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Objective: To investigate the specificity of Target of Myb1-Like1 (Tom1L1) expression in colorectal adenocarcinoma tissues and analyze the predictive value of Tom1L1 in the efficacy of neoadjuvant chemotherapy for patients with rectal adenocarcinoma., Methods: The cancerous tissues and paracancerous normal tissues of 102 patients diagnosed with colorectal adenocarcinoma without treatment were selected; quantitative polymerase chain reaction (qPCR), Western blot and immunohistochemistry (IHC) were adopted to validate the expression level of Tom1L1 in the two groups. Furthermore, 34 patients with locally progressive mid-low rectal adenocarcinoma, who were treated with neoadjuvant Xelox chemotherapy prior to the operation, IHC was adopted to detect the expression of Tom1L1 protein in patients before and after neoadjuvant chemotherapy and to analyze the relationship between the expression level of Tom1L1 and the sensitivity of neoadjuvant therapy., Results: The results of qPCR, Western blot and IHC showed that the expression of Tom1L1 in colorectal adenocarcinoma tissues was significantly higher than that in paracancerous normal tissues, with a statistically significant difference (P < 0.01); Neoadjuvant chemotherapy was significantly more effective in patients with low expression of Tom1L1 protein than in those with high expression of Tom1L1 protein, with a statistically significant difference (P < 0.05)., Conclusions: Tom1L1 is highly expressed in colorectal adenocarcinoma tissues; neoadjuvant Xelox chemotherapy can have an impact on Tom1L1 expression in progressive rectal cancer; patients with locally progressive mid-low rectal adenocarcinoma who have low Tom1L1 expression are more sensitive to neoadjuvant chemotherapy., Competing Interests: Declarations Ethics approval and consent to participate Informed consent and approval were obtained from all the patients and the Ethics Committee of The First Affiliated Hospital of Hebei North University (K2022058). The research was conducted in accordance with the guidelines of the Ethics Committee listed in the Ethics Statement. Patients signed informed consent regarding publishing their data and images. Consent for publication Written informed consent was obtained from the patient’s parent for publication of this case report and the accompanying images. A copy of the written consent obtained from the parent of the patient in this case report is available for review by the editorial office of this journal. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

This study explores the potential use of ChatGPT, an AI-based language model, in assessing herbal-drug interactions (HDi) to enhance clinical decision-making. HDi can pose significant health risks by reducing drug efficacy or causing unwanted side effects. Clinical pharmacists play a key role in identifying these HDIs, and currently, there are limited tools available for checking drug interactions. The research focuses on a case study of a rectal adenocarcinoma patient treated with capecitabine and 26 supplements, which contain a total of 80 herbal substances. ChatGPT 3.5 was asked three questions regarding potential HDIs: "Are there possible HDIs?", "What is the pharmacokinetic mechanism?", and "What is the bibliographic source of the interaction?". The results were reviewed by an oncology clinical pharmacist and compared to existing databases and independent bibliographic research. The findings highlight ChatGPT's advantage in processing large amounts of data quickly, with 16% of interactions classified as "unlikely", confirmed by the pharmacist. However, 73% of the suggested mechanisms were false positives, and 4% were categorized as "hallucinations". Additionally, most of the bibliographic sources provided by ChatGPT were outdated or unavailable. While ChatGPT proves useful for initial HDI screening, its limitations include outdated data (last updated in January 2022), lack of access to private databases, and occasional inaccuracies. Further applications of AI in this area are recommended, though expert validation remains essential in the clinical decision-making process.

Background/aim: During low anterior rectal resection for rectal cancer, a protective ileostomy (PI) is routinely created to reduce the severity of anastomotic complications. The aim of this study was to investigate the side-effects of PI during adjuvant chemotherapy., Patients and Methods: A retrospective cohort of patients was operated on for non-metastatic rectal cancer with a PI during 2005-2022. Patients treated with adjuvant chemotherapy (AC) were compared with those not receiving AC. A subgroup analysis compared patients with early PI closure (<10 weeks) and those with a PI in place during chemotherapy., Results: A total of 242 patients were included: 178 (73.6%) without adjuvant chemotherapy and 64 (26.4%) with. History, tumour location, neoadjuvant treatment and postoperative follow-up were similar for both groups. Patients treated with AC had a greater risk of renal failure (37.5% vs. 14.6%, p=0.0002), ionic disorders (45.3% vs. 26.9% p=0.008), malnutrition (23.4% vs. 5.6%, p=0.0002) and rehospitalization (35.9% vs. 18.5% p=0.007). Patients treated with AC needed significant dose adjustments of oxaliplatin in 40.6% of cases, this adjustment being higher in patients with a PI compared to patients with early closure (47.1 vs. 9.1%, p=0.021)., Conclusion: Presence of a PI during chemotherapy predisposes to increased episodes of renal failure, and requires major adaptation of chemotherapy doses, especially of oxaliplatin., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Standardized patient-reported outcomes (PRO) monitoring during and after rectal cancer treatment provides insight into treatment-related toxicities patients experience and improves health-related quality-of-life as well as overall survival. We aimed to select a subset of the PRO version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) for standardized monitoring of treatment-related symptomatic toxicities in rectal cancer., Methods: We used a mixed methods approach including a literature review, and semi-structured interviews with health care providers (HCPs) involved in rectal cancer care and rectal cancer patients. Results from literature and interviews were summarized and used in a modified Delphi procedure to select a PRO-CTCAE subset specific for rectal cancer., Results: Twenty-six PRO-CTCAE symptomatic toxicities were identified from literature. Fifteen HCPs from multiple disciplines (medical, radiation and surgical oncology), and a heterogeneous group of fifteen rectal cancer patients treated with chemotherapy and/or radiotherapy and/or surgery, participated in semi-structured interviews. Ten HCPs (67%) and nine patients (90%) participated in the first Delphi round. The final selected PRO-CTCAE core-subset contained 16 symptomatic toxicities: 'diarrhea', 'fecal incontinence', 'constipation','bloating of the abdomen', 'pain in the abdomen', 'vomiting', 'decreased libido', 'pain during vaginal sex', 'ability to achieve and maintain erection', 'fatigue', 'anxiety', 'feeling that nothing could cheer you up', 'urinary incontinence', 'painful urination', 'general pain', and 'hand-foot syndrome'., Conclusion: Based on a comprehensive mixed methods study, a PRO-CTCAE subset for standardized treatment-related symptomatic toxicity monitoring in rectal cancer was identified. Assessment of the effectiveness and compliance of symptomatic toxicity monitoring using this subset is recommended., (© 2024. The Author(s).)

Background: Colorectal cancer is a prevalent and serious health concern globally, particularly among the elderly population. Laparoscopic surgery is a commonly used approach for colorectal cancer treatment. However, the use of appropriate anesthesia and muscle relaxants is essential to ensure optimal surgical outcomes. Elderly patients undergoing surgery often have unique physiological characteristics and comorbidities, such as hypertension, diabetes, and coronary heart disease. These factors can affect treatment efficiency and patient outcomes., Objective: This study aimed to investigate the impact of different target-controlled infusion concentrations of rocuronium bromide on elderly patients undergoing laparoscopic colorectal cancer surgery., Methods: This is a prospective randomized controlled study. Ninety senior adults who underwent laparoscopic colorectal cancer surgery at our hospital between September 2018 and May 2020 were selected as the eligible participants. They were randomly divided into three groups: the low-dose group (0.6 mg/L of rocuronium bromide), the middle-dose group (0.9 mg/L of rocuronium bromide), and the high-dose group (1.2 mg/L of rocuronium bromide). The purpose of this division was to administer target-controlled infusions of rocuronium bromide to maintain skeletal muscle relaxation during the surgical procedure. Data on various outcome measures, including skeletal muscle relaxation effectiveness, patient satisfaction, skeletal muscle relaxation recovery times and indices, extubation duration, and remifentanil dosage, were collected and analyzed., Results: The middle-dose group and the high-dose group exhibited notably higher levels of satisfaction with skeletal muscle relaxation compared to the low-dose group. As the rocuronium bromide dosage increased, the patients experienced prolonged recovery times and had higher skeletal muscle indices (P < .05). Additionally, the middle-dose group demonstrated significantly reduced extubation times and lower remifentanil dosages compared to the other groups (P < .05). The enhanced satisfaction levels in the middle-dose and high-dose groups, indicating that higher concentrations of rocuronium bromide may be more effective in achieving optimal skeletal muscle relaxation during laparoscopic colorectal cancer surgery. The prolonged recovery times and higher skeletal muscle indices associated with increased dosage suggest a dose-dependent effect on muscle relaxation., Conclusion: For elderly patients undergoing laparoscopic rectal cancer surgery, the use of a target-controlled infusion of 0.9 mg/L of rocuronium bromide appears to be a viable option. It maintains adequate skeletal muscle relaxation, shortens postoperative recovery time, and reduces the demand for remifentanil, demonstrating excellent potential for clinical application. These findings provide valuable insights for anesthesiologists and healthcare professionals involved in the perioperative management of elderly patients undergoing laparoscopic rectal cancer surgery. Implementing the optimized dosage of rocuronium bromide can contribute to enhanced surgical outcomes, improved patient satisfaction, and more efficient resource utilization in the clinical setting.

Purpose: Regulatory guidance suggests capturing patient-reported overall side effect impact in cancer trials. We examined whether the Functional Assessment of Cancer Therapy (FACT) GP5 item ("I am bothered by side effects of treatment") post-neoadjuvant chemotherapy/radiotherapy differed between oxaliplatin vs. non- oxaliplatin arms in the National Surgical Adjuvant Breast and Bowel Project (NSABP) R-04 trial of stage II-III rectal cancer patients., Methods: The R-04 neoadjuvant trial compared local-regional tumor control between patients randomized to receive 5-fluorouracil or capecitabine with radiation, with or without oxaliplatin (4 treatment arms). Participants completed surveys at baseline and immediately after chemoradiotherapy. GP5 has a 5-point response scale: "Not at all" (0), "A little bit" (1), "Somewhat" (2), "Quite a bit" (3), and "Very much" (4). Logistic regression compared the odds of reporting moderate-high side effect impact (GP5 2-4) between patients receiving oxaliplatin or not after chemoradiotherapy, controlling for relevant patient characteristics. We examined associations between GP5 and other patient-reported outcomes reflecting side effects., Results: Analyses were performed among 1132 study participants. Participants receiving oxaliplatin were 1.58 times (95% CI: 1.22-2.05) more likely to report moderate-high side effect bother at post-chemotherapy/radiation. In both arms, worse overall side effect impact was associated with patient-reported diarrhea, nausea, vomiting, and peripheral sensory neuropathy (p < 0.01 for all)., Conclusion: This secondary analysis of R-04 found that GP5 distinguished between patients receiving oxaliplatin or not as part of their post-neoadjuvant chemoradiotherapy, adding patient-centric evidence on the reduced tolerability of oxaliplatin and demonstrating that GP5 is sensitive to known toxicity differences between treatments., Clinicaltrials: GOV: NCT00058474., (© 2024. The Author(s).)

Total neoadjuvant therapy (TNT) of rectal cancer improves rates of pathological complete remission and progression-free survival. With improved clinical response rates, interest grew in a non-operative approach/watch and wait (WaW) for this disease. In 2020, the working groups of ACO/AIO/ARO published a consensus statement on the use of TNT, including a non-operative approach. However, the best combination scheme remains unclear. Despite the increasing use of TNT, there is a lack of comprehensive data on its current implementation and practices. To address this knowledge gap, a multicenter survey was conducted to capture the use of TNT protocols in German-speaking radiotherapy departments. At the beginning of 2023, a GDPR-compliant online survey was conducted in Germany, Austria, and German-speaking Switzerland. The questionnaire comprised 43 questions covering various aspects of TNT, including chemotherapy and WaW concepts. Most respondents (98.4%) confirmed awareness of the consensus on TNT for rectal cancer. Institutions treated an average of 30.22 rectal cancer patients annually. Most respondents (76.2%) reported treating over 80% of patients neoadjuvantly. Regarding TNT, 33.3% treated 21-50% with such a protocol. No significant association was found between the institution type and TNT application. In 62/63 cases, tumor board discussion was standard before offering TNT. VMAT was the predominant technique (82.5%). For rectal cancer dosing, the 50/50.4Gy scheme was most common, followed by 45Gy with a boost and the 5 × 5Gy scheme. Dosing schemes for TNT varied slightly, with more participants reporting the use of 5 × 5Gy compared to radiation therapy for rectal cancer in general. CBCT was the primary IGRT method (88.9%). Larger hospitals typically administered chemotherapy themselves, while private practices collaborated with medical oncologists (p < 0.0001). The most common concurrent chemotherapy drugs were 5-fluorouracil/capecitabine (64.4%) and oxaliplatin (37.3%). A WaW strategy was reported to be institutional implemented by 63.8%. The timing of offering WaW was split, with 50% offering it after radiochemotherapy and 47% during the informed consent talk. For planned WaW, 62% prefer normofractionated TNT. TNT appears to be widely implemented in the German-speaking radio-oncological community, regardless of the type of institution. Image-guided therapy, multidisciplinary team decisions, and internal guidelines play an important role. TNT seems to have already altered treatment protocols for rectal cancer toward an organ-preserving approach in selected cases. In these WaW cases, normofractionation appears to be preferred over hypofractionation., (© 2024. The Author(s).)

Immuno-oncological cancer management is shifting to neoadjuvant treatments. In patients with gastrointestinal cancers, particularly locally advanced rectal cancer, neoadjuvant chemoimmunotherapy often induce complete responses, hence avoiding surgical intervention. Recent clinical trials indicate that combinations of oxaliplatin-based chemotherapy and PD-1/PD-L1-targeting immunotherapy can be safely administered before surgery with curative intent., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Background: Locally advanced rectal cancer (LARC) poses unique challenges in treatment, with current neoadjuvant chemoradiotherapy (NA-CRT) showing limitations. The CapeOX regimen emerges as a potential less aggressive neoadjuvant chemotherapy (NAC) for LARC., Methods: We conducted a retrospective study involving treatment-naïve patients with LARC from March 2014 to March 2021 who received 2-4 cycles of CapeOX NAC followed by radical surgery. Treatment response was evaluated using tumor regression grade (TRG), MRI-based TRG (MRI-TRG), and Neoadjuvant Rectal (NAR) score., Results: 94.7% of patients experienced symptom improvement and 96.4% achieved sphincter-preserving surgery. Post-NAC showed significant tumor regression and MRI confirmed a tumor length reduction (P < 0.001). Clinical and pathological staging discrepancies post-NAC suggest broader therapeutic advantages. 5-year overall and disease-free survival rates were 78.4% and 73.4%. NAR scores provided better prognostic accuracy than MRI-TRG., Conclusion: CapeOX NAC presents notable benefits for LARC patients and its clinical significance may be underestimated. The NAR score demonstrates superior prognostic value over MRI-TRG., (© 2024. The Author(s).)

Background: Neoadjuvant chemoradiotherapy followed by total mesorectal excision is a standard treatment for locally advanced rectal cancer. Mismatch repair-deficient locally advanced rectal cancer (LARC) was highly sensitive to PD-1 blockade. However, most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) subtypes for which PD-1 blockade is ineffective. Radiation can trigger the activation of CD8 + T cells, further enhancing the responses of MSS/pMMR rectal cancer to PD-1 blockade. Radioimmunotherapy offers a promising therapeutic modality for rectal cancer. Progenitor T exhausted cells are abundant in tumour-draining lymph nodes and play an important role in immunotherapy. Conventional irradiation fields include the mesorectum and regional lymph nodes, which might cause considerable damage to T lymphocytes and radiation-induced fibrosis, ultimately leading to a poor response to immunotherapy and rectal fibrosis. This study investigated whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be effective in patients with MSS/ pMMR LARC., Methods: This was a open-label, single-arm, multicentre, prospective phase II trial. 32 LARC patients with MSS/pMMR will receive node-sparing modified short-course radiotherapy (the irradiated planned target volume only included the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by CAPOX and tislelizumab. CAPOX and tislelizumab will be started two days after the completion of radiotherapy: oxaliplatin 130 mg/m 2 intravenous infusion, day 1; capecitabine 1000 mg/m 2 oral administration, days 1-14; and tislelizumab 200 mg, intravenous infusion, day 1. There will be four 21-day cycles. TME will be performed at weeks 14-15. We will collect blood, tumour, and lymphoid specimens; perform flow cytometry and in situ multiplexed immunofluorescence detection; and analyse the changes in various lymphocyte subsets. The primary endpoint is the rate of pathological complete response. The organ preservation rate, tumour regression grade, local recurrence rate, disease-free survival, overall survival, adverse effects, and quality of life will also be analysed., Discussion: In our research, node-sparing modified radiotherapy combined with immunotherapy probably increased the responsiveness of immunotherapy for MSS/pMMR rectal cancer patients, reduced the occurrence of postoperative rectal fibrosis, and improved survival and quality of life. This is the first clinical trial to utilize a node-sparing radiation strategy combined with chemotherapy and PD-1 blockade in the neoadjuvant treatment of rectal cancer, which may result in a breakthrough in the treatment of MSS/pMMR rectal cancer., Trial Registration: This study was registered at www., Clinicaltrials: gov ., Trial Registration Number: NCT05972655. Date of registration: 31 July 2023., (© 2024. The Author(s).)

Background: Sustained clinical complete remissions were reported in all of 23 mismatch repair deficient/microsatellite instable (dMMR/MSI) locally advanced rectal cancer (LARC) patients treated with dostarlimab alone in a recent phase II study. These results led to off-label use of dostarlimab or other immune checkpoint inhibitors (ICIs) in dMMR/MSI-LARC even before regulatory approval. The present study [STAR(t)-IT-REDUCE] describes the outcome of dMMR/MSI-LARC patients treated with ICI in Italy., Materials and Methods: Investigator-initiated, observational, retrospective-cohort, multicentric study of ICI treatment in dMMR/MSI-LARC. Patients were eligible if treated with ≥1 ICI dose from July 2022 to December 2023 (date of approval of dostarlimab for this indication in Italy)., Results: Seventeen dMMR/MSI-LARC patients (13 of 17 treatment-naïve) were eligible. Fourteen patients completed 6 months of treatment, two discontinued after four doses and one after five doses because of immune-related pneumonia, social constraints, or non-oncological bowel obstruction, respectively. Overall, 16 of 17 assessable patients [94.1%; 95% confidence interval (CI) 69.24% to 99.69%, 'ITT analysis'] achieved complete clinical response (cCR). Ten of 11 treatment-naïve patients completing 6 months of treatment had cCR (90.9%; 95% CI 57.12% to 99.52%, 'per-protocol analysis'). One patient with near-CR underwent rectal surgery and minimal residual intramucosal tumor was found. With a median follow-up of 9.5 months, no local relapse occurred. One patient developed unconfirmed lung metastases. Two grade 3 and no grade 4 adverse events were reported., Conclusion: The present STAR(t)-IT-REDUCE study documents the immunoablative and curative activity of ICI monotherapy in dMMR/MSI-LARC. Toxicity and compliance issues inherent to real-world practice are limited and do not affect achievement of initial complete tumor response but may limit response duration., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Neoadjuvant short-course radiotherapy (SCRT) followed by CAPOX and camrelizumab (a programmed cell death protein 1 monoclonal antibody) has shown potential clinical activity for locally advanced rectal cancer (LARC) in a phase II trial. This study aimed to further confirm the efficacy and safety of SCRT followed by CAPOX and camrelizumab compared to long-course chemoradiotherapy (LCRT) followed by CAPOX alone as neoadjuvant treatment for LARC., Patients and Methods: In this randomized, phase III trial, patients with T3-4/N+ rectal adenocarcinoma were randomly assigned (1 : 1) to receive SCRT or long-course chemoradiotherapy (LCRT), followed by two cycles of camrelizumab and CAPOX or CAPOX alone, respectively. After surgery, each arm underwent either six cycles of camrelizumab and CAPOX, followed by up to 17 doses of camrelizumab, or six cycles of CAPOX. The primary endpoint was pathological complete response (pCR) rate (ypT0N0) assessed by a blinded independent review committee. Key secondary endpoints tested hierarchically were 3-year event-free survival (EFS) rate and overall survival (OS)., Results: Between July 2021 and March 2023, the intention-to-treat population comprised 113 patients in the experimental arm and 118 patients in the control arm, with surgery carried out in 92% and 83.9%, respectively. At data cut-off (11 July 2023), the pCR rates were 39.8% [95% confidence interval (CI) 30.7% to 49.5%] in the experimental arm compared to 15.3% (95% CI 9.3% to 23.0%) in the control arm (difference, 24.6%; odds ratio, 3.7; 95% CI 2.0-6.9; P < 0.001). In each arm, surgical complication rates were 40.0% and 40.8%, and grade ≥3 treatment-related adverse events were 29.2% and 27.2%. Three-year EFS rate and OS continue to mature., Conclusions: In LARC patients, neoadjuvant SCRT followed by camrelizumab plus CAPOX demonstrated a significantly higher pCR rate than LCRT followed by CAPOX, with a well-tolerated safety profile. SCRT followed by camrelizumab and chemotherapy can be recommended as a neoadjuvant treatment modality for these patients., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Leukocytoclastic vasculitis (LCV) is a vasculitic inflammation against blood vessels. Various anticancer therapies can cause vasculitis, but capecitabine-induced LCV is an unusual entity. Here, we describe an LCV case associated with neoadjuvant capecitabine use for locally advanced rectal cancer (LARC)., Case Report: A 70-year-old man presented with rectal bleeding. A colonoscopic biopsy revealed rectal adenocarcinoma and he was diagnosed with LARC after imaging studies. Capecitabine plus radiation therapy was started as a neoadjuvant treatment., Management and Outcome: Seven days after the first capecitabine dose, the patient was admitted with a rash. The LCV diagnosis was histopathologically proven. Capecitabine was withheld. After the patient's rash began to regress under corticosteroid pressure, capecitabine was started at a lower dose. His treatment was completed successfully with oral corticosteroids plus low-dose capecitabine., Discussion: We aimed to point out a rare and unusual adverse effect of a frequently used drug in oncologic practice., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Neoadjuvant chemoradiotherapy has been a mainstay of the treatment of locally advanced rectal cancer. Programmed cell death protein 1 (PD-1) blockade therapy has demonstrated efficacy in combination with radiation. In this issue, Xiao et al. demonstrate promising efficacy with the addition of PD-1 blockade to neoadjuvant therapy for mismatch-repair proficient rectal cancer., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins. In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patients were randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell death protein 1 (PD-1) antibody sintilimab. As the primary endpoint, the total complete response (CR) rate is 26.9% (18/67, 95% confidence interval [CI] 16.0%-37.8%) and 44.8% (30/67, 95% CI 32.6%-57.0%) in the control and experimental arm, respectively, with significant difference (p = 0.031 for chi-squared test). Response ratio is 1.667 (95% CI 1.035-2.683). Immunohistochemistry shows PD-1 ligand 1 (PD-L1) combined positive score is associated with the synergistic effect. The safety profile is similar between the arms. Adding the PD-1 antibody sintilimab to NACRT significantly increases the CR rate in pMMR LARC, with a manageable safety profile. PD-L1 positivity may help identify patients who might benefit most from the combination therapy., Competing Interests: Declaration of interests H.-T.L. and C.-L.L. are employed by YuceBio Technology Co., Ltd. R.-H.X. has served as a consulting or advisory role for Bristol-Myers Squibb, Merck Serono, Roche, Astellas, and AstraZeneca., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The current gold standard for extraperitoneal locally advanced rectal cancer is total neoadjuvant therapy (TNT) followed by total mesorectal excision. This research explored the number of lymph nodes in patients with locally advanced rectal cancer after TNT and its correlation with survival., Materials and Methods: This is a post-hoc analysis based on the STELLAR trial, including patients with locally advanced rectal cancer from 16 tertiary centres who were randomized for short-term radiotherapy followed by chemotherapy (TNT group) or long-term concurrent chemotherapy group followed by total mesorectal excision between 2015 and 2018. This lymph node-related analysis is based on the TNT group. Subgroups were differentiated based on the lymph node harvest (below the median number: limited lymphadenectomy group, and greater than/equal to the median number: extended lymphadenectomy group). The primary outcomes were overall survival and disease-free survival (DFS). Correlations with clinical/pathological variables, lymphadenectomy categories and use of adjuvant chemotherapy were explored., Results: Among the 451 patients enrolled in the STELLAR trial, 227 patients (50.3%) were assigned to the TNT group, including 29.5% females. The median number of lymph nodes retrieved in the TNT group was 11.0. Patients in the limited lymphadenectomy subgroup exhibited worse overall survival than those with extended lymphadenectomy (HR 2.95 (95% c.i. 1.47 to 5.92), P = 0.001). The overall survival was similar in the ypN0-limited and ypN1-extended subgroups (HR 0.38 (95% c.i. 0.11 to 1.30), P = 0.109). Adjuvant chemotherapy was associated with better overall survival and DFS than no adjuvant chemotherapy overall (P < 0.001) and in the limited lymphadenectomy subgroup (P < 0.001). However, there was no significant difference in overall survival or DFS with or without adjuvant chemotherapy in the extended lymphadenectomy subgroup (P = 0.887 and P = 0.192, respectively)., Conclusion: In the STELLAR trial, the median number of lymph nodes harvested was 11. In patients with limited lymphadenectomy, the use of adjuvant therapy after TNT was beneficial and correlated with better prognosis compared with patients who did not receive adjuvant chemotherapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Background: Neoadjuvant chemotherapy is an option for patients with locally advanced rectal cancer at low risk for local recurrence. This randomized phase II trial investigated whether the addition of aflibercept to modified FOLFOX6 (mFOLFOX6) could improve the rates of centrally confirmed pathological complete remissions (pCR) and (disease-free) survival in magnetic resonance imaging (MRI)-staged cT3 rectal cancer., Patients and Methods: Patients with rectal cancer fulfilling the following criteria were included: lower border of tumor >5 cm and <16 cm from anal verge; circumferential resection margin >2 mm and T3-tumor with a maximum infiltration of 10 mm, as determined by MRI. Patients were randomized 1 : 2 to six cycles mFOLFOX6 ± aflibercept. Surgery was scheduled 4 weeks after chemotherapy. Primary endpoint was the rate of centrally confirmed pCR. The study was designed to detect an improvement of pCR from 10% to 27% (power 80%, type I error 20%)., Results: A total of 119 randomized patients started treatment (39 patients mFOLFOX6, arm A, and 80 mFOLFOX + aflibercept, arm B). The incidence of all grade adverse events was similar in both arms, however, adverse events grade ≥3 were more than twice as high in the experimental arm due to hypertension. Surgical complications were comparable. Aflibercept did not improve the pCR rate (arm A 26% versus arm B 19%, P = 0.47) and more patients in arm B had node positivity. With a median follow-up of 40.1 months, the 4-year disease-free survival was 83% in arm A and 85% in arm B (P = 0.82). Only two patients in arm A and one patient in arm B developed local recurrence., Conclusions: In patients with locally advanced rectal cancer and MRI-defined low risk of local recurrence, neoadjuvant mFOLFOX6 + aflibercept was feasible and did not compromise surgery. Survival data were favorable in both arms, but pCR rates were not increased by the addition of aflibercept., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Rectal cancer (RC) occupies a leading position in the structure of oncological morbidity and mortality. Aberrant methylation of tumor-suppressor genes and hypomethylation of retrotransposons were shown to be detectable in cell-free DNA, circulating in the blood (cfDNA) of cancer patients, indicating the possibility to use them as diagnostic and prognosis markers., Purpose: Evaluation of the changes in the methylation level of LINE-1 elements and SEPTIN9 and IKZF1 genes in the cell-surface-bound cfDNA (csb-cfDNA) from the blood of RC patients after antitumor therapy at a long-term follow-up., Methods: Blood samples were obtained from RC patients (n = 25) before treatment, after preoperative chemotherapy (3 courses according to the XELOX scheme), 10-15 days after surgery, and every 3 months during 12 months of dynamic observation. The methylation level of LINE-1, SEPTIN9, and IKZF1 in the csb-cfDNA was evaluated by quantitative methyl-specific PCR., Results: The LINE-1 methylation level in the csb-cfDNA increased 1.6 times in RC patients after chemotherapy and 3 times after tumor resection versus methylation level before therapy. The SEPTIN9 gene methylation level in the csb-cfDNA decreased by 1.7 times in RC patients after chemotherapy and by 2.3 times after tumor resection compared with the values before the treatment. The IKZF1 gene methylation level decreased by 2 times in RC patients after combined therapy. Notably, all patients with relapses (n = 5) showed an increase in methylation level for the SEPTIN9 and IKZF1 genes and a decrease of methylation level for the LINE-1 elements by 2 times or more in comparison with the level 10-15 days after surgery. There were no changes in the circulating SEPTIN9, IKZF1, and LINE-1 methylation levels during the 12-month follow-up period after the combined therapy of RC patients (n = 20) without relapses., Conclusion: The results indicate that SEPTIN9, IKZF1, and LINE-1 methylation levels in the csb-cfDNA are potential markers of the effectiveness of antitumor therapy and early detection of relapse in RC patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: This study evaluates the value of diffusion fractional order calculus (FROC) model for the assessment of pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC) by using histogram analysis derived from whole-tumor volumes., Materials and Methods: Ninety-eight patients were prospectively included. Every patient received MRI scans before and after nCRT using a 3.0-Tesla MRI machine. Parameters of the FROC model, including the anomalous diffusion coefficient (D), intravoxel diffusion heterogeneity (β), spatial parameter (μ), and the standard apparent diffusion coefficient (ADC), were calculated. Changes in median values (ΔX-median) and ratio (rΔX -median ) were calculated. Receiver operating characteristic (ROC) curves were used for evaluating the diagnostic performance., Results: Pre-treatmentβ -10th percentile values were significantly lower in the pCR group compared to the non-pCR group (p < 0.001). The Δβ -median showed higher diagnostic accuracy (AUC = 0.870) and sensitivity (76.67 %) for predicting tumor response compared to MRI tumor regression grading (mrTRG) scores (AUC = 0.722; sensitivity = 90.0 %)., Discussion: The use of FROC alongside comprehensive tumor histogram analysis was found to be practical and effective in evaluating the tumor response to nCRT in LARC patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To analyze the effect of cetuximab combined with radiotherapy in patients with rectal carcinoma (RC) by imaging analysis., Methods: The clinical data of 104 RC patients at our hospital from February 2021 to February 2022 were retrospectively analyzed. They were separated into control group ( n  = 52) and experimental group ( n  = 52) according to the order of admission, with the former treated with radiotherapy alone and the latter receiving cetuximab and radiotherapy. The clinical efficacy, tumor marker levels and imaging parameters of different treatment regimens were compared, and Quality of Life questionnaire (QLQ-C30) was used to evaluate the quality of life., Results: The incidence of tumor regression grade (TRG) downgrade, T stage downgrade and N stage downgrade was remarkably higher in the experimental group than in the control group ( P  < 0.05). The experimental group had remarkably lower tumor marker levels ( P  < 0.001) and higher mean score of EORTC Core QLQ-C30 ( P  < 0.001) than those in the control group. The relative signal intensity of tumor (SIT/M), relative signal intensity reduction rate of tumor (SIT/MRR) and apparent diffusion coefficient (ADC) values were remarkably higher ( P  < 0.001) and the absolute signal intensity of tumor (SIT) value was remarkably lower ( P  < 0.001) in the experimental group than the control group., Conclusion: Treatment with cetuximab and radiotherapy can greatly reduce serum tumor marker levels in RC patients and bring them health benefits, and further studies will help establish a better solution for such patients.

To examine the potential correlation between chemotherapy and the risk of individual of second primary endometrial cancer (SEC) in patients with rectal cancer (RC) and assess survival outcomes. The study employed the Surveillance, Epidemiology, and End Results database (SEER) as the primary data source, it encompasses a substantial cohort of patients diagnosed with RC between 1975 and 2018. This study involved a total of 30,847 individuals diagnosed with RC, of whom 168 individuals (5.45‰) experienced SEC. Among them, 107 patients (3.47‰) received chemotherapy treatment, while 61 patients (1.98‰) did not receive chemotherapy. The analysis of the overall occurrence of SEC revealed a significant association between SEC and chemotherapy treatment. Univariate and multivariate analyses confirmed a significant association between chemotherapy treatment and an increased risk of developing SEC in RC patients. Upon implementation of a dynamic analysis on the variables of relative risk and standardized incidence ratios, the results revealed that the likelihood of SEC escalated in tandem with advancing age. The examination of patients who developed SEC after receiving and not receiving chemotherapy revealed no substantial disparities in the 10-year overall survival (OS) and (cancer-specific survival) CSS rates. The results were the same after propensity score matching. Nevertheless, a notable discrepancy emerged when comparing the OS and CSS rates at 10 years between patients afflicted with SEC subsequent to chemotherapy and those afflicted with primary endometrial cancer, and the result was the same situation in the no-chemotherapy group. The use of chemotherapy in RC patients has been associated with an increased probability of developing specific SEC. Therefore, it is imperative to prioritize efforts aimed at reducing chemotherapy-related SEC occurrences and improving the prognosis of affected individuals., (© 2024. The Author(s).)

Background: LARC patients commonly receive adjuvant therapy, however, hidden micrometastases still limit the improvement of OS. This study aims to investigate the impact of VASN in rectal cancer with pulmonary metastasis and understand the underlying molecular mechanisms to guide adjuvant chemotherapy selection., Methods: Sequencing data from rectal cancer patients with pulmonary metastasis from Sun Yat-sen University Cancer Center (SYSUCC) and publicly available data were meticulously analyzed. The functional role of VASN in pulmonary metastasis was validated in vivo and in vitro. Coimmunoprecipitation (co-IP), immunofluorescence, and rescue experiments were conducted to unravel potential molecular mechanisms of VASN. Moreover, VASN expression levels in tumor samples were examined and analyzed for their correlations with pulmonary metastasis status, tumor stage, adjuvant chemotherapy benefit, and survival outcome., Results: Our study revealed a significant association between high VASN expression and pulmonary metastasis in LARC patients. Experiments in vitro and in vivo demonstrated that VASN could promote the cell proliferation, metastasis, and drug resistance of colorectal cancer. Mechanistically, VASN interacts with the NOTCH1 protein, leading to concurrent activation of the NOTCH and MAPK pathways. Clinically, pulmonary metastasis and advanced tumor stage were observed in 90% of VASN-positive patients and 53.5% of VASN-high patients, respectively, and VASN-high patients had a lower five-year survival rate than VASN-low patients (26.7% vs. 83.7%). Moreover, the Cox analysis and OS analysis indicated that VASN was an independent prognostic factor for OS (HR = 7.4, P value < 0.001) and a predictor of adjuvant therapy efficacy in rectal cancer., Conclusions: Our study highlights the role of VASN in decreasing drug sensitivity and activating the NOTCH and MAPK pathways, which leads to tumorigenesis and pulmonary metastasis. Both experimental and clinical data support that rectal cancer patients with VASN overexpression detected in biopsies have a higher risk of pulmonary metastasis and adjuvant chemotherapy resistance., (© 2024. The Author(s).)

Rationale: Late-stage cancer patients often experience severe pain due to bone metastasis, caused by structural damage and cancer-induced inflammation. Hyaluronan, known to alleviate pain by blocking the TRVP1 calcium channel, faces limitations due to its high molecular weight. However, 35 kDa low molecular weight hyaluronan fragment (HA35) have shown promise in relieving various pains, including cancer-related pain. Nonetheless, evidence regarding their efficacy in bone metastasis pain remains scarce., Patients Concerns: A 52-year-old female with a rectal malignant tumor and multiple secondary tumors in the sacrum and lungs, accompanied by bone metastasis pain. Despite undergoing radiotherapy, her pain relief was unsatisfactory. Before treatment with HA35, her numerical rating scale score was 10, severely affecting her sleep, appetite, and daily activities., Diagnoses: The patient was diagnosed with rectal malignant tumor with multiple metastases, presenting symptoms such as sacral metastasis pain, anal pain, lower limb pain, and anterior abdominal pain. Sacral metastasis pain and lower limb pain indicated a clear diagnosis of bone metastasis pain., Interventions: Treatment involved subcutaneous injection into the deep fat tissue layer of the abdomen. A subcutaneous injection of 100 mg/5 mL of HA35 was administered once into the deep fat tissue of the abdomen, with subsequent injections repeated every 3 days., Outcomes: Following 1 injection, the patient's pain score decreased to 6 points within 20 minutes, providing 40% pain relief. After 40 minutes, the score further dropped to 4 points, with 60% pain relief. After 50 injections, pain was consistently controlled at around 3 points., Lessons Subsections: Subcutaneous injection of HA35 into the abdominal fat tissue effectively alleviates pain in cancer and bone metastasis patients resistant to conventional treatments. Additionally, it helps alleviate anxiety and fatigue, and improves diet and sleep, thereby offering crucial palliative care for advanced cancer patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective To analyze the sensitivity of ARHGAP8 in predicting the efficacy of neoadjuvant chemotherapy in the patients with locally advanced mid-low colorectal cancer and provide accurate evidence for the treatment of advanced colorectal cancer. Methods The differentially expressed gene ARHGAP8 was screened out by bioinformatics analysis.Cancer tissue and rectal tissue of 68 patients with primary rectal cancer were selected.The rectal cancer tissue samples and the rectal tissue samples were collected for clinical validation of ARHGAP8 expression by quantitative real-time PCR,Western blotting,and immunohistochemistry.The clinical and pathological features such as gender,age,tumor stage,differentiation degree,and pathological type of the patients were collected for functional validation.Forty-four patients with locally advanced mid-low rectal cancer who received neoadjuvant chemotherapy were selected for immunohistochemical examination of ARHGAP8 expression.The expression level of ARHGAP8 was compared between before and after chemotherapy and among different efficacy groups. Results The bioinformatics analysis revealed differences in the expression level of ARHGAP8 between the cancer tissue and rectal tissue ( P <0.001).The expression level of ARHGAP8 was correlated with tumor stage ( P =0.024),lymph node metastasis ( P =0.007),and age ( P =0.005).Quantitative real-time PCR results showed that the mRNA level of ARHGAP8 in the cancer tissue was higher than that in the rectal tissue ( P <0.001).Western blotting and immunohistochemistry results demonstrated that the protein level of ARHGAP8 in the cancer tissue was higher than that in the rectal tissue ( P =0.011).The expression of ARHGAP8 was correlated with tumor size ( P =0.010) and pathological stage ( P =0.005),while it showed no significant association with tumor differentiation degree,lymph node metastasis,liver metastasis,Ki-67,or microsatellite instability expression level.The 44 patients receiving neoadjuvant chemotherapy included 13,8,8,and 15 patients of tumor regression grades 0,1,2,and 3,respectively.Among them,65.91% (29/44) patients showed responses to the treatment.After neoadjuvant chemotherapy,the expression of ARHGAP8 in the cancer tissue was down-regulated in the patients who responded to the chemotherapy ( P <0.001).The response rate in the patients with low protein level of ARHGAP8 was 92.86%,which was higher than that (53.33%) in the patients with high protein level of ARHGAP8 ( P =0.033). Conclusion ARHGAP8 is highly expressed in the rectal cancer tissue.The patients with locally advanced mid-low rectal cancer and low ARHGAP8 expression are more sensitive to neoadjuvant chemotherapy with the XELOX protocol.ARHGAP8 can serve as a potential biomarker for the occurrence and development of rectal cancer and an important index for evaluating the efficacy of neoadjuvant chemotherapy with the XELOX protocol in the patients with locally advanced mid-low rectal cancer.

We report a case of pathological complete response to neoadjuvant chemotherapy for abscess-forming rectal cancer. A woman in her 60s visited her primary care physician because she noticed an increase in the quantity of vaginal discharge. An irregular mass of goose-egg size found on the right vaginal wall was diagnosed as adenocarcinoma on biopsy, and she was referred to our hospital. After further examination, the mass was diagnosed as RbP, cT4b(vaginal), cN1a, cM0, cStage Ⅲc rectal cancer with abscess formation. After 6 courses of CAPOX as neoadjuvant chemotherapy, rectal resection(combined resection of the posterior vaginal wall) was performed. Pathological diagnosis showed no tumor cells and lymph node metastasis. Four courses of CAPOX were administered as postoperative adjuvant chemotherapy. The patient is still alive 4 years after surgery, without recurrence. When neoadjuvant chemotherapy is successful, radical resection is possible, even in cases with abscess formation, and long-term survival can be expected.

Background Neoadjuvant chemotherapy (NCT) is gaining acceptance for the management of locally advanced rectal cancer (LARC) in patients without negative prognostic factors. However, the value of MRI in evaluating tumor response after NCT remains unclear. Purpose To investigate the accuracy of MRI in assessing pathologic complete response in participants with LARC who underwent surgery after NCT without radiation. Materials and Methods A retrospective imaging substudy was conducted within two consecutive prospective clinical trials: the expanded phase II trial (from December 2017 to May 2021) and the COPEC trial (comparison of tumor response to two or four cycles of neoadjuvant chemotherapy alone, ongoing from August 2021). All included participants received four cycles of capecitabine combined with oxaliplatin (or CAPOX) before surgery. Three radiologists who were blinded to the clinicopathologic data independently evaluated the tumor response using five methods, namely, MR tumor regression grade (MR-TRG) alone, diffusion-weighted imaging (DWI) alone, DWI-modified MR-TRG (DWImodMR-TRG), MRI complete response, and radiologic neoadjuvant response score. With pathologic assessment serving as the reference standard, the positive and negative predictive values, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined to evaluate the accuracy and performance of these models. The AUCs of the models were compared using the DeLong test. Results A total of 224 participants were included, comprising 119 from the expanded phase II trial (median age, 61 years [IQR, 53-67]; 89 male) and 105 from the COPEC trial (median age, 59 years [IQR, 53-67]; 65 male). MR-TRG, DWI, DWImodMR-TRG, MRI complete response, and the radiologic neoadjuvant response score were associated with pathologic complete response. DWImodMR-TRG achieved the highest AUC of 0.90 (95% CI: 0.85, 0.95), with a specificity of 89% (162 of 182) and a negative predictive value of 93% (162 of 174). Conclusion MRI-based models were accurate for determining pathologic complete response in participants with LARC following NCT. DWI improved the predictive performance of MRI-based assessment. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Santiago and Shur in this issue.

Objective: In this study, we retrospectively analysed the efficacy and safety of three treatment models, namely, short-course radiotherapy sequential XELOX chemotherapy, neoadjuvant mFOLFOX6 concurrent radiotherapy and long-course concurrent radiotherapy with total mesorectal excision (TME) after treatment of locally advanced rectal cancer with high-risk factors., Methods: We collected clinical data on 177 patients with locally advanced rectal cancer (cT3-4 and/or cN+) who were treated at the Department of Abdominal Oncology of the Affiliated Cancer Hospital of Guizhou Medical University from December 2017 to December 2022. All patients were associated with 2-3 risk factors [T4b, N2, Extramural Vascular Invasion (EMVI), Mesorectal Fascia (MRF) positivity], positive lateral lymph nodes. Among them, there were 45 cases in the short course radiotherapy sequential XELOX chemotherapy group (RT + XELOX group); 64 cases in the neoadjuvant mFOLFOX6 concurrent radiotherapy group (mFOLFOX6 + CRT group); and 68 cases in the long course concurrent radiotherapy group (CRT group). The RT + XELOX group and mFOLFOX6 + CRT group completed radiotherapy and 4 cycles of neoadjuvant chemotherapy, respectively, and then rested for 1-2 weeks before TME surgery; the CRT group completed concurrent radiotherapy and then rested for 6-8 weeks before TME surgery.Adjuvant chemotherapy was conducted after surgery in each of the three groups: 2 cycles of adjuvant chemotherapy with XELOX regimen in the RT + XELOX group, 4-6 cycles of adjuvant chemotherapy with mFOLFOX6 in the mFOLFOX6 + CRT group, and 8-12 cycles of adjuvant chemotherapy with mFOLFOX6 in the CRT group.The pathological complete response rate (pCR rate), tumour downstage rate, tumour complete resection rate (R0 resection rate), local recurrence rate, distant metastasis rate, overall survival rate, incidence of adverse reactions, surgical complications and completion rate of perioperative systemic chemotherapy were compared among patients in the three groups of cases after TME., Results: The pCR rate (21.95% vs 17.24% vs 5.00%, p = 0.034) and and tumour downstage rate (78.05% vs 68.97% vs 53.33%, p = 0.029) were higher in the RT + XELOX group and mFOLFOX6 + CRT group compared to the CRT group. The RT + XELOX group had a lower 3-year distant metastasis rate (14.63% vs 36.67%, p = 0.048) and improved 3-year overall survival (76.57% vs 48.56%, p < 0.001) compared to the CRT group. There was no significant reduction in the 3-year distant metastasis rate in the mFOLFOX6 + CRT group versus the CRT group (27.59% vs 36.67%, p = 0.719), and the 3-year overall survival was similar (51.23% vs 48.56%, p = 0.35). Multi-logistic regression analysis and stratified analysis showed that patients in the RT + XELOX group and mFOLFOX6 + CRT group were more likely to achieve pCR than the CRT group (RT + XELOX group: OR 7.3, 95% CI [2.6-20.8], p < 0.001; mFOLFOX6 + CRT group OR 2.9, 95% CI [1.1-7.9], p = 0.036). The completion rates of perioperative systemic chemotherapy in the RT + XELOX, mFOLFOX6 + CRT, and CRT groups were 82.93% vs. 84.48% vs. 61.67% (χ 2 =9.95, p = 0.007), respectively. And there were significant differences in grade 3-4 leukopenia and thrombocytopenia (incidence of leukopenia: 15.50% vs. 7.81% vs. 1.47%, p = 0.045; incidence of thrombocytopenia: 13.33% vs 7.81% vs 1.47%, p = 0.027). There was no significant difference in the incidence of intraoperative and postoperative complications among the three groups (p > 0.05)., Conclusions: RT + XELOX group and mFOLFOX6 + CRT group significantly improved the near-term outcome (e.g., pCR rate) in patients with locally advanced rectal cancer with high-risk factors compared with CRT group. The RT + XELOX group also reduced the 3-year distant metastasis rate, increased the 3-year overall survival rate, and did not increase the incidence of perioperative surgical complications. It provides an effective means for the comprehensive treatment of locally advanced rectal cancer and has important clinical guidance and application value.

Introduction: This is the first report of a patient who developed cardiogenic shock after receiving oral chemotherapy with capecitabine and was treated with venoarterial extracorporeal membrane oxygenation combined with continuous renal replacement therapy., Clinical Findings: A 58-year-old man developed an arrhythmia that rapidly progressed to cardiogenic shock and cardiac arrest after receiving oral capecitabine tablets to treat a rectal malignancy., Interventions: The patient was treated with venoarterial extracorporeal membrane oxygenation in combination with continuous renal replacement therapy., Outcome: The patient made a full recovery and was discharged from the hospital., Conclusion: The use of comprehensive supportive treatments such as extracorporeal membrane oxygenation combined with continuous renal replacement therapy in patients with capecitabine-induced cardiac arrest can rapidly reduce drug concentrations, eliminate harmful substances, and improve the prognosis., (©2024 American Association of Critical-Care Nurses.)

Treatment of patients with locally advanced rectal cancer (RC) is based on neoadjuvant chemoradiotherapy followed by surgery. In order to reduce the development of therapy resistance, it is necessary to further improve previous treatment approaches. Recent in vivo experimental studies suggested that the reduction of tumor hypoxia by tumor vessel normalization (TVN), through the inhibition of the glycolytic activator PFKFB3, could significantly improve tumor response to therapy. We have evaluated in vitro and in vivo the effects of the PFKFB3 inhibitor 2E-3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) on cell survival, clonogenicity, migration, invasion, and metabolism using colorectal cancer cells, patient-derived tumor organoid (PDO), and xenograft (PDX). 3PO treatment of colorectal cancer cells increased radiation-induced cell death and reduced cancer cell invasion. Moreover, gene set enrichment analysis shows that 3PO is able to alter the metabolic status of PDOs toward oxidative phosphorylation. Additionally, in vivo neoadjuvant treatment with 3PO induced TVN, alleviated tumor hypoxia, and increased tumor necrosis. Our results support PFKFB3 inhibition as a possible future neoadjuvant addition for patients with RC., Significance: Novel therapies to better treat colorectal cancer are necessary to improve patient outcomes. Therefore, in this study, we evaluated the combination of a metabolic inhibitor (3PO) and standard radiotherapy in different experimental settings. We have observed that the addition of 3PO increased radiation effects, ultimately improving tumor cell response to therapy., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after TNT may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes., Methods: In this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N +) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N + vs N0) and distance from anal verge (0-4; 4-8; 8-12 cm). Patients will be randomized to receive neoadjuvant long-course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3-4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8-12 (± 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 312 evaluable patients (156 per arm) will provide statistical power of 90.5% to detect a 17% increase in cCR rate, at a one-sided alpha = 0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse event rates. Biospecimens including archival tumor tissue, plasma and buffy coat, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and had accrued 330 patients as of May 2024. Study support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org ., Discussion: Building on data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed The Janus Rectal Cancer Trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer., Trial Registration: Clinicaltrials.gov ID: NCT05610163; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG)., (© 2024. The Author(s).)

Background: Colorectal cancer (CRC) is a significant malignancy with widespread implications. Despite progress in surgical interventions for rectal cancer, improvements in overall prognosis remain disproportionate. Standard preoperative chemoradiation, while established as the standard treatment for the majority of rectal cancers, exhibits limited effectiveness in enhancing disease-free survival (DFS) and mitigating distant metastases, particularly in cases of locally advanced rectal cancer (LARC)., Methods: This randomised clinical trial assessed 286 patients with LARC in two paralleled groups. Group A underwent six courses of neoadjuvant MFOLFOX chemotherapy, chemoradiation, surgery, and six adjuvant chemotherapy cycles. Group B received concurrent chemoradiation, surgery, and twelve adjuvant chemotherapy cycles. Patient evaluations were achieved at multiple stages of treatment and follow-up., Results: Group A had significantly lower local recurrence (11.64%) than Group B (21.74%, P = 0.025). The distant metastasis rate in Group A (8.90%) was lower than in Group B (20.29%) but was not significant (p = 0.143). More patients in Group A experienced downstaging (80.82% vs. 60.87%, p < 0.001). Specifically, 72.60% demonstrated downstaging of tumour invasion and 54.79% downstaging of lymph node involvement, compared to 57.25% and 41.30% in Group B (p = 0.009 and p = 0.025, respectively) as well as higher pCR rate (26.03% vs. 15.25%, p = 0.030) and three-year DFS rate (82.19% vs. 71.01%, p = 0.035) in group A compare to group B., Conclusion: This innovative strategy for LARC showed promising results with lower local recurrence and higher rates of downstaging and pCR. Treatment side effects were similar in both groups but less frequent in Group A. Anaemia was the most common haematological side effect (A: 58%, B: 68%), and peripheral sensory neuropathy was the most common non-haematological complication (A: 63%, B: 64%). These findings suggest this regimen could be a valuable therapeutic approach for LARC., Trial Registration: This trial was registered on 2023-12-08 within the IRCT.IR database under the number IRCT20210308050628N1., (© 2024. The Author(s).)

Rationale: Bevacizumab (Bev) is a humanized monoclonal antibody that targets vascular endothelial growth factor A and is primarily used for the treatment of various solid tumors. Aortic dissection (AD) is a severe vascular disease caused by the tearing of the intimal layer of the aorta or bleeding within the aortic wall, resulting in the separation of different layers of the aortic wall. However, the pathogenesis is not fully understood. Some studies have suggested that Bev treatment is associated with the occurrence of AD., Patient Concerns: A 67-year-old Chinese male was diagnosed with rectal cancer accompanied by liver and lung metastasis. Three days after starting combined chemotherapy with Bev, the patient developed persistent abdominal pain. Abdominal CT scan revealed celiac trunk AD in the abdominal aorta., Diagnoses: The patient was diagnosed with rectal cancer accompanied by liver and lung metastases. Abdominal CT tomography revealed a celiac trunk AD., Interventions: Somatostatin combined with valsartan was used to control blood pressure. The patient was subsequently referred for vascular surgery and underwent an abdominal aortic angiography. Conservative treatment was continued., Outcomes: Three months after the initiation of treatment, follow-up abdominal CT scans showed stability in the condition of celiac trunk AD, with no abdominal pain or hypertension. There were no signs of worsening dissection, aneurysm formation, or inadequate perfusion of end organs., Lessons: There may be a connection between Bev and elevated blood pressure as well as celiac trunk AD., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: For decades, the standard neoadjuvant therapy regimen for locally advanced rectal cancer consisted of chemoradiation, surgical resection, and consideration of adjuvant systemic therapy. Additional data have emerged suggesting neoadjuvant systemic therapy as a reasonable alternative to chemoradiation in selected patients. In addition, a total neoadjuvant therapy approach integrating both chemotherapy and chemoradiation results in superior cancer outcomes and the potential for consideration of nonoperative management in patients with a clinical complete response. Despite a multitude of therapeutic pathways for the management of rectal cancer, what is clear, however, is the importance of a multidisciplinary approach with shared patient and provider decision-making., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Total neoadjuvant therapy (TNT) before surgical intervention represents a unique therapeutic approach for the management of locally advanced rectal cancer (LARC) and has witnessed a notable rise in utilization within recent years. However, the efficacy and safety of this treatment remain subjects of ongoing debate and investigation. This randomized controlled trial aimed to evaluate the potential impact of administering induction chemotherapy (IC) before the conventional neoadjuvant concomitant chemoradiotherapy (nCRT) in LARC patients., Materials & Methods: patients with resectable stage II-III LARC were randomly allocated to receive either biweekly 6 cycles of FOLFOX4 regimen as IC followed by CRT and total mesorectal excision (TME) (experimental group) or nCRT followed by TME (control group). The primary endpoint was the rate of pathological complete response (pCR). The secondary endpoints encompassed the evaluation of treatment-related adverse events as well as the assessment of survival outcomes., Results: 67 patients were enrolled in this study (32 in the experimental group and 35 in the control group). The median age of the patients was 45 years. Stage IIIB was observed in 46.3% of the patients. The patients who underwent induction chemotherapy demonstrated a notably higher rate of achieving pCR in comparison to the control group (28.1% vs 8.6%; P=0.001). There were no statistically significant differences observed in terms of their toxicity profile and survival outcomes., Conclusions: Implementation of induction chemotherapy utilizing the FOLFOX4 regimen has demonstrated a notable enhancement in the rate of pathological complete response. However, this improvement does not appear to translate into significant advancements in overall survival outcomes.

Aim: To explore the diverse profiles of adverse reactions caused by oxaliplatin between colon and rectal cancer, we investigated the toxicity of oxaliplatin in patients with colon and rectal cancer., Methods: From January 2017 to December 2021, 200 cases of sporadic CRC patients with adverse reactions after oxaliplatin were collected from Harbin Medical University Cancer Hospital, Harbin, China. All patients received a chemotherapy regimen containing oxaliplatin (100 colon cancer and 100 rectal cancer). We reviewed the adverse reactions induced by oxaliplatin in patients with colon and rectal cancer., Results: We found there was no significant difference in gastrointestinal toxicity, hematotoxicity, neurotoxicity, hepatotoxicity, respiratory toxicity, and cardiotoxicity caused by oxaliplatin between patients with colon cancer and patients with rectal cancer, but patients with rectal cancer were more prone to allergic reactions than patients with colon cancer after oxaliplatin. In addition, we found neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratios (PLR) were higher in patients with colon cancer than in patients with rectal cancer. This may reflect differences in immune status and inflammatory responses between colon cancer and rectal cancer, which might be the reason for more allergic reactions caused by oxaliplatin in colon cancer patients compared to rectal cancer patients., Conclusion: Except for a higher incidence of allergic reactions in patients with rectal cancer, no significant difference in the incidence of adverse drug reactions associated with oxaliplatin was noted between patients with colon cancer and rectal cancer. Our results suggested more attention should be paid to the allergic reaction caused by oxaliplatin in patients with colon cancer.

Purpose: Achieving a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) remains a challenge for most patients with rectal cancer. Exploring the potential of combining NCRT with immunotherapy or targeted therapy for those achieving a partial response (PR) offers a promising avenue to enhance treatment efficacy. This study investigated the impact of NCRT on the tumor microenvironment in locally advanced rectal cancer (LARC) patients who exhibited a PR., Methods: This was a retrospective, observational study. Five patients demonstrating a PR after neoadjuvant treatment for LARC were enrolled in the study. Biopsy samples before treatment and resected specimens after treatment were stained with a panel of 26 antibodies targeting various immune and tumor-related markers, each labeled with distinct metal tags. The labeled samples were then analyzed using the Hyperion imaging system., Results: Heterogeneity within the tumor microenvironment was observed both before and after NCRT. Notably, tumor-associated macrophages, CD4 + T cells, CD8 + T cells, CD56 + natural killer cells, tumor-associated neutrophils, cytokeratin, and E-cadherin exhibited slight increase in abundance within the tumor microenvironment following treatment (change ratios = 0.78, 0.2, 0.27, 0.32, 0.17, 0.46, 0.32, respectively). Conversely, the number of CD14 + monocytes, CD19 + B cells, CD45 + CD4 + T cells, collagen I, α-smooth muscle actin, vimentin, and β-catenin proteins displayed significant decreases post-treatment (change ratios = 1.73, 1.92, 1.52, 1.25, 1.52, 1.12, 2.66, respectively). Meanwhile, Foxp3 + regulatory cells demonstrated no significant change (change ratio = 0.001)., Conclusions: NCRT has diverse effects on various components of the tumor microenvironment in LARC patients who achieve a PR after treatment. Leveraging combination therapies may optimize treatment outcomes in this patient population., (© 2024. The Author(s).)

Background: Locally advanced rectal cancer (LARC) typically involves neoadjuvant chemoradiotherapy (nCRT) followed by surgery (total mesorectal excision, TME). While achieving a complete pathological response (pCR) is a strong indicator of a positive prognosis, the specific benefits of adjuvant chemotherapy after pCR remain unclear. To address this knowledge gap, we conducted a systematic review and meta-analysis to assess the potential advantages of adjuvant therapy in patients who achieve pCR., Methods: In this study, we searched Medline, Embase, and Web of Science databases for relevant research. We focused on binary outcomes, analyzing them using odds ratios (ORs) with 95% confidence intervals (CIs). To account for potential variability between studies, all endpoints were analyzed with DerSimonian and Laird random-effects models. We assessed heterogeneity using the I 2 statistic and employed the R statistical software (version 4.2.3) for all analyses., Results: Thirty-four studies, comprising 31,558 patients, were included. The outcomes demonstrated a significant difference favoring the AC group in terms of overall survival (OS) (HR 0.75; 95% CI 0.60-0.94; p = 0.015; I 2  = 0%), and OS in 5 years (OR 1.65; 95% CI 1.21-2.24; p = 0.001; I 2  = 39%). There was no significant difference between the groups for disease-free survival (DFS) (HR 0.94; 95% CI 0.76-1.17; p = 0.61; I 2  = 17%), DFS in 5 years (OR 1.19; 95% CI 0.82-1.74; p = 0.36; I 2  = 43%), recurrence-free survival (RFS) (HR 1.10; 95% CI 0.87-1.40; p = 0.39; I 2  = 0%), and relapse-free survival (OR 1.08; 95% CI 0.78-1.51; p = 0.62; I 2  = 0%)., Conclusion: This systematic review and meta-analysis found a significant difference in favor of the ACT group in terms of survival after pCR. Therefore, the administration of this treatment as adjuvant therapy should be encouraged in clinical practice., (© 2024. The Author(s).)

Rationale: Treatment strategies for rectal squamous cell carcinoma (rSCC) are yet to be established, given its rarity. Although squamous cell carcinoma has been reported to be highly sensitive to cetuximab and radiation, there is no report of combination therapy of cetuximab and radiation for rSCC. In this study, we firstly reported a case of rSCC in which a complete response was achieved with the original chemoradiotherapy comprising oxaliplatin, S-1, cetuximab, and simultaneous radiation., Patient Concerns: A 46-year-old women presented to our hospital with lower abdominal pain and fatigue., Diagnoses: Based on tumor marker analyses, histological examination of biopsy specimens, and comprehensive imaging, the patient was diagnosed with rSCC., Interventions: Neoadjuvant chemoradiotherapy (50.4 Gy) was administered in 28 fractions, along with concurrent chemotherapy comprising SOX (S-1: 80 mg/m2, days 1-5 and 8-12, oxaliplatin: 85 mg/m2, day 1) and cetuximab (400 mg/m2, day 1, 250 mg/m2, after day 8)., Outcomes: Five weeks after chemoradiation, the patient underwent laparoscopic partial intersphincteric resection, achieving a complete pathological response., Lessons: This case firstly highlights the usefulness of SOX plus cetuximab combined with radiation in the treatment of locally advanced rSCC. However, a large-scale study is required to establish safe and effective treatment regimens., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Colorectal cancer (CRC) ranks third in global cancer prevalence, with 40% presenting as metastatic colorectal cancer (mCRC). KRAS mutations in mCRC patients confer resistance to anti-EGFR treatments. Promising inhibitors such as sotorasib and adagrasib targeting KRASG12C mutations have demonstrated efficacy. Herein, we present a heavily pretreated mCRC case with a progression-free survival of 12 months with sotorasib and panitumumab. In 2017, a 27-year-old male presented with abdominal pain and received a diagnosis of stage IIIC KRAS G12C mutant CRC. Following surgery and adjuvant chemotherapy, he developed metastases in the liver and lungs in 2020. Treatment with FOLFIRINOX and bevacizumab, and later FOLFIRI and bevacizumab, with surgeries and local interventions resulted in partial responses. Upon disease progression, sotorasib and panitumumab were initiated, achieving a complete metabolic response. After 12 months of progression-free survival, oligoprogressive liver lesions were surgically resected. This case highlights the remarkable outcome of a heavily treated KRAS G12C mutant mCRC patient. The combination of sotorasib and panitumumab, along with multidisciplinary approaches including surgery and local interventions, played an important role in our patient's survival., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

A 44-year-old woman with Lynch syndrome was referred to our hospital for treatment of recurrence of microsatellite instability-high rectal cancer. [ 18 F]Fluorodeoxyglucose (18FDG)-positron emission tomography revealed a peritoneal metastasis with invasion to the small intestine and left ureter. The peritoneal metastasis was diagnosed initially as unresectable because of extensive invasion to the left ureter requiring nephrectomy. Hence, first-line treatment with pembrolizumab was started. After the first course of pembrolizumab, she developed hydronephrosis and a resulting urinary tract infection (UTI). A percutaneous nephrostomy was performed to control the UTI. After six courses of pembrolizumab, 18FDG-positron emission tomography showed that the peritoneal metastasis was smaller with significantly reduced 18FDG uptake, and it was then diagnosed as resectable without nephrectomy. She underwent R0 resection of the peritoneal metastasis with partial resection of the small intestine. Intraoperatively, the peritoneal metastasis showed no invasion of the left ureter, allowing its preservation. The percutaneous nephrostomy was removed postoperatively, and she has not developed any subsequent UTIs. Histopathologically, the tumor showed a pathological complete response to pembrolizumab. To the best of our knowledge, this is the first case of conversion therapy with pembrolizumab for peritoneal metastasis with hydronephrosis., (© 2024. Japanese Society of Gastroenterology.)

Clostridium paraputrificum bacteremia is very rare, and its clinical importance is poorly understood. An 86-year-old man was receiving lascufloxacin therapy for acute pharyngolaryngitis before presenting to our emergency department with a recurrent fever. Two sets of blood cultures on admission revealed C. paraputrificum. A stool culture showed a reduced presence of intestinal commensal bacteria. After admission, the patient's fever resolved without antibiotics. Colonoscopy revealed a rectal tumor. Rectal tumor and microbial substitutions caused by antibiotics may have led to bacteremia. When treating C. paraputrificum bacteremia, physicians should be mindful of coexisting gastrointestinal disorders and a history of antibiotic administration.

Aim: To explore the clinical factors associated with pathologic complete response (pCR) for locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy (nCRT) and develop a web-based dynamic nomogram., Methods: Retrospective analysis of patients with examination confirmed LARC from 2011 to 2022. Patients from the Union Hospital of Fujian Medical University were included as the training cohort (n = 1579) and Zhangzhou Hospital of Fujian Medical University as the external validation cohort (n = 246)., Results: In the training cohort, after nCRT, 350 (22.2%) patients achieved pCR. More stomas were avoided in pCR patients (73.9% vs. 69.7%, p = 0.043). After a median follow-up time of 47.7 months (IQR 2-145) shown OS (5-year: 93.7% vs. 81.0%, HR = 0.310, 95%CI: 0.189-0.510, p < 0.001) and DFS (5-year: 91.2% vs. 75.0%, HR = 0.204, 95%CI: 0.216-0.484, p < 0.001) were significantly better among patients with pCR than non-pCR. Multivariable Logistic analysis shown pCR was significantly associated with Pre-CRT CEA (HR = 0.944, 95%CI: 0.921-0.968; p < 0.001), histopathology (HR = 4.608, 95%CI: 2.625-8.089; p < 0.001), Pre-CRT T stage (HR = 0.793, 95%CI: 0.634-0.993; p = 0.043), Pre-CRT N stage (HR = 0.727, 95%CI: 0.606-0.873; p = 0.001), Pre-CRT MRI EMVI (HR = 0.352, 95%CI: 0.262-0.473; p < 0.001), total neoadjuvant therapy (HR = 2.264, 95%CI: 1.280-4.004; p = 0.005). Meanwhile, the online version of the nomogram established in this study was publicized on an open-access website (URL: https://pcrpredict.shinyapps.io/LARC2/). The model predicted accuracy with a C-index of 0.73 (95% CI: 0.70-0.75), with an average C-index of 0.73 for the internal cross validation and 0.78 (95% CI: 0.72-0.83) for the external validation cohort, showing excellent model accuracy. Delong test results showed the model has an important gain value for clinical characteristics to predict pCR in rectal cancer., Conclusions: Patients with pCR had a better prognosis, including OS and DFS, and were independently associated with Pre-CRT CEA, histopathology, Pre-CRT T/N stage, Pre-CRT MRI EMVI, and TNT. A web-based dynamic nomogram was successfully established for clinical use at any time., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Understanding the mechanism of brain functional alterations in rectal cancer (RC) patients is of great significance to improve the prognosis and quality of life of patients. Additionally, the influence of chemotherapy on brain function in RC patients is still unclear. In this study, we aimed to investigate the alterations of brain functional network dynamics in RC patients and explore the effects of chemotherapy on temporal dynamics of dynamic functional connectivity (DFC)., Methods: The group independent component analysis (GICA) and sliding window method were applied to investigate abnormalities of DFC based on resting-state functional magnetic resonance imaging (rs-fMRI) of 18 RC patients without chemotherapy (RC&#95;NC), 21 RC patients with chemotherapy (RC&#95;C) and 33 healthy controls (HC). Then, the Spearman correlation between aberrant properties and clinical measures was calculated., Results: Two discrete states were identified. Compared to HC, RC&#95;NC exhibited increased mean dwell time (MDT) and fractional windows (FW) in state 2 and decreased transition numbers between the two states. Notably, three temporal properties in RC&#95;C showed an intermediate trend in comparison with RC&#95;NC and HC. Furthermore, RC&#95;C also demonstrated abnormal intra- and inter-network connections, involving the visual (VIS), default mode (DM), and cognitive control (CC) networks, and most connections related to VIS were correlated with the severity of anxiety and depression., Conclusions: Our study suggested that abnormal DFC patterns could be manifested in RC patients and chemotherapy would further correct abnormalities of network dynamics, which may provide new insights into the brain functional alterations in patients with RC from the time-varying connectivity perspective.

Tumor-associated macrophages within the tumor microenvironment play an immunosuppressive role by promoting tumor growth and immune evasion. Macrophages are highly plastic and can be stimulated to adopt an anti-tumor M1 phenotype. In this study, we used microcystin-LR (MC-LR), a cyclic heptapeptide produced by cyanobacteria, to induce in vitro macrophage innate immunity and transition into the anti-tumor M1 phenotype. MC-LR was also tested in vivo in a mouse model of colorectal cancer. An intraperitoneal injection of MC-LR increased the proportion of CD86⁺ M1 macrophages and triggered the maturation of CD11c⁺ dendritic cells within tumor tissues. MC-LR combined with the chemotherapeutic drug oxaliplatin significantly inhibited tumor growth in vivo. Flow cytometry analysis revealed increased infiltration of activated cytotoxic (CD8⁺, PD-1⁺) T-cells and anti-tumor cytokines (IFNγ and Granzyme B) in the tumor tissues of the combination therapy group, suggesting that this may be the primary mechanism behind the anti-tumor effect of the combination treatment. These findings indicate that MC-LR regulates the immune stimulation of macrophage polarization and dendritic cell maturation, effectively reversing tumor immunosuppression, activating an anti-tumor immune response, and enhancing tumor therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Palmar-plantar erythrodysesthesia (PPE) is a slowly developing cutaneous reaction commonly experienced by patients treated with fluoropyrimidines. While erythrodysesthesia normally presents in a palmar-plantar distribution, it can also present with genital involvement, but this presentation is likely underreported and incorrectly attributed to an acute reaction from radiation therapy. This article aims to define erythrodysesthesia of the penis and scrotum as a rare but significant side effect of capecitabine., Case Presentation: We identified five cases of moderate to severe penis and scrotal erythrodysesthesia over a 2-year period at a large tertiary cancer center, representing an estimated incidence of 3.6% among male patients with rectal cancer who were treated with fluoropyrimidine-based chemoradiation within our institution., Conclusions: Improved understanding of erythrodysesthesia involving the penis and scrotum can facilitate early identification and treatment of symptoms, and possibly prevent the discontinuation or delay of cancer treatment in patients treated with capecitabine and similar drugs. These clinical advances would improve and prolong patient quality of life during cancer treatment and prevent complications that result in hospitalization., (© 2024. The Author(s).)

DNA methyltransferase inhibitors (DNMTi) have demonstrated benefit in reversing resistance to systemic therapies for several cancer types. In a phase II trial of guadecitabine and irinotecan compared to regorafenib or TAS-102 in pts with advanced mCRC refractory to irinotecan. Patients with mCRC refractory to irinotecan were randomized 2:1 to guadecitabine and irinotecan (Arm A) vs standard of care regorafenib or TAS-102 (Arm B) on a 28-day cycle. Between January 15, 2016 and October 24, 2018, 104 pts were randomized at four international sites, with 96 pts undergoing treatment, 62 in Arm A and 34 in Arm B. Median overall survival was 7.15 months for Arm A and 7.66 months for Arm B (HR 0.93, 95% CI: 0.58-1.47, P = .75). The Kaplan-Meier rates of progression free survival at 4 months were 32% in Arm A and 26% in Arm B. Common ≥Grade 3 treatment related adverse events in Arm A were neutropenia (42%), anemia (18%), diarrhea (11%), compared to Arm B pts with neutropenia (12%), anemia (12%). Guadecitabine and irinotecan had similar OS compared to standard of care TAS-102 or regorafenib, with evidence of target modulation. Clinical trial information: NCT01896856., (© 2024 UICC.)