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PURPOSE: Targeted Agent and Profiling Utilization Registry (TAPUR) is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with soft tissue sarcoma with cyclin-dependent kinase 4 (CDK4) amplification treated with palbociclib are reported. METHODS: Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0 to 2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration (SD16+) according to RECIST v1.1. The DC rate was estimated with a 90% CI. Secondary end points included OR, progression-free survival (PFS), overall survival (OS), duration of response, duration of SD, and safety. RESULTS: Forty-two patients with CDK4 amplification were enrolled. One patient was not evaluable for efficacy. One patient with partial response and 18 with SD16+ were observed for DC and OR rates of 46% (90% CI, 36 to 100) and 2% (95% CI, <1 to 13), respectively. Median PFS was 16 weeks (95% CI, 9 to 28) and median OS was 69 weeks (95% CI, 31 to 111) for evaluable patients. Twenty patients had at least one grade 3 to 4 adverse event (AE) at least possibly related to palbociclib, including alanine aminotransferase increase, anemia, fatigue, hypophosphatemia, leukopenia, neutropenia, and thrombocytopenia. No serious AEs were reported. CONCLUSION: Palbociclib met prespecified criteria to declare a signal of antitumor activity in patients with sarcoma and CDK4 amplification. Palbociclib met @ASCO #TAPUR criteria to declare antitumor activity in patients with CDK4-amplified liposarcoma. [ABSTRACT FROM AUTHOR]

Background: To elucidate the treatment and surgery outcomes with or without perioperative therapies in Japanese patients with clinical stage III non‐small cell lung cancer (NSCLC) in real‐world settings. Methods: We performed subset analyses of the SOLUTION study, a multicenter, noninterventional, observational study of Japanese patients diagnosed with clinical stage III NSCLC, for those who started first‐line treatment (surgery±perioperative therapy) between January 2013 and December 2014 (study registration: UMIN000031385). Follow‐up data were obtained using medical records from diagnosis to March 1, 2018. Results: Of 149 eligible patients, 67 underwent surgery alone (median age 71 years) and 82 underwent surgery+perioperative therapy (median age 63 years). Lung resection was performed in 137 patients and the others underwent exploratory thoracotomy or other procedures. Perioperative therapies included adjuvant therapy only (n = 41), neoadjuvant therapy only (n = 24), and neoadjuvant+adjuvant therapy (n = 17). The median overall survival (OS) and 3‐year OS rate were 29.3 months and 44.0%, respectively, in patients who underwent surgery alone, and not reached and 61.1%, respectively, in patients who underwent surgery+perioperative therapy. The 3‐year progression‐free survival (PFS) and disease‐free survival (DFS) rates were 42.4% and 47.1%, respectively, in patients who underwent surgery+perioperative therapy and 28.5% and 28.9%, respectively, in patients who underwent surgery alone. In multivariable Cox regression, perioperative therapy was associated with improved OS (hazard ratio [95% confidence interval] 0.49 [0.29–0.81]), PFS (0.62 [0.39–0.96]), and DFS (0.62 [0.39–0.97]) versus surgery alone. Conclusions: Our study suggested that perioperative therapy may be associated with better survival among patients undergoing surgical treatment of clinical stage III NSCLC. [ABSTRACT FROM AUTHOR]

Background: Anaplastic thyroid cancer (ATC) is highly invasive, prone to distant metastasis (DM), and has a very poor prognosis. This study aims to construct an accurate survival prediction model for ATC patients with DM, providing reference for comprehensive assessment and treatment planning. Methods: We extracted data of ATC patients with DM diagnosed between 2004 and 2019 from the SEER database, randomly dividing them into a training set and a validation set in a ratio of 7:3. Univariate and multivariate Cox regression analyses were sequentially performed on the training set to identify independent prognostic factors for overall survival (OS) and construct nomograms for 3-month, 6-month, and 8-month OS for ATC patients with DM based on all identified independent prognostic factors. Receiver operating characteristic (ROC) curve analysis, decision curve analysis (DCA) curve analysis, and calibration curves were separately plotted on the training and validation sets to demonstrate the model's performance. Furthermore, patients were stratified into high- and low-risk groups based on their risk scores, and the Kaplan-Meier (KM) survival curves were used to illustrate the survival differences between the two groups. Results: A total of 322 patients were included in this study. Univariate and multivariate Cox regression analyses identified five independent prognostic factors for OS in ATC patients with DM: surgery, tumor size, age, chemotherapy, and radiotherapy. Nomograms for 3-month, 6-month, and 8- month OS were established based on these factors. The training set AUC values (3-month AUC: 0.767, 6-month AUC: 0.789, 8-month AUC: 0.795) and validation set AUC values (3-month AUC: 0.753, 6-month AUC: 0.798, 8-month AUC: 0.806) as well as the calibration curves demonstrated excellent applicability and accuracy of the model. Additionally, the DCA curves indicated substantial clinical net benefit of the model. The KM curves also confirmed the model's excellent stratification ability for patient OS. Conclusion: The nomogram developed in this study accurately predicts OS for ATC patients with DM. It can assist clinicians in formulating appropriate treatment strategies for these patients. [ABSTRACT FROM AUTHOR]

Background: Nintedanib is a triple-angiokinase inhibitor with potential activity in patients with advanced thyroid cancers, as radioiodine refractory differentiated thyroid cancer (RAIR DTC) and medullary thyroid cancer (MTC). Design: EORTC-1209 (NCT01788982) was a double-blind randomized (2:1 ratio) placebo-controlled phase II, multi-cohort study exploring the efficacy and safety of nintedanib in patients with progressive, locally advanced, and/or metastatic RAIR DTC and MTC. The primary endpoint was progression-free survival (PFS) in the per-protocol (PP) population for both cohorts. Secondary endpoints included response rate, duration of response, overall survival (OS), and safety. Results: RAIR DTC cohort: Seventy out of the 75 planned patients with RAIR DTC (median age, 66 years; 39 women) who had progressed after one (76%) or two lines (24%) of previous systemic therapy were randomized to receive either nintedanib (N = 45) or placebo (N = 25). Of these, 69 patients started treatment and 56 met all inclusion criteria (PP). At data cutoff, the median duration of follow-up was 26.3 months in the nintedanib arm and 19.8 months in the placebo arm. In the PP population, themedian PFS was 3.7 months [80% confidence interval (CI), 1.9-6.5] in the nintedanib arm and 2.9 months (80% CI, 2.0-5.6) in the placebo arm(HR = 0.65; 80% CI, 0.42-0.99; one-sided log-rank test P = 0.0947). No objective response was observed. The median OS was 29.6 months [80% CI, 15.2-not reached (NR)] in the nintedanib arm and not reached in the placebo arm. Grade 3-4 adverse events of any attribution occurred in 50% of patients receiving nintedanib and in 36% of patients receiving placebo. MTC cohort: Thirty-one out of the 67 planned patients with MTC (median age, 57 years; eight women) who had progressed after one (68%) or two (32%) lines of previous systemic therapy were randomized to receive either nintedanib (N = 22) or placebo (N = 9). Of these, 20 patients (15 in the nintedanib arm and five in the placebo arm) started treatment and met all inclusion criteria (PP). The median PFS was 7.0 months (80% CI, 1.9-8.7) in the nintedanib arm and 3.9 months (80% CI, 3.0-5.5) in the placebo arm (HR = 0.49; 95% CI, 0.16-1.53). No objective response was reported. The median OS was 16.4 months (80% CI, 12.1-24.9) in the nintedanib arm and 12.3 months (80% CI, 7.1-NR) in the placebo arm. Grade 3-4 adverse events of any attribution during the blinded period occurred in 59.1% of patients receiving nintedanib and in 33.3% of patients receiving placebo. Conclusion: This study did not suggest a clinically significant improvement of PFS with nintedanib over placebo in patients with pretreated RAIR DTC and MTC. [ABSTRACT FROM AUTHOR]

Background: The newest clinical evidence that the relationship between the peritoneal cancer index (PCI) and the postoperative prognosis of advanced ovarian cancer patients remains controversial, and there are no large-sample and multicenter studies to clarify this matter. Therefore, in this paper, we used meta-analysis to systematically assess the postoperative prognostic value of PCI in subjects with advanced ovarian cancer to provide individualized treatment plans and thus improve the prognosis of patients. Methods: Literature on the correlation between PCI and the postoperative prognosis in subjects with advanced OC undergoing cytoreductive surgery (CRS) was searched in the Cochrane Library, Pubmed, Embase, and Web of Science from the database inception to April 20, 2023. The search was updated on February 28, 2024. We only included late-stage (FIGO stage: III-IV) patients who did not undergo neoadjuvant chemotherapy (NACT) or hyperthermic intraperitoneal chemotherapy (HIPEC). Afterwards, literature screening and data extraction were conducted using Endnote20 software. The literature quality was assessed using the Newcastle-Ottawa Scale (NOS). Lastly, statistical analysis was performed with STATA 15.0 software. Results: Five studies with 774 patients were included. The result indicated that patients with high PCI had a worse prognosis than those with low PCI. The combined hazard ratio was 2.79 [95%CI: (2.04, 3.82), p<0.001] for overall survival (OS) in patients with high PCI. Further subgroup analysis by the FIGO staging revealed that in stage III [HR: 2.61, 95%CI: (2.00, 3.40), p<0.001] and stage III-IV patients [HR: 2.69, 95%CI: (1.66, 4.36), p<0.001], a high PCI score was significantly associated with a worse prognosis. The PCI score had a greater impact on the OS of patients with higher stages. The combined hazard ratio was 1.89 [95%CI: (1.51, 2.36), p<0.001] for progression-free survival (PFS) in patients with high PCI. Conclusion: PCI may be used as a postoperative prognosis indicator in patients with advanced OC on primary debulking surgery. High PCI indicates a worse prognosis. However, further research is warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Introduction: Male breast cancer (MBC) is a rare condition, and recent research has underscored notable distinctions between MBC and breast cancer in women. This study aimed to assess and contrast the long-term survival outcomes and disease patterns of MBC patients with those of their female counterparts. Methods: We analyzed data from 113,845 patients diagnosed with breast cancer who had undergone curative surgery from the Korean Breast Cancer Registry (KBCR) between January 1990 and August 2014 in Seoul, Korea. The five-year overall survival was analyzed according to clinicopathological characteristics. Results: Among 113,845 patients with breast cancer, 473 MBC cases were included. The median duration of follow-up was 72 months. The median age at diagnosis was 60 and 48 years for MBC and female breast cancer, respectively. Most male patients (92.6%) underwent total mastectomy, while 50.4% of female patients underwent breast-conserving surgery. Among MBC, 63.2% received chemotherapy, and 83.9% of hormone receptor-positive male patients received endocrine therapy. In survival analysis, MBC demonstrated distinct 5-year overall survival patterns compared with female breast cancer, according to age at diagnosis. In women with breast cancer, the younger age group (=40 years) demonstrated worse 5-year overall survival than did the older age group (>40 years) (91.3% vs 92.7%, p <0.05). While in MBC, the younger age group (=40 years) demonstrated better 5-year overall survival than did the older age group (>40 years) (97.4% vs 86.4%, p <0.05). Discussion: In conclusion within this extensive cohort, we have revealed unique survival patterns in MBC that diverge from those observed in women with breast cancer. This study enhances our comprehension of MBC prognosis and can potentially shed light on unresolved questions, paving the way for future research in the realm of MBC. [ABSTRACT FROM AUTHOR]

Background: Poly (ADP-Ribose) Polymerase (PARP) inhibitors represent a novel class of drugs that hinder DNA repair mechanisms in tumor cells, leading to cell death. This systematic review aims to evaluate the effectiveness, safety, and potential adverse effects of PARP inhibitors (PARPi) in the management of patients with advanced lung cancer. Materials and Methods: We conducted a comprehensive search for relevant studies in PubMed, Embase, Cochrane, and ClinicalTrials.gov. We extracted primary and secondary outcome measures, including progression-free survival (PFS), overall survival (OS), and adverse events (AEs), from the identified literature for subsequent meta-analysis and systematic review. Results: This study encompassed twelve randomized controlled trials, involving 3,132 patients with advanced lung cancer. In comparison to non-PARPi treatments, the administration of PARPi significantly extended OS (hazard ratio (HR) = 0.90, 95% CI = 0.83–0.97, p = 0.006). However, the difference in PFS did not reach statistical significance. Conclusion: In summary, therapies incorporating PARPi provide a degree of benefit by extending OS in patients with advanced lung cancer. Nonetheless, further trials are necessary to furnish additional evidence regarding the efficacy and safety of PARPi in the treatment of lung cancer. [ABSTRACT FROM AUTHOR]

Introduction: We previously conducted a phase I/Ib study (NCT03712943) with regorafenib and nivolumab in patients with refractory metastatic mismatch repair proficient (pMMR) colorectal cancer (CRC). This study aimed to investigate the role of Xerna™ TME Panel in predicting the treatment response. Methods: Twenty-two archival pretreatment tumor samples were subjected to the Xerna™ TME Panel, a machine learning-based RNA-sequencing biomarker assay. The Xerna tumor microenvironment (TME) subtypes were evaluated for correlation with overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and other biomarkers including KRAS, PD-L1, CD8 expression, and Treg cells in TME. Results: Based on Xerna™ TME Panel, 4 patients with immune-active (IA) subtype and 6 patients with immune-suppressed subtype were classified as biomarker-positive, and five with angiogenic (A) subtype and seven with immune desert subtype were biomarker-negative. While not reaching statistical significance, Xerna TME biomarker-positive patients seemed to have longer median PFS (7.9 vs. 4.1 months, p = 0.254), median OS (15.75 vs. 11.9 months, p = 0.378), and higher DCR (70% vs. 58%, p = 0.675). The IA subtype in our cohort had higher levels of CD4+ FOXP3+ Treg cells, whereas the A subtype showed lower levels of Treg cells. Conclusion: Xerna™ TME Panel analysis in patients with refractory metastatic pMMR CRC who were treated with regorafenib plus nivolumab might be of value for predictive clinical benefit. Further studies are needed to evaluate the predictive role of Xerna™ TME Panel analysis in patients with refractory metastatic pMMR CRC. [ABSTRACT FROM AUTHOR]

Background To estimate the causal effect of surgery vs chemotherapy on survival in patients with T1-3NxM0 pancreatic cancer in a rigorous framework addressing selection bias and immortal time bias. Methods We used population-based Danish health-care registries to conduct a cohort study emulating a hypothetical randomized trial to estimate the absolute difference in survival, comparing surgery with chemotherapy. We included pancreatic cancer patients diagnosed during 2008-2021. Exposure was surgery or chemotherapy initiated within a 16-week grace period after diagnosis. At the time of diagnosis, data of each patient were duplicated; one copy was assigned to the surgery protocol, and one copy to the chemotherapy protocol of the hypothetical trial. Copies were censored when the assigned treatment deviated from the observed treatment. To account for informative censoring, uncensored patients were weighted according to confounders. For comparison, we also applied a more conventional analysis using propensity score-based inverse probability weighting. Results We included 1744 patients with a median age of 68 years: 73.6% underwent surgery, and 18.6% had chemotherapy without surgery; 7.8% received no treatment. The 3-year survival was 39.7% (95% confidence interval [CI] = 36.7% to 42.6%) after surgery and 22.7% (95% CI = 17.7% to 28.4%) after chemotherapy, corresponding to an absolute difference of 17.0% (95% CI = 10.8% to 23.1%). In the conventional survival analysis, this difference was 23.0% (95% CI = 17.0% to 29.0%). Conclusion Surgery was superior to chemotherapy in achieving long-term survival for pancreatic cancer. The difference comparing surgery and chemotherapy was substantially smaller when using the clone-censor-weight approach than conventional survival analysis. [ABSTRACT FROM AUTHOR]

Introduction: Survival data reported by randomised controlled trials are collected in a highly selected patient population and can thus only be transferred to a limited extent to real-world patients: the patients in routine care are mostly older, present with more comorbidities and a worse general state of health. This so-called efficacy-effectiveness gap typically results in inferior survival data in routine healthcare. Methods: Six prospective clinical tumour registries recruited a total of 11,679 patients receiving systemic therapy in haemato-oncological practices in Germany between 2006 and 2020. For these patients with advanced colorectal cancer, breast cancer, lung cancer, pancreatic cancer, renal cell cancer, and lymphatic neoplasms, overall survival was analysed. A comprehensive literature search was performed to identify suitable pivotal randomised controlled trials. Results: Median overall survival of patients treated in German routine care, with advanced colorectal, breast, lung, and pancreatic cancer, as well as with diffuse large B‐cell lymphoma and multiple myeloma, is not shorter than the respective survival data reported in trials. Patients with advanced renal cell carcinoma, chronic lymphocytic leukaemia, or indolent non-Hodgkin lymphoma showed slightly lower survival rates compared to clinical trials. Conclusions: Despite less favourable patient characteristics, survival data from patients with cancer treated in ambulatory routine care in Germany are in range with results from randomised controlled studies. [ABSTRACT FROM AUTHOR]

Aim: Extramural venous invasion detected by MRI (mrEMVI) has in several expert centre studies been identified as an important prognostic factor in rectal cancer, and in guiding neoadjuvant therapy. However, population‐based evidence for mrEMVI as a predictor for recurrent disease is lacking. Method: This was a multicentre retrospective study based on the Swedish Colorectal Cancer Registry. The study period encompassed patients operated with abdominal resection for rectal cancer 2017–2021, with follow‐up until January 2023. Patients diagnosed at hospitals with radiological registry data coverage <90% or with metastatic disease were excluded. Pretreatment mrEMVI constituted exposure, while recurrence‐free survival was the main outcome. Distant and local recurrence, and overall survival were secondary outcomes, and pretreatment and postoperative scenarios were explored using multivariable Cox regression with multiple imputation. Hazard ratios (HRs) with 95% confidence intervals (CIs) were reported. Results: A total of 2737 patients from 13 hospitals were eligible for analysis. Pretreatment mrEMVI was reported in 14.5% of patients, while 71.9% had negative findings and 13.6% had missing data. In the pretreatment scenario, mrEMVI was an independent predictor for worse recurrence‐free survival with an adjusted HR of 1.64 (95% CI: 1.31–2.06). In the postoperative MDT setting, the influence of mrEMVI on recurrence‐free survival decreased with an adjusted HR of 1.27 (95% CI: 1.00–1.61). Conclusion: mrEMVI at diagnosis is an independent predictor of recurrence‐free survival in an unselected population of rectal cancer patients undergoing abdominal resection. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is often diagnosed at advanced stage, where chemotherapy is the mainstay of treatment. Despite new chemotherapy regimens improving overall survival over the past decade, the median survival for advanced pancreatic cancer remains around one year. However, we occasionally encounter long-term survivors among patients with advanced pancreatic cancer. Analyzing these cases may provide valuable insights for understanding pancreatic cancer and improving treatment strategies. We report a case of 61-year-old patient with metastatic pancreatic cancer who survived for approximately five years. Single-cell transcriptome analysis of tissues obtained at the time of pancreatic cancer diagnosis and at 57 months post-diagnosis revealed changes in the tumor immune microenvironment. [ABSTRACT FROM AUTHOR]

Background: This study aims to compare treatment outcomes in patients with Triple-Negative Breast Cancer (TNBC) and HER2-Positive Breast Cancer, evaluating clinical responses, survival rates, recurrence rates, quality of life (QoL), and adverse events. Materials and Methods: A total of 100 female patients were included, with 50 diagnosed with TNBC and 50 with HER2-Positive Breast Cancer. Data on demographics, treatment regimens, clinical outcomes, survival rates, recurrence rates, QoL scores, and adverse events were collected and analyzed. Results: Mean age was 52.3 ± 9.7 years for TNBC and 54.1 ± 10.2 years for HER2-Positive patients. Surgery was performed in 90% of TNBC and 85% of HER2-Positive patients. Chemotherapy was administered to all patients. Radiation therapy was given to 60% of TNBC and 65% of HER2-Positive patients. Targeted therapy was administered to 10% of TNBC and 95% of HER2-Positive patients. Complete response rates were 20% for TNBC and 35% for HER2-Positive patients. Partial response rates were 40% for TNBC and 45% for HER2-Positive patients. Progressive disease occurred in 15% of TNBC and 10% of HER2-Positive patients. Survival rates at various time points are provided in Table 4. The 1-year overall survival (OS) rate was 80% (40 patients) for TNBC and 90% (45 patients) for HER2-Positive patients. The 2-year OS was 60% (30 patients) for TNBC and 75% (38 patients) for HER2- Positive patients. Local recurrence was 30% for TNBC and 20% for HER2- Positive patients. Distant metastasis occurred in 40% of TNBC and 25% of HER2-Positive patients. Grade 3-4 neutropenia was reported in 25% of TNBC and 20% of HER2-Positive patients. Cardiotoxicity was observed in 5% of TNBC and 10% of HER2-Positive patients. Conclusion: HER2-Positive patients exhibited better clinical outcomes and survival rates than TNBC patients but had a higher incidence of cardiotoxicity. These findings underscore the need for tailored treatment approaches and vigilant monitoring of adverse events. [ABSTRACT FROM AUTHOR]

Objectives Access to early phase trials for children with relapsed, refractory or progressive (RRPD) cancer is limited in Canada. Patients and families face barriers to access trials, which are poorly understood. The aims of this study were to assess availability of early phase trials and examine the impact of distance from home to study centre on trial enrolment among paediatric oncology patients with RRPD. Methods Oncology patients ≤18 years at diagnosis who later had RRPD were identified retrospectively via registry at the only quaternary paediatric oncology centre in British Columbia (BC). We determined if distance to home, as calculated using geocoding software, was predictive of trial offer or enrolment. Results Between January 2015 and July 2021, 266 patients experienced 396 RRPD events. Seventy-five patients (28.2%) were eligible for an early phase trial at least once. At first eligible event, 61 patients (22.9%) were offered trial (median age 11.8 years; 69.0% male; 46.0% with CNS tumour) and thirty patients (11.3%) enrolled. Distance was not associated with odds of offer (OR 1.01, CI 0.98 to 1.05) or enrolment (OR 0.99, CI 0.95 to 1.03) on univariate or multivariable analysis adjusted for sex and disease (OR 0.93, CI 0.86 to 1.00). For offered patients, 2-year event-free survival (EFS) and overall survival (OS) were 39.1% (CI 28.0% to 54.8%) and 51.8% (CI 39.9% to 67.2%), respectively. EFS/OS did not differ with distance or enrolment, but varied by disease (EFS P = 0.002, OS P < 0.0001). Conclusions Children in BC with cancer and RRPD have limited access to early phase trials. Distance was not predictive of enrolment, suggesting that families travel to access therapy. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The results of the phase 3 ALSYMPCA trial showed that Radium-223 (Ra-223) improves overall survival (OS) and delays onset of first symptomatic skeletal event vs. placebo in patients with metastatic castration-resistant prostate cancer (mCRPC). The purpose of the REACTIVATE study was to inform the optimal placement of Ra-233 in the treatment sequence by evaluating clinical outcomes and healthcare resource utilization using real-world data from multiple Canadian provinces. METHODS: This retrospective cohort study analyzed patient outcomes according to Ra-223 placement using administrative databases of four Canadian provinces, encompassing 4301 patients with mCRPC who received at least two lines of life-prolonging therapy (LPT) for mCRPC. Outcomes included OS, event-free survival (EFS), and healthcare resource utilization. Each province was analyzed separately. RESULTS: OS, measured from the start of second-line LPT, differed between provinces: those in Ontario receiving second-line Ra-223 had a longer OS vs. those receiving it in third-line or later (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.66-0.95). There was no difference between lines of therapy in patients in British Columbia (HR 1.165, 95% CI, 0.894-1.518, p=0.2576), and OS was numerically worse but not statistically significant in patients receiving Ra-223 in second-line in Quebec (HR 1.44, 95% CI, 0.93-2.24). Other outcomes also varied across provinces, with second-line use of Ra-223 being associated with longer EFS and reduced healthcare utilization vs. third-line use in Ontario but not in Quebec. CONCLUSIONS: Significant heterogeneity exists in the management and outcomes of mCRPC between provinces, particularly regarding the placement of Ra-223 in the treatment sequence. [ABSTRACT FROM AUTHOR]

The phase 2, multicohort, open-label LEAP-005 study evaluated lenvatinib plus pembrolizumab in patients with previously treated advanced solid tumors. We report outcomes from the ovarian cancer cohort. Eligible patients had metastatic/unresectable ovarian cancer and had received 3 previous lines of therapy. Patients received lenvatinib 20 mg/day plus pembrolizumab 200 mg every 3 weeks. Treatment continued until progression, unacceptable toxicity, or (for pembrolizumab) completion of 35 cycles. Primary endpoints were objective response rate (ORR) per RECIST version 1.1 and safety. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Thirty-one patients were enrolled. 39% had high grade serous ovarian cancer, 23% were platinum-sensitive, 55% were platinum-resistant, 23% were platinum-refractory, and 84% had tumors that had a PD-L1 combined positive (CPS) score ≥1. ORR (95% CI) was 26% (12%–45%) by investigator assessment and 35% (19%–55%) by blinded independent central review (BICR). Per BICR, median DOR was 9.2 (1.5+ to 37.8+) months. ORRs (95% CI) by BICR were 35% (9/26 patients; 17%–56%) for PD-L1 CPS ≥ 1 disease and 50% (2/4 patients; 7%–93%) for PD-L1 CPS < 1 disease. Median (95% CI) PFS by BICR and OS were 6.2 (4.0–8.5) months and 21.3 (11.7–32.3) months, respectively. Treatment-related AEs occurred in 94% of patients (grade 3–4, 77%). One patient died from treatment-related hypovolemic shock. Lenvatinib plus pembrolizumab demonstrated antitumor activity as fourth line therapy in patients with advanced ovarian cancer, and no unanticipated safety signals were identified. Responses were observed regardless of PD-L1 status. • We evaluated lenvatinib plus pembrolizumab as fourth-line therapy in 31 patients with advanced ovarian cancer. • Lenvatinib plus pembrolizumab had an objective response rate of 35% by blinded independent central review in this population. • Median duration of response by blinded independent central review was 9.2 (1.5+ to 37.8+) months. • Median progression-free survival was 6.2 months and median overall survival was 21.3 months. • Treatment-related adverse events occurred in 94% of patients (grade 3–4, 77%; grade 5, 3%). [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to assess the prognostic value of muscle invasion (MI), a key histopathological feature of tumor aggressiveness, and construct a superior prognostic prediction model combining the current TNM staging system. Materials and Methods: MI was analyzed in the whole‐slide images from a total of 301 patients with primary buccal mucosa squamous cell carcinoma (BMSCC). Survival times of patients with/without MI were evaluated by Kaplan–Meier analysis. MI was further combined with the TNM staging system to explore its predictive value for prognosis. Moreover, 204 cases of head and neck carcinoma from the TCGA database were included. Results: MI positive rate reached to 76% (229/301) in patients with BMSCC. MI was associated with poor overall survival (p = 0.012) and disease‐free survival (p = 0.022). The novel system (TNM staging combined with MI) revealed strong predictive performance, with the largest area under the curve (OS: p < 0.001, DFS: p < 0.004). MI and the established classification system were also had good predictive ability in the TCGA cohort. Conclusions: MI is an independent predictor of poor prognosis of BMSCC. The inclusion of MI in prediction system can augment the risk stratification of patients with oral squamous cell carcinoma and may assist in the clinical decision‐making process. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck squamous cell carcinoma (HNSCC) remains a global health concern due to the lack of precise early diagnostic biomarkers and often-delayed diagnosis. This study employs machine learning, weighted gene co-expression network analysis, and network biology to identify transcriptomic markers for HNSCC detection. We identified nine genes with significantly differentially expressed activity in samples from HNSCC patients. These gene signatures could greatly improve early HNSCC identification and warrant further investigation to confirm their predictive and therapeutic significance. The transcriptional landscape of platelets in head and neck cancer patients revealed distinct gene expression profiles compared to healthy controls, underscoring the systemic impact of the tumor on blood platelets. Additionally, the study emphasizes the role of tumor-educated platelets (TEPs), which carry RNA signatures indicative of tumor-derived material, offering a non-invasive source for early-detection biomarkers. Although there has been a reduction in head and neck squamous cell carcinoma occurrence, it continues to be a serious global health concern. The lack of precise early diagnostic biomarkers and postponed diagnosis in the later stages are notable constraints that contribute to poor survival rates and emphasize the need for innovative diagnostic methods. In this study, we employed machine learning alongside weighted gene co-expression network analysis (WGCNA) and network biology to investigate the gene expression patterns of blood platelets, identifying transcriptomic markers for HNSCC diagnosis. Our comprehensive examination of publicly available gene expression datasets revealed nine genes with significantly elevated expression in samples from individuals diagnosed with HNSCC. These potential diagnostic markers were further assessed using TCGA and GTEx datasets, demonstrating high accuracy in distinguishing between HNSCC and non-cancerous samples. The findings indicate that these gene signatures could revolutionize early HNSCC identification. Additionally, the study highlights the significance of tumor-educated platelets (TEPs), which carry RNA signatures indicative of tumor-derived material, offering a non-invasive source for early-detection biomarkers. Despite using platelet and tumor samples from different individuals, our results suggest that TEPs reflect the transcriptomic and epigenetic landscape of tumors. Future research should aim to directly correlate tumor and platelet samples from the same patients to further elucidate this relationship. This study underscores the potential of these biomarkers in transforming early diagnosis and personalized treatment strategies for HNSCC, advocating for further research to validate their predictive and therapeutic potential. [ABSTRACT FROM AUTHOR]

Simple Summary: Advancements in immune, targeted, and regional therapies have emerged in the past fifteen years in the management of high-risk, advanced, and metastatic melanomas. Rare melanoma variants include acral, mucosal, uveal, and desmoplastic melanoma. Though underrepresented in larger landmark trials for modern therapeutic options, results from these trials have been extrapolated and applied in the management of these rarer subtypes of melanoma. This article aims to review the current treatment recommendations for acral, mucosal, uveal, and desmoplastic melanomas. Rare histologic subtypes of melanoma, including acral, mucosal, uveal, and desmoplastic melanomas, only make up 5% of all diagnosed melanomas and are often underrepresented in large, randomized trials. Recent advancements in systemic therapy have shown marked improvement in pathologic response rates, improving progression-free and overall survival among cutaneous melanoma patients, but there are limited data to demonstrate improved survival among rarer subtypes of melanoma. Acral melanoma has a poor response to immunotherapy and is associated with worse survival. Mucosal melanoma has a large variability in its presentation, a poor prognosis, and a low mutational burden. Uveal melanoma is associated with a high rate of liver metastasis; recent adoption of infusion and perfusion therapies has demonstrated improved survival among these patients. Desmoplastic melanoma, a high-risk cutaneous melanoma, is associated with high locoregional recurrence rates and mutational burden, suggesting this melanoma may have enhanced response to immunotherapy. While these variants of melanoma represent distinct disease entities, this review highlights the clinicopathologic characteristics and treatment recommendations for each of these rare melanomas and highlights the utility of modern therapies for each of them. [ABSTRACT FROM AUTHOR]

Simple Summary: This study of nonsquamous lung cancer patients undergoing neoadjuvant chemotherapy with bevacizumab followed by surgery revealed that 20% were pathologic responders, experiencing 100% 5-year survival rates. In contrast, the 80% nonresponders demonstrated significantly lower rates. Pathologic response emerged as a survival predictor, indicating prolonged post-surgery survival for responders, while nonresponders required additional therapy for improved outcomes. The objective of this study was to evaluate the relationship between pathologic response and survival in patients with clinical stage II/IIIA nonsquamous non-small-cell lung cancer (NSCLC) who intended to undergo neoadjuvant chemotherapy with bevacizumab, followed by surgery. In this phase II NAVAL study evaluating the feasibility of neoadjuvant chemotherapy with cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg), followed by surgery, progression-free survival (PFS) and overall survival (OS) were assessed as the secondary endpoints. Patients were categorized based on the proportion of residual viable primary tumor in the resected specimen after neoadjuvant chemotherapy: those with residual tumor in less than one-third were classified as pathologic responders, the rest as nonresponders. Of the 30 patients, 25 underwent surgical resection after three cycles of neoadjuvant chemotherapy with bevacizumab; 5 did not undergo surgery. Among all 30 patients, the rates of 2- and 5-year PFS were 41.5% and 34.6%, respectively, and the rates of 2- and 5-year OS were 70.0% and 60.0%, respectively. A total of 6 patients (20%) were classified as pathologic responders; the other 24 (80%), as nonresponders. The five-year PFS differed significantly between pathologic responders (100%) and nonresponders (17.5%; p = 0.002). The five-year OS also differed significantly between pathologic responders (100%) and nonresponders (43.5%; p = 0.006). Pathologic response seems to be a predictor of survival. Long-term survival after surgery is expected for pathologic responders, whereas additional therapy is needed for nonresponders. [ABSTRACT FROM AUTHOR]

Simple Summary: The exploration of prognostic biomarkers in ovarian cancer (OC) persists due to the daunting challenge of therapy resistance and poor patient outcomes. Dysregulated components of haemostasis are recognized as pivotal players in OC pathogenesis, contributing to tumour growth, metastasis, and the onset of cancer-associated thrombosis (CAT). Drawing upon the concept of immunothrombosis, which elucidates the intricate crosstalk among immune cells, platelets, and endothelial cells, this study investigated the expression of haemostasis-related genes in peripheral blood entities (particularly platelets and immune cells). The aim was to uncover prognostic markers, potential therapeutic targets for cancer management, and CAT predictors. Lower pre-chemotherapy F3 and F8 expression levels were significantly associated with increased CAT susceptibility post tumour diagnosis. The latter was also associated with shorter progression-free and overall survival. These findings point out the prognostic potential of these genes in OC in the context of immunothrombosis. Validation in larger cohorts is essential for clinical translation. Ovarian cancer (OC) is the deadliest gynaecological malignancy. Identifying new prognostic biomarkers is an important research field. Haemostatic components together with leukocytes can drive cancer progression while increasing the susceptibility to venous thromboembolism (VTE) through immunothrombosis. Unravelling the underlying complex interactions offers the prospect of uncovering relevant OC prognostic biomarkers, predictors of cancer-associated thrombosis (CAT), and even potential targets for cancer therapy. Thus, this study evaluated the expression of F3, F5, F8, F13A1, TFPI1, and THBD in peripheral blood cells (PBCs) of 52 OC patients. Those with VTE after tumour diagnosis had a worse overall survival (OS) compared to their counterparts (mean OS of 13.8 ± 4.1 months and 47.9 ± 5.7 months, respectively; log-rank test, p = 0.001). Low pre-chemotherapy F3 and F8 expression levels were associated with a higher susceptibility for OC-related VTE after tumour diagnosis (χ2, p < 0.05). Regardless of thrombogenesis, patients with low baseline F8 expression had a shorter progression-free survival (PFS) than their counterparts (adjusted hazard ratio (aHR) = 2.54; p = 0.021). Among those who were not under platelet anti-aggregation therapy, low F8 levels were also associated with a shorter OS (aHR = 6.16; p = 0.006). Moving forward, efforts should focus on external validation in larger cohorts. [ABSTRACT FROM AUTHOR]

Simple Summary: Sacrectomy represents a radical indication for bone sarcomas (e.g., osteosarcoma or chondrosarcoma) and chordomas, as well as selected carcinomas with invasion of the sacrum. Extralesional en bloc excision is surgically demanding and associated with resection-induced neurologic deficits and risks. Due to the low incidence of bone sarcomas, the rare localization in the sacrum and the complexity of the surgical procedure, studies reporting on the oncological outcome and corresponding complications in larger patient numbers are rare. The aim was to describe the oncosurgical management and the complication profile and to analyze our own treatment results after partial/total sacrectomy, with attention paid to a possible benefit by using intraoperative 3D navigation. There was a significant difference in progression-free and metastasis-free survival between sarcoma, chordoma and carcinoma patients. Complications were common, but no independently influencing causative factors could be identified. Although there was a subjective impression of improved intraoperative 3D orientation and easier identification of resection planes, the use of navigation did not significantly influence resection status or oncological patient outcome. Introduction: Bone sarcoma or direct pelvic carcinoma invasion of the sacrum represent indications for partial or total sacrectomy. The aim was to describe the oncosurgical management and complication profile and to analyze our own outcome results following sacrectomy. Methods: In a retrospective analysis, 27 patients (n = 8/10/9 sarcoma/chordoma/locally recurrent rectal cancer (LRRC)) were included. There was total sacrectomy in 9 (incl. combined L5 en bloc spondylectomy in 2), partial in 10 and hemisacrectomy in 8 patients. In 12 patients, resection was navigation-assisted. For reconstruction, an omentoplasty, VRAM-flap or spinopelvic fixation was performed in 20, 10 and 13 patients, respectively. Results: With a median follow-up (FU) of 15 months, the FU rate was 93%. R0-resection was seen in 81.5% (no significant difference using navigation), and 81.5% of patients suffered from one or more minor-to-moderate complications (especially wound-healing disorders/infection). The median overall survival was 70 months. Local recurrence occurred in 20%, while 44% developed metastases and five patients died of disease. Conclusions: Resection of sacral tumors is challenging and associated with a high complication profile. Interdisciplinary cooperation with visceral/vascular and plastic surgery is essential. In chordoma patients, systemic tumor control is favorable compared to LRRC and sarcomas. Navigation offers gain in intraoperative orientation, even if there currently seems to be no oncological benefit. Complete surgical resection offers long-term survival to patients undergoing sacrectomy for a variety of complex diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: This study describes a large-scale analysis of cancer metabolism across The Cancer Genome Atlas and Multiple Myeloma Research Foundation MMRF-COMMPASS study encompassing 10,915 patients from 34 different cancer types. To the best of our knowledge, this is the first such large-scale metabolic analysis performed using these data. Our approach identified biologically interpretable metabolic biomarkers of overall survival in 31 out of 34 cancer types evaluated. Additionally, in a subset of 7 cancer types, we predict chemosensitivity to antifolate-based therapies and a biomarker of response based on our patient-specific metabolic models. Finally, this work introduces the concept of "interpretation-driven biomarker identification". In this framework, biological interpretability of biomarker signatures is ensured first by using network-based simulations to characterize tumor biology, then using survival analysis to identify any biological features associated with overall survival—essentially decoupling biomarker discovery and biological interpretation of biomarker scores. Despite the high variability in cancer biology, cancers nevertheless exhibit cohesive hallmarks across multiple cancer types, notably dysregulated metabolism. Metabolism plays a central role in cancer biology, and shifts in metabolic pathways have been linked to tumor aggressiveness and likelihood of response to therapy. We therefore sought to interrogate metabolism across cancer types and understand how intrinsic modes of metabolism vary within and across indications and how they relate to patient prognosis. We used context specific genome-scale metabolic modeling to simulate metabolism across 10,915 patients from 34 cancer types from The Cancer Genome Atlas and the MMRF-COMMPASS study. We found that cancer metabolism clustered into modes characterized by differential glycolysis, oxidative phosphorylation, and growth rate. We also found that the simulated activities of metabolic pathways are intrinsically prognostic across cancer types, especially tumor growth rate, fatty acid biosynthesis, folate metabolism, oxidative phosphorylation, steroid metabolism, and glutathione metabolism. This work shows the prognostic power of individual patient metabolic modeling across multiple cancer types. Additionally, it shows that analyzing large-scale models of cancer metabolism with survival information provides unique insights into underlying relationships across cancer types and suggests how therapies designed for one cancer type may be repurposed for use in others. [ABSTRACT FROM AUTHOR]

Background: The neoadjuvant rectal score (NAR score) has recently been proposed as a better prognostic model than the conventional TNM classification for rectal cancer patients that have undergone neoadjuvant chemoradiotherapy. We recently developed an apoptosis-detection technique for assessing the viability of residual tumors in resected specimens after chemoradiotherapy. This study aimed to establish an improved prognostic classification by combining the NAR score and the assessment of the apoptosis of residual cancer cells. Methods: We retrospectively enrolled 319 rectal cancer patients who underwent chemoradiotherapy followed by radical surgery. The recurrence-free survival and overall survival of the four models were compared: TNM stage, NAR score, modified TNM stage by re-staging according to cancer cell viability, and modified NAR score also by re-staging. Results: Downstaging of the ypT stage was observed in 15.5% of cases, whereas only 4.5% showed downstaging of ypN stage. C-index was highest for the modified NAR score (0.715), followed by the modified TNM, TNM, and NAR score. Similarly, Akaike's information criterion was smallest in the modified NAR score (926.2), followed by modified TNM, TNM, and NAR score, suggesting that the modified NAR score was the best among these four models. The overall survival results were similar: C-index was the highest (0.767) and Akaike's information criterion was the smallest (383.9) for the modified NAR score among the four models tested. Conclusion: We established a novel prognostic model, for rectal cancer patients that have undergone neoadjuvant chemoradiotherapy, using a combination of apoptosis-detecting immunohistochemistry and neoadjuvant rectal scores. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to analyze patterns of failure and disease volume-treatment outcomes in patients with Nasopharyngeal carcinoma (NPC) treated with definitive radiation with or without concurrent chemotherapy at a tertiary cancer centre in northeast India. Methods: From February 2018 to February 2022, 99 histopathologically proved non-metastatic NPC patients treated with curative-intent RT with or without chemotherapy were retrospectively analyzed. Locally advanced patients received neoadjuvant or adjuvant chemotherapy. The Cox proportional hazards model was used to investigate the impact of various prognostic factors on locoregional free survival (LRFS), distant metastasis free survival (DMFS), progression free survival (PFS) and overall survival (OS). The log-rank test and Kaplan–Meir curves compared outcome variables based on ROC analysis-classified tumor volume. Results: During a median follow up of 25.4 months (17.3–39.2), 35(35.4%) patients developed recurrence. Twenty-three patients developed locoregional failures, of which 11 were in-field; 12 patient showed an out-field failure. The 3-year LRFS, DMFS, PFS and OS was 71.10%, 70.90%, 64.10% and 74.10% respectively. There was statistically significant difference in LRFS according to T staging (p < 0.0001). Gross tumor volume (GTVp) and gross nodal volume (GTVn) were an independent prognostic factor for OS, PFS, LRFS and DMFS. The cut-off volumes for GTVp and GTVn for distant metastases and locoregional failure, respectively, were found to be 13 and 22.7 mL and 3.7 and 39.2 mL, respectively, by ROC curve analysis. Based on this, 99 patients were divided into three subgroups. OS demonstrated significant differences among patients in different volume subgroups for GTVp (p = 0.03) and GTVn (p = 0.00024). Conclusions: For NPC patients who undergo curative IMRT, primary tumour and nodal volumes are independent prognostic indicators. GTVp and GTVn are highly predictive of local control, distant metastases, disease-free survival, and overall survival. This justifies their use as quantitative prognostic indicator for NPC. [ABSTRACT FROM AUTHOR]

Background: Malignant mesothelioma (MM) is an exceedingly rare tumor with poor prognosis due to the limited availability of effective treatment. Immunotherapy has emerged as a novel treatment approach for MM, but less than 40% of the patients benefit from it. Thus, it is necessary to identify accurate and effective biomarkers that can predict the overall survival (OS) and immunotherapy efficacy for MM. Methods: DNA sequencing was used to identify the genomic landscape based on the data from 86 Chinese patients. T cell receptor (TCR) sequencing was used to characterize MM TCR repertoires of 28 patients between October 2016 and April 2023. Results: Patients with TP53, NF2, or CDKN2A variants at the genomic level, as well as those exhibiting lower Shannon index (<6.637), lower evenness (<0.028), or higher clonality (≥0.194) according to baseline tumor tissue TCR indexes, demonstrated poorer OS. Furthermore, patients with TP53, CDKN2A, or CDKN2B variants and those with a lower evenness (<0.030) in baseline tumor tissue showed worse immunotherapy efficacy. The present study is the first to identify five special TCR Vβ‐Jβ rearrangements associated with MM immunotherapy efficacy. Conclusions: The present study reported the largest‐scale genomic landscape and TCR repertoire of MM in Chinese patients and identified genomic and TCR biomarkers for the prognosis and immunotherapy efficacy in MM. The study results might provide new insights for prospective MM trials using specific genes, TCR indexes, and TCR clones as biomarkers and offer a reference for future antitumor drugs based on TCR‐specific clones. [ABSTRACT FROM AUTHOR]

Sarcomas constitute a group of rare malignant neoplasms, commonly subcategorized into soft tissue sarcomas (STS) and bone sarcomas. This study aims to describe the treatment modalities and outcome of head and neck sarcoma (HNS) patients in western Denmark and to identify prognostic factors for overall survival and recurrence in HNS patients. The Aarhus sarcoma registry, The National Danish Sarcoma Database, and the Danish National Pathology Registry were used to identify HNS adult patients diagnosed between 1979 and 2022. Altogether, 291 patients were included in this study. The prevalent histological subtypes were undifferentiated pleomorphic sarcoma (16%; 48/291) and leiomyosarcoma (15%; 44/291) for STS patients (n = 230) and chondrosarcoma (10%; 28/291) and osteosarcoma (7%; 19/291) for bone sarcoma patients (n = 61). Surgery with curative intent was performed in 71% (164/230) and 70% (43/61) of STS and bone sarcoma patients, respectively. Clear resection was achieved in 59% (97/164) of STS patients and 44% (19/43) of bone sarcoma patients. Eighty-nine patients relapsed (STS n = 66, bone sarcoma n = 23) after a median time of 2.7/5.5 years for STS/bone sarcoma patients. The five-year overall survival rates were 45% for STS patients and 66% for bone sarcoma patients. The following factors were significantly, negatively associated with overall survival in STS patients: Age (hazard ratio (HR)) = 1.02, p < 0.001), tumour size ≥5 cm (HR = 1.75, p = 0.003), metastatic disease (HR = 3.17, p < 0.001), high grade tumour (HR = 2.24, p = 0.004), previous cancer (HR = 2.84, p < 0.001), and high Aarhus composite biomarker score (ACBS) (HR = 4.56, p = 0.001). For relapse in STS patients, higher tumour grade (HR = 3.19, p = 0.014), intralesional margins (HR = 2.84, p < 0.001), ≥2 previous cancers (HR = 3.00, p = 0.004), and high ACBS (HR = 3.29, p = 0.047), were negatively associated. For bone sarcomas only higher age (HR = 1.02, p = 0.049) and intralesional margins (HR = 2.91, p = 0.042) were significant negative factors for overall survival. Multiple prognostic factors for overall survival and relapse were identified, especially for STS patients. • 5-year survival was 45% for soft tissue sarcoma patients and 66% for bone sarcoma patients. • The Aarhus composite biomarker score is a prognostic factor for soft tissue sarcoma. • A previous cancer diagnosis is negatively associated with overall survival in soft tissue sarcoma patients. [ABSTRACT FROM AUTHOR]

Long-term follow-up for the CLEAR trial confirms the deep and durable tumor-response benefit of lenvatinib plus pembrolizumab in patients with advanced renal cell carcinoma (aRCC). The results support the use of this combination as a standard-of-care first-line treatment for aRCC. In the phase 3 CLEAR trial, lenvatinib plus pembrolizumab (L + P) showed superior efficacy versus sunitinib in treatment-naïve patients with advanced renal cell carcinoma (aRCC). The combination treatment was associated with a robust objective response rate of 71%. Here we report tumor responses for patients in the L + P arm in CLEAR, with median follow-up of ∼4 yr at the final prespecified overall survival (OS) analysis. Tumor responses were assessed by independent review using Response Evaluation Criteria in Solid Tumors v1.1. Patients with a complete response (CR; n = 65), partial response (PR) with maximum tumor shrinkage ≥75% (near-CR; n = 59), or PR with maximum tumor shrinkage <75% (other PR; n = 129), were characterized in terms of their baseline characteristics. The median duration of response was 43.7 mo (95% confidence interval [CI] 39.2–not estimable) for the CR group, 30.5 mo (95% CI 22.4–not estimable) for the near-CR group, and 17.2 mo (95% CI 12.5–21.4) for the other PR group. The 36-mo OS rates were consistently high in the CR (97%), near-CR (86%), and other PR (62%) groups. Robust objective response rates were observed across International Metastatic RCC Database Consortium favorable-risk (69%, 95% CI 60–78%), intermediate-risk (73%, 95% CI 67–79%), and poor-risk (70%, 95% CI 54–85%) subgroups. The robust response to L + P supports this combination as a standard-of-care first-line treatment for patients with aRCC. The CLEAR trial enrolled patients with advanced kidney cancer who had not previously received any treatment for their cancer. Here we report results for tumor shrinkage observed in the group that received lenvatinib plus pembrolizumab combination treatment during the trial. Shrinkage of target tumors with this combination was long-lasting and was observed in patients irrespective of their disease severity. This trial is registered on ClinicalTrials.gov as NCT02811861. [ABSTRACT FROM AUTHOR]

Background: To assess the influence of diagnosis and referral provided by specialists in oral diagnosis on disease‐free survival and overall survival of patients with oral cancer. Methods: A cohort of 282 patients with oral cancer treated at a regional cancer hospital from 1998 to 2016 was analyzed retrospectively. The referral register of the patients was analyzed and assigned to two groups: (1) those referred by oral diagnosis specialists (n = 129), or (2) those referred by nonspecialized professionals (n = 153). The cancer treatment evolution was assessed from the patients' records, and the outcome was registered concerning cancer recurrence and death. Sociodemographic and clinicopathological variables were explored as predictors of disease‐free survival and overall survival. Results: Group 1 exhibited lower T stages and a reduced incidence of regional and distant metastases. Surgery was performed in 75.2% of cases in Group 1, while in Group 2, the rate was 60.8%. Advanced T stages and regional metastases reduced the feasibility of surgery. Higher TNM stages and tumor recurrence were associated with decreased disease‐free survival, while surgical intervention was a protective factor. Higher TNM stage had a negative impact on the overall survival. Conclusion: Specialized oral diagnosis did not directly impact disease‐free survival and overall survival and did not influence the indication of surgery in oral cancer; however, it was associated with the diagnosis of early tumors and better prognosis. [ABSTRACT FROM AUTHOR]

Background and objective Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung cancer (NSCLC), which is featured by low incidence, high malignancy rate, robust aggressive behavior and inferior prognosis. To date, there is no standardized treatment. The aim of this study is to better understand and accumulate more clinical experience of the disease by summarizing the clinicopathological features, diagnosis methods, therapeutic regimen and prognostic factors of PSC. Methods A total of 39 patients with PSC who diagnosed and received treatment in Beijing Chest Hospital from December 2013 to December 2023 were retrospectively recruited, and information including demographic characteristics, clinicopathological features, tumor-node-metastasis (TNM) stage, diagnosis method and therapeutic regimen were carefully collected. Meanwhile, follow-up was conducted. Kaplan-Meier method was used to analyze the prognostic factors of the disease. Results The PSC patients in this study ranged in age from 45 to 76 years old, including 35 males and 4 females. There were no specific clinical manifestations of PSC at initial diagnosis. Among the 39 patients, 20 underwent surgical resection and 19 received palliative chemoradiation or symptomatic supportive treatment. The 1-year and 5-year survival rates were 61.90% and 35.20% respectively. Univariate analysis indicated that family history of carcinoma, primary tumor site, TNM stage, lymph node metastasis, distant metastasis, whether or not received surgical resection, surgical method, treatment regimens, tumor tissue programmed cell death ligand 1 (PD-L1) expression ≥1% and mesenchymal-epithelial transition factor (MET) pathway abnormalities were correlated with the overall survival (OS) of patients (P<0.05). In the subsequent multivariate analysis, lymph node metastasis emerged as the only independent prognosticator in predicting inferior OS (P=0.037). Conclusion PSC is rarely seen in clinical practice and commonly occurs in elder men with smoking history. Tumor tissue PD-L1 expression ≥1% and MET abnormalities may predict inferior prognosis of PSC and lymph node metastasis was determined as the independent prognosticator of PSC. Surgical resection along with adjuvant medical treatment is the cornerstone for early and locally advanced patients, and the clinical utility of molecular targeting therapy and immunotherapy in PSC needs to be further investigated. [ABSTRACT FROM AUTHOR]

Background: The Prognostic Nutritional Index (PNI) has become an important predictive tool for assessing patients' nutritional status and immune competence. It is widely used in prognostic evaluations for various cancer patients. However, the prognostic relevance of the Prognostic Nutritional Index (PNI) in gastric or gastro-esophageal junction cancer patients (GC/GEJC) undergoing immune checkpoint inhibitors (ICIs) treatment remains unclear. This meta-analysis aimed to determine the prognostic impact of PNI in this specific patient cohort. Methods: We conducted a thorough literature search, covering prominent databases such as PubMed, Embase, Web of Science, SpringerLink, and the Cochrane Library. The search spanned from the inception of these databases up to December 5, 2023. Employing the 95% confidence interval and Hazard Ratio (HR), the study systematically evaluated the relationship between PNI and key prognostic indicators, including the objective remission rate (ORR), disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) in GC/GEJC patients undergoing ICI treatment. Results: Eight studies comprising 813 eligible patients were selected. With 7 studies consistently demonstrating superior Overall Survival (OS) in the high- Prognostic Nutritional Index (PNI) group compared to their low-PNI counterparts (HR 0.58, 95% CI: 0.47-0.71, P<0.001). Furthermore, the results derived from 6 studies pointed out that the significant correlation between he low-PNI and poorer progression-free survival (PFS) (HR 0.58, 95% CI: 0.47-0.71, P<0.001). Subgroup analyses were performed to validate the robustness of the results. In addition, we conducted a meta-analysis of three studies examining the correlation between PNI and objective response rate/disease control rate (ORR/DCR) and found that the ORR/DCR was significantly superior in the high PNI group (ORR: RR: 1.24, P=0.002; DCR: RR: 1.43, P=0.008). Conclusion: This meta-analysis indicates that the low-PNI in GC/GEJC patients undergoing ICI treatment is significantly linked to worse OS and PFS. Therefore, PNI can serve as a prognostic indicator of post-treatment outcomes in patients with GC receiving ICIs. Further prospective studies are required to assess the reliability of these findings. Systematic review registration: https://inplasy.com/, identifier INPLASY202450133. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is a global health concern, and identifying prognostic factors can improve outcomes. Myosteatosis is fat infiltration into muscles and is a potential predictor of the survival of patients with CRC. Methods: This systematic review and meta-analysis aimed to assess the prognostic role of myosteatosis in CRC. PubMed, Embase, and Cochrane CENTRAL were searched up to 1 August 2023, for relevant studies, using combinations of the keywords CRC, myosteatosis, skeletal muscle fat infiltration, and low skeletal muscle radiodensity. Case-control, prospective, and retrospective cohort studies examining the association between myosteatosis and CRC outcomes after curative intent surgery were eligible for inclusion. Primary outcomes were overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS). Results: A total of 10 studies with a total of 9,203 patients were included. The pooled hazard ratio (HR) for OS (myosteatosis vs. no myosteatosis) was 1.52 [95% confidence interval (CI), 1.38-1.67); for CSS, 1.67 (95% CI, 1.40-1.99); and for DFS, 1.89 (95% CI, 1.35-2.65). Conclusion: In patients with CRC undergoing curative intent surgery, myosteatosis is associated with worse OS, CSS, and DFS. These findings underscore the importance of evaluating myosteatosis in patients with CRC to improve outcomes. [ABSTRACT FROM AUTHOR]

Objective: JianPiHuaTan Formula (JPHTF), a traditional Chinese medicine (TCM), has been utilized as an adjunctive therapy for colorectal cancer (CRC). The study aims to evaluate the potential clinical benefits of JPHTF and its effectiveness in inhibiting tumor growth. Methods: 300 stage II/III CRC patients and 412 advanced CRC patients were enrolled to verify the clinical value of JPHTF in CRC treatment. Furthermore, CRC patient-derived xenograft (PDX) mice were utilized to investigate the regulatory mechanisms of JPHTF. Results: JPHTF significantly improved abdominal distension, shortness of breath, drowsiness, loss of appetite, sleep, and tiredness in stage II/III CRC patients, thereby improving their quality of life. Simultaneously, JPHTF served as a supportive therapy in extending the overall survival (OS) of stage IV CRC patients with RAS/RAF mutations undergoing chemotherapy. Additionally, JPHTF effectively impeded tumor progression in CRC PDX models with RAS mutation, accompanied by a reduction in tumor cell content in the JPHTF group. Transcriptomic analysis revealed the involvement of the Hippo and Hedgehog signaling pathways in JPHTF-mediated CRC inhibition. Furthermore, mice in the JPHTF group exhibited increased immune cell infiltration. Conclusion: These findings suggested that JPHTF may inhibits tumor growth in CRC with RAS mutation by modulating RAS/RAF downstream signaling pathways, specifically the Hippo and Hedgehog signaling, leading to increased immune cell infiltration. [ABSTRACT FROM AUTHOR]

Background & Objective: Anemia, thrombocytosis, and leukocytosis, are commonly found in a variety of malignancies. The prognostic role of preoperative leukocytosis, anemia, and thrombocytosis on stages and grades of endometrial cancer (EC) in women undergoing surgery was the subject of this study. Materials & Methods: In this cross-sectional study, 105 women suffering from EC at Babol Ayatollah Rouhani Hospital from 2011 to 2018 were considered. Anemia, thrombocytosis, and leukocytosis were defined as prognostic factors. Then, the patients were placed at stages I, II, III, and IV, and ECs were graded as well, moderately and poorly differentiated or undifferentiated. SPSS 22 software, Chi-square, analysis of variance (ANOVA), and receiver operating characteristic (ROC) were used for statistical analysis (p < 0.05). Results: Higher rates of leukocytosis (54.3%), anemia (47.4%), and thrombocytosis (66.7%) were detected in tumor grades III, II, and III, respectively. A higher rate of leucocytosis (51.4%), anemia (60.5%), and thrombocytosis (51.9%) were reported in tumor stages III, I, and III, respectively. The relationship between tumor grade and tumor stage with leucocytosis and thrombocytosis was statistically significant (p <0.001). The white blood cell (WBC) sensitivity (70%) and specificity (70%), Hb sensitivity (37%) and specificity (39%), and platelets sensitivity (73%) and specificity (74%) were determined. There was a significant relationship between levels below the 3-variable curve and tumor stage with WBC (p <0.001) and platelet (p <0.001). Conclusion: Preoperative leukocytosis and thrombocytosis are related to the severity, stages, and grades of EC. Both of them have a prognostic role in women suffering from EC. [ABSTRACT FROM AUTHOR]

Introduction: Medullary thyroid carcinoma (MTC) is a rare type of thyroid cancer and the main treatment is surgery. The extent of surgery depends on the spread of tumour and often involves thyroidectomy and neck dissection. Recurrent or metastasis tumour can be detected with raising calcitoninand there are various options of treatment. Methods: This was a retrospective study of MTC over seven years in a tertiary cancer centre which evaluated the treatment outcome and the non-surgical options available in recurrent and metastatic tumours. Results: Among the 601 thyroid cancers, 34 patients (5.3%) were MTC, of which 29 were studied. Majority were women, below 60 years, were diagnosed with fine needle aspiration cytology of thyroid nodule or nodes and had raised calcitonin value (Ctn). The value of Ctn was correlated with tumour burden rather than extent (p=0.7). Recurrence was seen in 35% and all patients with locoregional recurrence had curative surgery whereas metastatic patients were offered palliative treatment. Acceptance of palliative treatment was less due to financial burden. The five year overall survival for nonmetastatic disease was 89.4 % and for patients with metastatic disease at presentation was 54.7 %. Conclusion: The incidence of medullary thyroid carcinoma is low compared to the differentiated thyroid carcinoma. The main treatment is surgery and other treatment options are limited. [ABSTRACT FROM AUTHOR]

Background/Aim: The aim of the present study was to evaluate the clinical impact of the Global Immune-NutritionInformation Index (GINI) in patients with gastric cancer (GC) who received curative treatment and to clarify the potential of the GINI as a biomarker. Patients and Methods: Patients who underwent curative resection for GC at Yokohama City University between 2005 and 2020 were selected based on their medical records. The GINI was calculated as follows: GINI=[C-reactive protein × platelet × monocyte × neutrophil]/[albumin × lymphocyte]. Results: A total of 258 patients were included in this study. Of these, 169 patients were categorized into the GINI-low group and 89 into the GINI-high group using a cut-off value of 1,730. The three- and five-year overall survival (OS) rates were 86.4% and 78.4%, respectively, in the GINI-low group, and 66.4% and 58.3% in the GINI-high group (p<0.001). In a multivariate analysis for OS, the GINI was identified as an independent prognostic factor [hazard ratio (HR)=1.772; 95% confidence interval (CI)=1.053-2.979, p=0.031]. Similar results were observed for RFS. In addition, the GINI affected the perioperative clinical course, including postoperative surgical complications and postoperative adjuvant treatment. Conclusion: The GINI is a promising biomarker for the treatment and management of GC. [ABSTRACT FROM AUTHOR]

Background/Aim: Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β superfamily of ligands and have been shown to promote or suppress colorectal cancer (CRC) growth. Developing treatments that target BMPs is challenging due to their multiple roles, including involvement in the inflammatory response and nutritional status. The present study evaluated the prognostic value of BMP-4, which is believed to be highly expressed in CRC, and its correlation with inflammatory and nutrition statuses in patients with CRC. Materials and Methods: We analyzed BMP-4 expression in tumor tissues from 144 patients who underwent CRC surgery using immunohistochemistry and evaluated the relationship between BMP-4 levels and clinical outcomes. Results: Kaplan–Meier analysis revealed that patients with high expression levels of BMP-4 exhibited a shorter overall survival rate than those with low levels of expression. Multivariate analysis revealed that BMP-4 expression was an independent prognostic factor for overall survival and death from other diseases in CRC patients. Furthermore, high BMP-4 expression was significantly correlated with high C-reactive protein/Albumin ratio, sarcopenia, and osteopenia. Conclusion: BMP-4 is a significant prognostic factor in CRC, particularly in predicting death from other diseases, while also showing associations with inflammatory and nutritional statuses. [ABSTRACT FROM AUTHOR]

Aim: Serum cholinesterase (ChE) levels are considered to reflect nutritional status. Although ChE has been well documented as a prognostic factor for some cancers, no clear consensus on its use for colorectal cancer (CRC) has been reached. The aim of this study was to investigate the relationship between preoperative serum ChE and postoperative long‐term prognosis in CRC patients. Methods: A total of 1053 CRC patients who underwent curative surgery were included in this study. The correlations between the preoperative ChE value and overall survival (OS) or cancer‐specific survival (CSS) were assessed. By dividing patients into two groups according to their ChE value, OS and CSS were compared between the groups. Results: Multivariate analysis revealed that the continuous ChE value was a significant predictor of OS (hazard ratio, 0.996; 95% CI, 0.993–0.998; p = 0.002) and CSS (hazard ratio, 0.994; 95% CI, 0.991–0.998; p = 0.001), independent of other variables. The low‐ChE (≤234 U/L) group had a significantly poorer prognosis than the high‐ChE (>234 U/L) group for both OS (5‐year OS for low ChE and high ChE: 79.8% and 93.3%, respectively; p < 0.001) and CSS (5‐year CSS for low ChE and high ChE: 84.8% and 95.6%, respectively; p < 0.001). Conclusions: Lower preoperative serum ChE levels are a predictive factor of poor prognosis for CRC patients. As serum ChE levels can be measured quickly and evaluated easily, ChE could become a useful marker for predicting the postoperative long‐term outcomes of CRC patients. [ABSTRACT FROM AUTHOR]

Background CD8+ tumor-infiltrating lymphocyte (TIL) predicts response to anti-PD-(L)1 therapy. However, there remains no standardized method to assess CD8+ TIL in melanoma, and developing a specific, cost-effective, reproducible, and clinically actionable biomarker to anti-PD-(L)1 remains elusive. We report on the development of automatic CD8+ TIL density quantification via whole slide image (WSI) analysis in advanced melanoma patients treated with front-line anti-PD-1 blockade, and correlation immunotherapy response. Methods Seventy-eight patients treated with PD-1 inhibitors in the front-line setting between January 2015 and May 2023 at the University of Pittsburgh Cancer Institute were included. CD8+ TIL density was quantified using an image analysis algorithm on digitized WSI. Targeted next-generation sequencing (NGS) was performed to determine tumor mutation burden (TMB) in a subset of 62 patients. ROC curves were used to determine biomarker cutoffs and response to therapy. Correlation between CD8+ TIL density and TMB cutoffs and response to therapy was studied. Results Higher CD8+ TIL density was significantly associated with improved response to front-line anti-PD-1 across all time points measured. CD8+ TIL density ≥222.9 cells/mm2 reliably segregated responders and non-responders to front-line anti-PD-1 therapy regardless of when response was measured. In a multivariate analysis, patients with CD8+ TIL density exceeding cutoff had significantly improved PFS with a trend toward improved OS. Similarly, increasing TMB was associated with improved response to anti-PD-1, and a cutoff of 14.70 Mut/Mb was associated with improved odds of response. The correlation between TMB and CD8+ TIL density was low, suggesting that each represented independent predictive biomarkers of response. Conclusions An automatic digital analysis algorithm provides a standardized method to quantify CD8+ TIL density, which predicts response to front-line anti-PD-1 therapy. CD8+ TIL density and TMB are independent predictors of response to anti-PD-1 blockade. [ABSTRACT FROM AUTHOR]

Introduction The observational multicenter prospective FLOWER study (NCT04965701) confirmed effectiveness and safety of osimertinib in the real-world (RW) management of untreated EGFR -mutant advanced non-small cell lung cancer (aNSCLC) patients. Methods Herein, we report updated survival data, post-progression management, cost/effectiveness and budget impact (BI) of osimertinib compared with a RW population receiving gefitinib or erlotinib. Results Overall, 189 Caucasian patients receiving first-line osimertinib were included. After a follow-up of 20.7 months, 74(39.2%) patients discontinued osimertinib, median time-to-treatment discontinuation (mTTD) was 27.9 months, overall survival 36.8 months. At progression, tissue biopsy was performed in 29 (56.9%), liquid biopsy in 15 (29.4%) and both in 7 (13.7%) cases. The most frequent resistant mechanism was MET amplification (N  = 14, 29.8%). At data cutoff, 13 (6.9%) patients were continuing osimertinib beyond progression; 52 (67.5%) received second-line treatment; no further treatments were administered in 25 (32.5%) cases. Thirty-three (63.4%) patients received chemotherapy, 12(23.1%) TKIs combination. Cost–effectiveness analysis showed a total cost per patient based on RW mTTD of 98,957.34€, 21,726.28€ and 19,637.83€ for osimertinib, erlotinib and gefitinib, respectively. The incremental cost-effectiveness ratio (ICER)/month for osimertinib was 359,806.0€/life-year-gained (LYG) and 197,789.77€/LYG compared to erlotinib and gefitinib. For osimertinib, the BI-gap between RW-TTD and theoretical-TTD was 16,501.0€ per patient. Conclusions This updated analysis confirms the effectiveness of osimertinib in RW. Although the ICER of osimertinib seems not cost-effective, additional costs for the management of disease progression to old generation TKIs were not considered in this study. The BI-gap suggests RW mTTD as a more reliable measure for expense estimation. [ABSTRACT FROM AUTHOR]

Objective: Some patients with cancer admitted to palliative care have relatively long survivals of 1 year or more. The objective of this study was to find out factors associated with prolonged survival. Methods: Retrospective case-control study comparing the available data of patients with cancer who survived more than 1 year after admission in a palliative care service with patients with cancer who survived 6 months or less. The intended proportion was 4 controls for each case. Patients were identified through electronic records from 2012 until 2018. Results: And 1721 patients were identified. Of those patients, 111 (6.4%) survived for at least 1 year, and 363 (21.1%) were included as controls according to the established criteria. The intended proportion could not be reached; the proportion was only 3.3:1. The median survival of cases was 581 days (range: 371-2763), and the median survival of controls was 57 days (range: 1-182). In the multivariable analysis, patients with a hemoglobin ≥ 10.6 g/dL and a creatinine level >95 µmol/L had a higher probability of living more than 1 year. In contrast, patients with abnormal cognition, pain, anorexia, liver metastases, an Eastern Cooperative Oncology Group performance status >1, and a neutrophil/lymphocyte ratio ≥ 3.43 had a low probability of living more than 1 year. Conclusion: Several factors were statistically associated positively or negatively with prolonged survival. However, the data of this study should be confirmed in other studies. [ABSTRACT FROM AUTHOR]

Objective: Corticosteroids are commonly used for symptom relief in patients with terminal cancer, but their use may have an impact on patient survival. We compared the survival of patients with terminal cancer who did and did not receive corticosteroid treatment for symptom relief, stratified by their predicted prognosis. Methods: We retrospectively reviewed consecutive patients with cancer who received corticosteroid treatment for symptom relief in a single palliative care unit. We stratified the patients according to their predicted prognosis using the palliative prognostic (PaP) score either before starting the corticosteroid treatment or at admission for control patients who did not receive a corticosteroid treatment. The 2 groups were compared for survival based on the PaP Scores. Results: We analyzed 204 patients treated with a corticosteroid during the study period and 139 control patients who did not receive corticosteroids during their treatment. No difference was observed in the survival between the treatment and control groups. Conclusion: Corticosteroid treatment for symptom relief in patients with terminal cancer did not affect survival time. [ABSTRACT FROM AUTHOR]

Objectives Materials and Methods Results Conclusion To assess the prevalence of cutaneous and oral immune‐related adverse events (irAEs) in cancer patients, risk factors for its development, and overall survival (OS).This retrospective observational study which included 748 medical records of cancer patients who received immune checkpoint inhibitors (ICIs). Demographic and clinicopathological characteristics were collected and analyzed.Most patients were male (59.4%), with stage IV cancer (65%) and received pembrolizumab (46.7%). Four hundred fourteen (55.34%) patients developed cutaneous lesions, 84 (11.2%) developed oral mucosal lesions, and 70 (9.3%) developed xerostomia. The median time for irAEs development was 11 weeks for cutaneous and oral mucosal lesions, and 21.5 weeks for xerostomia. Patients who received PD‐1 + CTLA‐4 had a higher risk for developing cutaneous irAEs (p = 0.001), while those who underwent ICI and concurrent chemotherapy had a higher risk (p = 0.008) for developing oral mucosal lesions. Patients who presented oral and cutaneous irAEs had better OS than those who did not present (p = 0.0001).Cutaneous effects affected more than half of the patients, while oral effects and xerostomia were found in around 11% and 9% of patients, respectively. Concurrent chemotherapy and PD‐1 + CTLA‐4 were more associated with oral and cutaneous irAEs, respectively. Patients who developed such irAEs had better overall survival. [ABSTRACT FROM AUTHOR]

Purpose: Anatomical structures and organ preservation concepts of the head and neck are important for patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC). Neoadjuvant chemotherapy has been applied to improve organ preservation; however, pathological complete remission is still unsatisfactory. The purpose of this study was to explore the pathological complete response (pCR) rate and safety of immune checkpoint blockade combined with neoadjuvant chemotherapy (NAC) in patients with LA HNSCC. Methods: Fifty-one patients participated in this retrospective study, and of these, 25 received NAC only (cisplatin+5-fluorouracil+nab-paclitaxel), and 26 received NAC (cisplatin+5-fluorouracil) plus pembrolizumab. Pathological complete remission, the objective response rate (ORR), delayed surgery and toxicity were compared between the two groups. Results: A significant difference was observed in the pCR rate and ORR between the NAC+ICB group and the NAC group. Delaying surgery and Grade 3 or 4 AEs occurred more frequently in the NAC group. In the NAC-only group, during a median follow-up period of 31.80 months, the recurrence-free survival (RFS) rate was 80.0%, the disease-free survival (DFS) rate was 80.0% and the overall survival (OS) rate was 88.0%. In the NAC+ICB group, during the median follow-up period of 22.99 months, the RFS rate was 96.2%, the DFS rate was 96.2% and the OS rate was 100%. Conclusion: The combination of pembrolizumab with NAC could improve the pathological response without increasing the risk of toxicity, which provides pathological evidence for the treatment of LA HNSCC patients with NAC+ICB. [ABSTRACT FROM AUTHOR]

Background and aims: The impact of lipids on the overall survival (OS) of patients with malignancy has not yet been clarified. This study aimed to evaluate the effect of hyperlipidemia on the OS among Chinese patients based on Body Mass Index (BMI) stratifications and hyperlipidemia types. Method: The patients in this study were derived from the Investigation of the Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) trial. Kaplan–Meier was used to draw the survival curve, and the log-rank test was used to estimate the survival rates between each group. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). Results: A total of 9054 patients were included in the final study, with a median age of 59 years, and 55.3% (5004) of them were males. Regarding types of hyperlipidemia, only low high-density lipoprotein was an independent risk factor for the prognosis of all patients (HR = 1.35, 95% CI: 1.25–1.45, P < 0.001), while high total cholesterol (HR = 1.01, 95% CI: 0.90–1.15, P = 0.839) and high low-density lipoprotein (HR = 1.03, 95%CI: 0.91–1.16, P = 0.680) were not. In terms of BMI stratification, the effect of triglycerides on prognosis varied; high triglycerides were an independent risk factor for the prognosis of underweight patients (HR = 1.56, 95% CI:1.05–2.32, P = 0.027) and a protective factor for overweight patients (HR = 0.75, 95% CI: 0.63–0.89, P = 0.001). However, for normal-weight patients, there was no significant statistical difference (HR = 0.88, 95%CI: 0.75–1.03, P = 0.108). Conclusions: The impact of hyperlipidemia on the OS among patients with cancer varied by different BMI and hyperlipidemia types. BMI and hyperlipidemia type ought to be considered in combination to estimate the prognosis of patients with malignancy. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to compare safety and efficacy outcomes between immediate breast reconstruction (IBR) and mastectomy alone in locally advanced breast cancer patients. Methods: We conducted a comprehensive literature search of PUBMED, EMBASE, and Cochrane databases. The primary outcomes evaluated were overall survival, disease-free survival, and local recurrence. The secondary outcome was the incidence of surgical complications. All data were analyzed using Review Manager 5.3. Results: Sixteen studies, involving 15,364 participants were included in this meta-analysis. Pooled data demonstrated that patients underwent IBR were more likely to experience surgical complications than those underwent mastectomy alone (HR: 3.96, 95%CI [1.07,14.67], p = 0.04). No significant difference was found in overall survival (HR: 0.94, 95%CI [0.73,1.20], p = 0.62), disease-free survival (HR: 1.03, 95%CI [0.83,1.27], p = 0.81), or breast cancer specific survival (HR: 0.93, 95%CI [0.71,1.21], p = 0.57) between IBR group and Non-IBR group. Conclusions: Our study demonstrates that IBR after mastectomy does not affect the overall survival and disease-free survival of locally advanced breast cancer patients. However, IBR brings with it a nonnegligible higher risk of complications and needs to be fully evaluated and carefully decided. [ABSTRACT FROM AUTHOR]

PURPOSE: The estimation of prognosis and life expectancy is critical in the care of patients with advanced cancer. To aid clinical decision making, we build a prognostic strategy combining a machine learning (ML) model with explainable artificial intelligence to predict 1-year survival after palliative radiotherapy (RT) for bone metastasis. MATERIALS AND METHODS: Data collected in the multicentric PRAIS trial were extracted for 574 eligible adults diagnosed with metastatic cancer. The primary end point was the overall survival (OS) at 1 year (1-year OS) after the start of RT. Candidate covariate predictors consisted of 13 clinical and tumor-related pre-RT patient characteristics, seven dosimetric and treatment-related variables, and 45 pre-RT laboratory variables. ML models were developed and internally validated using the Python package. The effectiveness of each model was evaluated in terms of discrimination. A Shapley Additive Explanations (SHAP) explainability analysis to infer the global and local feature importance and to understand the reasons for correct and misclassified predictions was performed. RESULTS: The best-performing model for the classification of 1-year OS was the extreme gradient boosting algorithm, with AUC and F1-score values equal to 0.805 and 0.802, respectively. The SHAP technique revealed that higher chance of 1-year survival is associated with low values of interleukin-8, higher values of hemoglobin and lymphocyte count, and the nonuse of steroids. CONCLUSION: An explainable ML approach can provide a reliable prediction of 1-year survival after RT in patients with advanced cancer. The implementation of SHAP analysis provides an intelligible explanation of individualized risk prediction, enabling oncologists to identify the best strategy for patient stratification and treatment selection. The estimation of prognosis and life expectancy is critical in the care of patients with advanced cancer. To aid clinical decision making, we build a prognostic strategy combining a machine learning model with explainable artificial intelligence to predict one-year survival after palliative radiotherapy (RT) for bone metastasis. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative 18F‐FDG PET/CT imaging parameters in predicting patient outcomes in thymic epithelial tumors (TETs). Methods: This retrospective study included 100 patients diagnosed with TETs who underwent pretreatment 18F‐FDG PET/CT. The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were measured. Heterogeneity index‐1 (HI‐1; standard deviation [SD] divided by SUVmean) and heterogeneity index‐2 (HI‐2; linear regression slopes of the MTV according with different SUV thresholds), were evaluated as heterogeneity indices. Associations between these parameters and patient survival outcomes were analyzed. Results: The univariate analysis showed that Masaoka stage, TNM stage, WHO classification, SUVmax, SUVmean, TLG, and HI‐1 were significant prognostic factors for progression‐free survival (PFS), while MTV, HI‐2, age, gender, presence of myasthenia gravis, and maximum tumor diameter were not. Subsequently, multivariate analyses showed that HI‐1 (p < 0.001) and TNM stage (p = 0.002) were independent prognostic factors for PFS. For the overall survival analysis, TNM stage, WHO classification, SUVmax, and HI‐1 were significant prognostic factors in the univariate analysis, while TNM stage remained an independent prognostic factor in multivariate analyses (p = 0.024). The Kaplan Meier survival analyses showed worse prognoses for patients with TNM stages III and IV and HI‐1 ≥ 0.16 compared to those with stages I and II and HI‐1 < 0.16 (log‐rank p < 0.001). Conclusion: HI‐1 and TNM stage were independent prognostic factors for progression‐free survival in TETs. HI‐1 generated from baseline 18F‐FDG PET/CT might be promising to identify patients with poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Abnormal lipid levels have been associated with cancer incidence and progression. However, limited studies have investigated the relationship between apolipoprotein A-I (ApoA-I) and colorectal cancer (CRC). This study assessed the significance of ApoA-I levels in progression-free survival (PFS) and overall survival (OS) of patients with CRC. Methods: Survival curves were compared using Kaplan-Meier analysis, while the predictive values of various lipid indicators in CRC prognosis were evaluated based on receiver operating characteristic curves. The factors influencing PFS and OS in patients with CRC were analyzed using Cox proportional hazards regression models. Finally, the relationship between ApoA-I level and disease recurrence was investigated through logistic regression analysis. The optimal Apo-I level was determined through maximally selected rank statistics. Results: Using the optimal ApoA-I cutoff value (0.9 g/L), the 1,270 patients with CRCwere categorized into low (< 0.9 g/L, 275 cases) and high (=0.9 g/L, 995 cases) ApoA-I groups. Compared with other lipid indicators, ApoA-I demonstrated superior predictive accuracy. The high ApoA-I group exhibited significantly higher survival rates than the low ApoA-I group (PFS, 64.8% vs. 45.2%, P < 0.001; OS, 66.1% vs. 48.6%, P < 0.001). Each one-standard-deviation increase in ApoA-I level was related to a 12.0% decrease in PFS risk (hazard ratio [HR] 0.880; 95% confidence interval [CI], 0.801-0.968; P = 0.009) and an 11.2% decrease in OS risk (HR 0.888; 95%CI, 0.806-0.978; P = 0.015). Logistic regression analysis revealed that patients with low ApoA-I had a 32.5% increased risk of disease recurrence (odds ratio [OR] 0.675; 95%CI, 0.481-0.946; P = 0.0225) compared with those with high ApoA-I. PFS/OS nomograms based on ApoA-I demonstrated excellent prognostic prediction accuracy. Conclusions: Serum ApoA-I level may be a valuable and non-invasive tool for predicting PFS and OS in patients with CRC. [ABSTRACT FROM AUTHOR]

Background: Potentially inappropriate medications (PIMs) are common among older adults with cancer, but their association with overall survival (OS) among non-small cell lung cancer (NSCLC) patients remains unclear. This study aimed to investigate the association between the use of PIMs and OS in patients with NSCLC. Methods: In this cohort study, we included patients ≥ 65 years with newly diagnosed NSCLC from January 2014 to December 2020. Potentially inappropriate medication (PIM) is defined by the Beers criteria of 2019 at baseline and within six months following the initiation of systemic therapy. Multivariable Cox regression model was built to assess the association between PIMs and overall survival (OS). Results: We finally included 338 patients with a median follow-up for OS of 1777 days. The prevalence of patients receiving at least one PIM was 39.9% (135/338) and 61.2% (71/116) at baseline and after systemic therapy, respectively. The most important factor associated with PIM use was the number of prescribed medications (P < 0.001). Baseline PIM use and PIM after systemic therapy were significantly associated with inferior OS (476 days vs. 844 days, P = 0.044; and 633 days vs. 1600 days, P = 0.007; respectively). In multivariable analysis, both baseline PIM use and PIM after systemic therapy were independent predictors of poor prognosis (adjusted HR, 1.33; 95% CI, 1.01–1.75; P = 0.041; and adjusted HR, 1.86; 95% CI, 1.11–3.14; P = 0.020; respectively). Conclusions: PIMs are prevalent among older patients with NSCLC and are independent predictors of NSCLC prognosis. There is an urgent need for clinicians to conduct medication reconciliation and appropriate deprescribing for this population, especially for patients with multiple PIMs. [ABSTRACT FROM AUTHOR]