Following neoadjuvant chemotherapy (NAC), the optimal strategies for postmastectomy radiotherapy (PMRT) and regional nodal irradiation (RNI) after breast-conserving surgery (BCS) are controversial. ...In this analysis, we evaluate the impact of these radiotherapy (RT) approaches for women with clinically node-positive breast cancer treated with NAC in the National Cancer Database (NCDB).
Women with cT1–3 cN1 M0 breast cancer treated with NAC were divided into four cohorts by surgery Mastectomy (Mast) versus BCS and post-chemotherapy pathologic nodal status (ypN0 versus ypN+). Overall survival (OS) was estimated using the Kaplan–Meier method and RT approaches were analyzed using the log-rank test, multivariate Cox models, and propensity score-matched analyses.
From 2003 to 2011, 15 315 cases were identified including 3040 Mast-ypN0, 7243 Mast-ypN+, 2070 BCS-ypN0, and 2962 BCS-ypN+ patients. On univariate analysis, PMRT was associated with improved OS for both Mast-ypN0 (P = 0.019) and Mast-ypN+ (P < 0.001) patients. On multivariate analyses adjusted for factors including age, comorbidity score, cT stage, in-breast pathologic complete response, axillary surgery, ypN stage, estrogen receptor status and hormone therapy, PMRT remained independently associated with improved OS among Mast-ypN0 hazard ratio (HR) = 0.729, 95% confidence interval (CI) 0.566–0.939, P = 0.015 and Mast-ypN+ patients (HR = 0.772, 95% CI 0.689–0.866, P < 0.001). No differences in OS were observed with the addition of RNI to breast RT for BCS-ypN0 or BCS-ypN+ patients. Propensity score-matched analyses demonstrated identical patterns of significance. On subset analysis, OS was improved with PMRT in each pathologic nodal subgroup (ypN0, ypN1, and ypN2-3) (all P < 0.05).
In the largest reported analysis of RT for cN1 patients treated with NAC, PMRT was associated with improved OS for all pathologic nodal subgroups. No OS differences were observed with the addition of RNI to breast RT.
•Superiority of SBRT or surgery for early-stage NSCLC is a heated debate.•Operability is a key prognostic factor that impacts OS, regardless of treatment modality.•Most retrospective data comparing ...these treatments fails to acknowledge operability.•Retrospective work should include discussion of operability to avoid confounding.
Patients receiving stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) are typically inoperable, in concordance with guidelines that advocate surgical resection as preferred treatment for operable patients. This differential treatment allocation complicates retrospective comparisons of surgery with SBRT by introducing the potential for confounding by operability.
PubMed was queried for manuscripts reporting primary data from retrospective comparisons of overall survival (OS) between patients undergoing surgery versus SBRT for early-stage NSCLC. Each manuscript was categorized for two outcomes: (1) whether treatment allocation was based on a determination of patient operability, and (2) whether a direct OS comparison between operable SBRT patients and surgically treated patients was included. Associations with variables of interest were measured with statistical significance prespecified at p < 0.10.
From 3,072 manuscripts identified in our query, sixty-one analyses met screening criteria. Twenty-one (34 %) reported operability status influencing treatment allocation. These were more likely to be published in journals with a surgical focus (52 vs 20 %) and impact factor < 5 (81 vs 58 %), and to contain cohorts from institutional datasets (81 vs 55 %), and to have a radiation oncologist as first (43 vs 25 %) or senior (43 vs 28 %) author. Seven (11 %) manuscripts featured a direct OS comparison between SBRT and surgery.
Nearly-two-thirds of peer-reviewed retrospective studies that have compared OS between surgery and SBRT for early-stage NSCLC lack information on patient operability status, and nearly 90% lack a direct comparison between operable SBRT patients and those receiving surgery.
The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management ...challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.A 54-year-old man with a former 15-pack-year smoking history presents with cough and dyspnea. Initial work-up with imaging demonstrates a right suprahilar mass measuring 4.7 cm as well as several enlarged hilar and ipsilateral mediastinal lymph nodes. Bronchoscopy with biopsy reveals adenocarcinoma consistent with a lung primary. Staging with positron emission tomography/computed tomography (PET/CT) reidentifies the primary mass and lymph nodes and shows several PET-avid bone metastases. Brain magnetic resonance imaging (MRI) demonstrates a 1.6-cm right parietal mass with mild vasogenic edema and four additional brain metastases measuring 4 to 9 mm in size. Molecular testing is positive for an anaplastic lymphoma kinase (ALK) gene rearrangement using fluorescence in situ hybridization and negative for EGFR, ROS1, RET, BRAF, KRAS, and other oncogenes. The patient denies any neurologic symptoms and has no significant findings on neurologic exam. He is referred to you for management options for newly diagnosed stage IV (T2aN2M1b) lung adenocarcinoma.
The addition of bevacizumab to established therapies for metastatic and locally advanced cervical cancer is an area of evolving research and a potential strategy toward improving historically ...suboptimal outcomes for women with advanced disease. Bevacizumab, when added to first-line chemotherapy, has now been shown to improve overall survival among women with metastatic cervical cancer, and recent Phase II data suggests it is safe and effective for patients with locally advanced disease treated with curative intent. Here we review the rationale and current evidence for bevacizumab in clinical practice, with an emphasis on the emerging role of bevacizumab in the treatment of metastatic and locally advanced cervical cancer.
There is growing interest in the role of local therapies, including external beam radiotherapy (RT), for men with metastatic prostate cancer (mPCa). We used the National Cancer Database (NCDB) to ...evaluate the overall survival (OS) of men with mPCa treated with androgen deprivation (ADT) with and without prostate RT.
The NCDB was queried for men with newly diagnosed mPCa, all treated with ADT, with complete datasets for RT, surgery, prostate-specific antigen (PSA) level, Gleason score, and Charlson-Deyo comorbidity score. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses.
From 2004 to 2012, 6,382 men with mPCa were identified, including 538 (8.4%) receiving prostate RT. At a median follow-up of 5.1 years, the addition of prostate RT to ADT was associated with improved OS on univariate (P < .001) and multivariate analysis (hazard ratio, 0.624; 95% CI, 0.551 to 0.706; P < .001) adjusted for age, year, race, comorbidity score, PSA level, Gleason score, T stage, N stage, chemotherapy administration, treating facility, and insurance status. Propensity score analysis with matched baseline characteristics demonstrated superior median (55 v 37 months) and 5-year OS (49% v 33%) with prostate RT plus ADT compared with ADT alone (P < .001). Landmark analyses limited to long-term survivors of ≥1, ≥3, and ≥5 years demonstrated improved OS with prostate RT in all subsets (all P < .05). Secondary analyses comparing the survival outcomes for patients treated with therapeutic dose RT plus ADT versus prostatectomy plus ADT during the same time interval demonstrated no significant differences in OS, whereas both therapies were superior to ADT alone.
In this large contemporary analysis, men with mPCa receiving prostate RT and ADT lived substantially longer than men treated with ADT alone. Prospective trials evaluating local therapies for mPCa are warranted.
Preclinical studies suggest enhanced anti-tumor activity with combined radioimmunotherapy. We hypothesized that radiation (RT) + immunotherapy would associate with improved overall survival (OS) ...compared to immunotherapy or chemotherapy alone for patients with newly diagnosed metastatic non-small-cell lung cancer (NSCLC).
The National Cancer Database was queried for patients with stage IV NSCLC receiving chemotherapy or immunotherapy from 2013 to 2014. RT modality was classified as stereotactic radiotherapy (SRT) to intra- and/or extracranial sites or non-SRT external beam RT (EBRT). OS was analyzed using the Kaplan-Meier method and Cox proportional hazards models.
In total, 44,498 patients were included (13% immunotherapy, 46.8% EBRT, and 4.7% SRT). On multivariate analysis, immunotherapy (hazard ratio HR:0.81, 95% confidence interval CI:0.78-0.83) and SRT (HR:0.78, 95%CI:0.70-0.78) independently associated with improved OS; however, the interaction term for SRT + immunotherapy was insignificant (p = 0.89). For immunotherapy patients, the median OS for no RT, EBRT, and SRT was 14.5, 10.9, and 18.2 months, respectively (p < 0.0001), and EBRT (HR:1.37, 95%CI:1.29-1.46) and SRT (HR:0.78, 95%CI:0.66-0.93) associated with OS on multivariate analysis. In the SRT subset, median OS for immunotherapy and chemotherapy was 18.2 and 14.3 months, respectively (p = 0.004), with immunotherapy (HR:0.82, 95%CI:0.69-0.98) associating with OS on multivariate analysis. Furthermore, for patients receiving SRT, biologically effective dose (BED) > 60 Gy was independently associated with improved OS (HR:0.79, 95%CI:0.70-0.90, p < 0.0001) on multivariate analysis with a significant interaction between BED and systemic treatment (p = 0.008).
Treatment with SRT associated with improved OS for patients with metastatic NSCLC irrespective of systemic treatment. The high survival for patients receiving SRT + immunotherapy strongly argues for evaluation in randomized trials.
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