Relevant Prognostic Factors Research Articles

Prognostic significance of melanogenesis pathway and its association with the ultrastructural characterisation of melanosomes in uveal melanoma

BackgroundPigmentation could be a relevant prognostic factor in uveal melanoma (UM) development. Microphthalmia-associated transcription factor (MITF) regulates melanin synthesis by activating tyrosinase-related protein 2 (TYRP2) and silver protein (SILV) that...

Head and neck cancers survival in Europe, Taiwan, and Japan: results from RARECAREnet Asia based on a privacy-preserving federated infrastructure.

The head and neck cancers (HNCs) incidence differs between Europe and East Asia. Our objective was to determine whether survival of HNC also differs between European and Asian countries. We used population-based cancer registry data to calculate 5-year relative survival (RS) for the oral cavity, hypopharynx, larynx, nasal cavity, and major salivary gland in Europe, Taiwan, and Japan. We modeled RS with a generalized linear model adjusting for time since diagnosis, sex, age, subsite, and histological grouping. Analyses were performed using federated learning, which enables analyses without sharing sensitive data. Five-year RS for HNC varied between geographical areas. For each HNC site, Europe had a lower RS than both Japan and Taiwan. HNC subsites and histologies distribution and survival differed between the three areas. Differences between Europe and both Asian countries persisted even after adjustments for all HNC sites but nasal cavity and paranasal sinuses, when comparing Europe and Taiwan. Survival differences can be attributed to different factors including different period of diagnosis, more advanced stage at diagnosis, or different availability/access of treatment. Cancer registries did not have stage and treatment information to further explore the reasons of the observed survival differences. Our analyses have confirmed federated learning as a feasible approach for data analyses that addresses the challenges of data sharing and urge for further collaborative studies including relevant prognostic factors.

JS07.5.A PROGNOSTIC FACTORS ASSOCIATED WITH POOR OUTCOME IN ADULT PATIENTS WITH MEDULLOBLASTOMA

Abstract BACKGROUND Medulloblastoma (MB) is a rare tumor in adults. Current recommendations are based on scarce data available in adults, and mostly derived from pediatric series. Prognostic factors have not been uniformly defined in adults to date. MATERIAL AND METHODS We retrospectively collected all cases of adult patients diagnosed and treated between 1995 and 2019 in our institution for histopathological proven MB. We described patient´s characteristics, disease features, treatment modalities and studied the prognostic factors for survival outcomes using univariate and multivariate analysis. RESULTS We identified a total of 89 cases. Male gender (66%), lateral cerebellar location (48%), desmoplastic/nodular histology (43%), Sonic Hedgehog molecular group (76%) and Chang´s M0 (72%) were the most frequent patient´s and disease characteristics. Patients mostly achieved complete resection/near total resection (62%); surgery followed by chemotherapy/radiotherapy (CT/RT) was the most frequent initial strategy (76%), favoring carboplatin-based regimens (70%), posterior fossa RT ≥50 Gy (71%) and craniospinal RT ≥ 30 Gy (59%) as the most frequently regimen used. According to the Association of French Speaking Neuro-oncologists and the European Reference Network on Rare Adult Cancers risk scales (ANOCEF and EURACAN), we found 44 and 48% of intermediate-risk patients and 49 and 45% of high-risk patients, respectively. Both cerebral and spinal presentation at diagnosis was documented in 16 (18%) patients. Complete response was achieved in 71(80%) patients. Nine was the maximal number of progressions documented, 35(39%) patients relapsed, CT was the preferred strategy at relapses, privileging carboplatin-based regimens at first relapse. The median overall survival (mOS) was 124.42 months (95%CI 68.53 - 180.11) and the median progression free survival (mPFS) was 30.48 months (95%CI 13.46 - 47.51), the 5-year OS was 53% and the 5-year PFS was 51%. In multivariate analysis, Chang´s ≥ M2 metastatic classification (p=0.001), no CT in association to RT (p=0.005), and lower doses on craniospinal RT <30 Gy (p=0.015) were associated with poor prognosis for OS; Chang´s ≥ M2 (p=0.009) was also a prognostic factor for poor PFS. CONCLUSION This study dedicated specifically to adult MB patients suggests relevant prognostic factors for adult MB patients. We identify Chang´s ≥ M2 as poor prognostic factor of OS and PFS, and we confirm that the use of CT/RT at diagnosis and RT doses ≥ 30 Gy are associated with better survival in adults MB.

SAMHD1 expression is a surrogate marker of immune infiltration and determines prognosis after neoadjuvant chemotherapy in early breast cancer.

The lack of validated surrogate biomarkers is still an unmet clinical need in the management of early breast cancer cases that do not achieve complete pathological response after neoadjuvant chemotherapy (NACT). Here, we describe and validate the use of SAMHD1 expression as a prognostic biomarker in residual disease in vivo and in vitro. SAMHD1 expression was evaluated in a clinical cohort of early breast cancer patients with stage II-III treated with NACT. Heterotypic 3D cultures including tumor and immune cells were used to investigate the molecular mechanisms responsible of SAMHD1 depletion through whole transcriptomic profiling, immune infiltration capacity and subsequent delineation of dysregulated immune signaling pathways. SAMHD1 expression was associated to increased risk of recurrence and higher Ki67 levels in post-NACT tumor biopsies of breast cancer patients with residual disease. Survival analysis showed that SAMHD1-expressing tumors presented shorter time-to-progression and overall survival than SAMHD1 negative cases, suggesting that SAMHD1 expression is a relevant prognostic factor in breast cancer. Whole-transcriptomic profiling of SAMHD1-depleted tumors identified downregulation of IL-12 signaling pathway as the molecular mechanism determining breast cancer prognosis. The reduced interleukin signaling upon SAMHD1 depletion induced changes in immune cell infiltration capacity in 3D heterotypic in vitro culture models, confirming the role of the SAMHD1 as a regulator of breast cancer prognosis through the induction of changes in immune response and tumor microenvironment. SAMHD1 expression is a novel prognostic biomarker in early breast cancer that impacts immune-mediated signaling and differentially regulates inflammatory intra-tumoral response.

Prognostics of Systemic Malignancy ICD-O Topography and Morphology Types on Brain Metastases: An NCDB Time-to-event Cohort.

The primary site and histology of systemic malignancy are known predictors of progression to brain metastases (BM). We investigated the combinational interactions of International Classification of Diseases for Oncology (ICD-O) primary topography and morphology types on the survival of BM after adjusting for relevant clinical and demographic prognostic factors. The cohort included all adult patients with BM at diagnosis of an invasive malignancy in the National Cancer Database (2010 to 2018). The sample consisted of 180,150 entries out of 14,279,749 cancer patients screened. A survival analysis of the topography-specific and histology-specific time to death was performed. Multivariate Cox regression revealed violations of the proportional hazard assumption for multiple covariates. Parametric models using a log-logistic distribution best described the population survival pattern. The primary topography "prostate" and morphology "choriocarcinoma" provided the strongest survival benefit among ICD-O types, whereas BM from prostate demonstrated a 14-month median overall increase in survival probability. Favorable prognostics were BM from breast, bone/joints, and testis; also, the morphologies of carcinoid tumor, mature B-cell lymphoma, and papillary adenocarcinoma. Poor prognostics were BM from gastrointestinal (liver, biliary tree, pancreas, and gallbladder) and gynecologic malignancies. All morphologies of spindle cell carcinoma, hemangiosarcoma, undifferentiated carcinoma, Ewing sarcoma, pseudosarcomatous carcinoma, renal cell carcinoma/sarcomatoid, signet ring cell carcinoma, spindle cell sarcoma, and squamous cell carcinoma/spindle cell were associated with poor survival. This is the largest cohort providing an unbiased estimate of the adjusted ICD-O topography and morphology effect sizes. The results can be summarized as a booklet for prognostic classification of disease in patients with BM secondary to systemic malignancy.

Role of 18F-FDG PET/CT in evaluating lymph node status in patients with head and neck squamous cell carcinoma.

The presence of cervical lymph node metastases (CLNM) at diagnosis is one of the most relevant negative prognostic factors in patients with head and neck squamous cell carcinoma (HNSCC). The aim of this study was to analyse 2-deoxy-2[18F]fluoro-D-glucose (FDG) PET/CT findings for the identification of primary tumours and CLNM in a sample of patients affected by HNSCC. Moreover, a maximum standardised uptake value (SUVmax) threshold for the detection of CLNM was estimated. Clinical variables (i.e. smoking and alcohol habits), and tumour features (i.e. EBV and HPV positivity) were also evaluated in relation to FDG PET/CT findings. We retrospectively analysed patients who underwent FDG PET/CT for HNSCC staging between 2015-2020 at the University Hospital of Ferrara. All patients had cytological or histological confirmation of suspected cervical lymph nodes. In total, 65 patients were enrolled (53 males, 12 females, median age 65.7 years). CLNM of patients with smoking habit had significantly higher SUVmax values than those of patients with previous smoking habit and non-smokers (p = 0.04). p16 positive HNSCC demonstrated a trend for higher SUVmax values on CLNM, in comparison to p16 negative tumours (p = 0.089). ROC curve analysis identified 5.8 as the best cut-off value of SUVmax for the detection of CLNM (AUC = 0.62, sensitivity 71.4% and specificity 72.7%). FDG PET/CT is a useful tool to evaluate CLNM in patients with HNSCC, particularly in those with smoking habit and p16 positive disease. A SUVmax cut-off of 5.8, combined with the use of conventional radiological investigations, may represent a useful tool in the identification of CLNM.

Development of a nomogram for predicting survival in clinical T1N0M1 lung adenocarcinoma: a population-based study.

This study aimed to establish a prognostic model for clinical T1N0M1 (cT1N0M1) lung adenocarcinoma patients to evaluate the prognosis of patients in terms of overall survival (OS) rate and cancer-specific survival (CSS) rate. Data of patients with metastatic lung adenocarcinoma from 2010 to 2016 were collected from the Surveillance, Epidemiology and End Results database. Multivariate Cox regression analysis was conducted to identify relevant prognostic factors and used to develop nomograms. The receiver operating characteristic (ROC) curve and calibration curve are used to evaluate the predictive ability of the nomograms. A total of 45610 patients were finally included in this study. The OS and CSS nomograms were constructed by same clinical indicators such as age (<60 years or ≥60 years), sex (female or male), race (white, black, or others), surgery, radiation, chemotherapy, and the number of metastatic sites, based on the results of statistical Cox analysis. From the perspective of OS and CSS, surgery contributed the most to the prognosis. The ROC curve analysis showed that the survival nomograms could accurately predict OS and CSS. According to the points obtained from the nomograms, survival was estimated by the Kaplan-Meier method, then cT1N0M1 patients were divided into three groups: low-risk group, intermediate-risk group, and high-risk group, and the OS ( P < 0.001) and CSS ( P < 0.001) were significantly different among the three groups. The nomograms and risk stratification model provide a convenient and reliable tool for individualized evaluation and clinical decision-making of patients with cT1N0M1 lung adenocarcinoma.

TMEM200A is a potential prognostic biomarker and correlated with immune infiltrates in gastric cancer.

Gastric cancer (GC) is one of the most common malignant tumors in the digestive system. Several transmembrane (TMEM) proteins are defined as tumor suppressors or oncogenes. However, the role and underlying mechanism of TMEM200A in GC remain unclear. We analyzed the expression of TMEM200A in GC. Furthermore, the influence of TMEM200A on survival of GC patients was evaluated. The correlations between the clinical information and TMEM200A expression were analyzed using chi-square test and logistic regression. Relevant prognostic factors were identified performing univariate and multivariate analysis. Gene set enrichment analysis (GSEA) was performed based on the TCGA dataset. Finally, we explore the relationship between TMEM200A expression and cancer immune infiltrates using CIBERSORT. TMEM200A was up-regulated in GC tissues than that in adjacent non-tumor tissues based on TCGA database. Meta-analysis and RT-qPCR validated the difference in TMEM200A expression. Kaplan-Meier curves suggested the increased TMEM200A had a poor prognosis in GC patients. The chi-square test and logistic regression analyses showed that the TMEM200A expression correlates significantly with T stage. Multivariate analysis showed that TMEM200A expression might be an important independent predictor of poor overall survival in GC patients. GSEA identified five immune-related signaling pathways and five tumor-related signaling pathways significantly enriched in the high TMEM200A expression phenotype pathway. Finally, we found CD8+ T cells is apparently decreased in high TMEM200A expression group. Conversely, eosinophils is increased in high expression group compared with low expression group. TMEM200A is a potential prognostic biomarker and correlated with immune infiltrates in GC.

Risk Stratification in Pulmonary Arterial Hypertension, Update and Perspectives

Risk stratification in pulmonary arterial hypertension (PAH) is crucial in assessing patient prognosis. It serves a prominent role in everyday patient care and can be determined using several validated risk assessment scores worldwide. The recently published 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines underline the importance of risk stratification not only at baseline but also during follow-up. Achieving a low-risk status has now become the therapeutic goal, emphasising the importance of personalised therapy. The application of these guidelines is also important in determining the timing for lung transplantation referral. In this review, we summarise the most relevant prognostic factors of PAH as well as the parameters used in PAH risk scores and their evolution in the guidelines over the last decade. Finally, we describe the central role that risk stratification plays in the current guidelines not only in European countries but also in Asian countries.

Acinic Cell Carcinoma in the 21st Century: A Population-Based Study from the SEER Database and Review of Recent Molecular Genetic Advances

Background: Acinic cell carcinoma (AciCC) comprises 6–7% of all salivary gland neoplasms and is the second most common salivary gland malignancy in children. Like many salivary gland carcinomas, it is considered low grade but occasionally it behaves aggressively. Understanding the risk factors associated with recurrence, metastasis, and death is important to determine the counseling and management of individual patients. Older population-based studies are presumed to have been confounded by the misclassification of other neoplasms as AciCC, in particular secretory carcinoma and cystadenocarcinoma. Since diagnostic tools to reliably separate these entities have been available for over a decade, reevaluation of epidemiologic data limited to the 21st century should allow a better characterization of the clinicopathological characteristics of AciCC. Methods: Our study extracted data from the Surveillance, Epidemiology, and End Results (SEER) database for the period 2000 to 2018. Cox regression model analysis was performed to identify risk factors independently affecting survival. Results: Data for 2226 patients with AciCC were extracted from the database. Most patients were females: 59%, and white: 80.5%, with a mean age at diagnosis of 51.2 (SD ± 18.7) years. Most cases (81%) were localized at presentation. Tumor size was less than 2 cm in 42%, 2–4 cm in 47%, and &gt;4 cm in 11%. Low-grade tumors had 5-year survival &gt; 90%, whereas high-grade tumors had survival &lt; 50%. Of the patients with known lymph node status only 7.3% had nodal metastases. Distant metastases were documented in 1.1%, involving lungs 44%, bone 40%, liver 12%, and brain 4%. The most common treatment modality was surgery alone: 63.6% followed by surgery and adjuvant radiation: 33%. A few received chemotherapy (1.8%) or multimodality therapy (1.2%). The 5-year overall survival rate was 90.6% (95%CI 89.1–91.9), and disease-specific survival was 94.6% (95%CI 93.3–95.6). Multivariable cox regression analysis showed that undifferentiated (HR = 8.3) and poorly differentiated tumor grade (HR = 6.4), and metastasis (HR = 5.3) were the worst independent prognostic factors. Other poor risk factors included age &gt; 50 (HR = 3.5) and tumor size &gt; 4 cm (HR = 2.5). Conclusions: In the US, AciCC is more common in middle age white females, and most tumors are less than 4 cm and localized at diagnosis. The most relevant negative prognostic factor was high tumor grade which was associated with higher hazard ratios for death than all other variables, including regional or distant metastases at presentation.

Identification of predictors of long-term survival and prognostic outcomes in thymic squamous cell carcinoma: A real-world study.

Although thymic squamous cell carcinoma (TSCC) is among the most prevalent forms of thymic carcinoma, there are relatively few studies on this tumor type, and its staging, optimal treatment strategies, and relevant prognostic factors remain controversial. The present study analyzed 79 patients diagnosed with TSCC between January 2008 and January 2021. Kaplan-Meier curves and Cox univariate and multivariate regression analyses were used to explore factors associated with overall survival (OS) and progression-free survival (PFS) in the overall patient cohort and patient subgroups stratified according to the TNM stage. Time-dependent receiver operating characteristic (ROC) analyses were used to compare the TNM and Masaoka systems as predictors of patient prognosis. The 5- and 10-year OS rates in this study were 65.5% and 49.4%, respectively, with corresponding 5- and 10-year PFS rates of 52.3% and 37.9%. Survival outcomes were better for patients with early-stage disease (p < 0.001) and patients that underwent surgical treatment (p < 0.001). Neither extent of resection (p = 0.820) nor the surgical approach (p = 0.444) influenced patient survival. In individuals with advanced disease, all forms of adjuvant therapy including radiotherapy (p = 0.021), chemotherapy (p = 0.035), and chemoradiation (p = 0.01) significantly improved patient PFS, but only adjuvant chemoradiotherapy improved patient OS (p = 0.035). When predicting the patient survival outcomes, the TNM system was slightly superior to the Masaoka system (area under the ROC curve [AUC] at 5 years: OS, 0.742 vs. 0.723; PFS, 0.846 vs. 0.816). TSCC is an orphan malignancy with a poor prognosis. TNM staging may be superior to Masaoka staging as a predictor of TSCC patient prognosis. Surgery is the mainstay of TSCC treatment. Video-assisted thoracoscopy (VATS) should be considered for selected patients. Multimodal therapy was associated with excellent results for patients with advanced TNM stage, particularly when surgery was accompanied by adjuvant chemoradiation.

Novel Multi-Modal Therapies and Their Prognostic Potential in Gastric Cancer.

Gastric cancer has a poor prognosis and involves metastasis to the peritoneum in over 40% of patients. The optimal treatment modalities have not been established for gastric cancer patients with peritoneal carcinomatosis (GC/PC). Although studies have reported favourable prognostic factors, these have yet to be incorporated into treatment guidelines. Hence, our review aims to appraise the latest diagnostic and treatment developments in managing GC/PC. A systematic review of the literature was performed using MEDLINE, EMBASE, the Cochrane Review, and Scopus databases. Articles were evaluated for the use of hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurised intraperitoneal aerosolised chemotherapy (PIPAC) in GC/PC. A meta-analysis of studies reporting on overall survival (OS) in HIPEC and comparing the extent of cytoreduction as a prognostic factor was also carried out. The database search yielded a total of 2297 studies. Seventeen studies were included in the qualitative and quantitative analyses. Eight studies reported the short-term OS at 1 year as the primary outcome measure, and our analysis showed a significantly higher OS for the HIPEC/CRS cohort compared to the CRS cohort (pooled OR = 0.53; p = 0.0005). This effect persisted longer term at five years as well (pooled OR = 0.52; p < 0.0001). HIPEC and CRS also showed a longer median OS compared to CRS (pooled SMD = 0.61; p < 0.00001). Three studies reporting on PIPAC demonstrated a pooled OS of 10.3 (2.2) months. Prognostic factors for longer OS include a more complete cytoreduction (pooled OR = 5.35; p < 0.00001), which correlated with a peritoneal carcinomatosis index below 7. Novel treatment strategies, such as HIPEC and PIPAC, are promising in the management of GC/PC. Further work is necessary to define their role within the treatment algorithm and identify relevant prognostic factors that will assist patient selection.

Prognostic value of blood lipids on patients treated with oxaliplatin combined with S-1 (SOX) after radical gastrectomy and establishment of prognostic nomogram.

To analyze the prognostic significance of plasma total cholesterol (TC) and high-density lipoprotein (HDL) in patients with gastric cancer receiving oxaliplatin combination with S-1 (SOX) chemotherapy after radical resection and to establish models of relevant prognostic influencing factors. The clinicopathologic features of 301 patients treated with SOX after radical gastrectomy were retrospectively analyzed. Univariate analysis, multivariate analysis, and the Kaplan-Meier survival curve were used to analyze the prognostic value of TC and HDL in patients undergoing adjuvant SOX chemotherapy after curative gastric surgery. Based on the results of multivariate Cox regression, we constructed nomograms to predict 1 and 3-year CSS (cancer-specific survival time) and DFS (disease-free survival time) in patients with adjuvant chemotherapy after radical gastrectomy. We assessed the model's accuracy using the consistency index (C index) and calibration curve, and the ROC curve and DCA curve were applied to compare it with TNM staging. Multivariate analysis revealed that TC and HDL were independent influencing factors of CSS, while HDL was an independent factor unique to DFS. According to Kaplan-Meier curves, low TC and HDL suggested poor survival (P < 0.001). The relevant prognostic factors from the multivariate study were used to build nomograms for DFS and CSS. Both DFS and CSS had C index and AUC values that were higher than 0.71. The calibration curves demonstrated that the predicted results are consistent with the observed results. The AUC valves for DFS and CSS in our models were higher than TNM staging. The decision curve analysis indicated that net benefits were moderately positive. Significant differences in survival were seen between the high and low-risk groups according to the nomogram risk score. TC and HDL have a certain significance for the prognosis of patients with gastric cancer after radical resection receiving adjuvant SOX chemotherapy. Lower TC and HDL suggested poor DFS and CSS. Both prediction models for CSS and DFS demonstrated good predictive ability and had a higher predictive value than the TNM staging system.

TREATMENT STRATEGIES AND PROGNOSTIC FACTORS FOR THE OUTCOME OF PATIENTS WITH HODGKIN LYMPHOMA EXPERIENCING VERY LATE RELAPSES AFTER CHEMOTHERAPY ± RADIOTHERAPY

Background: Despite the excellent long-term outcome of patients with Hodgkin Lymphoma (HL), some cases will be primary refractory or will eventually relapse, mainly within the first 2 years from diagnosis. Patients with sustained complete remission (CR) for ≥5 years are generally considered “cured”. However, Very Late Relapses (VLRs), occurring ≥5 years after treatment initiation, are a non-negligible event and possibly comprise a distinct entity with unique characteristics. Aim: The aim of the current study is to describe the treatment strategies adopted for patients with VLRs as well as their outcome and relevant prognostic factors. Patients/Methods: Patients with HL who experienced VLRs ≥5 years after treatment Initiation with chemotherapy ± radiotherapy (CT±RT), were identified retrospectively from the databases of 8 referral centers. Statistical endpoints were the estimation of time to second failure (TT2F) and Overall Survival after failure (O2S). Results: 145 patients with VLRs were identified. The median age was 49 years (19–82), 69% were males and 18% were ≥65 years old. In 23% of the patients, relapse occurred >15 years after the initial diagnosis. Reinduction with the same regimen was given in 24% of the cases, and 26% were indented to proceeded to high-dose therapy and autologous stem cell transplantation (HDT/ASCT). The 5- and 10-year TT2F were 57% and 53% and the 10-year and 15-year O2S were 59% and 46% respectively. Among 52 deaths, only 28 were disease-related whereas others were attributed to secondary malignancies or unrelated causes. Re-induction with the same regimen did not significantly affect TTF2 and O2S. Despite the numerical difference regarding 5-year FF2P for patients <65 years old who received HDT/ASCT, this was not statistical significant and there was no difference at 10 years. In multivariate analysis B-symptoms, extranodal disease, age ≥65 at relapse, and occurrence of relapse <15 years from diagnosis were independent adverse prognostic factors for TT2F (p = 0.03, 0.003, 0.005 and 0.006 respectively). Anemia, age ≥ 65 and extranodal disease at relapse were also associated with impaired O2S (p = 0.02, <0.001 and 0.044 respectively). We assigned one point to each of the aforementioned unfavorable factors and constructed prognostic scores. Patients combining 2–3 adverse characteristics had significantly compromised outcomes. None of the patients survived at 10-years with the 10-year disease-free-survival being only 36%. Conclusion: The prognosis of VLRs does not appear very favorable, however a considerable proportion of patients were ≥65 years old at the time of relapse when treatment options are limited and also, many patients succumb to disease-unrelated causes. Treatment approaches were heterogenous. In our study B-symptoms, extranodal disease and age ≥65 at relapse were the most important prognostic factors for the outcome of patients with VLRs. Keyword: Hodgkin lymphoma No conflicts of interests pertinent to the abstract.

Infants’ immunisations, their timing and the risk of allergic diseases (INITIAL): an observational prospective cohort study protocol

IntroductionVaccinations are considered to have a large impact on disease control, hence a multitude of vaccines in infancy is recommended. Retrospective studies suggest a possible relation between timing, kind or...

Dissecting the prognostic role of baseline body mass index (BMI) in early breast cancer (BC): Individual patient-level analysis from five mammella interGruppo (MIG) and gruppo italiano mammella (GIM) randomized clinical trials (RCTs).

12067 Background: Nearly half of patients (pts) are overweight or obese at BC diagnosis (dx). Higher BMI at dx has been associated with cardiometabolic comorbidities, higher risk of severe treatment-related sequelae, and worse quality of life. Previous studies showed inferior survival outcomes among patients with early BC and high BMI, although not consistently. The aim of this study was to explore the prognostic role of BMI at dx using data from five RCTs of adjuvant therapy for early stage BC with long-term follow-up. Methods: Pts with known BMI at dx, randomized in the MIG-1, MIG-5, GIM-2, GIM-3 and GIM-6 phase III RCTs were included. BMI was categorized as lean ( &lt; 25 kg/m2), overweight (25-30 kg/m2) or obese (≥ 30 kg/m2). Outcomes included disease-free survival (DFS), breast cancer free-interval (BCFI) and overall survival (OS). Survival estimates were compared using the Kaplan-Meier method and log-rank test. Multivariable Cox proportional hazard models stratified by trial and relevant prognostic factors assessed associations between BMI and outcomes. Results: Among 7334 pts in the overall population, mean age was 56.4 years (SD 11.2), 67.8% had node-positive disease, 76.9% received chemotherapy and 83.0% endocrine therapy. Most pts were overweight (33.1%) or obese (21.0%) and 45.9% were lean. Higher BMI was associated with older age, larger tumor size, higher nodal status, and HR+/HER2- subtype. At a median follow-up of 10.0 years (IQR 6.1-15.1) there were 2165 DFS, 1674 BCFI and 1354 OS events. Pts with higher BMI had worse DFS and OS (log-rank p = 0.007 and p &lt; .0001, respectively), but similar BCFI (p = 0.48). BMI at dx was an independent risk factor for worse OS, but not for DFS and BCFI (Table). Results in the HR+/HER2- population (n = 4093) were consistent: pts with higher BMI had worse DFS, BCFI, and OS (log-rank p = 0.001, p &lt; .006, and p &lt; .0001, respectively) and BMI at dx was an independent risk factor only for worse OS (aHR [95%CI] 1.06 [0.84-1.32] and 1.31 [1.02-1.67] for overweight and obese vs lean pts, respectively). Conclusions: In this large study of pts with early BC treated in RCTs with long-term follow-up, higher BMI at dx was an independent risk factor for overall mortality but not for BC-specific outcomes. Weight loss interventions may mitigate the detrimental effect of excess body weight on outcomes of BC survivors, including by reducing the burden and risks of associated cardiometabolic comorbidities. [Table: see text]

Histopathological Analysis of Nodal Disease After Chemoradiation Reveals Viable Tumor Cells as the most Important Prognostic Factor in Head and Neck Squamous Cell Carcinoma

BackgroundIn head and neck squamous cell carcinoma (HNSCC), salvage neck dissection (ND) is required after primary chemoradiation in case of residual nodal disease. Upon histopathological examination, viability of tumor cells is assessed but little is known about other prognostic histopathological features. In particular, the presence of swirled keratin debris and its prognostic value is controversial. The aim of this study is to examine histopathological parameters in ND specimens and correlate them with patient outcome to determine the relevant parameters for histopathological reporting.Materials and MethodsSalvage ND specimen from a cohort of n = 75 HNSCC (oropharynx, larynx, hypopharynx) patients with prior (chemo) radiation were evaluated on H&E stains for the following parameters: viable tumor cells, necrosis, swirled keratin debris, foamy histiocytes, bleeding residues, fibrosis, elastosis, pyknotic cells, calcification, cholesterol crystals, multinucleated giant cells, perineural, and vascular invasion. Histological features were correlated with survival outcomes.ResultsOnly the presence / amount (area) of viable tumor cells correlated with a worse clinical outcome (local and regional recurrence-free survival, (LRRFS), distant metastasis-free survival, disease-specific survival, and overall survival, p < 0.05) in both the univariable and multivariable analyses.ConclusionWe could confirm the presence of viable tumor cells as a relevant negative prognostic factor after (chemo) radiation. The amount (area) of viable tumor cells further substratified patients with worse LRRFS. None of the other parameters correlated with a distinctive worse outcome. Importantly, the presence of (swirled) keratin debris alone should not be considered viable tumor cells (ypN0).

Adjuvant capecitabine in triple negative breast cancer patients with residual disease after neoadjuvant treatment: real-world evidence from CaRe, a multicentric, observational study.

In triple negative breast cancer patients treated with neoadjuvant chemotherapy, residual disease at surgery is the most relevant unfavorable prognostic factor. Current guidelines consider the use of adjuvant capecitabine, based on the results of the randomized CREATE-X study, carried out in Asian patients and including a small subset of triple negative tumors. Thus far, evidence on Caucasian patients is limited, and no real-world data are available. We carried out a multicenter, observational study, involving 44 oncologic centres. Triple negative breast cancer patients with residual disease, treated with adjuvant capecitabine from January 2017 through June 2021, were recruited. We primarily focused on treatment tolerability, with toxicity being reported as potential cause of treatment discontinuation. Secondarily, we assessed effectiveness in the overall study population and in a subset having a minimum follow-up of 2 years. Overall, 270 patients were retrospectively identified. The 50.4% of the patients had residual node positive disease, 7.8% and 81.9% had large or G3 residual tumor, respectively, and 80.4% a Ki-67 >20%. Toxicity-related treatment discontinuation was observed only in 10.4% of the patients. In the whole population, at a median follow-up of 15 months, 2-year disease-free survival was 62%, 2 and 3-year overall survival 84.0% and 76.2%, respectively. In 129 patients with a median follow-up of 25 months, 2-year disease-free survival was 43.4%, 2 and 3-year overall survival 78.0% and 70.8%, respectively. Six or more cycles of capecitabine were associated with more favourable outcomes compared with less than six cycles. The CaRe study shows an unexpectedly good tolerance of adjuvant capecitabine in a real-world setting, although effectiveness appears to be lower than that observed in the CREATE-X study. Methodological differences between the two studies impose significant limits to comparability concerning effectiveness, and strongly invite further research.

Prognostic factors in patients with uterine sarcoma: the SARCUT study

ObjectiveUterine sarcomas are a rare and heterogeneous group of malignancies that include different histological sub-types. The aim of this study was to identify and evaluate the impact of the different...

Clinical-pathologic profile of head and neck rhabdomyosarcoma in children: a systematic review

This systematic review aimed to analyze the clinicopathological profile and relevant prognostic factors of head and neck rhabdomyosarcoma in pediatric patients. The search was carried out in the electronic search portals PubMed, Lilacs, Embase, Scopus, and Web of Science. The search yielded studies that were then analyzed regarding study topic, data extraction, and risk of bias using the STROBE (Strengthening the Reporting of Observational Studies) guidelines. Finally, three studies were included for qualitative analysis. Most of the cases involved embryonic and alveolar rhabdomyosarcoma. Expression of MYOD1 was highly correlated with diagnosis of spindle cell/sclerosing rhabdomyosarcoma, which appears to have a poor prognosis in children. Furthermore, tumor size <5 cm and absence of metastasis accompanied by complete resection and administration of adjuvant therapies such as chemotherapy and radiotherapy favored a better prognosis.