Objective:to analyze treatment outcomes in patients with locally advanced rectal cancer that received various combinations of neoadjuvant chemotherapy and chemoradiotherapy.Materials and methods. In this retrospective study, we analyzed a cohort of prospectively recruited patients with stage mrT3(CRM+)/ T4N0–2M0 locally advanced rectal cancer. Participants were divided into three groups. Patients in Group 1 received preoperative longcourse radiotherapy given concurrently with capecitabine, followed by 2–6 cycles of consolidation chemotherapy with capecitabine and oxaliplatin (CapOx). In Group 2, patients initially received 1–2 cycles of induction chemotherapy with CapOx, followed by radiotherapy + capecitabine, and then consolidation chemotherapy with CapOx (“sandwich” method). Participants in Group 3 were treated with 1–3 cycles of induction CapOx chemotherapy with subsequent long-course chemoradiotherapy. After the combination treatment, all patients underwent surgery. The primary endpoint of this study was therapeutic pathomorphosis. Secondary endpoints included complete clinical response, toxicity, local recurrence, distant metastasis, and relapse-free survival.Results.This study included 155 patients (98 in Group 1, 44 in Group 2, and 13 in Group 3). Grade III toxicity was documented in 6.12 %, 4.55 %, and 23.08 % of cases in Groups 1, 2, and 3 respectively. None of the patients had grade IV toxicity. Grade III therapeutic pathomorphosis was achieved in 33.7 %, 22.7 %, and 23.1 % of patients in Groups 1, 2, and 3 respectively. Grade IV therapeutic pathomorphosis was observed in 14.3 %, 15.9 %, and 7.69 % of patients in Groups 1, 2, and 3 respectively. Complete clinical response was registered in 16.3 %, 11.4 %, and 0 % of cases in Groups 1, 2, and 3 respectively. Median follow-up was 47.2 months with no signs of progression. Relapses were observed in 1.02 % and 2.27 % of patients from Group 1 and Group 2 respectively, whereas Group 3 demonstrated no relapses. A total of 11.22 %, 13.64 %, and 23.1 % of participants from Groups 1, 2, and 3 respectively developed distant metastasis.Conclusion.Polychemotherapy used within the consolidation and «sandwich» treatment regimens is a promising option for the treatment of locally advanced rectal cancer. The efficacy of induction chemotherapy should be further studied with a larger sample.
The aim of the study: to increase the frequency of achieving pathologic complete response and increase disease-free survival in the investigational group of patients with locally advanced rectal cancer T3(MRF+)–4N0–2M0 by developing a new strategy for neoadjuvant therapy.Materials and methods. In total, 414 patients were assigned to treatment. Control group I included 89 patients who underwent radiotherapy (RT) 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week. Control group II included 160 patients who underwent RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and oxaliplatin once a week, during the course of RT. Study group III consisted of 165 patients. This group combined RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and additional consecutive CapOx cycles. This group was divided into 2 subgroups: subgroup IIIa included 106 patients with consolidating chemotherapy (after CRT); subgroup IIIb included 59 patients who underwent “sandwich” treatment. Therapy consisted of conducting from 1 to 2 cycles of induction CapOx (up to CRT) and from 1 to 2 cycles of consolidating CapOx with an interval of 7 days. In the interval between the courses of drug therapy, RT 52–56 Gy/26–28 fractions was performed. According to the results of the control examination, further treatment tactics were determined. The primary end points were 5-year disease-free survival and the achievement of a pathologic complete response.Results. Pathologic complete response was significantly more often recorded in patients in the investigational group III (17.48 %; p = 0.021) compared with control groups (7.95 % in the I group and 8.28 % in the II group). 5-year disease-free survival in patients in the study groups was: 71.5 % in the III group, 65.6 % in the II group and 56.9 % in the I group.Conclusion. The shift in emphasis on strengthening the neoadjuvant effect on the tumor and improving approaches to drug therapy regimens have significantly improved disease-free survival of patients with locally advanced rectal cancer.
Цель: оценка эффективности неоадъювантной последовательной индукционной химиотерапии (ХТ), химиолучевой терапии (ХЛТ) и консолидирующей (ХТ) по схеме CapOx у больных МРРПК по показателям 3‑летней безрецидивной выживаемости в сравнении с контрольной группой. В качестве дополнительных целей выделены оценка: частоты выполнения сфинктеросохранящих операций, токсических эффектов лечения, частоты полных морфологических эффектов, частоты рецидивов и метастазов.Методы: С 2019 года по настоящее время в исследование включены пациенты МРРПК со стадией T3 (CRM +) / 4N0–2M0.Результаты: В исследование включено 136 пациентов, полный курс лечения прошли 107 (78,7 %), еще 21 пациент находится в процессе лечения или ожидания операции, остальные исключены по тем или иным причинам (смерть, прогрессирование и др.) Частота токсических осложнений III–IV степени не превышала 4,7 % в группе ХЛТ и 6,8 % в группе ХЛТ + ХТ и была сопоставима. Сфинктеросохраняющие операции в группе ХЛТ + ХТ выполнены у 38 пациентов (67,5 %), по сравнению с 25 (56,7 %) в группе ХЛТ (p = 0,05). Частота послеоперационных осложнений по классификации Clavien‑Dindo оказалась сопоставима в двух группах. Полный морфологический ответ достигнут у 7 (15,9 %) пациентов в группе ХЛТ и у 7 (13,5 %) в группе ХТ + ХЛТ (р = 0,2). Отмечено увеличение частоты возникновения близкого к полному морфологическому ответу (TRG2) в группе ХЛТ + ХТ — 17 (32,7 %) пациентов, против 8 (18,2 %) (p = 0,048). В группе ХЛТ полный курс адъювантной химиотерапии завершили 28,3 % пациентов, в группе ХЛТ + ХТ — 64,9 % (р = 0,05). Медиана наблюдения за пациентами 17 мес. В обеих группах выявлено по 1 рецидиву (1,8 % для группы ХЛТ и 1,7 % для группы ХЛТ + ХТ). Частота отдаленных метастазов в группе ХЛТ составила 14,5 % (8 пациентов), в группе ХЛТ + ХТ 8,7 % (5 пациентов). Достоверности данная разница не имеет, однако различия между группами составили 5,8 %. Показатели 2‑летней безрецидивной выживаемости составили 81 % в группе ХЛТ и 86 % в группе ХЛТ + ХТ соответственно.Заключение: Тотальная неоадъювантая терапия является перспективным направлением в лечении больных МРРПК, позволившая в представленном исследовании продемонстрировать увеличение безрецидивной выживаемости (без статистической достоверности), увеличить частоту достижения близкого к полному морфологического ответа (TRGII) по сравнению с группой ХЛТ и тем самым значимо увеличить частоту выполнения сфинктеросохраняющих операций. Число проведенных курсов химиотерапии статистически значимо выше в группе ХЛТ + ХТ. Для окончательных выводов требуется дальнейшее наблюдение за пациентами из контрольной и исследуемой групп.
Background. Colorectal anastomotic leakage remains on of the most significant challenges in rectal surgery.Objective: to assess the impact of pelvic peritoneal floor reconstruction on the incidence of postoperative complications associated with colorectal anastomosis.Materials and methods. In this retrospective cohort study, we analyzed medical records of rectal cancer patients who had undergone rectal resection with anastomosis formation between 2013 and 2020. we compared patients who had no pelvic peritoneal floor reconstruction (from 2013 to 2017) and those who had it (2018–2020). Only patients with favorable prognosis (tumor located at least 5 cm above the transitional anal fold and no history of chemoradiotherapy) were included. The primary outcome measure was the incidence of peritonitis and colorectal anastomosis leakage. Secondary outcome measures included overall incidence of complications (Clavien–Dindo), mortality rate, blood loss, and duration of surgery.Results. A total of 120 patients were included into the experimental group, while the control group was composed of 125 patients. Ten patients from the control group developed peritonitis (8.0 %), whereas in the experimental group, there were no cases of peritonitis (p = 0.002). Anastomotic leakage was registered in 12 individuals from the experimental group (12.5 %) and 14 controls (11.2 %) (p = 0.753). The overall incidence of postoperative complications was 23.3 % (n = 28) among patients who had pelvic peritoneal floor reconstruction and 18.4 % (n = 23) among those who did not have it (p = 0.342). Colostomy was required in 92 patients from the experimental group (76.7 %) and 78 patients from the control group (62.4 %) (p = 0.018). The postoperative mortality was 0.8 % in the control group (n = 1) and 0 % in the experimental group (p = 1).Conclusion. Pelvic peritoneal floor reconstruction reduces the risk of peritonitis, but does not affect the overall risk of anastomotic leakage. This method is effective for the prevention of severe postoperative complications.
Background. The most important criteria for the effectiveness of the treatment of locally advanced rectal cancer are indicators of overall survival (OS) and disease-free survival (DSF). Conducting systemic chemotherapy in addition to chemoradiotherapy at the preoperative stage can increase these indicators.Objective: to study analyze the indicators of 3-year OS and DFS, as well as the frequency of local relapses and distant metastases.Materials and methods. From 2013 to 2020, 72 patients with T≥3(CRM+)N0–2M0 lower and middle ampullar rectal cancer were included in the study using sandwich therapy. At the first stage, 2 courses of induction polychemotherapy were carried out according to the CapOx scheme (capecitabine 2000 mg/m2 orally for 14 days and oxaliplatin 130 mg/m2 intravenously once every 3 weeks). Further, chemoradiation therapy was carried out with a total focal dose of 50–56 Gy while taking capecitabine 1650 mg/m2 per day orally on the days of irradiation. After the end of chemotherapy, the patients underwent 2 courses of consolidating polychemotherapy according to the CapOx scheme (capecitabine 2000 mg/m2 orally for 14 days and oxaliplatin 130 mg/m2 intravenously once every 3 weeks). The control group consisted of 72 patients who underwent neoadjuvant treatment in accordance with current clinical guidelines (chemotherapy course with a total focal dose of 50–56 Gy while taking capecitabine 1650 mg/m2 per day orally on the days of irradiation).Results. In 19 (26.4 %) patients from the study group and in 6 (8.3 %) patients from the control group, the achievement of pCR was recorded (p = 0.006). The overall complication rate was 48 (66.7 %) in the study group and 37 (51.4 %) in the control group (p = 0.072), the frequency of grade III–IV toxicity was 8 (11.1 %) and 7 (9.7 %), respectively (p = 0.072). Sphincter-sparing surgical interventions were performed in 52 (72.2 %) and 40 (55.6 %) patients in the sandwich-therapy group and the control group of chemoradiation therapy, respectively (p = 0.037). Resection in the R0 volume was achieved in 71 (98.6 %) and 72 (100 %) patients, respectively (p = 0.316).Conclusion. The use of sandwich therapy is a promising trend in the treatment of patients with locally advanced rectal cancer. There were no significant differences in the frequency of 3-year OS (96.1 % versus 91.5 %, p = 0.247), DFS (89.8 % versus 84.0 %, p = 0.117) and local relapses (0 % versus 4.2 %, p = 0.997). In our study, statistically significant differences were obtained in the incidence of distant metastases (6.9 % versus 18.1 %, p = 0.05), which may indicate a positive trend towards an increase in OS and DFS rates.
The results of numerous single-center and multicenter randomized and non-randomized studies on the treatment of patients with locally advanced rectal cancer (LARC) over a 70-year period are presented. The sequence of surgical, medicinal, radiation and chemoradiation treatment is represented. The doses and amount of radiation exposure are described, both in mono mode and with the use of various combinations of chemotherapeutic drugs in neoadjuvant and adjuvant regimens. The evolution of complex treatment that has shifted has shifted the emphasis to the use of chemoradiation therapy in the neoadjuvant period, and the introduction of new chemotherapeutic drugs and regimens have significantly increased the survival rates among patients with LARC. The approaches to the treatment of patients with LARC are not static and are constantly being improved. This literature review shows the chronological sequence and major current trends in the neoadjuvant and adjuvant components of the treatment of patients with locally advanced rectal cancer.
Ключевые слова: местнораспространенный рак прямой кишки, комплексное лечение, консолидирующая химиотерапия, индукционная химиотерапия, лечебный патоморфоз Актуальность. Достижение лечебного патоморфоза после предоперационного лечения является достоверным положительным прогностическим фактором при раке прямой кишки. Проведение системной химиотерапии в дополнение к химиолучевой терапии на предоперационном этапе может повысить вероятность достижения лечебного патоморфоза. Цель работы -изучить возможность достижения полного морфологического ответа (pCR) при использовании sandwich-терапии местнораспространенного рака прямой кишки. Материал и методы. С 2013 по 2020 г. 72 больных раком нижне-и среднеампулярного отделов прямой кишки стадий T3(CRM+)N0-2M0 были включены в исследование с использованием sandwich-терапии. На первом этапе было проведено 2 курса индукционной полихимиотерапии (ПХТ) по схеме CapOx (капецитабин 2000 мг/м 2 внутрь в течение 14 дней и оксалиплатин 130 мг/м 2 внутривенно 1 раз в 3 нед). Далее проводилась химиолучевая терапия (ХЛТ) суммарной очаговой дозой (СОД) 50-56 изоГр на фоне приема капецитабина 1650 мг/м 2 в сутки внутрь в дни облучения. После окончания ХЛТ пациентам были проведены 2 курса консолидирующей ПХТ по схеме CapOx (капецитабин 2000 мг/м 2 внутрь в течение 14 дней и оксалиплатин 130 мг/м 2 внутривенно 1 раз в 3 нед). Контрольную группу составили 72 пациента, которым было проведено неоадъювантное лечение в соответствии с действующими клиническими рекомендациями [курс ХЛТ суммарной очаговой дозой (СОД) 50-56 изоГр на фоне приема капецитабина 1650 мг/м 2 в сутки внутрь в дни облучения]. Результаты. У 19 (26,4%) больных из исследуемой группы и у 6 (8,3%) больных из контрольной группы зарегистрировано достижение pCR (р=0,006). Общая частота осложнений составила 48 (66,7%) в исследуемой и 37 (51,4%) в контрольной группе (р=0,072), частота токсичности III-IV степени -8 (11,1%) и 7 (9,7%) соответственно (р=0,072). Сфинктеросохраняющие хирургические вмешательства удалось выполнить 52 (72,2%) и 40 (55,6%) пациентам в группе sandwich-терапии и в контрольной группе ХЛТ соответственно (р=0,037). Резекция в объеме R0 достигнута у 71 (98,6%) и у 72 (100%) пациентов соответственно (р=0,316). Заключение. Использование sandwich-терапии является перспективным направлением при лечении больных местнораспространенным раком прямой кишки и может увеличить частоту достижения полного лечебного патоморфоза. Для окончательных выводов требуются дальнейшие исследования.
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.
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