Radiotherapy For Rectal Cancer Research Articles

Assessing the practice of total neoadjuvant therapy for rectal cancer: an online survey among radiation oncology departments in Germany and German-speaking regions of Austria and Switzerland.

Total neoadjuvant therapy (TNT) of rectal cancer improves rates of pathological complete remission and progression-free survival. With improved clinical response rates, interest grew in a non-operative approach/watch and wait (WaW) for this disease. In 2020, the working groups of ACO/AIO/ARO published a consensus statement on the use of TNT, including a non-operative approach. However, the best combination scheme remains unclear. Despite the increasing use of TNT, there is a lack of comprehensive data on its current implementation and practices. To address this knowledge gap, a multicenter survey was conducted to capture the use of TNT protocols in German-speaking radiotherapy departments. At the beginning of 2023, a GDPR-compliant online survey was conducted in Germany, Austria, and German-speaking Switzerland. The questionnaire comprised 43 questions covering various aspects of TNT, including chemotherapy and WaW concepts. Most respondents (98.4%) confirmed awareness of the consensus on TNT for rectal cancer. Institutions treated an average of 30.22 rectal cancer patients annually. Most respondents (76.2%) reported treating over 80% of patients neoadjuvantly. Regarding TNT, 33.3% treated 21-50% with such a protocol. No significant association was found between the institution type and TNT application. In 62/63 cases, tumor board discussion was standard before offering TNT. VMAT was the predominant technique (82.5%). For rectal cancer dosing, the 50/50.4Gy scheme was most common, followed by 45Gy with a boost and the 5 × 5Gy scheme. Dosing schemes for TNT varied slightly, with more participants reporting the use of 5 × 5Gy compared to radiation therapy for rectal cancer in general. CBCT was the primary IGRT method (88.9%). Larger hospitals typically administered chemotherapy themselves, while private practices collaborated with medical oncologists (p < 0.0001). The most common concurrent chemotherapy drugs were 5-fluorouracil/capecitabine (64.4%) and oxaliplatin (37.3%). A WaW strategy was reported to be institutional implemented by 63.8%. The timing of offering WaW was split, with 50% offering it after radiochemotherapy and 47% during the informed consent talk. For planned WaW, 62% prefer normofractionated TNT. TNT appears to be widely implemented in the German-speaking radio-oncological community, regardless of the type of institution. Image-guided therapy, multidisciplinary team decisions, and internal guidelines play an important role. TNT seems to have already altered treatment protocols for rectal cancer toward an organ-preserving approach in selected cases. In these WaW cases, normofractionation appears to be preferred over hypofractionation.

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.

Clinical evaluation of the convolutional neural network‑based automatic delineation tool in determining the clinical target volume and organs at risk in rectal cancer radiotherapy.

Delineating the clinical target volume (CTV) and organs at risk (OARs) is crucial in rectal cancer radiotherapy. However, the accuracy of manual delineation (MD) is variable and the process is time consuming. Automatic delineation (AD) may be a solution to produce quicker and more accurate contours. In the present study, a convolutional neural network (CNN)-based AD tool was clinically evaluated to analyze its accuracy and efficiency in rectal cancer. CT images were collected from 148 supine patients in whom tumor stage and type of surgery were not differentiated. The rectal cancer contours consisted of CTV and OARs, where the OARs included the bladder, left and right femoral head, left and right kidney, spinal cord and bowel bag. The MD contours reviewed and modified together by a senior radiation oncologist committee were set as the reference values. The Dice similarity coefficient (DSC), Jaccard coefficient (JAC) and Hausdorff distance (HD) were used to evaluate the AD accuracy. The correlation between CT slice number and AD accuracy was analyzed, and the AD accuracy for different contour numbers was compared. The time recorded in the present study included the MD time, AD time for different CT slice and contour numbers and the editing time for AD contours. The Pearson correlation coefficient, paired-sample t-test and unpaired-sample t-test were used for statistical analyses. The results of the present study indicated that the DSC, JAC and HD for CTV using AD were 0.80±0.06, 0.67±0.08 and 6.96±2.45 mm, respectively. Among the OARs, the highest DSC and JAC using AD were found for the right and left kidney, with 0.91±0.06 and 0.93±0.04, and 0.84±0.09 and 0.88±0.07, respectively, and HD was lowest for the spinal cord with 2.26±0.82 mm. The lowest accuracy was found for the bowel bag. The more CT slice numbers, the higher the accuracy of the spinal cord analysis. However, the contour number had no effect on AD accuracy. To obtain qualified contours, the AD time plus editing time was 662.97±195.57 sec, while the MD time was 3294.29±824.70 sec. In conclusion, the results of the present study indicate that AD can significantly improve efficiency and a higher number of CT slices and contours can reduce AD efficiency. The AD tool provides acceptable CTV and OARs for rectal cancer and improves efficiency for delineation.

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

Organ preservation after neoadjuvant long-course chemoradiotherapy versus short-course radiotherapy

Potential differences in organ preservation between total neoadjuvant therapy (TNT) regimens integrating long-course chemoradiotherapy (LCCRT) and short-course radiotherapy (SCRT) in rectal cancer remain undefined. This natural experiment arose from a policy change in response to the COVID-19 pandemic during which our institution switched from uniformly treating patients with LCCRT to mandating that all patients be treated with SCRT. Our study includes 323 locally advanced rectal adenocarcinoma patients treated with LCCRT-based or SCRT-based TNT from January 2018 to January 2021. Patients who achieved clinical complete response were offered organ preservation with watch-and-wait (WW) management. The primary outcome was 2-year organ preservation. Additional outcomes included local regrowth, distant recurrence, disease-free survival (DFS), and overall survival (OS). Patient and tumor characteristics were similar between LCCRT (n= 247) and SCRT (n= 76) cohorts. Median follow-up was 31 months. Similar clinical complete response rates were observed following LCCRT and SCRT (44.5% versus 43.4%). Two-year organ preservation was 40% [95% confidence interval (CI) 34% to 46%] and 31% (95% CI 22% to 44%) among all patients treated with LCCRT and SCRT, respectively. In patients managed with WW, LCCRT resulted in higher 2-year organ preservation (89% LCCRT, 95% CI 83% to 95% versus 70% SCRT, 95% CI 55% to 90%; P= 0.005) and lower 2-year local regrowth (19% LCCRT, 95% CI 11% to 26% versus 36% SCRT, 95% CI 16% to 52%; P= 0.072) compared with SCRT. The 2-year distant recurrence (10% versus 6%), DFS (90% versus 90%), and OS (99% versus 100%) were similar between WW patients treated with LCCRT and SCRT, respectively. While WW eligibility was similar between cohorts, WW patients treated with LCCRT had higher 2-year organ preservation and lower local regrowth than those treated with SCRT, yet similar DFS and OS. These data support induction LCCRT followed by consolidation chemotherapy as the preferred TNT regimen for patients with locally advanced rectal cancer pursuing organ preservation.

888: high rate of organ preservation with Papillon contact x-ray radiotherapy in rectal cancer

888: high rate of organ preservation with Papillon contact x-ray radiotherapy in rectal cancer

1294: A Multi-Omics Database Using Clinical Trial Data for Rectal Cancer Radiotherapy Outcome Prediction

1294: A Multi-Omics Database Using Clinical Trial Data for Rectal Cancer Radiotherapy Outcome Prediction

Arterial Mucosal Linear Enhancement at Contrast-enhanced MRI to Exclude Residual Tumor after Neoadjuvant Chemotherapy and Radiation Therapy for Rectal Cancer.

Background A watch-and-wait regimen for locally advanced rectal cancer after neoadjuvant chemotherapy and radiation therapy (NCRT) relies on identifying complete tumor response. However, the concordance between a complete response at combined T2-weighted and diffusion-weighted MRI (T2DWI) and pathologic complete response (pCR; ie, ypT0N0) in the tumor is unsatisfactory. Purpose To assess whether identification of mucosal linear enhancement (MLE) at arterial-phase contrast-enhanced (CE) T1-weighted MRI is associated with ypT0 status in patients with locally advanced rectal cancer after NCRT and to evaluate whether combining MLE at CE T1-weighted MRI and negative lymph node metastasis (LNM) at T2DWI can improve identification of pCR. Materials and Methods This retrospective study included patients with locally advanced rectal cancer who underwent total mesorectal excision after NCRT between July 2020 and July 2023 at a tertiary referral academic center. Restaging MRI included T2DWI and arterial-phase CE T1-weighted MRI for primary tumor assessment and T2DWI for evaluation of LNM status. Imaging features associated with ypT0 status were identified at multivariable regression analysis. Results In total, 239 patients (mean age, 58 years ± 12 [SD]; 180 male patients) were assessed. MLE was more common in the ypT0 group than in the ypT1-4 group after NCRT (73% vs 4%, respectively; P < .001). MLE was associated with higher odds of ypT0 status in an adjusted analysis (odds ratio, 137; 95% CI: 25, 767; P < .001). The combination of MLE and negative LNM status achieved an area under the receiver operating characteristic curve of 0.84 (95% CI: 0.79, 0.88) for pCR. Conclusion MLE at CE MRI was associated with higher odds of complete tumor response. Combining MLE and negative LNM status showed good performance for identifying complete tumor response and may exclude residual tumors after NCRT in patients with locally advanced rectal cancer. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Schoellnast in this issue.

Dosimetric effect of collimator rotation on intensity modulated radiotherapy and volumetric modulated arc therapy for rectal cancer radiotherapy.

Intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) are the main radiotherapy techniques for treating and managing rectal cancer. Collimator rotation is one of the crucial parameters in radiotherapy planning, and its alteration can cause dosimetric variations. This study assessed the effect of collimator rotation on the dosimetric results of various IMRT and VMAT plans for rectal cancer. Computed tomography (CT) images of 20 male patients with rectal cancer were utilized for IMRT and VMAT treatment planning with various collimator angles. Nine different IMRT techniques (5, 7, and 9 coplanar fields with collimator angles of 0°, 45°, and 90°) and six different VMAT techniques (1 and 2 full coplanar arcs with collimator angles of 0°, 45°, and 90°) were planned for each patient. The dosimetric results of various treatment techniques for target tissue (conformity index [CI] and homogeneity index [HI]) and organs at risk (OARs) sparing (parameters obtained from OARs dose-volume histograms [DVH]) as well as radiobiological findings were analyzed and compared. The 7-fields IMRT technique demonstrated lower bladder doses (V40Gy, V45Gy), unaffected by collimator rotation. The 9-fields IMRT and 2-arcs VMAT (excluding the 90-degree collimator) had the lowest V35Gy and V45Gy. A 90-degree collimator rotation in 2-arcs VMAT significantly increased small bowel and bladder V45Gy, femoral head doses, and HI values. Radiobiologically, the 90-degree rotation had adverse effects on small bowel NTCP (normal tissue complication probability). No superiority was found for a 45-degree collimator rotation over 0 or 30 degrees in VMAT techniques. Collimator rotation had minimal impact on dosimetric parameters in IMRT planning but is significant in VMAT techniques. A 90-degree rotation in VMAT, particularly in a 2-full arc technique, adversely affects PTV homogeneity index, bladder dose, and small bowel NTCP. Other evaluated collimator angles did not significantly affect VMAT dosimetrical or radiobiological outcomes.

Identification and validation of a machine learning model of complete response to radiation in rectal cancer reveals immune infiltrate and TGFβ as key predictors

It is uncertain which biological features underpin the response of rectal cancer (RC) to radiotherapy. No biomarker is currently in clinical use to select patients for treatment modifications. We identified two cohorts of patients (total N=249) with RC treated with neoadjuvant radiotherapy (45Gy/25) plus fluoropyrimidine. This discovery set included 57 cases with pathological complete response (pCR) to chemoradiotherapy (23%). Pre-treatment cancer biopsies were assessed using transcriptome-wide mRNA expression and targeted DNA sequencing for copy number and driver mutations. Biological candidate and machine learning (ML) approaches were used to identify predictors of pCR to radiotherapy independent of tumour stage. Findings were assessed in 107 cases from an independent validation set (GSE87211). Three gene expression sets showed significant independent associations with pCR: Fibroblast-TGFβ Response Signature (F-TBRS) with radioresistance; and cytotoxic lymphocyte (CL) expression signature and consensus molecular subtype CMS1 with radiosensitivity. These associations were replicated in the validation cohort. In parallel, a gradient boosting machine model comprising the expression of 33 genes generated in the discovery cohort showed high performance in GSE87211 with 90% sensitivity, 86% specificity. Biological and ML signatures indicated similar mechanisms underlying radiation response, and showed better AUC and p-values than published transcriptomic signatures of radiation response in RC. RCs responding completely to chemoradiotherapy (CRT) have biological characteristics of immune response and absence of immune inhibitory TGFβ signalling. These tumours may be identified with a potential biomarker based on a 33 gene expression signature. This could help select patients likely to respond to treatment with a primary radiotherapy approach as for anal cancer. Conversely, those with predicted radioresistance may be candidates for clinical trials evaluating addition of immune-oncology agents and stromal TGFβ signalling inhibition. The Stratification in Colorectal Cancer Consortium (S:CORT) was funded by the Medical Research Council and Cancer Research UK (MR/M016587/1).

Bone turnover biomarkers reflect radiation-induced bone injuries in women with non-metastatic rectal cancer.

Preoperative radiotherapy (RT) for non-metastatic rectal cancer reduces local recurrence rates but can cause pelvic insufficiency fractures. Despite the high morbidity from RT-induced skeletal injuries, predictive and preventive measures are lacking. How these injuries are reflected by bone biomarkers are largely unknown. The aim was to assess longitudinal changes in bone biomarkers and their relation to RT-related bone injuries in women with rectal cancer. This longitudinal cohort study includes 47 women with non-metastatic rectal cancer treated with surgery ± preoperative RT with or without chemotherapy. Sclerostin, bioactive sclerostin, C-terminal telopeptide cross-links of collagen type I (CTX), bone-specific alkaline phosphatase (BALP), and type I procollagen intact N-terminal propeptide (PINP) were measured at baseline, after RT, and 1 yr postoperatively. Pelvic magnetic resonance imaging was used for detection of skeletal injury. Sixteen of 36 (44%) irradiated women had radiation-induced bone injuries and were compared to 11 women (RT-) and 20 women (RT+) without bone injuries. Serum CTX, BALP, and PINP increased during the first year after RT in women with radiation-induced bone injuries. The difference in mean change of CTX (p=.037) and BALP (p=.042) was conferred by longitudinal regression analyses adjusted for serum estradiol. Serum sclerostin and bioactive sclerostin remained stable over time. Taken together, bone markers may be of interest for future research on fracture prediction or preventive measures in women susceptible to radiation-induced bone injury. Due to few measure points, the full pattern cannot be captured regarding the relation over time between bone biomarkers and skeletal injury from irradiation.

Measurement of the distance between tumor micro-foci and gross tumor in rectal cancer pathological specimens: implication on margin distance of clinical target volume treated with high-dose radiotherapy for rectal cancer.

To measure the micro-foci distance away from gross tumor and to provide reference to create the clinical target volume (CTV) margin for boost radiotherapy in rectal adenocarcinoma. Twenty-eight rectal cancer surgical specimens of only total mesorectal excision were collected. The pathological specimens were retrospectively measured, and the nearest distance between the tumor micro-foci and gross tumor was microscopically measured. The "in vivo-in vitro" retraction factor was calculated as the ratio of the deepest thickness laterally and the vertical height superior/inferiorly of the rectal tumor measured in MRI and those measured in immediate pathological specimens. The retraction factor during pathological specimen processing was calculated as the distance ratio before and after dehydration in the lateral, superior, and inferior sides by the "knot marking method." The distances of tumor micro-foci were individually corrected with these two retraction factors. The mean "in vivo-in vitro" tumor retraction factors were 0.913 peripherally and 0.920 superior/inferiorly. The mean tumor specimen processing retraction factors were 0.804 peripherally, 0.815 inferiorly, and 0.789 superiorly. Of 28 patients, 14 cases (50.0%) had 24 lateral micro-foci, 8 cases (28.6%) had 13 inferior micro-foci, and 7 cases (25.0%) had 19 superior micro-foci. The 95th percentiles of the micro-foci distance for 28 patients were 6.44mm (peripheral), 5.54mm (inferior), and 5.42mm (superior) after retraction correction. The micro-foci distances of 95% of rectal adenocarcinoma patients examined were within 6.44mm peripherally, 5.54mm inferiorly, and 5.42mm superiorly. These findings provide reference to set the boost radiotherapy CTV margin for rectal cancer.

Uterine Anastomosis with Low Anterior Resection.

In this surgical teaching video, we demonstrate the technique of robot-assisted uterine anastomosis combined with low anterior resection in a 27-year-old patient with T2 node-positive rectal cancer. The patient had undergone uterine transposition for fertility preservation prior to upfront chemotherapy and radiation therapy for rectal cancer. In this video, we review the key steps of both surgical procedures. We emphasize robot trocar placement and docking, demonstrate optimal organ manipulation and tissue handling, and include key operative modifications and pearls for successful perioperative management.

Localized fine-tuning and clinical evaluation of deep-learning based auto-segmentation (DLAS) model for clinical target volume (CTV) and organs-at-risk (OAR) in rectal cancer radiotherapy

Background and purposeVarious deep learning auto-segmentation (DLAS) models have been proposed, some of which have been commercialized. However, the issue of performance degradation is notable when pretrained models are deployed in the clinic. This study aims to enhance precision of a popular commercial DLAS product in rectal cancer radiotherapy by localized fine-tuning, addressing challenges in practicality and generalizability in real-world clinical settings.Materials and methodsA total of 120 Stage II/III mid-low rectal cancer patients were retrospectively enrolled and divided into three datasets: training (n = 60), external validation (ExVal, n = 30), and generalizability evaluation (GenEva, n = 30) datasets respectively. The patients in the training and ExVal dataset were acquired on the same CT simulator, while those in GenEva were on a different CT simulator. The commercial DLAS software was first localized fine-tuned (LFT) for clinical target volume (CTV) and organs-at-risk (OAR) using the training data, and then validated on ExVal and GenEva respectively. Performance evaluation involved comparing the LFT model with the vendor-provided pretrained model (VPM) against ground truth contours, using metrics like Dice similarity coefficient (DSC), 95th Hausdorff distance (95HD), sensitivity and specificity.ResultsLFT significantly improved CTV delineation accuracy (p < 0.05) with LFT outperforming VPM in target volume, DSC, 95HD and specificity. Both models exhibited adequate accuracy for bladder and femoral heads, and LFT demonstrated significant enhancement in segmenting the more complex small intestine. We did not identify performance degradation when LFT and VPM models were applied in the GenEva dataset.ConclusionsThe necessity and potential benefits of LFT DLAS towards institution-specific model adaption is underscored. The commercial DLAS software exhibits superior accuracy once localized fine-tuned, and is highly robust to imaging equipment changes.

Stratification to Neoadjuvant Radiotherapy in Rectal Cancer by Regimen and Transcriptional Signatures.

Rectal cancers with stromal features may respond better to RT and 5FU/Cap with the addition of Ox. Within patients not treated with Ox, high levels of cytotoxic lymphocytes associate with response only in immune and stromal tumors. Our analyses provide biological insights about the outcome by different radiotherapy regimens in rectal cancer.

Proton radiotherapy for rectal cancer

AIM: to assess the effectiveness of proton radiotherapy as part of a combined approach to the treatment of rectal malignancies and to assess acute radiation toxicity, which directly affects patients’ quality of life.PATIENTS AND METHODS: between 2020 and 2023, a study included 74 patients with rectal cancer. The mean age of the patients was 65 ± 9.9 years, 44 (60%) males. Stage I occurred in 8 (10.8%) patients, stage II — in 14 (18.9%) patients, stage III — in 52 (70.3%) patients. At the first stage, all patients completed proton radiation therapy in the classical fractionation mode.RESULTS: of the adverse events, 49 (66%) patients had grade 1–2 radiation reactions in the form of proctitis and cystitis. There were no local radiation reactions of grade 3 or higher. Systemic complications of grade 3 were noted in 2 (2%) patients in the form of hematological toxicity — anemia (1%), afebrile neutropenia (2%). Of the 62 operated patients, 12 (19.3%) people showed complete therapeutic pathomorphosis. With a median follow-up of 23 months (13;35), 1 (1.35%) patient showed continued tumor growth 28 months after completed radiotherapy, 2 (2.7%) patients had local recurrence 3 and 18 months after treatment. Distant metastases to the lungs, liver, or bones were detected in 9 (12.2%) patients, median — 12 months (6;23). Mortality during the entire observation period was 9 (12.2%) patients. Sixty-two (83.8%) patients showed no signs of relapse or progression of the disease, of which 9 (14.5%) patients did not receive any treatment after chemoradiotherapy and are in the process of active follow-up.CONCLUSION: proton radiation therapy in patients with rectal cancer in two-year overall survival (90.5%) and progression-free survival (88.9%) are comparable with the literature data of recent studies, but are superior in overall survival pathological response (19.3%).

Expert Commentary on Use of Intraoperative Radiation Therapy in Rectal Cancer.

Expert Commentary on Use of Intraoperative Radiation Therapy in Rectal Cancer.

Use of Intraoperative Radiation Therapy in Rectal Cancer.

Use of Intraoperative Radiation Therapy in Rectal Cancer.

Total neoadjuvant treatment with long-course radiotherapy versus concurrent chemoradiotherapy in local advanced rectal cancer with high risk factors (TNTCRT): A multicenter, randomized, open-label, phase 3 trial.

LBA3511 Background: Distant metastases remain a common problem in locally advanced rectal cancer (LARC) patients who received neoadjuvant chemoradiotherapy (NCRT) and surgery. Previous researchers have demonstrated the survival benefits of total neoadjuvant treatment (TNT) using short-course radiotherapy with CAPOX and long-course radiotherapy (LCRT) with mFOLFIRINOX. This study aimed to explore the efficacy of TNT using long-course radiotherapy (LCRT) combined with CAPOX. Methods: In this phase 3, open-label, multicenter, randomized trial, eligible pts were diagnosed as stage II/III and had at least one high risk factor: cT4a-b (resectable), cT3c-d with extramural venous invasion, cN2; involved mesorectal fascia, or enlarged lateral lymph nodes. Pts were randomly assigned to either Arm A to receive TNT (LCRT with six cycles of neoadjuvant CAPOX (one cycle of induction CAPOX, two cycles of concurrent CAPOX, and three cycles of consolidation CAPOX) followed by total mesorectal excision (TME)) or Arm B to receive NCRT (LCRT with concomitant capecitabine, followed by TME and adjuvant CAPOX). Radiotherapy in both groups was administered at 50-50.4 Gy in 25-28 fractions. The primary endpoint was disease free survival (DFS). The secondary endpoints were pathological response complete (pCR) rate, overall survival (OS), metastasis-free survival (MFS) and postoperative 30-day morbidity. Results: (ITT) Between June 6, 2017, and Mar 5, 2024, 458 pts were randomly assigned to two Arms (232 in Arm A, and 226 in Arm B). At a median follow-up of 44 months (IQR, 24-57.25), the 3-yr DFS was significantly increased in Arm A (77.0% vs 67.9% in Arm A/B respectively, HR 0.623, 95% CI 0.435-0.892, p = 0.009). 3-yr MFS was also significantly higher in arm A: 83.0% vs 74.2% in arm B (HR 0.595, 95% CI 0.392-0.903, p= 0.013). A total of 56 OS events was reported, and the 3-yr OS was 90.3% vs 87.9% (HR 0.747, 95% CI 0.441-1.266, p = 0.276) in arm A/B, respectively. TNT and NCRT in both arms were well tolerated. Thrombocytopenia was the most frequent grade 3-4 hematological adverse event in Arm A, occurring in 24 (10.3%) of 232 pts. Until now, 27.5% of pts achieved pCR in Arm A, compared to only 9.9% in Arm B. (OR 3.436, [1.1.941-6.084], p= 0.0001). In Arm A and B, 13 and 2 pts achieved clinical complete response (cCR) and received watch-and-wait strategy, respectively. No significant difference in severe morbidity within 30 days post-operation were found between the two arms. Conclusions: TNT with LCRT combined with CAPOX significantly improve DFS, MFS and pCR compared to standard concurrent neoadjuvant chemoradiotherapy in LARC patients with high risk factors, with acceptable toxicities. Clinical trial information: NCT03177382 .

Bowel bag sparing in palliative radiotherapy (pRT) of rectal cancer (rCa): Tradeoff between organs at risk (OARs) and use of AI to reduce radiation oncologist (RO) workload.

e15615 Background: We retrospectively studied the potential to reduce bowel toxicity after pRT of rCa using a bowel dose (BD) minimization strategy; also its effect on dose to remaining normal tissues (NT) and pelvic bone marrow (PBM). Finally, we studied the use of AI to reduce the RO workload. Methods: 25 consecutive rCa patients (pts) previously treated with pRT were included. Their treatments were planned without consideration to BD. The following OARs were manually segmented retrospectively: Bowel Bag (BB-M) excluding PTV, PBM (PBM-M), and NT defined as the patient contour excluding PTV and BB-M. The AI-Rad Companion software was used to autosegment: Bowel Loops (BL-AI) and PBM (PBM-AI). For the 25 pts, two Pareto optimal treatment plans (5 Gy x 5) were generated with the Monaco treatment planning system. The first plan (Reference) was optimized aiming to limit dose outside the PTV. The second plan (Opt-BB-M) was optimized aiming firstly to limit BB-M dose and secondly to limit NT dose. A third plan (Opt-BL-AI) was generated for the 10 worst-off pts (in terms of BD) aiming instead to limit BL-AI dose. Two volume-at-dose (VD) metrics (V18Gy, V10Gy) were used as endpoints. Endpoint differences (ΔVD-OAR) were tested using one-sided Wilcoxon signed-rank tests. Spearman (rs) and Pearson (r) correlation coefficients were used to study correlation between variables (ΔVD-BB vs. ΔVD-BM, and ΔVD-BB vs. ΔVD-NT). Dice Similarity Coefficient (DCS) was used to compare PBM-M and PBM-AI. Results: After reoptimization, BB-M VD (V18Gy; V10Gy) was lower (p &lt; 0.001; p &lt; 0.001), PBM-M VD was higher (p = 0.002; p &lt; 0.001), and NT VD was higher (p &lt; 0.001; p &lt; 0.001). For BB-M, ΔV18Gy and ΔV10Gy (median, min, max) were (-4, -46, 0) cm3 and (-33, -254, 0) cm3; for PBM-M: (+2, -4, +56) cm3 and (+33, -6, +189) cm3; for NT: (+10, -43, +194) cm3 and (+146, -18, +614) cm3. Table 1 presents results for the 10 worst-off pts. Medium/strong correlations were found for ΔV18Gy-BB vs. ΔV18Gy-PBM (rs = -0.72, p &lt; 0.001; r = -0.74, p &lt; 0.001), ΔV10Gy-BB vs. ΔV10Gy-PBM (rs = -0.66, p &lt; 0.001; r = -0.32, p = 0.11), ΔV18Gy-BB vs. ΔV18Gy-NT (rs = -0.74, p &lt; 0.001; r = -0.74, p &lt; 0.001), ΔV10Gy-BB vs. ΔV10Gy-NT (rs = -0.74, p &lt; 0.001; r = -0.51, p = 0.009). The DSC (median, min, max) for PBL was (92%, 87%, 94%). Conclusions: Bowel dose in pRT of rCa can be reduced at the expense of increasing dose to PBM and other NT. AI tools can be used effectively to limit RO workload. [Table: see text]