, No. 6. P. 803-811.
8. Fernandez-Martos C., Garcia-Albeniz X., Pericay C., et al. Chemoradiation, Surgery and Adjuvant Chemotherapy Versus Induction Chemotherapy Followed by Chemoradiation and Surgery: Long-Term Results of the Spanish GCR-3 Phase II Randomized Trial // Ann. Oncol. 2015. V.26, No. 8. P. 1722-1728.
9. Kim C.W., Kang B.M., Kim I.Y., et al. Korean Society of Coloproctology (KSCP) Trial of CONsolidation Chemotherapy for Locally Advanced Mid or Low Rectal Cancer after Neoadjuvant Concurrent Chemoradiotherapy: a Multicenter, Randomized Controlled Trial (KONCLUDE) // BMC Cancer. 2018. V.18, No. 1. P. 538.
10. Glynne-Jones R., Grainger J., Harrison M., et al. Neoadjuvant Chemotherapy Prior to Preoperative Chemoradiation or Radiation in Rectal Cancer: Should We Be More Cautious? // Br. J. Cancer. 2006. No. 94. P. 363-371.
11. Gao Y.H., Lin J.Z., An X. et al. Neoadjuvant Sandwich Treatment with Oxaliplatin and Capecitabine Administered Prior to, Concurrently with, and Following Radiation Therapy in Locally Advanced Rectal Cancer: a Prospective Phase 2 Trial // Int. J. Radiat. Oncol. Biol. Phys. 2014. V.90, No. 5. P. 1153-1160.
12. Landry J.C., Feng Y., Prabhu R.S., et al. Phase II Trial of Preoperative Radiation with Concurrent Capecitabine, Oxaliplatin, and Bevacizumab Followed by Surgery and Postoperative 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX), and Bevaci-zumab in Patients with Locally Advanced Rectal Cancer: 5-Year Clinical Outcomes ECOG-ACRIN Cancer Research Group E3204 // Oncologist. 2015. V.20, No. 6. R. 615-616.
13. Maas M., Nelemans P.J., Valentini V., et al. Long-Term Outcome in Patients with a Pathological Complete Response after Chemoradiation for Rectal Cancer: a Pooled Analysis of Individual Patient Data // Lancet Oncol. 2010. V.11, No. 9. P. 835-844.
14. Habr-Gama A., Perez R.O., Nadalin W., Sabbaga J., Ribeiro U.Jr., Silva e Sousa A.H.Jr., Campos F.G., Kiss D.R., Gama-Rodrigues J. Operative Versus Nonoperative Treatment for Stage 0 Distal Rectal Cancer Following Chemoradiation Therapy: Long-Term Results // Ann. Surg. 2004. V.240, No. 4. P. 711-717. Discussion 717-718.
15. Petrelli F., Sgroi G., Sarti E., et al. Increasing the Interval Between Neoadjuvant Chemoradiotherapy and Surgery in Rectal Cancer: A Meta-Analysis of Published Studies // Ann. Surg. 2016. V.263, No. 3. R. 458-464.