Adjuvant radiation therapy alone is associated with improved overall survival compared to hormonal therapy alone in older women with estrogen receptor positive early stage breast cancer

xloma.fota13 shared this article with you from Inoreader Adjuvant radiation therapy alone is associated with improved overall survival compared to hormonal therapy alone in older women with estrogen receptor positive early stage breast cancer Via Cancer Medicine In this cohort study of 130,194 women age ≥65 years with invasive ER+, node negative breast cancer who underwent breast conserving surgery, radiation (RT) with hormonal therapy (HT) was associated with the highest 5 and 10‐year survival rates (90.0% and 64.3%, respectively). Compared to patients receiving HT alone, those receiving RT alone had improved unadjusted and adjusted survival rates. Abstract Background Breast conserving surgery (BCS) and adjuvant hormonal therapy (HT) without radiation therapy (RT) is an acceptable approach for older women with early stage, estrogen receptor (ER) positive breast cancer. Toxicity and compliance remain issues with HT. Adjuvant RT alone may have better compliance, but its efficacy in the absence of HT is unclear. We aim to assess patterns of adjuvant therapy and survival outcomes among older women with early stage, ER positive (ER+) breast cancer. Methods The National Cancer Data Base (NCDB) was used to identify 130,194 women age ≥65 years with invasive ER+, node negative breast cancer diagnosed between 2004 and 2015. All patients underwent BCS. Kaplan‐Meier survival curves were used to examine overall survival (OS). The association between adjuvant therapy and OS was assessed in multivariable Cox proportional hazards regression models. Results Unadjusted 5/10‐year OS rates were 90.0%/64.3% for HT and RT, 84.2%/54.9% for RT alone, 78.7%/44.5% for HT alone, and 71.6%/38.0% for no treatment; p<0.001 for all. Compared to HT alone, the 10‐year multivariable hazard ratio (HR) for death for RT alone was 0.86 (95% CI 0.82‐0.91). In propensity‐matched patients who received RT alone or HT alone (n=21,326), RT alone had significantly better survival at 5 (HRadj: 0.84) and 10 (HRadj: 0.87) years. Conclusions Older women with early stage ER+ breast cancer who undergo BCS and receive both HT and RT have the best survival, while RT as single‐modality therapy had higher rates of OS at 5 and 10 years compared to HT alone. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Development and validation of prognostic nomogram in patients with nonmetastatic malignant melanoma: a SEER population‐based study

xloma.fota13 shared this article with you from Inoreader Development and validation of prognostic nomogram in patients with nonmetastatic malignant melanoma: a SEER population‐based study Via Cancer Medicine we constructed and validated a nomogram based on a large population database, which will predict the 3‐and 5‐year overall survival rates of patients with non‐metastatic malignant melanoma. Abstract Background The condition of tumor recurrence and overall death can be worried in the progress of nonmetastatic malignant melanoma (NMMM). Our goal was to construct and validate a prognostic nomogram from a large population database, which is vital for physicians to predict the 3‐ and 5‐year overall survival (OS) rates of patients with NMMM. Methods According to the Surveillance, Epidemiology, and End Results (SEER) program, patients were collected and randomly assigned into the training and validation cohorts. Several independent risk factors were identified based on the methods of univariable and multivariable cox hazards regression and were incorporated to develop a nomogram. The concordance index (C‐index), the area under the receiver operating characteristics (AUC) curve and calibration plot were confirmed to assess predictive power of the nomogram. Decision curve analysis (DCA) was performed to measure nomogram for the clinical practice. Results A total of 66192 eligible patients, randomly assigned into 70% of training (n = 46 336) and 30% of validation cohorts (n = 19 856), were selected in this study. The selected independent factors were applied to develop a nomogram, and validated indexes indicated nomogram had a good discrimination ability. The C‐index for OS rates was 0.817 (95% CI: 0.811‐0.823) in training cohort and 0.817 (95% CI: 0.809‐0.825) in validation cohort, respectively. The AUCs of 3‐ and 5‐year OS rates were more than 0.79, and the calibration plots also showed a good power for the nomogram. DCA demonstrated that constructed nomogram can provide clinical net benefit. Conclusion We constructed a novel nomogram that more accurately and comprehensively predict OS with nonmetastatic malignant melanoma patients, which is vital for clinician to improve individual treatment, make reasonable clinical decisions, and set appropriate follow‐up strategies. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Efficacy of bendamustine and rituximab in unfit patients with previously untreated chronic lymphocytic leukemia. Indirect comparison with ibrutinib in a real‐world setting. A GIMEMA‐ERIC and US study

xloma.fota13 shared this article with you from Inoreader Efficacy of bendamustine and rituximab in unfit patients with previously untreated chronic lymphocytic leukemia. Indirect comparison with ibrutinib in a real‐world setting. A GIMEMA‐ERIC and US study Via Cancer Medicine Bendamustine and Rituximab was a relatively effective first‐line regimen in real‐world untreated CLL patients with reduced renal function or coexisting conditions without TP53 disruption.In a matched‐adjusted indirect comparison with a cohort of CLL patients treated upfront, ibrutinib provided longer PFS than bendamustine and rituximab in those with advanced stage. Abstract Limited information is available on the efficacy of front‐line bendamustine and rituximab (BR) in chronic lymphocytic leukemia (CLL) with reduced renal function or coexisting conditions. We therefore analyzed a cohort of real‐world patients and performed a matched adjusted indirect comparison with a cohort of patients treated with ibrutinib. One hundred and fifty‐seven patients with creatinine clearance (CrCl) <70 mL/min and/or CIRS score >6 were treated with BR. The median age was 72 years; 69% of patients had ≥2 comorbidities and the median CrCl was 59.8 mL/min. 17.6% of patients carried TP53 disruption. The median progression‐free survival (PFS) was 45 months; TP53 disruption was associated with a shorter PFS (P = 0.05). The overall survival (OS) at 12, 24, and 36 months was 96.2%, 90.1%, and 79.5%, respectively. TP53 disruption was associated with an increased risk of death (P = 0.01). Data on 162 patie nts ≥65 years treated with ibrutinib were analyzed and compared with 165 patients ≥65 years treated with BR. Factors predicting for a longer PFS at multivariable analysis in the total patient population treated with BR and ibrutinib were age (HR 1.06, 95% CI 1.02‐1.10, P < 0.01) and treatment with ibrutinib (HR 0.55, 95% CI 0.33‐0.93, P = 0.03). In a post hoc analysis of patients in advanced stage, a significant PFS advantage was observed in patient who had received ibrutinib (P = 0.03), who showed a trend for OS advantage (P = 0.08). We arrived at the following conclusions: (a) BR is a relatively effective first‐line regimen in a real‐world population of unfit patients without TP53 disruption, (b) ibrutinib provided longer disease control than BR in patients with advanced disease stage. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Utility of a multigene testing for preoperative evaluation of indeterminate thyroid nodules: A prospective blinded single center study in China

xloma.fota13 shared this article with you from Inoreader Utility of a multigene testing for preoperative evaluation of indeterminate thyroid nodules: A prospective blinded single center study in China Via Cancer Medicine We introduced a multigene panal for cancer diagnosis in FNA‐indeterminate thyroid nodules, and evaluated its performance in Chinese population. Abstract Background Thyroid nodules are highly prevalent, with fine‐needle aspiration (FNA) commonly used as the standard preoperative tool for their diagnosis. However, the method classifies some of the samples as indeterminate, leading to unnecessary surgery. In this study, we evaluated the value of next‐generation sequencing (NGS) for cancer diagnosis in indeterminate thyroid nodules. Materials and methods We performed a prospective, blinded cohort study on 189 patients, with 196 Bethesda III/IV nodules. Specifically, we analyzed DNA mutations and RNA fusions across the FNA samples using NGS, then reviewed follow‐up reports from 84 nodules following definitive surgery, to determine the assay performance. Results Enough DNA and RNA were obtained in 188 nodules, revealing mutations or fusions in 34.6% of them. The most frequently mutated genes were RAS, followed by BRAF V600E. Based on surgical pathology, 39% (33/84) and 4.8% (4/84) of the nodules were malignant and intermediate, respectively. According to the risk stratification criteria, 28 cases were categorized High‐Risk group, all of the resected nodules (n = 20) were malignant. Twenty‐four thyroid nodules were in the Low‐Risk group, 28.6% (4/14) surgically removed nodules were malignant. In the Benign‐Like category, 18.0% (9/50) were malignant. Five out of 13 nodules with benign mutations were resected, including SPOP, EZH1, and ZNF148, all of them were benign. If genetic alterations annotated with High‐Risk or Low‐Risk was considered as positive, and negative if Benign‐Like. Multigene testing revealed sensitivity, specificity, positive predictive values (PPV), and negative predictive value (NPV) of 73%, 80%, 7 1%, and 82%, respectively. In addition, if four intermediate nodules were counted as malignant, the PPV and NPV were 71% and 74%. Conclusion Our results allow for further stratification of Bethesda III/IV thyroid nodules based on the risk of their malignancy. SPOP, EZH1, and ZNF148 mutations may be used as benign markers. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Develop a circular RNA–related regulatory network associated with prognosis of gastric cancer

xloma.fota13 shared this article with you from Inoreader Develop a circular RNA–related regulatory network associated with prognosis of gastric cancer Via Cancer Medicine Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment annotations of differentially expressed genes (DEGs) (up‐(A) and down (B)‐regulated DEGs). Abstract Background In gastric cancer (GC), circular RNAs (circRNAs) mainly play an important role in miRNA sponge, which not only indicate long‐term survival and prognosis but also increase resistance to the apoptosis. The purpose of the study is to explore new circRNAs and their underlying mechanisms in GC. Method Through rigorous retrieval strategies, we used the sva package to analyze and identify differentially expressed circRNAs (DECs) from three Gene Expression Omnibus microarray datasets (GSE83521, GSE89143, and GSE78092). Online website CSCD and CircInteractome were used to reveal the binding sites between miRNAs and DECs. The possible target miRNAs of the DECs identified based on miRNAs, and Cytoscape was used to create a regulatory network of circRNA‐m iRNA‐mRNA and identified the hub genes which were further validated using The Cancer Genome Atlas database and Human Protein Atlas. Results Twenty‐eight DECs were obtained using the sva package. A regulatory network of circRNA‐miRNA‐mRNA (competing endogenous RNA) containing 15 circRNAs, 24 miRNAs, and 158 genes was identified. A protein‐protein interaction network based on the 158 genes was established, and further determined that 10 hub genes (SKA1, ANLN, CHEK1, SKA3, TOP2A, BIRC5, RRM2, NCAPG2, FANCI, and RAD51) were associated with some cancer‐related pathways based on the functional enrichment analysis. Finally, six hub genes (BIRC5, TOP2A, FANCI, NCAPG2, RAD51, and RRM2) were proven to influence the overall survival of GC. Conclusion Our study established a circRNA‐miRNA‐mRNA regulatory network and defined six circRNA‐related hub genes in GC, which could serve as potential therapeutic targets or prognostic biomarker for GC treatment. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Health care‐related time costs in patients with metastatic breast cancer

xloma.fota13 shared this article with you from Inoreader Health care‐related time costs in patients with metastatic breast cancer Via Cancer Medicine In patients with metastatic breast cancer, time spent on health care ranged from 7% to 10% of all days included within the initial 3 months of treatment, depending on type of treatment received and its administration method. The greatest time contributions were time spent traveling for care and on inpatient services, and health care time was higher for patients receiving chemotherapeutic agents compared to those receiving hormonal agents. Abstract Background Burdens related to time spent receiving cancer care may be substantial for patients with incurable, life‐limiting cancers such as metastatic breast cancer (MBC). Estimates of time spent on health care are needed to inform treatment‐related decision‐making. Methods Estimates of time spent receiving cancer‐related health care in the initial 3 months of treatment for patients with MBC were calculated using the following data sources: (a) direct observations from a time‐in‐motion quality improvement evaluation (process mapping); (b) cross‐sectional patient surveys; and (c) administrative claims. Average ambulatory, inpatient, and total health care time were calculated for specific treatments which differed by antineoplastic type and administration method, including fulvestrant (injection, hormonal), letrozole (oral, hormonal), capecitabine (oral, chemotherapy), and paclitaxel (infusion, chemotherapy). Results Average total time spent on health care ranged from 7% to 10% of all days included within the initial 3 months of treatment, depending on treatment. The greatest time contributions were time spent traveling for care and on inpatient services. Time with providers contributed modestly to total care time. Patients receiving infusion/injection treatments, compared with those receiving oral therapy, spent more time in ambulatory care. Health care time was higher for patients receiving chemotherapeutic agents compared to those receiving hormonal agents. Conclusion Time spent traveling and receiving inpatient care represented a substantial burden to patients with MBC, with variation in time by treatment type and administration method. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Serum N‐Glycome analysis reveals pancreatic cancer disease signatures

xloma.fota13 shared this article with you from Inoreader Serum N‐Glycome analysis reveals pancreatic cancer disease signatures Via Cancer Medicine Serum protein glycosylation differences between pancreatic cancer patients and healthy individuals are discussed with regard to their potential to function as a diagnostic signature. Results were validated in an independent cohort and it was concluded that the serum N‐glycome analysis can serve as a basis for the development of a blood‐based diagnostic test for the detection of pancreatic cancer. Abstract Background &Aims Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer type with loco‐regional spread that makes the tumor surgically unresectable. Novel diagnostic tools are needed to improve detection of PDAC and increase patient survival. In this study we explore serum protein N‐glycan profiles from PDAC patients with regard to their applicability to serve as a disease biomarker panel. Methods Total serum N‐glycome analysis was applied to a discovery set (86 PDAC cases/84 controls) followed by independent validation (26 cases/26 controls) using in‐house collected serum specimens. Protein N‐glycan profiles were obtained using ultrahigh resolution mass spectrometry and included linkage‐specific sialic acid information. N‐glycans were relatively quantified and case‐control classification performance was evaluated based on glycosylation traits such as branching, fucosylation, and sialylation. Results In PDAC patients a higher level of branching (OR 6.19, P‐value 9.21 × 10−11) and (antenna)fucosylation (OR 13.27, P‐value 2.31 × 10−9) of N‐glycans was found. Furthermore, the ratio of α2,6‐ vs α2,3‐linked sialylation was higher in patients compared to healthy controls. A classification model built with three glycosylation traits was used for discovery (AUC 0.88) and independent validation (AUC 0.81), with sensitivity and specificity values of 0.85 and 0.71 for the discovery set and 0.75 and 0.72 for the validation set. Conclusion Serum N‐glycome analysis revealed glycosylation differences that allow classification of PDAC patients from healthy controls. It was demonstrated that glycosylation traits rather than single N‐glycan structures obtained in this clinical glycomics study can serve as a basis for further development of a blood‐based diagnostic test. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Impact of radiotherapy to the primary tumor on the efficacy of pembrolizumab for patients with advanced urothelial cancer: A preliminary study

xloma.fota13 shared this article with you from Inoreader Impact of radiotherapy to the primary tumor on the efficacy of pembrolizumab for patients with advanced urothelial cancer: A preliminary study Via Cancer Medicine Radiotherapy to the primary tumor was significantly associated with favourable therapeutic response and prognosis following pembrolizumab therapy in advanced urothelial cancer patients. Thus, radiotherapy to the primary tumor may enhance the efficacy of pembrolizumab, indicating the possibility that radiotherapy to the primary tumor in combination with pembrolizumab may be a promising therapeutic strategy for urothelial cancer. Abstract Radiotherapy plus immune checkpoint inhibitors can potentially induce synergistic antitumor immune responses. However, little clinical evidence is established regarding their combination therapy. Here, we aimed to assess whether radiotherapy to the primary tumor impacts on the efficacy of pembrolizumab in advanced urothelial cancer. We retrospectively reviewed 98 advanced urothelial cancer patients receiving pembrolizumab in a second‐ or later‐line setting using our multicenter cohort. Patients were categorized according to a history of radiotherapy to the primary tumor: patients previously exposed to radiotherapy to the primary tumor (Radiotherapy group, 17 patients [17%]) and those not (Nonradiotherapy group, 81 patients [83%]). The associations of radiotherapy to the primary tumor with objective response and survival were evaluated. The Radiotherapy group showed a significantly higher objective response ratio than did the Non‐radiotherapy group (65% vs 19%; P  < .001). The Radiotherapy group had a higher progression‐free survival rate compared with the Nonradiotherapy group (52% vs 28% at 12 months; P = .078), but statistical significance was not reached. The Radiotherapy group had a significantly higher overall survival rate compared with the Non‐radiotherapy group (77% vs 50% at 12 months; P = .025). From multivariate analysis, radiotherapy to the primary tumor was an independent predictor for longer overall survival (hazard ratio, 0.31; P = .032) along with Eastern Cooperative Oncology Group performance status ≤1 and the absence of visceral metastasis. Therefore, radiotherapy to the primary tumor may enhance the efficacy of pembrolizumab for patients with advanced urothelial cancer. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Age‐specific prevalence and determinants of depression in long‐term breast cancer survivors compared to female population controls

xloma.fota13 shared this article with you from Inoreader Age‐specific prevalence and determinants of depression in long‐term breast cancer survivors compared to female population controls Via Cancer Medicine Long‐term breast cancer survivors (5‐16 years post‐diagnosis) with recurrence reported significantly higher prevalence of mild/severe depression than disease‐free survivors and controls, but prevalence in disease‐free survivors and controls was comparable. Cancer recurrence, age, education, employment, income, living independently, and BMI were significant determinants of depression in breast cancer survivors. Abstract Background Depression is more prevalent in breast cancer (BC) survivors than in the general population. However, little is known about depression in long‐term survivors. Study objectives were: (1) to compare the age‐specific prevalence of depressive symptoms (a) in BC survivors vs female population controls, (b) in disease‐free BC survivors vs BC survivors with self‐reported recurrence vs controls, and (2) to explore determinants of depression in BC survivors. Methods About 3010 BC survivors (stage I‐III, 5‐16 years post‐diagnosis), and 1005 population controls were recruited in German multi‐regional population‐based studies. Depression was assessed by the Geriatric Depression Scale‐15. Prevalence of mild/severe and severe depression only were estimated via logistic regression, controlling for age and education. Multinomial logistic regression was used to explore determinants of mild and severe depression. Results Compared with population controls, BC survivors were more likely to report mild/severe depression (30.4% vs 23.8%, p = .0003), adjusted for age and education. At all age groups <80 years, prevalence of both mild/severe and severe depression only was significantly higher in BC survivors, while BC survivors ≥80 years reported severe depression less frequently than controls. BC survivors with recurrence reported significantly higher prevalence of mild/severe depression than disease‐free survivors and controls, but prevalence in disease‐free survivors and controls was comparable. Age, income, living independently, recurrence, and BMI were significant determinants of mild depression in BC survivors. Age, education, employment, income, recurrence, and BMI were significant determinants of severe depression. Conclusions Long‐term BC survivors <80 years report significantly higher prevalence of depressive symptoms than controls, which might be explained by recurrence and individual factors. The findings suggest that depression in BC survivors is common, and even more after BC recurrence. Clinicians should routinize screening and normalize referral to psychological care. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Molecular and immunological associations of elevated serum lactate dehydrogenase in metastatic melanoma patients: A fresh look at an old biomarker

xloma.fota13 shared this article with you from Inoreader Molecular and immunological associations of elevated serum lactate dehydrogenase in metastatic melanoma patients: A fresh look at an old biomarker Via Cancer Medicine The association between elevated serum lactate dehydrogenase (sLDH) and poor prognosis in metastatic melanoma patients is well‐established but poorly understood. Our multi‐omics analysis of multiple cohorts of patients with melanoma metastases identified no significant intratumoral molecular, immunological, or metabolic associations with sLDH, supporting that sLDH serves at least partially as a surrogate of tumor burden but not of adverse tumor features. ABSTRACT Elevated serum lactate dehydrogenase (sLDH) is associated with poor clinical outcomes in patients with stage IV metastatic melanoma (MM). It is currently unknown if sLDH elevation correlates with distinct molecular, metabolic, or immune features of melanoma metastases. The identification of such features may identify rational therapeutic strategies for patients with elevated sLDH. Thus, we obtained sLDH levels for melanoma patients with metastases who had undergone molecular and/or immune profiling. Our analysis of multi‐omics data from independent cohorts of melanoma metastases showed that elevated sLDH was not significantly associated with differences in immune cell infiltrate, point mutations, DNA copy number variations, promoter methylation, RNA expression, or protein expression in melanoma metastases. The only significant association observed for elevated sLDH was with the number of metastatic sites of disease. Our data support that sLDH correlates with disease burden, but not specific molecular or immunological phenotypes, in metastatic melanoma. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.