scholarly journals Direct effectiveness of adding local hyperthermia to the scheme of neoadjuvant chemoradiotherapy for locally advanced rectal cancer

2020 ◽  
Vol 7 (3) ◽  
pp. 10-20
Author(s):  
S. A. Ivanov ◽  
L. O. Petrov ◽  
D. V. Erygin ◽  
I. A. Gulidov ◽  
A. A. Karpov
Keyword(s):  
Rectal Cancer ◽  
Radiation Therapy ◽  
Surgical Treatment ◽  
Tumor Regression ◽  
Therapy Group ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Control Group ◽  
Study Group

Purpose of the study. Direct evaluation of the antitumor effectiveness of neoadjuvant chemoradiotherapy for rectal cancer using local electromagnetic hyperthermia. Materials and methods. The analysis of the direct results of treatment of patients with locally advanced rectal cancer in the clinic of the MRRC them. A.F.Tsyba is a branch of the Federal State Budgetary Institution Scientific Research Center for Radiology of the Ministry of Health of Russia from 2015 to 2018. The study included 2 groups of patients: the study group of 54 patients and the control group of 56 people. All patients underwent a comprehensive examination with the aim of staging and morphological verification of the tumor. Patients of the study group in the neoadjuvant mode received conventional radiation therapy with classical dose fractionation in ROD 2 Gy, up to SOD 50 Gy, for 5 weeks with CAPOX chemotherapy, and local electromagnetic hyperthermia on the Yacht 4 unit, in the amount of 6 sessions. Patients in the control group received neoadjuvant treatment in an absolutely identical manner, with the exception of local hyperthermia. After the end of neoadjuvant therapy after 8–10 weeks, a comprehensive examination was again performed to assess the response of the tumor and a decision was made to conduct surgical treatment. During the follow-up examination, the following parameters were evaluated: tumor regression according to clinical and radiological examination. After surgical treatment, a comprehensive evaluation of the removed drug was carried out, including an assessment of the degree of therapeutic tumor pathomorphism according to Lavnikova G. P. Results. When conducting a comparative analysis of the frequency of complete clinical regressions of the tumor in the thermo-chemoradiotherapy group, we more often recorded the full clinical response, 12 patients (22%), compared with the chemoradiotherapy group, 8 patients (14%). In terms of partial response and stabilization in the chemoradiotherapy group, partial regression was observed in 75% of patients, while in the thermochemioradiation group only in 52% of cases. Stabilization in the study and control groups was 14% and 6%, respectively. All patients of the study and control groups with partial tumor regression and stabilization underwent surgical treatment. As a result, the frequency of surgical operations in the control group was slightly higher than 48 (85.7%) versus 42 (77.7%) from the main group (p>0.05). When analyzing the frequency of a complete pathomorphological response, we noted that in the thermochemo-radiation therapy group it was 34% versus 4% in the chemo-radiation therapy group. On the contrary, pathomorphism of the 1st degree was much more common in patients of the control group — 21% versus 2% in the study group. The differences in both cases are statistically highly significant (p<0.001, χ2 15, χ27). Conclusion. The use of thermochemoradiotherapy with high statistical significance (p<0.001) increases the frequency of complete pathomorphological response: 34% in the study group versus 4% in the chemoradiotherapy group.

Immediate Results of a Prolonged Course of Neoadjuvant Chemoradiotherapy for Patients with Locally Advanced Rectal Cancer: a Comparison of Classical and Hypofractional Regimes

2020 ◽  
Vol 65 (2) ◽  
pp. 34-43
Author(s):  
A. Abdujapparov ◽  
Sergey Tkachev ◽  
V. Aliev ◽  
D. Romanov ◽  
A. Nazarenko ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Radiation Therapy ◽  
Lymph Nodes ◽  
Primary Tumor ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Main Group ◽  
Control Group

Purpose: To compare the effectiveness of the hypofractional and classical modes of radiation therapy in a neoadjuvant prolonged course of chemoradiotherapy for patients with locally advanced rectal cancer (LARC). Material and methods: This work is based on a retrospective analysis of the database of patients with LARC, who from 2013 to 2017 underwent a prolonged course of neoadjuvant chemoradiotherapy with subsequent surgical intervention. Patients were divided into two groups: the first (main) group, 71 patients with LARC, who, as part of the neoadjuvant treatment, underwent a course of chemoradiotherapy (CRT) in the hypofractionation mode (4 Gy, 3 fractions per week, 32 Gy to regional lymph nodes pelvis and up to 40 Gy to the primary tumor) in combination with chemotherapy with capecitabine 1650 mg/m2 in two doses daily on weekdays. The second group (control group) included 79 patients with LARC, who underwent CRT in the classical fractionation regimen (2 Gy, 5 fractions per week, 44 Gy to regional pelvic lymph nodes and up to 50–58 Gy to the primary tumor) in combination with capecitabine chemotherapy 1650 mg/m2 in two doses on the days of radiation therapy. Results: The average duration of a prolonged course of CRT in the main group was 22.56 (95 % CI from 21.94 to 23.18) calendar days, in the control group — 38.84 (95 % CI from 38.12 to 39.54), p = 0.0001. Pathological response of the III degree in the main group was recorded in 23 % of cases, and of the IV degree in 18 %, in the control group these indicators were 19 % and 15 %, respectively, p = 0.4. A decrease in the stage of the tumor process was recorded in 50 (70.4 %) cases in the main group and in 47 (59.5 %) cases in the control group, p = 0.16. No statistically significant differences were observed in the incidence and severity of cases of hematological and local toxicity. Conclusion: The results of our study confirm that the use of a prolonged course of neoadjuvant chemoradiotherapy in hypofractionation mode does not worsen oncological results, does not increase the frequency and severity of early and late radiation injuries, but at the same time reduces the duration of the course of treatment by two weeks. The hypofractionation regimen can be considered as an alternative and not inferior to the classical regimen in the neoadjuvant course of CRT of patients with LARC.

Serial ctDNA analysis as a real-time indicator of neoadjuvant chemoradiotherapy in rectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3569-3569 ◽  
Author(s):  
Jiaolin Zhou ◽  
Guole Lin ◽  
Yuhua Gong ◽  
Yanyan Zhang ◽  
Yan-Fang Guan ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Lymph Node ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Lymph Node Involvement ◽  
Tumor Regression Grade ◽  
Treatment Intensification

3569 Background: Neoadjuvant chemoradiotherapy (nCRT) is nowadays the standard of care for the locally advanced rectal cancer (LARC). However, there is no effective method to predict patients’ possible benefits from nCRT and monitor the response to it. Methods: Patients with locally advanced middle and low rectal cancer of stage cT3-4N0M0 or cTanyN+M0 were enrolled from August 2017 to July 2018. All patients received nCRT with long-term radiation plus fluorouracil based chemotherapy, followed by the radical surgery. Serial plasma samples were collected pre-nCRT, during nCRT, and preoperatively (8 weeks after the completion of nCRT). Somatic mutations were detected with next-generation sequencing using a 1021-gene panel with peripheral blood lymphocyte DNA as a germline control. Results: This prospective cohort study enrolled 61 patients with rectal cancer. The pathological complete response (pCR) rate and the downstage rate was 31% (19/61) and 80% (49/61), respectively. ctDNA was detectable in 77% (47/61), 18% (11/61) and 13% (8/61) of blood samples obtained pre-nCRT, during nCRT and preoperatively, respectively. No significant association was observed between pre-nCRT ctDNA status with any clinicopathological factors, including age, gender, differentiation or tumor circumferential extent. Among the 8 patients with detectable ctDNA preoperatively, pathological tumor regression grade (TRG) of CAP 2-3 were observed and hepatic metastasis was found in 4 patients within 2 months. For patients with undetectable pre-operative ctDNA, a higher proportion archived pathological downstaging (85% vs 50%). The correlation between preoperative ctDNA status and achievement of pathological downstage was independent of age, gender or differentiation (p = 0.02). In addition, preoperative ctDNA positivity was associated with the persistently involved lymph node (p = 0.02). However, neither pre-nCRT nor during-nCRT ctDNA status was associated with pathological downstaging or persistently lymph node involvement. Conclusions: Detectable ctDNA after the completion of nCRT is a predicator of unsatisfactory curative effect of patients with LARC, which might indicate novel treatment intensification studies. Clinical trial information: NCT03042000.

Three-year outcomes of sandwich therapy in patients with locally advanced cancer of the middle and lower rectum

2021 ◽  
Vol 11 (2) ◽  
pp. 29-35
Author(s):  
A. A. Aniskin ◽  
D. V. Kuzmichev ◽  
Z. Z. Mamedli ◽  
A. V. Polynovskiy
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Distant Metastases ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Chemoradiation Therapy ◽  
Control Group ◽  
Study Group ◽  
Positive Trend

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.

scholarly journals The effects of neoadjuvant chemoradiotherapy and an in-hospital exercise training programme on physical fitness and quality of life in locally advanced rectal cancer patients: a randomised controlled trial (The EMPOWER Trial)

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Lisa Loughney ◽  
Malcolm A. West ◽  
Helen Moyses ◽  
Andrew Bates ◽  
Graham J. Kemp ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Physical Fitness ◽  
Usual Care ◽  
Psychological Health ◽  
Locally Advanced ◽  
Cardiopulmonary Exercise Testing ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Control Group

Abstract Background The EMPOWER trial aimed to assess the effects of a 9-week exercise prehabilitation programme on physical fitness compared with a usual care control group. Secondary aims were to investigate the effect of (1) the exercise prehabilitation programme on psychological health; and (2) neoadjuvant chemoradiotherapy (NCRT) on physical fitness and psychological health. Methods Between October 2013 and December 2016, adults with locally advanced rectal cancer undergoing standardised NCRT and surgery were recruited to a multi-centre trial. Patients underwent cardiopulmonary exercise testing (CPET) and completed HRQoL questionnaires (EORTC-QLQ-C30 and EQ-5D-5L) pre-NCRT and post-NCRT (week 0/baseline). At week 0, patients were randomised to exercise prehabilitation or usual care (no intervention). CPET and HRQoL questionnaires were assessed at week 0, 3, 6 and 9, whilst semi-structured interviews were assessed at week 0 and week 9. Changes in oxygen uptake at anaerobic threshold (VO2 at AT (ml kg−1 min−1)) between groups were compared using linear mixed modelling. Results Thirty-eight patients were recruited, mean age 64 (10.4) years. Of the 38 patients, 33 were randomised: 16 to usual care and 17 to exercise prehabilitation (26 males and 7 females). Exercise prehabilitation significantly improved VO2 at AT at week 9 compared to the usual care. The change from baseline to week 9, when adjusted for baseline, between the randomised groups was + 2.9 ml kg −1 min −1; (95% CI 0.8 to 5.1), p = 0.011. Conclusion A 9-week exercise prehabilitation programme significantly improved fitness following NCRT. These findings have informed the WesFit trial (NCT03509428) which is investigating the effects of community-based multimodal prehabilitation before cancer surgery. Trial registration ClinicalTrials.gov NCT01914068. Registered 1 August 2013.

scholarly journals Pre-Treatment T2-WI Based Radiomics Features for Prediction of Locally Advanced Rectal Cancer Non-Response to Neoadjuvant Chemoradiotherapy: A Preliminary Study

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1894 ◽  
Author(s):  
Bianca Petresc ◽  
Andrei Lebovici ◽  
Cosmin Caraiani ◽  
Diana Sorina Feier ◽  
Florin Graur ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Imaging Biomarkers ◽  
Tumor Regression Grade ◽  
Pre Treatment

Locally advanced rectal cancer (LARC) response to neoadjuvant chemoradiotherapy (nCRT) is very heterogeneous and up to 30% of patients are considered non-responders, presenting no tumor regression after nCRT. This study aimed to determine the ability of pre-treatment T2-weighted based radiomics features to predict LARC non-responders. A total of 67 LARC patients who underwent a pre-treatment MRI followed by nCRT and total mesorectal excision were assigned into training (n = 44) and validation (n = 23) groups. In both datasets, the patients were categorized according to the Ryan tumor regression grade (TRG) system into non-responders (TRG = 3) and responders (TRG 1 and 2). We extracted 960 radiomic features/patient from pre-treatment T2-weighted images. After a three-step feature selection process, including LASSO regression analysis, we built a radiomics score with seven radiomics features. This score was significantly higher among non-responders in both training and validation sets (p < 0.001 and p = 0.03) and it showed good predictive performance for LARC non-response, achieving an area under the curve (AUC) = 0.94 (95% CI: 0.82–0.99) in the training set and AUC = 0.80 (95% CI: 0.58–0.94) in the validation group. The multivariate analysis identified the radiomics score as an independent predictor for the tumor non-response (OR = 6.52, 95% CI: 1.87–22.72). Our results indicate that MRI radiomics features could be considered as potential imaging biomarkers for early prediction of LARC non-response to neoadjuvant treatment.

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