Neoadjuvant Short Course Research Articles

Early outcomes of pre-operative short course radiotherapy with simultaneous integrated boost and response-adapted chemotherapy for advanced rectal cancer

Background and purposeLimited evidence exists for dose escalation in neoadjuvant short course radiotherapy (SCRT) for rectal cancer. With enhanced imaging and radiotherapy techniques over the past decades along with the valuable endpoint of pathological complete response (pCR), we believe SCRT with simultaneous integrated boost could potentially provide deeper pathological responses and improve local control. Methods and MaterialsBetween Jan-2020 to Dec 2022, Locoregional advanced rectal cancer patients that were treated with neoadjuvant SCRT with SIB up to 5.5-6Gy per fraction with 5 daily fractions followed by response adapted chemotherapy was retrospectively reviewed. pCR rates, R0 resection rates, tumour down staging, toxicities and early pattern of recurrence are reported. ResultsAmong the 76 patients, 67 (88%) were able to undergo curative intent surgery. R0 resection was achieved in 99% (n = 66) of patients with pCR rates of 28% (n = 19). 46% (n = 31) of patients had significant pathological down staging (ypT2N0) and 55% (n = 37) of patients had both T and N down staging. Most common grade 3 or above radiotherapy related side effects were proctitis, rectal pain and dermatitis found in 5% (n = 4), 3% (n = 2) and 3% (n = 2) of patients respectively. Grade 3 or above surgical complications were observed in 15% (n = 10) of patients. There was no treatment related deaths. With a median follow up of 27 months, only 6% (n = 4) had local recurrence after surgery. ConclusionNeoadjuvant short course radiotherapy with simultaneous boost for rectal cancer is feasible with no added toxicities. Patients who underwent surgery achieve a high R0 resection and pCR rates. Early data suggests low rates of locoregional recurrence. Further follow up and research is needed to validate and optimize the dose, method, and schedule of dose escalation.

47 A Single Institution Retrospective Study of Pelvic Insufficiency Fractures Following Neoadjuvant Short Course Intensity-Modulated Radiation Therapy for Rectal Cancer

47 A Single Institution Retrospective Study of Pelvic Insufficiency Fractures Following Neoadjuvant Short Course Intensity-Modulated Radiation Therapy for Rectal Cancer

Evaluation of the efficacy and toxicity of neo-adjuvant short course radiation therapy concurrently with continuous infusion 5-fluorouracil in the management of locally advanced rectal cancer patients.

Evaluation of the efficacy and toxicity of neo-adjuvant short course radiation therapy concurrently with continuous infusion 5-fluorouracil in the management of locally advanced rectal cancer patients.

Quality-of-life outcomes after total neoadjuvant short course radiotherapy, chemo-immunotherapy, and total mesorectal excision for locally advanced rectal cancer.

63 Background: A growing body of evidence supports total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC), however the optimal regimen is yet to be determined and little is known on the quality-of-life (QOL) implications of these therapies. We report QOL data from the Averectal study, which assessed the efficacy and safety of neoadjuvant short course radiotherapy (SCR) plus chemo-immunotherapy for patients with LARC. Methods: Between July 2018 and October 2020, patients enrolled in the Averectal study were invited to fill the Functional Assessment of Cancer Therapy for colorectal cancer (FACT-C) throughout their treatment. We analyzed results at baseline (T0), at completion of SCR and chemo-immunotherapy (T1), and at last-follow up after total mesorectal excision (TME) (T2). Paired sample t-test was used to compare mean scores for individual patients. Results: 39 patients completed the FACT-C form at the specified points. Median follow-up duration was 25.7 months. Median age was 58 years (range 31-74 years), 25 (64.1%) were males, 1 (3.1%) had stage II disease and the rest (96.9%) had stage III. All patients received SCR then 6 cycles of mFOLFOX-6 plus avelumab followed by TME. The mean score differences of the FACT-C subscales at different time-points are summarized. At the end of TNT, the social (SWB), emotional (EWB), functional well-being (FWB) and colorectal cancer subscale (CCS) scores improved compared to baseline (not significant) but physical well-being score (PWB) worsened (21.05 vs 22.94 p=0.025). After TME, all scores except EWB and FWB improved compared to T1, and all scores improved compared to baseline. The CCS, which assesses colorectal cancer specific concerns, significantly improved between T0 and T2 (19 vs 21.06, p=0.003). Overall, trial outcome index (TOI), reflecting functional status, improved after TME compared to baseline. Conclusions: Adopting neoadjuvant chemo-immuno-radiotherapy followed by TME for LARC does not result in QOL deterioration compared to baseline, and can improve colorectal cancer specific concerns. Clinical trial information: NCT03503630 . [Table: see text]

Tissue assessment of therapeutic responses to neoadjuvant short course radiotherapy with and without anti-CD40 immunotherapy sotigalimab (sotiga) in rectal cancer.

191 Background: There has been tremendous progress in the management of rectal cancer in the neoadjuvant setting and in non-operative management (NOM). However, there is a critical need to personalize systemic therapy and radiotherapy to achieve responses conducive for NOM. This study was initiated to profile immune changes to therapy in serial tumor tissue, blood, and stool from the INNATE trial (NCT04130854). Methods: INNATE, is a multi-institutional Phase II randomized trial for patients with Stage III or high-risk Stage II rectal cancer. Patients were randomized 3:2 to receive daily short course radiotherapy (SCRT- 5 Gy x 5) and 6 cycles of FOLFOX +/- 6 infusions of sotiga, an anti-CD40 agonist, followed by surgery. The primary end point is the pathologic complete response rate and additional clinical endpoints are being assessed. Biopsies of tumor and adjacent tissue before and 2 weeks after SCRT +/- sotiga prior to chemotherapy were obtained from consenting patients. Fresh tissue was digested into single cell suspension for scRNAseq with proteomic and immune repertoire analysis. Fixed tissue was processed for histology and multiplexed immunofluorescence. Here, we report integrated and batch effect removed data from 9 patients pre- and post-therapy and analyzed patients as their own control. Results: A total of 25 of 30 patients were enrolled at UTSW, 21 of whom underwent pre- and post-SCRT biopsies. The study population was diverse: 11 patients (37%) were Hispanic and 15 (50%) uninsured receiving care at the Dallas County hospital, Parkland. The median age was 55 (27-75) years and 13 (43.3%) were diagnosed prior to age 50. From integrated scRNAseq, we observed a significant induction of genes associated with M1- and M2-like macrophages, and dendritic cell antigen presentation in the SCRT alone group. This was accompanied by a robust Th1 and B cell response, but not T cell mediated cytotoxicity. In the SCRT + sotiga group there was a greater induction of genes associated with M1-like macrophages and dendritic cell antigen presentation, with no change in M2 genes. In lymphocytes, sotiga treatment led to an induction of genes related to Th1 and B cell response. Unlike SCRT, the combination therapy group had evidence of induced T cell mediated cytotoxicity. To better understand individual responses to therapy, we analyzed pre- and post-treatment samples for each patient. This enabled identification of features associated with poor and robust response in each treatment group. Conclusions: On treatment biopsies during neoadjuvant therapy for rectal cancer enables deep assessment of therapeutic response, provides insight into action of investigational agents, and may identify therapy specific predictive biomarkers. Our data shows that SCRT can induce immune responses and adaptive immune responses can be further induced by sotiga.

Comparison of Overall Response to Neoadjuvant Short Course Radiotherapy Followed by Consolidation Chemotherapy with Long Course Chemoradiotherapy in Locally Advanced Rectal Cancer

<h3>Purpose/Objective(s)</h3> Primary objective of this study was to compare the clinical and radiological response rates between patients receiving pre-operative Short Course Radiotherapy (SCRT) followed by chemotherapy versus conventional long course CRT in patients with locally advanced rectal cancer. secondary objectives included comparison of rates of pCR and acute toxicities among the 2 groups of patients. <h3>Materials/Methods</h3> 33 patients with locally advanced rectal cancer were randomized to standard long course CTRT arm (arm A) and SCRT followed by sequential chemotherapy (arm B) arm (17 and 16 patients respectively). Patients in arm A received long course RT at dose 45 Gy in 25 fractions over 5 weeks with concurrent oral capecitabine on days of radiotherapy. Patients in arm B was prescribed short course radiotherapy at dose 25 Gy in 5 fractions over 1 week. 3 cycles of 3 weekly CAPOX chemotherapy was followed. Patients were planned with 3DCRT technique in Versa HD with 6 MV and 15 MV photons. Clinical response assessment was done by comparing the 2 arms in terms of per rectal examination findings before starting radiotherapy and after completion of RT, right before surgery. The parameters used for assessment were palpability of lesion, tone, mobility, distance from anal verge and location of the lesion. Radiological response assessment was done by comparing 5-point tumor regression grades (TRG) post treatment in the 2 treatment arms. <h3>Results</h3> Radiological tumor regression showed statistically non-significant trend favoring the experimental arm (rates of complete tumor regression 35.7% in SCRT followed by chemotherapy arm versus 23.1% in long course CTRT arm, higher percent of patients with greater tumor regression in SCRT+CT arm). pathological tumor regression also favored experimental arm without showing statistical significance (pCR rates 20% in long course CTRT versus 30% in SCRT+CT). Most of patients in the interventional arm presented with higher pathological tumor regression (TRG 0 and TRG 1) while the most common TRG in the long-course CTRT arm was TRG 3. Higher rate of acute grade 3 bowel toxicities was seen in the interventional arm. Grade 3 acute skin toxicity occurred in the standard arm compared no skin toxicity in the interventional arm. This difference was also not statistically significant. <h3>Conclusion</h3> Short course radiotherapy followed by 3 cycles of CAPOX chemotherapy is comparable to Long-course CTRT in terms of tumor regression. In resource limited setting, short course radiotherapy and chemotherapy is favored due to smaller radiotherapy duration and lesser chances of treatment interruption

Toxicity and feasibility of total neoadjuvant therapy using short course radiation followed by chemotherapy

Introduction:Upfront neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy remained a standard of care for locally advanced rectal cancers. However this strategy is associated with high rates of distant failure. Total neoadjuvant therapy with short course radiation therapy (SCRT) followed by full course of chemotherapy is investigated to assess toxicity&amp;feasibility. Patients and methods: Fifty-one patients with locally advanced rectal cancer who presented to the National Cancer Institute (NCI), Cairo University, in the period from March 2018 to December 2020 were enrolled. Patients were assigned to neoadjuvant short course radiation therapy (25 Gy/ 5 fractions/1 week), then 2 weeks from the end of radiation they were commenced to full course chemotherapy CAPOX (capecitabine1000 mg/m2 BID, D1-14 and oxaliplatin 130 mg/m2 D1) for 6 cycles, followed by surgery within 4-6 weeks from the last chemotherapy cycle. Type of surgery was decided upon surgeon’s discretion. Results: All patients completed their planned radiation therapy. Only 1 patient had grade III radiation related diarrhea. Forty three patients completed their planned chemotherapy course, 8 patients had grade III diarrhea. As regard hematological toxicity, 6 patients developed grade 3 toxicity and only one patient developed grade 4 toxicity.

Neoadjuvant Short-Course Radiotherapy Followed by Consolidation Chemotherapy before Surgery for Treating Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis.

Neoadjuvant short course radiotherapy (SCRT) followed by consolidation chemotherapy (CCT) is an alternative treatment for locally advanced rectal cancer (LARC). We performed this systematic review and meta-analysis to explore the tumor response and oncological outcomes of this new approach compared to conventional chemoradiotherapy (CRT). An online search of the PubMed, Embase, and Cochrane Library databases was performed. This review included 7507 patients from 14 different cohorts. The pCR rate was higher with SCRT + CCT than that with CRT (RR: 1.60; 95% CI: 1.35–1.91; p < 0.01). SCRT + CCT provided a higher ypN0 response (RR: 1.06; 95% CI: 1.01–1.12; p = 0.02). There were no differences in R0 resection and positive CRM rates; however, more sphincter-preservation surgeries were performed in the SCRT + CCT arm (RR: 1.06; 95% CI: 1.01–1.11; p = 0.02). There was no difference in the OS and DFS between the SCRT + CCT and the CRT arms (OS: HR: 0.85, p = 0.07; DFS: HR: 0.88, p = 0.08). The compliance and toxicity were comparable between the SCRT and CRT groups. In the subgroup analysis, patients who underwent four or more cycles of CCT had better pCR and DFS events. Therefore, SCRT followed by consolidation chemotherapy might be an effective alternative treatment for LARC.

Liver First Approach for Synchronous Colorectal Liver Metastasis: Is First Approach the Best Approach?

Introduction: Liver first approach (LFA) for synchronous colorectal liver metastasis (CRLM) is an upcoming strategy for improving survival among patients with stage IV colorectal carcinoma. We share our experience of managing such patients using the LFA and their treatment outcome. Methods: We retrospectively studied 1038 patients who presented with synchronous CRLM over a 10 year period. The clinical history, management strategy and outcomes of patients undergoing the LFA were analysed in detail. Results: We formulated an algorithm for management of patients presenting with synchronous CRLM (picture). Out of 1038 such patients, 31 were selected for the LFA. 29 recto-sigmoid, one caecal and one descending colon carcinoma were part of the LFA group. All of them underwent neo-adjuvant short course radiotherapy with systemic chemotherapy and proceeded to have liver resection. Following this, 11 patients had disease progression and only 20 (64.5%) proceeded to have their primary tumor resected. The peri-operative characteristics and outcomes of patients who completed the LFA are listed in the table below. Among the patients who completed the LFA, the recurrence rate was 70% (n=14) and the median time to recurrence was 418.5 days (IQR 407). The 1-year, 3-year and 5-year survival rates for the LFA were 90%, 85% and 65% respectively, with a median survival of 1112.5 days (IQR 1025) which is similar to the conventional methods. Conclusions: LFA for synchronous CRLM better serves patients when appropriately selected and combined with a multi-modality approach especially in patients with a large disease burden in the liver.Tabled 1Demographics Mean age60.77 years Male : Female ratio13 : 7Tumor characteristics Primary locationRectum 19, Caecum 1 Average number of liver metastasis3.85 Average size of largest metastasis49.8 mm Bilobar liver metastasis11 (55%)Hepatic resection Right hepatectomy5 Right hepatectomy with non-anatomical resections3 Non-anatomical resection3 Extended left hepatectomy3 Extended right hepatectomy1 Left lateral sectionectomy2 Left hepatectomy with right posterior sectionectomy1 Central hepatectomy2Post hepatic resection Major morbidity (Clavien Dindo ≥3b)1 (5%) Mortality0 R1 margin5 (25%)Colorectal resection Anterior resection15 Abdomino-perineal resection4 Right hemicolectomy1Post colorectal resection Major morbidity (Clavien Dindo ≥3b)3 (15%) Mortality2 (10%) Open table in a new tab

119TiP Dual-immunotherapy and short-course medium-dose radiotherapy, followed by surgery for tumor microenvironment modification in early stage NSCLC: The DIRECT-trial

For fit patients with resectable NSCLC, surgery +/- adjuvant chemotherapy is standard of care. Despite this curative intent approach, rates of distant metastases are still substantial. To improve disease control, neoadjuvant administration of immune checkpoint inhibitors appears promising. Combining immune checkpoint inhibitors (anti PD-L1 and anti-CTLA-4) with chemotherapy and/or radiotherapy (RT) appears to further improve clinical efficacy, without unacceptable excess in toxicity. We hypothesize that neoadjuvant short course dual immunotherapy and medium dose RT improves both local and systemic disease control in resectable NSCLC with acceptable toxicity.

Survival Outcomes of Patients With Borderline Resectable and Resectable Pancreatic Adenocarcinoma Treated With Neoadjuvant Short-Course Chemoradiotherapy With Capecitabine-Based vs. Gemcitabine-Based Concurrent Chemotherapy

Neoadjuvant chemoradiotherapy is a critical treatment for borderline resectable and resectable pancreatic adenocarcinoma ((B)RPC). The PREOPANC trials employ a short course chemoradiation (SCCRT) regimen of 3600 cGy in 15 fractions with concurrent gemcitabine (GEM)-based chemotherapy, but little is known about the relative efficacy of capecitabine (CAPE)-based concurrent chemotherapy in this population. We hypothesize that patients treated with SCCRT with CAPE-based concurrent chemotherapy will have superior overall survival (OS) compared to GEM-based strategies.Medical records were retrospectively reviewed at a single center for patients diagnosed with (B)RPC between 1/2005 and 12/2020. Patients treated with neoadjuvant SCCRT were included in the analysis. Descriptive statistics were quantified for baseline characteristics. OS was estimated using Kaplan-Meier estimates, statistical difference was determined using the log-rank test. Multivariate Cox proportional hazards analysis was conducted to estimate hazard ratios (HR) when controlling for confounding factors.Thirty-one (n = 31) patients were included in the analysis. 71% of patients (n = 22) were treated with CAPE-based concurrent chemotherapy, while 29% of patients (n = 9) were treated with GEM-based concurrent chemotherapy. Median age at diagnosis was 65 (interquartile range (IQR): 60 to 71) for the CAPE group, compared to 66 (IQR: 63 to 71) for the GEM group, P = 0.414. 100% of patients in the CAPE group were borderline resectable, compared to 82% of patients in the GEM group, P = 0.171. 44% of patients in the CAPE group were treated with neoadjuvant FOLFIRINOX, compared to 14% in the GEM group, P = 0.016. Patients treated with concurrent 5-CAPE-based chemotherapy had a longer median OS than other concurrent chemotherapy approaches: Not reached (95% confidence interval (CI): 24 to not reached) vs. 17 months (95% CI: 6 to 22 months), P < 0.0001. Multivariate Cox proportional hazards models, controlling for borderline vs. resectable status, age at diagnosis, and use of neoadjuvant FOLFIRINOX, demonstrated that CAPE-based concurrent chemotherapy had a HR of death of 0.081 (95% CI: 0.018 to 0.369, P = 0.0012) compared to GEM-based concurrent chemotherapy.Patients diagnosed with (B)RPC have many therapeutic options; this study suggests a benefit to CAPE-based concurrent chemotherapy when treating patients with SCCRT, even after controlling for significant confounding by greater use of neoadjuvant FOLFIRINOX with CAPE-based concurrent chemotherapy. SCCRT may be more effective with concurrent capecitabine instead of concurrent gemcitabine for (B)RPC.

Management of the adenocarcinoma of the upper rectum: a reappraisal.

The present review attempts to assess whether upper rectal cancer (URC) should be treated either as colon cancer or as rectal one, namely to be managed with upfront surgery without neo-adjuvant treatment and partial mesorectal excision (PME), or with neo-adjuvant short course radiotherapy (SCRT) or chemoradiotherapy (CRT) as indicated, followed by surgery with total mesorectal excision. Reports from current evidence including studies, reviews and various guidelines are conflicting. Main reasons for inability to reach safe conclusions are (i) the various anatomical definitions of the rectum and its upper part, (ii) the inadequate preoperative local staging,(iii) the heterogeneity of selection criteria for the neo-adjuvant treatment,(iv) the different neo-adjuvant treatment regimens, and(v) the variety in the extent of surgical resection, among the studies. Although not adequately supported, locally advanced URC can be treated with neo-adjuvant CRT provided the lesion is within the radiation field of safety, and a PME if the lower border of the tumour is located above the anterior peritoneal reflection. There is evidence that adjuvant chemotherapy is of benefit in high-risk stage II and stage III lesions.

Neoadjuvant Short Course Radiation Therapy (SCRT) Followed By Chemotherapy And Delayed Surgery In Locally Advanced Rectal Adenocarcinoma: Initial Trends And Outcomes From Asian Population Cohort

Neoadjuvant short course RT (scRT) and chemotherapy followed by delayed surgery and adjuvant completion chemotherapy have been hypothesized to increase the pathological complete response (pCR), decrease distant failures and improve survival in locally advanced rectal cancer patients. Patients who have undergone scRT from November 2018 till July 2019 have been included in an intention to treat analysis. They received 25Gy/5fractions/5 days followed by FOLFOX based chemotherapy for 4-6 cycles followed by surgery and completion chemotherapy. Radio-biological evaluation was done by PET MRI at baseline and after completion of 4 cycles of chemotherapy. Inclusion criteria was locally advanced T3/T4, N0/N+ lesions including synchronous liver only metastasis patients. The primary endpoint is complete pathological response (cPR). Secondary endpoints are survival analysis, toxicity evaluation, additional radiological/ biological response grading and analysis. 65 patients were enrolled of whom 50 completed scRT.T3 disease was 86% (43/50) and T4, 14% (7/50). All except 3 (94%) had node positive on MRI.20% (10/50) had liver only metastatic disease and 80% (40/50) had locoregional disease. Local radical surgery was done in 52% (26/50) patients: 3/10 in the metastatic group after hepatic resection and 23/40 in non-metastatic group. In the metastatic cohort: 5 patients had progressive disease (PD) and 2 were lost to follow up (LFU). In non-metastatic cohort: 5 patients refused for surgery, 6 patients were LFU and 6 had PD. Surgery was done in 26 patients: 12/26 had ELAPE, 3/26 had APR, 9/26 had LAR and 2/16 had total proctocolectomy. All achieved negative resection margins. AJCC pathological tumor regression grade (pTRG) was assessed: 9/26(34.6%) had pTRG 0 (Complete response), 10/26(38.4%) patients had pTRG 1 (Moderate/significant response), 7/26(27%) had pTRG 2 (Minimal response), 0/26 (0%) had pTRG3 (Poor response). 8 patients had pathological node positivity. in which 62.5% (5/8) had a minimal response (TRG2), 25% (2/8) had pTRG1 and 12.5% (1/8) patient had pTRG0.PNI positivity in surgical specimen seen in 2/16 patients who had liver only metastasis and had minimal response (TRG2). GI toxicity was assessed in terms of diarrhea, pain abdomen, need for admission. Grade 2/3 neutropenia was seen in 49% of patients during chemotherapy. MRTRG& ADC value change in MRI and biological SUV change in PET were statistically analyzed in pretreatment and post neoadjuvant RT + chemotherapy scans. All parameters were correlated with pTRG and pathological T staging but none had a direct significant correlation (p<0.05) In our study, scRT followed by adjuvant chemotherapy and a delayed surgery, achieved high complete and near complete pathological response rates (73%). Such regimen looks promising and has the potential to change management paradigm in near future. Post-surgical complication rates, survival analysis and other late effects are awaited.

Outcomes of rectal cancer patients treated using Polish II neoadjuvant short course radiation therapy and chemotherapy approach in comprehensive cancer center.

e16088 Background: Neoadjuvant short-course (SC) radiation (RT) followed by fluoropyrimidine based chemotherapy prior to surgery (Polish II approach) is a less utilized treatment in the United States for rectal cancer. Based on data suggesting equivalent or improved outcomes at lower cost compared to the long course neoadjuvant chemoradiation, our team started utilizing this approach for rectal cancer management at Simmons Comprehensive Cancer Center. We aim to document our experience with Polish II approach at NCI-designated comprehensive cancer center program. Methods: A retrospective review of stage I-IV rectal cancer patients, seen at an academic center or the Dallas County safety net hospital and treated at Simmons Comprehensive Cancer Center from Nov 2017 to Dec 2019. Patients were treated with neoadjuvant SC-RT followed by 3 cycles of FOLFOX prior to surgery and followed by adjuvant FOLFOX. Descriptive data for demographic, radiation, chemotherapy and surgery, hospitalizations, 30 day post-surgery admission, time to relapse, and laboratory parameters was collected. Results: Thirty-nine patients met the inclusion criteria (average age 58 years; 74% men/26% women). Forty-six percent of patients were Hispanic, 28.2% White, 15.4% African American and 7.7% Asian. The majority of patients had stage IIIB (46.2%), followed by IIIC (17.9%), IIA (12.8%), IIIA (7.7%), while rest were stage I, IVA or unknown (5.1%). All patients received 5 x 5 SC-RT, 100% completed 3 cycles of planned neoadjuvant FOLFOX (12.8% received 4-8 cycles) and 36/39 (92%) of patients underwent planned surgery. Median duration from SC-RT to chemotherapy was 12 days, and from chemotherapy to surgery was 37 days. Hospitalization occurred in 3 patients (7.7%) during neoadjuvant therapy, and in 8 patients (20.5%) within 30 days post-surgery. Complete pathological response was seen in 6 patients (16.6%) and near-complete pathological response in 3 patients (8.3%). Relapse occurred in 10.3% patients at time of data acquisition. Grade 3 and 4 neutropenia, anemia, and thrombocytopenia in neoadjuvant phase was observed in 8.6%, 25.7%, and 2.8% patients, respectively. Conclusions: In rectal cancer patients treated at a comprehensive cancer center, neoadjuvant Polish-II approach was feasible and well tolerated. Pathological response rates were comparable to historical data. SC-RT based neo-adjuvant therapy approach should be favored due to lower pelvic radiation dose, tolerance and convenience to patients.

A phase II study to evaluate safety and efficacy of neoadjuvant pembrolizumab and radiotherapy in localized MSS rectal cancer.

TPS272 Background: Locally advanced rectal cancer remains a clinical challenge with few improvements noted over the past few decades. Although immunotherapy has no current clinical role in microsatellite stable (MSS) colorectal cancer, preclinical models suggest that radiotherapy (RT) can enhance neoantigen presentation, modulate the microenvironment, and improve the likelihood of anti-tumor activity with checkpoint inhibitors use. This prospective phase II trial will test that hypothesis in addition to confirming safety of this approach using a “window-of-opportunity” study design with the anti-PD-1 agent Pembrolizumab. Methods: This monocentric phase II trial, will enroll patients (pts) with rectal cancer who are undergoing neoadjuvant short course RT (scRT) (25 Gy in 5 fractions). according to the standard of care. Eligible includes pts with MSS stage II-III rectal cancer with adequate organ function and availability of pre-treatment tumor, who are undergoing scRT with intention to proceed to surgical resection. Standard ineligibility criteria include active infections, systemic steroid use, or other conditions making immunotherapy use unsafe. Treatment includes 4 doses of Pembrolizumab (200mg IV, once every 3 wks), the first dose being given before the first scRT fraction. Surgery will be performed within 12-16 weeks of the final scRT dose. Primary endpoint is tumor regression grade (TRG) using the Mandard regression grade score targeting a 30% pathological complete response (pCR) compared to 10% in historical controls. Secondary endpoints include OS, DFS, toxicity, local and distant relapse-free survival, negative surgical margins, QoL, quality of surgery and exploratory assessments of tumor infiltrating lymphocytes, profiling of circulating immune cell populations, and molecular predictors of response. A safety stopping rule is planned based on Wald’s sequential probability ratio test for the occurrence of the safety outcome. Enrollment target is 25 pts. Support: MSD. Clinical trial information: NCT04109755 .

Lymph Node Retrieval Following Neoadjuvant Short Course Radiotherapy in Patients with Rectal Cancer

Lymph Node Retrieval Following Neoadjuvant Short Course Radiotherapy in Patients with Rectal Cancer

The impact on health-related quality of life in the first 12 months: A randomised comparison of preoperative short-course radiation versus long-course chemoradiation for T3 rectal cancer (Trans-Tasman Radiation Oncology Group Trial 01.04)

PurposeTo assess health-related quality of life (HRQOL) in patients participating in a randomised trial of neoadjuvant short course radiation (SC) or long course chemoradiation (LC) for operable rectal cancer. Patients and methodsEligible patients with T3N0-2M0 rectal cancer completed the European Organisation for Research and Treatment of Cancer quality of life questionnaire (QLQ-C30) and the colorectal cancer specific module (QLQ C38) at randomisation and 1, 2, 3, 6, 9 and 12 months later. ResultsOf 326 patients randomised, 297 (SC 143, LC 154) were eligible for completion of HRQOL questionnaires. Baseline scores were comparable across the SC and LC groups. Patients reported low scores on sexual functioning and sexual enjoyment. Defaecation problems were the worst of the symptoms at baseline. Surgery had the most profoundly negative effect on HRQOL, seen in both the SC and LC treatment groups to the same extent. The most severely affected domains were physical function and role function and the most severely affected symptoms were fatigue, pain, appetite, weight loss and male sexual problems. Most domains and symptoms returned to baseline levels by 12 months apart from body image, sexual enjoyment and male sexual problems. Future perspective was better than prior to treatment. ConclusionThere is no overall difference in HRQOL between SC and LC neoadjuvant treatment strategies, in the first 12 months, after surgery. In the immediate postoperative period HRQOL was adversely affected in both groups but for the most part was temporary. Some residual sexual functioning concerns persisted at 12 months.

P-338 Non-Operative Treatment after Neo-Adjuvant Short Course Radiotherapy (The Tlalpan Regime) in a combined modality for Locally Advanced Rectal Cancer with risk factors at the Instituto Nacional de Cancerología (México)

P-338 Non-Operative Treatment after Neo-Adjuvant Short Course Radiotherapy (The Tlalpan Regime) in a combined modality for Locally Advanced Rectal Cancer with risk factors at the Instituto Nacional de Cancerología (México)

P-0286 - Neo-Adjuvant Short Course Radiotherapy (The Tlalpan Regime) in a Combined Modality Treatment for Locally Advanced Rectal Cancer with Risk Factors at the Instituto Nacional De Cancerología (México)

P-0286 - Neo-Adjuvant Short Course Radiotherapy (The Tlalpan Regime) in a Combined Modality Treatment for Locally Advanced Rectal Cancer with Risk Factors at the Instituto Nacional De Cancerología (México)

Phase I study of neoadjuvant accelerated short course radiation therapy with photons and capecitabine for resectable pancreatic cancer

PurposeIn this phase I study, we sought to determine the feasibility and tolerability of neoadjuvant short course radiotherapy (SC-CRT) delivered with photon RT with concurrent capecitabine for resectable pancreatic adenocarcinoma. Materials and methodsTen patients with localized, resectable pancreatic adenocarcinoma were enrolled from December 2009 to August 2011. In dose level I, patients received 3Gy×10. In dose level 2, patients received 5Gy×5 (every other day). In dose level 3, patients received 5Gy×5 (consecutive days). Capecitabine was given during weeks 1 and 2. Surgery was performed 1–3weeks after completion of chemotherapy. ResultsWith an intended accrual of 12 patients, the study was closed early due to unexpected intraoperative complications. Compared to the companion phase I proton study, patients treated with photons had increased intraoperative RT fibrosis reported by surgeons (27% vs. 63%). Among those undergoing a Whipple resection, increased RT fibrosis translated to an increased mean OR time of 69min. Dosimetric comparison revealed significantly increased low dose exposure to organs at risk for patients treated with photon RT. ConclusionsThis phase I experience evaluating the tolerability of neoadjuvant SC-CRT with photon RT closed early due to unexpected intraoperative complications.