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

Simple Summary: Myxoid liposarcoma (MLPS) is a rare soft tissue sarcoma, often affecting the proximal extremity. There is currently limited literature describing MLPS in older individuals. This retrospective study describes treatment outcomes and tolerability in older patients treated for non-metastatic MLPS. The study shows that older patients with MLPS tolerated systemic therapy, radiation therapy, and surgery with few toxicities. Background: Myxoid liposarcoma predominantly affects young and middle-aged individuals, and little is known regarding treatment tolerability and outcomes in older patients. This study aims to better understand this older patient population. Methods: This single institution retrospective study included patients aged 70 years and older with localized (non-metastatic) myxoid liposarcoma. Results: Sixteen patients were included. The median age was 75 years, and 9 (56%) were female. Fourteen (88%) were extremity tumors and two (12%) were trunk. The median tumor size was 10.4 cm (range, 3.6 to 28 cm). Five (31%) tumors had a round cell component. All patients had surgery. Fourteen (88%) had perioperative radiation, and three (19%) had perioperative chemotherapy. One patient had postoperative infection, and one patient had neutropenic fever from preoperative chemotherapy. The median follow up from surgery was 6.3 years. Eight (50%) patients died from MLPS. The median relapse-free survival and overall survival were 34 months and 75 months, respectively. Conclusions: Most older patients with localized MLPS received perioperative radiation therapy with surgery, and few serious toxicities were reported. Even with treatment, half of the patients relapsed. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck squamous cell carcinoma (HNSC) is the most common type of cancer in the head and neck region, affecting areas like the mouth and throat. Understanding how these cancers grow and spread is crucial for developing better treatments. This study focuses on a group of proteins called solute carrier (SLC) transporters, which help cancer cells survive and grow by moving nutrients and other molecules in and out of cells. We investigated the levels of these transporters in cancerous tissues compared to normal tissues and found that certain SLC transporters are much more active in tumors. These transporters are linked to worse outcomes for patients. By targeting these specific transporters with new drugs, we hope to create more effective treatments that can block cancer growth and improve survival rates for patients with HNSC. Background: Head and neck squamous cell carcinoma (HNSC) is the most prevalent cancer in the head and neck region, originating from the mucosal epithelium of the oral cavity, pharynx, and larynx. The solute carrier (SLC) transporter superfamily, consisting of over 400 proteins across 65 families, plays a crucial role in cellular functions and presents promising targets in precision oncology. This study aims to analyze the expression of SLC transporters in HNSC and their potential as biomarkers and therapeutic targets. Methods: We leveraged mRNA and protein expression data from The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (HPA) to examine SLC transporter expression in HNSC. Gene Set Enrichment Analysis (GSEA) was conducted to assess the involvement of SLC transporters in various oncogenic pathways. Results: Significant upregulation of SLC transporters was observed in tumor tissues compared to normal tissues, with notable increases in SLC16A3, SLC53A1, SLC25A32, and SLC2A3. This upregulation correlated with poorer overall survival (OS) and disease-specific survival (DSS). GSEA revealed that these transporters are significantly involved in critical oncogenic pathways, including epithelial-mesenchymal transition (EMT), angiogenesis, and hypoxia, which are vital for cancer progression and metastasis. Conclusions: The study identifies SLC transporters as potential biomarkers and therapeutic targets in HNSC. Targeting these transporters with small molecule inhibitors could disrupt essential supply routes for cancer cells, enhancing treatment efficacy and improving patient outcomes. This study paves the way for developing SLC-based target therapies in precision oncology, with the goal of improving survival rates for patients with HNSC. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. Traditional methods for predicting patient outcomes rely heavily on the physical characteristics of tumors. Our research aims to develop a new, simple risk score that uses three specific molecular markers found in tumor tissues. By examining the presence and levels of these markers, we hope to better predict which patients have a higher risk of poor outcomes. This can help doctors make more informed decisions about treatment options. Our findings may lead to improved survival rates by identifying high-risk patients who need more aggressive treatment and sparing low-risk patients from unnecessary procedures. Introduction: Several new molecular markers in colorectal carcinomas have been discovered; however, classical histopathological predictors are still being used to predict survival in patients. We present a novel risk score, which uses molecular markers, to predict outcomes in patients with colorectal carcinoma. Methods: The immunohistochemistry of tissue micro arrays was used to detect and quantify H2BUB1, RBM3 and Ki-67. Different intensities of staining were categorized for these markers and a score was established. A multivariate analysis was performed and survival curves were established. Results: 1791 patients were evaluated, and multivariate analysis revealed that our risk score, the 3-biomarker classifier, is an independent marker to predict survival. We found a high risk-score to be associated with dismal median survival for the patients. Conclusions: A more personalized score might be able to better discriminate low- and high-risk patients and suggest adjuvant treatment compared to classical pathological staging. Our score can serve as a tool to predict outcomes in patients suffering from colorectal carcinoma. [ABSTRACT FROM AUTHOR]

Simple Summary: The no specific molecular profile (NSMP) subtype of endometrial cancers remains a poorly understood class from a molecular standpoint, with a wide range of prognoses due to their internal heterogeneity. In this article, we confirm the value of a previously proposed further subdivision of NSMP into two risk classes: low-risk and high-risk; they are characterized by marked differences in oncological outcomes, including both the risk of recurrence and mortality. We are confident that this subdivision could bring significant benefits in the near future, not only in terms of modulating adjuvant therapy but also in standardizing research cohorts for more consistent and reproducible data. (1) Background: Endometrial carcinoma (EC) classified as no specific molecular profile (NSMP) represents a heterogeneous group with variable prognoses. This retrospective, single-center study aims to further stratify NSMP ECs to tailor treatment strategies and improve outcomes. (2) Methods: From 2020 to 2023, we collected data on 51 patients diagnosed with NSMP EC following the introduction of molecular profiling at our institution. Patients were retrospectively analyzed for estrogen receptor (ER) status, histotype, and grade to identify potential prognostic subgroups. (3) Results: Our analysis identified two distinct subgroups within NSMP EC: low-risk and high-risk, based on ER status, histotype, and grade. The low-risk NSMP group demonstrated significantly better survival outcomes compared to the high-risk group. With a median follow-up time of 16 moths (IQR 13.0–29.7), the disease-free survival (DFS) and overall survival (OS) for the low-risk group were 100%. For the high-risk group, the DFS and OS were 71.4% and 78.6%, respectively, which showed a statistically significantly difference (Log-Rank Mantel-Cox < 0.001). In the high-risk group, four patients experienced recurrence, and three of these patients died. (4) Conclusions: Stratifying NSMP EC into low-risk and high-risk categories based on ER status, histotype, and grade can lead to more accurate prognostic assessments. In time, it may require tailored adjuvant therapies and a personalized treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Relapses of acute promyelocytic leukemia (APL) remain a challenge despite the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Given the variability in salvage therapies and emerging evidence supporting the deferral of hematopoietic cell transplantation (HCT) in patients receiving ATO, we analyzed the outcomes of a multicentric cohort of 67 relapsed APL patients. Better outcomes were reported with ATO ± ATRA compared to chemo-based regimens and ATRA ± Gemtuzumab ozogamicin (GO). A significant survival advantage was observed for patients undergoing HCT in the chemo-based cohort (p = 0.017), but not in the ATO-based group (p = 0.12). Achieving molecular complete remission (CR) post salvage therapy emerged as the main prognostic factor for second relapses in both univariate and multivariate analyses. Our findings support the efficacy of ATO-based therapies in first relapse and enhance the role of molecular remission as an independent outcome predictor in both first and second APL relapses. Background: The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has radically improved the prognosis of acute promyelocytic leukemia (APL), with cure rates above 80%. While relapse occurs in less than 20% of cases, addressing this issue remains challenging. Identifying effective salvage therapies for relapsed APL is crucial to improve patient outcomes. Methods: A retrospective analysis was performed on a multicentric cohort of 67 APL patients in first relapse, treated in three Italian hematology centers from June 1981 to November 2021. The overall survival (OS) and cumulative incidence of relapse (CIR) were calculated, and predictive factors were assessed using Cox regression models. Results: Overall, 61 patients (91%) received ATO ± ATRA (40.3%), chemo-based regimens (40.3%), or ATRA ± Gemtuzumab ozogamicin (GO) (10.4%). Complete remission (CR) was achieved in 98.2% of patients (molecular CR, n = 71.4%). With a median follow-up time of 54.5 months, the 5-year OS was 73% in the ATO ± ATRA group, 44% in the chemo-based group, and 29% in the ATRA ± GO group (p = 0.035). The 5-year OS rate was also higher for transplant recipients vs. non-recipients within the chemo-based cohort (50% vs. 33%, p = 0.017), but not in the ATO-based cohort (p = 0.12). ATO-based salvage therapy resulted in better OS in both univariate (p = 0.025) and multivariate analyses (p = 0.026). The 2-year CIR was higher in patients without molecular CR vs. patients in molecular CR (66% vs. 24%, p = 0.034). Molecular CR was a significant predictor of second relapse in both univariate (p = 0.035) and multivariate analyses (p = 0.036). Conclusions: Our findings support the efficacy of ATO-based therapies in first relapse of APL and confirm the achievement of molecular remission as an independent outcome predictor in both first and second APL relapse. [ABSTRACT FROM AUTHOR]

Simple Summary: Upfront novel androgen receptor signaling inhibitors (ARSIs) are the first-line treatment for metastatic castration-sensitive prostate cancer (mCSPC). However, there are a certain number of cases in which androgen deprivation therapy (ADT) is more effective in patients of Asian descent. If we can identify patients who show a marked response to ADT within 12 weeks after ADT, which is the inclusion criterion for upfront ARSI clinical trials, it would be valuable from an economic standpoint. A total of 218 patients who received ADT treatment at Kanazawa University Hospital between 2000 and 2020 were included in this study. Multivariate analysis revealed that a decrease in PSA levels of <95% at 12 weeks after ADT initiation was a predictor of short time to castration resistance (TTCR) in low-risk patients. We propose a new treatment strategy, in which patients with low-risk mCSPC are treated with ADT and switched to ARSIs, based on the rate of PSA reduction at 12 weeks. Background: The treatment strategy for metastatic castration-sensitive prostate cancer (mCSPC) has changed significantly in recent years. Based on various guidelines, an upfront androgen receptor signaling inhibitor (ARSI) is the first choice, but in patients of Asian descent, including Japanese patients, there are a certain number of cases in which androgen deprivation therapy (ADT) and CAB are more effective. If patients can be identified who show a marked response to ADT within 12 weeks after the initiation of ADT, which is the inclusion criterion for ARSI clinical trials targeting mCSPC, it would be valuable from an economic standpoint. Methods: A total of 218 patients with pure prostate adenocarcinoma and treated with ADT at the Kanazawa University Hospital between January 2000 and December 2020 were included in this study. As a risk classification for mCSPC, in addition to the LATITUDE and CHAARTED criteria, we used the castration-sensitive prostate cancer classification proposed by Kanazawa University (Canazawa), developed by the Department of Urology of Kanazawa University. The Canazawa classification was based on three factors: Gleason pattern 5, bone scan index (BSI) ≥ 1.5, and lactate dehydrogenase (LDH) ≥ 300 IU/L. It defined patients with one factor or less as low-risk and patients with two or three factors as high-risk. The overall survival (OS) and time to castration resistance (TTCR) were estimated retrospectively using the Kaplan–Meier method, and factors associated with TTCR were identified using univariate and multivariate analyses. Results: The median follow-up period was 40.4 months, the median OS period was 85.2 months, and the median TTCR period was 16.4 months. The Canazawa risk classification provided the clearest distinction between the OS and TTCR in mCSPC patients. Multivariate analysis revealed a decrease in PSA levels of <95% at 12 weeks after ADT initiation and was a predictor of short TTCR in low-risk, low-volume patients across all risk classifications. Conclusion: The Canazawa classification differentiated the prognosis of mCSPC patients more clearly. A PSA reduction rate of <95% at 12 w after starting ADT in low-risk, low-volume patients of all risk classifications was significantly shorter than the TTCR. We propose a new treatment strategy, in which patients with low-risk mCSPC are treated with ADT and switched to ARSIs based on the rate of PSA reduction at 12 w. [ABSTRACT FROM AUTHOR]

Simple Summary: Approximately 40% of all diagnoses of rectal cancer in Spain are locally advanced. A multimodal treatment is needed, and one of its pillars is radiotherapy, with a classic dose scheme of up to 50–50.4 Gy concomitantly with oral capecitabine or 5-fluorouracil. Dose escalation is being explored to achieve higher rates of a pathological complete response, but the optimal dose and its impact on the outcomes are unclear. Our study aimed to evaluate the percentage of complete pathological responses obtained with an intensified neoadjuvant radiotherapy treatment scheme. We confirmed in a homogeneous population (49 patients treated with standard radiotherapy vs. 50 patients treated with dose-escalated radiotherapy) higher rates of a pathological complete response with a dose of up to 54 Gy concomitantly with oral capecitabine. Neoadjuvant radiotherapy intensification is useful for specimen sterilization and should be offered to selected patients. Locally advanced rectal cancer requires a multimodal treatment. Radiotherapy is being explored for intensification to improve the rates of pathological complete responses (ypCR rates) which are correlated with better outcomes. This study reports a comparison between standard versus escalated doses in a preoperative scenario. The ypCR rates, toxicity, postoperative complications, and disease-free and overall survival at 5 years are described. From 2012 to 2019, 99 patients were analyzed retrospectively: standard arm (mean of 47.5 Gy) vs. dose-escalated arm (mean of 54.3 Gy). All patients were treated with 3DRT in 25 fractions, with concomitant capecitabine and surgery performed according to the total mesorectal excision principles in both arms. The ypCR was reported using the "College of American Pathologist grades"; the gastrointestinal (GI) and genitourinary (GU) toxicity was reported using the "Common Terminology Criteria for Adverse Events" (CTCAE 4.0). The ypCR rates were higher in the dose-escalated group (25% vs. 10.64%; p = 0.07), with a lower rate of non-treatment response (61.36% vs. 38.64%; p = 0.11). No statistical differences between the arms were found in terms of the oncological outcomes, postoperative complications (p = 0.15), second surgeries (p = 0.62), or deaths (p = 0.62). The CTCAE acute GI and GU toxicity were grade I or II in both arms. Our study presents a long-term follow-up in comparative cohorts. [ABSTRACT FROM AUTHOR]

Simple Summary: HER2-low breast cancer is a newly recognized subtype that has shown promising responses to treatment with antibody–drug conjugates (ADCs). However, there is still little known about its clinical and molecular characteristics. In this study, we examined the clinical and pathological features, survival rates, and expression of HER2-related genes in Colombian patients with HER2-low breast cancer, comparing them to HER2-negative and positive groups. We found that HER2-low tumors were better differentiated and had a lower proliferation index compared to HER2-positive tumors. Additionally, compared to HER2-negative cases, HER2-low patients had higher mRNA expression of the ERBB2 gene and longer overall survival rates. Despite these findings, there were no significant differences in survival when adjusted for estrogen receptor status and clinical stage. These results highlight the need for further research on HER2-low breast cancer to optimize treatment strategies for this unique group. HER2-low tumors have shown promise in response to antibody–drug conjugates (ADCs) in recent clinical trials, underscoring the need to characterize this group's clinical phenotype. In this study, we aimed to explore the clinicopathological features, survival rates, and HER2 amplicon mRNA expression of women affected with HER2-low breast cancer, compared with HER2-negative and HER2-positive groups. We included 516 breast cancer patients from Colombia, for whom we compared clinicopathological features, mRNA expression of three HER2 amplicon genes (ERBB2, GRB7 and MIEN1), survival and risk of mortality between HER2-low cases (1+ or 2+ with negative in situ hybridization (ISH) result) with HER2-positive (3+ or 2+ with positive ISH test) and HER2-negative (0+) cases. A higher proportion of patients with better-differentiated tumors and a lower proliferation index were observed for HER2-low tumors compared to the HER2-positive group. Additionally, HER2-low tumors showed higher mRNA expression of the ERBB2 gene and longer overall survival rates compared to HER2-negative cases. Nonetheless, a Cox-adjusted model by ER status and clinical stage showed no statistically significant differences between these groups. Our results show differences in important clinicopathological features between HER2-low and both HER2-positive and negative tumors. Given this unique phenotype, it is crucial to evaluate the potential advantages of ADC therapies for this emerging subtype of breast cancer. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions The purpose of this phase 1 trial was to evaluate the safety and toxicity of repeated normothermic intraperitoneal paclitaxel (PTX) for patients with gastric cancer metastatic to the peritoneum.A Bayesian optimal interval design was used to prospectively identify the safety and tolerability of escalating doses of intraperitoneal paclitaxel at weekly treatments for 3 weeks, followed by a 1‐week break, and then three additional treatments. The primary objective was to define the maximum tolerated dose. Secondary end points included safety, tolerability, and antitumor activity.A total of 25 patients were treated between January 2020 and April 2023. Five dose‐limiting toxicities were observed at 100 mg/m2. Treatment‐related grade 3–4 toxicity included leukopenia (32%) and neutropenia (32%). Seven patients required a schedule change to every other week treatments. The maximum tolerated dose for intraperitoneal PTX was 100 mg/m2. The peritoneum post‐intraperitoneal PTX demonstrated progression in five (20%), stable disease in five (20%), improvement in 10 (40%), and not evaluable in five (20%). Eight patients (32%) had resolution of their peritoneal disease and seven (28%) underwent attempted resection. The median overall survival (OS) from the diagnosis of metastatic disease was 18.8 months and from the date of treatment initiation was 10.8 months. One‐, 2‐, and 3‐year OS rates from the diagnosis of metastatic disease were 84%, 38%, and 25%, respectively.Paclitaxel may be safely used at intraperitoneal doses of 100 mg/m2. Neutropenia associated with weekly treatments was common. Peritoneal complete clinical response rates with multimodality therapy including PTX were promising. [ABSTRACT FROM AUTHOR]

This single-arm multi-institutional prospective study aimed to evaluate the 10-year outcomes of sublobar resection for small-sized ground-glass opacity-dominant lung cancer. Among 73 patients prospectively enrolled from 13 institutions between November 2006 and April 2012, 53 ground-glass opacity-dominant lung cancer patients underwent sublobar resection with wedge resection as the first choice. The inclusion criteria were maximum tumor size of 8–20 mm; ≥ 80% ground-glass opacity ratio on high-resolution computed tomography; lower 18F-fluorodeoxyglucose accumulation than the mediastinum; intraoperative pathological diagnosis of adenocarcinoma in situ; and no cancer cells on intraoperative cut margins. The primary endpoint was a 10-year disease-specific survival. The 53 eligible patients had a mean tumor size of 14 ± 3.4 mm and a mean ground-glass opacity ratio of 95.9 ± 7.2%. Wedge resection and segmentectomy were performed in 39 and 14 patients, respectively. The final pathological diagnoses were adenocarcinoma in situ in 47 patients (88.7%) and adenocarcinoma with mixed subtype in 6 patients (11.3%). The 10-year disease-specific survival and overall survival were 100% and 96.2%, respectively, during a median follow-up period of 120 months (range, 37–162 months). Ground-glass opacity-dominant small lung cancer is cured by sublobar resection when patients are strictly selected by the inclusion criteria of this study. [ABSTRACT FROM AUTHOR]

Background: Maintaining the dose-intensity of cancer treatment is an important prognostic factor of aggressive hematological malignancies. The objective of this study was to assess the long-term outcomes of intensive care unit (ICU) survivors with acute myeloid leukemia (AML) or aggressive B-cell non-Hodgkin lymphoma (B-NHL) with emphasis on the resumption of the intended optimal regimen of cancer treatment. Patients and methods: We conducted a retrospective (2013–2021) single-center observational study where we included patients with AML and B-NHL discharged alive from the ICU after an unplanned admission. The primary endpoint was the change in the intended optimal cancer treatment following ICU discharge. Secondary endpoints were 1-year progression-free survival and overall survival rates. Determinants associated with modifications in cancer treatment were assessed through multivariate logistic regression. Results: Over the study period, 366 patients with AML or B-NHL were admitted to the ICU, of whom 170 survivors with AML (n = 92) and B-NHL (n = 78) formed the cohort of interest. The hematological malignancy was recently diagnosed in 68% of patients. The admission Sequential Organ Failure Assessment (SOFA) score was 5 (interquartile range 4–8). During the ICU stay, 30 patients (17.6%) required invasive mechanical ventilation, 29 (17.0%) vasopressor support, and 16 (9.4%) renal replacement therapy. The one-year survival rate following ICU discharge was 59.5%. Further modifications in hematologic treatment regimens were required in 72 patients (42%). In multivariate analysis, age > 65 years (odds ratio (OR) 3.54 [95%-confidence interval 1.67–7.50], p < 0.001), ICU-discharge hyperbilirubinemia > 20 µmol/L (OR 3.01 [1.10–8.15], p = 0.031), and therapeutic limitations (OR 16.5 [1.83–149.7], p = 0.012) were independently associated with modifications in cancer treatment. Post-ICU modifications of cancer treatment had significant impact on in-hospital, 1-year overall survival and progression-free survival. Conclusion: The intended cancer treatment could be resumed in 58% of ICU survivors with aggressive hematological malignancies. At the time of ICU discharge, advanced age, persistent liver dysfunction and decisions to limit further life-support therapies were independent determinants of cancer treatment modifications. These modifications were associated with worsened one-year outcomes. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Concurrent chemoradiotherapy is the standard therapy for locally advanced non‐small cell lung cancer (NSCLC). However, there is little evidence supporting its use in older adults. Low‐dose daily carboplatin combined with thoracic radiotherapy is considered a standard regimen for this population. To establish a simple and feasible carboplatin administration method, we conducted a study of weekly carboplatin and concurrent radiotherapy for older adults with locally advanced NSCLC.This prospective, single‐arm, multicenter, phase II clinical trial included patients aged ≥75 years with unresectable stage III NSCLC and Eastern Cooperative Oncology Group performance status 0–1. Patients received chemoradiotherapy (60 Gy/30 fractions plus concurrent weekly carboplatin at an area under curve of 2 mg mL−1 min−1). The primary endpoint was the overall response rate (ORR). Key secondary endpoints included progression‐free survival (PFS), overall survival (OS), and safety.From July 2020 to June 2022, 37 patients were enrolled from 15 institutions, and 36 patients were evaluable for efficacy and safety. The ORR was 63.9% (95% confidence interval [CI] = 47.6–77.5). Median PFS was 14.6 months (95% CI = 9.1–18.1). Median OS was 25.5 months (95% CI = 17.4–not reached). Grade 4 leucopenia, neutropenia, and thrombocytopenia were observed in one patient (2.8%) each.Weekly carboplatin and concurrent radiation therapy was safe in older adults with locally advanced NSCLC, and promising activity was observed. [ABSTRACT FROM AUTHOR]

Recent reports have shown that pre-treatment low muscle mass may lead to poorer outcomes for cancer patients. We explored the correlation between Visceral Adipose Tissue (VAT), Subcutaneous Adipose Tissue (SAT), and Muscle Mass (MM) as measured by CT scans, and overall survival (OS) following diagnosis of colorectal cancer (CRC). We conducted a retrospective review of medical records and CT scans of patients diagnosed with CRC between 2007 and 2018. Demographics, pathology, and clinical parameters were collected. Using Image-J software, we measured VAT, SAT, and MM. Survival rates were analyzed using Kaplan–Meier curves, and prognostic factors were assessed using multivariate Cox regression. Analysis included 408 patients with a mean age of 56.9 years and a median follow-up of 93.3 months. Colon and rectum/rectosigmoid colon cancers were equally distributed. The 5-year OS rate was 67.8%. There was no significant difference in OS rates based on SAT or VAT. However, higher MM was associated with a improved 5-year OS rate. Factors such as age, stage, grade, and surgery were also associated to OS rates. These findings suggest that higher muscle mass may lead to better outcomes for CRC patients, highlighting the potential impact of exercise and nutritional interventions on patient outcomes. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of palliative gastrectomy for advanced GC remains a topic of debate. This study sought to establish whether palliative gastrectomy has an impact on prolonging survival. Methods: We carried out systematic searches in PubMed, Cochrane Library, Web of Science, and the EMBASE databases from database inception to July 2023 to gather studies that examined the connection between palliative gastrectomy and the prognosis of advanced GC. The study employed overall survival as the primary outcome, with the hazard ratio serving as the selected parameter to gauge the association. Subgroup analyses were performed to delve into potential differences within the included studies, categorizing them by study region and sample size in order to examine possible sources of heterogeneity. The stability of individual studies was assessed through sensitivity analysis. The analysis included 20 articles, encompassing a total of 23,061 patients. Results: According to the meta-analysis results, patients who underwent palliative gastrectomy exhibited a noteworthy enhancement in overall survival (HR: 1.49; 95% CI: 1.12–1.99; P = 0.006) in comparison to those who did not receive this procedure. There was no association between the type of surgery and the length of hospital stay, as revealed by the analysis (HR = -0.02; 95% CI: -0.84–0.81; P = 0.970). Conclusions: Based on this meta-analysis, patients with advanced gastric cancer who underwent palliative gastrectomy may experience an extended survival duration without a significant prolongation of their hospitalization. [ABSTRACT FROM AUTHOR]

PURPOSE: Cancer of unknown primary (CUP) is a syndrome comprising metastatic cancers without a clinically identified primary site. Although patients with CUP have an unfavorable prognosis, treatment with site-specific therapies guided by clinical features, standard pathology, and molecular assays can improve overall survival. The 92-gene assay (CancerTYPE ID) is a gene expression–based classifier that helps identify the tissue of origin for metastatic cancers with unknown or uncertain diagnoses. This study reports the frequency of selected molecular aberrations of oncogenes, including KRAS , IDH1/2 , BRCA1/2 , and BRAF , in patients with CUP in the MOSAIC database to highlight potential treatment options. METHODS: MOSAIC is a database of patients with CUP submitted for CancerTYPE ID testing and NeoTYPE biomarker testing. Tumor biopsy samples were analyzed by CancerTYPE ID for tumor type identification and further tested for molecular aberrations of oncogenes, including KRAS , IDH1/2 , BRCA1/2 , and BRAF. RESULTS: CancerTYPE ID identified a specific tumor type in 92.5% (2,929 of 3,168) of CUP cases in the MOSAIC database. The most commonly identified histological type was adenocarcinoma (75.4%), with pancreaticobiliary being the most common molecularly diagnosed cancer (24.9%). Aberrations in KRAS , IDH1/2 , BRCA , and BRAF genes were identified in 18.8% (n = 597) of biopsies. A cancer-specific US Food and Drug Administration (FDA)–approved or investigational targeted therapy was potentially available for 24.6% (n = 147) of these patients. CONCLUSION: This retrospective analysis supports incorporating CancerTYPE ID into the evaluation for patients with CUP to help determine the tissue of origin and identify actionable genetic alterations. This approach may allow more patients with CUP to benefit from site-specific FDA-approved targeted therapies or enrollment into clinical trials. Enabling Precision Site-Specific Therapies in CUP Patients with CancerTYPE ID [ABSTRACT FROM AUTHOR]

Background: Most breast cancer-related deaths are caused by distant metastases and drug resistance. It is important to find appropriate biomarkers to monitor the disease and to predict patient responses after treatment early and accurately. Many studies have found that clustered circulating tumor cells, with more correlations with metastatic cancer and poor survival of patients than individual ones, are promising biomarkers. Methods: Eighty samples from eleven patients with breast cancer during follow-up visits were examined. By using a microfluidic chip and imaging system, the number of circulating tumor cells and microemboli (CTC/CTM) were counted to assess the distribution in stratified patients and the potential in predicting the disease condition of patients after treatments during follow-up visits. Specific components and subtypes of CTM were also preliminarily investigated. Results: Compared to CTC, CTM displayed a distinguishable distribution in stratified patients, having a better AUC value, in predicting the disease progression of breast cancer patients during follow-up visits in this study. Four subtypes were categorized from the identified CTM by considering different components. In combination with CEA and CA153, enumerated CTC and CTM from individual patients were applied to monitor the disease condition and patient response to the therapy during follow-up visits. Conclusions: The CTM and its subtypes are promising biomarkers and valuable tools for studying cancer metastasis and longitudinally monitoring cancer patients during follow-up visits. [ABSTRACT FROM AUTHOR]

Clinical staging in lung cancer has implications for treatment planning and prognosis. We sought to determine the rate of inaccurate clinical stage (relative to pathologic), identify risk factors for inaccuracy, and evaluate the association of inaccuracy on survival. We hypothesized that inaccurate staging was associated with poor survival. In this retrospective cohort study, adult patients who received surgical resection without neoadjuvant treatment for nonsmall cell lung cancer from 2004 to 2020 in the National Cancer Database were categorized by accuracy of clinical stage (relative to pathologic stage). Multivariate models were used to determine risk factors for inaccuracy. The association between inaccuracy and overall survival was also analyzed. We identified 255,598 patients with lung cancer, including 84,543 patients (33.1%) who were inaccurately staged. Stage inaccuracy was associated with higher tumor, node, metastasis stage (T-category 3: odds ratio [OR] = 1.2, 95% confidence interval [CI] 1.15-1.28; N-category 2: OR = 2.6, 95% CI 2.47-2.79), greater quantity of lymph nodes evaluated, and more extensive resection (extended lobectomy/bilobectomy: OR = 1.3, 95% CI 1.20-1.37; pneumonectomy: OR = 1.6, 95% CI 1.54-1.74). Patients undergoing robotic surgery were less likely to be inaccurately staged (OR = 0.89, 95% CI 0.852-0.939). Inaccurate staging was associated with worse overall survival (5-y 67.5% accurate versus 55.4% inaccurate, P < 0.001). Inaccurate staging was also associated with worse survival in a multivariate Cox model (hazard ratio [HR] = 1.3, 95% CI 1.29-1.33). Both "understaging" (path > clinical) and "overstaging" (clinical > path) were associated with inferior survival. Inaccurate clinical stage (relative to pathologic) occurs in one-third of patients receiving surgery for lung cancer. Inaccuracy is associated with poor survival. Quality improvement initiatives should focus on improving clinical staging accuracy. [ABSTRACT FROM AUTHOR]

Purpose: Quantifying the association of chemotherapy relative dose intensity (RDI) with overall survival may enable supportive care interventions that improve chemotherapy RDI to estimate their magnitude of potential clinical benefit. Methods: This cohort study included 533 patients with stage II–III colon cancer who initiated a planned regimen of 12 cycles of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. The primary exposure was chemotherapy RDI. The primary outcome was overall survival. Restricted cubic splines estimated hazard ratios (HR). Results: Chemotherapy regimen RDI was associated with overall survival in an L-shaped pattern (linear P = 0.006; nonlinear P = 0.057); the risk of death was flat above 85% but increased linearly below 85%. For example, a decrease in RDI from 85 to 75% was associated with an increased risk of death [HR: 1.20 (95% CI: 1.08, 1.52)], whereas an increase in RDI from 85 to 95% was not associated with the risk of death [HR: 1.06 (95% CI: 0.82, 1.38)]. Conclusion: If chemotherapy RDI is considered a potential surrogate of overall survival, supportive care interventions that improve chemotherapy RDI might confer a potential clinical benefit in this population. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is the third most common type of cancer worldwide. Gastric cancer has a 15% to 20% 5-year overall survival rate, even if the disease just affects the stomach wall. The prognosis is favorable if tumors and their precursors are discovered early on. The current study intended to enhance the prognosis of patients suffering from early-stage stomach cancer. Methods: In this study, 24 patients with stomach cancer who attended to Zagazig University Hospitals' outpatient clinic were included. Every patient underwent a complete medical history, a general examination, and an abdominal examination that included PR and PV. Laboratory tests were performed. Along with gastroscopy and biopsies, all patients also underwent CT, ultrasonography, and CXR scans. Results: There were six women and eighteen men in the study. The distal portion of the stomach was the site of malignancy in all 100 cancer patients under study. A statistically significant correlation was not observed between the sex of the cancer cases under study and either the age distribution or the tumor site. Conclusions: Laparoscopic distal gastrectomy is a safe and effective treatment that offers advantages over open conventional gastrectomy for treating stomach cancer. These advantages include a lower risk of intraoperative blood loss and overall consequences. [ABSTRACT FROM AUTHOR]

Background: A minority of patients with MSS tumors present a high tumor mutation burden (TMB) without underlying MMR defects. Methods: Publicly available genomic series were assessed for identification of patients with MSS gastric gastroesophageal junction, and esophageal adenocarcinomas and a high TMB, defined as more than 10 mutations per Mb. These were compared with MSS cancers and a low TMB for genetic alterations and for survival outcomes. Results: Patients with MSS cancers with high TMB in the MSK series were older but did not differ in other clinicopathologic parameters compared with MSS patients with low TMB. Mutations in tumor suppressors TP53 and APC and oncogenes KRAS and ERBB4 as well as amplifications of ERBB2 were more prevalent in the high TMB group of MSS cancers. Mutations in DDR associated genes, in epigenetic modifiers and in genes associated with immune response were more prevalent in the hIgh TMB group patients. However, high TMB was not associated with an improved survival in MSS gastric/gastroesophageal junction/esophageal adenocarcinomas (Log Rank p = 0.5). Conclusion: MSS Gastric/gastroesophageal junction/esophageal adenocarcinomas with TMB above 10 mutations per Mb possess a genomic landscape with increased alteration frequencies in common gastroesophageal cancer genes and pathways. [ABSTRACT FROM AUTHOR]

Background: The National Comprehensive Cancer Network (NCCN)-recommended treatment for patients with borderline-resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) involves a combination of neoadjuvant FOLFIRINOX chemotherapy and the curative surgical resection of the tumor. This study seeks to identify the clinical, radiological, laboratory, and pathologic predictors that can anticipate the oncological outcomes of patients. Methods: In this study, we conducted a retrospective analysis of patients who had undergone curative surgical resection for BRPC, LAPC, or resectable disease with high-risk features after receiving neoadjuvant FOLFIRINOX at two institutions. We evaluated by means of multivariate analysis whether clinical and laboratory response, tumor markers, radiological response, and pathologic tumor response grade correlated with overall survival (OS) and disease-free survival (DFS). Results: The study enrolled a total of 70 patients with BRPC, LAPC, and resectable disease with high-risk features who underwent resection after neoadjuvant FOLFIRINOX. Age above 65 years and fewer than nine cycles of chemotherapy (OR 4.2; 95% CI 1.4–12.0; p-value 0.007); locally advanced tumors after neoadjuvant treatment (NAT) (OR 7.0; 95% CI 1.9–25.7; p-value 0.003); and lymph node disease and histological tumor regression grade 2 and 3 (OR 4.3; 95% CI 0.9–19.2; p-value 0.05) were risk factors linked to adverse OS and DFS. The median OS and DFS were 33 (22–43.9) months and 16.5 (11.3–21.6) months, respectively. Conclusions: Classification as a LA tumor after NAT was the only preoperative radiological factor that predicted adverse survival in patients undergoing curative surgery after NAT. Other clinical, biochemical, and radiological measures of response were not found to predict OS. Patient age, the cumulative administration of more than eight cycles of chemotherapy, and a significant pathological response were associated with better OS. The results of this study are important for treatment decision-making and prognostication in patients with BRPC and LAPC. [ABSTRACT FROM AUTHOR]

Simple Summary: In this retrospective study of 61 patients with diffuse gliomas, APT-weighted imaging in the solid tumor component provided quantitative metrics associated with WHO grade and survival. Mean APT values of the necrotic component showed high variability between subjects, warranting further investigation. These results highlight the importance of assessing the different tumor components with APT-weighted imaging, to provide useful diagnostic and prognostic information for the management of patients with gliomas. Amide Proton Transfer-weighted (APTw) imaging is a molecular MRI technique used to quantify protein concentrations in gliomas, which have heterogeneous components with varying cellularity and metabolic activity. This study aimed to assess the correlation between the component-specific APT signal of the neoplasm and WHO grade, molecular profile and survival status. Sixty-one patients with adult-type diffuse gliomas were retrospectively analyzed. APT values were semi-automatically extracted from tumor solid and, whenever present, necrotic components. APT values were compared between groups stratified by WHO grade, IDH-mutation, MGMT promoter methylation and 1- and 2-year survival status using Wilcoxon rank-sum test, adjusting for multiple comparisons. Overall survival (OS) was analyzed in the subgroup of 48 patients with grade 4 tumors using Cox proportional-hazards models. Random-effects models were used to assess inter-subject heterogeneity of the mean APT values in each tumor component. APT values of the solid component significantly differed between patients with grades 2–3 and 4 tumors (mean 1.58 ± 0.50 vs. 2.04 ± 0.56, p = 0.028) and correlated with OS after 1 year (1.81 ± 0.58 in survivors vs. 2.17 ± 0.51 in deceased patients, p = 0.030). APT values did not differ by IDH-mutation, MGMT methylation, and 2-year survival status. Within grade 4 glioma patients, higher APT kurtosis of the solid component was a negative prognostic factor (hazard ratio = 1.60, p = 0.040). Mean APT values of the necrosis showed high inter-subject variability, although most necrotic tumors were grade 4 and IDH wildtype. In conclusion, APTw imaging in the solid component provided metrics associated with glioma grade and survival status but showed weak correlation with IDH-mutation and MGMT promoter methylation status, in contrast to previous works. Further research is needed to understand APT signal variability within the necrotic component of high-grade gliomas. [ABSTRACT FROM AUTHOR]

Simple Summary: The survival of glioblastoma (GBM) patients remains at just 12–15 months with a 5% 5 year survival despite them undergoing a harsh and brutal treatment regimen involving surgery, radiation and chemotherapy. This is because GBMs are impossible to completely resect and almost always recur at the borders of the resection margin, while the presence of the blood–brain barrier limits the amount of chemotherapy that can access the brain, requiring the patient to receive high and extremely toxic doses of chemotherapy. In this study, we demonstrate that local delivery of the chemotherapeutic drug irinotecan directly into the border of the resection margin offers a safe route of administration with none of the normal side effects associated with traditional chemotherapy. Glioblastomas are impossible to completely resect and almost always recur at the borders of the resection margin. There is no established chemotherapy regimen available to patients who recur, while systemic treatment is hampered by the blood–brain barrier. Here, we report on the first evaluation in humans of the intraparenchymal injection of irinotecan into the resection cavity after surgical resection of recurrent glioblastoma patients. The cytotoxicity of irinotecan was compared to SN-38 in primary cells from recurrent glioblastoma patients. Irinotecan was injected at multiple (~30) sites of the resection cavity wall at a depth of 3 to 5 mm. SN-38 was more cytotoxic than irinotecan at concentrations below 1 µM due to enzyme kinetics. The intraparenchymal administration of irinotecan was safe, with good wound healing and an absence of swelling, inflammation, or pseudo-abscess formation. The median survival post irinotecan administration was 32.6 weeks. The median overall survival was 30.5 months, with a two-year survival rate of 56%. This study demonstrates that local delivery of irinotecan into the brain parenchyma offers a safe route of administration over systemic delivery in the treatment of recurrent glioblastoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Peritoneal metastases from gastric cancer are linked to a poor prognosis, with median survival ranging from 2 to 9 months. Standard treatments, including systemic chemotherapy and targeted therapies, have demonstrated only limited effectiveness. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an experimental approach under investigation for treating these metastases, but its widespread clinical use is hindered by insufficient evidence regarding its safety and efficacy. This retrospective study presents outcomes from the first PIPAC program in Lithuania, where 32 patients underwent 71 PIPAC procedures between 2015 and 2022. Intraoperative and postoperative complications occurred in 4.2% of cases. Although reductions in peritoneal carcinomatosis index (PCI) and ascites volume were noted, they were not statistically significant. The median overall survival after PM diagnosis was 12.5 months. These findings suggest that PIPAC is a safe and feasible treatment, but further research is needed to establish its efficacy. Background: Peritoneal metastases (PM) of gastric cancer (GC) are considered a terminal condition, with reported median survival ranging from 2 to 9 months. Standard treatment typically involves systemic chemotherapy alone or combined with targeted therapy or immunotherapy, though efficacy is limited. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged as a novel technique for treating GC PM, although it remains an experimental treatment under investigation. This study aimed to summarize the outcomes of GC PM treatment with PIPAC from the Lithuanian PIPAC program. Methods: All patients who underwent PIPAC for GC PM at Vilnius University Hospital Santaros Klinikos between 2015 and 2022 were included in this retrospective study. The safety of PIPAC was assessed by postoperative complications according to the Clavien–Dindo classification. Efficacy was evaluated based on the peritoneal carcinomatosis index (PCI), ascites dynamics throughout the treatment, and long-term outcomes. Results: In total, 32 patients underwent 71 PIPAC procedures. Intraoperative and postoperative morbidity related to PIPAC occurred after three (4.2%) procedures. Following PIPAC, there was a tendency towards a decrease in median PCI from 10 (Q1 3; Q3 13) to 7 (Q1 2; Q3 12), p = 0.75, and a decrease in median ascites volume from 1300 mL (Q1 500; Q3 3600) at the first PIPAC to 700 mL (Q1 250; Q3 4750) at the last PIPAC, p = 0.56; however, these differences were not statistically significant. The median overall survival after PM diagnosis was 12.5 months (95% CI 10–17), and the median survival after the first PIPAC procedure was 5 months (95% CI 4–10). Conclusions: PIPAC is a safe and feasible treatment option for GC PM; however, well-designed prospective studies are needed to fully assess its efficacy. [ABSTRACT FROM AUTHOR]

Simple Summary: Oropharyngeal Squamous Cell Carcinoma (OPSCC) represents a significant fraction of head and neck cancers, with a challenging five-year survival rate of only 50%. Key risk factors include tobacco and alcohol consumption and infection with human papillomavirus (HPV), particularly HPV16. Distinct biological differences exist between HPV-positive and HPV-negative OPSCC, including differences in mutation patterns and gene expression profiles. This study focuses on aldo-keto reductases (AKRs), specifically AKR1C2, which are involved in cellular stress management and detoxification processes, particularly in cisplatin-resistant tumors. This study investigates the role of AKR1C2 in HPV-positive OPSCC and its effect on patient outcomes. The findings indicate that increased levels of AKR1C2 are linked to unfavorable prognosis, particularly in male patients, while higher levels in female patients indicate a favorable prognosis. Head and Neck Squamous Cell Carcinoma (HNSCC), particularly Oropharyngeal Squamous Cell Carcinoma (OPSCC), is a major global health challenge due to its increasing incidence and high mortality rate. This study investigates the role of aldo-keto reductase 1C2 (AKR1C2) in OPSCC, focusing on its expression, correlation with Human Papillomavirus (HPV) status, oxidative stress status, and clinical outcomes, with an emphasis on sex-specific differences. We analyzed AKR1C2 expression using immunohistochemistry in formalin-fixed, paraffin-embedded tissue samples from 51 OPSCC patients. Additionally, we performed RT-qPCR in cultured HPV16-E6*I and HPV16-E6 overexpressing HEK293 cell lines (p53WT). Statistical analyses were performed to assess the correlation between AKR1C2 expression and patient data. Our results indicate a significant association between increased AKR1C2 expression and higher AJCC classification (p = 0.009) as well as positive HPV status (p = 0.008). Prognostic implications of AKR1C2 varied by sex, whereby female patients with high AKR1C2 expression had better overall survival, whereas male patients exhibited poorer outcomes. Additionally, AKR1C2 expression was linked to HPV status, suggesting a potential HPV-specific regulatory mechanism. These findings underscore the complex interplay among AKR1C2, HPV, and patient sex, highlighting the need for personalized treatment strategies for OPSCC. Targeted inhibition of AKR1C2, considering sex-specific differences, may enhance therapeutic outcomes. Future research should investigate these mechanisms to enhance treatment efficacy. [ABSTRACT FROM AUTHOR]

Simple Summary: This study examined the outcomes of patients with gallbladder cancer over 20 years in Saskatchewan, Canada, focusing on geographic, demographic, and clinical factors. A total of 331 patients diagnosed between 2000 and 2019 were included. The majority (64%) had advanced stage 4 disease, with a significant proportion (66%) being rural residents. Key factors associated with poorer overall survival included stage 4 disease, lack of surgery, older age, a higher neutrophil-to-lymphocyte ratio, and no referral to a regional cancer center. Among early-stage patients, stage III disease and urban residence were associated with worse disease-free survival. The findings highlight the late-stage diagnosis and referral challenges impacting the outcomes of gallbladder cancer. Background: Gallbladder cancer (GBC) is an uncommon cancer. This study aimed to determine the outcomes of GBC in relation to geographic, demographic, and clinical factors in a Canadian province from 2000 to 2019. Methods: This population-based retrospective cohort study included all patients diagnosed with gallbladder cancer (GBC) in Saskatchewan, Canada, from 2000 to 2019. Cox proportional multivariate regression analysis was conducted to identify factors associated with poorer outcomes. Results: In total, 331 patients with a median age of 74 years and male–female ratio of 1:2 were identified. Of these patients, 305 (92%) had a pathological diagnosis of GBC. Among patients with documented staging data, 64% had stage IV disease. A total of 217 (66%) patients were rural residents, and 149 (45%) were referred to a cancer center. The multivariate analysis for patients with stage I–III GBC showed that stage III disease [hazard ratio (HR), 2.63; 95% confidence interval (CI), 1.09–6.34)] and urban residence (HR, 2.20; 95% CI, 1.1–4.39) were correlated with inferior disease-free survival. For all patients, stage IV disease (HR, 3.02; 95% CI, 1.85–4.94), no referral to a cancer center (HR, 2.64; 95% CI, 1.51–4.62), lack of surgery (HR, 1.63; 95% CI, 1.03–2.57), a neutrophil–lymphocyte ratio of >3.2 (HR, 1.57; 1.05–2.36), and age of ≥70 years (HR, 1.51; 95% CI, 1.04–2.19) were correlated with inferior overall survival. Conclusions: In this real-world context, the majority of patients with GBC were diagnosed at a late stage and were not referred to a cancer center. For those with early-stage GBC, living in an urban area and having stage III disease were linked to worse outcomes. Across all stages of GBC, stage IV disease, older age, absence of surgery, lack of referral to a cancer center, and a high neutrophil-to-lymphocyte ratio were associated with poorer survival. [ABSTRACT FROM AUTHOR]

Simple Summary: Azacytidine and donor lymphocyte infusions were combined effectively in a single-center high-risk patient cohort (n = 29) for post-transplant relapse of acute myeloid leukemia and myelodysplastic syndrome. Bone marrow Wilms tumor gene 1 (WT1) expression was measured at time of transplant and post-transplant relapse. By using the Cox proportional hazards model, cut-off values for WT1 at both time points were obtained. The disease risk index incorporating initial cytogenetics and the disease stage at transplant as well as WT1 expression was significantly associated with overall survival, indicating that WT1 may represent a minimal residual disease marker in this context of cell therapy response evaluation, especially in high-risk patients currently considered to be in complete remission. Cut-off values for bone marrow WT1 expression for the two decisive treatment time points were proposed. Introduction: Post-transplant relapse of acute myeloid leukemia and myelodysplastic syndrome faces restricted effective salvage regimens. We retrospectively analyzed the use of Azacitidine–donor lymphocyte infusion (AZA/DLI) in this setting. Furthermore, data on bone marrow Wilms tumor gene 1 (WT1) expression were collected. Methods: A Cox proportional hazards model, an outcome-oriented approach for the lowest smoothed plot of the martingale residuals, was performed for the cut-point determination of the respective WT1 expression levels. Finally, a Cox proportional hazards model investigated the association of overall survival (OS) with predictors. Results: An overall response of 41.4% with a median duration of 11.9 months for stable disease and 19.5 months for complete response (CR) patients was achieved. The disease risk index (DRI) high-/very high-risk patients had a shorter OS of 4.4 months than intermediate-risk patients, with 14.5 months, p = 0.007. At transplant, WT1-overexpressing patients (>150 copies) had a shorter median OS of 5.3 months than low-WT1-expressing ones, with 13.5 months, p = 0.024. Furthermore, patients with ≤1000 WT1 copies at relapse had a significantly longer OS with 15.3 months than patients overexpressing WT1, with 4.4 months, p = 0.0002. Conclusions: DRI and WT1 expression associate significantly with OS after AZA/DLI. Hence, WT1 may represent an MRD marker, especially in CR patients at high risk. [ABSTRACT FROM AUTHOR]

Purpose: In laryngeal squamous cell carcinoma (LSCC) treated with transoral laser microsurgery (TOLMS), the status of margins significantly affected local control. When a positive or close margin is present, there is no ubiquitous consensus regarding further treatments. The rationale of the present systematic review and meta-analysis is to investigate the survival impact of the status of the margins in patients affected by LSCC treated with TOLMS. Data sources: PubMed, EMBASE, and Cochrane Library. Methods: We performed a systematic search, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria were: patients affected by LSCC, staged according to the American Joint Committee on Cancer Staging System and treated by TOLMS without any previous treatment; margins status (close, positive, negative) and the adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) of overall survival, disease-specific survival, and disease-free survival has to be reported. Results: Nine studies were deemed eligible for the qualitative analysis, and 3 for the quantitative analysis to investigate the association between margin status and OS. The cumulative number of patients was 3130. The sample size ranged from 96 to 747 patients. The follow-up period ranged from 0 to 201 months. The meta-analysis results show that positive margins have an aHR of 1.30 yet with CI range (0.56 to 2.97). Conclusions: Our current meta-analysis results are unable to definitively assess the real impact of resection margins on OS. Few authors provide accurate data regarding position and types of margins. Further prospective or high-quality studies are required. [ABSTRACT FROM AUTHOR]

Introduction: Older patients (≤75 years) with advanced colorectal cancer (CRC) may have worse survival than non-older patients. We hypothesized that, rather than age alone, concurrent factors may be more relevant for real-world survival. Methods: Patients diagnosed with CRC in a 5-year period (2014–2018) were analyzed to determine which factors influenced in overall survival (OS). Kaplan-Meier method was used to estimate OS. Univariate and multivariate analysis was conducted by Cox regression analysis. The study was approved by Ethics Committee. Results: Out of 477 patients diagnosed with CRC, 231 had advanced disease. Ninety-two patients (40%) were older than 75 years; median OS (mOS) was 17.1 m (95% CI: 14.3–23.3), p < 0.001. In non-older patients, mOS was 26.7 m (95% CI: 21.9–32.6), p < 0.001. We evaluated eighteen concurrent factors that included characteristics related to the patient (age, sex, comorbidities, polypharmacy, Eastern Cooperative Oncology Group (ECOG), and nutritional status), to the tumor (stage at diagnosis, tumor side, molecular profile, tumor burden, location, and number of metastasis), and to the treatment administered (systemic treatment for advanced disease, chemotherapy schedule and number of lines, severe adverse events and dose reductions, and surgery of liver metastasis). In the univariate analysis, age at diagnosis, ECOG, nutritional status, tumor side, molecular profile, tumor burden, systemic treatment for advanced disease, and surgery of liver metastases had significant impact on survival. However, multivariate analysis revealed that only four factors (tumor burden, nutritional status, systemic treatment for advanced disease, and surgery of liver metastases) were independently associated with OS but not older age at diagnosis. Conclusion: Older age is not an independent survival prognostic factor for advanced CRC. Tumor burden, nutritional status, systemic treatment for advanced disease, and surgery of liver metastasis were significant factors associated with OS. These findings suggest that older patients should not be excluded from cancer treatment based on age alone. Plain Language Summary: Older patients with advanced CRC constitute a heterogeneous population, including patients with excellent health status and others with multiple comorbidities, functional dependence, or limited life expectancy. Furthermore, the definition of an "elderly" or "older" patient is not widely accepted and may vary between studies, although 75 years may be an appropriate cut-off point, as confirmed in our study. At present, there are few prospective and randomized studies focused on the progression and treatment of advanced colorectal cancer in elderly patients, so understanding the factors that influence its clinical course is a difficult challenge. In this retrospective real-world study, we analyze the influence of advanced age on the survival of patients with advanced colorectal cancer. The analysis of eighteen characteristics that were grouped in three subcategories: characteristic related to the patient (age, sex, comorbidities, polypharmacy, ECOG, and nutritional status [albumin levels at diagnosis]), to the tumor (stage at diagnosis, tumor side, molecular profile, tumor burden [CEA levels at diagnosis], location and number of metastasis), and to the treatment administrated (systemic treatment for advanced disease, chemotherapy schedule and number of lines, severe adverse events and dose reductions, and surgery of liver metastasis) showed that older age at diagnosis is not an independent prognostic factor of overall survival in patients with metastatic colorectal cancer. However, tumor burden, nutritional status, systemic treatment of advanced disease, or surgery of liver metastases are independent predictors of survival. [ABSTRACT FROM AUTHOR]

Purpose: [18F]-FDG PET/CT and brain MRI are common approaches to detect metastasis in patients of lung cancer. Current guidelines for the use of PET/CT and MRI in clinical T1-category lung cancer lack risk-based stratification and require optimization. This study stratified patients based on metastatic risk in terms of the lesions' size and morphological characteristics. Methods: The detection rate of metastasis was measured in different sizes and morphological characteristics (solid and sub-solid) of tumors. To confirm the cut-off value for discriminating metastasis and overall survival (OS) prediction, the receiver operating characteristic (ROC) analysis was performed based on PET/CT metabolic parameters (SUVmax/SUVmean/SULpeak/MTV/TLG), followed by Kaplan–Meier analysis for survival in post-operation patients with and without PET/CT plus MRI. Results: 2,298 patients were included. No metastasis was observed in patients with solid nodules < 8.0 mm and sub-solid nodules < 10.0 mm. The cut-off of PET/CT metabolic parameters on discriminating metastasis were 1.09 (SUVmax), 0.26 (SUVmean), 0.31 (SULpeak), 0.55 (MTV), and 0.81 (TLG), respectively. Patients undergoing PET/CT plus MRI exhibited longer OS compared to those who did not receive it in solid nodules ≥ 8.0 mm & sub-solid nodules ≥ 10.0 mm (HR, 0.44; p < 0.001); in solid nodules ≥ 8.0 mm (HR, 0.12; p<0.001) and in sub-solid nodules ≥ 10.0 mm (HR; 0.61; p=0.075), respectively. Compared to patients with metabolic parameters lower than cut-off values, patients with higher metabolic parameters displayed shorter OS: SUVmax (HR, 12.94; p < 0.001), SUVmean (HR, 11.33; p <0.001), SULpeak (HR, 9.65; p < 0.001), MTV (HR, 9.16; p = 0.031), and TLG (HR, 12.06; p < 0.001). Conclusion: The necessity of PET/CT and MRI should be cautiously evaluated in patients with solid nodules < 8.0 mm and sub-solid nodules < 10.0 mm, however, these examinations remained essential and beneficial for patients with solid nodules ≥ 8.0 mm and sub-solid nodules ≥ 10.0 mm. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy‐induced anorexia is a common occurrence in patients undergoing treatment for advanced lung cancer. However, the relationship between chemotherapy‐induced anorexia and weight loss during platinum‐based chemotherapy combined with immune checkpoint inhibitors is unclear. This study explored the relationship between chemotherapy‐induced anorexia and therapeutic outcomes in patients with stage IV non‐small‐cell lung cancer undergoing platinum‐based chemotherapy combined with immune checkpoint inhibitors. Methods: The study retrospectively reviewed the medical records of 106 patients with stage IV non‐small‐cell lung cancer treated with platinum‐based chemotherapy and immune checkpoint inhibitors between January 2019 and October 2022. The incidence of weight loss and its association with treatment efficacy was assessed in the chemotherapy‐induced anorexia group. Chemotherapy‐induced anorexia, nausea, and vomiting were evaluated using Common Terminology Criteria for Adverse Events v 5.0. Progression‐free and overall survival were used to measure treatment efficacy. Results: Chemotherapy‐induced anorexia was observed in 13.2% of patients. These patients exhibited significant weight loss at 6 and 9 weeks after treatment initiation compared to those in the non‐chemotherapy‐induced anorexia group. Progression‐free and overall survival were shorter in the chemotherapy‐induced anorexia group than in the non‐chemotherapy‐induced anorexia group, but the difference was not statistically significant. Conclusions: Chemotherapy‐induced anorexia was associated with significant weight loss and reduced treatment efficacy in patients with stage IV non‐small‐cell lung cancer. These results highlight the importance of implementing robust supportive care for chemotherapy‐induced anorexia to mitigate weight loss and uphold treatment effectiveness during platinum‐based chemotherapy combined with immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

KIF2C/MCAK (KIF2C) is the most well-characterized member of the kinesin-13 family, which is critical in the regulation of microtubule (MT) dynamics during mitosis, as well as interphase. This systematic review briefly describes the important structural elements of KIF2C, its regulation by multiple molecular mechanisms, and its broad cellular functions. Furthermore, it systematically summarizes its oncogenic potential in malignant progression and performs a meta-analysis of its prognostic value in cancer patients. KIF2C was shown to be involved in multiple crucial cellular processes including cell migration and invasion, DNA repair, senescence induction and immune modulation, which are all known to be critical during the development of malignant tumors. Indeed, an increasing number of publications indicate that KIF2C is aberrantly expressed in multiple cancer entities. Consequently, we have highlighted its involvement in at least five hallmarks of cancer, namely: genome instability, resisting cell death, activating invasion and metastasis, avoiding immune destruction and cellular senescence. This was followed by a systematic search of KIF2C/MCAK's expression in various malignant tumor entities and its correlation with clinicopathologic features. Available data were pooled into multiple weighted meta-analyses for the correlation between KIF2Chigh protein or gene expression and the overall survival in breast cancer, non-small cell lung cancer and hepatocellular carcinoma patients. Furthermore, high expression of KIF2C was correlated to disease-free survival of hepatocellular carcinoma. All meta-analyses showed poor prognosis for cancer patients with KIF2Chigh expression, associated with a decreased overall survival and reduced disease-free survival, indicating KIF2C's oncogenic potential in malignant progression and as a prognostic marker. This work delineated the promising research perspective of KIF2C with modern in vivo and in vitro technologies to further decipher the function of KIF2C in malignant tumor development and progression. This might help to establish KIF2C as a biomarker for the diagnosis or evaluation of at least three cancer entities. [ABSTRACT FROM AUTHOR]

Introduction: Most patients with advanced gallbladder cancer are treated with multiagent chemotherapy. Immune checkpoint inhibitors offer the possibility of a durable response with less toxicity. This prospective, multicenter, open‐label study was designed to evaluate the anticancer activity of nivolumab plus ipilimumab in patients with advanced gallbladder cancer. Methods: Nineteen patients with advanced gallbladder cancer refractory to ≥1 previous therapy received nivolumab 240 mg intravenously every 2 weeks and ipilimumab 1 mg/kg intravenously every 6 weeks until disease progression or unacceptable toxicity. The primary end point was confirmed radiographic overall response rate (ORR) (complete response [CR] + partial response [PR] confirmed on subsequent scan); secondary end points included unconfirmed overall response, clinical benefit rate (confirmed and unconfirmed responses + stable disease >6 months), progression‐free survival, overall survival, and toxicity. Results: The confirmed ORR was 16% (CR, n = 1 [5%]; PR, n = 2 [11%]); all were microsatellite stable, and the confirmed CR had undetectable programmed death‐ligand 1 by immunohistochemistry. The unconfirmed ORR and clinical benefit rates were both 32%. The median duration of response was 14.8 months (range, 4–35.1+ months). The 6‐month progression‐free survival was 26% (95% CI, 12–55). The median overall survival was 7.0 months (95% CI, 3.9–19.1). The most common toxicities were fatigue (32%), anemia (26%), and anorexia (26%). Aspartate aminotransferase elevation was the most common grade 3/4 toxicity (11%). There was 1 possibly related death (sepsis with attendant hepatic failure). Conclusions: Ipilimumab plus nivolumab was well tolerated and showed modest efficacy with durable responses in previously treated patients with advanced gallbladder cancer. Clinical Trial Registration: NCT02834013 (ClincialTrials.gov). Plain Language Summary: This prospective study assessed the efficacy and safety of nivolumab plus ipilimumab in 19 patients with advanced gallbladder cancer refractory to previous therapy. The combination demonstrated modest efficacy with a 16% confirmed overall response rate, durable responses, and manageable toxicities, suggesting potential benefits for this challenging patient population. Ipilimumab plus nivolumab demonstrated modest efficacy with durable responses and manageable toxicity in previously treated patients with advanced gallbladder cancer. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic distal gastrectomy (LDG) has become a common procedure for treating advanced gastric cancer (AGC) in China. However, there is uncertainty regarding its oncological outcomes compared to open distal gastrectomy (ODG). This study aims to compare the 3-year disease-free survival (DFS) rates among patients who underwent surgery for AGC in northern China. Methods: A multicenter, non-inferiority, open-label, parallel, randomized clinical trial was conducted to evaluate patients with AGC who were eligible for distal gastrectomy at five tertiary hospitals in North China. In this trial, patients were randomly assigned preoperatively to receive either LDG or ODG in a 1:1 allocation ratio. The primary endpoint was postoperative morbidity and mortality within 30 days and the secondary endpoint was the 3-year DFS rate. This trial has been registered at ClinicalTrials.gov (Identifier: NCT02464215). Results: A total of 446 patients were randomly allocated to LDG (n = 223) or ODG group (n = 223) between March 2014 and August 2017. After screening, a total of 214 patients underwent the open surgical approach, while 216 patients underwent laparoscopic surgery. The 3-year DFS rate was 85.9% for the LDG group and 84.72% for the ODG group, with no significant statistical difference (Hazard ratio 1.12; 95% CI 0.68–1.84, P = 0.65). Body mass index (BMI) < 25 kg/m2, advanced pathologic T4, and pathologic N2-3 category were confirmed as independent risk factors for DFS in the Cox regression. Conclusions: In comparison to ODG, LDG with D2 lymphadenectomy yielded similar outcomes in terms of 3-year DFS rates among patients diagnosed with AGC. [ABSTRACT FROM AUTHOR]

Objectives: Insight into the aggressiveness of potential breast cancers found in screening may optimize recall decisions. Specific growth rate (SGR), measured on mammograms, may provide valuable prognostic information. This study addresses the association of SGR with prognostic factors and overall survival in patients with invasive carcinoma of no special type (NST) from a screened population. Methods: In this historic cohort study, 293 women with NST were identified from all participants in the Nijmegen screening program (2003–2007). Information on clinicopathological factors was retrieved from patient files and follow-up on vital status through municipalities. On consecutive mammograms, tumor volumes were estimated. After comparing five growth functions, SGR was calculated using the best-fitting function. Regression and multivariable survival analyses described associations between SGR and prognostic factors as well as overall survival. Results: Each one standard deviation increase in SGR was associated with an increase in the Nottingham prognostic index by 0.34 [95% confidence interval (CI): 0.21–0.46]. Each one standard deviation increase in SGR increased the odds of a tumor with an unfavorable subtype (based on histologic grade and hormone receptors; odds ratio 2.14 [95% CI: 1.45–3.15]) and increased the odds of diagnosis as an interval cancer (versus screen-detected; odds ratio 1.57 [95% CI: 1.20–2.06]). After a median of 12.4 years of follow-up, 78 deaths occurred. SGR was not associated with overall survival (hazard ratio 1.12 [95% CI: 0.87–1.43]). Conclusions: SGR may indicate prognostically relevant differences in tumor aggressiveness if serial mammograms are available. A potential association with cause-specific survival could not be determined and is of interest for future research. [ABSTRACT FROM AUTHOR]

The oncology community has shown growing interest to understand how body composition measures can be utilized to improve cancer treatment and survivorship care for about 20 million individuals diagnosed with cancer annually. Recent observational studies demonstrate that muscle and adipose tissue distribution are risk factors for clinical outcomes such as postoperative complications, and worse overall survival. There is an emergent recognition that body mass index (BMI) is neither adequate to identify patients with adverse health outcomes due to poor muscle health or excess adiposity, nor does BMI accurately classify the distribution of adiposity. Abdominal CT is a most frequently imaging examination for a wide variety of clinical indications, but it is only used to diagnose the immediate problem. Additionally, each CT examination contains very robust data on body composition which generally goes unused in routine clinical practice. The field is eager to identify therapeutic interventions that modify body composition and reduce the incidence of poor clinical outcomes in this population. Large scale population based screening is feasible now by making all of these relevant biometric measures fully automated through the use of artificial intelligence algorithms, which provide rapid and objective assessment. [ABSTRACT FROM AUTHOR]

Introduction: Limited data exist on interphase fluorescent in situ hybridization (iFISH)-based survival outcomes in newly diagnosed multiple myeloma (NDMM) from India. Objectives: To study the demographics and iFISH-based survival outcomes in NDMM patients treated with proteasome inhibitors from a community-based cancer setup. Materials and Methods: We reviewed the records of 25 patients treated with proteasome inhibitors between June 2017 and April 2023 using five high-risk (HR) iFISH markers based on mSMART 3.0. Results: The median age was 60 years (range 34–87). HR iFISH was detected in 12 (48%) patients. With a median follow-up of 27 months, the overall response at the last follow-up was 80% (very good partial response - 52%, complete remission - 20%, and partial response - 8%), with 8 (32%) relapses. Twenty (80%) patients remain alive, with five deaths in HR (sepsis [ n = 3]). The 2.5-year overall survival in HR and standard risk was 55.6% ± 15.2% and 100% (P = 0.01), and event-free survival was 32.4% ± 16.5% and 77.8% ± 13.8% (P = 0.02), respectively. Conclusions: Using limited iFISH HR markers helps in the early and effective stratification of NDMM in the real world. Sepsis remains an important cause of mortality in an Indian setup. [ABSTRACT FROM AUTHOR]

) Objective To explore effective treatments and prognostic factors for diffuse intrinsic pontine glioma (DIPG). Methods Clinical and imaging information and survival data of 14 DIPG patients, treated with radiotherapy combined with temozolomide and nitolizumab or radiotherapy combined with ACT001, were retrospectively analysed at Beijing Tiantan Hospital, Capital Medical University from April 2021 to January 2024. The median progression free survival (PFS) and overall survival (OS) were calculated using Kaplan - Meier survival curves, and multifactorial Cox regression analysis was used to investigate the effects of different factors on PFS and OS. Results The objective response rate (ORR) was 10/14, and the median PFS and OS were 7.83 and 8.30 months, respectively. Multfactorial Cox regression analysis identified the absence of enhancement on baseline imaging as a good prognostic variable for both PFS (RR = 0.052, 95%CI: 0.006-0.416; P = 0.005) and OS (RR = 0.046, 95%CI: 0.005-0.413; P = 0.006), while male (RR = 0.085, 95%CI: 0.009-0.764; P = 0.028), older age (RR = 0.631, 95%CI: 0.423-0.942; P = 0.024), and the absence of symptoms of cranial nerve involvement at the onset (RR = 0.116, 95%CI: 0.017- 0.781; P = 0.027) were also good prognostic variables for OS. Conclusions Female, younger age at diagnosis, cranial nerve involvement at the onset, and enhancement on baseline imaging are risk factors for the survival of children with DIPG. Key words: Diffuse intrinsic pontine glioma; Radiotherapy; Antineoplastic combined chemotherapy protocols; Molecular targeted therapy; Child [ABSTRACT FROM AUTHOR]

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Recurrence after colorectal cancer resection is rarely documented in the general population while a key clinical determinant for patient survival. We identified 8785 patients with colorectal cancer diagnosed between 2010 and 2013 and clinically followed up to 2020 in 15 cancer registries from seven European countries (Bulgaria, Switzerland, Germany, Estonia, France, Italy, and Spain). We estimated world age‐standardized net survival using a flexible cumulative excess hazard model. Recurrence rates were calculated for patients with initially resected stage I, II, or III cancer in six countries, using the actuarial survival method. The proportion of nonmetastatic resected colorectal cancers varied from 58.6% to 78.5% according to countries. The overall 5‐year net survival by country ranged between 60.8% and 74.5%. The absolute difference between the 5‐year survival extremes was 12.8 points for stage II (Bulgaria vs Switzerland), 19.7 points for stage III (Bulgaria vs. Switzerland) and 14.8 points for Stage IV and unresected cases (Bulgaria vs. Switzerland or France). Five‐year cumulative rate of recurrence among resected patients with stage I–III was 17.7%. As compared to the mean of the whole cohort, the risk of developing a recurrence did not differ between countries except a lower risk in Italy for both stage I/II and stage III cancers and a higher risk in Spain for stage III. Survival after colorectal cancer differed across the concerned European countries while there were slight differences in recurrence rates. Population‐based collection of cancer recurrence information is crucial to enhance efforts for evidence‐based management of colorectal cancer follow up. [ABSTRACT FROM AUTHOR]

Non‐small cell lung cancer (NSCLC) patients infected with COVID‐19 experience much worse prognosis. However, the specific mechanisms behind this phenomenon remain unclear. We conducted a multicentre study, collecting surgical tissue samples from a total of 36 NSCLC patients across three centres to analyse. Among the 36 lung cancer patients, 9 were infected with COVID‐19. COVID‐19 infection (HR = 21.62 [1.58, 296.06], p = 0.021) was an independent risk factor of progression‐free survival (PFS). Analysis of RNA‐seq data of these cancer tissues demonstrated significantly higher expression levels of cuproptosis‐associated genes in COVID‐19‐infected lung cancer patients. Using Lasso regression and Cox regression analysis, we identified 12 long noncoding RNAs (lncRNA) regulating cuproptosis. A score based on these lncRNA were used to divide patients into high‐risk and low‐risk groups. The results showed that the high‐risk group had lower overall survival and PFS compared to the low‐risk group. Furthermore, Tumor Immune Dysfunction and Exclusion (TIDE) database revealed that the high‐risk group benefited more from immunotherapy. Drug sensitivity analysis identified cetuximab and gefitinib as potentially effective treatments for the high‐risk group. Cuproptosis plays a significant role NSCLC patients infected with COVID‐19. Promisingly, cetuximab and gefitinib have shown potential effectiveness for managing these patients. [ABSTRACT FROM AUTHOR]

Due to its anti-angiogenic properties, trebananib is frequently employed in the treatment of cancer patients, particularly those with ovarian cancer. We conducted a meta-analysis to assess the efficacy and safety profile of trebananib in combination with other drugs for treating both ovarian and non-ovarian cancer patients. Our search encompassed PubMed, Medline, Cochrane, and Embase databases, with a focus on evaluating study quality. Data extraction was conducted from randomized controlled trials (RCTs), and RevMan 5.3 facilitated result analysis. Combining trebananib with other drugs extended progression-free survival (PFS) [HR 0.81, (95%CI: 0.65, 0.99), p = 0.04] and overall survival (OS) [HR 0.88, (95%CI: 0.79, 1.00), p = 0.04] in ovarian cancer patients. Ovarian cancer patients exhibited a higher objective response rate (ORR) with trebananib compared to non-ovarian cancer cohorts. Moreover, the incorporation of trebananib into the standard treatment regimen for malignant tumors did not significantly elevate drug-related adverse events [RR 1.05, (95% CI: 1.00, 1.11), p = 0.05]. Trebananib plus other drugs can improve the PFS, OS and ORR in patients with cancer, especially ovarian cancer. Our recommendation is to use trebananib plus other drugs to treat advanced cancer, and to continuously monitor and manage drug-related adverse events. PROSPERO (No. CRD42023466988) [ABSTRACT FROM AUTHOR]

Serum carbohydrate antigen 19-9 (Ca19-9) is the only approved biomarker approved for the screening and diagnosis of pancreatic cancer (PC), but its value remains controversial. The aim of our study is to evaluate the role of CA 19-9 in the management of PC patients in jaundiced patients staged by both Computed Tomography (CT) and Endoscopic Ultrasound (EUS). Additionally, we evaluated traditional cholestasis marker behavior. Medical records of 73 patients have been retrospectively reviewed. We considered tumor size, tumor stage, CA 19-9, cytolysis, and cholestasis biomarkers. All patients underwent CT scan for staging. EUS +/− fine-needle biopsy (FNB) was performed in doubtful cases. Median alkaline phosphatase (ALP) and y-glutamyltransferase (GGT) levels were significantly lower compared to baseline after the biliary drainage (204 vs. 465 U/L, p < 0.0001, 204. U/L vs. 608.5, p < 0.0001, respectively), whilst no differences were observed for CA 19-9 levels. CA 19-9 showed significant association with the tumor stage in the pre-drainage setting. CT and EUS showed a low agreement in estimating tumor size (mean difference 4.8 mm 95% LoA −10.82–20.38). We did not find any significant correlation between CA 19-9 and bilirubin levels (r = −0.05, p = 0.7). In our cohort, survival rate was lower in patients with higher CA 19-9 levels (log rank p = 0.007). CA 19-9 has some limitations as a biomarker in the PC setting, thus it cannot address the treatment strategy alone. Nonetheless, it provides valuable information, and is not replaceable for the time being. [ABSTRACT FROM AUTHOR]

Introduction Predictive markers of LV5FU2 maintenance benefit after first-line induction with FOLFIRINOX in patients with metastatic pancreatic cancer are necessary to select patients who will not be harmed by this strategy. Patients and Methods We focused on patients who received 12 cycles of FOLFIRINOX (arm A, N  = 88) or 8 cycles of FOLFIRINOX followed by LV5FU2 maintenance in controlled patients (arm B, N  = 91) from the PRODIGE-35 trial. Prognostic factors and predictors of efficiency were identified by using Cox regression. Median progression-free survival (PFS), overall survival (OS), and time to deterioration of quality of life (TTD-QoL) were evaluated. Results Poor independent prognostic factors were primary tumor in place, age <65 years and the presence of liver metastases for PFS, a baseline neutrophil/lymphocyte ratio (NLR) ≥5 and CA19.9 ≥500 UI/L for OS, independent of the treatment arm. Patients with one metastatic site had a longer PFS in arm A, whereas patients with ≥2 metastatic sites had a longer PFS in arm B. We also identified predictors of OS and TTD-QoL in arm B but these differences were not statistically significant. Conclusion Except for patients with one metastatic site who benefited more from 12 cycles of FOLFIRINOX, a maintenance strategy with LV5FU2 should be widely offered to mPC patients whose survival and QoL are preserved after 4 months of FOLFIRINOX. (ClinicalTrials.gov: NCT02352337). [ABSTRACT FROM AUTHOR]

Introduction: A dynamic molecular biomarker that can identify early efficacy of immune checkpoint inhibitor (ICI) therapy remains an unmet clinical need. Here we evaluate if a novel circulating tumor DNA (ctDNA) assay, xM, used for treatment response monitoring (TRM), that quantifies changes in ctDNA tumor fraction (TF), can predict outcome benefits in patients treated with ICI alone or in combination with chemotherapy in a real-world (RW) cohort. Methods: This retrospective study consisted of patients with advanced cancer from the Tempus de-identified clinical genomic database who received longitudinal liquid-based next-generation sequencing. Eligible patients had a blood sample ≤ 40 days prior to the start of ICI initiation and an on-treatment blood sample 15–180 days post ICI initiation. TF was calculated via an ensemble algorithm that utilizes TF estimates derived from variants and copy number information. Patients with molecular response (MR) were defined as patients with a ≥ 50% decrease in TF between tests. In the subset of patients with rw-imaging data between 2 and 18 weeks of ICI initiation, the predictive value of MR in addition to rw-imaging was compared to a model of rw-imaging alone. Results: The evaluable cohort (N = 86) was composed of 14 solid cancer types. Patients received either ICI monotherapy (38.4%, N = 33) or ICI in combination with chemotherapy (61.6%, N = 53). Patients with MR had significantly longer rw-overall survival (rwOS) (hazard ratio (HR) 0.4, P = 0.004) and rw-progression free survival (rwPFS) (HR 0.4, P = 0.005) than patients with molecular non-response (nMR). Similar results were seen in the ICI monotherapy subcohort; HR 0.2, P = 0.02 for rwOS and HR 0.2, P = 0.01 for rwPFS. In the subset of patients with matched rw-imaging data (N = 51), a model incorporating both MR and rw-imaging was superior in predicting rwOS than rw-imaging alone (P = 0.02). Conclusions: xM used for TRM is a novel serial quantitative TF algorithm that can be used clinically to evaluate ICI therapy efficacy. [ABSTRACT FROM AUTHOR]

Introduction: Hepatic visceral crisis (VC), characterized by a rapid total bilirubin increase with disease progression, poses a life-threatening risk in advanced breast cancer (ABC). International consensus guidelines define VC and touch on impending VC (IVC). Limited data exist on systemic treatments for hepatic VC/IVC. This study explores the safety and efficacy of cisplatin monotherapy in patients with Human Epidermal Growth Factor Receptor 2- negative breast cancer (BC) and hepatic IVC/VC. Methods: In this retrospective single-center cohort study data of patients treated with cisplatin monotherapy (60–80 mg/m2, every 3–4 weeks) between 2016 and 2023 at a reference Cancer Centre in Southern Poland were analyzed. Results: 33 female patients (24/33 hormonal-positive) with the mean age 53.84 years were included. Participants progressed on median 2 prior palliative systemic treatment lines. In 10/23 patients hepatic VC and in 23/33 IVC (rapid, symptomatic liver progression; extensive liver involvement; alanine or aspartate aminotransferase > 2 × normal limit; significant increases in lactate dehydrogenase, alkaline phosphatase, or gamma-glutamyl transferase) were identified. Median progression-free survival was 1.87 months and median overall survival 2.67 months. 33% of the patients presented stable disease or partial response. Eight patients experienced adverse events grade ≥ 3: in five the dose of cisplatin was reduced; two stopped the treatment. Conclusion: Due to the hepatotoxicity of BC-active drugs, specific recommendations for systemic treatment are scarce. Our study explored cisplatin's potential use, finding it to be a viable option in patients with performance status 0 or 1 experiencing hepatic IVC/VC, irrespective of liver function parameters and other factors. [ABSTRACT FROM AUTHOR]

Background: The pTNM staging system is widely recognized as the most effective prognostic indicator for cancer. The latest update of this staging system introduced a new pathological staging system (ypTNM) for patients receiving neoadjuvant chemoradiotherapy (NACRT). However, whether the prognostic value of the ypTNM staging system for rectal cancer is similar to that of the pTNM staging system remains unclear. This study was conducted to compare the ypTNM and pTNM staging systems in terms of their prognostic value for patients with nonmetastatic rectal cancer undergoing proctectomy. Material and Methods: This study was conducted at a large teaching hospital. Between January 2014 and December 2022, 542 patients with rectal cancer were analyzed (median follow-up period, 60 months; range, 6–105 months). Of them, 258 and 284 were included in the pTNM and ypTNM groups, respectively. Inverse probability of treatment weighting (IPTW) was performed to account for the effects of confounders. Cox proportional-hazards regression was performed for the between-group comparison of overall survival (OS). Results: The crude model revealed that OS was similar between the two groups (p = 0.607). After performing IPTW, we found that patients with the same ypTNM- and pTNM-classified stages had similar overall survival (hazard ratio = 1.15; 95% CI = 0.76–1.73; p = 0.5074). Conclusions: For patients with rectal cancer who have received preoperative NACRT, the prognostic value of ypTNM staging appears to be similar to that of pTNM staging, mostly because of the downstaging effect of neoadjuvant chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to investigate the long-term outcomes of laparoscopic total gastrectomy (LTG) versus open total gastrectomy (OTG) in patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NACT). Methods: Patients with AGC who received NACT before surgery were enrolled in either the LTG or OTG group. Propensity score matching (PSM) (1:2) was performed between the two groups based on the propensity score using a 0.15 calliper width. Three-year overall survival (OS) and disease-free survival (DFS) were compared between these two groups before and after PSM. OS and DFS rates were calculated by the Kaplan‒Meier method, and any differences in survival were evaluated with a log-rank test. Univariate and multivariate Cox proportional hazards analyses were used to estimate the simultaneous effects of prognostic factors on survival and the hazard ratio (HR) between LTG and OTG patients. Results: A total of 144 patients completed the follow-up, with 24 patients in the LTG group and 120 patients in the OTG group. After a mean follow-up of 64.40 months, there were no significant differences in the 3-year OS or DFS rates between the two groups before (P = 0.453 and P = 0.362, respectively) or after PSM (P = 0.972 and P = 0.884, respectively). Multivariate Cox proportional hazards analysis indicated that ypN stage was an independent risk factor for worse OS (P = 0.013). Conclusions: This study showed that LTG with D2 lymphadenectomy performed by an experienced surgical team resulted in comparable 3-year OS and DFS compared with OTG in patients with AGC after NACT. Trial registration: This study is not registered. [ABSTRACT FROM AUTHOR]

Background: Obesity and sarcopenia are both viewed as pathological body composition issues and indicators of compromised nutritional status. The aim of this study was to evaluate the effects of sarcopenic obesity on short- and long-term clinical outcomes. Methods: The clinical data of patients who underwent radical gastrectomy between 2013 and 2019 were prospectively collected. Sarcopenia is defined by European Working Group on Sarcopenia in Older People (EWGSOP2) and obesity is defined by the body mass index (BMI). To identify the independent predictors of postoperative complications and overall survival, we performed univariate and multivariate logistic and Cox regression analyses. Results: In a total of 508 cases, 372 (73.2%) cases were diagnosed with non-sarcopenia, 112 (22.0%) with non-obese sarcopenia, and 24 (4.7%) with sarcopenic obesity. In the multivariate logistic regression, both of non-obese sarcopenia (OR = 2.305, 95% CI = 1.444–3.679, P < 0.001) and sarcopenic obesity (OR = 2.589, 95% CI = 1.088–6.156, P = 0.031) were independent risk factors for postoperative complications. In the multivariate Cox analysis, only non-obese sarcopenia (HR = 2.614, 95% CI = 1.882–3.631, P < 0.001) was independent risk factor for overall survival. Conclusions: Sarcopenic obesity serves as an independent risk factor for postoperative complications, but not for overall survival. [ABSTRACT FROM AUTHOR]