Overall Survival Outcomes Research Articles

The Benefit of Short-Term Androgen Deprivation Therapy with Radiotherapy for Intermediate-Risk Prostate Cancer.

A previous, individual patient-level meta-analysis of randomized controlled trials (RCTs) demonstrated the overall survival (OS) benefit of short-term androgen deprivation therapy (ST-ADT) when delivered with radiotherapy for the subset of patients with intermediate-risk prostate cancer (IR-PCa). However, due to inclusion criteria, several studies such as NRG/RTOG 0815, GETUG-14, and DFCI 95-096 were excluded. Thus, we conduct the present analysis, inclusive of all studies to define the current role for ST-ADT in IR-PCa. A systematic review was conducted of phase III RCTs published or presented between 1/1980 and 10/2024 which profiled the comparative efficacy of radiotherapy ± ST-ADT in patients with IR-PCa. A study-level, random-effects meta-analysis was performed. The primary endpoint of this meta-analysis was OS, with secondary endpoints of time-to-biochemical failure (BF) ± biochemical-progress-free survival (bPFS). Meta-regression was utilized to explore trial-level factors associated with treatment effects. Synthetic individual patient-level OS data was pooled for confirmation and used to estimate the relative and absolute survival benefit. Seven RCTs (NRG/RTOG 9408, DFCI 95-096, TROG 96.01, PCS III, EORTC 22991, NRG/RTOG 0815, and GETUG-14) reporting outcomes of 6,279 patients were identified. The pooled HROS, HRBF, and HRBF+bPFS were 0.88 (95% confidence interval [CI]: 0.79-0.97; p = 0.01), 0.50 (95% CI: 0.37-0.68; p<0.001), and 0.54 (95% CI: 0.46-0.65; p<0.001), respectively. ST-ADT duration, RT dose, and Gleason score trial population composition were each associated with an increased benefit of ST-ADT for biochemical disease control (all p<0.05) but not for OS (all p>0.05). Pooling of simulated, patient-level data confirmed the presence of a survival benefit (HROS: 0.85 [95% CI: 0.76-0.96], log-rank p = 0.021), corresponding to an absolute survival benefit of 5% benefit at 10 years. The present analysis confirms current knowledge that ST-ADT improves both OS and PSA-based outcomes for unselected patients with IR-PCa to a clinically significant degree.

Evaluation of event-free survival (EFS) as a surrogate for overall survival (OS) in patients with locally advanced esophageal carcinoma (LA EC) receiving definitive chemoradiotherapy (dCRT).

412 Background: Drug development in esophageal cancer is rapidly evolving, and identifying surrogates for patient outcomes to accelerate clinical drug development remains an important unmet medical need. Although early clinical endpoints such as EFS, disease free survival (DFS) are proven to be valid surrogates for overall survival (OS) in early esophageal (Ajani JA et al. 2022), gastric (Oba K et al. 2013; Wainberg ZA et al. 2023), and gastroesophageal junction tumors (Ronellenfitsch U. et al. 2013) after disease resection, there are no such surrogacy data evaluating patients who underwent non-operative management. Specifically, there has been no prior systemic evaluation of the predictive value of EFS as a surrogate for OS among LA EC patients treated with dCRT. This study evaluated the trial-level correlation between EFS and OS in unresectable LA EC patients receiving dCRT. Methods: A systematic literature review was conducted to identify randomized controlled trials (RCTs) of dCRT interventions in unresectable LA EC (search cutoff date: April 2023). Studies reporting EFS (or similar outcomes such as progression free survival (PFS), defined as time from randomization to local, regional, or distant recurrence, or death) and OS were included. EFS and OS hazard ratios (HRs) of each treatment comparison were extracted. Correlation between the log(HR) of EFS and OS was assessed using weighted linear regression (WLR). The coefficient of determination (R 2 ) was used to evaluate the strength of the correlation. A good surrogate was defined as an R 2 ≥ 0.65 (Ciani et al . 2017) or an R 2 ≥ 0.75 (Lassere et al . 2008). Leave-one-out cross-validations and sensitivity analyses were conducted to assess the robustness of the WLR model and correlation analyses, respectively. Results: The final analysis included 14 between-treatment comparisons from 11 RCTs (total number of patients = 2,812). We found a strong statistical correlation between EFS and OS, with an estimated slope coefficient of 0.91 ( p &lt; 0.001) and R 2 of 0.80 (95% confidence interval [CI]: 0.38, 0.96). In the leave-one-out cross validation, 71.4% of observed OS HRs fell within the predicted 95% CIs. Sensitivity analyses showed R 2 of 0.75 among studies conducted in China and R 2 of 0.73 after including studies that did not report EFS definition. Conclusions: In a pooled analysis of 11 clinical trials corresponding to over 2800 patients, we observed a strong statistical correlation between EFS and OS outcomes. This analysis supports the utility of EFS as a valid surrogate of OS in patients with unresectable LA EC receiving dCRT.

Disease-free survival as a surrogate endpoint for overall survival in adults with early-stage pancreatic cancer: A trial-level surrogacy analysis.

708 Background: In early-stage cancer, overall survival (OS) is the gold-standard endpoint for assessing therapeutic efficacy. However, long follow-up periods make OS challenging and costly to measure in clinical trials. Disease-free survival (DFS), which captures the time to recurrence or death, has been proposed as a surrogate endpoint for OS in early-stage pancreatic cancer (PC). This surrogacy relationship could allow for a more rapid assessment of treatment benefits, but its validity requires robust analysis across clinical trials. Understanding the trial-level correlation between DFS and OS is crucial to optimizing trial design and grant accelerated drug approval. Methods: We conducted a systematic search of Embase, PubMed, and Cochrane databases through August 2024, identifying randomized controlled trials (RCTs) that evaluated adjuvant or neoadjuvant systemic therapies in adult patients with PC. Included studies reported both OS and DFS outcomes. Hazard ratios for DFS (HR_DFS) were analyzed as surrogate endpoints for OS (HR_OS). Statistical analyses utilized linear regression models, weighted by trial sample sizes, to determine the strength of the correlation. Surrogacy strength was categorized by the coefficient of determination (R²), with R² ≥ 0.7 indicating a strong correlation, 0.69–0.5 a moderate correlation, and values &lt; 0.5 indicating weak correlation. Results: Out of 3,048 studies screened, 30 RCTs met the inclusion criteria, comprising 5,275 patients in adjuvant therapy trials and 557 patients in neoadjuvant therapy trials. The median follow-up duration ranged from 16 to 53.5 months, with 12 phase II trials included. Overall, DFS showed strong surrogacy for OS in adjuvant trials (R² = 0.70; 95% CI, 0.50–0.91). Subgroup analysis indicated strong correlation in phase III trials (R² = 0.71; 95% CI, 0.46–0.96) and moderate correlation in phase II trials (R² = 0.67; 95% CI, 0.21–1.00). The strongest surrogacy was observed in studies incorporating adjuvant radiation therapy (R² = 0.81; 95% CI, 0.52–1.00). In the analysis of neoadjuvant trials, HR-DFS also presented strong correlation with OS (R² = 0.90; 95% CI, 0.56–1.00). Conclusions: There is a strong trial-level correlation between DFS and OS in both adjuvant and neoadjuvant therapy trials for early-stage pancreatic cancer, particularly in phase III studies and trials incorporating adjuvant radiation therapy. However, the strength of this surrogacy varies depending on the treatment setting and trial design.

Carbon ion radiotherapy with pencil beam scanning for stage III non-small cell lung cancer: toxicity profiles, survival outcomes, and prognostic indicators.

To evaluate the toxicities and survival outcomes associated with carbon ion radiotherapy (CIRT) using pencil beam scanning (PBS) and to assess the prognostic factors for patients with stage III non-small cell lung cancer (NSCLC) using a local effect model (LEM)-based biological dose calculation. This analysis included patients with stage III NSCLC (n = 181) who received CIRT between December 2016 and June 2023. CIRT was administered at a relative biological effectiveness (RBE)-weighted dose of 77 Gy (range, 69-83.6 Gy) in 22 fractions (Fx) (range, 19-24 Fx). Most patients (96.1%) underwent systemic therapy before and/or after CIRT. Toxicities and survival outcomes were recorded, and statistical analyses conducted. The median follow-up period was 18.2 months. Grades 1, 2, 3, and 4 acute toxicities were observed in 62.4%, 30.4%, 2.8%, and 0.6% of patients, respectively, with hematological toxicities accounting for all grade ≥ 3 acute toxicities. Grades 1, 2, 3, and 4 late toxicities occurred in 40.3%, 30.9%, 4.4%, and 1.7% of patients, respectively, with most grade ≥ 3 CIRT-induced late toxicities (72.7%) observed in patients receiving a CIRT dose ≥ 79.2 Gy. The median overall survival (OS) and progression-free survival (PFS) were 37.1 and 16.7 months, respectively. The 2-year locoregional control (LRC), OS, PFS, and distant metastasis-free survival (DMFS) rates were 66.1%, 64.2%, 40.3%, and 49.5%, respectively. Patients who received a CIRT dose ≤ 77 Gy had better OS (p = 0.047), but worse LRC compared to those who received higher doses (p = 0.026). Post-CIRT immunotherapy was an independent prognostic factor for improved OS, DMFS, and PFS (p = 0.002, p < 0.001, and p < 0.001, respectively). CIRT with PBS was effective for locally advanced NSCLC, resulting in acceptable toxicities and promising OS outcomes, particularly with doses of 69-77 Gy and post-CIRT immunotherapy.

Real world characteristics and outcomes of patients with BRAFV600E-mutant metastatic colorectal cancer in Australia: The COALA project.

70 Background: BRAFV600E-mutant metastatic colorectal cancer (mCRC) represents a unique molecular subset with poor prognosis and less responsiveness to chemotherapy. The BEACON CRC study demonstrated that encorafenib plus cetuximab (EC) significantly improved overall survival (OS) compared to FOLFIRI plus cetuximab in BRAF-mutant mCRC as 2 nd or 3 rd line therapy. This combination was reimbursed in Australia from January 2022. Methods: We analysed data from the Australian TRACC mCRC clinical registry, encompassing patients (pts) with BRAF-mutant mCRC diagnosed in Australia from 2009 to 2024 at 31 hospitals. We assessed baseline demographics, uptake of EC following reimbursement and efficacy analysis of progression-free survival (PFS) and OS for pts that received EC and those who did not. Pts receiving EC on a clinical trial were excluded. Results: Among 2,800 pts with known BRAF mutation status, 365 (13%) were BRAF mutated. The BRAF mutant cohort had a median age of 63 years, with a significantly higher mutation rate in the 20-39 age group than other age groups (age 20-39, 25.5%; age 40-59, 10%; age 60+, 13.2%; P&lt;0.001); 54.5% were female, 58% right-sided tumours, 64% with synchronous metastatic disease and 21.7% deficient mismatch repair (dMMR). Overall, 314 (86%) pts with BRAF mutant tumours and 2,079 (85%) BRAF wild-type (WT) tumours received 1 st line treatment, and 156 (43%) BRAF mutant and 1,144 (47%) BRAF WT pts received 2 nd line therapy. The median OS from diagnosis was 17.3 months for BRAF mutant pts versus 34.7 months for BRAF WT pts (p &lt; 0.0001). All dMMR BRAF mutant pts received 1 st line pembrolizumab since its reimbursement in August 2021. Among 41 BRAF mutant pts progressing on 1 st line therapy since January 2022,(32 pMMR, 9 dMMR), 33 (80%) were subsequently treated with EC, and 4 (10%) did not receive further treatment. OS from the start of 2 nd line therapy was 9.6 months (95% CI: 7.2-12.5) for pts who received EC and 7.1 months (95% CI: 6.4-8.6) for those who received other systemic treatment. Median PFS for pts receiving EC was 4.6 months (95% CI: 3.4-5.8) and 3.3 months (95% CI: 2.5-5.3) for other 2 nd line treatments. Conclusions: mCRC pts younger than 40 have a high rate of BRAF mutation, where 1 in 4 tumours harbour the mutation. BRAF mutant mCRC has a poorer outcome than BRAF WT despite a similar proportion receiving 1 st and 2 nd line treatment. The majority of eligible BRAF mutant mCRC pts received EC following reimbursement in Australia, with PFS and OS outcomes consistent with the BEACON CRC trial.

Evaluating survival outcomes and treatment recommendations in resectable gastric cancer

No consensus exists on the optimal therapy for resectable gastric cancer (GC) and gastroesophageal junction (GEJ) tumors, including the effectiveness of chemoradiotherapy versus perioperative chemotherapy (PC). Our study aimed to compare overall survival (OS) outcomes associated with the recommended treatment modalities for GC and GEJ tumors and evaluate treatment trends from 2010 to 2020. A national registry cohort identified patients with ≥ cT2 nonmetastatic GC and GEJ cancer. Treatment modalities were classified as neoadjuvant chemotherapy (NC), neoadjuvant chemoradiotherapy (NCR), PC, adjuvant chemotherapy (AC), and adjuvant chemoradiation (ACR). Kaplan-Meier curve and multivariable Cox regression models evaluated factors associated with OS. A cohort of 7665 patients were included. Patients who received PC had the highest OS (median 86.80 months, 95% CI 73.40-NE), while chemoradiotherapy in the neoadjuvant and adjuvant settings had worse OS than PC and NC (NCR median 47.15 months, 95% CI 44.58–52.27, and ACR median 52.67 months, 95%CI 42.78–63.93). The Cox proportional hazards model showed that NCR and NC had worse survival than PC (HR 1.74, 95% CI 1.50–2.02, p < 0.001 and HR 1.26, 95% CI 1.10–1.44, p = 0.0008, respectively). Additionally, the most utilized modality during 2020 was NC (35.8%), followed by PC (28.0%) and NCR (24.9%). The utilization of PC and NC had the most substantial rise between 2010 and 2020, increasing by 11.0%. The study demonstrates the association of PC with improved OS outcomes for nonmetastatic GC and GEJ tumors. Therapies combining radiation with chemotherapy and extended lymph node dissection correlated with a worse prognosis compared to PC and NC. Despite the association with improved outcomes, national data reveals low utilization rates for PC.

Hypoxia Promotes Malignant Progression of Colorectal Cancer by Inducing POSTN+ Cancer-Associated Fibroblast Formation.

Colorectal cancer (CRC) is one of the most common malignancies. Hypoxia can promote the occurrence and development of CRC. However, how hypoxia regulates the CRC immune microenvironment needs to be further explored. The bulk RNA sequencing data and clinicopathological information of CRC patients were enrolled from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The single-cell RNA sequencing (scRNA-seq) datasets of CRC were collected from and analyzed from the GEO database and the ArrayExpress database. The score of the hypoxia gene set was estimated using the "ssGSEA" algorithm in the "GSVA" R package. The functional characteristics of CAF subtypes were studied by bioinformatics analysis and in vitro experiments, and a prognostic model was constructed based on machine learning correlation. Hypoxia is associated with poor prognosis in CRC patients. Periostin (POSTN) + Fib is a cancer-associated fibroblast (CAF) closely associated with hypoxia, and high infiltration of POSTN + Fib is associated with adverse outcomes in overall survival (OS) and relapse-free survival (RFS) in CRC patients. Hypoxia can induce POSTN expression and secretion in CAFs. Hypoxia-induced increase of POSTN expression in CAFs can significantly promote the migration and proliferation of CRC cells. Hypoxia-induced increase of POSTN expression in CAFs can significantly promote the proliferation and migration of CRC cells. The POSTN+Fib Hypoxia-Related Risk Model (PFHRM) can predict the survival and immunotherapy response of CRC patients. Our study identified a POSTN+Fib cell subpopulation closely associated with hypoxia, which promotes the malignant progression of CRC. The development of PFHRM provides a theoretical basis for improving patient survival and prognosis.

Prognostic value of serum cholinesterase and 18F-FDG PET/CT-derived metabolic parameters in non-small cell lung cancer patients: a retrospective cohort study.

The primary objective of this study was to explore the prognostic significance of serum cholinesterase (CHE) and metabolic parameters obtained from 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) scans in patients with nonsmall cell lung cancer (NSCLC). A retrospective observational cohort study was conducted with 202 NSCLC patients. Serum CHE was evaluated alongside metabolic tumor volume (MTV) and total lesion glycolysis (TLG) derived from PET/CT scans. The correlation between these parameters and overall survival (OS) was analyzed using log-rank tests, as well as univariate and multivariate Cox regression analyses. A nomogram prediction model was developed and assessed using time-dependent receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). High MTV (≥16) and TLG (≥108) were found to be significantly correlated with worse OS outcomes (both P < 0.001), whereas lower CHE levels (<6818) were associated with worse OS (P = 0.002). A multivariate analysis revealed that MTV, TLG, serum CHE, and the presence of distant metastasis were independent prognostic factors for OS. The nomogram prediction model, incorporating these variables, exhibited strong predictive performance, as indicated by area under the curve values of 0.826, 0.796, and 0.845 for 1-, 3-, and 5-year OS predictions, respectively. Calibration curves demonstrated good concordance between predicted and observed survival rates, and DCA confirmed clinical relevance. Serum CHE and 18F-FDG PET/CT metabolic parameters may serve as important prognostic indicators for patients with NSCLC. The integration of these factors into a nomogram prediction model can assist in clinical decision-making and patient risk stratification.

An exosome-based liquid biopsy predicts depth of response and survival outcomes to cetuximab and panitumumab in metastatic colorectal cancer: The EXONERATE Study.

PURPOSE EXONERATE (EXOsome and cell-free micro-RNAs of anti-EGFR ResistAnce) was an open-label, biomarker interventional study designed to develop, test, and validate a liquid biopsy predictive of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) for first-line EGFR inhibitors in metastatic colorectal cancer (mCRC). PATIENTS AND METHODS Patients with newly diagnosed RAS-WT, chemotherapy-naïve mCRC, both right- and left-sided, were enrolled in 2-nationwide trials to receive cetuximab or panitumumab along with chemotherapy. The primary endpoint was 12-month PFS, which was hierarchically tested in left- and right-sided mCRC to predict PFS, OS, and ORR. RESULTS Genome-wide small-RNA sequencing identified 12 cell-free and 14 exosomal candidates that were differentially expressed in both plasma and tumor tissue of good vs. poor responders (based on PFS <12 months). The 8 and 9 best-performing candidates, respectively, were used to generate the EXONERATE assay. In left-sided mCRC, 65% were EXONERATE-high, correlating with shorter mPFS (9.5 vs. 18.5 months, p<0.001). In the independent right-sided mCRC cohort, 80.8% were EXONERATE-high and experienced a similarly shorter mPFS (8.6 vs. 41.2 months, p=0.0004). In the right-sided group, EXONERATE predicted PFS≥12 months with 100% sensitivity. A linear relationship existed between EXONERATE values and response depth. Multivariate analysis revealed that EXONERATE predicts PFS and OS independently of tumor-sidedness. CONCLUSION The EXONERATE assay robustly predicted PFS and OS outcomes in patients with mCRC, both right- and left-sided, before they received either panitumumab or cetuximab. It stratified PFS, OS, and ORR better than a right vs. left approach.

The prognostic importance of the negative regulators of ferroptosis, GPX4 and HSPB1, in patients with colorectal cancer.

The prognostic value of negative regulators of ferroptosis in patients with colorectal cancer (CRC) has not yet been fully elucidated. The present study performed a systematic in silico identification and selection of candidate negative regulators of ferroptosis using The Cancer Genome Atlas data cohort (n=367), followed by clinical validation through immunohistochemistry of samples from patients with CRC (n=166) and further in vitro evaluation. In silico analysis identified specific light-chain subunit of the cystine/glutamate antiporter, AIFM2, NFE2L2, FTH1, GLS2, glutathione peroxidase 4 (GPX4) and heat shock protein β-1 (HSPB1) genes as possible candidates. Furthermore, patients with high expression of GPX4 or HSPB1 exhibited significantly worse overall survival (OS) compared with those with low expression (P<0.01 for both). Immunohistochemical analysis revealed that both OS and recurrence-free survival (RFS) of patients with CRC and high GPX4 or HSPB1 expression were significantly worse compared with in patients with low expression (P<0.01 for all). Furthermore, multivariate analysis showed that high GPX4 and HSPB1 expression were independent risk factors for poor oncological outcome for OS and RFS (GPX4: RFS, P=0.03; HSPB1: OS, P=0.006 and RFS, P<0.0001). Moreover, the effects of GPX4 and HSPB1 small interfering RNAs on two CRC cell lines (DLD-1 and SW480) indicated that GPX4 and HSPB1 may exhibit important roles in attenuating the cytotoxic effect of 5-fluorouracil-based chemotherapy. In conclusion, the current study confirmed that GPX4 and HSPB1 may serve as substantial prognostic- and recurrence-predictive biomarkers in patients with CRC.

Association between the Achievement of Textbook Outcomes in Liver Surgery (TOLS) and Overall Survival in Perihilar Cholangiocarcinoma Patients Following Major Hepatectomy: A Multicenter Study.

Introduction Major hepatectomy is the mainstay of curative-intent resection for perihilar cholangiocarcinoma (pCCA) patients. Textbook Outcomes in Liver Surgery (TOLS) are a new composite parameter for evaluating the short-term outcomes of surgery; however, their association with overall survival (OS) is unknown. Therefore, this study aimed to investigate the association between TOLS and OS in pCCA patients following major hepatectomy. Methods Consecutive pCCA patients who underwent major hepatectomy between 2014 and 2020 at 5 hospitals were included in this analysis. TOLS were defined as no intraoperative grade ≥ 2 incidents, no postoperative grade B/C bile leakage, no postoperative grade B/C liver failure, no postoperative major morbidity, no readmission within 90 days due to surgery-related major morbidity, no mortality within 90 days after hospital discharge, and R0 resection. The Kaplan‒Meier method was used to compare OS rates between patients who achieved TOLS and those who did not. Cox regression analysis was used to identify independent risk factors for poor OS. Results In total, 399 patients were included in this study, 214 (53.6%) of whom achieved TOLS. After excluding patients who died within 90 days, the 5-year OS rate of patients who achieved TOLS were significantly greater than that of patients who did not achieve TOLS (5-year OS rate: 26.2% vs. 17.3%, P=0.001). TOLS were independently associated with OS for pCCA patients following major hepatectomy. Conclusions TOLS were achieved in approximately half of the pCCA patients following major hepatectomy, and the patients who achieved TOLS had better survival.

Better Outcomes for Ovarian Cancer Associated With the Detection of Anti-EBV TCR CDR3s: Potential Relevance to Diffuse Large B-Cell Lymphoma.

Given the ongoing challenges regarding the specific roles of viral infections in cancer etiology, or as cancer co-morbidities, this study assessed potential associations between anti-viral, T-cell receptor (TCR) complementarity domain region-3 (CDR3s), and clinical outcomes for ovarian cancer. TCR CDR3s were isolated from ovarian cancer specimens for a determination of which patients had anti-viral CDR3s and whether those patients had better or worse outcomes. Analyses revealed that patients with exact matches of anti-Epstein-Barr virus (EBV) CDR3 amino acid sequences exhibited better outcomes for both overall and disease-specific survival. However, better outcomes were not observed when assessing anti-viral CDR3s representing cytomegalovirus, influenza A, or Sars-CoV-2. Due to previous occurrences of the occasional misdiagnoses of lymphoma as ovarian cancer, the frequency of anti-EBV CDR3s in lymphoma patients was determined. These frequencies were relatively high, particularly for diffuse large B-cell lymphoma. These findings (i) underscore the potential value of anti-EBV immune responses in terms of patient outcomes; (ii) raise questions about the potential value of anti-EBV immunotherapies; and (iii) support further inquiry into the relationship between EBV infection and previously reported cases of ovary-resident lymphoma.

Adjuvant Sequential Chemotherapy for Salivary Duct Carcinomas: A Retrospective Comparative Analysis.

This study aimed to report the efficacy and safety of adjuvant sequential chemotherapy after definitive treatment of salivary duct carcinoma (SDC) compared with the standard treatment alone (surgery with postoperative radiation therapy). This was a retrospective study of pathologically confirmed 135 SDC patients (study period 2009 to 2022). After curative surgery and adjuvant radiation therapy, 55 of 135 patients decided to receive additional chemotherapy (OP + RT + chemo group), while 80 opted for surgery and radiation (OP + RT group). Treatment outcomes of overall survival (OS), disease-free survival (DFS), and distant metastasis-free survival (DMFS) were compared using a propensity score matching (PSM) analysis. Adjuvant chemotherapy consisted of three cycles of cisplatin-based regimen, which was well tolerated in most patients with minimal adverse events. Multivariable analyses indicated that the addition of chemotherapy did not improve OS (p = 0.05), DFS (p = 0.386), and DMFS (p = 0.735), although there was a trend toward favoring adjuvant chemotherapy in terms of OS. With PSM analysis, OS (OP + RT + chemo to OP + RT, hazard ratio [HR] = 0.40, 95% confidence interval [95% CI] = 0.12-1.29, p = 0.126), DFS (HR = 0.69, 95% CI = 0.30-1.56, p = 0.367), and DMFS (HR = 0.96, 95% CI = 0.46-1.99, p = 0.903) were not statistically different. Current cisplatin-based adjuvant chemotherapy did not significantly improve treatment outcomes of SDC patients over the surgery and adjuvant radiation. Further development or clinical studies are required to improve the outcomes of SDC, including chemotherapeutic, biomarkers, immune checkpoint inhibitors, or treatment strategies.

Pooled clinical trial analyses evaluating outcomes of HER2-low vs HER2-0 expression in patients with metastatic breast cancer following chemotherapy.

The therapeutic importance of subsetting patients with HER2-negative breast cancer according to their tumors' cellular HER2 expression (e.g., HER2-low vs. HER2-0) is relatively new, stemming from the dramatic results of the DESTINY-04 trial which established HER2-low expression as actionable. Most prior observational research of traditionally HER2-negative patients suggests that tumor behavior and biology do not vary according to HER2-low vs. HER2-0 expression, though some studies suggest otherwise. Here we studied this question in women with metastatic breast cancer (MBC) who were treated with standard single agent chemotherapy in the setting of clinical trials carried out in the pre-DESTINY-04 era. After pooling data from 142 female patients with MBC across historic clinical trials and categorizing them according to HER2 expression (i.e., HER2-0 or HER2-low), we evaluated associations between HER2 expression and the outcomes of both progression-free survival (PFS) and overall survival (OS) with both Kaplan-Meier and Cox proportional hazards methods. Studying data from an era when quantifying amounts of tumor HER2 expression in HER2-negative patients was neither standardized nor clinically actionable, we found no meaningful clinical differences in PFS or OS according to HER2-low vs. HER2-0 status, supporting prior findings of no biologic differences.

Major pathologic response predicts survival in resectable stage IIIA non-small cell lung cancer after neoadjuvant therapy.

Major pathologic response is more common in survival analyses than pathological complete response. Whether major pathologic response can predict survival of patients with resectable stage IIIA non-small cell lung cancer and whether neoadjuvant chemotherapy or immunochemotherapy affect the prognosis of patients remains questionable. Patients with resectable stage IIIA non-small cell lung cancer receiving neoadjuvant chemotherapy(≥2 cycles) with/without immunotherapy were enrolled and divided into two groups according to pathological response. Comparison between the two groups was through chi-square test. Univariate Cox regression analysis and log-rank test were made to identify predictive factors of overall survival and disease-free survival. Kaplan-Meier survival curves were constructed to evaluate the prognostic impact of these factors. Totally 38 patients were enrolled. Significant difference was observed in overall survival(P = 0.005) and disease-free survival(P = 0.007) between patients with/without major pathologic response. For patients failing to reach major pathologic response, those who underwent ≥2 cycles of neoadjuvant therapy exhibited improved outcomes in overall survival(P = 0.021) and disease-free survival(P = 0.046). Notably, within this subgroup, patients receiving ≥ 2 cycles of neoadjuvant immunochemotherapy showed a trend towards better overall survival(P = 0.076) and disease-free survival(P = 0.062). Major pathologic response can predict survival of patients with resectable stage IIIA non-small cell lung cancer. For patients potentially not achieving major pathologic response after two cycles of neoadjuvant therapy, extended cycles of feasible neoadjuvant therapy are advisable for survival benefits.

Current efficacy of hepatic arterial infusion chemotherapy in hepatocellular carcinoma

Newer systemic therapies for hepatocellular carcinoma (HCC) have led to growing interest in combining hepatic arterial infusion chemotherapy (HAIC) with systemic treatments. To evaluate the effectiveness and safety of HAIC and combination therapies in treating advanced HCC, a network meta-analysis was conducted by Zhou et al . The study included data from 44 articles. HAIC was superior in overall survival (OS), progression-free survival (PFS), and response rates compared to transarterial chemoembolization and sorafenib. Moreover, combinations of HAIC with other treatments and single agents (e.g. , lenvatinib, ablation, anti-programmed cell death 1 therapy, radiotherapy) provided better OS and PFS outcomes than HAIC alone. In this editorial, we will discuss the study findings, the strengths and weaknesses of the metanalysis, and future advances in the field of HAIC for advanced HCC.

Survival Impacts of Mitochondrial Status in Esophageal Squamous Cell Carcinoma Patients.

Little is known about the survival impacts of mitochondrial status in esophageal squamous cell carcinoma (ESCC) patients who undergo neoadjuvant chemotherapy (NAC) followed by surgery. In total, 260 pre-NAC samples from ESCC patients were analyzed. Mitochondrial status was estimated employing an objective, immunohistochemistry-based system (Mito-score). Mito-scores were dichotomized according to the median value of our cohort. We also evaluated the immune microenvironment (CD4, CD8, Foxp3, HLA class-1, Ki-67 and programmed death ligand-1) on pre-NAC specimens. Multivariate Cox hazards models were applied to determine independent predictors of poor overall survival (OS). Patients with cT3-4 tumors had higher Mito-scores than those with cT1-2 tumors (p=0.06), and good responders to NAC had significantly higher Mito-scores than poor responders to NAC (p=0.04). CD8 cells and Ki-67 expression were significantly higher in Mito-high than Mito-low tumors (p=0.017 and p<0.001, respectively). Patients with low Mito-scores had significantly poorer OS than those with high Mito-scores (3-year OS: 57.6% vs. 68.2%; p=0.03). A survival difference by Mito-score was evident in cStage III-IV patients (3-year OS: low 50.6% vs. high 66.1%; p=0.006). Multivariable analysis revealed that a low Mito-score (hazard ratio 1.59, 95% confidence interval 1.12-2.24; p=0.009) as well as pT3-4 disease (p<0.001) and pN2-3 disease (p<0.001) were independently associated with poor OS outcomes. A low Mito-score before NAC had a significant survival impact in ESCC patients, especially in those with advanced disease. Mitochondrial status might be associated with tumor aggressiveness and responsiveness to NAC, thereby possibly affecting the survival outcomes of ESCC patients.

Prognostic value of preoperative D-dimer to albumin ratio in patients with locally advanced rectal cancer after neoadjuvant chemoradiotherapy

BackgroundThe prognostic value of Albumin and D-dimer has been established for multiple tumor types, indicating their potential for predicting tumor development. Nevertheless, the predictive capability of the DDI-to-albumin ratio (DAR) in locally advanced rectal cancer (LARC) remains uncertain.PurposeThe objective of this study was to investigate the prognostic significance of the DAR in LARC.MethodsA total of 513 patients who underwent neoadjuvant chemoradiotherapy (nCRT) prior to total mesorectal excision (TME) between March 2013 to October 2019 were included in this study. Patients were divided into high-level DAR (> 0.016) or low-level DAR (≤ 0.016) groups based on ROC curve analysis optimum cut-off value. The prognostic value of the DAR in LARC was analyzed.ResultsThe study enrolled 513 patients. Patients were stratified into high-level DAR (> 0.016) and low-level DAR (≤ 0.016) cohorts according to the optimal cut-off value determined by ROC curve analysis. The 5-year overall survival (OS) rates for patients in the low DAR group (≤ 0.016) and the high DAR group (> 0.016) were 89.4% and 80.9%, respectively (p = 0.013). The 5-year disease-free survival (DFS) rates were 85.7% and 77.4% (p = 0.027). Multivariate analyses demonstrated that DAR were independent prognostic factors for OS (p = 0.02) and DFS (0.025). Predictive nomograms that included the DAR score group (C-index: OS-0.743, DFS-0.705) were superior to those without DAR scores (C-index: OS-0.721, DFS-0.697).ConclusionThe DAR demonstrates high usability and prognostic value in predicting OS and DFS outcomes among patients diagnosed with LARC who undergo nCRT.

Feasibility and usefulness of symptom monitoring with electronic patient-reported outcomes: an experience at single-center outpatient oncology clinic.

The benefit of patient-reported outcomes (PRO) in routine oncology practice is increasingly recognized. This study aimed to develop a team-based monitoring and intervention system using electronic PRO (ePRO) and to evaluate its impact at an outpatient oncology clinic. Patients receiving chemotherapy at our department were eligible for this study. Those who had access to a smartphone or tablet (Bring Your Own Device [BYOD]) and consented participated, and reported 28 symptoms weekly via 3H P-guardian downloaded on their BYOD. E-mail alerts were sent to attending healthcare providers when participants reported at least grade 3 severity for any of nine symptoms (decreased appetite, nausea, vomiting, diarrhea, shortness of breath, pain, insomnia, fatigue, and sadness), which prompted interventions. Comparisons of overall survival (OS), emergency room visits, and hospitalizations were conducted using propensity scores. Among 203 patients who received chemotherapy from September 2021 to August 2023, 77 participated in ePRO monitoring. The overall response rate was 55% (1991 valid responses out of a total of 3597 expected time points), and the median individual response rate was 66% (range, 0-100%). Of 1991 valid responses, 250 (13%) prompted alerts, and most interventions were initiated by making telephone calls. OS and other clinical outcomes were better in ePRO participants compared with non-participants, but these outcomes did not differ significantly between the ePRO and pre-ePRO eras. It was feasible to develop a multi-professional team-based monitoring and intervention system using ePRO at a single-center outpatient oncology clinic. Our results indicate that weekly monitoring of ePRO, along with corresponding interventions, may benefit patients receiving chemotherapy.

Analysis of Genitourinary Rhabdomyosarcoma in Phase 3 clinical trials.

Pediatric Rhabdomyosarcoma (RMS) is a morbid and often lethal condition characterized by a paucity of clinical data. Beyond a detailed risk categorization system, it is unclear if genitourinary (GU) sites (bladder/prostate, paratesticular, female organs) have outcomes distinct from non-GU sites. This study pools primary data from phase-3 clinical trials involving pediatric RMS to evaluate this question. We obtained primary data from three Children's Oncology Group pediatric RMS trials (NCT00075582, NCT00354835, NCT00354744) evaluating low- (LR), intermediate- (IMR), and high risk (HR) Pediatric RMS. Survival analysis was conducted using the Kaplan-Meier method, with Event-Free Survival (EFS) defined per protocol specifications. 599 subject records were included in the analysis (111 GU RMS, 488 non-GU RMS). For subjects with GU RMS, overall survival (OS) was superior to non-GU RMS (HRR 0.55 [95% CI, 0.35-0.87], p = 0.009). In this same group, EFS superiority was not statistically significant compared to non-GU RMS (HRR 0.88 [95% CI, 0.63-1.22], p = 0.43). In the LR population, GU primary site was associated with improved OS that was not statistically significant (HRR 0.37 [95% CI 0.07-1.84], p = 0.21) and less favorable EFS (HRR 2.84 [95% CI, 1.13-7.12], p = 0.02). In RMS, a GU primary site is linked to improved OS compared to non-GU sites, although LR GU RMS shows less favorable EFS. Our findings reinforce the association between GU primary sites and better OS outcomes in RMS, warranting further investigation into the surrogacy of EFS for OS in GU RMS. Not applicable.