Worse Overall Survival Research Articles

Tumor Hypoxia on 18F-fluoromisonidazole Positron Emission Tomography and Distant Metastasis From Head and Neck Squamous Cell Carcinoma.

Given high rates of locoregional control after definitive management of head and neck squamous cell carcinoma (HNSCC), better methods are needed to project distant metastasis (DM) risk. Tumor hypoxia on 18F-fluoromisonidazole (FMISO) positron emission tomography (PET) is associated with locoregional failure, but data demonstrating an association with DM are limited. To determine whether tumor hypoxia on FMISO PET is associated with DM risk after chemoradiotherapy (CRT) for HNSCC. This cohort study assessed patients with HNSCC enrolled in 2 prospective clinical trials at a single academic referral center from 2004 to 2021 in which participants received FMISO PET before and during CRT. Data analysis occurred from May 2023 to May 2024. FMISO PET scans before and 1 to 2 weeks after starting CRT were evaluated for tumor hypoxia by nuclear medicine physicians. The primary outcome was DM, defined as biopsy-proven HNSCC outside the primary site and regional lymph nodes. Time to DM was modeled with competing risk regression, with death as a competing risk. Overall survival (OS) was assessed secondarily and modeled with Cox regression. Among 281 patients (median [range] age at CRT, 58.7 [25.5-85.6] years; 251 male [89.3%]) included in this study, 242 (86.1%) had oropharyngeal primary cancer, and 266 (94.7%) had human papillomavirus-positive disease. Of all patients, 217 (77.2%) had T stage 1 or 2, and 231 patients (82.2%) had N stage 2b or less. De-escalated 30 Gy CRT was delivered to 144 patients (51.2%), and the remainder received standard 70 Gy CRT. On FMISO PET examination, 73 patients (26.0%) had hypoxia-negative disease before CRT, 138 patients (49.1%) had hypoxia-positive disease before CRT and then hypoxia-negative disease during CRT, and 70 patients (24.9%) persistently had hypoxia-positive disease before and during CRT. At a median (IQR) 58 (46-91) months of follow-up, 12 DM events and 22 deaths were observed. Persistent intratreatment hypoxia was associated with increased DM risk (hazard ratio, 3.51; 95% CI, 1.05-11.79; P = .04) and worse OS (hazard ratio, 2.66; 95% CI, 1.14-6.19; P = .02). No patients with hypoxia-negative disease before CRT experienced DM. In this cohort study using pooled analysis of prospective nonrandomized clinical trials incorporating FMISO PET in the definitive management of HNSCC, persistent intratreatment hypoxia was associated with increased risk of DM and worse OS. Conversely, all patients with hypoxia-negative disease before treatment remained free of DM. These findings suggest that pretreatment and intratreatment FMISO PET results may serve as biomarkers for DM risk and aid in identifying candidates for escalated therapeutic strategies.

Trends in the Care of Locally Advanced Pancreatic Cancer in the Modern Era of Chemotherapy.

Current guidelines for treatment for locally advanced pancreatic cancer recommend chemotherapy ± radiation, or radiation alone when multimodal therapy is contraindicated. In a subset of patients, guideline-recommended treatment (GRT) achieves sufficient response to qualify for potentially curative resection. This study evaluated trends in treatment utilization and aimed to identify barriers to GRT. Patients with clinical T4M0 disease in the National Cancer Database from 2010 to 2017 were included. Potential predictors were assessed by relative risk regression with Poisson distribution and compared by log-link function. In total, 28 056 patients met the criteria. Among 17 059 (67.67%) patients treated primarily with chemotherapy, 41.19% also had radiation and 8.89% went onto resection. Many received no cancer-directed treatment or failed to receive GRT. Another 710 patients had radiation (±surgery) without chemotherapy despite few contraindications to chemotherapy. Over time, patients were more likely to undergo resection after chemotherapy (aRR = 1.58; p < 0.0001) and less likely to have chemoradiation (aRR = 0.78; p < 0.0001) or go untreated (aRR = 0.90; p < 0.0001). Socioeconomic factors (race, education, income, and insurance status) affected the likelihood of receiving chemotherapy and surgery. Median overall survival (OS) was significantly improved for patients treated with chemotherapy and particularly in those patients who went on to receive RT or undergo surgical resection. OS was also longer for patients treated at high-volume academic centers. Patients insured by Medicaid, Medicare, or those without insurance had worse OS. Despite improvement over time, many patients go untreated. Clinical factors were influential, but the impact of vulnerable social standing suggests persistent inequity in access to care.

Prognostic role of platelet-to-lymphocyte ratio in patients with rectal cancer undergoing resection: a systematic review and meta-analysis.

Inflammation plays a pivotal role in tumor growth, with the platelet-to-lymphocyte ratio (PLR) emerging as a promising serum biomarker for prognostic assessment in patients with cancer. However, its specific role in rectal cancer remains controversial. A comprehensive literature review encompassing PubMed, EMBASE, and the Cochrane Library, spanning from their inception to March 2024, was conducted. The systematic review and meta-analysis strictly adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA). Quality assessment was conducted using the Newcastle-Ottawa scale (NOS). This study aimed to assess the available literature on the association of PLR with both overall survival (OS) and disease-free survival (DFS) in patients with rectal cancer undergoing resection. Twenty-three observational studies, encompassing 7577 patients, were included in the analysis. These comprised 20 retrospective and 3 prospective cohort studies, with NOS scores ranging from 5 to 8. A significant association was found between high PLR and worse OS (hazard ratio [HR] 1.00; 95% confidence interval [CI] 1.00-1.01; P = 0.01). Conversely, no significant association was observed between PLR and DFS (HR 1.14; 95% CI 0.98-1.32; P = 0.09). PLR serves as an independent clinical predictor of OS in patients with rectal cancer treated with curative surgery, but not of DFS. This easily accessible biomarker appears to be an optimal prognostic index and may aid clinicians in predicting the prognosis of rectal cancer, facilitating the development of individualized treatment strategies.

Functional Liver Imaging Score Derived from Gadoxetic Acid-enhanced MRI Predicts Cachexia and Prognosis in Hepatocellular Carcinoma Patients.

Cachexia occurs in approximately half of hepatocellular carcinoma (HCC) patients as the disease progresses and is correlated with a poor prognosis. Therefore, early identification of HCC patients at risk of developing cachexia and their prognosis is crucial. This study investigated the functional liver imaging score (FLIS) derived from gadoxetic acid-enhanced magnetic resonance imaging (MRI) to identify cachexia in HCC patients and their prognosis. Pretreatment clinical and MRI data from 339 HCC patients who underwent gadoxetic acid-enhanced MRI scans were retrospectively collected. Patient weights were recorded for 6 months following the MRI scan to diagnose cachexia. The FLIS was calculated as the sum of the enhancement quality score, the excretion quality score, and the portal vein sign quality score. A Cox proportional hazards model was used to determine the significant factors affecting overall survival (OS). Multivariable logistic regression was then conducted to identify variables predicting cachexia in HCC patients, which were subsequently used to predict OS. Cox regression analysis revealed a significant association between cachexia and worse OS. Both FLIS (0-4 vs. 5-6 points) (OR, 9.20; 95% CI: 4.68-18.10; P<0.001) and α-fetoprotein >100 ng/mL (OR, 4.08; 95% CI: 2.13-7.83; P<0.001) emerged as significant predictors of cachexia in patients with HCC. Furthermore, FLIS (0-4 vs. 5-6 points) (HR, 1.73; 95% CI: 1.19-2.51; P=0.004) was significantly associated with OS. Patients in the FLIS 0-4 points group had shorter OS than those in the FLIS 5-6 points group [20 months (95% CI, 14.7-25.3) vs. 43 months (95% CI, 27.7-58.3); P=0.001]. Cachexia was associated with worse OS. The functional liver imaging score emerged as a significant predictor of cachexia in HCC patients and their prognosis.

Pleomorphic Liposarcoma of the Extremity and Trunk: Multimodality Therapy for Some but Not All?

Pleomorphic liposarcoma (PLPS) is an ultra-rare malignancy distinct from well-differentiated/dedifferentiated and myxoid liposarcoma. In this study, we sought to (1) assess outcomes after surgery for primary, non-metastatic PLPS and (2) explore potential indications for multimodality therapy. Clinicopathologic data were retrospectively collected for patients treated from 2002 to 2019 at our sarcoma referral center. Descriptive data were summarized and Kaplan-Meier plots were constructed for overall survival (OS) and crude cumulative incidences (CCI) of disease-specific death (DSD), local recurrence (LR), and distant metastasis (DM). Univariable models were performed to assess the association of specific variables of interest on outcome. Forty-four pathology-verified PLPS cases were included in this study. Median tumor size was 8.5 cm; 75% were FNCLCC Grade 3. All patients underwent complete resection, including 15 patients (34%) who required re-excision to secure microscopic negative margins. Radiation therapy was given to 75% of patients, chemotherapy in 36%. At 5 years, OS was 75.3%; CCI of DSD, LR, and DM were 17.5%, 2.3%, and 32.5%. Larger tumor size was strongly associated with worse OS (p = 0.028) and DSD (p ≤ 0.001). A subgroup of patients (n = 10, 23%) with smaller, predominantly Grade 2 tumors underwent surgery alone without any LR or DM event at a median follow-up of 7.9 years. In PLPS, aggressive surgery and when appropriate, radiation therapy, results in excellent local control. Chemotherapy can be considered for larger tumors. Patients with smaller, Grade 2 tumors may be potentially cured with surgery alone.

Prognostic Significance of Albumin-Globulin Ratio in Urachal Carcinoma

Introduction: Although albumin-globulin ratio (AGR) has been used in the prognostic assessment of multiple solid malignancies, so far no research has confirmed the prognostic significance of AGR as a biomarker for urachal carcinoma. We analyzed the relationship between AGR and prognosis in urachal carcinoma, aiming to identify a promising prognostic biomarker for urachal carcinoma. Methods: We reviewed the clinical data of 25 patients diagnosed with urachal carcinoma in the Xiangya Hospital, Central South University, from January 2008 to October 2021. The best cut-off value of preoperative AGR was determined according to the receiver operator characteristic curve. The Kaplan-Meier curve was used to analyze the effect of preoperative AGR on the overall survival (OS) and relapse-free survival (RFS) of patients. Cox proportional hazards model was used to analyze prognostic factors including preoperative AGR. Results: The best cut-off value of preoperative AGR in urachal carcinoma patients is 1.45. Low preoperative AGR is significantly associated with worse OS and RFS. Univariate analysis and multivariate analysis indicated that low preoperative AGR is an independent and reliable factor to predict poor prognosis, OS, and RFS in urachal carcinoma patients. Conclusion: Urachal carcinoma patients with low preoperative AGR have worse prognosis, and preoperative AGR is a valuable prognostic indicator for urachal carcinoma research.

Choice of Adjuvant Radiotherapy Facility in Sinonasal Squamous Cell Carcinoma.

Undergoing surgery and adjuvant radiotherapy (aRT) at the same facility has been associated with higher overall survival (OS) in head and neck squamous cell carcinoma. Our study investigates whether undergoing surgery and aRT at the same academic facility is associated with higher OS compared with separate facilities in sinonasal squamous cell carcinoma (SNSCC). The 2006 to 2017 National Cancer Database was queried for patients with SNSCC undergoing surgery at an academic facility followed by aRT with or without adjuvant chemotherapy. Multivariable binary logistic and Cox proportional hazards regression models were implemented. Of 419 patients satisfying inclusion criteria, 299 (71.4%) underwent surgery and aRT at the same academic facility. Residence in a less populated area (adjusted odds ratio [aOR] 1.75, 95% confidence interval [CI] 1.02-2.99, p = 0.042) and surgical facility case volume (aOR 2.51, 95% CI 1.21-5.21, p = 0.014) were associated with undergoing surgery and aRT at different facilities on multivariable logistic regression adjusting for patient demographics, clinicopathologic features, and adjuvant therapy (p < 0.05). Five-year OS was higher among patients undergoing surgery and aRT at the same academic facility (64% vs. 55%, p = 0.039). Undergoing surgery and aRT at different facilities remained associated with worse OS on multivariable Cox regression (aHR 1.90, 95% CI 1.09-3.32, p = 0.023). Undergoing surgery and aRT at the same academic facility is associated with higher OS in SNSCC. Academic physicians should carefully consider the recommendation of aRT treatment facility based on the level of benefit that the patient may derive from coordinated multidisciplinary care. 3 Laryngoscope, 2024.

Local excision vs. proctectomy in patients with ypT0–1 rectal cancer following neoadjuvant therapy: a propensity score matched analysis of the National Cancer Database

BackgroundWe aimed to evaluate outcomes of organ preservation by local excision (LE) compared to proctectomy following neoadjuvant therapy for rectal cancer.MethodsThis retrospective observational study using the National Cancer Database (NCDB) included patients with locally advanced non-metastatic rectal cancer (ypT0–1 tumors) treated with neoadjuvant therapy between 2004 and 2019. Outcomes of patients who underwent LE or proctectomy were compared. 1:1 propensity score matching including patient demographics, clinical and therapeutic factors was used to minimize selection bias. Main outcome was overall survival (OS).Results11,256 of 318,548 patients were included, 526 (4.6%) of whom underwent LE. After matching, mean 5-year OS was similar between the groups (54.1 vs. 54.2 months; p = 0.881). Positive resection margins (1.2% vs. 0.6%; p = 0.45), pathologic T stage (p = 0.07), 30-day mortality (0.6% vs. 0.6%; p = 1), and 90-day mortality (1.5% vs. 1.2%; p = 0.75) were comparable between the groups. Length of stay (1 vs. 6 days; p < 0.001) and 30-day readmission rate (5.3% vs. 10.3%; p = 0.02) were lower in LE patients. Multivariate analysis of predictors of OS demonstrated male sex (HR 1.38, 95% CI 1.08–1.77; p = 0.009), higher Charlson score (HR 1.52, 95% CI 1.29–1.79; p < 0.001), poorly differentiated carcinoma (HR 1.61, 95% CI 1.08–2.39; p = 0.02), mucinous carcinoma (HR 3.53, 95% CI 1.72–7.24; p < 0.001), and pathological T1 (HR 1.45, 95% CI 1.14–1.84; p = 0.002) were independent predictors of increased mortality. LE did not correlate with worse OS (HR 0.91, 95% CI 0.42–1.97; p = 0.82).ConclusionOur findings show no overall significant survival difference between LE and total mesorectal excision, including ypT1 tumors. Moreover, patients with poorly differentiated or mucinous adenocarcinomas generally had poorer outcomes, regardless of surgical method.

Abstract A043: Improving our understanding of social determinants of health and neighborhood deprivation on survival in patients after radical cystectomy for urothelial carcinoma

Abstract Introduction: To determine the effects of Social Determinants of Health (SDoH) represented by neighborhood deprivation (ND) and ethnicity on bladder cancer survival by using a state-specific neighborhood deprivation index(the healthy places index, HPI) in measuring recurrence-free survival (RFS) and overall-survival (OS). Methods: We queried our IRB-approved institutional database for patients receiving radical cystectomy with diversion from 2013 to 2019. HPI values already linked to 5-digit zip codes via crosswalk method of census block association were obtained and assigned to our population in quartiles(Q1 representing most deprivation). Patients without associated HPI values were excluded. Multivariable (MVA) logistic regression and Cox models were fit to assess the relationship between HPI and OS and RFS when adjusting for age, race, sex, stage, node status, smoking, diabetes. Kaplan-meier(KM) curves were generated for OS and RFS. Results: 729 patients were included for analysis, of which 81% were male with a median age of 71 years (Range: 35 – 93) at the time of cystectomy. No differences were seen between quartiles for age. 82.99% were non-hispanic white and ethnic minorities comprising 17.01% of patients. Non-white patients were associated with more ND (Q1 41.94%, Q2 29.03%, Q3 16.94%, Q4 12.10%, p&amp;lt;000.1). There were 65 (8.92%) non-white hispanic and black patients (Q1 56.92%, Q2 23.08%, Q3 13.85%, Q4 6.15%, p&amp;lt;0.0001). On MVA Age (HR 95% 1.024 p=0.0026), extravesical disease (HR 95% 2.605 p &amp;lt;0.0001), Node positive status (HR 95% 2.948 p&amp;lt;0.0001), lymphovascular invasion (HR 95% 2.005 p&amp;lt;0.0001), and worse ND measured by HPI (Q4 vs Q1 HR 95% 1.759 p = 0.0055) were associated with worse overall survival(OS). Non-white race was associated with better OS (HR 95% 0.499 p = 0.0017) and RFS (HR 95% 0.581 p=0.0108). Kaplan-Meier demonstrated worse recurrence-free survival p=0.0118 and OS p=0.0109 for the most deprived quartile(Q1). Conclusion: More neighborhood deprivation is correlated with worse OS in UBC. Black and non-white hispanic patients receiving surgery for UBC experienced a higher proportion of deprivation, but non-white race is correlated with better OS in UBC. Higher powered studies are required to confidently identify disparities in care for non-white patients experiencing UBC. Additionally, analysis of individual SDoH included in the HPI is merited to investigate a more specific correlation with UBC. Citation Format: Anosh Dadabhoy, Chirag Doshi, Sejal Mehta, Farshad Sheybaee Moghaddam, Luis Santos Molina, Erika Wood, Leilei Xia, Hooman Djaladat, Anne Schuckman, Siamak Daneshmand. Improving our understanding of social determinants of health and neighborhood deprivation on survival in patients after radical cystectomy for urothelial carcinoma [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A043.

Evaluation of AJCC Nodal Staging for Intraductal Papillary Mucinous Neoplasm-Derived Pancreatic Ductal Adenocarcinoma

BackgroundThe American Joint Committee on Cancer (AJCC) eighth edition is based on pancreatic intraepithelial neoplasia-derived pancreatic ductal adenocarcinoma (PDAC), a biologically distinct entity from intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic cancer. The role of nodal disease and the AJCC’s prognostic utility for IPMN-derived pancreatic cancer are unclear. This study aimed to evaluate the prognostic role of nodal disease and the AJCC eighth-edition N-staging for IPMN-derived pancreatic cancer.MethodsUpfront-surgery patients with IPMN-derived PDAC from four centers were stratified according to the AJCC eighth-edition N stage. Disease characteristics were compared using descriptive statistics, and both overall survival (OS) and recurrence-free survival (RFS) were evaluated using log-rank tests. Multivariable Cox regression was performed to determine the prognostic value of N stage for OS, presented as hazard ratios with 95 % confidence intervals (95 % CIs). A lowest p value log-rank statistic was used to derive the optimal cutoff for node-positive disease.ResultsFor 360 patients, advanced N stage was associated with worse T stage, grade, tubular histology, and perineural and lymphovascular invasion (all p < 0.05). The median OS was 98.3 months (95 % CI 82.8–122.0 months) for N0 disease, 27.8 months (95 % CI 24.4–41.7 months) for N1 disease, and 18.1 months (95 % CI 16.2–25.9 months) for N2 disease (p < 0.001). The AJCC N stage was validated and associated with worse OS (N1 [HR 1.64; range, 1.05–2.57], N2 [HR2.42; range, 1.48–3.96]) and RFS (N1 [HR 1.81; range, 1.23–2.68], N2 [HR 3.72; range, 2.40–5.77]). The optimal cutoff for positive nodes was five nodes.ConclusionThe AJCC eighth-edition N-staging is valid and prognostic for both OS and RFS in IPMN-derived PDAC.

Molecular, Socioeconomic, and Clinical Factors Affecting Racial and Ethnic Disparities in Colorectal Cancer Survival

Disparity in overall survival (OS) and differences in the frequency of driver gene variants by race and ethnicity have been separately observed in patients with colorectal cancer; however, how these differences contribute to survival disparity is unknown. To quantify the association of molecular, socioeconomic, and clinical covariates with racial and ethnic disparities in overall survival among patients with colorectal cancer. This single-center cohort study was conducted at a tertiary-level cancer center using relevant data on all patients diagnosed with colorectal cancer from January 1, 1973, to March 1, 2023. The relative contribution of variables to the disparity was determined using mediation analysis with sequential multivariate Cox regression models. OS, from diagnosis date and from start of first-line chemotherapy. The study population of 47 178 patients (median [IQR] age, 57.0 [49-66] years; 20 465 [43.4%] females and 26 713 [56.6%] males; 3.0% Asian, 8.7% Black, 8.8% Hispanic, and 79.4% White individuals) had a median (IQR) follow-up from initial diagnosis of 124 (174) months and OS of 55 (145) months. Compared with White patients, Black patients had worse OS (hazard ratio [HR], 1.16; 95% CI, 1.09-1.24; P <.001), whereas Asian and Hispanic patients had better OS (HR, 0.66; 95% CI, 0.59-0.74; P <.001; and 0.86; 95% CI, 0.81-0.92; P <.001, respectively). When restricted to patients with metastatic disease, the greatest disparity was between Black patients compared with White patients (HR, 1.2; 95% CI, 1.06-1.37; P <.001). Evaluating changes in OS disparity over 20 years showed disparity decreasing among Asian, Hispanic, and White patients, but increasing between Black patients and White patients (HRs, 1.18; 95% CI, 1.07-1.31 for 2008-2012; 1.24, 95% CI, 1.08-1.42 for 2013-2017; and 1.50; 95% CI, 1.20-1.87 for 2018-2023). Survival outcomes for first-line chemotherapy were worse for Black patients compared with White patients (median OS, 18 vs 26 months; HR, 1.30; 95% CI, 1.01-1.70). Among 7628 patients who had clinical molecular testing, APC, KRAS, and PIK3CA showed higher variant frequency in Black patients (false discovery rate [FDR], 0.01; < 0.001; and 0.01, respectively), whereas BRAF and KIT were higher among White patients (FDR, 0.001 and 0.01). Mediation analysis identified neighborhood socioeconomic status as the greatest contributor to OS disparity (29%), followed by molecular characteristics (microsatellite instability status, KRAS variation and BRAF variation, 10%), and tumor sidedness (9%). This single-center cohort study identified substantial OS disparity and differing frequencies of driver gene variations by race and ethnicity. Socioeconomic status had the largest contribution but accounted for less than one-third of the disparity, with substantial contribution from tumor molecular features. Further study of the associations of genetic ancestry and the molecular pathogenesis of colorectal cancer with chemotherapy response is needed.

PAM50 breast cancer subtypes and survival of patients in rural Ethiopia without adjuvant treatment: a prospective observational study

PurposeSurvival rates of breast cancer (BC) patients are particularly low in rural regions in sub-Saharan Africa (SSA) which is due to limited access to therapy. In recent years, gene expression profiling (GEP) of BC showed a strong prognostic value in patients with local tumour surgery and (neo)adjuvant treatment. The aim of this study was to evaluate the impact of intrinsic subtypes on survival of patients in rural Ethiopia without any (neo)adjuvant therapy.MethodsIn total, 113 female patients from Aira Hospital with histologically proven BC and treated only with surgery were included in this study. All samples were analysed by immunohistochemistry (IHC) for estrogen receptor, progesterone receptor, HER2 and Ki67, as well as RNA-expression analysis for PAM50 subtyping.ResultsA positive hormone receptor status was found in 69.0% of the tumours and intrinsic subtyping demonstrated Luminal B to be the most common subtype (34.5%). Follow-up data was available for 79 of 113 patients. Two-year overall survival (OS) was 57.3% and a considerably worse OS was observed in patients with Basal-like BC compared to Luminal A BC. Moreover, advanced tumours showed an increased risk of mortality.ConclusionThe OS was very low in the patient cohort that received no (neo)adjuvant treatment. Immunohistochemistry and GEP confirmed endocrine-sensitive tumours in more than half of the patients, with a large proportion of Luminal B, HER2-enriched and Basal-like tumours so that adjuvant chemotherapy should be recommended.

Impact of Adjuvant Chemotherapy on Resected Intraductal Papillary Mucinous Neoplasm-Derived Pancreatic Cancer: Results From an International Multicenter Study.

The benefit of adjuvant therapy for intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) remains unclear because of severely limited evidence. Although biologically distinct entities, adjuvant therapy practices for IPMN-derived PDAC are largely founded on pancreatic intraepithelial neoplasia-derived PDAC. We aimed to evaluate the role of adjuvant chemotherapy in IPMN-derived PDAC. This international multicenter retrospective cohort study (2005-2018) was conceived at the Verona Evidence-Based Medicine meeting. Cox regressions were performed to identify risk-adjusted hazard ratios (HR) associated with overall survival (OS). Kaplan-Meier curves and log-rank tests were employed for survival analysis. Logistic regression was performed to identify factors motivating adjuvant chemotherapy administration. A decision tree was proposed and categorized patients into overtreated, undertreated, and optimally treated cohorts. In 1,031 patients from 16 centers, nodal disease (HR, 2.88, P < .001) and elevated (≥37 to <200 µ/mL, HR, 1.44, P = .006) or markedly elevated (≥200 µ/mL, HR, 2.53, P < .001) carbohydrate antigen 19-9 (CA19-9) were associated with worse OS. Node-positive patients with elevated CA19-9 had an associated 34.4-month improvement in median OS (P = .047) after adjuvant chemotherapy while those with positive nodes and markedly elevated CA19-9 had an associated 12.6-month survival benefit (P < .001). Node-negative patients, regardless of CA19-9, did not have an associated benefit from adjuvant chemotherapy (all P > .05). Based on this model, we observed undertreatment in 18.1% and overtreatment in 61.2% of patients. Factors associated with chemotherapy administration included younger age, R1-margin, poorer differentiation, and nodal disease. Almost half of patients with resected IPMN-derived PDAC may be overtreated or undertreated. In patients with node-negative disease or normal CA19-9, adjuvant chemotherapy is not associated with a survival benefit, whereas those with node-positive disease and elevated CA19-9 have an associated benefit from adjuvant chemotherapy. A decision tree was proposed. Randomized controlled trials are needed for validation.

Prognostic value of nucleotide excision repair and translesion DNA synthesis proteins in muscle-infiltrating bladder carcinoma

BackgroundCisplatin (CDDP) remains a key agent in the treatment of muscle-infiltrating bladder carcinoma (MIBC). However, a proportion of MIBC patients do not respond to chemotherapy, which may be caused by the increased repair of CDDP-induced DNA damage. The purpose of this study was to explore the prognostic value of proteins involved in nucleotide excision repair (NER) and translesion DNA synthesis (TLS) in MIBC patients.MethodsThis is a retrospective analysis of 86 MIBC patients. The XPA, XPF, XPG, ERCC1, POLI, POLH and REV3L proteins were stained in primary bladder tumors and their levels were analyzed both in the total cohort and in a subgroup with metastatic urothelial carcinoma (mUC) that received gemcitabine and CDDP as a first-line therapy. Both cohorts were divided by percentage of cancer cells stained positive for each protein into subgroups with high and low expression. In the same manner, the combined expression of NER (XPA + ERCC1 + XPF + XPG) and TLS (POLI + POLH + REV3L), as the whole pathways, was analyzed.ResultsMortality was 89.5% at the median follow-up of 120.2 months. In the total cohort, patients with tumors stained positive for XPA, XPG and POLI had significantly worse overall survival (OS) compared to those with negative staining [hazard ratio (HR) = 0.60, 0.62 and 0.53, respectively]. Both XPG and POLI were independent prognostic factors in multivariate analyses (MVA). In addition, an increase in NER and TLS pathway expression was significantly associated with worse OS in the total cohort (HR = 0.54 and 0.60, respectively). In the mUC subgroup, high POLI expression was associated with significant deterioration of OS (HR = 0.56) in univariate analyses, and its independent prognostic value was shown in MVA.ConclusionsOur study showed significant correlations between the tumor expression of XPG and POLI, as well as NER and TLS as the whole pathways, and inferior OS. Hence, they could constitute prognostic biomarkers and potentially promising therapeutic targets in MIBC. However, a prospective trial is required for further validation, thereby overcoming the limitations of this study.

Epidemiology, prognostic factors, and survival analysis in small cell esophageal carcinoma: A population-based study with external validation.

Small cell esophageal carcinoma (SCEC) is a poorly differentiated esophageal neuroendocrine neoplasm with a poor prognosis. This study aimed to explore the factors and treatment approaches influencing the prognosis of SCEC. In this retrospective study, we collected data from the 18 Surveillance, Epidemiology, and End Results (SEER) registries cohort between 2004 and 2019, as well as from a Chinese institutional registry covering the period from 2012 to 2022. We assessed the annual percentage change (APC) in incidence of SCEC. Kaplan-Meier and Cox regression analyses were conducted to evaluate survival outcomes. Additionally, nomograms were developed for overall survival (OS) and cancer-specific survival (CSS) in the SEER cohort for SCEC and validated in an independent Chinese cohort. This analysis included 299 SCEC patients from the SEER cohort and 66 cases from the Chinese cohort. During the period of 2004-2019, the incidence of SCEC reached a plateau, with an APC of -1.40 (95% confidence interval [CI]: -4.3 to 1.40, P > 0.05). Multivariable Cox regression analysis revealed that age, distant metastasis, and chemotherapy were independent factors for OS, while distant metastasis and chemotherapy were independent factors for CSS. The nomograms developed for OS and CSS in SCEC exhibited remarkable accuracy and reliable predictive capacity in estimating 1-year, 3-year, and 5-year OS and CSS. SCEC is a rare malignancy with aggressive behavior. Distant metastasis is significantly associated with worse OS and CSS in patients with SCEC. Currently, chemotherapy remains the primary treatment approach for SCEC.

Impact of mediastinal tumor burden and lymphatic spread in locally advanced non-small-cell lung cancer: A secondary analysis of the multicenter randomized PET-Plan trial

PurposeThe aim of this secondary analysis of the prospective randomized phase 2 PET-Plan trial (ARO-2009-09; NCT00697333) was to evaluate the impact of mediastinal tumor burden and lymphatic spread in patients with locally advanced non-small-cell lung cancer (NSCLC). MethodsAll patients treated per protocol (n = 172) were included. Patients received isotoxically dose-escalated chemoradiotherapy up to a total dose of 60–74 Gy in 30–37 fractions, aiming as high as possible while adhering to normal tissue constraints. Radiation treatment (RT) planning was based on an 18F-FDG PET/CT targeting all lymph node (LN) stations containing CT positive LNs (i.e. short axis diameter > 10 mm), even if PET-negative (arm A) or targeting only LN stations containing PET-positive nodes (arm B). LN stations were classified into echelon 1 (ipsilateral hilum), 2 (ipsilateral station 4 and 7), and 3 (rest of the mediastinum, contralateral hilum). The endpoints were overall survival (OS), progression-free survival (PFS), and freedom from local progression (FFLP). ResultsThe median follow-up time (95 % confidence interval [CI]) was 41.1 (33.8 − 50.4) months. Patients with a high absolute number of PET-positive LN stations had worse OS (hazard ratio [HR] = 1.09; 95 % CI 0.99 − 1.18; p = 0.05) and PFS (HR = 1.12; 95 % CI 1.04 − 1.20; p = 0.003), irrespective of treatment arm allocation. The prescribed RT dose to the LNs did not correlate with any of the endpoints when considering all patients. However, in patients in arm B (i.e., PET-based selective nodal irradiation), prescribed RT dose to each LN station correlated significantly with FFLP (HR=0.45; 95 % CI 0.24–0.85; p = 0.01). Furthermore, patients with involvement of echelon 3 LN stations had worse PFS (HR = 2.22; 95 % CI 1.16–4.28; p = 0.02), also irrespective of allocation. ConclusionMediastinal tumor burden and lymphatic involvement patterns influence outcome in patients treated with definitive chemoradiotherapy for locally advanced NSCLC. Higher dose to LNs did not improve OS, but did improve FFLP in patients treated with PET-based dose-escalated RT.

Combination of neutrophil-to-lymphocyte ratio and serum CA 19-9 as a prognostic factor in pancreatic cancer.

Traditionally, serum carbohydrate antigen 19-9 (CA 19-9) has been used as a key biomarker for pancreatic cancer and recently other biomarkers which reflect the systemic immune and inflammatory responses also have been explored as potential prognostic factors. The study aims to evaluate the significance of pretreatment neutrophil-to-lymphocyte ratio (NLR) and serum CA 19-9 as prognostic factor in pancreatic cancer patients. A retrospective analysis was conducted in 153 consecutive patients with pancreatic cancer in Instituto Nacional de Cancerología from 2013 to 2018. Pretreatment NLR and serum CA 19-9 values were recorded as well as survivals. The cut-off value determined for NLR was 2.4 and for serum CA 19-9 was 553 U/mL. Survival analysis showed that the 5-year overall survival (OS) was 9% in patients with low-NLR compared with 2% for patients with high-NLR (P=0.008), and 5-year progression-free survival (PFS) was 5.7% in patients with low-NLR compared with 1.3% in patients with high-NLR (P=0.007). For patients with low-CA 19.9, 5-year OS was 8.5% compared with 0% for patients with high-CA 19-9 (P=0.002), and 5-year PFS was 4.1% in patients with low-CA 19-9 compared with 0% in patients with high-CA 19-9 (P=0.005). Classification groups created showed that 5-year OS in Group 1 (low-NLR and low-CA 19-9) was 11.8% compared with 1.9% for patients in Group 2 (either one or both high-NLR or CA 19-9) (P<0.001), and 5-year PFS was 8.6% in Group 1 and 0% in Group 2 (P=0.001). High-NLR and high-CA 19-9 values used separately are both independently associated with worse OS and PFS in patients with pancreatic cancer. The classification groups created combining both biomarkers showed better prognostic significance than when used separately as demonstrated by survival analysis and multivariate analysis.

Identification of a Proteomic Signature for Predicting Immunotherapy Response in Patients With Metastatic Non-Small Cell Lung Cancer

Immunotherapy has improved survival rates in patients with cancer, but identifying those who will respond to treatment remains a challenge. Advances in proteomic technologies have enabled the identification and quantification of nearly all expressed proteins in a single experiment. Integrating mass spectrometry with high-throughput technologies has facilitated comprehensive analysis of the plasma proteome in cancer, facilitating early diagnosis and personalized treatment. In this context, our study aimed to investigate the predictive and prognostic value of plasma proteome analysis using the SWATH-MS (Sequential Window Acquisition of All Theoretical Mass Spectra) strategy in newly diagnosed patients with non-small cell lung cancer (NSCLC) receiving pembrolizumab therapy. We enrolled 64 newly diagnosed patients with advanced NSCLC treated with pembrolizumab. Blood samples were collected from all patients before and during therapy. A total of 171 blood samples were analyzed using the SWATH-MS strategy. Plasma protein expression in metastatic NSCLC patients prior to receiving pembrolizumab was analyzed. A first cohort (discovery cohort) was employed to identify a proteomic signature predicting immunotherapy response. Thus, 324 differentially expressed proteins between responder and non-responder patients were identified. In addition, we developed a predictive model and found a combination of seven proteins, including ATG9A, DCDC2, HPS5, FIL1L, LZTL1, PGTA, and SPTN2, with stronger predictive value than PD-L1 expression alone. Additionally, survival analyses showed an association between the levels of ATG9A, DCDC2, SPTN2 and HPS5 with progression-free survival (PFS) and/or overall survival (OS). Our findings highlight the potential of proteomic technologies to detect predictive biomarkers in blood samples from NSCLC patients, emphasizing the correlation between immunotherapy response and the idenfied protein set.

Characterizing the Mutational Landscape of Diffuse Large B-Cell Lymphoma in a Prospective Cohort of Mexican Patients.

Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell malignancy worldwide. Molecular classifications have tried to improve cure rates. We prospectively examined and correlated the mutational landscape with the clinical features and outcomes of 185 Mexican patients (median age 59.3 years, 50% women) with newly diagnosed DLBCL. A customized panel of 79 genes was designed, based on previous international series. Most patients had ECOG performance status (PS) < 2 (69.2%), advanced-stage disease (72.4%), germinal-center phenotype (68.1%), and double-hit lymphomas (14.1%). One hundred and ten (59.5%) patients had at least one gene with driver mutations. The most common mutated genes were as follows: TP53, EZH2, CREBBP, NOTCH1, and KMT2D. The median follow-up was 42 months, and the 5-year relapse-free survival (RFS) and overall survival (OS) rates were 70% and 72%, respectively. In the multivariate analysis, both age > 50 years and ECOG PS > 2 were significantly associated with a worse OS. Our investigation did not reveal any discernible correlation between the presence of a specific mutation and survival. In conclusion, using a customized panel, we characterized the mutational landscape of a large cohort of Mexican DLBCL patients. These results need to be confirmed in further studies.

Chitinase-3 like-protein-1, a prognostic biomarker in patients with hepatocellular carcinoma and concomitant myosteatosis

BackgroundChitinase-3 like-protein-1 (CHI3L1) is a member of the mammalian chitinase-like proteins and elevated serum CHI3L1 level has been proved to be associated with poor prognosis in hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between serum CHI3L1 levels and body composition parameters in patients with HCC after liver transplantation (LT).MethodsThis retrospective study enrolled 200 patients after LT for HCC. Blood samples were collected and serum concentrations of CHI3L1 were measured by enzyme-linked immunosorbent assay. Computer tomography (CT) were used to estimate skeletal muscle and adipose tissue mass. Spearman’s rank correlation test was performed to assess associations between serum CHI3L1 levels and these body composition parameters. A Cox proportional-hazards regression model was performed to identify independent prognostic factors. Overall survival (OS) and recurrence-free survival (RFS) curves were constructed using the Kaplan-Meier method and compared by the log-rank test.ResultsTotal 71 patients (35.5%) were diagnosed with myosteatosis according to skeletal muscle radiation attenuation (SMRA). The 5-year OS rates were 66.9% in non-myosteatosis group, significantly higher than 49.5% in myosteatosis group (p = 0.025), while the RFS of myosteatosis group (5-year RFS: 52.6%) or non-myosteatosis group (5-year RFS: 42.0%) shown no significant difference (p = 0.068). The serum CHI3L1 level were significantly negative correlated with SMRA (r = -0.3, p < 0.001). Interestingly, in patients with myosteatosis, Kaplan-Meier analysis revealed that elevated serum CHI3L1 levels were associated with worse OS (p < 0.001) and RFS (p = 0.047). However, in patients without myosteatosis, Kaplan-Meier analysis found elevated serum CHI3L1 levels were not associated with OS (p = 0.070) or RFS (p = 0.104).ConclusionsElevated CHI3L1 was negatively correlated with SMRA, and predicted poorer prognosis in Chinese population after LT for HCC, especially in those patients with concomitant myosteatosis. Monitoring serum CHI3L1 can predict prognosis and effectively guide individual nutrition intervention.