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Cancer is a global health concern influenced by genetics, environment and lifestyle choices. Recent research shows that a ketogenic diet (KD) might ease cancer symptoms and reduce tumour size. We hypothesised that the KD could result in improvements in cancer‐related variables. Therefore, this study aims to perform a systematic review and meta‐analysis to assess the KD's efficacy for patients with cancer. The databases PubMed (MEDLINE), Web of Science, CINAHL and Open Grey were utilised for conducting a systematic review and meta‐analysis. The analysis was limited to randomised controlled trials with adult participants aged 18 years and above. Levels of glucose, cholesterol, insulin‐like growth factor 1, weight and quality of life were evaluated following the KD. After identifying 596 articles in the initial search, eight studies, lasting between 4 and 16 weeks, were included in the systematic review and seven in the meta‐analysis. The KD led to decreased glucose levels in patients with cancer but did not show significant improvements in cholesterol, insulin‐like growth factor 1, weight or quality of life. Based on the results of this systematic review and meta‐analysis, there is insufficient evidence to establish a definitive link between the KD and cancer‐related parameters. While some studies suggest potential benefits in terms of some outcomes and tumour size reduction, further research is required to fully comprehend the effects of this diet. [ABSTRACT FROM AUTHOR]

Background: This study examined temporal shifts in adjuvant therapy patterns in Japanese patients with resectable gastric cancer (GC) and treatment patterns of first-line and subsequent therapy among those with recurrent disease. Methods: This retrospective analysis of hospital-based administrative claims data (April 1, 2008 to March 31, 2022) included adults (aged ≥ 20 years) with GC who started adjuvant therapy on or after October 1, 2008 (adjuvant cohort) and patients in the adjuvant cohort with disease recurrence (recurrent cohort), further defined by the time to recurrence (≤ 180 or > 180 days after adjuvant therapy). Results: In the adjuvant cohort (n = 17,062), the most common regimen during October 2008–May 2016 was tegafur/gimeracil/oteracil potassium (S-1; 95.7%). As new standard adjuvant regimen options were established, adjuvant S-1 use decreased to 65.0% and fluoropyrimidine plus oxaliplatin or docetaxel plus S-1 use increased to 15.0% and 20.0%, respectively, in September 2019–March 2022. In the recurrent cohort with no history of trastuzumab/trastuzumab deruxtecan treatment (n = 1257), the most common first-line regimens were paclitaxel plus ramucirumab (34.0%), capecitabine plus oxaliplatin (CapeOX; 17.0%), and nab-paclitaxel plus ramucirumab (10.1%) in patients with early recurrence, and S-1 plus oxaliplatin (26.3%), S-1 plus cisplatin (15.3%), CapeOX (14.0%), S-1 (13.2%), and paclitaxel plus ramucirumab (10.8%) in those with late recurrence. Conclusions: This study demonstrated temporal shifts in adjuvant treatment patterns that followed the establishment of novel regimens, and confirmed that post-recurrent treatment patterns were consistent with the Japanese Gastric Cancer Association guideline recommendations. [ABSTRACT FROM AUTHOR]

Introduction The bladder exstrophy‐epispadias complex is a rare congenital disease. Urothelial carcinomas rarely occur in patients with this disease, and there have been few reports on its treatment. Case presentation We report the case of a 44‐year‐old man with a hemorrhage from the external urethral meatus. He was diagnosed with bladder exstrophy‐epispadias complex and underwent urinary diversion with substitution cystoplasty and Mitrofanoff appendicovesicostomy. Because computed tomography and magnetic resonance imaging suggested invasive bladder carcinoma in the defunctionalized bladder, we performed a cystectomy. The patient was diagnosed with urothelial carcinoma with glandular differentiation. One month after the surgery, nivolumab adjuvant chemotherapy was administered. The patient showed no signs of recurrence or metastasis after the treatment. Conclusion This is the first case of adjuvant nivolumab therapy for urothelial carcinoma with the bladder exstrophy‐epispadias complex.

After the successful development of targeted therapy and immunotherapy for the treatment of advanced-stage non-small cell lung cancer (NSCLC), these innovative treatment options are rapidly being applied in the adjuvant setting for early-stage NSCLC. Some adjuvants that have recently been approved include osimertinib for epidermal growth factor receptor-mutated tumors and atezolizumab and pembrolizumab for selected patients with resectable NSCLC. Numerous studies on various targeted therapies and immunotherapy with or without chemotherapy are currently ongoing in the adjuvant setting. However, several questions regarding optimal strategies for adjuvant treatment remain unanswered. The present review summarizes the available literature, focusing on recent advances and ongoing trials with targeted therapy and immunotherapy in the adjuvant treatment of early-stage NSCLC.

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A significant proportion of patients with non-small cell lung cancer (NSCLC) is diagnosed in the early and resectable stage. Despite the use of platinum-based adjuvant chemotherapy, there was only a marginal increase in overall survival and a 15% decrease in relapse. With the advents of immunotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), the landscape of adjuvant treatment in completely resectable NSCLC is changing. Postoperative radiotherapy can be beneficial to patients who underwent surgical resection in certain clinical settings. In addition, new biomarkers that predict efficacy of EGFR TKI and immunotherapy as adjuvant treatment are also necessary. In this review, recent updates in adjuvant treatment in resectable NSCLC were briefly explained.

Trabalho apresentado no Simpósio Internacional sobre Doença de Hodgkin, realizado no Instituto Nacional de Câncer no Rio de Janeiro — 16 a 20 de Janeiro de 1967. Transcrição da gravação, revisto o original pelo autor.

Purpose: We describe a novel application of the reverse thermal polymer gel of mitomycin C (UGN-101) as adjuvant therapy after complete endoscopic ablation of upper tract urothelial carcinoma. Materials and Methods: We retrospectively reviewed patients treated with UGN-101 from 15 high-volume centers. Adjuvant therapy was defined as treatment administered following visually complete endoscopic ablation. Response at primary endoscopic evaluation was defined as no visual tumor or negative biopsy. Ipsilateral diseasefree and progression-free survival were estimated by the Kaplan-Meier method. Ureteral stenosis and other adverse events were abstracted from the medical records. Ureteral stenosis was defined as a condition requiring ureteral stent or nephrostomy, or that would typically warrant stent or nephrostomy. Results: Adjuvant UGN-101 after complete endoscopic ablation was used in 52 of 115 (45%) renal units in the oncologic analysis. At first endoscopic evaluation, 36/52 (69%) were without visible disease. At 6.8 months’ median follow-up, the ipsilateral disease-free rate was 63%. Recurrence after adjuvant UGN-101 therapy was more likely in multifocal tumors compared to unifocal (HR 3.3, 95% CI 1.07-9.91). Compared with UGN-101 treatment for chemoablation of measurable disease, there were significantly fewer disease detections with adjuvant therapy (P < .001). Ureteral stenosis after UGN-101 was diagnosed in 10 patients (19%) undergoing adjuvant therapy compared to 17 (29%) undergoing chemoablative therapy (P [ .28). Conclusions: In patients being considered for UGN-101, maximal endoscopic ablation prior to UGN-101 treatment may result in fewer patients with disease at first endoscopy and possibly fewer adverse events than primary chemoablative therapy. Longer follow-up is needed to determine if UGN-101 after complete endoscopic ablation will lead to durable disease-free interval. [ABSTRACT FROM AUTHOR]

Background: Patients with estrogen receptor (ER)-positive, HER2-negative breast cancer (BC), and high-risk 21-gene recurrence score (RS) results benefit from chemotherapy. We evaluated chemotherapy refusal and survival in healthy older women with high-RS, ER-positive BC. Methods: Retrospective review of the National Cancer Database (2010–2017) identified women ≥ 65 years of age, with ER-positive, HER2-negative, high-RS (≥ 26) BC. Patients with Charlson Comorbidity Index ≥ 1, stage III/IV disease, or incomplete data were excluded. Women were compared by chemotherapy receipt or refusal using the Cochrane–Armitage test, multivariable logistical regression modeling, the Kaplan–Meier method, and Cox's proportional hazards modeling. Results: 6827 women met study criteria: 5449 (80%) received chemotherapy and 1378 (20%) refused. Compared to women who received chemotherapy, women who refused were older (71 vs 69 years), were diagnosed more recently (2014–2017, 67% vs 61%), and received radiation less frequently (67% vs 71%) (p ≤ 0.05). Refusal was associated with decreased 5-year OS for women 65–74 (92% vs 95%) and 75–79 (85% vs 92%) (p ≤ 0.05), but not for women ≥ 80 years old (84% vs 91%; p = 0.07). On multivariable analysis, hazard of death increased with refusal overall (HR 1.12, 95% CI 1.04–1.2); but, when stratified by age, was not increased for women ≥ 80 years (HR 1.10, 95% CI 0.80–1.51). Conclusions: Among healthy women with high-RS, ER-positive BC, chemotherapy refusal was associated with decreased OS for women ages 65–79, but did not impact the OS of women ≥ 80 years old. Genomic testing may have limited utility in this population, warranting prudent shared decision-making and further study. [ABSTRACT FROM AUTHOR]

The retrospective study aimed to analyze the clinical characteristics, primary treatment, and prognosis of cervical clear cell adenocarcinoma in a tertiary referral center. The medical data of cervical clear cell adenocarcinoma patients treated in our institution between 1993 and 2020 were reviewed. Their clinical characteristics and information on treatment and follow-up were collected. Seventy-four cases were included. Six early-stage patients successfully preserved their fertility. Forty-five patients underwent a radical hysterectomy. Patients with pathological risk factors all received adjuvant treatment including chemotherapy, radiotherapy, and chemoradiation. Fifteen patients without risk factors underwent surveillance and five patients received adjuvant chemotherapy for poorly differentiated disease. Twenty cases had radiation for primary treatment. Six of them underwent surgery after chemoradiotherapy, and five had pathological residual disease, including three who had pathological risk factors. The median follow-up interval was 36 months, with a 3-year OS and PFS rate of 82.4% and 81.4%, respectively. No recurrence or death was observed in patients with fertility-sparing treatment. FIGO stage was prognostic factors of PFS (P =.001) and OS(P =.006) and lymph node status was that of PFS (P =.023). FIGO stage and lymph node status were prognostic factors for survival. Fertility-sparing treatment is a safe option for young patients in early stage. Early-stage patients without risk factors may benefit from postoperative surveillance. Occult tumor after chemoradiotherapy is common, and surgical resection is recommended when operable residual disease is detected. [ABSTRACT FROM AUTHOR]

Objective To explore the relationship between the expression level of reticulin 1C (RTN-1C) in peripheral blood mononuclear cells of patients with triple negative breast cancer (TNBC) and the efficacy of neoadjuvant chemotherapy. Methods A total of 154 TNBC patients were selected as the study subjects. Patients were divided into the complete remission group (n=47) and the incomplete remission group (n=107) according to the efficacy of neoadjuvant chemotherapy. Data of age, menstrual status, type of pathology, TNM stage, histological grade, Ki-67 expression >30% and tumour diameter were collected from all subjects. Fasting elbow venous blood samples were collected from TNBC patients before chemotherapy (T0), 7 days after chemotherapy (T1), 14 days after chemotherapy (T2) and 21 days after chemotherapy (T3). Peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation. The expression levels of RTN-1C in mononuclear cells were detected by Western blot assay. The receiver operating characteristic curve (ROC) was used to evaluate the efficacy of RTN-1C in determining neoadjuvant chemotherapy efficacy. Logistic regression was used to analyse risk factors for neoadjuvant chemotherapy efficacy. Nomogram regression models were constructed to predict complete remission of pathology after neoadjuvant chemotherapy, and consistency index (C-index), calibration curves and decision tree curves were used to assess model efficacy. Results The relative expression levels of RTN-1C were lower at T1 and T3 in the complete remission group than those in the incomplete remission group (P＜0.05). The relative expression levels of RTN-1C at T0, T1 and T2 decreased over time in the 2 groups (P＜0.01). The area under the ROC curve (AUC) of T3-RTN- 1C was higher than T0-RTN-1C, T1-RTN-1C and T2-RTN-1C in judging pathological complete remission after neoadjuvant chemotherapy (P＜0.01). Logistic regression analysis showed that T3-RTN-1C＞0.91 (OR=12.178, 95%CI: 4.796-30.924), risk factors for pathological incomplete remission after neoadjuvant chemotherapy (P＜0.05). Model A (constructed by N stage, histological grade and T3-RTN-1C) had a high degree of coincidence between the fitting curve and the ideal curve, while model B (constructed by N stage and histological grade) had a poor degree of coincidence between the fitting curve and the ideal curve. The C-index of model A and model B were 0.866 and 0.772, respectively. When the threshold probability was higher than 0.40, the net benefit of model A in judging pathological complete response after neoadjuvant chemotherapy was higher than that of model B. Conclusion The model constructed by N stage, histological grade and T3-RTN-1C has a high degree of differentiation, accuracy and clinical application value in judging pathological complete response after neoadjuvant chemotherapy [ABSTRACT FROM AUTHOR]

Introduction: Genomic assays are useful tools for tailoring adjuvant treatment in early breast cancer. We aimed to analyse the role of an institutional protocol of a genomic assay for chemotherapy de-escalation. Material and Methods: Prospective cohort study of all consecutive women diagnosed with hormone receptor-positive and human epidermal growth factor receptor 2-negative early breast cancer, tested with the 21-gene Recurrence Score (RS) assay from August 2015 to July 2018 at a Portuguese cancer centre. For being tested, patients should meet at least one of the pre-defined inclusion criteria: i) luminal A-like, pT2pN0; ii) luminal A-like, 1 – 3 positive nodes and comorbidities with higher risk of chemotherapy-induced toxicity; iii) pT1-2pN0, progesterone receptor ≤ 20% and/or Ki67 14% – 40%. Adjuvant treatment was de-escalated to isolated endocrine therapy if RS was less than 18. We measured the reduction in chemotherapy prescribing and its clinical impact, the RS association with pathologic features, and the protocol feasibility. Results: We tested 154 women with a median age of 61 years old (range: 25 – 79), 69% postmenopausal. Tumours were mainly pT1 (55%), pN0 (82%), invasive ductal (73%), G2 (86%), luminal B-like (69%) and stage IA (85%). We obtained a RS less than 18 in 60% of women, with an overall adjuvant chemotherapy reduction of 65%. Seven (95% confidence interval: 5 – 10) patients needed to be screened with the 21-gene RS assay to prevent one clinically relevant adverse event during the first six months of adjuvant treatment. Considering the currently used RS cut-off, only 9% of node-negative and 11% of node-positive patients had RS over 25. We found no relevant associations between RS and pathologic features. The protocol was feasible and did not compromise the adequate timing for adjuvant treatment. Conclusion: These criteria allowed the de-escalation of adjuvant systemic treatment in at least six out of ten women.

Objectives: Cancer chemotherapy potentially increases the risk of myocardial ischemia. This study assessed myocardial microvascular function by cardiac magnetic resonance (CMR) first-pass perfusion in patients treated with chemotherapy for gynecologic malignancies.Methods: A total of 81 patients treated with chemotherapy for gynecologic malignancies and 39 healthy volunteers were prospectively enrolled and underwent CMR imaging. Among the patients, 32 completed CMR follow-up, with a median interval of 6 months. The CMR sequences comprised cardiac cine, rest first-pass perfusion, and late gadolinium enhancement.Results: There were no significant differences in the baseline characteristics between the patients and normal controls (all p > 0.05). Compared with the normal controls, the patients had a lower myocardial perfusion index (PI) (13.62 ± 2.01% vs. 12% (11 to 14%), p = 0.001) but demonstrated no significant variation with an increase in the number of chemotherapy cycles at follow-up (11.79 ± 2.36% vs. 11.19 ± 2.19%, p = 0.234). In multivariate analysis with adjustments for clinical confounders, a decrease in the PI was independently associated with chemotherapy treatment (β = - 0.362, p = 0.002) but had no correlation with the number of chemotherapy cycles (r = - 0.177, p = 0.053).Conclusion: Myocardial microvascular dysfunction was associated with chemotherapy treatment in patients with gynecologic malignancies, and can be assessed and monitored by rest CMR first-pass perfusion.Key Points: • Chemotherapy was associated with but did not aggravate myocardial microvascular dysfunction in patients with gynecologic malignancies. • Rest CMR first-pass perfusion is an ideal modality for assessing and monitoring alterations in myocardial microcirculation during chemotherapy treatment. [ABSTRACT FROM AUTHOR]

Abstract Background To determine whether additional chemotherapy after concurrent chemoradiation (CCRT) improves survival outcomes in patients with early cervical cancer who undergo radical hysterectomy (RH). Methods We included high- or intermediate-risk patients from two institutions, with 2009 FIGO stage IB–IIA, who underwent primary RH and pelvic lymphadenectomy between January 2007 and June 2020, and had completed adjuvant CCRT. Survival outcomes were compared between patients who received additional chemotherapy (study group) and those who did not (control group). Results A total of 198 patients were included in this analysis. The study (n = 61) and control groups (n = 137) had similar patient age, histologic cancer type, 2009 FIGO stage, and tumor size. However, minimally invasive surgery was performed less frequently in the study group than in the control group (19.7% vs. 46.0%, P

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Background: The primary treatment approach for addressing low-risk nonmetastatic gestational trophoblastic neoplasia (LR-NMGTN) in women desiring fertility preservation involves chemotherapy. An alternative option for treatment is fertility-sparing surgical interventions, either alone or in combination with adjuvant chemotherapy. The hypothesised advantages of choosing fertility-sparing surgery in cases of LR-NMGTN include potential avoidance of adverse effects associated with chemotherapy, potential reduction in the number of chemotherapy cycles required to achieve complete remission, and potential reduction in time to remission., Objectives: To measure the benefits and harms of fertility-sparing surgical interventions, with or without adjuvant chemotherapy, compared to primary chemotherapy alone, for the treatment of women with low-risk, non-metastatic gestational trophoblastic neoplasia (LR-NMGTN)., Search Methods: We searched CENTRAL, MEDLINE, Embase, Web of Science, ClinicalTrials.gov and WHO ICTRP on 31 January 2024. We also searched abstracts of scientific meetings and reference lists of included studies., Selection Criteria: We included all randomised controlled trials (RCTs) comparing fertility-sparing surgical interventions, with or without subsequent adjuvant chemotherapy, versus primary chemotherapy as standard care for the treatment of women with LR-NMGTN., Data Collection and Analysis: We employed standard Cochrane methodological procedures. We used the GRADE approach to assess the certainty of evidence for each outcome, if available. We focused on the following outcomes: treatment success rate, relapse, disease-specific mortality, death due to treatment, pregnancy rate, quality of life, and any adverse events., Main Results: We included two RCTs, with a total of 151 participants contributing data to our analyses. Both studies used uterine curettage as the fertility-sparing surgical intervention. Fertility-sparing surgical intervention without subsequent adjuvant chemotherapy versus primary chemotherapy alone One RCT involving 62 participants with varying hCG (human chorionic gonadotrophin) levels evaluated this comparison. Most of our outcomes of interest were not measured in this study. The relative risk of experiencing any adverse event could not be estimated as chemotherapy adverse effects were not reported. The study reported that there were no surgical complications. Chemotherapy was administered to 50% of participants in the intervention group after curettage because their hCG levels increased. Fertility-sparing surgical intervention with subsequent adjuvant chemotherapy versus primary chemotherapy alone One RCT involving 89 participants with hCG levels < 5000 IU/L evaluated this comparison. We judged the risk of bias in the study to be high. The evidence was very uncertain about the effect of uterine curettage with subsequent adjuvant chemotherapy on treatment success rate (RR 1.03, 95% CI 0.86 to1.23; 86 participants), relapse (RR 0.5, 95% CI 0.05 to 5.31; 86 participants), pregnancy rate (RR 0.86, 95% CI 0.31 to 2.34; 86 participants), and rate of adverse events (RR 1.15, 95% CI 0.63 to 2.13; 86 participants), all very low certainty evidence. The relative risks of disease-specific mortality and death due to treatment could not be estimated as there were no deaths in either group. There were no results for quality of life as this outcome was not reported., Authors' Conclusions: Uterine curettage is the only fertility-sparing surgical intervention for LR-NMGTN that has been evaluated in a randomised controlled trial. The evidence is very uncertain about the benefits and harms of uterine curettage, with or without subsequent adjuvant chemotherapy, compared to primary chemotherapy alone. The two available studies are small with a high risk of bias, and future research may find substantially different results for all reported outcomes. Larger RCTs, with appropriate clinical outcome measures, would be required to determine the benefits or harms of fertility-sparing surgical interventions for this population., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Metaplastic breast tumour is a rare, aggressive, mostly triple- negative, dedifferentiated malignancy, which poorly responds to chemotherapy compared to other invasive breast tumours. Since 2000, the WHO has considered it as a separate entity among breast tumours. Given the extremely poor prognosis of the tumour, more studies are needed to establish the most effective treatment strategy supported by data to increase overall survival. The objective of our research was a retrospective analysis of 77 patients with metaplastic breast cancer treated between 01.01.2012 and 28.02.2023 at our institute. Following the descriptive statistics of the patients, the pathological or clinical response was examined in cases of 15 patients treated with neoadjuvant and 14 patients with palliative chemotherapy. Finally, we compared the overall and progression-free survival of metaplastic breast cancer patients treated at our institute with those described in the international literature. The research results, both at our institute and in the literature, are limited by the small number of cases. In our research, with similar numbers of cases as many other investigations, we obtained results close to international data, thereby supporting the collection of data and further research necessary for the most effective treatment strategy for this rare tumour.

Aims: Hormone receptor-positive (HR)+/HER2- breast cancer (BC) is highly heterogeneous, with PI3K/PTEN/mTOR pathway alterations emerging as possible players within this complexity. We longitudinally tracked PI3K/PTEN/mTOR pathway dynamics from baseline biopsy to residual disease (RD)-and to metastases in case of relapse-in HR+/HER2- BC patients receiving neoadjuvant chemotherapy (NACT)., Methods: HR+/HER2- BC patients with RD after NACT were identified. We assessed PIK3CA mutational, Pten-loss and phosphorylation levels of mTOR and its substrates (p70S6K and 4EBP1) on baseline biopsies and matched RD samples; in case of disease relapse, we also assessed PIK3CA mutational status on metastatic samples. Recurrence-free survival (RFS) was adopted as endpoint., Results: 92 patient were included. The conversion rate of PIK3CA mutational status was 12.8%; 1 patient acquired PIK3CA mutation at relapse; the rate of Pten conversion was 33.3%; mTOR phosphorylation levels significantly increased from baseline biopsy to RD, while its substrates significantly decreased. Baseline phosphorylated-mTOR significantly predicted poorer RFS in patients with PIK3CA wild-type status; baseline phosphorylated-70S6K was positively associated with RFS., Conclusions: We observed that PI3K/PTEN/mTOR pathway is highly dynamic under NACT exposure and the assessment of PIK3CA mutations may capture only a small fraction of such complexity. In this context, mTOR activation trough alternative pathways with respect to PIK3CA signalling may have a crucial role in shaping the molecular landscape of HR+/HER2- BC with RD after NACT. It is imperative to further elucidate the role of PIK3CA and mTOR-dependent pathways in shaping chemoresistance and endocrine resistance in high-risk HR+/HER2- early/locally advanced BC patients., Competing Interests: Competing interests: FM received personal fee from Roche, Novartis and Gilead, outside the submitted manuscript. GG reports personal fee from Novartis, Eli Lilly, and Gilead outside the submitted work. VG reports personal fees for advisory board membership from Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Olema Oncology and Sanofi; personal fees as an invited speaker from Amgen, Eli Lilly, GSK, Astra Zeneca, Novartis; personal fees for expert testimony from Eli Lilly; institutional funding as a local PI from AstraZeneca, BMS, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Merck, MSD, Nerviano, Novartis, Roche and Synton Biopharmaceutical. MF has been involved in consulting/advisory roles in Astellas Pharma, Tesaro, MSD, Pierre Fabre, Astra Zeneca, Incyte, GlaxoSmithKline, Diaceutics and Roche, received research funding from Astellas Pharma, QED Therapeutics, and Macrophage Pharma and is supported by grants from the Italian Health Ministry/Veneto region research program NET-2016-02363853 and AIRC 5 per mille 2019 (ID. 22759 programme). MVD reports personal fees from Eli Lilly, MSD, Exact Sciences, Novartis, Pfizer, Seagen, outside the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Pancreatic ductal adenocarcinoma (PDAC) has a high recurrence rate even after radical resection because of subclinical tumors. To manage them, a reliable biomarker that can indicate the presence of subclinical tumors and predict their chemosensitivity is required. This study aimed to identify a miRNA as a biomarker that can be used to individualize postoperative adjuvant chemotherapy using postoperative peripheral blood samples. Integrating miRNA microarray data from the blood of 18 patients with PDAC and the in vitro results regarding the phenotypes of chemoresistant PDAC cells, a candidate miRNA was identified. The relationships between candidate miRNA expression and chemosensitivity were examined in vitro and in clinical samples from other cohorts of 33 patients with recurrence. Comprehensive analyses of blood samples detected 5 candidate miRNAs. Of these, miR-26a-5p was considered a candidate biomarker of chemosensitive phenotypes. In validation experiments, chemosensitivity was inversely correlated with miR-26a-5p expression in vitro. Moreover, the ability of miR-26a-5p to predict chemosensitivity was clinically evaluated using blood samples. Patients with high miR-26a-5p expression in the blood after radical resection exhibited a significantly longer survival time after recurrence. Thus, we concluded that miR-26a-5p is a potentially useful biomarker for managing patients with PDAC, especially those undergoing adjuvant chemotherapy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Takeda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported .Although dose-dense adjuvant chemotherapy administered once every 2 weeks leads to superior outcomes compared with standard regimens once every 3 weeks, the observed improvement is largely limited to studies using the suboptimal paclitaxel schedule once every 3 weeks as control. PANTHER is an international phase III trial which compared sequential epirubicin/cyclophosphamide and docetaxel administered either once every 2 or once every 3 weeks, with tailored dosing at the dose-dense schedule according to hematologic toxicity. In this end-of-study analysis, the median follow-up was 10.3 years. Compared with standard adjuvant chemotherapy, dose-dense treatment improved breast cancer recurrence-free survival (hazard ratio [HR], 0.80 [95% CI, 0.65 to 0.98]; P = .030), event-free survival (HR, 0.78 [95% CI, 0.65 to 0.94]; P = .009), and distant disease-free survival (HR, 0.79 [95% CI, 0.64 to 0.98]; P = .030) while the improvement in overall survival was not statistically significant (HR, 0.82 [95% CI, 0.65 to 1.04]; P = .109). To our knowledge, this is the first trial that confirms the benefit of a dose-dense regimen over a control regimen containing docetaxel once every 3 weeks.

Objectives: To investigate the clinicopathological characteristics and prognosis of patients with uterine sarcoma treated following surgery for presumed benign disease., Methods: We identified all patients with uterine sarcoma found incidentally after primary surgery for presumed benign disease who presented to our institution and received re-exploration for completion surgery from January 1, 2004 to January 1, 2021. We analyzed the clinicopathological characteristics and prognosis., Results: Overall, 95 patients were included in our study. For the initial surgery, myomectomy was performed in 50 (52.6%, 50/95) patients, hysterectomy was performed in 45 (47.4%, 45/95) patients. All patients were re-explored to complete the staging operation. The median time to the staging surgery was 40 days (range 15-90 days). There were 29 patients (30.5%, 29/95) had remnant sarcomas, with 17 patients (17/95, 17.9%) on the remaining uterus, 9 patients (9/95, 9.5%) had disseminated diseases, and 4 patients (4/95, 4.2%) had positive lymph nodes. About 40 patients (42.1%) received adjuvant chemotherapy, 55.2% (16/29) and 36.4% (24/66) patients with/without remnant diseases received adjuvant chemotherapy, respectively (P = 0.087). The median follow-up duration was 76.7 months (IQR: 34.8-118.1 months). And 17 patients (17.9%) had recurrence following re-exploration surgery. 5-year progression-free survival (PFS) and 5-year overall survival (OS) for the entire cohort was 81.7% and 92.1%, respectively. Patients with remnant sarcomas had a tendency towards a worse 5-year PFS and 5-year OS, compared with those without (5-year PFS: 75.6% vs. 84.5%, P = 0.224; 5-year OS: 85.5% vs. 95.1%, P = 0.217). Patients with disseminated diseases had a worse 5-year OS (62.5% vs. 95.1%, P = 0.007) and non-significantly worse 5-year PFS (64.8% vs. 83.4%, P = 0.153) compared with those without., Conclusions: Patients with uterine sarcoma treated following surgery for presumed benign disease have a favorable survival. Patients with disseminated diseases had a worse 5-year OS compared with those without. Surgical re-exploration may be valuable for removing remnant sarcomas and disseminated diseases., (© 2024. The Author(s).)

Background: Sarcopenic obesity (SO) affects outcomes in various malignancies. However, its clinical significance in patients undergoing neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC) remains unclear. This study investigated the impact of pre- and post-NAC SO on postoperative morbidity and survival., Methods: Data from 207 patients with LAGC, who underwent NAC followed by radical gastrectomy between January 2010 and October 2019, were reviewed. Skeletal muscle mass and visceral fat area were measured pre- and post-NAC using computed tomography to define sarcopenia and obesity, the coexistence of which was defined as SO., Results: Among the patients, 52 (25.1%) and 38 (18.4%) developed SO before and after NAC, respectively. Both pre- (34.6%) and post- (47.4%) NAC SO were associated with the highest postoperative morbidity rates; however, only post-NAC SO was an independent risk factor for postoperative morbidity [hazard ratio (HR) = 9.550, 95% confidence interval (CI) = 2.818-32.369; P < .001]. Pre-NAC SO was independently associated with poorer 3-year overall [46.2% vs. 61.3%; HR = 1.258 (95% CI = 1.023-1.547); P = .049] and recurrence-free [39.3% vs. 55.4%; HR 1.285 (95% CI 1.045-1.579); P = .017] survival., Conclusions: Pre-NAC SO was an independent prognostic factor in patients with LAGC undergoing NAC; post-NAC SO independently predicted postoperative morbidity., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: If communicated adequately, numerical decision-relevant information can support informed and shared decision making. Visual formats are recommended, but which format supports patients depending on their health literacy (HL) levels for specific decisions is unclear., Study Aim: The aim of this study is to investigate: 1) the effect of survival rates and side-effects presentation formats on comprehension and 'feeling informed'; 2) differential effects among women with higher/lower HL, with adjuvant systemic breast cancer therapy as case example., Methods: Two online experiments among women from the Dutch population without a history of breast cancer were conducted. Experiment 1 had a 3 (survival rate format: text block-bar graph-icon array) x 2 (HL: low-high) between-subjects design. Experiment 2 had a 5 (side-effects format: no probability information-probability information in numbers with or without a visualisation-probability information in numbers with or without a visualisation accompanied by a description of the side-effects) x 2 (HL: low-high) design. Primary outcomes were comprehension and feeling informed (Experiment 2 only). Formats were previously designed in co-creation with patients., Results: In Experiment 1, presentation format did not affect gist or verbatim comprehension. Higher HL was associated with higher gist comprehension. Experiment 2 showed an interaction between presentation format and HL on 'feeling informed'. When provided with visualised probability information without a description of the side-effects, women with lower HL felt better informed than women with higher HL., Conclusion: Visual formats did not enhance comprehension of survival rate information beyond a well-designed text block format. However, none of the formats could overcome HL differences. When designing decision-relevant information, visualisations might not necessarily provide an advantage over structured numerical information for both patients with lower and higher HL. However, a deeper understanding of presenting side-effect information is warranted., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 van Strien-Knippenberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To evaluate the impact of adjuvant chemotherapy, type of ovarian surgery, and the surgical approach on fertility in patients with stage I immature teratoma of the ovary., Methods: Clinicopathologic data were retrospectively collected and analyzed from a cohort of 47 patients with childbearing desire treated for a stage I immature teratoma of the ovary at IRCCS San Gerardo dei Tintori Hospital, Monza, Italy. Multivariate logistic regression was used to address the influence of chemotherapy and type of surgery on the outcome., Results: Among the patients included, 78.7% (37/47) were able to get pregnant, with a live birth rate of 80.9% (51/63 pregnancies). These rates were not different between adjuvant chemotherapy versus surveillance group (62.5% (5/8) and 82.0% (32/39), respectively; p=0.22) nor between the type of ovarian surgery (cystectomy vs unilateral salpingo-oophorectomy; p=0.57) and surgical approach (laparotomy or laparoscopy; p=0.18). A statistically significant difference was found for stage of disease (a decrease in pregnancy rate from 86.5% (32/37) for stage IA to 50.0% for stage IC (5/10); p=0.02), but it was not confirmed in the multivariate analysis. After relapse diagnosis and management, a total of 62.5% (5/8) of patients conceived and had at least one live birth baby., Conclusions: The fertility-sparing approach is feasible in this population, and fertility does not depend on surgical approach or post-operative treatment. However, adjuvant chemotherapy should be carefully evaluated in this setting., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim of this study was to investigate the impact of adjuvant treatments, factors influencing recurrence, and survival data in patients with 2023 International Federation of Gynecology and Obstetrics (FIGO) stage IIB endometrial cancer., Methods: A retrospective analysis was conducted on patients with endometrial cancer who underwent surgery between 2005 and 2022 at seven different centers in Turkey. Demographic, clinicopathological, and survival data were collected and analyzed., Results: Among 7323 patients, 565 (7.7%) were classified as 2023 FIGO stage IIB based on pathological results. Of 565 patients, 214 were followed without receiving adjuvant treatment, while 335 (95.4%) received adjuvant radiotherapy, and 16 (4.6%) received radiotherapy and chemotherapy. The locoregional recurrence rate was higher in patients with a tumor size >4 cm (p=0.038) and myometrial invasion >50% (p=0.045). In patients with distant metastasis, the recurrence rate was lower in those with myometrial invasion <50% compared with myometrial invasion ≥50% (p=0.031). The impact of adjuvant treatment on endometrial cancer patients revealed no significant differences for both disease free survival (p=0.85) and overall survival (p=0.54). Subgroup analyses showed that in patients with deep myometrial invasion, adjuvant treatment was associated with a significant increase in overall survival (p=0.044), but there was no effect on disease-free survival (p=0.12)., Conclusions: Patients with stage IIB endometrial cancer with myometrial invasion ≥50% were more likely to have locoregional and distant metastases. Adjuvant radiotherapy or chemoradiotherapy did not demonstrate an overall survival benefit in these patients., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Breast-conserving surgery, adjuvant systemic therapy, and radiotherapy are the standard of care for most women with early breast cancer. There are few reports of clinical outcomes beyond the first decade of follow-up of randomised trials comparing breast-conserving surgery with or without radiotherapy. We present a 30-year update of the Scottish Breast Conservation Trial., Methods: In this randomised, controlled, phase 3 trial across 14 hospitals in Scotland, women aged younger than 70 years with early breast cancer (tumours ≤4 cm [T1 or T2 and N0 or N1]) were included. They underwent breast-conserving surgery (1 cm margin) with axillary node sampling or clearance. Oestrogen receptor (ER)-rich patients (≥20 fmol/mg protein) received 20 mg oral tamoxifen daily for 5 years. ER-poor patients (<20 fmol/mg protein) received chemotherapy (cyclophosphamide 600 mg/m 2 , methotrexate 50 mg/m 2 , and fluorouracil 600 mg/m 2 every 21 days intravenously in eight courses). Stratification was by menstrual status (within or more than 12 months from last menstrual period) and ER status (oestrogen concentration ≥20 fmol/mg protein, <20 fmol/mg protein, or unknown) and patients were randomly assigned (1:1) to high-dose (50 Gy in 20-25 fractions) local or locoregional radiotherapy versus no radiotherapy. No blinding was possible due to the nature of the treatment. We report the primary endpoint of the original trial, ipsilateral breast tumour recurrence, and the co-primary endpoint, overall survival. Clinical outcomes were compared by the log-rank test. Hazard ratios (HRs) are reported, with no radiotherapy as the reference group. Failures of the proportional hazards assumption are reported if significant. All analyses are by intention to treat., Findings: Between April 1, 1985, and Oct 2, 1991, 589 patients were enrolled and randomly assigned to the two treatment groups (293 to radiotherapy and 296 to no radiotherapy). After exclusion of four ineligible patients (two in each group), there were 291 patients in the radiotherapy group and 294 patients in the no radiotherapy group. Median follow-up was 17·5 years (IQR 8·4-27·9). Ipsilateral breast tumour recurrence was significantly lower in the radiotherapy group than in the no radiotherapy group (46 [16%] of 291 vs 107 [36%] of 294; HR 0·39 [95% CI 0·28-0·55], p<0·0001). Although there were differences in the hazard rate for ipsilateral breast tumour recurrence in the first decade after treatment (HR 0·24 [95% CI 0·15-0·38], p<0·0001), subsequent risks of ipsilateral breast tumour recurrence were similar in both groups (0·98 [0·54-1·79], p=0·95). There was no difference in overall survival between the two groups (median 18·7 years [95% CI 16·5-21·5] in the no radiotherapy group vs 19·2 years [16·9-21·3] in the radiotherapy group; HR 1·08 [95% CI 0·89-1 ·30], log-rank p=0·43)., Interpretation: Our findings suggest that patients whose biology predicts a late relapse a decade or more after breast-conserving surgery for early breast cancer might gain little from adjuvant radiotherapy., Funding: Breast Cancer Institute (part of Edinburgh and Lothian Health Foundation) and PFS Genomics (now part of Exact Sciences)., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Although robotic pancreatectomy may facilitate an earlier functional recovery, the impact of a robotic pancreatectomy program during its early experience on the timing of return to intended oncologic therapy (RIOT) after surgery is unknown., Methods: In this retrospective cohort study, we used propensity score matching with a 1:2 ratio to compare patients who underwent robotic or open surgery (distal pancreatectomy or pancreatoduodenectomy) for pancreatic ductal adenocarcinoma (PDAC) during the first 3 years of our robotic pancreatectomy experience (January 2018-December 2021). Generalized estimating equations modeling was used to evaluate the effect of surgical approach on early RIOT, defined as adjuvant chemotherapy initiation within 8 weeks after surgery, and late RIOT, defined as initiation within 12 weeks after surgery., Results: The matched cohort included 26 patients who underwent robotic pancreatectomy and 52 patients who underwent open pancreatectomy. Rates of receipt of adjuvant chemotherapy were 96.2% and 78.9%, respectively. Rate of early RIOT in the robotic group (73.1% was higher than that in the open group (44.2%; P = 0.018). In multivariable analysis, a robotic approach was associated with early RIOT (odds ratio, 3.54; 95% confidence interval 1.08-11.62; P = 0.038). Surgical approach did not impact late RIOT (odds ratio, 3.21; 95% confidence interval 0.71-14.38; P = 0.128)., Conclusions: Compared with open pancreatectomy, robotic pancreatectomy did not delay RIOT. In fact, odds of early RIOT were increased, which supports the oncological safety of our robotic pancreatectomy program during its implementation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: Adjuvant chemotherapy has been advised for high-risk stage II and III colon cancer since 2004. After the IDEA study showed no clinically relevant difference in outcome, reduction of adjuvant CAPOX duration from 6 to 3 months was rapidly adopted in the Dutch treatment guideline in 2017. This study investigates the real-world impact of the guideline change on overall survival (OS) and patient-reported outcomes (PROs)., Methods: Patients with high-risk stage II (pT4 +) and III (pN+) colon cancer were selected from the Netherlands Cancer Registry, based on surgical resection and adjuvant CAPOX before (2015-2016) versus after (2018-2019) the guideline change. Both groups were compared on OS, using multivariable Cox regression, and on PROs., Results: Patients treated before (n = 2330) and after (n = 2108) the guideline change showed similar OS (HR 1.02; 95 %CI [0.89-1.16]), also in high-risk stage III (pT4/N2, HR 1.06 [0.89-1.26]). After the guideline change, 90 % of patients were treated for 3 months with no inferior OS to those still receiving 6 months (HR 0.89 [0.66-1.20]). PROs 2 years after CAPOX completion, available for a subset of patients, suggest a lower neuropathy (n = 366; 26.2 [21.3-31.1] to 16.5 [14.4-18.6]) and better quality of life (n = 396; 80.9 [78.6-83.2] to 83.9 [82.8-84.9]), but no significant difference in workability (n = 120; 31.5 [27.9-35.1]) to 35.3 [33.8-36.7]), with reduction from 6 to 3 months of CAPOX., Conclusion: This real-world study confirmed that shorter adjuvant CAPOX did not compromise OS and may improve PROs, complementing the IDEA study and supporting 3 months of adjuvant CAPOX in daily clinical practice., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: I.A.F: Grant to institution: DoMore Diagnostics. F.H.B: Payment to institution from Personal Genome Diagnostics. G.R.V: Grants to institution and/or nonfinancial support: BMS, Merck, Servier, Personal Genome Diagnostics, Bayer, Sirtex, Pierre Fabre, Lilly, Delfi Diagnostics, Nordic all financial supports transferred to the institute. A.M.M and W.M.U.G: declare no potential conflicts of interests. M.K: advisory role: Eisai, Nordic Farma, Merck-Serono, Pierre Fabre, Servier. Institutional scientific grants: Bayer, Bristol Myers Squibb, Merck, Personal Genome Diagnostics (PGDx), Pierre Fabre, Roche, Sirtex, Servier. Non-financial interests: chair of the ESMO RWD-DH working group, co- chair: DCCG, PI PLCRC (national observational cohort study), involved in several clinical trials as PI or co-investigator in CRC. J.M.L.R: institutional financial interests: Bayer, BMS, Merck-Serono, Pierre Fabre, Servier, HUB 4 organoids, Cleara Biotech., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Accurate prediction of patients at risk for early recurrence (ER) among patients with colorectal liver metastases (CRLM) following preoperative chemotherapy and hepatectomy remains limited., Methods: Patients with CRLM who received chemotherapy prior to undergoing curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. Multivariable Cox regression analysis was used to assess clinicopathological factors associated with ER, and an online calculator was developed and validated., Results: Among 768 patients undergoing preoperative chemotherapy and curative-intent resection, 128 (16.7 %) patients had ER. Multivariable Cox analysis demonstrated that Eastern Cooperative Oncology Group Performance status ≥1 (HR 2.09, 95%CI 1.46-2.98), rectal cancer (HR 1.95, 95%CI 1.35-2.83), lymph node metastases (HR 2.39, 95%CI 1.60-3.56), mutated Kirsten rat sarcoma oncogene status (HR 1.95, 95%CI 1.25-3.02), increase in tumor burden score during chemotherapy (HR 1.51, 95%CI 1.03-2.24), and bilateral metastases (HR 1.94, 95%CI 1.35-2.79) were independent predictors of ER in the preoperative setting. In the postoperative model, in addition to the aforementioned factors, tumor regression grade was associated with higher hazards of ER (HR 1.91, 95%CI 1.32-2.75), while receipt of adjuvant chemotherapy was associated with lower likelihood of ER (HR 0.44, 95%CI 0.30-0.63). The discriminative accuracy of the preoperative (training: c-index: 0.77, 95%CI 0.72-0.81; internal validation: c-index: 0.79, 95%CI 0.75-0.82) and postoperative (training: c-index: 0.79, 95%CI 0.75-0.83; internal validation: c-index: 0.81, 95%CI 0.77-0.84) models was favorable (https://junkawashima.shinyapps.io/CRLMfollwingchemotherapy/)., Conclusions: Patient-, tumor- and treatment-related characteristics in the preoperative and postoperative setting were utilized to develop an online, easy-to-use risk calculator for ER following resection of CRLM., 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. No funding was received for this study., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Adjuvant therapy is an important tool in the arsenal of brain tumor management and can improve patients' outcomes significantly but low- and middle-income countries (LMICs) often face challenges in provision. Therefore, our study aims to highlight barriers and strategies to adjuvant therapy of brain tumors in low-resource settings., Method: A comprehensive search of literature was conducted using PubMed, CINAHL, Google Scholar, and Scopus, from inception to October 20, 2022. The review included studies on adjuvant therapy for brain tumors in LMICs and identified themes using the National Surgical, Obstetric, and Anesthesia Plan (NSOAP) domains., Results: 32 studies were included in the review. The most reported barriers to adjuvant care were limited access to healthcare (14 %), limited access to chemotherapy and radiation equipment (25 %), and traditional or alternative medications (11 %). Strategies for improvement include improving the availability of specialized radiation oncology training (8 %) and improving access to neuro-diagnostics and neurotherapeutics (12 %). In addition, efforts to subsidize treatment (4 %) and provide financial coverage through the Ministry of Health (4 %) can help to address the high cost of care and improve access to funding for chemotherapy. Finally, establishing documentation systems and registries (16 %), implementing standardized national treatment guidelines (8 %) can help to improve overall care for brain tumor patients in LMICs., Conclusion: A multimodal approach of strategies targeting workforce, infrastructure, service delivery, financing, and information management is needed to improve adjuvant care for brain tumors. International collaboration and partnerships can also play a key role in addressing barriers and improving care in LMICs., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Different imaging tools, including digital breast tomosynthesis (DBT), are frequently used for evaluating tumor response during neoadjuvant chemotherapy (NACT). This study aimed to explore whether using artificial intelligence (AI) for serial DBT acquisitions during NACT for breast cancer can predict pathological complete response (pCR) after completion of NACT., Methods: A total of 149 women (mean age 53 years, pCR rate 22 %) with breast cancer treated with NACT at Skane University Hospital, Sweden, between 2014 and 2019, were prospectively included in this observational cohort study (ClinicalTrials.gov: NCT02306096). DBT images from both the cancer and contralateral healthy breasts acquired at three time points: pre-NACT, after two cycles of NACT, and after the completion of six cycles of NACT (pre-surgery) were analyzed. The deep learning AI system used to predict pCR consisted of a backbone 3D ResNet and an attention and prediction module. The GradCAM method was used to obtain insights into the model decision basis through a quantitative analysis of the importance maps on the validation set. Moreover, specific model choices were motivated by ablation studies., Results: The AI model reached an AUC of 0.83 (95% CI: 0.63-1.00) (test set). The spatial correlation of importance maps for input volumes from the same patient but at different time points was high, possibly indicating that the model focuses on the same areas during decision-making., Conclusions: We demonstrate a high discriminative performance of our algorithm for predicting pCR/non-pCR. Availability of larger datasets would permit more comprehensive training of the models and more rigorous evaluation of their prediction performance for future 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Melanoma is the most common skin cancer in children. While the current literature establishes treatment protocols for adult-type melanoma, very few pediatric-specific studies exist, and children are often excluded from melanoma clinical trials 2 . We report a case series of 23 pediatric patients aged 2-20 years old diagnosed with melanoma at the University of Rochester Medical Center between 1/1/2011 and 1/1/2022. 9/23 patients were Stage III; all patients underwent wide local excision and 9 received adjuvant therapies. 2/23 (8.7%) patients had recurrence of their malignancy after therapy while 21/23 (91.3%) remained without disease progression; 1 patient died from unknown cause, but the rest are alive and currently without disease. All patients whose initial therapy included nivolumab in addition to wide local excision did not have recurrence or progression of their disease. This case series highlights trends in the presentation, treatment, and outcomes of pediatric melanoma; however, additional multi-center studies are needed to establish the clinical utility of such features in pediatric melanoma.

Purpose: The role of neoadjuvant chemotherapy (NAC) in colon cancer remains unclear. This trial investigated whether 3 months of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery., Patients and Methods: OPTICAL was a randomized, phase III trial in patients with clinically staged locally advanced colon cancer (T3 with extramural spread into the mesocolic fat ≥5 mm or T4). Patients were randomly assigned 1:1 to receive six preoperative cycles of mFOLFOX6 or four cycles of CAPOX, followed by surgery and adjuvant chemotherapy (NAC group), or immediate surgery and the physician's choice of adjuvant chemotherapy (upfront surgery group). The primary end point was 3-year disease-free survival (DFS) assessed in the modified intention-to-treat (mITT) population., Results: Between January 2016 and April 2021, of the 752 patients enrolled, 744 patients were included in the mITT analysis (371 in the NAC group; 373 in the upfront surgery group). At a median follow-up of 48.0 months (IQR, 46.0-50.1), 3-year DFS rates were 82.1% in the NAC group and 77.5% in the upfront surgery group (stratified hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.03]). The R0 resection was achieved in 98% of patients who underwent surgery in both groups. Compared with upfront surgery, NAC resulted in a 7% pathologic complete response rate (pCR), significantly lower rates of advanced tumor staging (pT3-4: 77% v 94%), lymph node metastasis (pN1-2: 31% v 46%), and potentially improved overall survival (stratified HR, 0.44 [95% CI, 0.25 to 0.77])., Conclusion: NAC with mFOLFOX6 or CAPOX did not show a significant DFS benefit. However, this neoadjuvant approach was safe, resulted in substantial pathologic downstaging, and appears to be a viable therapeutic option for locally advanced colon cancer.

Introduction: Incorporation of AKT inhibitors into adjuvant therapy for advanced or metastatic breast cancer has improved clinical outcomes. However, the safety of AKT inhibitors should be better evaluated, given the possibility of prolonging survival and impacting patient quality of life. Our aim was to assess how the addition of AKT inhibitors to adjuvant therapy affects treatment-related adverse events., Methods: We evaluated binary outcomes with risk ratios (RRs), with 95% confidence intervals (CIs). We used DerSimonian and Laird random-effect models for all endpoints. Heterogeneity was assessed using I 2 statistics. R, version 4.2.3, was used for statistical analyses., Results: A total of seven RCTs comprising 1619 patients with BC. The adverse effects that show significance statistical favoring the occurrence of adverse effects in AKT inhibitor were diarrhea (RR 3.05; 95% CI 2.48-3.75; p < 0.00001; I 2  = 49%), hyperglycemia (RR 3.4; 95% CI 1.69-6.83; p = 0.00058; I 2  = 75%), nausea (RR 1.69; 95% CI 1.34-2.13; p = 0.000008; I 2  = 42%), rash (RR 2.79; 95% CI 1.49-5.23; p = 0.0013; I 2  = 82%), stomatitis (RR 2.24; 95% CI 1.69-2.97; p < 0.00001; I 2  = 16%) and vomiting (RR 2.99; 95% CI 1.85-4.86; p = 0.00009; I 2  = 42%). There was no significant difference between the groups for alopecia (p = 0.80), fatigue (p = 0.087), and neuropathy (p = 0.363380)., Conclusion: The addition of AKT inhibitors to adjuvant therapy was associated with an increase in treatment-related adverse events. These results provide safety information for further clinical trials evaluating AKT inhibitor therapy for patients with metastatic BC. Clinicians should closely monitor patients for treatment-related adverse events to avoid discontinuation of therapy and morbidity caused by these early-stage therapies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The phase III PRODIGY study demonstrated that neoadjuvant chemotherapy with docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 chemotherapy (CSC) improved progression-free survival (PFS) compared with surgery followed by adjuvant S-1 (SC) for patients with resectable locally advanced gastric cancer (LAGC) with clinical T2-3N+ or T4Nany disease. The primary end point was PFS. Overall survival (OS) was the secondary end point. We herein report the long-term follow-up outcomes, including OS, from this trial. A total of 238 and 246 patients were randomly assigned to the CSC and SC arms, respectively, and were treated (full analysis set). As of the data cutoff (September 2022), the median follow-up duration of the surviving patients was 99.5 months. Compared with SC, CSC significantly increased the OS (adjusted hazard ratio [HR], 0.72; stratified log-rank P = .027) with an 8-year OS rate of 63.0% and 55.1% for the CSC and SC arms, respectively. CSC also significantly improved the PFS (HR, 0.70; stratified log-rank P = .016). In conclusion, neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, prolonged the OS of Asian patients with LAGC relative to patients treated with surgery and adjuvant S-1. It should be considered one of the standard treatment options for patients with LAGC in Asia.

Background: To evaluate survival outcomes of pulmonary resection for isolated metachronous pancreatic cancer metastasis., Methods: A systematic search of electronic data sources and reference lists were conducted. Proportion meta-analysis model was constructed to quantify 1- to 5-year survival after pulmonary resection for isolated metachronous pancreatic cancer metastasis. Random-effects modelling was applied to calculate pooled outcome data., Results: Twenty-four retrospective studies were included reporting a total of 168 patients who underwent pulmonary resection for isolated pancreatic cancer metastasis. The nature of the index pancreatic surgery included 65% pancreaticoduodenectomies, 17.5% distal pancreatectomies, 0.5% total pancreatectomy, and 17% unspecified. Adjuvant chemotherapy was given to 88% of the patients. The median disease-free interval was 35 (8-96) months. The type of pulmonary resection included 54% wedge resections, 26% lobectomies, 4% segmentectomies, 1% pneumonectomies, and 15% unspecified. Pulmonary resection was associated with 1-year survival of 91.1% (95% CI 86.6%-95.5%), 2-year survival of 77.5% (95% CI 68.9%-86.0%), 3-year survival of 65.0% (95% CI 50.7%-79.3%), 4-year survival of 52.0% (95% CI 37.2%-66.9%), and 5-year survival of 37.0% (95% CI 25.0%-49.1%)., Conclusion: Pulmonary resection for isolated pancreatic cancer metastasis is associated with acceptable overall patient survival. We recommend selective pulmonary resection for isolated pulmonary metastasis from pancreatic cancer. Our findings may encourage conduction of better-quality studies in this context to help establishment of definitive treatment strategies., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: Breast cancer has an average 10-year relative survival reaching 84%. This favorable survival is due, in part, to the introduction of biomarker-guided therapies. We estimated the population-level effect of the introduction of two adjuvant therapies-tamoxifen and trastuzumab-on recurrence using the trend-in-trend pharmacoepidemiologic study design., Methods: We ascertained data on women diagnosed with nonmetastatic breast cancer who were registered in the Danish Breast Cancer Group clinical database. We used the trend-in-trend design to estimate the population-level effect of the introduction of (1) tamoxifen for postmenopausal women with estrogen receptor (ER)-positive breast cancer in 1982, (2) tamoxifen for premenopausal women diagnosed with ER-positive breast cancer in 1999, and (3) trastuzumab for women <60 years diagnosed with human epidermal growth factor receptor 2-positive breast cancer in 2007., Results: For the population-level effect of the introduction of tamoxifen among premenopausal women diagnosed with ER-positive breast cancer in 1999, the risk of recurrence decreased by nearly one-half (OR = 0.52), consistent with evidence from clinical trials; however, the estimate was imprecise (95% confidence interval [CI] = 0.25, 1.85). We observed an imprecise association between tamoxifen use and recurrence from the time it was introduced in 1982 (OR = 1.24 95% CI = 0.46, 5.11), inconsistent with prior knowledge from clinical trials. For the introduction of trastuzumab in 2007, the estimate was also consistent with trial evidence, though imprecise (OR = 0.51; 95% CI = 0.21, 22.4)., Conclusions: We demonstrated how novel pharmacoepidemiologic analytic designs can be used to evaluate the routine clinical care and effectiveness of therapeutic advancements in a population-based setting while considering some limitations of the approach., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Limited data exist on the frequency with which clinical progression during neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) impacts eligibility for a vaginal-sparing surgical approach or on the utility of interim imaging assessment. We sought to evaluate the incidence of clinical upstaging following NAC that would render a patient ineligible for a vaginal-sparing cystectomy., Methods: Eighty-nine female patients with non-metastatic MIBC treated with NAC and radical cystectomy (RC) (2012-2023) were retrospectively reviewed. Tumor location(s) was determined from transurethral resection of bladder tumor operative reports. Pre- and post-NAC clinical staging was determined from imaging. Outcomes of interest included clinical upstaging and upstaging to vaginal invasion after NAC., Results: 75/89 patients had pre- and post-NAC imaging. Fifty-five had no change in clinical staging, 6 patients were upstaged (4 cT2→cT3, 2 cT3→cT4), and 14 patients were downstaged (13 cT3→cT2, 1 cT4→cT2). Of the 75 patients with pre- and post-NAC imaging, 39 had trigone tumors. Of these, 28 had no change in clinical staging, 2 were upstaged (1 cT2→cT3, 1 cT3→cT4) and 9 were downstaged (8 cT3→cT2, 1 cT4→cT2). Overall, 6/75 (8%) of patients demonstrated clinical upstaging after NAC. 2/39 (5%) of patients with trigone tumors clinically progressed after NAC and both had vaginal invasion (pT4) on final pathology., Conclusion: Although clinical upstaging after NAC was infrequent, 5% of patients with trigonal MIBC were rendered ineligible for vaginal-sparing cystectomy following NAC due to progression. Interim imaging assessment may identify non-responders and preserve eligibility for vaginal-sparing RC., 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 Inc. All rights reserved.)

Background: Adjuvant chemotherapy following curative surgery for locally advanced gastric cancer (AGC) significantly improves long-term patient prognosis. However, delayed chemotherapy (DC), in which patients are unable to receive timely treatment, is a common phenomenon in clinical practice for various reasons. This study aimed to investigate the impact of DC on the prognosis of patients with stage II-III locally AGC and explore the associated risk factors., Methods: Data from four prospective studies were included in the pooled analysis. The planned chemotherapy (PC) group was defined as the time interval between surgery and the first chemotherapy ≤ 49 d, while the DC group was defined as the time interval between surgery and chemotherapy > 49 d. The prognosis, recurrence, and risk factors were compared, and a nomogram for predicting DC was established., Results: In total, 596 patients were included, of whom 531 (89.1%) had PC and 65 (10.9%) had DC. Survival analysis revealed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower in the DC group than those in the PC group (log-rank P < 0.001). Cox univariable and multivariable analyses showed that DC was an independent risk factor for OS and DFS in stage II-III patients (P < 0.05). Based on the significant factors for DC, a prediction model was established that had a good fit, high accuracy (AUC = 0.780), and clinical applicability in both the training and validation sets., Conclusion: Delayed chemotherapy after gastrectomy is associated with poor long-term prognosis in patients with locally advanced stage II-III GC disease. But standardized, full-cycle adjuvant chemotherapy after surgery may play a remedial role, and can to a certain extent compensate the poor effects caused by delayed chemotherapy., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Endocrine therapy plays a crucial role in the treatment of women with hormone receptor-positive breast cancer. However, non-adherence remains a frequent issue known to negatively impact survival. Based on a comprehensive literature review, this article explores the terminologies employed to describe adherence and methods used for its assessment, the adherence data reported with adjuvant endocrine therapy with targeted therapies, the determinants of adherence or non-adherence, and finally, tested solutions to address it. The results show that a better understanding of the causes of non-adherence would help to better identify patients at risk, and to develop personalized intervention programs capable of improving adherence to adjuvant endocrine therapy. In light of the literature, interventions are likely to require a multimodal approach and integration into our future healthcare pathways., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background and Objective: EVEREST is a phase 3 trial in patients with renal cell cancer (RCC) at intermediate-high or very high risk of recurrence after nephrectomy who were randomized to receive adjuvant everolimus or placebo. Longer recurrence-free survival (RFS) was observed with everolimus (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.72-1.00; p = 0.051), but the nominal significance level (p = 0.044) was not reached. To contextualize these results with positive phase 3 trials of adjuvant sunitinib and pembrolizumab, we conducted a secondary analysis in a similar population of EVEREST patients with very high-risk disease and clear cell histology., Methods: Postnephrectomy patients with any clear cell component and very high-risk disease, defined as pT3a (grade 3-4), pT3b-c (any grade), T4 (any grade), or node-positive status (N+), were identified. A Cox regression model stratified by performance status was used to compare RFS and overall survival (OS) between the treatment arms., Key Findings and Limitations: Of 1499 patients, 717 had clear cell histology and very high-risk disease; 699 met the eligibility criteria, of whom 348 were randomized to everolimus arm, and 351 to the placebo arm. Patient characteristics were similar between the arms. Only 163/348 (47%) patients in the everolimus arm completed all treatment as planned, versus 225/351 (64%) in the placebo arm. Adjuvant everolimus resulted in a statistically significant improvement in RFS (HR 0.80; 95%CI 0.65-0.99, p = 0.041). Evidence of a survival benefit was not seen (HR 0.85; 95%CI 0.64-1.14, p = 0.3) CONCLUSIONS AND CLINICAL IMPLICATIONS: In patients with clear cell RCC at very high-risk for recurrence, adjuvant everolimus resulted in significantly improved RFS compared to placebo but resulted in a high discontinuation rate due to adverse events. Although the treatment HR for OS was consistent with RFS findings, it did not reach statistical significance. With a focus on risk stratification tools and/or biomarkers to minimize toxicity risk in those not likely to benefit, this information can help inform the design of future adjuvant trials in high-risk RCC., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)