Neoadjuvant Radiotherapy Research Articles

"Defendit Numerus": A Pooled Analysis of 6145 Locally Advanced Rectal Cancer Treated with Preoperative Chemoradiotherapy.

Objective: The optimal management of rectal cancer remains a subject of ongoing research. This meta-analysis of individual patient data assessed the benefit of chemoradiotherapy (fluorouracil-based) in local advanced rectal cancer: disease-free survival and overall survival. Methods: We pooled the data of 6145 patients from 24 studies of rectal cancer who received neoadjuvant radiotherapy with concomitant fluorouracil or capecitabine and surgery. The PRISMA 2020 abstract checklist was followed. Individual participant survival was reconstructed with an algorithm from published Kaplan-Meier curves. Results: The median OS was not reached; the mean survival time was 135.4 months (127.9-141.5). The median DFS was 176.9 months, and the mean disease-free survival time was 122.6 months (111.7-131.9). Conclusions: We provided a benchmark for future studies on rectal cancer treatment. The present results can be used in decision-making for locally advanced rectal cancer patients.

Neo-adjuvant radiation and intratumoral immunotherapy followed by surgery-NARIS trial for extremity soft tissue sarcoma.

Extremity soft tissue sarcoma (ESTS) is a rare malignant nonepithelial disease, calling for combined modality treatments with surgery to further improve local control rates and long-term survival, especially in patients with multiple local recurrences with or without risk of amputation. In this double-arm, open-label, Phase II clinical trial, we will enroll 30 patients with pathologically confirmed ESTS without nodal involvement or distant metastases. Patients are randomly assigned to the combination treatment group or the radiation monotherapy group. Additionally, tumor and biological samples will be obtained directly before and after neoadjuvant therapy, allowing for studies of immune response and primary drug resistance mechanisms.Clinical Trial Registration: ChiCTR2200060659 (http://www.chictr.org.cn) (ClinicalTrials.gov).

What To Do With Suspected Nodal Regrowth on Magnetic Resonance Imaging During Follow-up in an Organ Preservation Approach for Rectal Cancer?

BACKGROUND: For nodal regrowth in patients with rectal cancer following watch-and-wait standardized protocols on diagnostic procedures and subsequent treatment are lacking. OBJECTIVE: Evaluate the diagnosis and treatment of suspected nodal regrowth following an organ preservation approach. SETTINGS: Patients were included from national and institutional watch-and-wait -databases. DESIGN: Thirty-five rectal cancer patients with suspected nodal regrowth on magnetic resonance imaging were retrospectively identified during watch-and-wait follow-up. PATIENTS: Twenty-seven of 35 patients followed watch-and-wait after neoadjuvant (chemo)radiotherapy and 8/35 followed watch-and-wait schedule after local excision for early rectal cancer. MAIN OUTCOME MEASURES: Diagnostic procedures, treatment and histopathological outcome. RESULTS: Median follow-up was 34 months. Median time from end of (chemo)radiotherapy or local excision to first detection of suspected nodal regrowth on magnetic resonance imaging following watch-and-wait was 9 and 10 months. After first detection, 17 of 35 patients underwent immediate treatment without further diagnostics, of whom 7 also had luminal regrowth. In 18 of 35 patients, additional diagnostic procedures were performed. In 4 of 18 patients, positron emission tomography-computed tomography or endorectal ultrasound-guided biopsy was performed and treatment was initiated based on increased nodal regrowth suspicion. In 14 of 18 patients, MRI was repeated after 8-12 weeks: growth of suspected lymph nodes was the most decisive factor to proceed to treatment. In 8 patients, repeated magnetic resonance imaging was combined with positron emission tomography-computed tomography and/or endorectal ultrasound-guided biopsy: in half of them it contributed to treatment initiation. In total, 34/35 patients were treated: 9 received (re-)irradiation and 33 underwent total mesorectal excision. In 27 of 33 patients, nodal regrowth was pathologically confirmed in the total mesorectal excision-resection specimen; 5 of 6 patients without nodal involvement had pathologically confirmed luminal regrowth. LIMITATIONS: Highly selected study population. CONCLUSIONS: During watch-and-wait follow-up of patients with rectal cancer in an organ preservation strategy, magnetic resonance imaging plays an important role in diagnosis of nodal regrowth. Repeated magnetic resonance imaging after an interval can be helpful in making treatment decisions, and the role of positron emission tomography-computed tomography and endorectal ultrasound-guided biopsy appears limited. See Video Abstract.

Spatially resolved analysis of pancreatic cancer identifies therapy-associated remodeling of the tumor microenvironment.

In combination with cell-intrinsic properties, interactions in the tumor microenvironment modulate therapeutic response. We leveraged single-cell spatial transcriptomics to dissect the remodeling of multicellular neighborhoods and cell-cell interactions in human pancreatic cancer associated with neoadjuvant chemotherapy and radiotherapy. We developed spatially constrained optimal transport interaction analysis (SCOTIA), an optimal transport model with a cost function that includes both spatial distance and ligand-receptor gene expression. Our results uncovered a marked change in ligand-receptor interactions between cancer-associated fibroblasts and malignant cells in response to treatment, which was supported by orthogonal datasets, including an ex vivo tumoroid coculture system. We identified enrichment in interleukin-6 family signaling that functionally confers resistance to chemotherapy. Overall, this study demonstrates that characterization of the tumor microenvironment using single-cell spatial transcriptomics allows for the identification of molecular interactions that may play a role in the emergence of therapeutic resistance and offers a spatially based analysis framework that can be broadly applied to other contexts.

Neoadjuvant radiation target volume definition in esophageal squamous cell cancer: a multicenter recommendations from Chinese experts

BackgroundThis study aimed to establish a consensus on the delineation of target volumes for neoadjuvant radiation therapy (nRT) in esophageal squamous cell carcinoma (ESCC) within China.MethodsFrom February 2020 to June 2021, nine ESCC patients who received nRT were retrospectively selected from Sun Yat-sen University Cancer Center and Shandong Cancer Hospital. A panel from eight cancer radiotherapy centers performed two rounds of nRT target volume delineation for these patients: the first round for cases 1–6 and the second for cases 7–9. Online meetings were held after each delineation round to discuss findings. The consistency of delineations across centers was compared using mean undirected Hausdorff distances (Hmean), dice similarity coefficients (DSC), and total volumes, analyzed with the Mann-Whitney U test.ResultsThe second round of delineations showed improved consistency across centers (total clinical target volume (CTVtotal): mean DSC = 0.76–0.81; mean Hmean = 2.11–3.14 cm) compared to the first round (CTVtotal: mean DSC = 0.63–0.64; mean Hmean = 5.66–7.34 cm; DSC and Hmean: P < 0.050 between rounds), leading to the formation of a consensus and an atlas for ESCC nRT target volume delineation. A proposal was reached through evaluating target volume delineations, analyzing questionnaire survey outcomes, and reviewing pertinent literature.ConclusionsWe have developed guidelines and an atlas for target volume delineation in nRT therapy for ESCC in China. These resources are designed to facilitate more consistent delineation of target volumes in both clinical practice and clinical trials.

204. ALTERATIONS IN LOCAL OESOPHAGEAL MICROBIOTA AND OUTCOMES AFTER OESOPHAGECTOMY FOR OESOPHAGO-GASTRIC CANCER: A PILOT STUDY

Abstract Oesophageal cancer is a global health burden, with an estimated 600,000 new cases and 550,000 deaths per year. It is the 9th most common cancer yet is ranked fifth for cancer mortality. The current gold standard curative strategy includes oesophagectomy, which is a morbid procedure. In particular, anastomotic leaks are a feared complication postoperatively that result in significant morbidity. Studies of patients undergoing colorectal cancer surgery show that alterations in the local microbiota can contribute to complications including anastomotic leak. Furthermore, some pathogenic bacterial species have been implicated in shorter recurrence-free survival periods after curative oncologic surgery. Unlike bacterial culture, which requires viable bacteria to be preserved from the time of sampling through to processing, 16S RNA sequencing can be performed on both fresh and fixed tissues. However, there are few studies using either tissue source and to date, none that compare results from the same patient. The aims of this pilot study were to: 1. Assess the feasibility of testing archived histological specimens (i.e. formalin fixed) that in turn facilitates retrospective analysis of patients with known clinical outcomes (i.e. anastomotic leaks) 2. Identify any difference (variance, reduce or over-abundance) between the microbiota of patients who suffered anastomotic leak and those who did not 3. Generate preliminary data to inform sample sizes, statistical methods, workflow and cost of a future prospective trial Using an established Upper GI Cancer Surgery Database, we performed propensity score matching to identify 15 patients who had a clinically evident anastomotic leak to be matched with 15 patients who did not have an anastomotic leak. Known predictors of anastomotic leak (e.g. neoadjuvant radiotherapy, smoking status, COPD, chronic kidney disease, diabetes mellitus, chronic liver disease) have been controlled for. Fresh frozen and formalin-fixed samples for the same patients were available. The formalin-fixed tissue was comprised of the "anastomotic doughnuts" created at the time of the circular stapled anastomosis. This tissue was chosen because of its immediate proximity to the anastomosis. All samples were analysed using 16S RNA sequencing to obtain a full microbial profile. Sequencing data was analysed by scientific investigators blinded to the clinical outcome (i.e. anastomotic leak vs. no leak) using a pre-existing workflow and bioinformatics pipeline.

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

438. TECHNIQUE OF COMPLETELY ROBOTIC MCKEOWN (3-HOLE) ESOPHAGECTOMY WITH INTRA-CORPOREAL GASTRIC CONDUIT CREATION, AND CERVICAL ESOPHAGO-GASTRIC ANASTOMOSIS FOR MID-ESOPHAGEAL ADENOCARCINOMA

Abstract Background Esophageal cancer is the 7th leading cause of cancer deaths, with an estimated total case of 22,370 in both males and females in 2024. Adenocarcinoma and squamous cell carcinoma account for over 90% of histology at diagnosis. The incidence of adenocarcinoma continues to rise due to the rising incidence and prevalence of obesity, gastro-esophageal reflux disease and Barrett's esophagus. Multi-modality treatment is currently the standard of care for locally advanced disease. This consists of neoadjuvant concurrent chemotherapy and radiation therapy, followed by esophagectomy. Minimally invasive approaches to esophagectomy are associated with decreased post-operative morbidities and overall satisfactory outcomes. While the Ivor Lewis esophagectomy with intra-thoracic anastomosis is the most common surgical approach to resection of distal esophageal and gastroesophageal (GE) junction tumors, the McKeown (3-hole) esophagectomy with cervical esophago-gastric anastomosis is best suited for tumors located in the proximal and mid-esophagus. Methods We describe our technique of robotic McKeown (3-hole) esophagectomy for mid-esophageal adenocarcinoma after neoadjuvant concurrent chemo-radiation therapy for clinical stage uT3N0M0 tumor. The thoracic esophagus is completely mobilized from the esophageal hiatus of the diaphragm up to the thoracic inlet via a right thoracoscopic approach, with harvesting of the regional lymph nodes together with the specimen. The left neck incision is made along the anterior border of the sternocleidomastoid muscle and the inferior belly of the omohyoid muscle is transected. The cervical esophagus is then completely mobilized into the wound and secured using a Penrose drain. Using a laparoscopic approach, the entire stomach is mobilized with division of the left gastric vessels but careful preservation of the right gastro-epiploic arcade while transecting the greater omentum and the short gastric vessels. An intra-corporeal creation of the gastric conduit then follows. The gastric conduit, secured to the proximal stomach at the resection staple line, is subsequently tunneled via the esophageal hiatus and through the mediastinum to exit at the left neck incision by applying traction on the cervical esophagus. The specimen is separated from the conduit, and the cervical esophagus is transected at the desired location for the anastomosis. A stapled end-to-side but functional end-to-end esophago-gastric anastomosis (Orringer's technique) is then created. Results A completely robotic technique of McKeown (3-hole) esophagectomy without the need to exteriorize the stomach to fashion the gastric conduit via a (mini)laparotomy is successfully accomplished in the majority of our patients with proximal or mid-esophageal tumors. An uneventful postoperative recovery was made. Fluoroscopic esophagram on post-operative day 5 did not demonstrate leakage from the anastomotic site. Gastric conduit emptying was satisfactory despite the lack of a routine gastric drainage procedure or injection of botulinum toxin into the pyloric ring. Conclusion Robotic-assisted thoracoscopic esophageal mobilization combined with laparoscopic completely intra-corporeal fashioning of gastric conduit with cervical esophago-gastric anastomosis is a technically feasible minimally invasive approach to performing McKeown esophagectomy with satisfactory post-operative outcomes and conduit functioning. https://www.dropbox.com/scl/fi/gzc1vzdzhzqn7niz95b8t/Robotic-McKeown-Esophagectomy-Video-3.mp4?rlkey=c4ja7s1aob10ah6ps500z7y29&amp;dl=0

1239TiP NEO-PIONEER: Neoadjuvant hypofractionated radiotherapy plus tislelizumab with anlotinib followed by adjuvant tislelizumab with anlotinib in patients with resectable non-small cell lung cancer (NSCLC): A phase II trial in progress

1239TiP NEO-PIONEER: Neoadjuvant hypofractionated radiotherapy plus tislelizumab with anlotinib followed by adjuvant tislelizumab with anlotinib in patients with resectable non-small cell lung cancer (NSCLC): A phase II trial in progress

Patterns of Locoregional Pancreatic Cancer Recurrence After Total Neoadjuvant Therapy and Implications on Optimal Neoadjuvant Radiation Treatment Volumes

PurposeThis study aimed to generate a map of local recurrences after neoadjuvant chemotherapy and radiation (total neoadjuvant therapy [TNT]) followed by surgical resection for pancreatic ductal adenocarcinoma (PDAC). Such recurrence patterns will serve to inform radiation treatment planning volumes that should be given in the neoadjuvant setting. Methods and MaterialsLocoregional recurrences after TNT followed by surgery treated between 2009 and 2022 were radiologically identified. Recurrences were individually segmented using MIM software and complied in a single base scan. All contour compilations were used to create a threshold contour encompassing 80% of recurrences among all patients, head only, and body/tail only. The distance between organs at risk and the threshold contour were measured to design an optimal clinical target volume contour for patients treated with TNT. Recurrence patterns were also compared with existing adjuvant guidelines to assess coverage. ResultsA database of 484 patients managed with TNT for PDAC was queried. While locoregional recurrences were rare in this cohort, we identified 80 patients with either isolated locoregional or simultaneous local and distant recurrences. Patients with diagnostic imaging at the time of recurrence were identified. The majority of recurrences were partially in the field of published contouring guidelines or volumetric expansions off of vessels, and volumetric coverage was low for all. Common areas of recurrence include the aorticodiaphragmatic junction, retropancreatic duodenal nodal basin, and the region to the right of the superior mesenteric artery. A novel set of proposed neoadjuvant contours was designed to cover the central-most 80% of recurrences. ConclusionsThis is the largest collection of local/regional PDAC recurrences from a cohort of patients treated exclusively with TNT. Patterns of local/regional recurrence using TNT in PDAC vary significantly from those patients with PDAC treated with a surgery-first approach. Novel contouring guidelines presented in this study can help to ensure optimal coverage of high risk regions and avoid reliance on the current adjuvant guidelines to guide treatment planning.

1164P The influence of neoadjuvant radiotherapy on surgical management and prognostic outcomes in locally advanced rectal neuroendocrine carcinoma

1164P The influence of neoadjuvant radiotherapy on surgical management and prognostic outcomes in locally advanced rectal neuroendocrine carcinoma

Assessment of Intermediate-Term Mortality Following Pancreatectomy for Cancer.

Pancreatic cancer remains highly lethal and resection represents the only chance for cure. Although patients are counseled regarding short-term (0-3 months) mortality, little is known about mortality 3-6 months (intermediate-term) following surgery. We assessed predictors of intermediate-term mortality, evaluated hospital-level variation, and developed a nomogram to predict intermediate-term mortality risk. Patients undergoing pancreatic cancer resection were identified from the National Cancer Database (2010-2020). Multivariable logistic regression identified predictors of intermediate-term mortality and assessed differences between short-term and intermediate-term mortality. Multinomial regression grouped by intermediate-term mortality quartiles evaluated hospital-level variation. A neural network model was constructed to predict intermediate-term mortality risk. All statistical tests were 2-sided. Of 45,297 patients, 3,974 (8.9%) died within 6-months of surgery of which 2,216 (5.1%) were intermediate-term. Intermediate-term mortality was associated with increasing T-category, positive nodes, lack of systemic therapy, and positive margins (all p < .05) compared with survival beyond 6-months. Compared with short-term, intermediate-term mortality was associated with treatment at high-volume hospitals, positive nodes, neoadjuvant systemic therapy, adjuvant radiotherapy, and positive margins (all p < .05). Median intermediate-term mortality rate per hospital was 4.5% (IQR 2.6-6.5). Highest quartile hospitals had decreased odds of treatment with neoadjuvant systemic therapy, neoadjuvant radiotherapy, and adjuvant radiotherapy (all p < .05). The neural network nomogram was highly accurate (Accuracy: 0.9499; AUC-ROC of 0.7531) in predicting individualized intermediate-term mortality risk. Nearly 10% of patients undergoing pancreatectomy for cancer died within 6-months of which half occurred in the intermediate-term. These data have real-world implications to improve shared decision-making when discussing curative-intent pancreatectomy.

Post-hoc analysis of clinicopathological factors affecting lateral lymph node metastasis based on STELLAR study for rectal cancer

PurposeIn post-hoc analyses of phaseIII randomized controlled study(STELLAR), to analyzethe prognostic impact oflateral pelvic lymph node (LPLN)metastasis in locally advanced rectal cancer (LARC). MethodsLPLN metastasis was defined as a short diameter > 7 mm on magnetic resonance imaging (MRI).The studyincluded 591 patients with LARC.All patients received neoadjuvant (chemo)radiotherapy combined withradical resection. ResultsAmong 591 patients, 99 (16.8 %) were diagnosed with LPLN metastasis, mostly with unilateral metastasis (79.8 %), with internal iliac lymph node metastasis being more common (81.8 %).Significant differences were found among with and without LPLN metastasis in rectal segmentation (P=0.001),N disease (P<0.001), mesenteric LN metastasis or not (P=0.030). The median follow-up timewas 34.0 months, three-year disease-free survival (DFS),overall survival (OS), andmetastasis-free survival (MFS)were significantly lower in LPLN metastaticgroup than those in LPLN non-metastaticgroup (51.4 % vs. 68.2 %, P<0.001; 71.8 % vs. 84.2 %, P=0.006; 60.8 % vs. 80.1 %,P<0.001), respectively; while there were no significant differences in locoregional recurrence(11.4 % vs. 8.5 %, P=0.564). Multivariate analysis found that LPLN metastasis was an independent prognostic factor affecting DFS (P=0.005), OS (P=0.036),MFS (P=0.001).No significantly survival benefit was observed for the short-term radiotherapy based total neoadjuvant therapy compared to long-term concurrent chemoradiotherapy. ConclusionsLPLN metastasis observed byMRI should be considered in LARC patients, especially in populations with lowrectal cancer, N2 disease, and mesenteric LN metastasis. LPLN metastasis diagnosed by MRI is a significant and independent risk factor and is associated with worse DFS, OS, MFS.

Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: How to Select the Most Suitable?

Rectal cancer shows specific characteristics in terms of pattern of recurrence, which occurs commonly at both local and distant sites. The standard of care for locally advanced rectal cancer (LARC) including neoadjuvant chemoradiotherapy, followed by surgery based on the total mesorectal excision principles leads to a reduction in the rates of local recurrences to 6-7% at 5 years. However, the outcomes among those with high-risk lesions remain unsatisfactory. On the contrary, neoadjuvant chemoradiotherapy results in long-term morbidities among those with low-risk lesions. Furthermore, the overall survival benefit of neoadjuvant therapy is still a subject to be debated, except for patients with complete or near-complete response to neoadjuvant therapy. Total neoadjuvant therapy (TNT) is a new paradigm of management of high-risk rectal cancer that includes early administration of the most effective systemic therapy either before or after neoadjuvant radiotherapy with or without chemotherapy prior to surgery with or without adjuvant chemotherapy. TNT potentially improves disease-free survival, even though whether it can prolong survival has been debatable. Recently, neoadjuvant chemotherapy only has been proved to be non-inferior to neoadjuvant chemoradiotherapy in patients with low-risk lesions. This review intends to review the current evidences of neoadjuvant therapy and propose a more customized paradigm of management of LARC.

Increased IFN-β indicates better survival in hepatocellular carcinoma treated with radiotherapy.

Preclinical data suggest that type I interferon (IFN) responsiveness is essential for the antitumor effects of radiotherapy (RT). However, its clinical value remains unclear. This study aimed to explore this from a clinical perspective. In cohort 1, data from 152 hepatocellular carcinoma (HCC) patients who received RT were analyzed. Blood samples were taken 1 day before and 2 weeks after RT. RT was found to increase serum levels of IFN-β (a subtype of IFN-I) in HCC patients (3.42 ± 1.57 to 5.51 ± 2.11 pg/ml, P < 0.01), particularly in those with favorable responses. Higher post-RT serum IFN-β levels (≥4.77 pg/ml) were associated with better progression-free survival (HR = 0.58, P < 0.01). Cohort 2 included 46 HCC patients, including 23 who underwent preoperative RT and 23 matched control HCC who received surgical resection without RT. Formalin-fixed paraffin-embedded samples were obtained. Neoadjuvant RT significantly increased IFN-β expression in tumor tissues compared to direct surgery (8.13% ± 5.19% to 15.10% ± 5.89%, P < 0.01). Higher post-RT IFN-β (>median) indicated better disease-free survival (P = 0.049). Additionally, increased CD11c+MHCII+CD141+ antigen-presenting cell subsets and CD103+CD39+CD8+ tumor-infiltrating lymphocytes were found in the higher IFN-β group (P = 0.02, P = 0.03), which may contribute to the favorable prognosis in higher IFN-β group. Collectively, these findings suggest that IFN-β response activated by radiation may serve as a prognostic biomarker for HCC patients undergoing RT.

Risk factors and treatment strategies for local recurrence of locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by total mesorectal excision

BackgroundDespite advancements in total mesorectal excision (TME) and neoadjuvant radiotherapy, locally advanced rectal cancer remains challenging, impacting patient quality of life and mortality. This study aimed to identify the risk factors for local recurrence in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy (CRT) and assess treatment strategies for recurrence. MethodsThis retrospective analysis included 682 patients diagnosed with locally advanced rectal cancer who were treated with neoadjuvant CRT and TME at Samsung Medical Center from 2008 to 2017. The exclusion criteria ensured a homogenous cohort. Clinical staging involved colonoscopies, computed tomography, magnetic resonance imaging, and digital rectal exam. Risk factors, treatment modalities, and oncological outcomes for local recurrence were evaluated. ResultDuring a median 62-month follow-up, 47 patients (6.9 %) experienced local recurrence. The risk factors for local recurrence included a positive circumferential resection margin (CRM), venous invasion, and perineural invasion. Of the 47 patients with local recurrence, 25 (53.2 %) were considered resectable. Out of these, 23 patients underwent curative resections, and 15 (65.2 %) achieved R0 resection. Patients with R0 resections exhibited superior 5-year survival rates compared to R1-2 resection or non-surgical treatment, and there was no survival difference between R1-2 resection and non-surgical treatment. ConclusionIn locally advanced rectal cancer, positive CRM, venous invasion, and perineural invasion were associated with local recurrence. R0 resection showed favorable outcomes, emphasizing the importance of surveillance in high-risk patients. Treatment decisions should consider these factors for improved oncologic outcomes and quality of life.

Does neoadjuvant therapy contribute to increased risk in anastomotic leakage of esophageal cancer? A network meta-analysis.

Conflicting results have been reported about the impact of neoadjuvant therapy on anastomotic leakage (AL) after esophagectomy. We aimed to unravel the potential effect of neoadjuvant therapy on AL after esophagectomy through a network meta-analysis. A Bayesian network meta-analysis was performed by retrieving relevant literature from PubMed, EMbase, The Cochrane Library and Web of Science Core Collection. Randomized clinical trials (RCTs) and retrospective studies (RS) comparing the following treatment modalities were included: neoadjuvant chemoradiation (nCRT), neoadjuvant chemotherapy (nCT), neoadjuvant radiotherapy (nR), neoadjuvant immunochemotherapy (nICT), and surgery alone (SA). Subgroup analyses by radiation dose, examined lymph nodes (ELN), route of reconstruction, site of anastomosis, and surgical approach were also conducted. A total of 62 studies with 12,746 patients were included for the present study, among which 17 were RCTs. There were no significantly statistical differences observed among the five treatment modalities in AL for both RCTs (nCRT-nICT: risk ratio 1.51, 95% confidence interval 0.52-4.4; nCT-nICT: 1.71, 0.56-5.08; nICT-nR: 0.79, 0.12-8.02; nICT-SA: 0.59, 0.2-1.84) and RS (nCRT-nICT: odds ratio 1.53, 95% confidence interval 0.84-2.84; nCT-nICT: 1.56, 0.87-2.88; nICT-SA: 0.6, 0.31-1.12; nICT-nR: 1.08, 0.09-36.02). Subgroup analysis revealed that no significant difference in AL was observed among the five treatment modalities except for the impact of nCRT versus nCT (0.21, 0.05-0.73) on AL with a radiation dose ≥41.4Gy. Neoadjuvant therapy do not significantly increase the incidence of AL after esophagectomy. Administration of irradiation with a moderate dose is not associated with elevated risk in AL. Clinicians can be less apprehensive about prescribing nCRT.

Effect of Radiotherapy in Neoadjuvant Treatment of Borderline Resectable and Locally Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis

Abstract Background Pancreatic cancer is a malignant tumor with poor prognosis and bad curative effect. Previous studies did not confirm the role of radiotherapy in neoadjuvant treatment of borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC). By reviewing new findings reported in recent years, we conducted this study to evaluate the survival impact by comparing chemoradiotherapy (CRT) with chemotherapy alone. Methods PubMed, Embase, MEDLINE, Web of Science, Scopus and Cochrane Library were searched for studies reporting median overall survival (OS) in patients with BRPC or LAPC treated with neoadjuvant treatment. Secondary outcomes included progression-free survival (PFS) or disease-free survival (DFS) or recurrence-free survival (RFS) and R0 resection rate. Results A total of eighteen studies were included in the meta-analysis. OS (Hazard Ratio [HR] = 0.76, 95% confidence interval [CI]: 0.64-0.91, I2 = 61.7%) and PFS/DFS/RFS (HR = 0.72, 95% CI: 0.58-0.91, I2 = 52.3%) are both favored CRT. Although R0 resection rate was increased in CRT group, significant survival benefit of radiotherapy was found in LAPC and low resection rate subgroup in stratification analysis. Regression analysis showed that only tumor resectability was associated with OS. Conclusion For patients with LAPC and who are unlikely to receive resection, neoadjuvant radiotherapy appears to improve OS and PFS/DFS/RFS.

Nerve graft reconstruction of irradiated oncologic segmental nerve defects in the extremities: A case series

BackgroundNeurovascular involvement of extremity neoplasms is historically considered a contraindication for limb-salvage surgery, due to concerns of limb dysfunction secondary to motor and/or sensory loss. Theoretically, large nerve defects may be amenable to reconstruction using grafts, but the outcomes of these techniques in irradiated oncologic patients remain unclear. MethodsThis study investigates reconstruction of oncologic nerve defects in the extremities in patients who underwent (neo)adjuvant radiotherapy. A retrospective series of ten patients with extremity sarcoma is provided, with six lower extremity and four upper extremity cases. Reconstruction consisted of nerve grafting with or without the addition of tendon transfers. The mean duration of clinical follow-up was 42.5 months. ResultsNerve graft reconstruction led to recovery of motor or sensory function in eight out of ten patients thereby allowing functional limb preservation, with none of the patients developing significant neuropathic pain, a common complication in oncologic resections of the extremities with nerve involvement or following amputation. Thus, radiotherapy does not seem to completely preclude successful graft reconstruction of large oncologic extremity nerve defects. ConclusionsAlthough the oncologic disease itself is associated with significant mortality, the results of the nerve reconstruction were encouraging despite the concomitant use of radiation. Based on the available data and literature, we recommend to at least discuss the option of graft-based nerve reconstruction with affected patients if relevant characteristics such as patient comorbidities and the viability of recipient muscle are favorable. SynopsisIn this study, the results of nerve graft reconstruction of large sarcoma-related nerve defects were evaluated. This type of reconstruction seems feasible even in irradiated limbs, thereby aiding in functional limb preservation.

The impact of anastomotic leakage characteristics on the occurrence of anastomotic stenosis after colorectal resection, a retrospective cohort study.

Anastomotic stenosis (AS) is a common complication after colorectal resection. However, the predisposing factors for stricture formation are not fully understood. Previous studies have shown anastomotic leakage (AL) to be a risk factor for the occurrence of AS. Therefore, we aim to investigate the impact of anastomotic leakage characteristics on the occurrence of anastomotic stenosis after colorectal resection. Consecutive patients with AL following elective, sphincter preserving, colorectal resection, with or without diversion ostomy, between January 2009 and March 2023 were identified from a prospectively collected database. The characteristics of the anastomotic leakage, patient baseline and operative characteristics as well as the postoperative outcomes were analyzed using univariate and multivariate logistic regression to identify factors associated with the occurrence of post-leakage AS. A total of 129 patients developed AL and met the inclusion criteria. Among these, 28 (21.7%) patients were diagnosed with post-leakage AS. There was a significantly higher frequency of patients with neoadjuvant radiotherapy (18% vs 3%; p = .026) and hand-sewn anastomoses (39% vs 17%; p = .011) within the AS group. Furthermore, the extent of the anastomotic defect was significantly higher in the AS group compared with the non-AS group (50%, IQR 27-71 vs. 20%, IQR 9-40, p = 0.011). Similar findings were observed between the study groups regarding age, sex, BMI, ASA score, medical comorbidities, diagnosis, surgical procedure, surgical approach (open vs. minimally invasive), and anastomotic fashioning (side-to-end vs. end-to-end). On multivariate analysis, the extent of the anastomotic defect (OR 1.01; 95% CI 1.00-1.03; p = 0.034) and hand-sewn anastomoses (OR 2.68; 95% CI 1.01-6.98; p = 0.043) were confirmed as independent risk factors for post-leakage AS. No correlation could be observed between the occurrence of post-leakage AS and the ISREC grading of AL, the anastomotic height or the management of AL. Time to ostomy reversal was significantly longer in the AS group (202d, IQR 169-275 vs. 318d IQR 192-416, p = 0.014). The extent of the anastomotic defect and hand-sewn anastomoses were confirmed as independent risk factors for the occurrence of post-leakage AS. No correlation could be observed between the ISREC grading of AL, the anastomotic height or AL management, and the occurrence of post-leakage AS.