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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]

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]

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: 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]

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]

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: 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]

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: 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]

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]

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]

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]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Background: Local therapies may benefit patients with oligometastatic cancer. However, there were limited data about pancreatic cancer. Here, we compared the efficacy and safety of stereotactic body radiation therapy (SBRT) to the primary tumor and all oligometastases with SBRT to the primary tumor alone in patients with metastatic pancreatic cancer. Methods: A retrospective review of patients with synchronous oligometastatic pancreatic cancer (up to 5 lesions) receiving SBRT to all lesions (including all oligometastases and the primary tumor) were performed. Another comparable group of patients with similar baseline characteristics, including metastatic burden, SBRT doses, and chemotherapy regimens, receiving SBRT to the primary tumor alone were identified. The primary endpoint was overall survival (OS). The secondary endpoints were progression frees survival (PFS), polyprogression free survival (PPFS) and adverse events. Results: There were 59 and 158 patients receiving SBRT to all lesions and to the primary tumor alone. The median OS of patients with SBRT to all lesions and the primary tumor alone was 10.9 months (95% CI 10.2–11.6 months) and 9.3 months (95% CI 8.8–9.8 months) (P < 0.001). The median PFS of two groups was 6.5 months (95% CI 5.6–7.4 months) and 4.1 months (95% CI 3.8–4.4 months) (P < 0.001). The median PPFS of two groups was 9.8 months (95% CI 8.9–10.7 months) and 7.8 months (95% CI 7.2–8.4 months) (P < 0.001). Additionally, 14 (23.7%) and 32 (20.2%) patients in two groups had grade 3 or 4 treatment-related toxicity. Conclusions: SBRT to all oligometastases and the primary tumor in patients with pancreatic cancer may improve survival, which needs prospective verification. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated one of the treatment options for advanced breast cancer patients after they completed standard therapy that combines hormone therapy and specific targeted agents called cyclin-dependent kinase 4/6 inhibitors. We wanted to understand why in real-world patients start chemotherapy after finishing standard initial treatment, how they respond to it, and what factors might affect their outcomes. We found that chemotherapy was often used when patients faced dissemination to internal organs with the risk of further progression, but it provided limited benefits. We suggest that modern drugs recommended by guidelines before chemotherapy should be better reimbursed in Poland. This research could help doctors make better treatment decisions and improve future clinical trials. The standard therapy for hormone-receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer includes the use of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy. The optimal post-CDK4/6i treatment sequence is unclear. This cohort study evaluated the initiation, characteristics, and outcomes of chemotherapy following CDK4/6i-based treatment. Among the 227 patients who began CDK4/6i therapy, 114 completed it. Seventy-nine female patients received further treatment, including 55 receiving chemotherapy. The average age was 60.1 years. Post-CDK4/6i chemotherapy was typically (69.1%) first-line due to an impending visceral crisis. The median progression-free survival (mPFS) was 3.0 months (range 0.5–18.9), and the median overall survival (mOS) was 8.3 months (0.5–26.1). The median OS from the end of CDK4/6i treatment was 12.4 months (1.5–26.8). In univariate analysis, neither mPFS nor mOS was associated with age, tumor grade, receptor status, Ki67 status, time from diagnosis to CDK4/6i cessation, therapy line, or CDK4/6i type. Dose reduction occurred in 12 patients (21.8%), and chemotherapy was ceased due to adverse events in 8 patients (14.6%). Chemotherapy showed limited benefit regardless of the regimen. The role of chemotherapy may evolve with broader CDK4/6i use in adjuvant treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-small cell lung cancer in stages II and III is a significant health challenge, requiring ongoing improvements in treatment strategies. One promising approach is neoadjuvant therapy, which is given before surgery to shrink tumours and treat unseen cancer spread. This early treatment can help doctors see how well the tumour responds, which can guide further therapy after surgery. Testing for specific markers in the tumour, like certain gene mutations and protein levels, helps doctors choose the most effective treatments for each patient. By doing this, the chances of successful surgery and long-term survival improve. Managing this type of cancer requires a team of specialists working together to create personalised treatment plans. Despite its promise, neoadjuvant therapy comes with challenges, such as determining which tumours can be removed after treatment and recognising if a tumour appears larger due to treatment effects rather than actual growth. However, the medical community's ongoing research and dedication are essential to overcoming these obstacles and enhancing the benefits of neoadjuvant therapy. This approach aims to increase survival rates and improve the quality of life for patients with non-small cell lung cancer, making it a valuable advancement for society. Non-small cell lung cancer (NSCLC) poses a significant challenge in clinical oncology, necessitating continual refinement of treatment approaches in stages II and III. Recent advancements have highlighted the potential of neoadjuvant therapy in optimising patient outcomes. Biomarker testing guides neoadjuvant therapy decisions, including epidermal growth factor receptor (EGFR) mutation and programmed death-ligand 1 (PD-L1) expression testing. Neoadjuvant therapy aims to improve oncological outcomes by treating micrometastatic disease and assessing tumour response before surgery. Disease-free survival is a surrogate endpoint for overall survival in both neoadjuvant and adjuvant settings. Multidisciplinary collaboration is crucial for individualised treatment planning and optimising patient care. The management of NSCLC requires a comprehensive approach, integrating expertise across disciplines and tailoring treatment strategies to individual patient needs. Neoadjuvant therapy shows promise in improving long-term outcomes, with biomarker testing guiding treatment decisions. Challenges such as defining borderline resectability and differentiating pseudoprogression highlight the need for ongoing research and collaboration. [ABSTRACT FROM AUTHOR]

Simple Summary: Although the high mutation burden in small-cell lung cancer (SCLC) suggests that it should be responsive to immune checkpoint blockade (ICB), relatively few patients have shown durable clinical benefit (DCB). To identify biomarkers of responses, biopsies from 35 patients treated with ICB (21 first-line and 14 second-line) were subjected to transcriptomic analysis and gene signatures were studied. Patients with DCB were compared to those with no clinical benefit (NCB). The response to ICB in the second-line, but not the first-line, setting was associated with gene signatures of inflammation, antigen presentation, interferon responses, and increased CD8 T cells. Our data suggest that responses to ICB in the second-line setting can be predicted by the baseline inflammatory state of the tumor; however, this strong association with inflammation was not observed in the first-line setting, likely because chemotherapy alters the immune milieu allowing a response to ICB. Although immune checkpoint blockade (ICB) is currently approved for the treatment of extensive-stage small-cell lung cancer (SCLC) in combination with chemotherapy, relatively few patients have demonstrated durable clinical benefit (DCB) to these therapies. Biomarkers predicting responses are needed. Biopsies from 35 SCLC patients treated with ICB were subjected to transcriptomic analysis; gene signatures were assessed for associations with responses. Twenty-one patients were treated with ICB in the first-line setting in combination with platinum-based chemotherapy; fourteen patients were treated in the second-line setting with ICB alone. DCB after ICB in SCLC in the second-line setting (3 of 14 patients) was associated with statistically higher transcriptomic levels of genes associated with inflammation (p = 0.003), antigen presentation machinery (p = 0.03), interferon responses (p < 0.05), and increased CD8 T cells (p = 0.02). In contrast, these gene signatures were not significantly different in the first-line setting. Our data suggest that responses to ICB in SCLC in the second-line setting can be predicted by the baseline inflammatory state of the tumor; however, this strong association with inflammation was not seen in the first-line setting. We postulate that chemotherapy alters the immune milieu allowing a response to ICB. Other biomarkers will be needed to predict responses in first-line therapy patients. [ABSTRACT FROM AUTHOR]

Objective: Cyclin-dependent kinase (CDK) 4 and 6 inhibitors (abemaciclib, palbociclib and ribociclib) have been recommended in the first-line treatment of hormone receptor-positive (HR+) breast cancer in China. Our study aims to evaluate the efficacy and safety of CDK4/6 inhibitors by processing survival data using fractional polynomial modeling methods. Methods: Phase II or III randomized controlled trials in treatment-naive HR + patients with advanced breast cancer were systematically searched through the preset search strategy. The fractional polynomial (FP) model was used to relax the proportional hazard assumption and obtain time-varying hazard ratio (HR). Progression-free life years (PFLYs) and life years (LYs) were calculated from the area under curve (AUC) of the predicted progression-free survival (PFS) and overall survival (OS) curves to evaluate the long-term efficacy benefit. Odds ratio (OR) of grade≥3 adverse events were analyzed for safety outcomes. Results: 6 randomized controlled trials with 2,638 patients were included. The first-order FP model (p = -1) and the first-order FP model (p = 1) were used to calculate the time-varying HR of PFS and OS, respectively. Extrapolating to 240 months, abemaciclib obtained a PFS benefit of 3.059 PFLYs and 6.275 LYs by calculating the AUC of the PFS and OS curves. Palbociclib obtained 2.302 PFLYs and 6.351 LYs. Ribociclib obtained 2.636 PFLYs and 6.543 LYs. In terms of safety, the use of CDK4/6 inhibitors resulted in a higher risk of adverse events (OR = 9.84, 95% CI: 8.13-11.95), especially for palbociclib (OR = 14.04, 95% CI: 10.52-18.90). Conclusion: The use of CDK4/6 inhibitors in treatment-naive patients with HR + advanced breast cancer significantly improves survival, but also increases the risk of adverse events. Abemaciclib and ribociclib may be the best options for prolonging PFS and OS in treatment-naïve patients, respectively. [ABSTRACT FROM AUTHOR]

Introduction: The treatment of hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE) and lenvatinib individually has shown favorable outcomes, but there is currently no meta-analysis based on randomized controlled trials (RCTs) to investigate the efficacy and safety of this combined treatment for HCC. The aim of this study was to identify the efficacy and safety of TACE plus lenvatinib for the treatment of HCC. Methods: A systematic search of MEDLINE (via PubMed), the Cochrane Library, EMBASE, and the Web of Science was conducted on July 31, 2023. RCTs evaluating the efficacy and safety of TACE in combination with lenvatinib for the treatment of HCC were included. The risk of bias in the included studies was assessed using the Risk of Bias 2 tool. Outcome measures such as objective response rate (ORR), complete remission (CR), progression-free survival (PFS), overall survival (OS), and safety parameters were extracted from the included studies. Binary outcomes were analyzed using odds ratio (OR), risk ratio, or hazard ratio (HR), while continuous variables were analyzed using mean difference (MD) or standardized MD in RStudio. The quality of the evidence was graded using the GRADE approach. Heterogeneity was considered significant when the I-squared was 50% or less. Results: Five RCTs involving 638 patients were included. The meta-analysis revealed that patients in the TACE plus lenvatinib group had a significantly higher mean ORR compared to the control group (OR: 3.65, 95% confidence interval [CI]: 2.50–5.32, fixed-effects model; OR: 3.58, 95% CI: 2.45–5.24, random-effects model, I2 = 0, moderate quality). Specifically, 40.9% of patients in the TACE plus lenvatinib group achieved a PR, which was significantly higher than the control group (OR: 3.51, 95% CI: 2.41–5.13, fixed-effects model; OR: 3.46, 95% CI: 2.36–5.07, random-effects model, I2 = 0, moderate quality). The HR for OS was 0.47 (95% CI: 0.35–0.62, fixed-effects model and random-effects model, I2 = 0, moderate quality). The meta-analysis revealed that the TACE plus lenvatinib group had a significantly higher total adverse effects rate than the control group (OR: 1.86, 95% CI: 1.01–3.43, fixed-effects model; OR: 1.85, 95% CI: 1.00–3.43, random-effects model, I2 = 0, moderate quality). Conclusion: Our study suggests that the combination of TACE and lenvatinib in the treatment of HCC has shown promising results, with extended OS and improved ORR. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to evaluate the derived neutrophil to lymphocyte ratio (dNLR) in predicting the prognosis of patients with locally advanced oral squamous cell carcinoma, as well as the survival benefits from induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (5-FU). The dNLR is an independent negative predictive factor for the disease. Patients with cTNM stage III disease and a low dNLR may benefit from induction chemotherapy. Background: This study aimed to evaluate the derived neutrophil to lymphocyte ratio (dNLR) in predicting the prognosis of patients with locally advanced oral squamous cell carcinoma (LAOSCC) and to assess the survival benefits from docetaxel, cisplatin, and 5-fluorouracil (5-FU) (TPF) induction chemotherapy (IC). Methods: Patients from a phase III trial involving TPF IC in stage III/IVA OSCC patients (NCT01542931) were enrolled. Receiver operating characteristic curves were constructed, and the area under the curve was computed to determine dNLR cutoff points. Kaplan–Meier survival estimates and Cox proportional hazards models were used for longitudinal analysis. Results: A total of 224 patients were identified (median age: 55.4 years; range: 26 to 75 years; median follow-up: 90 months; range: 3.2 to 93 months). The cutoff point for the dNLR was 1.555. Multivariate analysis showed that the dNLR was an independent negative predictive factor for survival (overall survival (OS): hazard ratio (HR) = 1.154, 95% confidence interval (CI): 1.018–1.309, p = 0.025; disease-free survival (DFS): HR = 1.123, 95% CI: 1.000–1.260, p = 0.050; local recurrence-free survival (LRFS): HR = 1.134, 95% CI: 1.002–1.283, p = 0.047; distant metastasis-free survival (DMFS): HR = 1.146, 95% CI: 1.010–1.300, p = 0.035). A low dNLR combined with cTNM stage III disease predicted benefit from TPF IC for the patients [OS (χ2 = 4.674, p = 0.031), DFS (χ2 = 7.134, p = 0.008), LRFS (χ2 = 5.937, p = 0.015), and DMFS (χ2 = 4.832, p = 0.028)]. Conclusions: The dNLR is an independent negative predictive factor in LAOSCC patients. Patients with cTNM stage III disease and a low dNLR can benefit from TPF IC. [ABSTRACT FROM AUTHOR]

Simple Summary: Response to treatment and prognosis after 223Ra treatment varies among patients. Using a combination of clinical, biochemical, and radiomic data from bone scintigraphy and 18F-Fluorocholine PET/CT obtained from our prospective ChoPET-Rad study, we identified predictive and prognostic variables. The goal was to create a nomogram able to predict therapeutic failure and overall survival, aiding in the selection of more suitable candidates for this treatment. Purpose: We aimed to develop a nomogram able to predict treatment failure, skeletal events, and overall survival (OS) in patients with castration-resistant prostate cancer with bone metastases (CRPC-BM) treated with Radium-223 dichloride (223Ra). Patients and Methods: Patients from the Castilla-La Mancha Spanish region were prospectively included in the ChoPET-Rad multicenter study from January 2015 to December 2022. Patients underwent baseline, interim, and end-of-treatment bone scintigraphy (BS) and 18F-Fluorocholine PET/CT (FCH PET/CT) scans, obtaining multiple imaging radiomics as well as clinical and biochemical variables during follow-up and studying their association with the previously defined end-points. Survival analysis was performed using the Kaplan–Meier method and Cox regression. Multivariate logistic and Cox regression models were calculated, and these models were depicted by means of nomograms. Results: Median progression-free survival (PFS) and OS were 4 and 14 months (mo), respectively. The variables that showed independent and significant association with therapeutic failure were baseline alkaline phosphatase (AP) levels (p = 0.022) and the characteristics of BM on the CT portion of PET/CT (p = 0.017). In the case of OS, the significant variables were therapeutic failure (p = 0.038), the number of lines received after 223Ra (p < 0.001), average SUVmax (p = 0.002), bone marrow infiltration in FCH PET/CT (p = 0.006), and interim FCH PET/CT response (p = 0.048). Final nomograms included these variables, showing good discrimination among the 100 patients included in our study. In the study of skeletal events, only OS showed a significant association in the multivariate analysis, resulting in an inconsistent nomogram design. Conclusions: FCH PET/CT appears to be a good tool for evaluating patients eligible for treatment with 223Ra, as well as for their follow-up. Thus, findings derived from it, such as the morphological characteristics of BM in the CT, bone marrow infiltration, or the response to 223Ra in the interim study, have proven to be solid and useful variables in the creation of nomograms for predicting therapeutic failure and OS. [ABSTRACT FROM AUTHOR]

Simple Summary: Tertiary lymphoid structures (TLS) arise in non-lymphoid tissues due to inflammation or cancer and play a key role in adaptive immune responses. In this study, we analyzed the TLS maturity in 78 patients with pathological T4 colorectal cancer (CRC). Mature TLS, identified by organized T (CD3+) and B (CD20+) lymphocytes with Ki-67-positive B cells, have been linked to microsatellite instability and improved cancer-specific and post-recurrence survival. High tumor Ki-67 expression correlated with poorer outcomes. The absence of mature TLS independently predicted poor survival. Tumors with mature TLS showed a higher infiltration of CD3+ T cells, FOXP3+ T cells, and CD86+ immune cells, including M1-like macrophages. Focusing on the Ki-67 expression pattern, the simultaneous evaluation of TLS maturity and tumor proliferation potency is suggested to be a potential prognostic indicator in CRC. Tertiary lymphoid structures (TLSs) are complex lymphocyte clusters that arise in non-lymphoid tissues due to inflammation or cancer. A mature TLS with proliferating germinal centers is associated with a favorable prognosis in various cancers. However, the effect of TLS maturity on advanced colorectal cancer (CRC) remains unexplored. We analyzed the significance of TLS maturity and tumor Ki-67 expression in surgically resected tumors from 78 patients with pathological T4 CRC. Mature TLS was defined as the organized infiltration of T and B cells with Ki-67-positive proliferating germinal centers. We analyzed the relationship between TLS maturity and intratumoral immune cell infiltration. Mature TLS with germinal center Ki-67 expression was associated with microsatellite instability and improved survival; however, high tumor Ki-67 expression was associated with poor survival in the same cohort. Multivariate analysis identified the absence of mature TLS as an independent predictor of poor post-recurrence overall survival. Intratumoral infiltration of T lymphocytes and macrophages was significantly elevated in tumors with mature TLS compared to those lacking it. High Ki-67 levels and absent mature TLS were identified as poor prognostic factors in advanced CRC. Mature TLS could serve as a promising marker for patients at high-risk of CRC. [ABSTRACT FROM AUTHOR]

Background & Aims: Accumulating data has shown the rising incidence and poor prognosis of early‐onset gastrointestinal cancers, but few data exist on biliary tract cancers (BTC). We aimed to analyse the clinico‐pathological, molecular, therapeutic characteristics and prognosis of patients with early onset BTC (EOBTC, age ≤50 years at diagnosis), versus olders. Methods: We analysed patients diagnosed with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder adenocarcinoma between 1 January 2003 and 30 June 2021. Baseline characteristics and treatment were described in each group and compared. Progression‐free survival, overall survival and disease‐free survival were estimated in each group using the Kaplan‐Meier method. Results: Overall, 1256 patients were included, 188 (15%) with EOBTC. Patients with EOBTC demonstrated fewer comorbidities (63.5% vs. 84.5%, p <.0001), higher tumour stage (cT3–4: 50.0% vs. 32.3%, p =.0162), bilobar liver involvement (47.8% vs. 32.1%, p =.0002), and metastatic disease (67.6% vs. 57.5%, p =.0097) compared to older. Patients with EOBTC received second‐line therapy more frequently (89.5% vs. 81.0% non‐EOBTC, p =.0224). For unresectable patients with BTC, median overall survival was 17.0 vs. 16.2 months (p =.0876), and median progression‐free survival was 5.8 vs. 6.0 months (p =.8293), in EOBTC vs. older. In advanced stages, fewer actionable alterations were found in EOBTC (e.g., IDH1 mutations [7.8% vs. 16.6%]; FGFR2‐fusion [11.7% vs. 8.9%]; p =.029). Conclusions: Patients with EOBTC have a more advanced disease at diagnosis, are treated more heavily at an advanced stage but show similar survival. A distinctive molecular profile enriched for FGRF2 fusions was found. [ABSTRACT FROM AUTHOR]

Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin–paclitaxel compared with placebo plus carboplatin–paclitaxel in patients with primary advanced or recurrent endometrial cancer (EC). At the first interim analysis, the trial met one of its dual primary endpoints with statistically significant progression-free survival benefits in the mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis. RUBY is a phase III, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent EC who were randomly assigned (1 : 1) to receive either dostarlimab (500 mg) or placebo, plus carboplatin–paclitaxel every 3 weeks for 6 cycles followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. OS was a dual primary endpoint. A total of 494 patients were randomized (245 in the dostarlimab arm; 249 in the placebo arm). In the overall population, with 51% maturity, RUBY met the dual primary endpoint for OS at this second interim analysis, with a statistically significant reduction in the risk of death [hazard ratio (HR) = 0.69, 95% confidence interval (CI) 0.54 - 0.89, P = 0.0020] in patients treated with dostarlimab plus carboplatin–paclitaxel versus carboplatin–paclitaxel alone. The risk of death was lower in the dMMR/MSI-H population (HR = 0.32, 95% CI 0.17 - 0.63, nominal P = 0.0002) and a trend in favor of dostarlimab was seen in the mismatch repair-proficient/microsatellite stable population (HR = 0.79, 95% CI 0.60 - 1.04, nominal P = 0.0493). The safety profile for dostarlimab plus carboplatin–paclitaxel was consistent with the first interim analysis. Dostarlimab in combination with carboplatin–paclitaxel demonstrated a statistically significant and clinically meaningful OS benefit in the overall population of patients with primary advanced or recurrent EC while demonstrating an acceptable safety profile. • RUBY compared dostarlimab + chemotherapy to chemotherapy alone in patients with primary advanced/recurrent EC. • RUBY showed statistically significant and clinically relevant improvements in OS with dostarlimab + chemotherapy. • These are clinically important results for patients with primary advanced/recurrent EC. • This represents a new standard of care for primary advanced/recurrent EC. [ABSTRACT FROM AUTHOR]

• Diaphragmatic stripping is associated with acceptable postoperative morbidity. • The procedure offers significant advantage on patients' survival. • The survival benefit seems to be independent of the stage at diagnosis or adequacy of tumor debulking. Diaphragmatic stripping is a standard procedure that is performed in a significant proportion of patients undergoing surgical cytoreduction for advanced ovarian cancer. The objective of the present study is to evaluate morbidity and survival outcomes among patients offered diaphragmatic surgery for primary diagnosed optimally resected ovarian cancer. We conducted a retrospective cohort study, identifying patients that were offered surgery between 2016 and 2021 for primary diagnosis of ovarian cancer. Cases that had diaphragmatic stripping or partial diaphragmatic resection were selected and compared to cases that did not require this procedure. Kaplan-Meier and Cox-regression analyses were applied to evaluate survival outcomes. Overall, 61 patients that had diaphragmatic stripping were identified. Severe postoperative complications (Clavien-Dindo 3 +) were noted in 19 patients (31 %). Survival analyses denoted that the stage of the disease at the time of diagnosis, as well as the timing of the surgical procedure (PDS vs IDS) and the completion of tumor debulking were factors that significantly affected the recurrence free and overall survival of patients. Severe postoperative morbidity was a significant predictor of the overall survival. Multivariate cox-regression analysis that was adjusted for the stage of the disease revealed that preoperative pleural effusion, optimal (compared to complete) tumor resection and the occurrence of postoperative complications significantly affected the overall survival of patients. Compared to patients that did not have diaphragmatic surgery, patients submitted to diaphragmatic stripping or resection had improved progression free and overall survival rates, irrespective of the stage of the disease at diagnosis or the adequacy of resection status. Diaphragmatic surgery is feasible in advanced ovarian cancer patients with acceptable morbidity that mainly refers to postoperative pleural effusion. Its positive impact on patients' survival requires further investigation. [ABSTRACT FROM AUTHOR]

Myristoylation, the N-terminal addition of the fatty acid myristate to proteins, regulates membrane-bound signal transduction pathways important in cancer cell biology. This modification is catalyzed by two N-myristoyltransferases, NMT1 and NMT2. Zelenirstat is a first-in-class potent oral small molecule inhibitor of both NMT1 and NMT2 proteins. Patients with advanced solid tumors and relapsed/refractory (R/R) B-cell lymphomas were enrolled in an open label, phase I dose escalation trial of oral daily zelenirstat, administered in 28-day cycles until progression or unacceptable toxicity. The endpoints were to evaluate dose-limiting toxicities (DLT) to establish a maximum tolerated dose (MTD), pharmacokinetic parameters, and anticancer activity. Twenty-nine patients were enrolled (25 advanced solid tumor; 4 R/R B-cell lymphoma) and 24 were DLT-evaluable. Dosing ranged from 20 mg once daily (OD) to 210 mg OD without DLT, but gastrointestinal DLTS were seen in the 280 mg cohort. MTD and recommended phase 2 dose were 210 mg OD. Common adverse events were predominantly Gr ≤ 2 nausea, vomiting, diarrhea, and fatigue. Plasma concentrations peaked at 2 h with terminal half-lives averaging 10 h. Steady state was achieved by day 15, and higher doses achieved trough concentrations predicted to be therapeutic. Stable disease as best response was seen in eight (28%) patients. Progression-free survival and overall survival were significantly better in patients receiving 210 mg OD compared to those receiving lower doses. Zelenirstat is well-tolerated, achieves plasma exposures expected for efficacy, and shows early signs of anticancer activity. Further clinical development of zelenirstat is warranted. [ABSTRACT FROM AUTHOR]

Summary: This study aimed to complement the results of the REACH-2 study by prospectively evaluating the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma (HCC) in a real-world setting. This was an open-label, nonrandomized, multicenter, prospective study conducted at 13 institutions in Japan (jRCTs031190236). The study included Child–Pugh Class A patients with advanced HCC who had received pretreatment with atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib. Ramucirumab was introduced as a second-line treatment after Atez/Bev or lenvatinib and as a third-line treatment after Atez/Bev and lenvatinib. Between May 2020 and July 2022, we enrolled 19 patients, including 17 who received ramucirumab. Additionally, seven patients received lenvatinib, another seven patients received Atez/Bev, and three patients received Atez/Bev followed by lenvatinib as prior treatment. The primary endpoint was a 6-month progression-free survival (PFS) rate, which was 14.3%. The median PFS and overall survival were 3.7 and 12.0 months, respectively. The most common grade ≥ 3 adverse events (AEs) were hypertension (23.5%), proteinuria (17.6%), and neutropenia (11.8%). The discontinuation rate due to AEs was 29.4%. Six patients progressed from Child–Pugh A to B after treatment with ramucirumab. Thirteen patients were eligible for post-ramucirumab treatment, including systemic therapy. Despite the limited number of patients, the efficacy of ramucirumab was comparable to that observed in the REACH-2 study when used after lenvatinib and Atez/Bev. However, the incidence of AEs was higher than that in the REACH-2 study. [ABSTRACT FROM AUTHOR]