Neoadjuvant Radiotherapy Research Articles

Three-staged minimally invasive esophagectomy with end-to-end esophago-gastric anastomosis for thoracic esophageal cancers: An experience from a low middle-income country

BackgroundEsophageal cancer is on a steady rise and carries significant mortality and morbidity. Depending upon the clinical stage at presentation, either chemotherapy, radiotherapy with or without surgical resection is the treatments in practice. Traditionally, open esophagectomy was performed but over time, the importance of minimally invasive esophagectomy has been established. In this study, we aimed to report our data of totally minimally invasive esophagectomies performed for thoracic esophageal cancers in last four years. MethodologyA prospective cross-sectional study was conducted at the Department of Upper GI Surgery, Dow University of Health Sciences, Karachi. All diagnosed cases of esophageal carcinoma undergoing minimally invasive esophagectomy, from 2019 to 2022 were included in this study. Outcomes measured were operative time, intra operative complications, conversion rate to open, postoperative complications, number of lymph nodes harvested, margin clearance, in-hospital mortality and 90-days mortality. ResultsA total of 53 cases were included in the study, the most prevalent histological type was squamous cell carcinoma 42(79.2%) as compared to adenocarcinoma 8(15.1%). Most common tumor site was lower thoracic esophagus (30–38 cm) in 20 (56.6%) cases. Neo-adjuvant chemotherapy was given in all 53(100%) cases, whereas neo-adjuvant radiation therapy was offered to 49(92.5%) patients. There was a significant and favorable patient response to the neo-adjuvant treatment in 37(69.8%) cases, leading to a decrease in tumor size. Laparoscopic McKeown Esophagectomies were performed in 44 (83.0%) and 9(17.0%) were Robot-assisted Minimally Invasive esophagectomy (RAMIE). Intraoperative injuries (i.e., lung parenchymal injury and bleeding) were reported in only 2(3.8%) patients. Post-operative complications were recorded in 12(22.6%) patients. Margin clearance was observed in 53 (100%) of the patients. The 90-day mortality rate was 3(5.7%), one due to bleeding and other two mortalities were due to COVID related respiratory complications. ConclusionMinimally invasive esophagectomy was found to be safe and feasible technique with encouraging results in terms of decreased intraoperative and post operative complications as well as achieving the standard oncological surgery with acceptable lymph node yield and margin clearance and in hospital and 90 days mortality.

The health-related quality of life of sarcoma patients treated with neoadjuvant versus adjuvant radiotherapy – Results of a multi-center observational study

AimThe sequence of radiotherapy and resection in patients with soft tissue sarcomas is usually discussed on an individual basis. Better understanding of potential differences of health-related quality of life (QoL) between patients undergoing adjuvant (ART) versus neoadjuvant radiotherapy (NART) is therefore helpful for clinical decision making. MethodsAdult sarcoma patients from 39 hospitals completed the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30). Differences in global QoL, physical functioning, role functioning, fatigue, pain, and insomnia between ART versus NART were investigated with multivariate regression, adjusting for age, gender, chemotherapy, grading, stage, tumor location, recurrence/distant metastasis, sarcoma type, time since last treatment, and treatment status using validated thresholds. ResultsA total of 1110 patients participated. Of them, 340 had received radiotherapy (NART: n = 95, 28%; ART: n = 245, 72%). Global QoL was 59.3 on average after NART and 60.5 after ART (Badj = 1.0, p = 0.74). Physical functioning was 65.9 compared to 70.5 (Badj = 4.2; p = 0.16), role function 48.8 vs. 56.7 (Badj = 7.0, p = 0.08), fatigue 47.5 vs. 45.4 (Badj = -1.2; p = 0.71), pain 40.2 vs. 34.1 (Badj = -6.8; p = 0.08), and insomnia 33.7 vs. 41.6 (Badj = 5.5, p = 0.16). Among patients with NART, clinically relevant QoL impairments were less frequent 2 years after treatment compared to < 2 years thereafter (n = 6 vs. n = 4 on average). ConclusionThere is little evidence for QoL differences in most domains and overall QoL between the two irradiation groups. However, patients after NART might experience worse role functioning and pain but fewer problems with insomnia compared to patients after ART.

The benefits of adjuvant chemotherapy are associated with the kind of neoadjuvant therapy in stage ypI rectal cancer: evidence based on population analysis.

The oncological role of adjuvant chemotherapy (ACT) remains debated in locally advanced rectal cancer (RC) after neoadjuvant therapy (NAT), especially ypI RC. In this study, we used population-based data to evaluate the benefits of ACT in stage ypI RC after NAT and surgery. Moreover, we tried to differentiate what kind of NAT (radiotherapy alone or chemoradiotherapy) was administered because this may affect the further efficacy of ACT. All patients with stage ypI primary rectal malignancy were diagnosed in the SEER database between 2004 and 2017. The Kaplan-Meier method was applied to estimate the effects of ACT in survival analysis. Cox regression was performed to calculate the hazard ratio (HR) and the prognosis factors of survival. Propensity score matching (PSM) was used to balance the parameters between therapy groups. The overall cohort's median follow-up time was 105 months. For 5-year OS and CSS, there were no significant differences between the ACT ( +) and ACT (-) groups (p = 0.105; p = 0.788). However, subgroup analyses according to the kind of NAT found that ACT improved overall survival (OS) and cancer-specific survival (CSS) in patients who received neoadjuvant radiotherapy (nRT) (p < 0.001, p = 0.015). Among patients who received neoadjuvant chemoradiotherapy (nCRT), no significant survival benefits were found between the ACT ( +) and ACT (-) groups (p = 0.526, p = 0.288). Our population-based cohort study suggested that the efficacy of ACT was associated with the kind of NAT. The ACT provides survival benefits in stage ypI RC for patients who received nRT. However, among patients who received nCRT, ACT did not improve long-term survival.

Single-Fraction Versus Fractionated Preoperative Radiosurgery for Resected Brain Metastases: A PROPS-BM International Multicenter Cohort Study

Preoperative stereotactic radiosurgery (SRS) is a feasible alternative to postoperative SRS for resected brain metastases (BM). Most reported studies of preoperative SRS used single-fraction SRS (SF-SRS). The goal of this study was to compare outcomes and toxicity of preoperative SF-SRS with multifraction (3-5 fractions) SRS (MF-SRS) in a large international multicenter cohort (Preoperative Radiosurgery for Brain Metastases-PROPS-BM). Patients with BM from solid cancers, of which at least 1 lesion was treated with preoperative SRS followed by planned resection, were included from 8 institutions. SRS to synchronous intact BM was allowed. Exclusion criteria included prior or planned whole brain radiation therapy. Intracranial outcomes were estimated using cumulative incidence with competing risk of death. Propensity score matched (PSM) analyses were performed. The study cohort included 404 patients with 416 resected index lesions, of which SF-SRS and MF-SRS were used for 317 (78.5%) and 87 patients (21.5%), respectively. Median dose was 15 Gy in 1 fraction for SF-SRS and 24 Gy in 3 fractions for MF-SRS. Univariable analysis demonstrated that SF-SRS was associated with higher cavity local recurrence (LR) compared with MF-SRS (2-year: 16.3% vs 2.9%; P=.004), which was also demonstrated in multivariable analysis. PSM yielded 81 matched pairs (n=162). PSM analysis also demonstrated significantly higher rate of cavity LR with SF-SRS (2-year: 19.8% vs 3.3%; P=.003). There was no difference in adverse radiation effect, meningeal disease, or overall survival between cohorts in either analysis. Preoperative MF-SRS was associated with significantly reduced risk of cavity LR in both the unmatched and PSM analyses. There was no difference in adverse radiation effect, meningeal disease, or overall survival based on fractionation. MF-SRS may be a preferred option for neoadjuvant radiation therapy of resected BMs. Additional confirmatory studies are needed. A phase 3 randomized trial of single-fraction preoperative versus postoperative SRS (NRG-BN012) is ongoing (NCT05438212).

Outcomes Following Recent and Distant Neoadjuvant Radiation in Rectal Cancer: An Institutional Retrospective Review and Analysis of NSQIP

BackgroundNeoadjuvant chemoradiotherapy (nCRT) is the standard of care in locally advanced rectal cancer (LARC). However, radiation therapy is thought to increase operative difficulty due to induction of fibrosis. Total neoadjuvant therapy (TNT) protocols increase the time between completion of radiation and surgical resection which may lead to increased operative difficulty and complications. MethodsA single institution retrospective review of patients ≥18 years with LARC undergoing nCRT from 2015 to 2022. Patients were dichotomized in 2 cohorts: <90 days from radiation to surgery (recent radiation), and ≥90 days from radiation to surgery (distant radiation). Institutional data was compared to National Surgical Quality Improvement Program (NSQIP) rectal cancer data from 2016 to 2020. Outcomes included intraoperative complications, 30-day morbidity, and oncologic outcomes. ResultsOne hundred forty-six institutional patients included, 120 had recent radiation, 26 had distant radiation. Thirty-day morbidity and intraoperative complications did not differ. There was greater radial margin positivity (7% vs. 24%), fewer lymph nodes harvested (17 ± 5 vs. 15 ± 6), and a lower rate of complete mesorectal dissection (88% vs. 65%,) in distant radiation patients 3059 patients were included in NSQIP analysis, 2029 completed radiation <90 days before surgery and 1030 without radiation 90 days before surgery. Patients without radiation 90 days preoperatively had more radial margin positivity (9.2% vs. 4.6%), organ space infection (8.6% vs. 6.4%), and pneumonia (2.2% vs. 0.9%). ConclusionThe present study suggests that increased time between radiation and surgery results in more challenging dissection with less complete mesorectal dissection and increased radial margin positivity without increasing technical complications.

Abstract PO-005: Phase 1/2 study of Ad/PNP with fludarabine for the treatment of head &amp; neck squamous cell carcinoma (HNSCC)

Abstract The project pursues clinical testing of a gene-based treatment for refractory malignancy of the head and neck. Background We are evaluating intratumoral nucleoside cleavage by E. coli purine nucleoside phosphorylase (PNP) as an experimental therapy for refractory solid tumors. The approach requires delivery of PNP transgene to tumor parenchyma followed by prodrug administration, and provides “bystander” killing by a very potent purine antimetabolite (F-Ade) generated intratumorally. F-Ade is 1,000-times more potent than fluorouracil, the chemotherapeutic produced by cytosine deaminase (CD; a first-generation construct used for tumor sensitization). PNP/F-Ade has been found to be superior to CD/fluorouracil by several laboratories. In a Phase 1 study (Rosenthal et al., Ann. Oncol.), antitumor activity was observed after IT injections of a recombinant adenovirus encoding PNP (Ad/PNP), followed by IV fludarabine phosphate (F-araAMP, a prodrug converted by PNP to F-Ade). Methods Patients in the present trial have RECIST 1.1 measurable HNSCC amenable to local injection and no other palliative treatment options. A single-arm protocol is being used to evaluate safety of repeat cycles of Ad/PNP and F-araAMP. Ad/PNP is injected intratumorally twice on Day 1 and once on Day 2, followed by infusion of F-araAMP on Days 3, 4, and 5 every 4 weeks for up to 5 cycles. Results Eight patients have been enrolled to date. There have been no dose limiting toxicities, no serious adverse events (SAEs) definitively attributable to treatment, and no AEs above grade 3 severity. Up to five cycles of Ad/PNP treatment have been administered without limiting sequelae. Intratumoral expression of PNP transgene by RT-PCR has been established in treated tumors. Other correlative endpoints are in process and will be discussed. One patient exhibited tumor volume reduction by approximately 21% (as judged by CT imaging) and did not increase during five months of treatment, consistent with clinically stable disease. Two other patients completed three months of Ad/PNP with stable disease by RECIST criteria during the treatment period. Another patient’s tumor (largest dimension 3.1 cm) demonstrated 25% decrease after one treatment cycle. Challenges have included: 1) complexity of distribution of agent into large volume tumors (e.g., &amp;gt;100 ml) with small volume of Ad/PNP, and 2) acute swelling of tumor tissue following intratumoral virus injection in two patients, consistent with inflammatory response and/or disease progression. Conclusions Administration of Ad/PNP is safe and feasible. Injections of large volume tumors remains a challenge. The strategy is also being considered for earlier-stage HNSCC with less tumor burden, including a role similar to neoadjuvant or cytoreductive radiotherapy in combination with checkpoint blockade inhibition. A muti-center trial is planned to define MTD and feasibility in smaller tumors. Citation Format: A. Dimitrios Colevas, Eric J. Sorscher, William B. Parker, Roan Courtney Raymundo, Jeong S. Hong, Regina Rab, Camilo Henao, Nikki Schmitt, Madison Stallings, Kelly T. McKee, Eben Rosenthal, Joseph Curry. Phase 1/2 study of Ad/PNP with fludarabine for the treatment of head &amp; neck squamous cell carcinoma (HNSCC) [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-005.

Impact of geographical health disparities on outcomes following pelvic exenteration at a centralised quaternary referral centre

IntroductionPelvic exenteration (PE) is an ultra-radical procedure performed for primary or recurrent malignancies confined to the pelvis. Health outcomes for rural Australian populations are generally inferior compared to those from metropolitan centres, however, the effect of geographical location on outcomes following PE is poorly defined. The aim of this study was to investigate how geographical location affects oncological, quality of life (QoL) and survival outcomes following PE. MethodsConsecutive patients undergoing PE between 1994 and 2022 at a single centre were included. Patient post codes were linked with the Australian Statistical Geography Standard Remoteness Structure to stratify patients into five groups based on the geographical location of their residence. Primary outcome measures included patient survival, QoL and oncological outcomes. ResultsA total of 953 patients were included, of which 626 (65.7%) were from major cities, 227 (23.8%) inner regional, 84 (8.8%) outer regional, 9 (0.9%) remote, and 7 (0.7%) very remote areas. Rural patients were more likely to undergo PE for primary rectal cancer (p = 002) and less likely for recurrent, non-rectal carcinoma (p = 0.027). Rural patients less frequently had health insurance (p < 0.001) but were more likely to have undergone neoadjuvant radiotherapy (p = 0.022). No difference in length-of-admission, in-hospital complication rates, QoL at 36 months or survival was observed between groups. ConclusionsDespite geographical disparities, rural populations undergoing PE achieved equally favourable outcomes as populations from metropolitan areas. Enhancing access to specialised care may facilitate better outcomes of patients residing in regional and remote areas.

Randomized Controlled Trial of Neoadjuvant Short-Course Radiotherapy Followed by Consolidation Chemotherapy Versus Long-Course Chemoradiotherapy in Locally Advanced Rectal Cancer: Comparison of Overall Response Rates.

Management of locally advanced rectal cancer (LARC) is evolving with current emphasis on the addition of chemotherapy to short course radiotherapy (SCRT). We primarily aimed to analyse the difference in overall response rates between SCRT with sequential chemotherapy and standard long-course chemoradiotherapy (LCCRT)in LARC. After randomization, patients in arm A received 45Gy in 25 fractions over 5weeks with concurrent capecitabine while patients in arm B received 25Gy in 5 fractions over 1week followed by 3 cycles of CAPOX (capecitabine and oxaliplatin) chemotherapy. Clinical and radiological response assessment was made after the completion of neoadjuvant treatment, a week prior to surgery. Adjuvant chemotherapy was added to complete 6months of peri-operative chemotherapy. Surgery was performed between 8 and 10weeks of completion of radiation treatment in both arms. Of the 33 patients recruited in this study between February 2020 to July 2021, 17 patients were randomized to arm A and 16 to arm B. The rates of complete tumour regression were 23.1% in arm A versus 35.7% in arm B (p-value = 0.683). Pathological complete response (pCR) rate was 20% arm A versus 30% in arm B (0.446). A higher number of patients in arm B experienced grade 3 diarrhoea, whereas acute skin toxicity was seen only in arm A. SCRT had fewer treatment interruptions compared to LCCRT. SCRT followed by three cycles of CAPOX chemotherapy in the neoadjuvant setting is comparable to LCCRT in terms of tumour response. This may be a better alternative regimen with fewer treatment interruptions in a resource-limited setting.

Multicenter phase II trial of transanal total mesorectal excision for rectal cancer: preliminary results

BackgroundTransanal TME (taTME) combines abdominal and transanal dissection to facilitate sphincter preservation in patients with low rectal tumors. Few phase II/III trials report long-term oncologic and functional results. We report early results from a North American prospective multicenter phase II trial of taTME (NCT03144765).Methods100 patients with stage I–III rectal adenocarcinoma located ≤ 10 cm from the anal verge (AV) were enrolled across 11 centers. Primary and secondary endpoints were TME quality, pathologic outcomes, 30-day and 90-day outcomes, and stoma closure rate. Univariable regression analysis was performed to assess risk factors for incomplete TME and anastomotic complications.ResultsBetween September 2017 and April 2022, 70 males and 30 females with median age of 58 (IQR 49–62) years and BMI 27.8 (IQR 23.9–31.8) kg/m2 underwent 2-team taTME for tumors located a median 5.8 (IQR 4.5–7.0) cm from the AV. Neoadjuvant radiotherapy was completed in 69%. Intersphincteric resection was performed in 36% and all patients were diverted. Intraoperative complications occurred in 8% including 3 organ injuries, 2 abdominal and 1 transanal conversion. The 30-day and 90-day morbidity rates were 49% (Clavien–Dindo (CD) ≥ 3 in 28.6%) and 56% (CD ≥ 3 in 30.4% including 1 mortality), respectively. Anastomotic complications were reported in 18% including 10% diagnosed within 30 days. Higher anastomotic risk was noted among males (p = 0.05). At a median follow-up of 5 (IQR 3.1–7.4) months, 98% of stomas were closed. TME grade was complete or near complete in 90%, with positive margins in 2 cases (3%). Risk factors for incomplete TME were ASA ≥ 3 (p = 0.01), increased time between NRT and surgery (p = 0.03), and higher operative blood loss (p = 0.003).ConclusionWhen performed at expert centers, 2-team taTME in patients with low rectal tumors is safe with low conversion rates and high stoma closure rate. Mid-term results will further evaluate oncologic and functional outcomes.Graphical abstract

Clinical predictors of rectal cancer response after neo-adjuvant (Chemo)Radiotherapy in Australia and New Zealand: Analysis of the Bi-National Colorectal Cancer Audit (BCCA)

Pathological complete response (pCR) is observed in 11–26% of locally advanced rectal cancers undergoing neoadjuvant chemoradiotherapy (nCRT). This study aims to determine pCR rates and clinicopathological predictors in the Australian and New Zealand (ANZ) cohort. The Bi-National Colorectal Cancer Audit (BCCA) was interrogated for all rectal cancer patients who underwent nCRT prior to surgical resection between 2007 and 2020. Patients were divided in two groups: pCR (AJCC tumour regression grade 0) and partial/no response (pPR, regression grade 1,2 or 3). In total, 3230 patients were included. Rates of pCR and pPR were 704 (21.8%) and 2526 (78.2%), respectively. Long-course nCRT (p < 0.0001), lower clinical tumour stage (cT; p < 0.0001), and nodal stage (cN; p = 0.003) were associated with pCR on univariate analysis. On multivariable analysis, cN0 stage and long-course nCRT remained independent factors for a pCR. Awareness of these predictors provides valuable information when counseling patients regarding prognosis and treatment options.

Predictors and survival outcomes of having less than 12 harvested lymph nodes in proctectomy for rectal cancer.

Current recommendations suggest that a minimum of 12 lymph nodes (LNs) should be harvested during curative rectal cancer resection. We aimed to assess predictors and survival outcomes of harvesting < 12 lymph nodes in rectal cancer surgery. A retrospective case-control analysis of factors associated with harvesting < 12 LNs in rectal cancer surgery was conducted. Data were derived from the National Cancer Database 2010-2019. Univariate and multivariate binary logistic regression analyses were performed to determine predictors of harvesting < 12 LNs. Association between harvesting < 12 LNs and 5-year overall survival (OS) was assessed using Cox regression and Kaplan Meier statistics. 67,529 patients (60.8% male; mean age: 61.2 ± 12.5years) were included. Median number of harvested LNs was 15 (IQR: 11-20); 27.1% of patients had < 12 harvested LNs. Independent predictors of harvesting < 12 LNs were older age (OR: 1.016;p < 0.001), neoadjuvant systemic treatment (OR: 1.522;p < 0.001), neoadjuvant radiation treatment (OR: 1.367;p < 0.001), longer duration of radiation therapy (OR: 1.003;p < 0.001) and abdominoperineal resection (OR: 1.071;p = 0.017). Higher clinical TNM stage and tumor grade, pull-through coloanal anastomosis, and minimally invasive surgery were independently associated with ≥ 12 harvested LNs. < 12 harvested LNs was independently associated with lower 5-year OS (HR: 1.24;p < 0.001) and shorter mean OS (96.7 vs 102.8months;p < 0.001) than ≥ 12 harvested LNs. Older age, open resection, and neoadjuvant therapy were independent predictors of < 12 harvested LNs. Conversely, higher clinical TNM stage and tumor grade, coloanal anastomosis, and minimally invasive surgery were predictive of ≥ 12 harvested LNs. < 12 LNs harvested was associated with lower OS.

P11.44.A THE ROLE OF RADIOTHERAPY IN MALIGNANT PERIPHERAL NERVE SHEATH TUMORS: A MULTICENTER COHORT STUDY

Abstract BACKGROUND Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are rare and aggressive malignant soft-tissue sarcomas (STS), of which 40% are associated with neurofibromatosis type 1 (NF1). Current treatment in localized disease mainly revolves around surgical excision, yet MPNSTs harbor a high probability of local recurrence (LR). Radiotherapy (RT) is increasingly being used, as it improves local control in STS, yet does not impact survival. Nevertheless, its use is controversial in some cases as major wound complications can be much higher and NF1 patients harbor a potential higher risk for secondary malignancies as MPNST commonly arise within plexiform neurofibromas. This study evaluates the use of RT in these rare tumors and tries to understand its impact in local control, especially in the NF1 setting. MATERIAL AND METHODS Surgically treated primary MPNSTs between 1988 to 2019 in the MONACO multicenter cohort were included. Demographic and treatment differences, especially the use of RT, between NF1 and non-NF1 were analyzed. Univariate and multivariable logistic regression analyses were used to identify factors independently associated with the use of radiotherapy. Multivariate Cox regression analyses were performed to identify factors associated with LR in NF1 patients. RESULTS A total of 528 patients (31.8% NF1) were included, of which 149 (28.2%) developed a LR. RT was administered in 53.2% of patients (55.6% in NF1). Of these, 26.7% received neoadjuvant RT, and 71.2% adjuvant RT. The use of both treatment modalities was similar between patients with and without NF1. Multivariable regression showed that microscopically positive margins and high-grade tumors were independent factors for the use of RT. The rate of RT use in NF1 did not alter after correcting for tumor-, patient- and surgical factors. RT did not impact overall survival in sporadic and NF1 associated MPNST. In NF1 patients, microscopically positive margins (R1) (HR 3.2; 95% CI, 1.41-7.62), tumor size &amp;gt;5cm (HR 2.2; 95% CI, 1.14-4.3), and a high grade (HR 3.13; 95% CI, 1.23-7.98) were independent risk factors for the development of a LR. Correcting for tumor-, patient- and surgical factors, use of RT was not associated lower rates of LR, in contrast to the sporadic population. CONCLUSION Radiotherapy is commonly used in MPNST treatment regardless of its origin in NF1. While it may impact LR rate in sporadic patients, this is less clear in NF1 patients. Further studies are needed to evaluate its role and indications in NF1 associated MPNST.

Pelvic insufficiency fractures and pelvic bone metastases after neoadjuvant (chemo)radiotherapy for rectal cancer

Background: Pelvic insufficiency fractures (PIFs) are a late complication of radiotherapy for pelvic malignancies. We evaluated the incidence, radiologic findings, clinical course, and outcome of PIFs in patients treated with neoadjuvant (chemo)radiotherapy ((C)RT) for rectal cancer. Material and methods: Data of patients diagnosed with rectal cancer from a large teaching hospital treated from 2002 to 2012 were extracted from the Dutch Cancer Registry. All hospital records were reviewed for the diagnosis of PIFs or pelvic bone metastases. An expert radiologist reassessed all imaging procedures of the lower back, abdomen, and pelvis. Results: A total of 513 rectal cancer patients were identified of whom 300 patients (58.5%) were treated with neoadjuvant (C)RT (long- vs. short-course radiotherapy: 91 patients [17.7%] vs. 209 [40.7%], respectively). Twelve PIFs were diagnosed initially according to hospital records and imaging reports of all 513 patients. These 12 patients were treated with neoadjuvant (C)RT. After reassessment of all pelvic imaging procedures done in this patient group (432 patients (84.2%)), 20 additional PIFs were detected in patients treated with neoadjuvant (C)RT, resulting in a 10.7% PIF rate in irradiated patients. One PIF was detected in the group of patients not treated with neoadjuvant (C)RT for rectal cancer. This patient had palliative radiotherapy for prostate cancer and is left out of the analysis. Median follow-up time of 32 PIF patients was 49 months. Median time between start of neoadjuvant (C)RT and diagnosis of PIF was 17 months (IQR 9–28). Overall median survival for patients with PIF was 63.5 months (IQR 44–120). Conclusion: PIFs are a relatively common late complication of neoadjuvant (C)RT for rectal cancer but are often missed or misdiagnosed as pelvic bone metastases. The differentiation of PIFs from pelvic bone metastases is important because of a different treatment and disease outcome.

Long-course chemoradiation plus concurrent/sequential PD-1 blockade as neoadjuvant treatment for MMR-status-unscreened locally advanced rectal cancer: protocol of a multicentre, phase 2, randomised controlled trial (the POLAR-STAR trial)

IntroductionRecent preclinical studies have discovered unique synergism between radiotherapy and immune checkpoint inhibitors, which has already brought significant survival benefit in lung cancer. In locally advanced rectal cancer (LARC), neoadjuvant...

43660 Neoadjuvant Radiation to Facilitate Surgical Treatment of a Microcystic Adnexal Carcinoma with Perineural Invasion of the Vulvar Region

43660 Neoadjuvant Radiation to Facilitate Surgical Treatment of a Microcystic Adnexal Carcinoma with Perineural Invasion of the Vulvar Region

1041 Audit of Enhanced Recovery After Surgery (ERAS) Protocol in Elective Colorectal Surgery (A Loop Audit)

Abstract Aim Audit of current adherence to the ERAS guidelines for all elective colorectal surgical procedures in our hospital. Comparison was made with first audit which was done in 2018 and subsequently improvement was done in second loop in 2019. Method Retrospective review of all elective patient’s admitted for Colorectal surgery between January 1st 2019 – December 31st 2019. Inclusion Criteria: All elective colorectal surgeries including right hemicolectomy, extended right hemicolectomy, left hemicolectomy, anterior resection, and abdominoperineal resections. All colorectal surgeries after either adjuvant or neoadjuvant chemotherapy or radiotherapy 37 patients were identified for the audit. Every component of Enhanced recovery after surgery (ERAS) was carefully noted in patient's records. All the data was collected and collaborated manually in excel sheet. The data was then presented in graphical manner. Exclusion Criteria:Emergency colorectal procedures. Results Audit in 2018:Percentage adherence:Pre-admission – 59.2%Pre-operative – 73.9%Intra-operative – 70.1%Post-operative – 52.7%No ERAS Anaesthetic component was includedOverall Adherence to guidelines – 63.9%Mean Length of Stay – 9.8 days Loop Audit in 2019:Percentage adherence:Pre-admission – 88 %Pre-operative – 80.25%Intra-operative – 76.8%Post-operative – 79.6%All ERAS Anaesthetic components includedOverall Adherence to guidelines – 81.1%Mean Length of Stay –7.1 days Conclusions Very Good compliance to ERAS. Improved as compared to previous audit.

18. ASSOCIATION OF TUMOR PATHOLOGICAL COMPLETE RESPONSE WITH THE USE OF METFORMIN DURING NEOADJUVANT CHEMORADIOTHERAPY IN ESOPHAGEAL CANCER PATIENTS: RETROSPECTIVE STUDY

Abstract Background Metformin is a standard treatment for type 2 diabetes mellitus (DM). Previous in vitro and in vivo studies have reported the association of metformin’s additive anticancer response with chemotherapy in esophageal cancer. However, no clinical studies have been reported. Therefore, this study is to aim the administration of metformin use can improve clinical outcomes of esophageal cancer patient with neoadjuvant combined chemotherapy and radiation (CCRT). Methods A total of 209 patients with esophageal cancer and underlying DM who underwent neoadjuvant CCRT before surgical resection were included from 1998 to 2022. There were 22 patients with metformin medication (10.5%) and 186 patients without metformin (89%). Univariable and multivariable regression analysis were done for complete response effect of metformin medication. Moreover, early clinical outcomes such as, overall survival and disease free survival were compared between the two groups. Results The complete response rate was higher for the metformin group (45.5% vs 22.6%; p = 0.019) and the recurrence rate was significantly lower (21.1% vs 45.7%, p = 0.040). The metformin group was associated with complete response rate in univariate logistic regression analysis (odds ratio [OR] = 2.86 [1.15–7.08], p = 0.023) and multivariable analysis (odds ratio [OR] = 2.84 [1.12–7.23], p = 0.028). Median follow-up duration was 19.8 months for metformin group, 17.3 months for non-metformin group. Overall 2-year survival rate and disease free survival was higher for metformin group than non-metformin group, (40% vs 26.5%, p = 0.380, 31.6% vs 24.3%, p = 0.095), however, not significant. Conclusion An association of metformin use with complete response rate in neoadjuvant CCRT esophageal cancer patients has been shown. The potential of metformin’s tumor response after neoadjuvant CCRT for esophageal cancer has been demonstrated in our study. Further prospective study should be needed for clinical evidence.

325. CAMRELIZUMAB IN COMBINATION WITH CHEMOTHERAPY VERSUS CHEMORADIOTHERAPY FOR THE CONVERSION OF UNRESECTABLE ESOPHAGEAL CARCINOMA: A PROSPECTIVE CLINICAL STUDY PROTOCOL

Abstract Background Neoadjuvant chemoradiotherapy followed by esophagectomy is the standard of care for locally advanced esophageal squamous cell carcinoma (ESCC). However, approximately 30% of patients still develop distant metastases and have a high incidence of treatment-related adverse events. Immunotherapy, as a new modality for anti-cancer treatment, has shown promising clinical benefits for patients with ESCC. The synergistic effects of immunotherapy and radiotherapy make their combination promising as neoadjuvant treatment for locally advanced ESCC. Methods All participants who meet the inclusion criteria will be enrolled after signing the informed consent form. Patients with thoracic segment esophageal cancer with clinical stage T2–3 N0 M0 or T2–3 N+ M0 will be included. They will be treated with radical surgery within 4–8 weeks after the completion of two cycles of neoadjuvant radiotherapy in combination with camrelizumab according to the study schedule. The primary endpoint is the major pathological remission rate of all per-protocol patients. The secondary endpoints are the R0 resection rate, pathological complete remission rate, and adverse events. The interim analysis will be conducted after half of the planned number of patients have been enrolled. The trials will be terminated when more than two treatment-related deaths occur or fewer than five patients have major pathological remission. Discussion We designed this prospective single-arm phase II clinical study to evaluate the combination of camrelizumab and standard radiotherapy as preoperative neoadjuvant therapy for patients with resectable ESCC as part of the quest for better treatment options for patients with locally advanced ESCC. Trial registration: This trial protocol has been registered on NIH Clinical Trials database (www.clinicaltrials.gov/, NCT05176002). The posted information will be updated as needed to reflect protocol amendments and study progress.

Development and Validation of a Post-Radiotherapy Prediction Model for Bowel Dysfunction After Rectal Cancer Resection

The benefit of radiotherapy for rectal cancer is based largely on a balance between a decrease in local recurrence and an increase in bowel dysfunction. Predicting postoperative disability is helpful for recovery plans and early intervention. We aimed to develop and validate a risk model to improve the prediction of major bowel dysfunction after restorative rectal cancer resection with neoadjuvant radiotherapy using perioperative features. Eligible patients more than 1 year after restorative resection following radiotherapy were invited to complete the low anterior resection syndrome (LARS) score at 3 national hospitals in China. Clinical characteristics and imaging parameters were assessed with machine learning algorithms. The post-radiotherapy LARS prediction model (PORTLARS) was constructed by means of logistic regression on the basis of key factors with proportional weighs. The accuracy of the model for major LARS prediction was internally and externally validated. A total of 868 patients reported a mean LARS score of 28.4 after an average time of 4.7 years since surgery. Key predictors for major LARS included the length of distal rectum, anastomotic leakage, proximal colon of neorectum, and pathologic nodal stage. PORTLARS had a favorable area under the curve for predicting major LARS in the internal dataset (0.835; 95% CI, 0.800-0.870, n= 521) and external dataset (0.884; 95% CI, 0.848-0.921, n= 347). The model achieved both sensitivity and specificity >0.83 in the external validation. In addition, PORTLARS outperformed the preoperative LARS score for prediction of major events. PORTLARS could predict major bowel dysfunction after rectal cancer resection following radiotherapy with high accuracy and robustness. It may serve as a useful tool to identify patients who need additional support for long-term dysfunction in the early stage. gov, number NCT05129215.

Chemoradiotherapy plus hyperthermia (CRTH) versus chemoradiotherapy (CRT) alone in neoadjuvant treatment of soft tissue sarcoma: tumor response, treatment toxicity and disease control

Introduction Neoadjuvant chemotherapy and radiotherapy for the management of soft tissue sarcomas (STS) are still preferably delivered sequentially, with or without concurrent hyperthermia. Concurrent delivery of chemo-, radio- and thermotherapy may produce synergistic effects and reduce chemotherapy-free intervals. The few available studies suggest that concurrent chemoradiation (CRT) has a greater local effect. Data on the efficacy and toxicity of adding hyperthermia to CRT (CRTH) are sparse. Materials and methods A cohort of 101 patients with STS of the extremities and trunk who received CRT (n = 33) or CRTH (n = 68) before resection of macroscopic tumor (CRT: n = 19, CRTH: n = 49) or re-resection following a non-oncological resection, so called ‘whoops procedure’, (CRT: n = 14, CRTH: n = 19) were included in this retrospective study. CRT consisted of two cycles of doxorubicine (50 mg/m2 on d2) plus ifosfamide (1500 mg/m2 on d1-5, q28) plus radiation doses of up to 60 Gy. Hyperthermia was delivered in two sessions per week. Results All patients received the minimum dose of 50 Gy. Median doses of ifosfamide and doxorubicin were comparable between CRT (75%/95%) and CRTH (78%/97%). The median number of hyperthermia sessions was seven. There were no differences in acute toxicities. Major wound complications occurred in 15% (CRT) vs. 25% (CRTH) (p = 0.19). In patients with macroscopic disease, the addition of hyperthermia resulted in a tendency toward improved remission: regression ≥90% occurred in 21/48 (CRTH) vs. 4/18 (CRT) patients (p = 0.197). With a median postoperative follow-up of 72 months, 6-year local control and overall survival rates for CRTH vs. CRT alone were 85 vs. 78% (p = 0.938) and 79 vs. 71% (p = 0.215). Conclusions Both CRT and CRTH are well tolerated with an expected rate of wound complications. The results suggest that adding hyperthermia may improve tumor response.