The effect of postmastectomy radiotherapy in node-positive triple-negative breast cancer

Cancer shared this article with you from Inoreader The effect of postmastectomy radiotherapy in node-positive triple-negative breast cancer Via Latest Results for BMC Cancer Abstract Background The value of postmastectomy radiotherapy (PMRT) for pathological node-positive triple-negative breast cancers (TNBC) remains debatable. The aim of this population-based retrospective study was to evaluate the effect of PMRT on survival outcomes in this population. Methods Patients diagnosed with stage T1-4N1-N3M0 TNBC between 2010 and 2014 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. We used univariate and multivariate Cox regression hazards method to determine the independent prognostic factors associated with 3-year breast cancer-specific survival (BCSS). The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. Results Of the 4398 patients included in this study, 2649 (60.2%) received PMRT. Younger age, black ethnicity, and advanced tumor (T) and nodal (N) stage were the independent predictors associated with PMRT receipt (all P < 0.05). Patients who received PMRT showed better 3-year BCSS (OR = 0.720, 95% CI = 0.642–0.808, P < 0.001) than those that did not. The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. The results showed that PMRT was associated with better 3-year BCSS in patients with stage T3–4N1 (P = 0.042), T1-4N2 (P < 0.001), and T1-4N3 (P < 0.001), while comparable 3-year BCSS was found between the PMRT and non-PMRT cohorts with T1–2N1 disease (P = 0.191). Conclusions Radiotherapy achieved better 3-year BCSS in TNBC patients with stage T3–4N1 and T1-4N2–3 disease. However, no survival benefit was found with the addition of PMRT in patients with T1–2N1 TNBC. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Analysis of the expression and potential molecular mechanism of interleukin-1 receptor antagonist (IL1RN) in papillary thyroid cancer via bioinformatics methods

Cancer shared this article with you from Inoreader Analysis of the expression and potential molecular mechanism of interleukin-1 receptor antagonist (IL1RN) in papillary thyroid cancer via bioinformatics methods Via Latest Results for BMC Cancer Abstract Background Interleukin-1 receptor antagonist (IL1RN) has been reported as a biomarker of many cancers. However, the biological function of IL1RN in papillary thyroid carcinoma (PTC) remains undetermined. Methods We obtained IL1RN expression data from The Cancer Genome Atlas (TCGA) database. Enrichment analysis of coexpressed genes and IL1RN methylation analysis were performed via LinkedOmics. The correlations between IL1RN and immune infiltrates were investigated via ESTIMATE, TIMER and TISIDB. We analyzed the association of IL1RN expression with pancancer overall survival (OS) via Gene Expression Profiling Interactive Analysis (GEPIA). Results IL1RN showed higher expression levels and lower methylation levels in PTC tissues than in normal tissues. Higher IL1RN expression was significantly associated with shorter progression-free survival (PFS), advanced tumor stage, tumor metastasis, increased incidence of BRAF mutations, and decreased incidence of N-RAS and H-RAS mutations. Genes coexpressed with IL1RN participate primarily in immune-related pathways. IL1RN expression positively correlated with immune infiltration, tumor progression and poor OS for all cancers. Conclusions IL1RN is a good prognostic and diagnostic biomarker for PTC. IL1RN may promote thyroid cancer progression through immune-related pathways. Methylation may act as an upstream regulator of IL1RN expression and biological function. Additionally, IL1RN was shown to have broad prognostic value in a pancancer cohort. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Benefit of dosimetry distribution for patients with multiple brain metastases from non-small cell lung cancer by a Cyberknife stereotactic radiosurgery (SRS) system

Cancer shared this article with you from Inoreader Benefit of dosimetry distribution for patients with multiple brain metastases from non-small cell lung cancer by a Cyberknife stereotactic radiosurgery (SRS) system Via Latest Results for BMC Cancer Abstract Background In order to obtain a high dose conformal index of tumor and steep dose fall-off in healthy tissues for brain metastasis stereotactic radiosurgery (SRS), the aim of this study was to investigate SRS planning optimization by comparing one multiple-lesions plan (MLP) with multiple single-lesion plans (SLPs) for patients with multiple brain metastases using the Cyberknife (CK) system. Methods Fifty non-small cell lung cancer (NSCLC) patients (28 males and 22 females) with 2–4 brain metastases, inter-tumour distances less than 3 cm, were retrospectively replanned with the original prescription dose (12–32 Gy) in the original fractions (1–3). Two different clinical CK SRS plans (SLPs and MLP) were generated for the same patients with the same collimator and prescription isodose line (62–68%) by the CK Multiplan System. Both SLPs and MLP were able to achieve > 95% PTV volume covered prescription dose and met the Timmerman 2011 organs at risk (brainstem, optic nerve and pituitary) constraints. Results Compared with those in the SLPs, the maximum dose (Dmax) and mean dose (Dmean) of brainstem in the MLP were reduced 0.22–3.13% (2.62%) and 2.71–12.56% (5.57%), respectively, all P < 0.05. Meanwhile, the volumes of the whole brain minus the tumors that received a single dose equivalent of 8–16 Gy (V8Gy-V16Gy) were effectively reduced in the MLP. The treatment time parameters, the total number of beams and monitor units, of the MLP were reduced by 3.31 and 1.47% (P < 0.05), respectively. Although there were a few differences in the conformity index (CI) and homogeneity index (HI) between the two treatment plans, the differences were not statistically significant (P = 2.94 and 1.08 > 0.05). Conclusion One multiple-lesions plan for brain metastases could achieve higher precision in the target and lower doses in healthy tissue while shortening the treatment time and improving the treatment efficiency over multiple single-lesion plans. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Patients with pretreatment leukoencephalopathy and older patients have more cognitive decline after whole brain radiotherapy

Cancer shared this article with you from Inoreader Patients with pretreatment leukoencephalopathy and older patients have more cognitive decline after whole brain radiotherapy Via Latest Results for Radiation Oncology Abstract Purpose To investigate predictors of cognitive decline after whole brain radiotherapy (WBRT) for brain metastases. Methods A secondary analysis of a phase 2 clinical trial was conducted in patients who received stereotactic radiosurgery for 1–10 brain metastases and WBRT (NCT01046123). The Montreal Cognitive Assessment (MoCA) was performed at baseline and every 3 months after WBRT. Baseline T2-weighted fluid attenuation inversion recovery magnetic resonance imaging was independently assessed by two neuroradiologists for the presence of white matter hyperintensities (WMH) using the Fazekas visual rating scale. WMH were also manually segmented for volumetric analysis. Univariable and multivariable logistic regression were used to test the association between baseline variables and MoCA score decline. Results Forty-six patients survived ≥ 3 months after treatment. Age (OR 1.12 (1.04–1.21), p < 0.01), baseline WMH volume (OR 1.20, 95% CI 1.06–1.52, p = 0.02) and baseline Fazekas score ≥ 3/6 (OR 6.4, 95% CI 1.7–24.7, p < 0.01) were predictive of MoCA score decline. In multivariable analysis, age was the only significant predictor of MoCA decline. However, all three patients with pre-treatment leukoencephalopathy (Fazekas score = 6/6) had notable adverse outcomes due to cognitive impairment: one required full-time home nursing support and two were institutionalized. Conclusion A greater decline in cognition after WBRT was observed in older patients and patients with a higher baseline WMH burden. Although this study is small and hypothesis-generating, we propose that radiation oncologists should exercise caution in prescribing WBRT if leukoencephalopathy is present on pre-treatment imaging. Trial Registration: clinicaltrials.gov identifier NCT01046123. First posted January 11, 2010. https://clinicaltrials.gov/ct2/show/NCT01046123 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Short-term mortality risks among patients with non-metastatic bladder cancer

Cancer shared this article with you from Inoreader Short-term mortality risks among patients with non-metastatic bladder cancer Via Latest Results for BMC Cancer Abstract Background Population-based analysis for the short-term non-bladder cancer related mortality among patients with non-metastatic bladder cancer is currently lacking. The objective of the current study was to assess and quantify cause of death after bladder cancer diagnosis. Methods The custom Surveillance, Epidemiology, and End Results (SEER) dataset for standardized mortality ratios (SMRs) was utilized to identify 24,074 patients who were diagnosed with nonmetastatic (M0) bladder cancer from 2014 to 2015. SMRs for causes of death were calculated. Risk factors for bladder cancer-specific mortality, competing mortality, second-cancer mortality, and noncancer mortality were determined using either multivariable Cox or competing risk regression models. Results Among all the 4179 (17.4%) deaths occurred during the follow-up period, almost half of them (44.2%) were attributed to non-bladder cancer cause, including second non-bladder cancer (10%) and other non-cancer causes (34.2%). The most common noncancer causes of death were heart diseases followed by chronic obstructive pulmonary disease. Patients had a higher risk of death from second malignancies (SMR, 1.59; 95% CI, 1.47–1.74) compared with death from first malignancies in the US general population, and also had higher risks of death from heart diseases (SMR, 1.29; 95% CI, 1.18–1.40) and chronic obstructive pulmonary disease (SMR, 1.52; 95% CI, 1.29–1.79) compared with the US general population. Additionally, some risk factors for competing second malignancies or noncancer mortality were determined, such as age, gender, marital status and treatment modalities. Conclusions Death from non-bladder cancer cause contributed to almost half of all deaths in bladder cancer survivors during the short-term follow-up period. These findings can inform medical management and assist clinicians in counseling those survivors regarding their short-term health risks. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Predictive and prognostic role of tumour-infiltrating lymphocytes in breast cancer patients with different molecular subtypes: a meta-analysis

Cancer shared this article with you from Inoreader Predictive and prognostic role of tumour-infiltrating lymphocytes in breast cancer patients with different molecular subtypes: a meta-analysis Via Latest Results for BMC Cancer Abstract Background Whether tumour-infiltrating lymphocytes (TILs) play different roles in different molecular subtypes of breast cancer remains unknown. Additionally, their prognostic and predictive value in different molecular subtypes of breast cancer is still controversial. The aim of our meta-analysis was to assess the prognostic and predictive value of TILs in different molecular subtypes of breast cancer by summarizing all relevant studies performing multivariate analysis. Methods PubMed, Embase, EBSCO, ScienceDirect, the Cochrane Database and Web of Science were comprehensively searched (until March 2020). Hazard ratios (HRs), odds ratios (ORs) and their 95% confidence intervals (CIs) were used as effect measures to perform our meta-analysis. A random effect model was used. Stata software, version 15 (2017) (StataCorp, College Station, TX, USA) was used to perform the statistical analysis. Results Thirty-three studies including 18,170 eligible breast cancer patients were analysed. The meta-analysis showed that high TIL expression was significantly associated with increased pathological complete response (pCR) rates after neoadjuvant chemotherapy in patients with the HER2-enriched molecular subtype (OR = 1.137, 95% CI [1.061 ~ 1.218], p < 0.001) and triple-negative breast cancer (TNBC) subtype (OR = 1.120, 95% CI [1.061 ~ 1.182], p < 0.001). However, high TIL expression was not significantly associated with high pCR rates after neoadjuvant chemotherapy in patients with the luminal molecular subtype of breast cancer (OR = 1.154, 95% CI [0.789 ~ 1.690], p = 0.460). We carried out a meta-analysis on the HRs of overall survival (OS) and disease-free survival (DFS) to assess the prognostic value of TILs in breast cancer with different molecular subtypes more deeply. Our meta-analysis con firmed that high TILs were associated with significantly improved DFS in patients with the HER2-enriched molecular subtype [HR = 0.940, 95% CI (0.903 ~ 0.979), p = 0.003] and TNBC molecular subtype [HR = 0.907, 95% CI (0.862 ~ 0.954), p < 0.001]. However, high TILs were not associated with significantly better DFS in patients with the luminal molecular subtype of breast cancer [HR = 0.998, 95% CI (0.977 ~ 1.019), p = 0.840]. Furthermore, the results confirmed that high TILs were significantly related to better OS in patients with the HER2-enriched molecular subtype [HR = 0.910, 95% CI (0.866 ~ 0.957), p < 0.001] and TNBC molecular subtype [HR = 0.869, 95% CI (0.836 ~ 0.904), p < 0.001]. Conversely, the summarized results indicated that high TILs were significantly associated with poor OS in patients with the luminal molecular subtype of breast cancer [HR = 1.077, 95% CI (1.016 ~ 1.141), p = 0.012]. Conclusions Our meta-analysis confirms that high TILs are associated with favourable survival and predicts pCR in breast cancer patients with the TNBC and HER2-enriched molecular subtypes. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Prediction of mortality in metastatic colorectal cancer in a real-life population: a multicenter explorative analysis

Cancer shared this article with you from Inoreader Prediction of mortality in metastatic colorectal cancer in a real-life population: a multicenter explorative analysis Via Latest Results for BMC Cancer Abstract Background Metastatic colorectal cancer (mCRC) remains a lethal disease. Survival, however, is increasing due to a growing number of treatment options. Yet due to the number of prognostic factors and their interactions, prediction of mortality is difficult. The aim of this study is to provide a clinical model supporting prognostication of mCRC mortality in daily practice. Methods Data from 1104 patients with mCRC in three prospective cancer datasets were used to construct and validate Cox models. Input factors for stepwise backward method variable selection were sex, RAS/BRAF-status, microsatellite status, treatment type (no treatment, systemic treatment with or without resection of metastasis), tumor load, location of primary tumor, metastatic patterns and synchronous or metachronous disease. The final prognostic model for prediction of survival at two and 3 years was validated via bootstrapping to obtain calibration and discrimination C-indices and dynamic time dependent AUC. Results Age, sidedness, number of organs with metastases, lung as only site of metastasis, BRAF mutation status and treatment type were selected for the model. Treatment type had the most prominent influence on survival (resection of metastasis HR 0.26, CI 0.21–0.32; any treatment vs no treatment HR 0.31, CI 0.21–0.32), followed by BRAF mutational status (HR 2.58, CI 1.19–1.59). Validation showed high accuracy with C-indices of 72.2 and 71.4%, and dynamic time dependent AUC's of 76.7 ± 1.53% (both at 2 or 3 years), respectively. Conclusion The mCRC mortality prediction model is well calibrated and internally valid. It has the potential to support both, clinical prognostication for treatment decisions and patient communication. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Toluidine blue versus frozen section for assessment of mucosal tumor margins in oral squamous cell carcinoma

Cancer shared this article with you from Inoreader Toluidine blue versus frozen section for assessment of mucosal tumor margins in oral squamous cell carcinoma Via Latest Results for BMC Cancer Abstract Background When the resected specimen is sent for intraoperative margin assessment, all margins are grossly checked, and selected margins undergo a frozen section (FS) examination. Therefore, there is a possibility of sampling error. This study evaluated the effectiveness of using toluidine blue (TB) as an intraoperative triage screening tool to detect positive mucosal margins of the resected specimens of oral squamous cell carcinoma (OSCC) and serve as a guide for FS sampling. Methods Surgical samples of 30 consecutive patients with biopsy-proven OSCC were included in the study. A total of 140 mucosal margins were analyzed intraoperatively by TB and FS, the results were compared with the final histopathology. Results Of the 140 examined mucosal tumor margins, 14 stained positives with TB, six were true-positives, eight were false-positives, and there were no false-negatives, as confirmed by final histopathology of the same margins. The diagnostic performance measures were sensitivity 100.0%; specificity 94.0%; positive predictive value (PPV) 42.9%; negative predictive value (NPV) 100.0%; and accuracy 94.3% (95% CI: 89.0–97.5%). For FS, there were three true-positives, three false-negatives, and no false-positives. The diagnostic performance measures were sensitivity 50.0%; specificity 100.0%; PPV 100.0%; NPV 97.8%; and accuracy 97.9% (95% CI: 93.9–99.6%). Conclusion TB is less specific but more sensitive than FS for detecting positive mucosal margins of resected OSCC. Screening the tumor mucosal margins with TB before FS sampling may help identify more tumor-bearing margins. Trial registration This trial was registered at ClinicalTrials.gov. Registration number: NCT03554967. Registration date: June 13, 2018. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Concurrent Dexamethasone Limits the Clinical Benefit of Immune Checkpoint Blockade in Glioblastoma

Cancer shared this article with you from Inoreader Concurrent Dexamethasone Limits the Clinical Benefit of Immune Checkpoint Blockade in Glioblastoma Via Clinical Cancer Research Online First Articles Purpose: Dexamethasone, a uniquely potent corticosteroid, is frequently administered to patients with brain tumors to decrease tumor-associated edema, but limited data exist describing how dexamethasone affects the immune system systemically and intratumorally in patients with glioblastoma (GBM), particularly in the context of immunotherapy. Experimental Design: We evaluated the dose-dependent effects of dexamethasone when administered with programmed cell death 1 (PD-1) blockade and/or radiotherapy in immunocompetent C57BL/6 mice with syngeneic GL261 and CT-2A GBM tumors. Clinically, the effect of dexamethasone on survival was evaluated in 181 patients with isocitrate dehydrogenase (IDH) wild-type GBM treated with PD-(L)1 blockade, with adjustment for relevant prognostic factors. Results: Despite the inherent responsiveness of GL261 to immune checkpoint blockade, concurrent dexamethasone administration with anti–PD-1 therapy reduced survival in a dose-dependent m anner. Concurrent dexamethasone also abrogated survival following anti–PD-1 therapy with or without radiotherapy in immune-resistant CT-2A models. Dexamethasone decreased T-lymphocyte numbers by increasing apoptosis, in addition to decreasing lymphocyte functional capacity. Myeloid and natural killer cell populations were also generally reduced by dexamethasone. Thus, dexamethasone appears to negatively affect both adaptive and innate immune responses. As a clinical correlate, a retrospective analysis of 181 consecutive patients with IDH wild-type GBM treated with PD-(L)1 blockade revealed poorer survival among those on baseline dexamethasone. Upon multivariable adjustment with relevant prognostic factors, baseline dexamethasone administration was the strongest predictor of poor survival [reference, no dexamethasone; <2 mg HR, 2.16; 95% confidence interval (CI), 1.30–3.68; P = 0.003 and ≥2 mg HR, 1.97; 95% CI, 1.23–3.16; P = 0.005]. Conclusions: Our pre clinical and clinical data indicate that concurrent dexamethasone therapy may be detrimental to immunotherapeutic approaches for patients with GBM. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

FDA Approval Summary: Selpercatinib for the Treatment of Lung and Thyroid cancers with RET Gene Mutations or Fusions

Cancer shared this article with you from Inoreader FDA Approval Summary: Selpercatinib for the Treatment of Lung and Thyroid cancers with RET Gene Mutations or Fusions Via Clinical Cancer Research Online First Articles On May 8, 2020, the Food and Drug Administration granted accelerated approval to selpercatinib for 1) adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC), 2) adult and pediatric patients ≥12 years of age with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, and 3) adult and pediatric patients ≥12 years of age with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). Approval was granted based on the clinically important effects on overall response rate (ORR) with prolonged duration of responses observed in a multicenter, open-label, multi-cohort clinical trial (LIBRETTO-001, NCT03157128) in patients whose tumors had RET alterations. ORRs within the approved patient populations ranged from 64% (95% CI: 54, 73) in prior platinum treated RET fusion-positive NSCLC t o 100% (95% CI: 63, 100) in systemic therapy naïve RET fusion-positive thyroid cancer, with the majority of responders across indications demonstrating responses of at least 6 months. The product label includes warnings and precautions for hepatotoxicity, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, risk of impaired wound healing, and embryo-fetal toxicity. This is the first approval of a drug specifically for patients with RET alterations globally. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Darolutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer

Cancer shared this article with you from Inoreader Darolutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer Via Latest Results for Targeted Oncology Abstract Oral darolutamide (Nubeqa™) is a novel second-generation, nonsteroidal, selective androgen receptor (AR) inhibitor indicated for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). In the pivotal multinational, phase 3 ARAMIS trial in men with nmCRPC, relative to placebo plus ongoing androgen deprivation therapy (ADT), darolutamide (+ ADT) significantly prolonged metastasis-free survival (MFS) at the time of the primary analysis and overall survival (OS) at the time of the final OS analysis and was generally well tolerated in extended follow-up. Albeit long-term data from the real-world setting are required to fully define the safety profile of darolutamide, current evidence from the final ARAMIS analysis indicates that darolutamide has a low propensity for CNS-related adverse events (AEs) associated with other currently approved second-generation AR inhibitors. Given the efficacy and safety evidence from the final ARAMIS analysis and the key role of second-generation AR inhibitors in the management of nmCRPC, darolutamide + ADT represents an important emerging option for the treatment of men with nmCRPC who are at high risk of developing metastatic prostate cancer. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.