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Stage IV rectal cancer with resectable disease presents challenging issues, as the radical treatment of the whole disease is difficult. Surgery and chemotherapy (CT) play an unquestionable role, but the contribution of pelvic radiotherapy (RT) is not very clear. In 2009, we established a prospective treatment protocol that included CT, short-course preoperative radiotherapy (SCRT) with surgery of the primary tumour and all metastatic locations. Forty patients were included. Eight (20%) patients did not receive CT due to significant comorbidities. Radical surgery treatment was possible in 22 (55%) patients. The mean follow-up was 42.81 months (3.63–105.97). Overall survival at 24 and 36 months was 71.4% and 58.2%, respectively. There was good local control of the disease, as 97.2% of pelvic surgeries were R0 and there were no local recurrences. In stage IV with resectable metastatic disease, the proposed therapeutic regimen seems very appropriate in well selected patients able to tolerate the treatment. We bet on the role of pelvic RT, due to the good local control of the disease in our series.

Aim A prolonged interval (>4 weeks) between short-course radiotherapy (25 Gy in five fractions) (SCRT-delay) and total mesorectal excision for rectal cancer has been associated with a decreased postoperative complication rate and offers the possibility of organ preservation in the case of a complete tumour response. This prospective cohort study systematically evaluated patient-reported bowel dysfunction and physician-reported radiation-induced toxicity for 8 weeks following SCRT-delay. Method Patients who were referred for SCRT-delay for intermediate risk, oligometastatic or locally advanced rectal cancer were included. Repeated measurements were done for patient-reported bowel dysfunction (measured by the low anterior resection syndrome [LARS] questionnaire and categorized as no, minor or major LARS) and physician-reported radiation-induced toxicity (according to Common Terminology Criteria for Adverse Events version 4.0) before start of treatment (baseline), at completion of SCRT and 1, 2, 3, 4, 6 and 8 weeks thereafter. Results Fifty-one patients were included; 31 (61%) were men and the median age was 67 years (range 44-91). Patient-reported bowel dysfunction and physician-reported radiation-induced toxicity peaked at weeks 1-2 after completion of SCRT and gradually declined thereafter. Major LARS was reported by 44 patients (92%) at some time during SCRT-delay. Grade 3 radiation-induced toxicity was reported in 17 patients (33%) and concerned predominantly diarrhoea. No Grade 4-5 radiation-induced toxicity occurred. Conclusion During SCRT-delay, almost every patient experiences temporary mild-moderate radiation-induced toxicity and major LARS, but life-threatening toxicity is rare. SCRT-delay is a safe alternative to SCRT-direct surgery that should be proposed when counselling rectal cancer patients on neoadjuvant strategies.

BACKGROUND Radiotherapy or chemoradiotherapy is widely used for the treatment of rectal cancer preoperatively. Although the combination of radiotherapy and chemotherapy as an established preoperative neoadjuvant therapy shows high efficacy in the treatment of rectal cancer, some patients experience a response of poor tolerance and outcomes due to the long duration radiotherapy. The study compared short duration radiotherapy plus chemotherapy vs long duration radiotherapy plus chemotherapy for rectal cancer to determine whether short duration radiation treatment should be considered to diminish complications, reduce risk of recurrence and improve survival in patients with rectal cancer. AIM To evaluate the efficacy and safety of short duration radiotherapy combined with chemotherapy for the treatment of advanced rectal cancer. METHODS One hundred patients with stage IIIB or higher severe rectal cancer were selected as the study subjects at The First Affiliated Hospital of Hebei North University between December 2018 and December 2019. The patients were assigned to different groups based on the treatment regimens. Fifty patients who received preoperative short durations of radiotherapy plus chemotherapy were enrolled in an observation group and fifty patients who received conventional radiotherapy and chemotherapy were enrolled in a control group. Colonoscopic biopsy was performed for all patients with pathological diagnosis of rectal cancer. The expression of tumor-related factors such as RUNX3 and Ki-67 was quantitatively analyzed using immunohistochemistry in the tissues of the patients before and after treatment. Moreover, the duration of procedure, the amount of bleeding during the operation, the anus-conserving rate, the incidence of postoperative complications (wound infection, anastomotic leakage, postoperative intestinal obstruction, etc.) and postoperative pathology were compared between the two groups. The overall survival rate, recurrence rate and distant metastasis rate were also compared through postoperative reexamination and regular follow-up. RESULTS There was no significant difference in the positive expression rate of RUNX3 and Ki-67 between the two groups before the treatment (P > 0.05). Compared with the pretreatment value, the positive rate of RUNX3 was increased and the positive rate of Ki-67 was decreased in both groups after the treatment (all P < 0.05). The incidence of leukopenia, thrombocytopenia, neutropenia and diarrhea were higher in the observation group than in the control group (all P < 0.05). There was no significant difference in the incidence of anemia, fatigue, neurotoxicity and nausea and vomiting between the two groups (all P > 0.05). No significant difference was observed in the duration of procedure, intraoperative bleeding, the anus-conserving rate and the incidence of postoperative complications between the two groups (P > 0.05). After 1 year of follow-up, the 1-yr survival rate was 80.0% in the observation group and 68.0% in the control group, the recurrence rate was 8.0% in the observation group and 10.0% in the control group, the distant metastasis rate was 6.0% in the observation group and 8.0% in the control group difference (all P < 0.05). CONCLUSION Short duration radiotherapy combined with chemotherapy can improve the cure rate, prolong the survival time and reduce the incidence of complications in patients with advanced rectal cancer.

Summary Objective To evaluate the optimal timing of surgery after short-course radiation therapy and to compare the efficacy of short-course radiotherapy (SCRT) and long-course radiotherapy (LCRT) in patients with rectal cancer, a systematic review with network analysis was conducted. Methods A systematic literature search of the Cochrane Central Register of Controlled Trials, Embase, and MEDLINE (PubMed) was conducted to identify papers published before June 4, 2018, without language or publication date restrictions. The use of surface under the cumulative ranking curve (SUCRA) within a network meta-analysis framework provided a numerical presentation of the overall ranking, thus providing a ranking of treatment options from which patients can choose from. Within the primary search that yielded 1435 studies, 11 relevant randomized trials were identified. Results No statistically significant difference was found in overall mortality and metastasis between short-course radiotherapy with early surgery (SCES), short-course radiotherapy with delayed surgery (SCDS), and long-course radiotherapy with delayed surgery (LCDS). For overall metastasis, using SUCRA analysis, SCES, LCDS, and SCDS respectively had the highest to lowest SUCRA rank, respectively. Thus, SCES was the most likely to be effective, followed by LCDS and SCDS. Conclusion Regarding the optimal timing of surgery for patients with advanced rectal cancer undergoing short-course radiation therapy, SCES is recommended as the optimal choice according to the available evidence and considering the control of future metastasis.

SummaryNeoadjuvant chemoradiotherapy is a well-established standard treatment for locally advanced rectal cancer and has led to a remarkable improvement in local control. However, distant recurrences still pose a notable threat and local failure, albeit increasingly rare, can lead to unfavorable clinical situations. In this short review, we discuss three promising new strategies to improve rectal cancer treatment: total neoadjuvant therapy, short course radiotherapy, and immune checkpoint inhibitors.

Background Non-operative management of rectal cancer is increasingly being used in selected patients. Most reports include patients treated with chemoradiotherapy (CRT) before inclusion into a Watch & Wait (W&W) programme. The aim of this study was to report outcomes from a single-centre W&W programme involving a large cohort of patients. Methods Patients treated with chemoradiotherapy (CRT) or short-course radiotherapy (SCRT) with or without chemotherapy, between 2008 and 2020, who showed signs of a clinical complete response (cCR) were reviewed. Patients were assessed using digital rectal examination, flexible endoscopy, carcinoembryonic antigen measurement, MRI, and CT imaging, discussed at the multidisciplinary tumour board meeting, and followed up in a dedicated W&W programme as from 2015. Outcomes including regrowth and 3-year survival (time to regrowth or death) were prospectively evaluated. Results Of 142 patients who were assessed, 88 fulfilled the criteria for cCR. Treatment before cCR included CRT, SCRT with chemotherapy, and SCRT alone in 16 (18 per cent), 28 (32 per cent), and 44 (50 per cent) patients, respectively. Patients treated with CRT and SCRT with chemotherapy had more advanced clinical T- and N-stage, compared with patients treated with SCRT alone (clinical T-stage > 2: 81 per cent and 89 per cent versus 47 per cent, respectively; clinical N-stage > 0: 75 per cent and 93 per cent versus 68 per cent, respectively). Overall rate of regrowth was 19 per cent, with 31 per cent, 21 per cent, and 14 per cent following CRT, SCRT with chemotherapy, and SCRT alone, respectively. Uni- and multivariable analyses evaluating the clinical parameters revealed no statistically significant associations with risk of local regrowth. All but one patient with regrowth underwent salvage surgery. The 3-year survival rate (death with regrowth as competing risk) was 93 per cent, with no significant difference between treatment groups. Conclusion In this cohort of W&W patients, the vast majority received SCRT with or without chemotherapy and results consistent with previous W&W reports were obtained. No statistically significant differences in terms of regrowth rate were obtained when comparing CRT, SCRT with chemotherapy, and SCRT alone. SCRT can induce sustained cCR and may precede a W&W strategy., This study describes the prospective evaluation of outcomes in 88 Watch & Wait rectal cancer patients (72 treated with short-course radiotherapy with or without chemotherapy). Overall regrowth rate was 19 per cent, and all but one patient underwent salvage surgery. Short-course radiotherapy can lead to sustained complete response and precede a Watch & Wait strategy.

Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control. In this publication the primary endpoint 3-year disease-related treatmentfailure, (defined as the first occurrence of locoregional failure, distant metastasis, new primary colorectal tumour, ortreatment-related death), is assessed in the intention-to-treat population.

Background Despite recent improvements, management of locally advanced rectal cancer (LARC) remains challenging, and many patients (pts) still experience recurrence. In preclinical models, combining Rego with an anti-PD-1 inhibitor led to superior tumour growth suppression as compared with either treatment alone. In a phase I clinical trial, remarkable results were reported for the combination of Rego and Nivo in advanced MSS colorectal cancer. This synergistic effect is thought to be secondary to the anti-angiogenic effects of Rego and its potential to reduce TAMs, promote M1 macrophage conversion, and downregulate expression of immunosuppressive factors. Building on these data, we designed a trial of Rego-Nivo with standard SCRT in the neoadjuvant setting of RC. Trial design REGINA is an academic, multicentre, single-arm, phase II trial sponsored by Institut Jules Bordet. Eligible patients are treated according to the following plan: induction phase (Nivo 240 mg IV D1&15, and Rego 80 mg PO D1-14), SCRT (D22-26), consolidation phase (Nivo 240 mg IV D29,43&57, and Rego 80 mg PO D29-49), and surgery (7-8 weeks after SCRT). Key eligibility criteria include age ≥18 years, ECOG PS ≤1, adenocarcinomas below the peritoneal reflection, intermediate-risk, stage II-III tumour (ie, cT3/T4aNany or cT1-2N+, no involvement/threatening of the mesorectal fascia, no involvement of lateral pelvic lymph nodes). The primary endpoint is pathological complete response (pCR). Secondary endpoints include, among others, toxicity, compliance to treatment, pTRG, event-free survival, and overall survival. The study follows a Simon’s two-stage design (null hypothesis pCR=12%, alternative hypothesis pCR=24%; α=5%, β=20%) with a maximum of 60 pts to be enrolled. A safety interim analysis is planned after the first 6 pts have completed treatment. Serial collection of tumour, blood, and stool samples is mandatory at pre-specified time points for exploratory correlative biomarker analyses. The trial is planned to be run at 8-10 centres across Belgium. Study recruitment started in Q1 2021 and is anticipated to complete in Q3 2023. Clinical trial information: NCT04503694.

The optimal treatment of locally advanced rectal cancer with synchronous liver metastases remains controversial. In this study, we aimed to evaluate the safety, efficacy, and oncologic outcomes of upfront chemotherapy and short-course radiotherapy with delayed surgery in patients with locally advanced rectal cancer and synchronous liver metastases.Forty-four patients who underwent upfront chemotherapy and short-course radiotherapy with delayed surgery for locally advanced rectal cancer (cT3/4,2.0 mm from the mesorectal fascia) with synchronous liver metastases between January 2010 and June 2017 were reviewed retrospectively. Primary and metastatic liver lesions were resected with curative intent. Upfront chemotherapy and short-course radiotherapy were administered. Thereafter, restaging, surgery only, or additional chemotherapy followed by surgery was performed.At the time of initial diagnosis, 20 patients had3 liver metastases; 24 patients had ≥3 liver metastases. Twenty-three patients had hemi-liver metastases; 21 patients had bilobar liver metastases. R0 resection of rectal lesions was achieved in 43 patients. Synchronous R0 resection of liver metastases was achieved in 41 patients. Postoperative complications (Clavien-Dindo Grade ≥ III) were noted in 5 patients. Grade 3/4 adverse events were observed in 26 patients. All adverse events were managed effectively with medication and supportive care. The 3-year overall survival and progression-free survival rates were 65.3% and 26.9%, respectively.Upfront chemotherapy and short-course radiotherapy with delayed surgery appear to be safe and effective in patients with locally advanced rectal cancer and synchronous liver metastases without substantially increasing treatment induced morbidity.

Objective The endpoint of the present study was to evaluate the outcomes of short-course radiotherapy (SCRT) and SCRT with delayed surgery (SCRT-DS) on a selected subgroup of frail patients with locally advanced middle/low rectal adenocarcinoma. Methods From January 2008 to December 2018, a total of 128 frail patients with locally advanced middle-low rectal adenocarcinoma underwent SCRT and subsequent restaging for eventual delayed surgery. Rates of complete pathological response, down-staging, disease free survival (DFS) and overall survival (OS) were analyzed. Results 128 patients completed 5 × 5 Gy pelvic radiotherapy. 69 of these were unfit for surgery; 59 underwent surgery 8 weeks (average time: 61 days) after radiotherapy. Downstaging of T occurred in 64% and down-staging of N in 50%. The median overall survival (OS) of SCRT alone was 19.5 months. The 1-year, 2-year, 3-year and 5-year OS was 48%, 22%, 14% and 0% respectively. In the surgical group, the median disease-free survival (DFS) and median OS were, respectively, 67 months (95% CI 49.8–83.1 months) and 72.1 months (95% CI 57.5–86.7 months). The 1, 2, 3, 5-year OS was 88%, 75%, 51%, 46%, respectively. Post-operative morbidity was 22%, mortality was 3.4%. Conclusions Frail patients with advanced rectal cancer are often “unfit” for long-term neoadjuvant chemoradiation. A SCRT may be considered a valid option for this group of patients. Once radiotherapy is completed, patients can be re-evaluated for surgery. If feasible, SCRT and delayed surgery is the best option for frail patients.

The Publisher regrets that errors had been introduced within the above mentioned article. The article is now correct online and in print. The Publisher would like to apologise for any inconvenience caused.

4006 Background: Local control in locally advanced rectal cancer (LARC) has improved. However, systemic relapses remain high even with postoperative chemotherapy, possibly due to low compliance. Short-course radiotherapy (SCRT) followed by delayed surgery with, in the waiting period, chemotherapy, may lead to better compliance, downstaging and fewer distant metastases. The main objective of the international multicenter phase III RAPIDO trial is to decrease Disease-related Treatment Failure (DrTF), defined as locoregional failure, distant metastasis, a new primary colon tumor or treatment-related death, by reducing the risk of systemic relapse without compromising local control. Methods: MRI-diagnosed LARC patients with either cT4a/b, extramural vascular invasion, cN2, involved mesorectal fascia or enlarged lateral lymph nodes considered to be metastatic were randomly assigned to SCRT (5x5 Gy) with subsequent six cycles of CAPOX or nine cycles of FOLFOX4 followed by total mesorectal excision (TME) (experimental arm) or, capecitabine-based chemoradiotherapy (25-28 x 2.0-1.8 Gy) followed by TME and optional, predefined by hospital policy, postoperative eight cycles of CAPOX or twelve cycles of FOLFOX4 (standard arm). Results: Between June 2011 and June 2016, 920 patients were randomized. Pathological complete response rates were 27.7% vs 13.8% (OR 2.40 [1.70 – 3.39]; p < 0.001) in the experimental and standard arms, respectively. At three years, cumulative probability of DrTF was 23.7% in the experimental arm and 30.4% in the standard arm (HR 0.76 [0.60 – 0.96]; p = 0.02). Probability at three years of distant metastasis and locoregional failure were, in the experimental and standard arms, 19.8% vs 26.6% (HR 0.69 [0.53 – 0.89]; p = 0.004) and 8.7% vs 6.0% (HR 1.45 [0.93 – 2.25]; p = 0.10), respectively. No differences in DrTF between hospitals with or without policy for postoperative chemotherapy were found (p = 0.37). Overall health ( p = 0.192), quality of life ( p = 0.125) and low anterior resection syndrome score ( p = 0.136) were comparable between the two treatment arms. Conclusions: A lower rate of DrTF, as a result of a lower rate of distant metastases, in high-risk LARC patients can be achieved with preoperative short-course radiotherapy, followed by chemotherapy and TME than by conventional chemoradiotherapy. In addition, the high pCR rate, achieved with the experimental treatment regimen can contribute to organ preservation. This treatment can be considered as a new standard of care. Clinical trial information: NCT01558921 .

The name of author Do Hoon Lim was incorrect in the initial online publication. The original article has been corrected.

The optimal radiotherapy regimen in elderly patients with glioblastoma treated by chemoradiation needs to be addressed. We provide the results of a comparison between conventionally fractionated standard radiotherapy (CRT) and short-course radiotherapy (SRT) in those patients treated by temozolomide-based chemoradiation.Patients aged 65 years or older from the GBM-molRPA cohort were included. Patients who were planned for a ≥ 6-week or ≤ 4-week radiotherapy were regarded as being treated by CRT or SRT, respectively. The median RT dose in the CRT and SRT group was 60 Gy in 30 fractions and 45 Gy in 15 fractions, respectively.A total of 260 and 134 patients aged older than 65 and 70 years were identified, respectively. CRT- and SRT-based chemoradiation was applied for 192 (73.8%) and 68 (26.2%) patients, respectively. Compared to SRT, CRT significantly improved MS from 13.2 to 17.6 months and 13.3 to 16.4 months in patients older than 65 years (P 0.001) and 70 years (P = 0.002), respectively. Statistical significance remained after adjusting for age, performance status, surgical extent, and MGMT promoter methylation in both age groups. The benefit was clear in all subgroup analyses for patients with Karnofsky performance score 70-100, Karnofsky performance score ≤ 60, gross total resection, biopsy, methylated MGMT promoter, and unmethylated MGMT promoter (all P 0.05).CRT significantly improved survival compared to SRT in elderly glioblastoma patients treated with chemoradiation in selected patients amenable for chemoradiation. This study is hypothesis-generating and a prospective randomized trial is urgently warranted.

Short-course preoperative radiotherapy is indicated in patients with resectable rectal cancer to control local recurrence. Although no clear evidence is available, short-course radiotherapy with operation within a week is common practice. The aim of this study was to investigate the impact of timing of operation for rectal cancer after short-course radiotherapy on anastomotic leakage.Data from the Dutch Colorectal Audit were used. All patients who received short-course preoperative radiotherapy and underwent elective operation within 14 days for rectal cancer between January 1, 2011 and December 31, 2016 were included. Interval between radiotherapy and operation was calculated by extracting date of start of radiotherapy from the date of operation. Patients were divided into short interval (4 days) and long interval (4 or more days). The interval and other patient or perioperative parameters were included in univariable and multivariable logistic regression analyses to identify independent associations with anastomotic leakage.In total, 2,131 patients were eligible for analysis: 1,055 (49.5%) patients had operations4 days after radiotherapy and 1,076 (50.5%) patients had operations after 4 or more days. One hundred and eighty-five (8.7%) patients experienced anastomotic leakage. The incidence of anastomotic leakage was significantly higher in patients who underwent operation within4 days (10.1% vs 7.2%; p = 0.018). In the multivariable analysis, an interval of4 days was significantly associated with anastomotic leakage (odds ratio 1.438; 95% CI 1.054 to 1.962; p = 0.022).Elective surgery for rectal cancer4 days after preoperative short-course radiotherapy resulted in an increase of anastomotic leakage.

AIM To study the outcomes of patients presenting with locally advanced rectal cancers with distant metastasis (mLARC), treated with short course radiotherapy (SCRT). METHOD Between May 2012 and August 2015, 70 patients diagnosed with mLARC, treated with SCRT (25 Gy/5#) and three to six cycles of CAPOX chemotherapy (CT), were assessed for surgical feasibility for the primary and metastatic sites. RESULTS Sixty-five patients could complete the planned SCRT and three to six cycles of CT. Response rate and disease control rate for the primary was 68% and 97%, respectively. Radiologically, CRM became free in 44 (72%) patients out of 61 initially involved. Fifty-two (74%) were planned to receive treatment with a potentially curative intent and 18 (26%) with palliative intent. Of those treated with curative intent, 34 (65%) underwent primary tumor resection (PTR). Successful intervention for metastatic disease was done in 27 (52%) patients. At a median follow up of 43 months, the median overall survival (OS) for patients undergoing PTR was 36 months versus 12 months for those in which the tumor was still unresectable or had distant progression (P

4 Background: Neoadjuvant therapy followed by total mesorectal surgery is the standard of care for locally advanced rectal carcinoma (RC). In the elderly, often underrepresented in clinical trials, but who represent a very large number of patients, therapeutic proposals are not based on high levels of evidence. The NACRE study investigated the role of short course radiotherapy with delayed surgery in this population. Methods: The PRODIGE 42-GERICO 12 NACRE is a multicenter randomized clinical trial aimed at comparing Arm A preop radiochemotherapy (RCT) (50 Gy, 2Gy/fraction [fr]; 25 fr + capecitabine) and delayed surgery and Arm B short course radiotherapy (25 gy, 5Gy/fr, 5fr) and delayed surgery. Eligible patients (pts) had cT3 or cT4 (or cT2 of the very low rectum), M0 rectal adenocarcinomas 80 years). Two primary end-points will be analyzed according to the hierarchical sequential procedure: firstly R0 resection rate (non-inferiority test with a 8% non-inferiority margin), secondly preservation of autonomy using IADL score (superiority test with 15% absolute difference margin); secondary end-point will be survival and toxicity. We present here the results for R0 resection, survival and toxicities. Results: 29 sites randomized 101 patients from 01/2016 to 08/2019, 59 were males (58.4%), median age was 80 years (range 75-91). Pts characteristics were well balanced. 14% of pts in arm A did not receive all of the planned neoadjuvant treatment compared to 0% in arm B. The R0 resection rate in arm B (86.0% [IC95% 73-94%]) was not-inferior to the R0 resection rate in arm A (89.8% [ic95% 77-97%]), p=0.04 (non inferiority test). With a median follow-up of 15.8 months (CI95%: 14.8-26.0), the 6 months death rate was 10.0% (CI95%: 3.0-22.0) in arm A and 3.92% (CI95%: 0 -13.0) in arm B. There is a significant difference in overall survival between the two arm in favor of arm B (p=0.04, LogRank test), and there is a trend in favor of arm B for specific survival (p=0.06 LogRank test). Disease free survival is not statistically different (p=0.9). 13 serious adverse events were observed in arm A during preoperative phase, 7 in arm B, 16 and 10 respectively during the post-operative phase. Conclusions: These preliminary results show that short course radiotherapy with delayed surgery is associated with better compliance than radiochemotherapy in elderly patients and could give an advantage in overall survival. This regimen may be preferred in elderly patients. Clinical trial information: NCT02551237.

63 Background: Chemoradiotherapy followed by radical surgery is standard treatment for patients with locally advanced rectal cancer (LARC). Short-course radiotherapy (SCRT), either with immediate or delayed surgery, provides similar oncological results compared with long-course radiotherapy with delayed surgery. Delayed surgery with the addition of neoadjuvant immunotherapy may bring better downstaging effect and minimize the risk of distant relapse. We conducted this single-arm phase 2 trial to investigate the efficacy and safety of SCRT combined with subsequent capecitabine and oxaliplatin (CAPOX) plus Camrelizumab (anti-PD-1 antibody) followed by delayed surgery in patients with LARC. Methods: Patients with histologically confirmed T3–4N0M0 or T1-4N+M0 rectal cancer, previously untreated disease, and ECOG performance status of 0-1, received SCRT (5×5 Gy) with subsequent two 21-day cycles of CAPOX (oxaliplatin 130 mg/m2 ivgtt, d1; capecitabine 1000 mg/m2 po bid, d1-14) plus Camrelizumab (200 mg iv drip, d1) after 1 week, followed by radical surgery after 1 week. Adjuvant therapy was decided by the investigator. The primary endpoint was pathological complete response (pCR) rate, defined as the absence of viable tumor cells in the primary tumor and lymph nodes. The study is ongoing to follow up the survival outcomes and obtain the results of next generation sequencing and PD-L1 expression. The data cutoff date was September 8, 2020. Results: From November 2019 to September 2020, a targeted number of patients (n = 29) were enrolled and are expected to complete the surgery by November 2020. The median age was 57 (range 31-73) years, 55% (16/29) of patients had ECOG performance status of 1, and the median distance from tumor to the anal verge was 5 (range, 1.9-9) cm. At data cutoff, 10 patients had undergone the surgery, with R0 resection rate of 100%. The pCR rate was 60% (6/10), including 56% (5/9) for those with mismatch repair-proficient, and 100% (1/1) for those with mismatch repair-deficient. Of 4 patients without pCR, 2 only received one cycle of CAPOX plus Camrelizumab due to the outbreak of COVID-19 in Wuhan, and 1 had signet-ring cell rectal carcinoma. At data cutoff, 20 patients had received at least one dose of Camrelizumab. Immune-related adverse events (irAEs) were all grade 1-2, and the most common irAE was reactive cutaneous capillary endothelial proliferation in 10 (50%) of 20 patients. Postoperative bleeding and infection occurred in 1 (10%) and 2 (20%) of 10 patients, respectively. No treatment-related death was observed. Conclusions: SCRT combined with subsequent CAPOX plus Camrelizumab followed by delayed surgery showed promising pCR rate with good tolerance in patients with LARC, regardless of the mismatch repair status, suggesting a candidate strategy for the neoadjuvant therapy. Clinical trial information: NCT04231552.

Purpose An adaptive plan selection strategy can account for daily target volume variations for radiotherapy in rectal cancer patients. The aim was to quantify the daily dosimetric consequences of plan selection compared to a non-adaptive approach. Materials and methods Ten patients with rectal cancer, treated with 25Gy in five fractions to the mesorectum and pelvic lymph nodes, were selected. The adaptive strategy was simulated by creating three plans per patient, with varying upper ventral PTV margins, and selecting the smallest PTV covering the entire mesorectum on every daily CBCT scan. Subsequently, mesorectum, bladder, and bowel cavity were delineated on these scans. Daily dose–volume histograms were calculated for both the adaptive and non-adaptive plan, with a ventral PTV margin of 20mm. Coverage of the mesorectum, defined as V95%>99%, was calculated, as well as bladder and bowel cavity V95% and V15Gy. Results In one patient, mesorectum coverage improved. A reduction in bladder V95% and bowel cavity V15Gy was found, of 6.9% and 18.4cm 3 ( p Conclusion Plan selection for radiotherapy in rectal cancer can improve coverage of the target volume. Overall dosimetric sparing of bladder and bowel cavity was limited but could be beneficial for individual patients.

Background Rectal carcinoma [RC] is often managed with preoperative radiotherapy or radio-chemotherapy followed by total mesorectal excision (TME). Efforts are being made to improve outcome by intensifying the preoperative treatment. However, the optimum therapy remains unclear. There is ongoing controversy regarding the optimum radiation dose, chemotherapy regimen and schedule. In addition there exists growing disagreement regarding the role of adjuvant chemotherapy after neoadjuvant radiation or chemoradiation. Methodology We reviewed the recent land mark trials to find a road map in the management of locally advanced rectal carcinoma. Results Preoperative short course radiotherapy has long been proven to improve local disease control. The initial trials with long course chemoradiotherapy, comparing short course radiotherapy have shown to increase local control and pathological complete response rates. Since then treatment intensification of this neoadjuvant schedule has been tried by many researchers. But initial results of these treatment intensification trials, show no significant benefit and are associated with increased toxicity. There is an unmet need to stratify patients depending on risk to assign them to long course chemoradiotherapy or short course radiotherapy. Current evidence does not support the use of adjuvant chemotherapy in patients who were treated with preoperative (chemo)radiotherapy. Conclusion Preoperative radiotherapy appears to improve disease control with favorable toxicity profile and there is very little to choose between long course chemoradiotherapy and short course radiotherapy. However, long course chemoradiotherapy may be beneficial for patients with high risk features like positive circumferential resection margin [CRM] and extramural spread of >5 mm. There is no role for adjuvant chemotherapy in patients who were treated preoperative (chemo)radiotherapy.

The Stockholm III randomized trial showed that short-course radiotherapy and delayed surgery can be used routinely for resectable tumours [1,2]. The interim analysis of this trial demonstrated path...

Introduction: Patients with locally advanced rectal cancer (LARC) who are unfit for chemoradiation (CRT), are often offered short-course radiotherapy followed by delayed surgery (SCRT-delay). This entails a lower radiation dose, no chemotherapy and a shorter treatment period. This may lower their chances for complete tumor response and, as such, organ-sparing approaches. The purpose of this study was to compare the pathological complete response (pCR) rates between neoadjuvant CRT and SCRT-delay in patients with LARC in a nationwide database from the Netherlands. Methods: In the population based Netherlands Cancer Registry, clinical stage III rectal cancer patients, diagnosed between 2008 and 2014, who underwent CRT or SCTR-delay were selected. pCR (ypT0N0), near pCR (ypT0-1N0), and tumor and nodal downstaging were compared between the treatment groups using multivariable logistic regression analysis. Results: 386 patients underwent SCRT-delay and 3659 patients underwent CRT. The pCR-rate in the SCRT-delay group was significantly lower compared to the CRT-group (6.4% vs. 16.2%, p < 0.001). After adjustment for clinical tumor stage, clinical nodal stage and time interval to surgery, SCRT-delay patients were significantly less likely to reach pCR (adjusted odds ratio 0.3, 95%CI 0.2–0.5). Also, near-pCR (ypT0–1N0) as well as tumor and nodal downstaging was observed less often in the SCRT-delay group. Conclusion: Compared to patients treated with neoadjuvant CRT, those receiving SCRT and delayed surgery are less likely to develop pCR. Novel neoadjuvant treatment strategies for patients not fit enough for CRT are needed to increase their eligibility for organ-sparing treatments.

Radiation therapy plays an important role in the management of patients with rectal cancer. Radiation therapy can improve local control and increase sphincter preservation rates. Preoperative chemoradiation and preoperative short course radiotherapy are now considered standards of care for appropriate rectal cancer patients. Specific radiation therapy techniques such as reirradiation and intraoperative radiation therapy may also improve outcomes in selected patients with rectal cancer. This chapter will discuss the various roles of radiation therapy for rectal cancer and review modern approaches for radiation therapy delivery.

Introduction The aim of this study was to compare the short- and long-term outcomes between short-course radiotherapy with delayed surgery (SRT-delay) and a standard conventional chemoradiotherapy (CRT) regimen. Methods Two collaborating institutions adopted different regimens; the SRT-delay regimen was selected by Meiwa Hospital and the CRT regimen was selected by Hyogo College of Medicine. The inclusion criteria were T3 middle and low rectal cancer patients treated with radical surgery after preoperative therapy. The median follow-up period was 44 months (range, 12–85). Results From 2007 to 2013, 104 patients were treated using the SRT-delay regimen and 61 patients were treated using the CRT regimen. The pretreatment characteristics of the 2 groups were not significantly different. The sphincter-preserving rate (93.3%, 85.2%), T downstaging (37.5%, 37.7%), ypN(−) (74.0%, 67.2%), postoperative complications and the bowel, and urinary and sexual functioning of the SRT-delay regimen were noninferior to those of the CRT regimen. The 3-year local recurrence-free survival, recurrence-free survival, and overall survival in the SRT-delay and CRT groups were 90.6% and 90.6% ( P = .764), 83.8% and 78.3% ( P = .687) and 96.0% and 92.8% ( P = .833), respectively. Conclusion The SRT-delay regimen was noninferior in terms of the downstaging effect, and oncologic and functional outcomes compared with the CRT regimen for T3 middle and low rectal cancer.

Aim: To evaluate outcome of an accelerated radiotherapy (RT) regimen in elderly patients with an early stage non-melanoma skin cancer (NMSC). Methods: Total RT dose was 30 Gy in 5 Gy fractions in six consecutive days. Results: Thirty-one patients were enrolled. Fourteen were aged ≥80 years. Acute skin and observed late toxicity were exclusively of grade 1. Thirty patients showed a complete response (median follow-up 30 months). Two-year actuarial local control was 93.2%. The cosmetic result was mostly judged as good or excellent. Conclusions: Short-course RT in elderly NMSC patients produces >90% local control of disease.

// Maria Napolitano 1 , Crescenzo D’Alterio 1 , Eleonora Cardone 2 , Anna Maria Trotta 1 , Biagio Pecori 3 , Daniela Rega 2 , Ugo Pace 2 , Dario Scala 2 , Giosue Scognamiglio 4 , Fabiana Tatangelo 4 , Carmela Cacciapuoti 5 , Roberto Pacelli 6 , Paolo Delrio 2 , Stefania Scala 1 1 Immunology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione Giovanni Pascale” – I.R.C.C.S.-Naples, Italy 2 Colorectal Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione Giovanni Pascale” – I.R.C.C.S.-Naples, Italy 3 Radiotherapy, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione Giovanni Pascale” – I.R.C.C.S.-Naples, Italy 4 Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione Giovanni Pascale” – I.R.C.C.S.-Naples, Italy 5 Trasfusional Service, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione Giovanni Pascale” – I.R.C.C.S.-Naples, Italy 6 Department of Advanced Biomedical Sciences, Federico II University School of Medicine, and Istituto di Biostrutture e Bioimmagini – C.N.R., Naples, Italy Correspondence to: Stefania Scala, e-mail: scalaste@gmail.it ; s.scala@istitutotumori.na.it Keywords: MDSC, Treg, radiotherapy, rectal cancer Received: November 03, 2014 Accepted: December 31, 2014 Published: January 21, 2015 ABSTRACT Short-course preoperative radiotherapy (SC-RT) followed by total mesorectal excision (TME) is one therapeutic option for locally advanced rectal cancer (LARC) patients. Since radio-induced DNA damage may affect tumor immunogenicity, Myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs) were evaluated in 13 patients undergoing SC-RT and TME for LARC. Peripheral Granulocytic-MDSCs (G-MDSC) [LIN − /HLA-DR − /CD11b + /CD14 − /CD15 + /CD33 + ], Monocytic (M-MDSC) [CD14 + /HLA-DR −/low CD11b + /CD33 + ] and Tregs [CD4 + /CD25 hi+ /FOXP3 + - CTLA-4/PD1] basal value was significantly higher in LARC patients compared to healthy donors (HD). Peripheral MDSC and Tregs were evaluated at time 0 (T0), after 2 and 5 weeks (T2-T5) from radiotherapy; before surgery (T8) and 6–12 months after surgery (T9, T10). G-MDSC decreased at T5 and further at T8 while M-MDSC cells decreased at T5; Tregs reached the lowest value at T5. LARC poor responder patients displayed a major decrease in M-MDSC after SC-RT and an increase of Treg-PD-1. In this pilot study MDSCs and Tregs decrease during the SC-RT treatment could represent a biomarker of response in LARC patients. Further studies are needed to confirm that the deepest M-MDSC reduction and increase in Treg-PD1 cells within 5–8 weeks from the beginning of treatment could discriminate LARC patients poor responding to SC-RT.

Introduction Low rectal cancers requiring abdominoperineal resection tend to have a worse prognosis than higher tumours, which may be treated by anterior resection. One of the reasons for this may be inadequate local surgery, in particular the narrow waist of the resection specimen of a standard abdominoperineal resection may be associated with a high positive circumferential resection margin. The extralevator abdominoperineal excision (ELAPE) aims to improve the R0 resection rate but carries significant morbidity. We examined our own results of standard abdominoperineal resection to assess the need for a change of policy. Methods We operformed a retrospective analysis of consecutive standard abdominoperineal resections for rectal cancer in a single centre from June 2002 to December 2011. Results A total of 102 patients underwent standard abdominoperineal resection with curative intent; 19 had no preoperative treatment, 42 had short course radiotherapy, 9 had long course radiotherapy and 32 had neoadjuvant chemotherapy followed by long course chemoradiotherapy. In 17/102(16.6%), there was a positive circumferential resection margin. Over a median follow up of 32 months, 20 patients developed recurrence of any type. Local recurrence occurred in five patients (two of which also had distant recurrence), of whom two had a positive circumferential resection margin (P = 0.10). Actuarial two-year local only recurrence was 3.4% and any recurrence was 17.7%. Overall five-year cancer specific survival was 77%. Conclusions In this series we found low rates of local recurrence after standard abdominoperineal resection even with a circumferential margin rate positivity of 16.6%.Performing an ELAPE in selected cases may improve these results further but is not necessarily required for all patients.

Aims Pre-operative radiotherapy has proven to reduce local recurrences after curative surgery for rectal cancer. Radiotherapy is generally well tolerated, although postoperative morbidity and mortality was increased in some patients. Current study was undertaken to analyse whether the interval between preoperative radiotherapy and surgery influences post-operative mortality and recurrence for two cohorts. Methods All Dutch patients included in the total mesorectal excision (TME)-trial receiving radiotherapy for resectable rectal cancer were included in this study ( n = 642). The verification set consisted of all patients receiving short-course radiotherapy for resectable rectal cancer in two radiotherapy clinics in The Netherlands ( n = 600). Univariate and multivariable survival analyses for overall survival, disease-free survival, local recurrence-free survival and non-cancer related survival were calculated. Results Patients aged 75 years and older treated during the TME-trial showed a worse overall and non-cancer-related survival when surgically treated 4–7 days after the last fraction of radiotherapy. No differences in survival between the interval groups were found in the verification set. Conclusion Present study found that elderly patients aged 75 years and older operated 4–7 days after the last fraction of radiotherapy had a higher chance of dying due to non-cancer-related causes during the TME-trial as compared to patients with an interval of 0–3 days. In the verification set similar differences could not be confirmed, which could be due to awareness of the clinicians who avoided delayed surgery after radiotherapy since the results have been presented during congresses. A longer than recommended interval between radiotherapy and surgery should be avoided. Besides, the verification set suggests that radiotherapy duration of 7 days is acceptable.

Purpose To evaluate long-term quality-of-life (QoL) after neoadjuvant short-course radiotherapy (SC-RT) and long-course radiochemotherapy (LC-RCHT) for locally advanced rectal cancer. Methods Between 1999 and 2008, 225 patients were treated with curative intent for locally advanced rectal cancer using neoadjuvant SC-RT ( n =108) or LC-RCHT ( n =117). SC-RT delivered 10×2.9Gy twice daily with immediate surgery. LC-RCHT delivered 28×1.8Gy concomitant with 5-FU based chemotherapy and delayed surgery. A cross-sectional QoL analysis was performed in disease-free patients using the EORTC-QLQ-C30 and EORTC-QLQ-CR29 questionnaires. Results After a median follow-up of 67months, 133 patients were disease-free of which 120 (90%) returned the QoL questionnaires. Patients in the LC-RCHT cohort had a higher rate of uT4, uN+ and low tumor location. No difference in QoL was observed between SC-RT and LC-RCHT except an improved physical functioning in the LC-RCHT group ( p =0.04). Comparing our total patient cohort with the general German population showed no difference in global health status but decreased QoL in several functional and bowel symptom scores. Conclusions The finding of comparable long-term QoL after SC-RT and LC-RCHT adds to our knowledge of equivalent oncological outcome and may be useful in the decision making process between the two neoadjuvant approaches.