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Background: Locally advanced rectal cancer (LARC) poses a significantly challenge in clinical management, requiring a multimodal treatment approach. Among innovative strategies, Total Neoadjuvant Therapy (TNT) has emerged, delivering all planned chemotherapy before surgery. Objective: Our aim was to evaluate the real-world application and efficacy of TNT and to compare it with the non-TNT standard strategy. Methods: This retrospective study compared locally advanced rectal adenocarcinoma patients treated with Total Neoadjuvant Therapy (TNT) in 2022 with those who underwent traditional chemoradiotherapy (CRT) in 2020–2021. The primary endpoints were the pathologic complete response rate and the sustained clinical complete response rate in patients under W&W. Results: Among 107 patients (54.2% male, mean age 62.48 years), non-TNT (67 patients) and TNT (40 patients) mean follow-ups were 26.7 and 8.2 months, respectively. No differences in gender(p = 0.163), staging (p = 0.707), or location (p = 0.727) were noted. TNT patients received more short-course radiotherapy (42.5% vs1.5%, p < 0.001). Clinical responses favored TNT (p = 0.030) with no significant differences in pathological responses, recurrence rates, or survival. TNT exhibited higher chemotherapy completion (p = 0.007) and lower adverse events (p < 0.001). Post-surgery events showed no significant differences (p = 0.470). Single center with retrospective design and carries limitations that may restrict the generalizability of the findings and the relatively short follow-up duration are our main limitations. Conclusion: Our data add to the body of literature favoring the TNT treatment strategy for locally advanced rectal cancer, aiming to achieve comparable complete response rates with less adverse events. [ABSTRACT FROM AUTHOR]

Abstract Background Locally advanced rectal cancer (LARC) poses a significantly challenge in clinical management, requiring a multimodal treatment approach. Among innovative strategies, Total Neoadjuvant Therapy (TNT) has emerged, delivering all planned chemotherapy before surgery. Objective Our aim was to evaluate the real-world application and efficacy of TNT and to compare it with the non-TNT standard strategy. Methods This retrospective study compared locally advanced rectal adenocarcinoma patients treated with Total Neoadjuvant Therapy (TNT) in 2022 with those who underwent traditional chemoradiotherapy (CRT) in 2020–2021. The primary endpoints were the pathologic complete response rate and the sustained clinical complete response rate in patients under W&W. Results Among 107 patients (54.2% male, mean age 62.48 years), non-TNT (67 patients) and TNT (40 patients) mean follow-ups were 26.7 and 8.2 months, respectively. No differences in gender(p = 0.163), staging (p = 0.707), or location (p = 0.727) were noted. TNT patients received more short-course radiotherapy (42.5% vs1.5%, p

Background: In patient with a complete or near-complete clinical response after neoadjuvant treatment for locally advanced rectal cancer, the organ-sparing approach [watch & wait (W&W) or local excision (LE)] is a possible alternative to major rectal resection. Although, in case of local recurrence or regrowth, after these treatments, a total mesorectal excision (TME) can be operated. Method: In this retrospective study, we selected 120 patients with locally advanced rectal cancer (LARC) who had a complete or near-complete clinical response after neoadjuvant treatment, from June 2011 to June 2021. Among them, 41 patients were managed by W&W approach, whereas 79 patients were managed by LE. Twenty-three patients underwent salvage TME for an unfavorable histology after LE (11 patients) or a local recurrence/regrowth (seven patients in LE group – five patients in W&W group), with a median follow-up of 42 months. Results: Following salvage TME, no patients died within 30 days; serious adverse events occurred in four patients; 8 (34.8%) patients had a definitive stoma; 8 (34.8%) patients undergone to major surgery for unfavorable histology after LE – a complete response was confirmed. Conclusion: Notably active surveillance after rectal sparing allows prompt identifying signs of regrowth or relapse leading to a radical TME. Rectal sparing is a possible strategy for LARC patients although an active surveillance is necessary. [ABSTRACT FROM AUTHOR]

Aim: The standard treatment for low rectal cancer is preoperative chemoradiotherapy followed by surgery with low anterior resection with diverting ileostomy or abdominoperineal resection, both of which have significant long‐term effects on bowel and sexual function. Due to the high morbidity of surgery, there has been increasing interest in nonoperative management for low rectal cancer. The aim of this work is to conduct a pan‐Canadian Phase II trial assessing the safety of nonoperative management for low rectal cancer. Method: Patients with Stage II or III low rectal cancer completing chemoradiotherapy according to standard of care at participating centres will be assessed for complete clinical response 8–14 weeks following completion of chemoradiotherapy. Subjects achieving a clinical complete response will undergo active surveillance including endoscopy, imaging and bloodwork at regular intervals for 24 months. The primary outcome will be the rate of local regrowth 2 years after chemoradiotherapy. Nonoperative management will be considered safe (i.e. as effective as surgery to achieve local control) if the rate of local regrowth is ≤30% and surgical salvage is possible for all local regrowths. Secondary outcomes will include disease‐free and overall survival. Conclusion: The results will be highly clinically relevant, as it is expected that nonoperative management will be safe and lead to widespread adoption of nonoperative management in Canada. This change in practice has the potential to decrease the number of patients requiring surgery and the costs associated with surgery and long‐term surgical morbidity. [ABSTRACT FROM AUTHOR]

Aim: Health Technology Wales sought to evaluate the clinical and cost‐effectiveness of contact X‐ray brachytherapy (CXB) for early‐stage rectal cancer. Methods: Relevant studies were identified through systematic searches of MEDLINE, Embase, Cochrane Library and Scopus. A cost‐utility model was developed to estimate the cost‐effectiveness of CXB in National Health Service Wales, using results of the Organ Preservation in Early Rectal Adenocarcinoma (OPERA) trial. Patient perspectives were obtained through the Papillon Patient Support group and All‐Wales Cancer Network. Results: The OPERA randomized controlled trial showed that CXB improved complete response and organ preservation rates compared with external‐beam boost for people with T2–3b, N0–1, M0 rectal cancer who are fit for surgery. Managing more of this population non‐operatively after CXB was estimated to provide 0.2 quality‐adjusted life years at an additional cost of £887 per person. CXB was cost effective compared with external‐beam boost at a cost of £4463 per quality‐adjusted life year gained. This conclusion did not change in scenario analysis and CXB was cost effective in 91% of probabilistic sensitivity analyses. Patients valued receiving clear information on all available options to support their individual treatment choices. The detrimental impact of a stoma on quality of life led some patients to reject the idea that surgery was their only option. Conclusion: This evidence review and cost‐utility analysis indicates that CXB is likely to be clinically and cost effective, as part of a watch and wait strategy for adults fit for surgery. Wider access to CXB is supported by patient testimonies. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical and immunological characteristics of anti-synthetase syndrome (ASS) patients overlap with rheumatoid arthritis (RA)., Methods: A retrospective analysis was conducted on ASS patients with arthritis who were treated at Peking University People' s Hospital. Data collected included demographic information, clinical manifestations, laboratory features, lymphocyte subsets in peripheral blood, and treatments. The patients with ASS were divided into two groups based on the presence or absence of RA for comparative analysis., Results: A total of 104 ASS patients with arthritis were included, among whom 23.1% (24/104) were diagnosed with RA. The ASS with RA group had a significantly higher incidence of rapidly progressive interstitial lung disease (RP-ILD) (41.7% vs . 17.6%, P =0.032), number of tender joints [10 (7, 14) vs . 4 (0, 8), P < 0.001], number of swollen joints [4 (2, 8) vs . 2 (0, 4), P =0.012], and rate of bone erosion (47.8% vs . 2.5%, P < 0.001) compared with the non-RA group. Levels of platelets [(289.57±68.74)×10 3 /μL vs . (247.94±77.04)×10 3 /μL, P =0.022], erythrocyte sedimentation rate (ESR) [43 (19, 59) mm/h vs . 18 (10, 44) mm/h, P =0.019], and C-reactive protein (CRP) [19.20 (4.80, 55.36) mg/L vs . 5.68 (1.10, 14.96) mg/L, P =0.006] were found significantly higher in the ASS with RA group than those in non-RA group. Analysis of immune cells in peripheral blood mononuclear cell (PBMC) showed that significantly decreased proportions of CLA + Treg cells [(11.12±4.10)% vs . (17.22±8.49)%, P =0.003], B cells [8.56% (4.80%, 11.90%) vs . 14.55% (8.75%, 20.29%), P =0.025], and natural killer (NK) cells [7.56% (4.65%, 13.20%) vs . 13.25% (7.46%, 19.25%), P =0.045] in the overlap group compared with non-RA group. Proportion of Naïve Th cells [(52.66±17.66)% vs . (40.76±14.96)%, P =0.033)] was significantly increased in overlap group compared with non-RA group. Overlap group had lower rate of complete clinical response than non-RA group (16.7% vs . 43.8%, P =0.031)., Conclusion: Among ASS patients with arthritis, those with RA have more severe lung and joint involvement and a lower treatment response rate, highlighting the need for early recognition and aggressive intervention.

Objective: Chemoradiation followed by esophagectomy is a standard treatment option for patients with locally advanced esophageal cancer (LAEC). Esophagectomy is a high-risk procedure, and recent evidence suggests select patients may benefit from omitting or delaying surgery. This study aims to compare surgery versus active surveillance for LAEC patients with complete clinical response (cCR) after neoadjuvant chemoradiotherapy (nCRT)., Methods: Decision analysis with Markov modeling was used. The base case was a 60-year-old man with T3N0M0 esophageal cancer with cCR after nCRT. The decision was modeled for a 5-year time horizon. Primary outcomes were life-years and quality-adjusted life-years (QALY). Probabilities and utilities were derived through the literature. Deterministic sensitivity analyses were performed using ranges from the literature with consideration for clinical plausibility., Results: Surgery was favored for survival with an expected life-years of 2.89 versus 2.64. After incorporating quality of life, active surveillance was favored, with an expected QALY of 1.70 versus 1.56. The model was sensitive to probability of recurrence on active surveillance (threshold value 0.598), probability of recurrence being resectable (0.318), and disutility of previous esophagectomy (-0.091). The model was not sensitive to perioperative morbidity and mortality., Conclusions: Our study finds that surgery increases life expectancy but decreases QALY. Although the incremental change in QALY for either modality is insufficient to make broad clinical recommendations, our study demonstrates that either approach is acceptable. As probabilities of key factors are further defined in the literature, treatment decisions for patients with LAEC and a cCR after nCRT should consider histology, patient values, and quality of life., Competing Interests: Conflict of Interest Statement Dr Kidane discloses receiving speaker and advisory board honoraria from AstraZeneca, Merk, Bristol-Meyers-Squibb, and Medtronic. Dr Kidane is the associate statistical editor for the American Association for Thoracic Surgery. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background This study aimed to evaluate tumor-infiltrating lymphocytes (TILs) as predictors of response to neoadjuvant chemotherapy (NACT) in patients with locally advanced breast cancer (LABC). Methods Overall, 35 patients with LABC were included in the study. Information on demographic profile, medical history, and signs and symptoms was collected for each patient, and a complete clinical evaluation was conducted, which involved physical examination, imaging studies (mammogram/ultrasound imaging), biopsy of each patient, and a metastatic workup. Patient consent was obtained for core-needle biopsy under local anesthesia, followed by a pathologic assessment of the type of breast cancer, before NACT and after mastectomy. Patients treated with NACT were followed up for response using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and were scheduled for modified radical mastectomy (MRM) on completion of NACT. MRM specimens were sent for immunohistopathologic analysis for CD3 and CD5, and for grading. Subsequently, correlations between TILs and grading with NACT response and type of cancer were analyzed. Results Of the 35 patients, 24 were positive for CD3. A correlation was identified between NACT in LABC patients and CD3 TILs, as 68.6% of patients were CD3-positive, with 54.3% showing stromal CD3 variants and 14.3% showing intramural CD3 variants. This result indicates that CD3 TILs can be an indicator of response to NACT in LABC patients. In the sample, 48.6% of patients showed CD5 positivity, with stromal predominance. Overall, 17 patients (48.6%) had a RECIST complete response to NACT, 16 (45.7%) had a partial response, and 1 (2.9%) had progressive disease. Therefore, the study showed a significant response to NACT in LABC patients (p-value < 0.0001), and reductions in tumor size could be evaluated using RECIST criteria. Conclusions NACT had a significant effect on tumors, as shown by RECIST assessments in patients with LABC. TILs can be used as promising prognostic markers to evaluate and predict patients' responses to NACT. Evaluating TILs is expensive but may be useful for the diagnosis and prediction of immunologic responses in breast cancer and other types of carcinomas following chemotherapy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Vardhaman Mahavir Medical College and Safdarjung Hospital issued approval IEC/VMMC/SJH/THESIS/2020-11/CC-131. After a detailed scrutinization, discussion and assessment of the research project/thesis, the members of IPRC arrived at a unanimous resolution approving this research project/thesis for all ethical purposes. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kumar et al.)

Background Watchful waiting and non-operative management of patients with complete clinical response to neoadjuvant treatment in locally advanced rectal cancers is an emerging practice now, especially in patients whose surgery would require permanent stoma. Methodology This is a retrospective study of patients presenting to the National Cancer Institute, Cairo University, Egypt from January 2005 to December 2019 with pathologically proven locally advanced rectal cancer who had a complete clinical response after neoadjuvant treatment. Patients who underwent surgery after achieving complete clinical response and patients who were kept under watchful waiting were compared in terms of overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS), and local recurrence-free survival (LRFS). Results Of the 51 patients identified, 31 (61%) went to surgery, and 20 (39%) were kept under watchful waiting. There was no difference in five-year OS between both groups (65% for both, p = 0.57). Five-year DFS for the watchful waiting group was 68% versus 62% for the surgery group (p = 0.75). Five-year LRFS was 100% in the watchful waiting group versus 83% in the surgery group (p = 0.15). Conclusions Watchful waiting after a complete clinical response to neoadjuvant treatment in locally advanced rectal cancer is feasible without compromising disease-related outcomes, especially in patients with distal rectal cancers requiring permanent stoma after surgery. However, further prospective validation is needed., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board of National Cancer Institute, Cairo University, Egypt issued approval NA. IRB approval was obtained before data collection from the ethical committee, National Cancer Institute, Cairo University. A waiver for patient consent was obtained given the retrospective nature of the study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ashour et al.)

Background: Rectal malignancy ranks among the most prevalent malignancies in humans. Neoadjuvant chemoradiotherapy (nCRT) is advocated as the standard treatment for locally advanced rectal cancer. In patients who achieve complete clinical response (cCR), successive surgical intervention may result in favorable immediate and long-lasting results; however, it may be associated with decreased quality of life. This study aims to evaluate the incidence of local recurrence in rectal adenocarcinoma between patients who underwent a watch-and-wait approach and those who underwent abdominoperineal resection following the achievement of a cCR after nCRT., Methods: This is an analytic cohort study that included 68 patients and was conducted in Baghdad Teaching Hospital/Medical City, Baghdad. The data were collected from the 1st of April 2021 to the 1st of October 2023. All patients with stage II and III rectal adenocarcinoma who achieved cCR after receiving nCRT were included in the study., Results: There was no statistically significant difference between the two study groups regarding non-regrowth disease-free survival (p-value = 0.708). Cox-regression multivariate analysis revealed that baseline T stage and serum carcinoembryonic antigen (CEA) were significantly associated with locoregional failure., Conclusion: The present study reveals that implementing the watch-and-wait strategy had the benefit of avoiding major surgery, stoma, and their complications without coming at the cost of reduced locoregional recurrence., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Iraqi Board for Medical Specializations issued approval 1053. Verbal and written consent has been obtained from all participants before data collection. An official letter of approval has been obtained from the Scientific Committee of the Scientific Council of General Surgery – Iraqi Board for Medical Specializations. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mahmood et al.)