N.H. Lester-Coll

Management of Brain Metastases in Tyrosine Kinase Inhibitor–Naïve Epidermal Growth Factor Receptor–Mutant Non–Small-Cell Lung Cancer: A Retrospective Multi-Institutional Analysis

Purpose Stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT), and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are treatment options for brain metastases in patients with EGFR-mutant non-small-cell lung cancer (NSCLC). This multi-institutional analysis sought to determine the optimal management of patients with EGFR-mutant NSCLC who develop brain metastases and have not received EGFR-TKI. Materials and Methods A total of 351 patients from six institutions with EGFR-mutant NSCLC developed brain metastases and met inclusion criteria for the study. Exclusion criteria included prior EGFR-TKI use, EGFR-TKI resistance mutation, failure to receive EGFR-TKI after WBRT/SRS, or insufficient follow-up. Patients were treated with SRS followed by EGFR-TKI, WBRT followed by EGFR-TKI, or EGFR-TKI followed by SRS or WBRT at intracranial progression. Overall survival (OS) and intracranial progression-free survival were measured from the date of brain metastases. Results The median OS for the SRS (n = 100), WBRT (n = 120), and EGFR-TKI (n = 131) cohorts was 46, 30, and 25 months, respectively ( P < .001). On multivariable analysis, SRS versus EGFR-TKI, WBRT versus EGFR-TKI, age, performance status, EGFR exon 19 mutation, and absence of extracranial metastases were associated with improved OS. Although the SRS and EGFR-TKI cohorts shared similar prognostic features, the WBRT cohort was more likely to have a less favorable prognosis ( P = .001). Conclusion This multi-institutional analysis demonstrated that the use of upfront EGFR-TKI, and deferral of radiotherapy, is associated with inferior OS in patients with EGFR-mutant NSCLC who develop brain metastases. SRS followed by EGFR-TKI resulted in the longest OS and allowed patients to avoid the potential neurocognitive sequelae of WBRT. A prospective, multi-institutional randomized trial of SRS followed by EGFR-TKI versus EGFR-TKI followed by SRS at intracranial progression is urgently needed.

Role of Chemoradiotherapy in Elderly Patients With Limited-Stage Small-Cell Lung Cancer

Purpose To investigate outcomes for elderly patients treated with chemotherapy (CT) alone versus chemoradiotherapy (CRT) in the modern era by using a large national database. Patients and Methods Elderly patients (age ≥ 70 years) with limited-stage small-cell lung cancer clinical stage I to III who received CT or CRT were identified in the National Cancer Data Base between 2003 and 2011. Hierarchical mixed-effects logistic regression with clustering by reporting facility was performed to identify factors associated with treatment selection. Overall survival (OS) of patients receiving CT versus CRT was compared by using the log-rank test, Cox proportional hazards regression, and propensity score matching. Results A total of 8,637 patients were identified, among whom 3,775 (43.7%) received CT and 4,862 (56.3%) received CRT. The odds of receiving CRT decreased with increasing age, clinical stage III disease, female sex, and the presence of medical comorbidities (all P < .01). Use of CRT was associated with increased OS compared with CT on univariable and multivariable analysis (median OS, 15.6 v 9.3 months; 3-year OS, 22.0% v 6.3%; log-rank P < .001; Cox P < .001). Propensity score matching identified a matched cohort of 6,856 patients and confirmed a survival benefit associated with CRT (hazard ratio, 0.52; 95% CI, 0.50 to 0.55; P < .001). Subset analysis of CRT treatment sequence showed that patients alive 4 months after diagnosis derived a survival benefit with concurrent CRT over sequential CRT (median OS, 17.0 v 15.4 months; log-rank P = .01). Conclusion In elderly patients with limited-stage small-cell lung cancer, modern CRT appears to confer an additional OS advantage beyond that achieved with CT alone in a large population-based cohort. Our findings suggest that CRT should be the preferred strategy in elderly patients who are expected to tolerate the toxicities of the combined approach.

Increase in the use of lung stereotactic body radiotherapy without a preceding biopsy in the United States

BACKGROUND Stereotactic body radiotherapy (SBRT) is an efficacious treatment for early stage non-small cell lung cancer (NSCLC). Patients with clinically suspected NSCLC may have medical comorbidities that increase biopsy risks, making them more likely to receive SBRT without biopsy. This study characterizes the pervasiveness of this management approach nationally. METHODS Patients with stage I NSCLC who received SBRT from 2003 to 2011 were identified within National Cancer Database. Changes in the proportion treated without biopsy were compared by year of diagnosis using binomial logistic regression. Demographics were compared between patients with and without biopsy with Chi-square and t-tests. Multivariate logistic regression was used to determine factors independently associated with SBRT delivery without biopsy. RESULTS We identified 6960 patients. Most had biopsy before SBRT (95.5%). Over time the proportion treated without biopsy increased (OR 1.11, p=0.038). Univariate comparisons demonstrated that older, medically inoperable patients treated at academic centers located in the New England or Pacific regions were less likely to have biopsy before SBRT. Facility type and location (p<0.001), medical inoperability (p<0.001), and smaller tumor size (p=0.013) were associated with odds of SBRT without biopsy in multivariate analyses. A trend toward increased use of SBRT with a biopsy with later year of diagnosis (p=0.093) was observed in multivariate analysis. CONCLUSIONS The percentage of patients nationally undergoing SBRT without biopsy has increased over time. The reasons for this trend and ramifications of this approach on cost-effectiveness of care must be studied.

Addition of radiotherapy to adjuvant chemotherapy is associated with improved overall survival in resected pancreatic adenocarcinoma: An analysis of the National Cancer Data Base.

The optimal treatment for resected pancreatic cancer is controversial because direct comparisons of adjuvant chemotherapy (CT) alone and chemotherapy and radiotherapy (CRT) are limited. This study assessed outcomes of CT versus CRT in a national cohort to provide a modern estimate of comparative effectiveness.

Death from high-risk prostate cancer versus cardiovascular mortality with hormonal therapy: a decision analysis.

Randomized trials have demonstrated improved survival when hormonal therapy (HT) is added to radiation therapy (RT) for high‐risk prostate cancer. However, it is still unknown whether men who have a history of myocardial infarction (MI) or MI risk factors achieve a superior outcome from HT.

The evolving role of adjuvant radiotherapy for elderly women with early-stage breast cancer

Elderly patients with early‐stage breast cancer (ESBC) derive a local control benefit from radiotherapy (RT) after lumpectomy, without any apparent effect on overall survival. Therefore, the use of RT is controversial. In the current study, the authors characterized updated trends in RT for elderly patients with estrogen receptor (ER)‐positive ESBC.

Adjuvant chemotherapy and overall survival in adult medulloblastoma

Background Although chemotherapy is used routinely in pediatric medulloblastoma (MB) patients, its benefit for adult MB is unclear. We evaluated the survival impact of adjuvant chemotherapy in adult MB. Methods Using the National Cancer Data Base, we identified patients aged 18 years and older who were diagnosed with MB in 2004-2012 and underwent surgical resection and adjuvant craniospinal irradiation (CSI). Patients were divided into those who received adjuvant CSI and chemotherapy (CRT) or CSI alone (RT). Predictors of CRT compared with RT were evaluated with univariable and multivariable logistic regression. Survival analysis was limited to patients receiving CSI doses between 23 and 36 Gy. Overall survival (OS) was evaluated using the Kaplan-Meier estimator, log-rank test, multivariable Cox proportional hazards modeling, and propensity score matching. Results Of the 751 patients included, 520 (69.2%) received CRT, and 231 (30.8%) received RT. With median follow-up of 5.0 years, estimated 5-year OS was superior in patients receiving CRT versus RT (86.1% vs 71.6%, P < .0001). On multivariable analysis, after controlling for risk factors, CRT was associated with superior OS compared with RT (HR: 0.53; 95%CI: 0.32-0.88, P = .01). On planned subgroup analyses, the 5 year OS of patients receiving CRT versus RT was improved for M0 patients (P < .0001), for patients receiving 36 Gy CSI (P = .0007), and for M0 patients receiving 36 Gy CSI (P = .0008). Conclusions This national database analysis demonstrates that combined postoperative chemotherapy and radiotherapy are associated with superior survival for adult MB compared with radiotherapy alone, even for M0 patients who receive high-dose CSI.

Cost-Effectiveness of Surgery, Stereotactic Body Radiation Therapy, and Systemic Therapy for Pulmonary Oligometastases

INTRODUCTION Pulmonary oligometastases have conventionally been managed with surgery and/or systemic therapy. However, given concerns about the high cost of systemic therapy and improvements in local treatment of metastatic cancer, the optimal cost-effective management of these patients is unclear. Therefore, we sought to assess the cost-effectiveness of initial management strategies for pulmonary oligometastases. METHODS AND MATERIALS A cost-effectiveness analysis using a Markov modeling approach was used to compare average cumulative costs, quality adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) among 3 initial disease management strategies: video-assisted thoracic surgery (VATS) wedge resection, stereotactic body radiation therapy (SBRT), and systemic therapy among 5 different cohorts of patient disease: (1) melanoma; (2) non-small cell lung cancer adenocarcinoma without an EGFR mutation (NSCLC AC); (3) NSCLC with an EGFR mutation (NSCLC EGFRm AC); (4) NSCLC squamous cell carcinoma (NSCLC SCC); and (5) colon cancer. One-way sensitivity analyses and probabilistic sensitivity analyses were performed to analyze uncertainty with regard to model parameters. RESULTS In the base case, SBRT was cost effective for melanoma, with costs/net QALYs of

Decision analysis of stereotactic radiation surgery versus stereotactic radiation surgery and whole-brain radiation therapy for 1 to 3 brain metastases.

467,787/0.85. In patients with NSCLC, the most cost-effective strategies were SBRT for AC (

Concurrent chemoradiotherapy versus radiotherapy alone for “biopsy‐only” glioblastoma multiforme

156,725/0.80), paclitaxel/carboplatin for SCC (