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Background: The phase III KEYNOTE-913 study was conducted to evaluate the efficacy and safety of pembrolizumab as first-line therapy in patients with advanced Merkel cell carcinoma (MCC). Objective: The aim was to report results from the primary analysis of KEYNOTE-913. Patients and Methods: Patients with recurrent locally advanced or metastatic MCC received pembrolizumab 200 mg intravenously every 3 weeks for up to 35 treatments (~ 2 years). The primary end point was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary end points were duration of response (DOR) and progression-free survival (PFS) per RECIST v1.1 by BICR, overall survival (OS), and safety and tolerability. Results: Fifty-five patients were treated with pembrolizumab. The median time from first dose to data cutoff (February 15, 2024) was 50.3 months (range 38.7–59.4). The ORR was 49% (95% confidence interval [CI] 35–63), with 12 complete responses and 15 partial responses. The median DOR was 39.8 months (range 4.8–52.5+), and the 24-month DOR rate was 69%. The median PFS was 9.3 months (95% CI 3–26), and the 24-month PFS rate was 39%. The median OS was 24.3 months (95% CI 12.4 to not reached), and the 24-month OS rate was 51%. Any-grade treatment-related adverse events (AEs) occurred in 38 patients (69%); 13 patients (24%) experienced grade 3–5 AEs. The most common treatment-related AEs were fatigue (n = 12 [22%]), pruritus (n = 12 [22%]), and lipase increase (n = 10 [18%]). One patient died of treatment-related Guillain-Barré syndrome. Conclusions: Pembrolizumab provided durable antitumor activity and promising survival and had a manageable safety profile in patients with recurrent locally advanced or metastatic MCC, supporting its use in this population. Trial Registration: Clinicaltrials.gov, NCT03783078. [ABSTRACT FROM AUTHOR]

To establish whether there are geographic differences in treatments and outcomes for patients with kidney cancer (KC) in England which could potentially be improved by the creation of national guidelines. A multidisciplinary group convened by the charity Kidney Cancer UK developed Quality Performance Indicators (QPIs) for the treatment of KC. Adherence to these QPIs was reported for all patients with a histological diagnosis of KC diagnosed in England between 2017 and 2018. Utilising data extracted from national datasets, logistic and linear probability models were used to estimate geographic variation in the delivery of surgery and systemic anti-cancer therapy at Cancer Alliance and NHS trust levels. Results were adjusted for a priori confounders, including age at diagnosis, area deprivation of residence, and Charlson Comorbidity Index. Differences in overall survival are reported. The cohort comprised 18,640 tumours in 18,421 patients. Of tumours diagnosed, median patient age was 68 (interquartile range 58–77) years and 63.4% were in males. When stratified by Cancer Alliance, the proportions of T1a/T1b/N0/M0 KC that had radical nephrectomy (RN), nephron sparing surgery or ablation ranged from 53.3% (95% CI [48.7, 57.8]) to 80.3% (95% CI [73.0, 86.0]). For stage T1b-3 cancers, the proportion that received RN ranged from 65.6% (95% CI [60.3, 70.5]) to 77.3% (95% CI [72.1, 81.7]). Patients with M0 (n = 12,365) and M1 KC (n = 3312) at diagnosis had 24-month survival of 87.5% and 25.1%, respectively. Of patients diagnosed with M1 KC, 50.3% received systemic anti-cancer therapy, ranging from 39.7% (95% CI [33.7, 46.1]) to 70.7% (95% CI [59.6, 79.8]) between Cancer Alliances. The six-month survival of these patients was 77.4% compared to 27.6% for those that did not receive SACT. These major geographical differences in surgical and systemic therapy practice have led to national guideline development. • Analysis of 18,421 patients with Kidney Cancer presenting in England 2017–18. • Marked variations between Cancer Alliances in rates of surgery for primary kidney cancer. • Systemic anti-cancer therapy improves outcomes in metastatic kidney cancer patients. • Significant variations between Cancer Alliances in systemic anti-cancer therapy use. • Low rates of clinical trial recruitment. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the demographic and molecular characteristics, overall survival (OS), cancer-specific survival (CSS), and prognostic factors affecting the survival of patients with single primary breast cancer (SPBC) and patients with multiple primary cancers in their life time in which one of them is breast cancer (MPC). Methods: Using data from SEER 17 Research Plus, patients with breast cancer diagnosed between 2010 and 2019 were included in this study. Race, marital status, laterality, tumor size, molecular subtype, grade, stage, radiotherapy-chemotherapy treatment, and surgery data were analyzed in the data obtained after excluding patients with missing values. Kaplan-Meier survival analysis was used for survival analysis, and Cox regression analysis was used to evaluate the prognostic factors. Results: 573175 patients were included in the study. The mean age of MPC patients was significantly higher than SPBC patients (65.99 ± 12.68, 60.33 ± 13.47, P < .001, respectively). Patients with SPBC had significantly more hormone receptor (HR)-positive/Her2 positive, HR-negative/Her2-negative, and HR-negative/Her2-positive molecular subtypes; patients with MPC had more HR-positive/Her2-negative subtypes (P < .001). Grade 3 tumor status, locoregional spread, and distant metastasis were significantly higher in SPBC patients (P < .001). Overall survival and CSS rates were significantly higher in SPBC patients (P < .001). In MPC patients, overall hazard ratio was 1.631 times higher than SPBC, and the cancer-specific hazard ratio was 1.096 times higher (95% CI [1.606-1.656], 95% CI [1.071-1.121], respectively). Conclusion: Although patients with SPBC have worse prognostic tumor characteristics, OS and CSS rates are better than patients with MPC. [ABSTRACT FROM AUTHOR]

Background: Pivotal clinical trials supported survival benefits of liposomal irinotecan (nal‐IRI) plus fluorouracil/leucovorin in patients with pancreatic ductal adenocarcinoma (PDAC) who previously received gemcitabine‐based therapy. There are concerns about the benefits of nal‐IRI in patients who received FOLFIRINOX (combined fluorouracil, leucovorin, IRI, and oxaliplatin) because of potential cross‐resistance to IRI. The objective of this meta‐analysis was to characterize the impact of the previous receipt of IRI on the outcomes of nal‐IRI regimens in patients with advanced PDAC. Methods: Real‐world studies evaluating the outcomes of nal‐IRI in patients who had prior IRI exposure published up to April 2023 were searched using electronic databases. The meta‐analysis was conducted using a random effects model to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Eight studies (n = 1368 patients) were included. The pooled median progression‐free survival (PFS) was 2.02 months (95% CI, 1.43–2.57 months), and the median overall survival (OS) was 4.26 months (95% CI, 3.03–5.39 months). Patients with prior IRI exposure had PFS (HR, 1.17; 95% CI, 0.94–1.47; p =.17) and OS (HR, 1.16; 95% CI, 0.95–1.42; p =.16) comparable to patients without prior IRI exposure. Likewise, patients who had progressive disease on conventional IRI had PFS (HR, 1.50; 95% CI, 0.73–3.08; p =.24) and OS (HR, 1.70; 95% CI, 0.68–4.27; p =.26) with nal‐IRI comparable to patients who had no progressive disease. Conclusions: Prior IRI exposure does not affect the survival outcomes of nal‐IRI regimens in patients who have advanced PDAC. The selection of later lines of chemotherapy regimens should be based on the differential safety profile, patient status, the cost of treatment, and health‐related quality of life. In this meta‐analysis of real‐world evidence, the authors evaluated the outcomes of liposomal irinotecan in patients with advanced pancreatic ductal adenocarcinoma who had prior irinotecan exposure by using electronic databases. The results indicate that prior irinotecan exposure does not significantly affect the survival outcomes of patients who receive regimens containing liposomal irinotecan. [ABSTRACT FROM AUTHOR]

Recent studies have explored the prognostic role of the C-reactive protein to albumin ratio (CAR) in patients with bile duct cancer (BTC), but the results have been inconsistent. This study aimed to provide insight into the prognostic significance of the CAR in BTC prior to treatment using a meta-analysis. Summarized hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for prognosis and clinicopathological features using fixed or random effects models. Fourteen studies with a total of 1,543 subjects were included in this meta-analysis. Elevated CAR was significantly associated with poor overall survival (HR = 2.17, 95% CI = 1.81–2.60, P < 0.001) and decreased disease-free survival or recurrence-free survival (HR = 2.53, 95% CI = 1.98–3.25, P < 0.001) in BTC. In addition, high CAR was significantly associated with the presence of lymph node metastasis (OR = 1.54, 95% CI = 1.12– 2.13, P = 0.008), bile duct invasion (OR = 2.64, 95% CI = 1.54–4.54, P < 0.001), and tumor stages III–IV (OR = 3.11, 95% CI = 1.05–9.20, P = 0.040). However, there was no significant association between CAR and sex, microvascular invasion, or resection. An elevated CAR was significantly related to worse long-term and short-term survival and advanced clinicopathological features of BTC. CAR could serve as a valuable, noninvasive prognostic marker in patients with BTC. [ABSTRACT FROM AUTHOR]

Background: Although de novo metastatic breast cancer (dnMBC) is acknowledged as a heterogeneous disease, the current staging systems do not distinguish between patients within the M1 or stage IV category. This study aimed to refine the M1 category and prognostic staging for dnMBC to enhance prognosis prediction and guide the choice of locoregional treatment. Methods: We selected patients with dnMBC from the SEER database (2010–2019), grouping them into training (N = 8048) and internal validation (N = 3450) cohorts randomly at a 7:3 ratio. An independent external validation cohort (N = 660) was enrolled from dnMBC patients (2010–2023) treated in three hospitals. Nomogram‐based risk stratification was employed to refine the M1 category and prognostic stage, incorporating T/N stage, histologic grade, subtypes, and the location and number of metastatic sites. Both internal and external validation sets were used for validation analyses. Results: Brain, liver, or lung involvement and multiple metastases were independent prognostic factors for overall survival (OS). The nomogram‐based stratification effectively divided M1 stage into three groups: M1a (bone‐only involvement), M1b (liver or lung involvement only, with or without bone metastases), and M1c (brain metastasis or involvement of both liver and lung, regardless of other metastatic sites). Only subtype and M1 stage were included to define the final prognostic stage. Significant differences in OS were observed across M1 and prognostic subgroups. Patients with the M1c stage benefited less from primary tumor surgery in comparison with M1a stage. Conclusion: Subdivision of the M1 and prognostic stage could serve as a supplement to the current staging guidelines for dnMBC and guide locoregional treatment. [ABSTRACT FROM AUTHOR]

Objectives: Numerous studies have investigated the predictive significance of the platelet-to-lymphocyte ratio (PLR) in oral squamous cell carcinoma(OSCC). However, the results of studies on its prognostic value remain controversial. This study aims to evaluate the prognostic significance of the PLR in patients with OSCC. Materials and methods: We conducted a comprehensive search of PubMed, Embase, the Cochrane Library, and Web of Science databases for all studies investigating the association between PLR and prognosis in OSCC, from the inception of each database up to November 2023. The outcome measures included overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS). To identify potential sources of heterogeneity, sensitivity and subgroup analyses were performed, alongside an assessment of publication bias. The analyses in this study were conducted using RevMan and Stata software. Results: According to the inclusion criteria, 20 articles were included, including 5,714 patients.The meta-analysis revealed that an elevated PLR adversely affects OS (HR = 1.58; 95% CI: 1.29–1.94; p < 0.0001), DFS (HR = 1.71; 95% CI: 1.20–2.42; p < 0.003), and DSS (HR = 2.41; 95% CI: 1.79–3.25; p < 0.00001). The results of the subgroup analysis showed that a preoperative high PLR was associated with reduced OS when the PLR threshold was ≤ 150 (HR = 1.49, P = 0.0003).When the PLR threshold was > 150, Preoperative PLR was not significantly associated with the prediction of overall survival (OS) in OSCC. (P > 0.05). Conclusion: The prognostic significance of PLR in patients with oral cancer is evident in terms of OS, DSS, and DFS. Nonetheless, it is crucial to note that the predictive value of PLR might depend on specific threshold values. [ABSTRACT FROM AUTHOR]

Background: The effect of supplements on mortality risk in patients with cancer remains uncertain and has scarcely been investigated in subgroups of patients with varying characteristics. This study aimed to investigate the association between two popular supplements, fish oil and glucosamine, and mortality risk in a large population-based cohort and determine whether cardiovascular health and clinical prognosis influence these associations. Methods: This prospective cohort study analyzed the data of UK Biobank participants who were diagnosed with cancer. The associations of fish oil and glucosamine consumption with mortality were analyzed using Cox proportional hazards models. Subgroup analyses were performed to assess the effects of Life Essential 8 [LE8] scores (a measure of cardiovascular health) and cancer prognosis (grouped according to the survival rates of specific cancer types) on the associations between supplement use and mortality. Results: This analysis included 14,920 participants (mean age = 59.9 years; 60.2% female). One third (34.1%) of the participants reported using fish oil, and one fifth (20.5%) reported using glucosamine. Over a median follow-up of 12.0 years, 2,708 all-cause deaths were registered. The use of fish oil was associated with reduced risks of all-cause mortality (adjusted hazard ratio [aHR] = 0.89, 95% Confidence Interval [CI] = 0.81–0.97) and cancer mortality (aHR = 0.89, 95% CI = 0.81–0.98). Similarly, glucosamine use was associated with reduced risks of all-cause mortality (aHR = 0.83, 95% CI = 0.74–0.92) and cancer mortality (aHR = 0.83, 95% CI = 0.74–0.93) in the fully adjusted model. Subgroup analyses revealed that the protective effects of fish oil and glucosamine against mortality risk were only observed in patients with LE8 scores lower than the mean score or a poor cancer prognosis. Additionally, the association between glucosamine use and a reduced risk of CVD-related mortality was only observed in patients with lower LE8 scores. Conclusions: This large cohort study identified the potential differential impact of LE8 scores and cancer prognosis on the associations of fish oil and glucosamine supplementation with survival in patients with cancer. This suggests the importance of considering these factors in future research on supplements and in the provision of personalized integrative cancer care. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is a significant global malignancy with poor prognosis. Although the emergence of immune checkpoint inhibitors (ICIs) prolonged the duration of survival, resistance and progression are inevitable. We aim to evaluate the effectiveness of programmed death-1 (PD-1) inhibitors in immunotherapy beyond progression (IBP). Method: We divided the advanced gastric cancer patients who received two lines immunotherapy into same regimen group (with same PD-1 inhibitor regime after IBP) and different regimen group (with different PD-1 inhibitor regime after IBP). Statistical analysis conducted to compare patient characteristics and evaluate survival differences between groups. Result: The clinical outcome analysis showed that the same PD-1 inhibitor regime seemed to exhibit a higher disease control rate (DCR) (51.8% vs. 29.2%, P = 0.062), significantly prolonged progression-free survival 2 (PFS2) (162 vs. 75 days, P = 0.001) and overall survival (OS) (312 vs. 166 days, P = 0.022) when compared with those of cross line. In the multivariate analysis, when using different regimen group as reference, the same regimen group was found to be independently associated with improved PFS2 [hazard ratio (HR) = 0.467, 95% confidence interval (CI): 0.267–0.816, P = 0.008] and OS (HR = 0.508, 95%CI: 0.278–0.927, P = 0.027). Conclusion: Continuation of the same type of PD-1 inhibitor regime in IBP shows clinical benefits and represents a promising therapeutic approach. [ABSTRACT FROM AUTHOR]

Purpose: Determining the potential benefit of neoadjuvant androgen deprivation therapy (ADT) and adjuvant ADT in patients with locally advanced prostate cancer (LAPC) undergoing complete resection. Methods: 139 patients diagnosed with cT3–4, or cN+ LAPC in Xiangya Hospital and The First Affiliated Hospital of University of South China from 2010 to 2021 were collected. Cancer-specific survival (CSS) and overall survival (OS) of patients were assessed using Kaplan–Meier and Cox proportional risk analysis. We also analyzed the functional outcomes of two subgroups of patients who underwent radical prostatectomy (RP). Results: Of the 182 patients with cT3–4, or cN+ LAPC, 139 patients (76.4%) were enrolled in the study with a 5-year survival rate of 82.3%. 45 patients (32.4%) received ADT alone, 46 patients (33.1%) received neoadjuvant ADT before surgery, and the remaining 48 patients (34.5%) received surgery with adjuvant ADT. Neoadjuvant ADT before surgery and surgery with adjuvant ADT were associated with significantly improved survival compared with ADT alone. Multivariate Cox models showed that neoadjuvant ADT before surgery (hazard ratio [HR], 0.29; 95% CI 0.13–0.92) or surgery with adjuvant ADT (HR, 0.26; 95% CI 0.16–0.78) was associated with improved CSS compared with ADT alone. Regional lymph node metastasis, positive lymphovascular invasion, and Gleason score 9 + were independent predictors of LAPC CSS and OS. More patients in the neoadjuvant ADT before surgery group achieved final continence status within 12 months after surgery (93.48% v 77.08%). Conclusion: CSS and OS were significantly prolonged in cT3–4, or cN+ LAPC patients who received neoadjuvant ADT before surgery and surgery with adjuvant ADT compared to ADT alone. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the outcomes after stereotactic body radiotherapy (SBRT) for locally advanced primary liver cancer. Materials and methods: Patients with locally advanced liver cancer unsuitable for other loco-regional treatments were treated with SBRT with 50--60 Gy in 3--12 fractions in two consecutive prospective trials. Results: A total of 83 patients were included, of whom 14 were excluded, leaving 69 evaluable patients with 74 treated lesions. A total of 50 patients had hepatocellular carcinoma (HCC), and 11 patients had cholangiocarcinoma (CCC). Approximately 76% had a Child-Pugh (CP) score of A, while 54% had an albumin--bilirubin (ALBI) score of 1. With a median follow-up of 29 months, the median overall survival (OS) was 11 months, and the progression-free survival (PFS) was 18 months. The ALBI score was an important predictor of overall survival (HR 2.094, p = 0.001), which remained significant also in the multivariate analysis. Patients with an ALBI grade of ≥1 had an OS of 4 months versus 23 months in patients with an ALBI grade of 1 (p ≤ 0.001). The local control at 1 and 2 years was 91%. Thirteen patients developed grade ≥ 3 toxicities, of whom nine patients experienced liver toxicities. Patients with a higher ALBI score had a high risk for developing hepatic failure (OR 6.136, p = 0.006). Discussion: SBRT is a very effective treatment with low toxicity and should be considered as a local treatment option in patients with HCC and CCC. Patients with a higher ALBI grade are at risk for developing toxicities after SBRT and have a significantly lower survival rate. [ABSTRACT FROM AUTHOR]

Background: Few studies have explored the expression profile of RPL3 in breast cancer (BRCA). Our research provided an in-depth analysis of RPL3 expression patterns in BRCA, highlighting its significance for therapy prediction and prognosis. Methods: RPL3 was notably elevated in malignant cells, and its expression level was closely associated with tumor size and overall survival outcomes. Our study also identified RPL3-related terms and pathways and revealed a strong correlation between RPL3 expression and breast carcinoma immunity, demonstrating inconsistent expression levels in various immune cell lines. In addition, we examined the relationship between RPL3 expression and tumor mutational burden (TMB) in BRCA. To assess the clinical implications of BRCA chemotherapy, we investigated the correlation between RPL3 expression levels and drug sensitivity. Results: Our findings suggest that RPL3 plays a critical role in the BRCA process and is associated with immune infiltration, indicating its potential as a novel immunotherapy target in BRCA treatment. Conclusions: In summary, our research underscores the importance of RPL3 expression levels in tumorigenesis and its potential for guiding BRCA immunotherapy. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion Studies have shown the antitumor efficacy of immune checkpoint inhibitors (ICI) in patients with non‐small cell lung cancer (NSCLC) and brain metastases (BM). However, it is unclear whether the efficacy of ICI is similar between patients with and without BM. It is yet unclear whether the efficacy of ICI in patients with BM increases with higher levels of programmed cell death‐ligand 1 (PD‐L1) expression, as observed in patients without BM.We compared the outcomes of ICI treatment between patients with and without BM using a cohort containing 1741 prospectively enrolled patients with lung cancer. We investigated whether there were differences in the outcomes of ICI based on PD‐L1 expression levels between these patients.We enrolled 240 patients with NSCLC with or without BM who were treated with ICI or both chemotherapy and ICI. There were no significant differences in overall survival (OS) between all patients with or without BM (p = 0.489). However, OS was significantly shorter in patients with BM than in those without in the PD‐L1 ≥ 50% group (16.5 M vs. 30.6 M, p = 0.003) but not in the PD‐L1 ≥ 1% or negative group. BM was an independent poor prognostic factor for OS (hazard ratio: [95% confidence interval], 2.045; [1.058–3.953], p = 0.033) in the PD‐L1 ≥ 50% group.Our study indicated that the outcomes of patients with or without BM treated with ICI were not significantly different. The efficacy of ICI in patients with PD‐L1 expression ≥50% would be lower in patients with BM than in those without. [ABSTRACT FROM AUTHOR]

Purpose: This review primarily discusses the current research advance of predictive biomarkers for melanoma immunotherapy. The aim of the present review is to summarize the biomarkers and evaluate the advantages and disadvantages. Methods: All reference can be found through Pubmed. This review mainly focuses on three main directions: tumor-related factors, host factors, and the tumor microenvironment. In the end, there exhibits some unusual aspects of predictive biomarkers and forecasts the future model. Results: The mainsteam of predictive biomarkers focuses on PD-L1, TMB, gene mutations, immune cells, IDO1, LDH, tertiary lymphoid structures (TLS), HLA-DR, tumor-associated macrophages (TAMs), tumor-infiltrating lymphocytes (TILs), and Extracellular vesicles (EVs). Conclusion: The current research advance of predictive biomarkers for melanoma immunotherapy can be mainly divided into three parts: tumor-related factors, host factors, and the tumor microenvironment. The predictive biomarkers include PD-L1, TMB, gene mutations, immune cells, IDO1, LDH, TLS, HLA-DR, TAMs, TILs, and EVs. A model based on multiple biomarkers is expected to become the answer to predicting prognosis. [ABSTRACT FROM AUTHOR]

Background: In recent years, the incidence of endometrial cancer (EC) has been rising. This meta-analysis aims to clarify the prognostic significance of serum CA- 125 levels in EC. Methods: Articles up to March 1, 2024, were systematically searched in EMBASE, Cochrane Library, PubMed, and Web of Science. This analysis pooled hazard ratios (HR) and 95% confidence intervals (CI) from qualifying studies to evaluate the association of CA-125 levels with overall survival (OS), progression-free survival (PFS), disease-free/relapse-free survival (DFS/RFS), and disease-specific survival (DSS). Results: 25 studies involving 7,716 patients were included. The analysis revealed that elevated CA-125 levels correlate with poorer OS (HR = 1.848, 95% CI: 1.571-2.175, p < 0.001). This association persisted across various study regions and sample sizes, and was notably strong in subgroups with a CA-125 cut-off value of less than 35 (HR = 2.07, 95% CI: 1.13-3.80, p = 0.019) and equal to 35 (HR = 2.04, 95% CI: 1.49-2.79, p < 0.001), and among type II pathology patients (HR = 1.72, 95% CI: 1.07-2.77, p = 0.025). Similarly, high CA-125 levels were linked to reduced PFS, particularly in subgroups with a CA-125 cut-off value less than 35 (HR = 1.87, 95% CI: 1.15-3.04, p = 0.012) and equal to 35 (HR = 4.94, 95% CI: 2.56-9.54, p < 0.001), and in endometrioid endometrial cancer patients (HR = 2.28, 95% CI: 1.18-4.40, p = 0.014). Elevated CA-125 levels were also indicative of worse DFS/RFS (HR = 2.17, 95% CI: 1.444-3.262, p < 0.001) and DSS (HR = 2.854; 95% CI: 1.970-4.133, p < 0.001). Conclusion: Serum CA-125 levels before treatment was highly associated with prognosis of EC patients. [ABSTRACT FROM AUTHOR]

Background: The most prevalent subtype of non-Hodgkin lymphoma is diffuse large B-cell lymphoma (DLBCL). Germinal center B-cell (GCB) and non-germinal center B-cell (non GCB) are the two main biologically different molecular subtypes identified utilizing an immunohistochemistry-based approach. Aim: Our objective in this study is to analyze the impact of immunohistochemical subtypes of DLBCL (GCB or non GCB) on demographic and clinicopathological parameters, response to chemotherapy and survival outcomes. Subjects and methods: This is a retrospective study including 106 cases of DLBCL collected in the department of pathology, Hassan II university hospital, Fez (Morocco), over a period of 12 years (January 2010-September 2022). The subtypes of DLBCLs were defined according to Hans algorithm, using immunohistochemistry by three biomarkers (CD10, BCL6, MUM1). Statistical analysis used: Independent t tests and analyses of variance were used for the comparison of mean values. We employed the SPSS 26.0 program to achieve this. A statistically significant value was set at P <.05. Results: Seventy-five patients (71%) were non-GCB subtype, while thirty-one patients (29%) had the GCB immunosubtype. We have found a significant (P <.05) correlations between DLBCL immunosubtypes and treatment responses on one hand and survival in the other hand. In the GCB subtype, the response rate and survival were significantly improved. A significant association was found between Ki 67 expression and survival on univariate analysis. On multivariate analysis, we note a correlation between Ki 67 expression, DLBCL immunohistochemical subtypes and survival outcome. Conclusion: Non GCB subtype is associated with poor response to treatment and inferior survival outcome compared to GCB subtype in Moroccan context, especially when combined with high expression of Ki 67 marker. [ABSTRACT FROM AUTHOR]

Purpose: To explore whether tumor-associated lymphatic vessel density (LVD) could be a biomarker for the prognosis of patients with esophageal cancer after radical resection. Methods: A systematic literature search was performed through PubMed, EMBASE, Wanfang Data, and Cochrane Library from the inception of databases until March 19, 2024. The selected studies investigated overall survival (OS) and/or recurrence-free survival (RFS) of patients with esophageal cancer with different levels of LVD after radical resection. The OS and RFS data were pooled as hazard ratios (HR) and 95% confidential interval (CI). Furthermore, the standardized mean differences (SMDs) and 95% CI were aggregated to evaluate the correlation between LVD and clinicopathological features. Results: A total of 10 retrospective studies of 1,201 patients were finally included for the meta-analysis. Patients with esophageal cancer with a high level of LVD exhibited worse OS (HR 1.65, 95% CI 1.18 to 2.31) and RFS (HR 1.57, 95% CI 1.09 to 2.26) than those with a low level of LVD. Subgroup analysis of different pathological subtypes revealed that patients with esophageal adenocarcinoma with a high level of LVD had significantly worse RFS (HR 2.84, 95% CI 1.61 to 5.02) than those with a low level of LVD; while patients with esophageal squamous cell carcinoma with a high level of LVD had similar OS (HR 1.52, 95% CI 0.93 to 2.47) and RFS (HR 1.03, 95% CI 0.72 to 1.48) to those with a low level of LVD. Furthermore, tumors with lymph node metastasis had significantly higher levels of LVD than those without lymph node metastasis (SMD = 1.11, 95% CI 0.54 to 1.67). Tumors at the stages III-IV had significantly higher levels of LVD than those at the stages I-II (SMD = 1.62, 95% CI 0.90 to 2.34). Conclusion: A high level of LVD in tumor was associated with worse survival of patients with esophageal cancer after radical resection, especially in patients with esophageal adenocarcinoma. Tumor-associated LVD is a new parameter that should be measured in postoperative pathology for predicting the prognosis of patients with esophageal cancer. [ABSTRACT FROM AUTHOR]

Background: Patients with metastatic gastric cancer (mGC) endure a significant symptom burden following subsequent lines of therapy. Accurate survival estimation is crucial for healthcare professionals and patients to make informed decisions regarding therapy options. This study evaluates Chuang's Prognostic Scale (CPS) for predicting survival in mGC patients after receiving at least two lines of palliative systemic therapy (PST). Method: This prospective study involved 202 patients with mGC. The CPS includes eight categories: cognitive impairment, performance status, weight loss, tiredness, edema, and ascites, with a scoring range from 0 to 8.5. A higher score indicates a poorer prognosis. Results: After a median follow-up period of 3.35 months, the median CPS value was 4.2. 99 patients had a CPS < 4.2, with a median overall survival (mOS) of 5.86 months, while 103 patients with a CPS ≥ 4.2 had an mOS of 3.96 months (P < 0.001). According to the receiver-operating curve, the cut-off value for CPS was ≤ 4.7, with a disease prevalence of 76.7% and an area under the curve of 0.949 (P < 0.0001). The sensitivity was 82.6%, specificity was 97.87%, positive predictive value was 99.2%, and negative predictive value was 63%. Cox regression analysis revealed that CPS was statistically significantly associated with mOS (P < 0.001). Furthermore, CPS was statistically significantly correlated with metastases to the liver, lung, lymph nodes, and bone (P values were 0.03, 0.02, <0.001, and <0.001, respectively). Conclusion: CPS is a valuable and accessible tool that can assist in selecting appropriate therapy for patients with mGC after two lines of PST. [ABSTRACT FROM AUTHOR]

Background: Triple-negative breast cancer (TNBC) is characterized by a poor prognosis. Consequently, the current research aims to identify new therapeutic targets for TNBC patients. Trichorhinophalangeal syndrome type 1 (TRPS1), a novel GATA transcription factor, and CYP4Z1, a fatty acid hydroxylase, present potential targets for novel therapies. Method: This retrospective study included 70 TNBC patients. The immunohistochemical expression of TRPS1, GATA3, and CYP4Z1 was evaluated. Data regarding the patient's clinical and pathological responses to chemotherapy were collected and analyzed for response assessment. SPSS version 20 software facilitated the data analysis. Quantitative variables were described using means and standard deviations, whereas categorical variables were examined using the chi-square test or Fisher's exact test as appropriate. Survival analysis was performed using Kaplan-Meier plots, including disease-free and overall survival. A P-value of less than 0.05 was considered statistically significant. Results: The analysis showed that 37 cases (53%) were positive for TRPS1 expression, 45 cases (65%) for GATA3, and 40 cases (57%) for CYP4Z1. There was a significant association between the expression of GATA3, TRPS1, and CYP4Z1 and various prognostic factors such as tumor size, grade, stage, lymphovascular invasion, recurrence, and mortality. Notably, the overall recurrence and progression rates were significantly correlated with the overexpression of GATA3, TRPS1, and CYP4Z1. Conclusion: The overexpression of TRPS1, GATA3, and CYP4Z1 in TNBC patients may be novel prognostic factors for predicting tumor prognosis. Furthermore, these markers could assist in selecting patients for future therapies in both localized and metastatic breast carcinoma settings. [ABSTRACT FROM AUTHOR]

Objectives: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have significantly improved the survival of patients with hormone receptor-positive HER2-negative advanced breast cancer (ABC). Although stereotactic ablative radiotherapy (SABR) is used more often in routine clinical practice, data on the safety and efficacy of combining SABR with CDK4/6i are lacking. Herein, we present the results of SABR combined with CDK4/6i in ABC. Methods: Patients with ABC who received CDK4/6i and SABR between 2018 and 2023 were analysed. Results: Among 384 patients treated with CDK4/6i, 34 patients received 44 courses of SABR. Two-year progression-free survival (PFS) was 63.6% (95% CI, 45.8-88.3), and the median PFS was 32 months. Three-year overall survival (OS) was 88.9% (95% CI, 77.7-100). Two-year local control (LC) was 92.7% (95% CI, 83.4-100). Median OS and LC were not reached. The subgroup analysis showed the difference in survival between oligometastatic patients (OMD) and non-OMD subgroup. Two-year PFS was 69.2% (95% CI, 44.5-100) in OMD compared with 57.4% (95% CI, 36-91.7) in the non-OMD (P = .042). Three-year OS was 90% (95% CI, 73.2-100) in OMD compared with 86.2% (95% CI, 70-100) in the non-OMD (P = .67). Median PFS and OS in the non-OMD were 26 and 56 months, respectively, and were not reached in OMD. Fifteen patients required CDK4/6i dose reduction, and 2 discontinued treatment due to toxicity. No difference in high-grade toxicity was observed between the sequential and concurrent SABR. Conclusion: The addition of SABR to CDK4/6i seems to be safe and effective, especially in patients with oligometastatic disease. Advances in knowledge: In advanced breast cancer patients treated with CDK4/6i, SABR provides a high local control and may provide additional benefit in an oligometastatic setting. [ABSTRACT FROM AUTHOR]

Objective: Exploring the clinical efficacy and safety of targeted therapy, immunotherapy combined with chemotherapy in the treatment of advanced gastric cancer. Methods: A retrospective analysis was performed on the medical records of 134 patients with advanced gastric cancer who visited Renmin Hospital, Hubei University of Medicine from January 2019 to December 2022. According to therapeutic regimens, enrolled patients were divided into the control group and the study group. Patients in the control group received chemotherapy intervention, while those in the study group were provided with a combined intervention of apatinib, PD-1 inhibitor and chemotherapy. We analyze the tumor control effect and incidence of adverse reactions in two groups of patients. Results: The disease control rate (DCR) of patients in the study group and the control group was 72.06% and 42.42%, with an overall response rate (ORR) of 8.82% and 4.55%, The differences are statistically significant(P<0.05). By the end of follow-up, the median progression-free survival (mPFS) and the median overall survival (mOS) of the control group patients were 3.0±0.266 and 5.0±0.224 months respectively; while the mPFS and mOS of the study group were 5.0±0.261 and 7.0±0.172 months respectively, the differences are statistically significant (P<0.05). However, there was no significant difference in adverse reactions between the two groups (P>0.05). Conclusion: The therapeutic regimen of apatinib, a PD-1 inhibitor combined with chemotherapy exhibits relatively high clinical efficacy and safety for the treatment of patients with advanced gastric cancer. It can be considered as an interventional option for this type of patient. [ABSTRACT FROM AUTHOR]

Simple Summary: This study assessed the prognostic impact of sarcopenic obesity (SO) in colorectal cancer patients. Among 211 sarcopenic patients, those with obesity (SO group) demonstrated significantly shorter cancer-related relapse-free survival (CRRFS) compared to their non-obese counterparts (non-SO group). While cancer-specific survival (CSS) was also poorer in the SO group, this difference did not reach statistical significance. Additionally, there was no significant difference in overall survival (OS) between the two groups. Multivariate analysis identified sarcopenic obesity, elevated CEA levels, and unfavorable histological types as independent predictors of poor CRRFS. These findings underscore the importance of routine assessment of both sarcopenia and obesity in clinical practice. Moreover, they highlight the potential benefits of interventions aimed at increasing muscle mass and reducing visceral fat to enhance patient outcomes. Background: Sarcopenia, the age-related loss of muscle mass, is a negative prognostic factor in gastrointestinal cancer. Sarcopenia combined with visceral obesity (sarcopenic obesity) is associated with poor outcomes. We explored the influence of obesity and other factors on the prognosis of patients with colorectal cancer diagnosed with sarcopenia. Methods: We enrolled 211 patients with colorectal cancer diagnosed with preoperative sarcopenic obesity who underwent radical resection at Osaka University Hospital between January 2009 and January 2012. Muscle mass was assessed using the psoas muscle mass index. Obesity was evaluated by measuring the visceral fat area in the umbilical region. Patients were categorized into two groups: sarcopenia with obesity (SO) and sarcopenia without obesity (non-SO). Overall survival, cancer-specific survival, and cancer-related relapse-free survival (CRRFS) were compared between the two groups. Patient characteristics, including age, sex, body mass index, serum albumin, C-reactive protein, tumor markers, prognostic nutritional index (PNI), modified Glasgow prognostic score (mGPS), and geriatric nutritional risk index (GNRI), were also analyzed. Results: CRRFS was significantly shorter in the SO group than in the non-SO group (p = 0.028). PNI, mGPS, and GNRI were not identified as significant prognostic factors for CRRFS. Multivariate analysis highlighted sarcopenic obesity, elevated carcinoembryonic antigen levels, and unfavorable histological types as significant predictors of poor CRRFS outcomes. Conclusions: Sarcopenic obesity is an independent predictor of poor prognosis in patients with CRC. Thus, interventions aimed at increasing muscle mass and reducing visceral fat could potentially improve the prognosis of these patients. [ABSTRACT FROM AUTHOR]

Simple Summary: In a retrospective study of 86 patients, we identified independent predictors of recurrence-free survival (RFS) and overall survival (OS) after the resection of liver metastases of uveal melanoma using a multivariable Cox model. A disease-free interval of ≤24 months and a chromosome 8q surgain were associated with worse survival. With these two parameters, we built a novel clinico-genetic score that defined three risk groups with distinct prognoses. This novel score identified patients with a high risk of relapse after surgery. These patients may benefit from neoadjuvant or adjuvant systemic therapy following complete surgical resection with the hope of improving survival outcomes. Surgical treatment of liver metastases of uveal melanoma (LMUM) could be proposed for selected patients. This retrospective study examined the prognostic significance of the genetic profiles of liver metastases after LMUM resection. A total of 86 patients treated with resection for LMUM, who underwent genetic analysis of liver metastasis, were included. A multivariable Cox model identified the independent predictors of recurrence-free survival (RFS) and overall survival (OS). The disease-free interval (DFI) and a chromosome 8q surgain (>3 copies) were independent predictors and categorized patients into three risk groups with distinct postoperative prognoses. For the low-, intermediate-, and high-risk scores of recurrence, the median RFS values were 15 months (95% CI: 10–22), 6 months (95% CI: 4–11), and 4 months (95% CI: 2–7), and the median OS values were 86 months (95% CI: 55-NR), 25 months (95% CI: 17–48), and 19 months (95% CI: 12–22), respectively. The predictive accuracy of this scoring system was demonstrated by a mean area under the curve (AUC(t)) of 0.77 (95% CI: 0.65–0.90) for RFS and 0.81 (95% CI: 0.70–0.92) for OS. This novel score, based on a DFI of ≤24 months combined with a chromosome 8q surgain, identifies patients at a high risk of early recurrence and could help clinicians to propose perioperative treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Para-aortic lymphadenectomy can be used for both staging and therapeutic purposes in ovarian, endometrial, gastric and bladder cancers. However, Para-aortic lymphadenectomy is associated with high rates of morbidity and mortality and with no evidence of benefits in terms of overall survival and disease-free survival. A systematic review of the literature was performed to look into the published randomized controlled studies (RCTs) that have reported the effectiveness of lymphadenectomy. The total number of patients was 4231. The studies reported that para-aortic lymphadenectomy did not improve overall survival and disease-free survival in advanced ovarian cancers, early endometrial cancers, advanced gastric, and bladder cancers. All of the studies had a low risk of bias. Conclusions: Para-aortic lymphadenectomy is not advised in advanced ovarian cancers, early endometrial cancers with low risks, advanced gastric cancers, and bladder cancers. Clinicians should inform patients regarding the benefits of para-aortic lymphadenectomy in terms of survival and the potential risks associated with it. Background: Para-aortic lymphadenectomy can be used for both diagnostic and therapeutic purposes as it aids in staging, provides prognostic data, and influences the patient's options for adjuvant therapy. However, there is still contention over its potential in treating cancer. A systematic review of the literature was performed to look into the published randomized controlled studies (RCTs) that have reported the effectiveness of lymphadenectomy. Methods: Five different electronic databases, including PubMed, Cochrane Library, Clinical trials.gov, ICTRP, and Embase, were used to conduct a comprehensive search. Original RCTs reporting on the impact of lymphadenectomy on the overall survival in various cancers were included. Information related to the study population, intervention, type of cancer, primary endpoints, and key findings of the study were extracted. Quality assessment of the selected studies was conducted using the Revised Cochrane Risk of Bias Tool Rob 2 for randomized trials. Results: A total of 1693 citations, with 1511 from PubMed, 80 from the Cochrane Library, 67 from Embase, 18 from ICTRP, and 17 from Clinicaltrials.gov were retrieved. Preliminary screening was performed, and after applying selection criteria, nine articles were included in the final qualitative analysis. The total number of patients was 4231, and the sample size ranged from 70 to 1408. Among these nine studies, four studies were on genital cancers (two ovarian cancers, one endometrial cancer, and one cervical cancer); four on digestive cancers (advanced gastric cancers); and one on urinary cancer (advanced bladder cancer). These studies reported that para-aortic lymphadenectomy did not improve overall survival and disease-free survival in advanced ovarian cancers, early endometrial cancers, advanced gastric, and bladder cancers. All of the studies had a low risk of bias. Conclusions: Para-aortic lymphadenectomy is not advised in advanced ovarian cancers, early endometrial cancers with low risks, advanced gastric cancers, and bladder cancers. SNB could be an alternative to lymphadenectomy for ovarian cancer in the future. Clinicians should inform patients regarding the benefits of para-aortic lymphadenectomy in terms of survival and the potential risks associated with it. [ABSTRACT FROM AUTHOR]

Simple Summary: This research was conducted to evaluate the impact of ipilimumab treatment in patients with metastatic melanoma when monotherapy with PD-1 inhibitors has failed. In particular, the aim was to evaluate the efficacy of ipilimumab in this setting based on the presence or absence of BRAF or NRAS mutations. The present study could allow us to understand when salvage treatment with ipilimumab would have the best impact, although an analysis on a larger patient cohort would be necessary. Background: When monotherapy with PD-1 inhibitors in metastatic melanoma fails, there are currently no standard second-line choices. In case of the unavailability of clinical trials, ipilimumab represents a possible alternative treatment. Methods: We collected data of 44 patients who received ipilimumab after the failure of PD-1 inhibitors from July 2017 to May 2023 at our Institute. Overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS) based on BRAF or NRAS mutation status, sex, and the presence of brain metastases were estimated using the Kaplan–Meier method. Cox regression was used to evaluate independence in multivariate analysis. The objective response rate (ORR) was estimated based on RECIST 1.1. Results: Among the 44 patients enrolled in this study, 28 BRAF-wildtype, 9 BRAF-mutated, and 7 NRAS-mutated patients were identified. OS analysis showed a significant difference between wildtype and BRAF- or NRAS-mutated patients: 23.2 months vs 5.3 and 4.59, respectively, p = 0.017. The presence of brain metastases and BRAF or NRAS mutation were independent factors for mortality in multivariate analysis. Conclusions: In case of failure to enroll patients in innovative clinical trials, second-line ipilimumab still represents an effective therapy in patients with metastatic wildtype melanoma and in the absence of brain metastases. [ABSTRACT FROM AUTHOR]

Simple Summary: This structured review evaluated prospective trials that included non-metastatic advanced stage (Stage III) non-small cell lung cancer patients to determine if survival was different for high radiation dose per day (>2 Gy per day), given over a shortened number of radiation treatments (less than 30), known as hypofractionation, as compared to the usual standard radiation regimen, known as conventionally fractionated radiation therapy (2 Gy radiation dose, given once daily on weekdays for 30 daily treatments). There was no evidence that hypofractionation improves survival as compared to conventionally fractionated radiation therapy. Toxicity varied among the studies. Larger trials are needed to assess whether hypofractionated radiation is equivalent to conventional radiation. It is unclear whether the use of systemic therapy will improve survival outcomes with hypofractionated radiation and how the use of systemic therapy may negatively affect radiation toxicity with hypofractionation. Introduction: This systematic review evaluated whether curative intent hypofractionated radiation therapy improved survival (primary endpoint) as compared to standard conventionally fractionated radiation therapy for stage III non-small cell lung cancer (NSCLC) patients. Toxicity was also examined as a secondary endpoint. Methods: Electronic bibliographic databases were searched from 1 January 1990 to 31 March 2024. Phase II and phase III trials were included to assess survival (primary outcome) and toxicity (secondary outcome) for newly diagnosed stage III NSCLC patients. Results: Eight phase II trials (n = 349 participants), 3 randomized phase II trials (n = 382 participants), and 5 randomized phase III trials (n = 811 participants), for a total of 1542 participants, were identified. The published trials were heterogeneous, with a wide variety of dose prescriptions. A wide range of survivals (median survival 13.6 months–42.5 months) and toxicities such as grade 3 or higher esophagitis (0–42%) and grade 3 or higher pneumonitis (0–18%) were reported. Conclusions: There is no level 1 evidence to date that suggests that any hypofractionated regimen (dose escalated or not) improves survival as compared to conventionally fractionated radiation. The published phase III trials have been powered for superiority (not equivalence) for the hypofractionated arm. Toxicity with hypofractionated regimens may be similar to conventionally fractionated regimens when normal tissue radiotherapy constraints are kept within tolerance limits. It is unclear how the use of systemic therapy may negatively affect radiation toxicity with hypofractionated radiation therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: The study evaluated the long-term outcomes of chemoradiotherapy (CRT) with S-1 after limited surgery for T1 or T2 lower rectal cancer. The 3-year and 5-year relapse-free survival rates were 90.17% and 85.87%, respectively, showing favorable outcomes for T1 cancer patients, with effective anal function preservation. However, further treatment is needed to improve outcomes for T2 cancer patients. Background: The short-term outcomes of chemoradiotherapy (CRT) with S-1 (a combination of tegafur, gimeracil, and oteracil) following limited surgery for patients with T1 or T2 lower rectal cancer have shown encouraging results. Objectives: This study was designed to delve deeper into the long-term outcomes of CRT with S-1 after limited surgery, with the goal of evaluating both the long-term efficacy and potential risks associated with this treatment approach in patients diagnosed with T1 or T2 lower rectal cancer. Methods: This was conducted as a multicenter, single-arm, prospective phase II trial. The patient population consisted of individuals clinically diagnosed with either T1 or T2 lower rectal or anal canal cancer, with a maximum tumor diameter of 30 mm and classified as N0 or M0. Patients underwent local excision or endoscopic resection. After surgery, CRT with S-1 was administered to patients meeting several criteria, including the confirmation of well-differentiated or moderately differentiated adenocarcinoma, negative surgical margins, submucosal invasion depth of ≥1000 µm, and high tumor-budding grade (2/3). The primary endpoint of this study was relapse-free survival, while secondary endpoints included local recurrence-free survival, overall survival, anal sphincter preservation rate, and safety. Results: A total of 52 patients were included, with pathological diagnoses revealing T1 in 36 patients and T2 in 16 patients. The 3-year and 5-year relapse-free survival rates were 90.17% and 85.87%, respectively. The 3-year and 5-year local recurrence-free survival rates were 90.17% and 88.07%, respectively, while the 3-year and 5-year overall survival rates were 94.03% and 91.94%, respectively. Conclusions: CRT with S-1 after limited surgery for T1 lower rectal cancer demonstrated favorable outcomes in terms of recurrence, survival, and local control rates while effectively maintaining anal function in patients. However, further treatment approaches may be necessary to improve outcomes for patients diagnosed with stage T2 lower rectal cancer [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we investigated whether the anatomical location of metastases from posterior uveal melanoma affects survival. We found that patients with newly diagnosed metastatic posterior uveal melanoma who only have extrahepatic metastases had a significantly longer survival compared to patients with liver metastases. This insight could help clinicians improve the prediction of patient outcomes and enhance the selection of patients in clinical trials. Background/Objectives: Metastatic posterior uveal melanoma (PUM) is one of the deadliest types of melanomas. Though the median survival is short, some patients with metastatic disease live for a long time. In this study, we investigated whether the anatomical location of the metastatic lesions is associated with differences in survival. Methods: One hundred and seventy-eight patients with metastatic PUM with baseline whole-body imaging were retrospectively included. The patients were divided into three groups based on the anatomical location of metastases: (1) exclusive liver metastases (hepatic pattern), (2) both hepatic and extrahepatic metastatic lesions (hepatic–extrahepatic pattern), and (3) exclusive extrahepatic lesions (extrahepatic pattern). Survival was investigated using Kaplan–Meier plots, log-rank test, and the Cox proportional hazard model. Results: In total, 95 patients (53%) presented with hepatic pattern, 66 patients (37%) presented with hepatic–extrahepatic pattern, and 17 patients (10%) presented with extrahepatic pattern. Overall survival was significantly longer in patients with extrahepatic pattern (median 17.0 months) compared to those with hepatic pattern (median 11.0 months) and hepatic–extrahepatic pattern (median 7.0 months) (p < 0.001, log-rank test). Multivariate Cox regression analysis showed increased hazard ratios (HR) for hepatic pattern (HR 2.37, 95% CI 1.08–5.17, p = 0.031) and hepatic–extrahepatic pattern (3.25, 95% CI 1.42–7.41, p = 0.005) compared to extrahepatic pattern. Most patients with hepatic (95%) and hepatic–extrahepatic patterns (82%) were diagnosed with metastases by liver ultrasonography screening, whereas 81% of patients with extrahepatic pattern developed symptoms that led to the diagnosis. Conclusions: Extrahepatic pattern was associated with prolonged survival in patients with metastatic PUM, despite there being a larger proportion of symptomatic patients. It is therefore important to consider the anatomical location of the metastatic lesions when stratifying patients into clinical trials. [ABSTRACT FROM AUTHOR]

Simple Summary: There is a significant gap in research and guidelines for treating octogenarian multiple myeloma (MM) patients. This retrospective study examined 101 MM patients, median age 84 years (80–98), treated outside clinical studies at TASMC between 2010 and 2023, aiming to review real-world practices and outcomes experienced by this vulnerable group of patients. Of these patients, 87% received a bortezomib-based regimen; 20% received lenalidomide ± bortezomib; 44% were treated with novel agent-based doublets, and 51% with triplets/quadruplets. Despite the employment of reduced doses of steroids and lenalidomide, treatment-related toxicity was high, including 9% who suffered grade 5 events. Of these patients, 67% received subsequent lines, resulting in an impressive median overall survival of 42 months (1–141) in the entire cohort. These results highlight the effectiveness of personalized therapy for octogenarian multiple myeloma (MM) patients and emphasize the need for further real-time studies to establish guidelines for the management of this vulnerable and growing population. Background: Data on the outcome of octogenarian multiple myeloma (MM) patients (pts), especially if treated outside clinical studies, are scanty. Aims and Methods: MM pts ≥ 80 years, treated at TASMC with first-line therapy between 2010 and 2023, were reviewed. Characteristics and outcomes were analyzed. Results: A total number of 101 pts, of whom 54 were males with a median age of 84 years (80–98), were included. Among them, 67.4% had a Charlson comorbidity index of ≥5, 37% had ISS-3 (International staging system) and 20% had Revised-ISS-3. In our study, 44.5% received doublets and 50.5% received triplets/quadruplets. A bortezomib-based regimen was applied in 87%, and IMiDs were used in 27.7%. Despite an upfront employment of a low lenalidomide dose, dose reductions were required in 48%. Grade ≥ 3 adverse events (AEs) (mainly infections) were documented in 36.6% of patients, including grade 5 events in 9%, all attributed to infections. The overall response rate was 69%, including 31% ≥ VGPRs (Very good partial response). Sixty-seven percent (67%) received second-line therapy, administered within a median period of 12 months (1–84). Within a median follow-up period of 36 m (1–141), the median overall survival (OS) approached 42 m (range: 1–141); being shorter in pts > 84 years (HR = 1.7, p = 0.03), pts with lung disease (HR = 1.8, p = 0.044) and pts with ISS = 3 and R-ISS = 3 (HR = 1.65, p = 0.0016 and HR = 2.45, p = 0.006, respectively); Conclusions: Octogenarians treated outside clinical studies often have a lower tolerance to treatment. Nevertheless, upfront administration of low doses of anti-MM agents provided a response in the majority of patients, translated into impressive OS. Nevertheless, mortality due to AEs was high, emphasizing the need for new, "octogenarian-oriented" treatment protocols. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates racial disparities in the stage of gastric cancer at diagnosis and overall survival among different racial groups using data from the SEER database (2018–2021). The retrospective cohort study of 18,984 patients found that Hispanics are 19% more likely to be diagnosed at a later stage of gastric cancer compared to non-Hispanics. Additionally, both Hispanics and Black patients showed poorer overall survival compared to Non-Hispanic Whites. The disparities are attributed to factors such as healthcare access, insurance coverage, language barriers, and preventive health service utilization. These findings highlight the need for targeted interventions to address these disparities in cancer outcomes. Introduction: Racial disparities in gastric cancer outcomes, including stage at diagnosis and overall survival, continue to affect Hispanic and non-Hispanic populations. This study aims to evaluate these disparities across different racial groups. Patients and methods: We conducted a retrospective cohort study using SEER data from 2018 to 2021, including 18,984 patients diagnosed with gastric cancer. Patients were selected based on ICD-O-3 codes for "stomach" with malignant behavior. Using ordered logistic regression, the association between race and stage at diagnosis was analyzed, while Cox proportional hazards models were used to assess OS and CSS. Results: Hispanic patients were significantly more likely to be diagnosed at a later stage compared to non-Hispanic patients (OR: 1.19; 95% CI: 1.10–1.28). Both Hispanic and Black patients had worse OS compared to Non-Hispanic Whites (HR 1.10 CI 1.03–1.17, p = 0.003 and HR 1.13 CI 1.04–1.22, p = 0.002, respectively) as well as CSS. Conclusions: Hispanic patients are more likely to be diagnosed with advanced-stage gastric cancer and have poorer survival outcomes compared to non-Hispanic Whites. These disparities may be linked to differences in healthcare access, insurance, language barriers, and preventive care utilization. [ABSTRACT FROM AUTHOR]

Simple Summary: Research shows that Black women generally have poorer breast cancer survival rates than White women in the U.S. Our study aims to identify genomic variants and socioeconomic determinants that might explain this racial disparity using mediation analysis. Based on the All of US research program, we identified 15 gene mutations along with factors age, general health, and general quality of life that can explain the observed racial disparity. By studying how these genes behave differently in Black and White breast cancer patients, researchers can gain important insights into the mechanism underlying the cancer development and prognosis among different populations. This understanding could help create better, personalized treatments, especially to address the differences in breast cancer outcomes among racial groups. Background: Breast cancer outcomes are worse among Black women in the U.S. compared to White women. While extensive research has focused on risk factors contributing to breast cancer; the role of genomic elements in health disparities between these racial groups remains unclear. This study aims to identify genomic variants and socioeconomic status (SES) determinants influencing racial disparities in breast cancer survival through multiple mediation analyses. Methods: Our investigation is based on the NIH-supported All of Us (AoU) program and analyzes 7452 female participants with malignant tumors of breast, including 5073 with genomic data. A log-rank test reveals significant racial differences in overall survival time between Black and White participants (p-value = 0.04). Multiple mediation analysis examines the effects of 9481 genetic variables across 23 chromosomes in explaining the racial disparity in survival, adjusting for SES variables. Results: 15 gene mutations, in addition to age, general health, and general quality of life, have significant effects (p-values < 0.001) in explaining the observed racial disparity. Mutations in TMEM132B, NARFL, SALL1, PAD12, RIPK1, ASB14, DCX, GNB1L, ARHGAP32, AL135787.1, WBP11, SLC16A12AS1, AP000345.1, IKBKB, and SUPT20H have significantly different distributions between Black and White participants. The disparity is completely explained by the included variables as the direct effect is insignificant (p-value = 0.73). Conclusions: The combined impact of SES determinants and genetic mutations can explain the observed differences in breast cancer survival among Black and White participants. Future studies will explore pathways and design in vivo and in vitro experiments to validate the functions of these genes [ABSTRACT FROM AUTHOR]

Objective: Textbook outcome (TO) is widely recognized as a comprehensive prognostic indication for patients with gastric cancer (GC). This study aims to develop a modified TO (mTO) for elderly patients with GC. Methods: Data from the elderly patients (aged ≥ 65 years) in two Chinese tertiary referral hospitals were analyzed. 1389 patients from Fujian Medical University Union Hospital were assigned as the training cohort and 185 patients from Affiliated Hospital of Putian University as the validation cohort. Nomogram was developed by the independent prognostic factors of Overall Survival (OS) based on Cox regression. Results: In the training cohort, laparoscopic surgery was significantly correlated with higher TO rate (P < 0.05). Cox regression analysis revealed that surgical approach was also an independent factor of OS (P < 0.001), distinct from the traditional TO. In light of these findings, TO parameters were enhanced by the inclusion of surgical approach, rendering a modified TO (mTO). Further analysis showed that mTO, tumor size, pTNM staging, and adjuvant chemotherapy were independent prognostic factors associated with OS (all P < 0.05). Additionally, the nomogram incorporating these four indicators accurately predicted 1-, 3-, and 5-year OS in the training cohort, with AUC values of 0.793, 0.814, and 0.807, respectively, and exhibited outstanding predictive performance within the validation cohort. Conclusion: mTO holds a robust association with the prognosis of elderly patients with GC, meriting intensified attention in efforts aimed at enhancing surgical quality. Furthermore, the predictive model incorporating mTO demonstrates excellent predictive performance for elderly patients with GC. [ABSTRACT FROM AUTHOR]

We explored the prognostic impact of simple indices that reflect the immunological milieu (neutrophils to lymphocyte ratio [NLR] and systemic immune-inflammation [SII]) in 49 platinum-resistant relapsed ovarian cancer patients. The median progression-free survival (PFS) and overall survival (OS) were 4 and 8 months, respectively. Patients with a lower NLR (≤2.89) had a better PFS (5 vs. 2months [p=0.02]) and OS (9 vs. 5 months [p=0.20]). Factors associated with a worse PFS were NLR >2.8 (hazard ratio [HR] =2.32, p=0.02) and SII>639 (HR =3.70, p=0.002). SII>639 independently predicted PFS (HR =4.13, p=0.03). Future studies should study the validity of inflammatory markers and could consider incorporating it as a biomarker in clinical trials. [ABSTRACT FROM AUTHOR]

Background: The relationship between the combination of platelet count and neutrophil‐lymphocyte ratio (COP‐NLR) and prognosis in patients with advanced non‐small cell lung cancer (NSCLC) treated with immune checkpoint inhibitor (ICI) combination therapy with chemotherapy remains unclear. Thus, we investigated prognostic factors, including the COP‐NLR, to identify patients who could benefit from the therapeutic efficacy of ICI combination therapy for advanced NSCLC. Furthermore, we evaluated the relationship between the COP‐NLR score during ICI combination therapy and treatment response. Methods: We conducted a retrospective cohort study of 88 patients with NSCLC who initially received ICI combination therapy. The primary outcome was overall survival (OS). The prognostic factors were extracted using the Cox proportional hazards model. The relationship between COP‐NLR score at 3 weeks after starting ICI combination therapy and a good response (complete response [CR] and partial response [PR]) to treatment was analyzed using the chi‐square test. Results: The median OS was 15.7 months. In the multivariable analysis, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2, distant metastatic sites ≥2, and baseline COP‐NLR scores of 1, 2 were extracted as significant poor prognostic factors. The proportion of patients with CR and PR in the 3‐week COP‐NLR score of 0 group was significantly higher than that in scores of 1, 2 group. Conclusions: Baseline COP‐NLR, ECOG PS, and number of distant metastatic sites were prognostic factors in patients with NSCLC with ICI combination therapy. A lower 3‐week COP‐NLR was associated with a good response to treatment. [ABSTRACT FROM AUTHOR]

Background: This study explored the significance of consolidation maintenance chemotherapy after concurrent chemoradiotherapy with different regimens in patients with esophageal squamous cell carcinoma. Method: A prospective randomized controlled phase III clinical trial was designed and registered in the China Clinical Trials Registry (Registration number: ChiCTR‐TRC‐12002719). Survival data were analyzed in terms of intention‐to‐treat (ITT) and per‐protocol (PP) sets for patients undergoing cisplatin and 5‐fluorouracil (PF) (group A), or cisplatin and paclitaxel (TP) (group B). Results: The incidence risk of grade III–IV leukopenia in group B was higher than in group A (49.2% vs. 25.5%, p = 0.012). The survival rates at 1, 2, 3, and 5 years were 83.8%, 62.6%, 53.1%, and 41.3%, respectively. Consolidation chemotherapy after concurrent chemoradiation therapy had no benefit on median progression‐free survival (PFS) (p = 0.95) and overall survival (OS) (p = 0.809). According to the ITT analysis, the median PFS in group A and group B was 28.6 months and 30.3 months (X2 = 0.242, p = 0.623), while the median OS was 31.0 months and 50.3 months (X2 = 1.25，p = 0.263). For the PP analysis, the median PFS in group A and group B were 28.6 months and 30.3 months (p = 0.584), while the median OS was 31.0 months and 50.3 months (p = 0.259), respectively. Patients receiving consolidation chemotherapy did not show significant OS benefits (46.9 months vs. 38.3 months; X2 = 0.059, p = 0.866). Conclusion: Similar PFS and OS were found between PF and TP regimens with concurrent chemoradiotherapy. Consolidation chemotherapy did not show any significant OS benefits. [ABSTRACT FROM AUTHOR]

Background: Patients with programmed cell death‐ligand 1 (PD‐L1) ≥50% metastatic non‐small cell lung cancer (NSCLC) treated with first‐line immunotherapy showed heterogeneous tumor responses. In this study, we investigated the clinical and immune‐inflammatory markers distinguishing patients with metastatic NSCLC achieving high depth of tumor response (HDPR) from those with non‐high depth of response (NHDPR). The impact of clinical features on the prognosis of patients with PD‐L1 ≥50% were further clarified. Methods: The clinical characteristics and immune‐inflammatory markers of 17 patients with PD‐L1 ≥50% metastatic NSCLC at Beijing Tiantan Hospital between July 2020 and December 2023 were retrospectively analyzed. Results: Among the 17 patients, seven (41.2%) patients achieved HDPR (range: −50%, −72%) and 10 (58.8%) patients achieved NHDPR (range: −13%, −45%). Below normal CD4 + T lymphocytes/CD8 + T lymphocytes (CD4/CD8) ratio (p = 0.01) and oncogenes and/or tumor suppressor gene mutations (TP53/KRAS/EGFR) (p = 0.001) were found enriched for NHDPR compared with HDPR. With a median follow‐up of 26.0 months (range: 17.2–34.8 months), the median progression‐free survival (PFS) following first‐line immunotherapy and overall survival (OS) were 9.0 months (95% CI: 5.0–13.0) and not reached (NR), respectively. The neutrophil‐to‐lymphocyte ratio (NLR) was identified as an independent prognostic factor on first‐line PFS. Patients with an NLR ≥4 exhibited a shorter median PFS (7.0 months vs. NR; p = 0.033; 95% CI: 1.2–80.2) than those with an NLR <4 following first‐line immunotherapy. Conclusions: Among patients with PD‐L1 ≥50% metastatic NSCLC who received first‐line immunotherapy, a lower CD4/CD8 ratio and the presence of genes mutations showed a diminished tumor response and a higher NLR ratio exhibited a worse median PFS. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) is an integral component in the treatment of breast cancer. The aims of this study were to estimate the cost per 5-year Local Control (LC) and Overall Survival (OS) benefits of the first course of RT, based on breast cancer stage, and the potential cost savings with adoption of the FAST-Forward protocol. All RT activities for breast cancer RT July 2017-June 2020 and their associated costs were consolidated together. The average cost of treatment course was calculated (average cost per fraction X average no. of fractions). Cost per outcome was estimated based on published gains in 5-year LC and OS with optimal use of radiotherapy. 481 patients with breast cancer were analysed. The average cost per fraction was $285 AUD (£148 GBP) for all stages. The average costs for 5-year LC and OS gain were $31,483 AUD (£16 392 GBP) and $235,435 AUD (£122 566 GBP) respectively for all stages. The estimated costs for 5-year LC outcomes were $29,675 AUD (£15 450 GBP), $34,675 AUD (£18 053 GBP) and $32,478 AUD (£16 910 GBP) for Stage I-III respectively. The estimated costs for 5-year OS were $455,909 AUD (£237 378 GBP), $532,727 AUD (£ 277 375 GBP) and $60,717 AUD (£31 614 GBP) for Stage I-III respectively. 266 patients had characteristics that made them eligible for the FAST-Forward protocol. A cost saving of $2592–3864 AUD (£1350–2012 GBP) per patient was estimated had these patients been treated with the protocol. The cost of RT for LC outcome is similar across stages. The greatest value for OS outcome was seen in patients with Stage III breast cancer, due to the greater survival benefit with RT in these patients compared with Stage I-II breast cancer. Significant cost savings can be made by implementing the FAST-Forward protocol. • Cost per 5-year local control outcome was similar for Stage I-III breast cancer ranging from $29,675 AUD to $32,478 AUD. • Cost per 5-year overall survival outcome was cheaper for stage III breast cancer compared with Stage I-II breast cancer. • Use of the FAST-Forward ultrahypofractionation protocol significantly reduces RT costs. [ABSTRACT FROM AUTHOR]

Purpose: The present study aimed to investigate CT imaging features, pathological findings, and prognosis in patients with thyroid hemiatrophy (THA) associated with papillary thyroid carcinoma (PTC). Methods: This retrospective study included 225 patients with histopathologically proven PTC treated by surgical resection who underwent preoperative CT scanning. On CT images, THA was defined as thyroid parenchymal hemiatrophy on the ipsilateral side of PTC. CT findings, overall survival, and disease-free survival were compared between patients with and without THA. Pathological findings were also assessed in PTCs with and without THA. Results: THA was observed in 35 of 225 (16%) patients with PTC. Atrophic thyroid parenchyma was observed in the right lobe of 20 patients (57%) and in the left lobe of the remaining 15 patients (43%). With respect to the solid components within PTCs, contrast-enhanced CT attenuation (114.2 ± 18.2 vs. 126.7 ± 31.3 HU; p < 0.05) and CT attenuation change for contrast-enhanced CT minus unenhanced CT (60.2 ± 18.1 vs. 72.3 ± 31.0 HU; p < 0.05) were significantly lower in PTCs with THA than in those without THA. Histopathologically, almost all PTCs with THA (97%) had keloid-like collagen, which is broad bundles of hypocellular collagen with bright eosinophilic hyalinization, typically observed in keloid. However, no significant differences were observed in the prognosis between the two groups. Conclusion: THA was occasionally observed in patients with PTC. Weak contrast-enhancement was distinct characteristic of PTC patients with THA, which is probably caused by keloid-like collagen. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the IRECAP study was to evaluate the rate of locally advanced pancreas cancer patients (LAPC) who could undergo R0 or R1 surgery after irreversible electroporation (IRE). Materials and methods: IRECAP study is a phase II, single-center, open-label, prospective, non-randomized trial registered at clinicaltrials.gov (NCT03105921). Patients with LAPC were first treated by 3-month neo-adjuvant chemotherapy in order to avoid inclusion of either patients with LAPC having become resectable after chemotherapy or patients with rapid disease progression. In cases of stable disease, IRE was performed percutaneously under CT guidance. Surgery was planned between 28 and 90 days after IRE. Tumor specimens were studied to evaluate the resection margins (R0/R1/R2). Results: Six men and 11 women were included (median age 61 years, range 37–77 years). No IRE-related death was observed. Ten patients (58%, 10/17) experienced 25 serious adverse events related to IRE. Four patients progressed between IRE and surgery and were excluded from surgery. Thirteen patients were finally operated, six withheld for pancreas resection, three for diffuse peritoneal carcinosis, two for massive vascular entrapment, and one for hepato-cellular carcinoma not diagnosed before surgery. Rate of R1-R0 was 35% (n = 6/17). Median overall survival was 31 months (95% CI; 4–undefined) for the six patients with R0/R1 resection and 21 months (95% CI; 4–25) for the 11 patients without resection or R2 resection (logrank p = 0.044). Conclusion: After neoadjuvant chemotherapy, IRE could provide R0 or R1 resection in 35% of LAPC, which seems to be associated with higher OS. Clinical relevance statement: After induction chemotherapy, stable locally advanced pancreatic cancers can be treated by irreversible electroporation, which could lead to a secondary 35% rate of R0 or R1 surgical resection which may be associated with a significantly higher overall survival. Key Points: • In cases of unresectable LAPC (locally advanced pancreatic cancer), percutaneous irreversible electroporation (pIRE) is feasible (100% success rate of the procedure), but is associated with a 58% rate of grade 3–4 adverse events. • In patients with unresectable LAPC, pIRE could lead 35% of patients to R0-R1 surgical resection. • From IRE, median overall survival was 31 months (95% CI; 4–undefined) for the patients with R0/R1 resection and 21 months (95% CI; 4–25) for the patients without resection or R2 resection (logrank p = 0.044). [ABSTRACT FROM AUTHOR]

The study aims to evaluate the performance of Vitamin D/calcitriol-induced miR-589-3p in predicting the prognosis of cervical cancer patients and its role in cancer cell function. To identify differentially expressed miRNAs (DEMs) related to calcitriol treatment, the GSE61829 dataset was analyzed. MiR-589-3p expression levels were verified in cervical cancer patients. The association of miR-589-3p with overall survival was investigated using Kaplan-Meier survival analyses and the multi-variate Cox proportional hazards model analysis. The effects of miR-589-3p on cervical cancer cells and calcitriol-treated cells were examined using the MTT assay and Transwell migration/invasion assay. From GSE61829 dataset, a total of eleven DEMs were identified, including miR-589-3p. MiR-589-3p was found to be decreased in cervical cancer but increased after one-year intake of Vitamin D. Low miR-589-3p after one-year intake of Vitamin D was identified as a predictive factor for low survival probability (p = 0.0059) with a significant impact on the death risk (HR: 3.04; 95%CI: 1.47-6.29; p = 0.003). MiR-589-3p overexpression inhibited the proliferation and migration/invasion of cervical cancer cells and calcitriol-treated cervical cancer cells. In conclusion, miR-589-3p can be induced by Vitamin D/calcitriol treatment and inhibit cervical cancer progression. MiR-589-3p has the potential to predict overall survival in patients with cervical cancer. [ABSTRACT FROM AUTHOR]

Background Patients with non-small cell lung cancer (NSCLC) experience a considerable disease burden, evident in symptomatic and psychological spheres. Advanced cancer represents a complex scenario for patients and the healthcare team. Early palliative care (EPC) has been proven as a clinically meaningful strategy in this context by several randomized trials but not in a resource-limited setting. This study aimed to evaluate the effect of EPC compared with standard oncological care (SOC) in patients with metastatic NSCLC in Mexico. Materials and Methods A prospective, randomized clinical trial was conducted at Instituto Nacional de Cancerologia in Mexico. All patients had histologically confirmed metastatic NSCLC without previous treatment. Patients were randomly assigned (1:1) to receive SOC or SOC + EPC. The EPC group was introduced to the palliative care team at baseline after randomization, which was integrated by psychologists, bachelor's in nutrition, specialized nurses, and physicians. Patients randomized to this arm had programmed visits to meet with the team at baseline and through the 2nd, 4th-, and 6th cycles thereafter. The primary endpoint was overall survival (OS); secondary outcomes included quality of life (QoL), anxiety and depression, and symptom intensity. They were assessed using the instruments EORTC QLQ-C30 questionnaire, Edmonton Symptom Assessment Scale (ESAS), and the Hospital Anxiety and Depression Scale (HADS) (clinicaltrials.gov [NCT01631565]). Questionnaires were completed at baseline, at 2nd, 4th, and 6th cycles of treatment. Results Between March 2012 and June 2015, 201 patients were assessed for eligibility and 146 were enrolled and allocated to receive EPC (73) or SOC (73). Median OS for patients in the EPC vs SOC arm was 18.1 months (95% CI, 7.9-28.4) and 10.5 months (95% CI, 4.7-16.2) (P  = .029). Having a poor performance status (HR 1.7 [1.2-2.5]; P  = .004) and allocation to the control group (HR 1.5 [1.03-2.3]; P  = .034) were independently associated with a worse OS. Those patients with a global QoL > 70 at baseline had a better OS if they were In the EPC arm (38.7 months (95% CI, 9.9-67.6) vs SOC 21.4 months (95% CI, 12.4-30.3)). Mean QoL had a numerical improvement in patients allocated to EPC after 6 cycles of follow-up, nonetheless this difference was not statistically significant (55.1 ± 23.7 vs 56.9 ± 25.3; P  = .753). There were no significant differences in anxiety and depression at all study points. Conclusions EPC is associated with a significant improvement in OS, although, we observed that the greatest benefit of providing EPC was observed in those with a global QoL > 70 at baseline. This study did not identify significant changes in terms of QoL or symptom burden between the study groups after follow-up. Evidence robustly suggests that EPC should be considered part of the multidisciplinary treatment of metastatic NSCLC patients since diagnosis. According to our study, EPC can be implemented in low- or middle-income countries (LMIC). [ABSTRACT FROM AUTHOR]

Context The real world efficacy and tolerabiltiy of NTRK inhibitor larotrectinib has not yet been reported in the literature although trial data has shown promising results. Objective We report a retrospective analysis of patients with thyroid cancer harboring NTRK fusions who underwent treatment with larotrectinib. Methods A single-institution, retrospective case series of patients with NTRK fusion-positive thyroid cancers treated with neurotrophic tyrosine receptor kinase (NTRK) inhibitors from January 1, 2007, to January 1, 2023, was performed. This study was conducted at a single academic tertiary referral center. Patients with confirmed NTRK -fusion thyroid cancer who received larotrectinib were included. Larotrectinib was administered in accordance with clinical judgment from oncology providers. The primary end point was progression-free survival (PFS). Results Eight patients with NTRK fusion-positive thyroid cancer treated with larotrectinib were identified: 4 with papillary thyroid cancer (PTC) (50%), 3 with poorly differentiated thyroid cancer (PDTC) (38%), and 1 with anaplastic thyroid cancer (ATC) (12%). The median PFS (mPFS) for all patients was 24.7 months (95% CI, 11.3-38.1). mPFS in PTC was higher than PDTC (34.6 months [24.7-48.7 months] vs 17.5 [7.1-21.1 months]; P =.017). The median overall survival (OS) was 43.8 months (29.8-56.8 months) overall. The single patient with ATC had a PFS and OS of 23 months. Two patients remained on treatment/alive at data cutoff, with a duration of response of 33.5 months and a median follow-up of 52 months. Patients achieved 1 complete response (12%), 6 partial responses (75%), and 1 stable disease (12%). Conclusion In this single-institution cohort of patients with NTRK fusion-positive thyroid cancer, NTRK inhibition led to an mPFS of 25 months, with survival surpassing historic benchmarks for ATC and PDTC. [ABSTRACT FROM AUTHOR]

Background. Breast cancer is an important cause of cancer‐related death in women worldwide and represents the second most frequent cause of brain metastases after lung cancer. The aim of this study was to determine the characteristics and outcomes of triple‐negative breast cancer (TNBC) patients with brain metastasis (BM). Methods. We retrospectively reviewed a cohort of patients diagnosed with TNBC at the "Instituto Nacional de Enfermedades Neoplasicas" (period 2000–2014) to evaluate patients who developed BM. Survival rates were assessed by the Kaplan–Meier method, and prognostic factors were identified with the Cox regression analysis. Results. Of a total of 2007 TNBC patients, 193 (9.62%) developed BM. Of these, 169 stages I–III patients with a median age of 45 years (range:21–78) were included. The stage in this cohort was 4 (2.4%) clinical stage (CS) I, 23 (13.6%) with CS II and 142 (84.0%) with CS III. Most of these patients presented ECOG ≥2 (68.6%). The most common symptom was headache (74.0%), followed by nausea‐vomiting (46.7%). Imaging showed that 80 patients (53.0%) had ≥1 metastatic brain lesion. Regarding the treatment of BM in this cohort, 132 patients (84.6%) received radiotherapy (RT), 2 (1.5%) surgery, and 6 (4.5%) surgery plus RT. The overall survival (OS) rate of BM was 59.8%, 37.3%, and 15.0% at 3, 6, and 12 months, respectively. A multivariate analysis showed RT to be the only factor with a positive impact on the OS of BM (hazard ratio (HR) = 0.48, 95% confidence interval (CI):0.30‐0.77, and p = 0.002), while ECOG ≥2 was associated with a worse OS (HR = 1.69, 95%CI:1.15–2.48, and p = 0.007). Conclusion. Despite the poor prognosis of TNBC patients who develop BM, RT showed a benefit in OS rates, while ECOG ≥2 was the only prognostic factor associated with a worse OS. These results may be useful for multidisciplinary teams for treatment planning in patients with TNBC and BM. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to analyse the clinical outcomes of preoperative adjuvant denosumab therapy (PADT) combined with resection and arthrodesis for recurrent grade 3 giant cell tumor of bone (GCTB) in the distal radius. Methods: A retrospective study was conducted on twenty-three patients (8 males, 15 females) who were treated with the adjuvant denosumab combined with en bloc resection (EBR) and arthrodesis for biopsy confirmed recurrent Campanacci III giant cell tumor of bone in the distal radius between January 2015 and December 2022. All 23 patients were treated with wrist arthrodesis reconstruction using autogenous free iliac crest bone graft (ICBG), bridging plate and screws. The local control, metastasis and overall survival were evaluated during the follow-up period. Functional outcomes were evaluated using the Disabilities of the Arm, Shoulder and Hand (DASH) score, Musculoskeletal Tumor Society Score (MSTS-87 and MSTS-93), and grip strength in the follow-up period. Additionally, all surgical or denosumab-related complications that occurred were recorded in this study. Results: Twenty-three patients were included in this retrospective study and no patients were lost in the follow-up period. The average patient age was 32.5 ± 10.2 years (range, 19–53 years) and the mean follow-up time was 35.5 ± 18.4 months (range, 13–72 months). The average tumor length was 71.7 ± 8.7 mm (range, 50 to 85 mm) and bone reconstruction length was 78.5 ± 8.5 mm (range, 60 to 90 mm). Four patients (17.4%) had secondary local recurrence after reoperation and two patients had (8.7%) multiple recurrences. One patient (4.3%) was deceased in the last follow-up due to multiple metastases. The estimated 5-year recurrence-free survival rate was 81.3% and 5-year metastasis-free survival rate was 95.7%. The mean union time was 8.5 ± 1.9 (6–12) months and the overall survivorship of the allograft was 82.7% (21/23) at an average 35 month follow-up. The average MSTS-87 and MSTS-93 scores were 27.8 ± 1.6 (range, from 23 to 30) and 91.5 ± 5.0 (range, from 76 to 100), and the average DASH score was 8.9 ± 3.2 (range, from 3 to 15), respectively. The average grip strength was 64.6 ± 15.7% (range, from 30 to 95%) of the uninvolved side. Eight patients (34.7%) had at least one complication in the follow-up time. Two autografts (8.7%) were removed due to local recurrence and bone nonunion, and the average autograft survival time was 32.8 ± 18.5 months (range, 12 to 72 months). Conclusions: Preoperative adjuvant denosumab therapy (PADT) combined with en bloc resection and arthrodesis is a promising method for the treatment of recurrent Campanacci III GCTB in distal radius with acceptable short-term local control and functional satisfaction. Level of evidence: level IV Therapeutic. [ABSTRACT FROM AUTHOR]

Background: The prognostic value of tumor deposits (TDs) in stage III colorectal cancer (CRC) patients is poorly described based on the current tumor node metastasis (TNM) stage system. Materials and methods: Based on the data from the Surveillance, Epidemiology, and End Result (SEER) database between 2010 to 2020 and local hospital between 2006 to 2022, the clinicopathological features of stage III CRC patients with TDs were screened by Chi-square test. Kaplan-Meier curves were performed to describe the significant difference in overall survival (OS) among the different groups, and log-rank tests were used to compare the cumulative survival distributions. Result: Patients with TDs exhibited more aggressive tumors, characterized by advanced T staging (T3&T4), N staging (N2), perineural invasion, and more advanced TNM stage. The presence of TDs was identified as a negative prognostic factor in stage III CRC patients, with the co-existence of TDs and lymph node metastasis associated the poorest prognosis. A pairwise comparison revealed no statistically significant difference between TD+N1a/b and N1c groups, while the OS of TD-LN+ (TD- N1a/b) patients was the most favorable within the N1 stage. Notably, patients with a single lymph node positive had a significantly better OS than those with a single TD positive. Conclusion: The presence of tumor deposits was a negative prognostic factor in stage III colorectal cancer patients, and the significance of tumor deposits was underestimated in the current TNM staging system. [ABSTRACT FROM AUTHOR]

Objective Methods Results and limitations Conclusions To report real‐world outcomes for high‐risk non‐muscle‐invasive bladder cancer (HRNMIBC), including bacillus Calmette‐Guérin (BCG) and radical cystectomy (RC), as randomised comparisons of these have not been possible.We detail consecutive participants screened for the BRAVO randomised controlled trial comparing RC with BCG (International Standard Randomised Controlled Trial Number [ISRCTN]12509361). Patients were prospectively registered and case‐note review used for outcomes. The primary outcome was overall survival. Secondary outcomes included recurrence, progression, metastasis, and bladder cancer‐specific survival.A total of 193 patients were screened, including 106 (54.9%) who received BCG, 43 (22.3%) primary RC, 37 (19.2%) ‘other’ treatment and seven (3.6%) hyperthermic intravesical mitomycin C. All‐cause death occurred in 55 (28.5%) patients at median (interquartile range [IQR]) of 29.0 (19.5–42.0) months. In multivariable analysis, overall mortality was more common in older patients (hazard ratio [HR] 2.63, 95% confidence interval [CI] 1.35–5.13; Cox P = 0.004 for age >70 years), those recruited from district hospitals (HR 0.53, 95% CI 0.3–0.95; P = 0.032) and those who did not undergo RC as their first treatment (HR 2.16, 95% CI 1.17–3.99; P = 0.014). In all, 17 (8.8%) patients died from bladder cancer (BC) at median (IQR) of 22.5 (19–36.25) months. In multivariable analysis, BC‐specific mortality was more common in older patients (HR 4.87, 95% CI 1.1–21.6; P = 0.037) and those with Tis/T1 disease (HR 2.26, 95% CI 1.23–4.16; P = 0.008) but did not vary with initial treatment.Patients with HRNMIBC are at high‐risk of mortality. Those choosing RC as their initial treatment have lower risks of mortality than others, although this may reflect fitness and selection. [ABSTRACT FROM AUTHOR]

AbstractIntroductionMaterial and methodsResultsConclusionsComplete mesocolic excision (CME) is widely adopted for its assumed superior oncological outcome. However, it’s unclear if all right-sided colon cancer patients benefit from CME. The aim of this systematic review is to investigate whether CME contributes to postoperative outcomes and to determine the surgical indications for CME.We searched eligible articles about CME versus non-CME procedures for right-sided colon cancer in the OVID Medline, Embase, and Cochrane CENTRAL databases, and a meta-analysis was conducted.Twenty-two articles and seven abstracts involving 8088 patients were included in this study. Among them, 3803 underwent CME and 4285 non-CME procedures. The analysis showed that CME was favoured for three-year disease-free survival (DFS) and overall survival (OS), for local, systemic, and total recurrence, and for hospital stay durations. However, increased vascular injury and longer surgery time were observed in CME. Regarding the three-year OS, the superiority of CME was observed only in Stage III. Additionally, no significant differences were observed between CME and non-CME groups regarding overall complications, 30-day readmission rates, reoperation, or postoperative mortality rates.CME for right-sided colon cancer should be considered, particularly in Stage III patients, to contribute to improved oncological outcomes. However, careful attention must be paid to the increased risk of vascular injury. [ABSTRACT FROM AUTHOR]

Objective: Vulvar carcinoma exhibits a robust correlation alongside HPV infection; however, the impact of HPV rank on the prognostic outcomes of radiation therapy within vulvar malignancies stays ambiguous. In the present study, we performed a comprehensive examination as well as meta-analysis to assess the influence of infection with HPV upon the long-term outlook as well as sensitivity of individuals with vulvar cancer undergoing radiation therapy. Methods: A meticulous examination of the existing research was conducted in accordance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A thorough search was conducted in the PubMed, Embase, Web of Science, as well as Cochrane Library databases, covering the entire available literature till April 1, 2023. The studies that met the inclusion criteria contained data about HPV infection and oncological outcomes in patients with vulvar cancer who received radiation therapy. This study was registered in PROSPERO (CRD42023417957). Results: We identified 12 retrospective studies meeting our inclusion criteria, which included a total of 3967 patients. Patients with HPV-associated vulvar cancer achieved a better overall survival rate after radiotherapy (HR=0.71, 95%CI: 0.54-0.93, P=0.01), and showed a significant improvement in disease-free survival (HR=0.75, 95%CI: 0.58-0.97, P=0.09) and progression-free survival (HR=0.31, 95%CI: 0.22-0.45, P,<0.01). Meanwhile, the complete remission rate after radiotherapy was higher for HPV-associated vulvar cancer patients (MH= 4.02, 95% CI: 1.87-8.61, P=0.0003), and the local control rate was better (HR=1.90, 95% CI: 1.15-3.15, P=0.01), exhibiting a reduced incidence of relapse within the field of study (HR=0.21, 95% CI: 0.10-0.42, P<0.001). Conclusion: In comparison to HPV-independent vulvar squamous cell carcinoma, patients with HPV-associated vulvar cancer exhibit higher sensitivity to radiotherapy, with a significant difference in prognosis. Further research should investigate the mechanisms underlying this high sensitivity to radiotherapy caused by HPV, and should be evaluated using high-quality randomized controlled trials. [ABSTRACT FROM AUTHOR]

Background: Recently, we could show that the co-mutations of KRAS + KEAP1, STK11 + KEAP1 and KRAS + STK11 + KEAP1 lead to a significantly shorter median overall survival (mOS) in patients with lung cancer across treatments by analyzing multiple dataset. TP53, a tumor suppressor gene, plays a crucial role in regulating cell cycle progression. Its mutations occur in approximately 40-50% of nonsmall lung cancer (NSCLC). Co-occurrence of all four mentioned mutations has been a matter of debate for years. The aim of this study was to assess the distribution of these four mutations and the influence of the different comutational patterns on survival. Methods: We present a comparative bioinformatic analysis and refer to data of 4,109 patients with lung adenocarcinoma (LUAD). Results: Most of the mutations within the LUAD belong to TP53-only (29.0%), quadruple-negative (25.9%) and KRAS-only (13.4%). Whereas TP53-mutations seem to have protective effects in the context of further KEAP1- and KRAS + KEAP1-alterations (improved mOS), their role seems contrary if acquired in an already existing combination of mutations as KRAS + STK11, KRAS + STK11 + KEAP1 and STK11 + KEAP1. TP53 co-mutations had a negative influence on KRASonly mutated LUAD (mOS reduced significantly by more than 30%). Discussion: These data underline the need for complex mutational testing to estimate prognosis more accurately in patients with advanced LUAD. [ABSTRACT FROM AUTHOR]

Background: Advances in anticancer drugs for lung cancer (LC) have improved the prognosis of LC. Chronic pulmonary aspergillosis (CPA) is a progressive and often exacerbating respiratory disease with a poor prognosis. To date, the prognosis of LC complicated by CPA has not been elucidated. This study investigated the clinical implications of concomitant CPA in patients with LC undergoing anticancer drug treatment. Methods: Between January 2010 and May 2020, we consecutively enrolled patients with LC complicated with CPA at five different institutions in Japan. We analyzed patients with LC complicated by CPA who received anticancer drug treatment. Results: A total of 10 patients with LC complicated by CPA received anticancer drug treatment. The median overall survival (OS) was 14.57 months (95% confidence interval [CI]: 5.37–21.67). The cause of death in all patients was LC. Six of the seven patients with LC did not show worsening pulmonary aspergillosis lesions during the anticancer drug treatment. Although two patients discontinued anticancer drug treatment due to pneumonitis, CPA complications did not interfere with the continuation of anticancer drug treatment. In univariate analyses, squamous histology (p = 0.01) and body mass index (<18.5 kg/m2) (p = 0.0008) were significantly associated with poorer OS. Conclusions: This study demonstrated that the cause of death in LC patients with concomitant CPA who received anticancer drug treatments and effective antifungal treatment was LC progression. Further large‐scale studies are needed to identify the effect of CPA in patients with LC. [ABSTRACT FROM AUTHOR]