Three Perspectives: The Approach of Neoadjuvant Treatment of Rectum Cancer According to Medical Oncologists, Radiation Oncologists, and Surgeons

Purpose Two treatment modalities are considerable for radiation therapy: short-course radiotherapy and immediate surgery or chemoradiation with 5-Fluorouracil based chemotherapy with delayed surgery. In this study, we try to evaluate the real-life treatment approaches of medical, radiation, and surgical oncologists for neoadjuvant treatment of rectal cancers. Method The online survey form was established via Google Forms. The survey was taken voluntarily by medical oncologists, radiation oncologists, surgical oncologists, and general surgeons. Results One hundred eighty-three of the participants were medical oncologists while 36 were radiotherapists and 36 were surgeons. Most of the study population preferred long-course radiation therapy and chemotherapy which was consisting eighty-five percent. Two-thirds of the participants apply chemotherapies before operation. The most frequent chemotherapy cycles for the pre-operative setting were ‘three’ or ‘four-or-more’ with the percent of 27,8 and 25,1 respectively. Medical oncologists had a significantly higher tendency of offering chemotherapy between radiation therapy and surgery compared with the other groups. The optimal time of surgery was different between groups. There was no difference among groups between surgery and the ‘watch & wait’ strategy. A significant difference was observed between groups in offered neoadjuvant chemotherapy regimens. Conclusion In our study, we found the new pre-operative chemotherapy regimen with short-course radiotherapy was slowly adopted in current practice. Also, medical oncologists tend pre-operative chemotherapy compared with other groups. The optimal surgery time for patients receiving neoadjuvant treatment is still controversial.

Short-course radiotherapy and chemotherapy for conversion surgery in patients with unresectable metastatic rectal cancer: a preliminary case series study

Purpose: Curative treatment is challenging in patients with locally advanced rectal cancer and unresectable metastases. The aim of this study was to evaluate the clinical outcomes of short-course radiotherapy (RT) followed by systemic chemotherapy for patients with rectal cancer with mesorectal fascia (MRF) involvement and unresectable distant metastases.Methods: The study included consecutive patients diagnosed as having metastatic mid-to-low rectal cancer treated with short-course RT followed by systemic chemotherapy for conversion radical or palliative surgery between 2014 and 2019 at Gil Medical Center. The patients had primary rectal tumors involving the MRF and unresectable distant metastases. The treatment strategies were determined in a multidisciplinary team discussion.Results: Seven patients (five men and two women) underwent short-course RT (5 × 5 Gy) and preoperative systemic chemotherapy. The median age was 68 years (range, 46–84 years), and the median distance from the anal verge to the primary tumor was 6.0 cm (range, 2.0–9.0 cm). During the median follow-up period of 29.4 months, three patients underwent conversion radical surgery with R0 resection, two underwent palliative surgery, and two could not undergo surgery. No postoperative major morbidity or mortality occurred. The patients who underwent conversion complete radical surgery showed good long-term survival outcomes, with an overall survival time of 29.4–48.8 months and progression-free survival time of 14.7–41.1 months.Conclusion: Short-course RT followed by systemic chemotherapy could provide patients with unresectable stage IV rectal cancer a chance to undergo to conversion radical surgery with good long-term survival outcomes.

Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer

BackgroundIn locally advanced rectal cancer (LARC), preoperative short-course radiotherapy (SCRT) with delayed surgery has been shown to be as effective as long-course chemoradiotherapy, with only modest benefits. This study aimed to evaluate the efficacy and safety of preoperative SCRT combined with subsequent CAPOX (capecitabine and oxaliplatin) and the anti-PD-1 antibody camrelizumab in patients with LARC.MethodsThis was a prospective, single-arm, phase II trial. Treatment-naïve patients with histologically confirmed T3-4N0M0 or T1-4N+M0 rectal adenocarcinoma received 5×5 Gy SCRT with two subsequent 21-day cycles of CAPOX plus camrelizumab after 1 week, followed by radical surgery after 1 week. The primary endpoint was pathological complete response (pCR) rate. Biomarker analysis was performed to identify a potential predictor of pCR to treatment.ResultsFrom November 7, 2019 to September 14, 2020, 30 patients were enrolled, and 27 patients received at least one dose of CAPOX plus camrelizumab. Surgery was performed in 27 (100%) patients. The pCR (ypT0N0) rate was 48.1% (13/27), including 46.2% (12/26) for proficient mismatch repair (MMR) tumors and 100% (1/1) for deficient MMR tumors. Immune-related adverse events were all grade 1–2, with the most common being reactive cutaneous capillary endothelial proliferation (81.5%). No grade 4/5 adverse events occurred. Biomarker analysis showed patients without FGFR1–3 deletions had a better tendency for pCR.ConclusionsSCRT combined with subsequent CAPOX plus camrelizumab followed by delayed surgery showed a favorable pCR rate with good tolerance in patients with LARC, especially in the proficient MMR setting. A randomized controlled trial is ongoing to confirm these results.Trial registration numberClinicalTrials.gov identifier: NCT04231552.

Study Protocol of A Phase II Study to Evaluate Safety and Efficacy of Neo-adjuvant Pembrolizumab and Radiotherapy in Localized Rectal Cancer

Background: Reshaping the tumor microenvironment by novel immunotherapies represents a key strategy to improve the treatment of cancers. Nevertheless, responsiveness to these treatments is often correlated with the extent of the T cell infiltration at the tumor site. Remarkably, microsatellite stable rectal cancer is characterized by poor infiltration and, therefore, do not respond to immune checkpoint blockade. To date, the only available curative option for these patients relies on extensive surgery. With the aim to broaden the application of promising immunotherapies, it is necessary to develop alternative approaches to promote T cell infiltration into the tumor microenvironment of these tumors. In this regard, recent evidence shows that radiotherapy may have profound immunostimulatory effects, hinting at the possibility of combining it with immunotherapy. The combination of long-course chemoradiotherapy and immunotherapy was recently shown to be safe and yielded promising results in rectal cancer, however short-course radiotherapy and immunotherapy have never been tested in these tumors. Methods: Our clinical trial investigates the clinical and biological impact of combining pembrolizumab with short-course radiotherapy in the neo-adjuvant treatment of localized microsatellite stable rectal cancer. This phase II non-randomized study will recruit 25 patients who will receive short-course preoperative radiotherapy (5Gy x 5 days) and four injections of pembrolizumab starting on the same day and on weeks 4, 7 and 10. Radical surgery will be performed after three weeks from the last pembrolizumab injection. Our clinical trial also includes an extensive research program involving the transcriptomic and proteomic analysis of blood and tumor samples throughout the course of the treatment. Discussion: Our study is the first clinical trial to provide with safety and efficacy information of this novel treatment approach in rectal cancer, leading to a major breakthrough in the treatment of this cancer. Additionally, the translational research program will offer better insight into immunological changes within the tumor and blood during treatment. Taken together, our work will help optimizing future treatment combinations and, possibly, better selecting patients.

A randomized phase III study of short-course radiotherapy combined with Temozolomide in elderly patients with newly diagnosed glioblastoma; Japan clinical oncology group study JCOG1910 (AgedGlio-PIII)

Background The current standard treatment for elderly patients with newly diagnosed glioblastoma is surgery followed by short-course radiotherapy with temozolomide. In recent studies, 40 Gy in 15 fractions vs. 60 Gy in 30 fractions, 34 Gy in 10 fractions vs. 60 Gy in 30 fractions, and 40 Gy in 15 fractions vs. 25 Gy in 5 fractions have been reported as non-inferior. The addition of temozolomide increased the survival benefit of radiotherapy with 40 Gy in 15 fractions. However, the optimal regimen for radiotherapy plus concomitant temozolomide remains unresolved. Methods This multi-institutional randomized phase III trial was commenced to confirm the non-inferiority of radiotherapy comprising 25 Gy in 5 fractions with concomitant (150 mg/m2/day, 5 days) and adjuvant temozolomide over 40 Gy in 15 fractions with concomitant (75 mg/m2/day, every day from first to last day of radiation) and adjuvant temozolomide in terms of overall survival (OS) in elderly patients with newly diagnosed glioblastoma. A total of 270 patients will be accrued from 51 Japanese institutions in 4 years and follow-up will last 2 years. Patients 71 years of age or older, or 71–75 years old with resection of less than 90% of the contrast-enhanced region, will be registered and randomly assigned to each group with 1:1 allocation. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, and proportion of health-related quality of life preservation. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in April 2020. Ethics approval was granted by the National Cancer Center Hospital Certified Review Board. Patient enrollment began in August 2020. Discussion If the primary endpoint is met, short-course radiotherapy comprising 25 Gy in 5 fractions with concomitant and adjuvant temozolomide will be a standard of care for elderly patients with newly diagnosed glioblastoma. Trial registration Registry number: jRCTs031200099. Date of Registration: 27/Aug/2020. Date of First Participant Enrollment: 4/Sep/2020.

28 Colorectal Cancer Resections During COVID-19: To Do or Not to Do?

Introduction Ascertaining the practice of colorectal cancer (CRC) resections during the COVID-19 pandemic in England and Wales. Method A list of all colorectal multi-disciplinary teams (MDTs) was obtained from the National Bowel Cancer Audit (NBOCA) database. A survey was designed using Google Forms and emailed to at least one consultant colorectal surgeon of each MDT. One response per MDT was used in the analysis. All responses were anonymous. Study duration was from 15th April 2020 to 30th June 2020. Results Sixty-eight of the 150 MDTs enlisted on the NBOCA database in England and Wales responded. 86.6% were performing CRC resections and 86% were screening patients pre-operatively for COVID-19. 84.9% were using full Personal Protective Equipment (PPE - FFP3 and eye protection) in all cases whereas 12.3% were using PPE only in suspected cases. 44.4% had resorted to open resections due to risk of laparoscopy being an aerosol generating procedure. 13.7% attributed post-operative complications to COVID-19 and 4 centres reported death due to COVID-19 related complications. 40% of MDTs used short course radiotherapy in rectal cancer patients where resections were postponed either by patient or by the team. 55% responded to feeling uncomfortable/very uncomfortable to cancel cancer resections while 31.7% were equivocal and others comfortable not to operate during the pandemic. Conclusions This survey demonstrates a snapshot of practice during the peak of the COVID-19 pandemic. The majority of the centres continued to perform CRC resections safely where possible. There has been obvious disruption to services and change to normal practice.