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MICROABSTRACT: We evaluated the association of operability status with early post-treatment mortality among patients with early-stage non-small cell lung cancer undergoing stereotactic body radiotherapy. In this cohort study of 80,108 patients from a large US cancer dataset, operable patients undergoing stereotactic body radiotherapy experienced

The treatment for locally advanced non–small-cell lung cancer has changed dramatically over the past several years, with consolidative immunotherapy after concurrent chemoradiation becoming the new standard of care. Five-year survival outcomes have substantially improved with this approach. Despite these advances, further improvements are needed as the majority of patients ultimately develop progression of disease. The next-generation immunotherapy trials are currently being conducted that include approaches such as concurrent immunotherapy and addition of other therapeutic agents in the concurrent and consolidative settings. Specific unmet needs continue to exist for patients who develop disease progression after concurrent chemoradiation and immunotherapy, as well as defining the best treatment for patients with driver mutations. Future directions also include refinement of radiation techniques to reduce toxicities as much as possible, as well as the use of circulating tumor DNA in the surveillance setting. The current scientific landscape shows promising approaches that may further improve outcomes for patients with locally advanced non–small-cell lung cancer.

Brain metastases from non-small cell lung cancer often cause neurologic symptoms which lead to initial diagnosis or identification of recurrence. In other patients, they are identified on surveillance imaging or when a patient undergoing treatment develops neurological symptoms. Patients with symptomatic lesions should be started on dexamethasone and evaluated by a neurosurgeon as soon as possible. If feasible, surgery should be offered to decrease intracranial pressure, alleviate symptoms, and prevent irreversible neurological damage. Postoperative stereotactic radiosurgery (SRS) to the resection cavity and any additional brain metastases should follow within 4 weeks of surgery, as early as 2 weeks post-op. Tissue from surgery is used to confirm the diagnosis and test for targetable oncogenic driver mutations. Treatment response and surveillance for development of additional lesions is assessed with MRI of the brain 1 month after SRS and every 3 months thereafter. Patients who are not surgical candidates or who have small, asymptomatic brain metastases should proceed with SRS, the preferred treatment, or sometimes whole-brain radiation therapy (WBRT) if multifocal disease requires more extensive treatment, such as for leptomeningeal spread of disease. The number of brain metastases that warrants use of WBRT over SRS is controversial and a topic of ongoing investigation, and is discussed in this review. When possible, SRS is preferred over WBRT due to reduce morbidity and cognitive side effects. When patients are already on systemic therapy at time of brain metastases diagnosis, systemic therapy should continue, with radiation therapy occurring between cycles. Regarding systemic therapy for new diagnosis at time of brain metastases presentation, molecular testing will guide treatment choice, when available. If there is no neurosurgical intervention, biopsy of another site of disease may provide tissue for molecular testing. If there are no targetable oncogenic driver mutations, concurrent immune checkpoint blockade (ICB) and chemotherapy is preferable for patients who can tolerate it. Single-agent ICB is an alternative option for patients who cannot tolerate chemotherapy. Systemic therapy should start as soon as possible. In some patients with poor performance status, best supportive care may be the most appropriate choice. Treatment decisions should always incorporate patients' goals of care and in many cases should be discussed in a multidisciplinary setting.

Treatment for advanced lung adenocarcinoma (AC) has become increasingly personalized based on molecular results. However, for patients with AC brain metastases (BMs), intracranial outcomes based on molecular subtype and the frequency of molecular aberrations are less well defined. This study sought to report targeted next-generation sequencing results and investigate molecularly based outcomes for patients with AC-BMs treated with radiotherapy.The records of 132 patients with AC-BMs treated at Emory University from September 2008 to August 2016 with successful next-generation sequencing were reviewed. Rates of local disease recurrence, distant brain failure (DBF), and salvage whole-brain radiotherapy (WBRT) were estimated using cumulative incidence with competing risk analysis. Univariate and multivariate analyses were performed.The most common aberrations included tumor protein 53 (TP53) (60%), KRAS (29%), epidermal growth factor receptor (EGFR) (20.5%), phosphatase and tensin homolog (PTEN) loss (15.5%), and MET amplification (13%). The majority of patients (62%) were treated with stereotactic radiosurgery alone. In these patients, KRAS mutation, anaplastic lymphoma kinase (ALK) rearrangement, and having ≥ 6 BMs were associated with an increased risk of salvage WBRT (P .05). KRAS mutation remained significant for an increased risk of salvage WBRT when compared with EGFR/ALK/KRAS-negative patients (hazard ratio, 5.17; P .05), despite a similar risk of DBF. PTEN loss was associated with increased risk of DBF (P .05), whereas EGFR and ALK aberrations were associated with a decreased risk of local disease recurrence (P .05).The results of the current study quantified the frequency of genetic aberrations in patients with AC-BMs and demonstrated their association with intracranial outcomes. In particular, a cohort of patients with KRAS mutations and ≥6 BMs were identified to be at high risk of requiring salvage WBRT after undergoing upfront stereotactic radiosurgery.

The treatment of patients with advanced stage laryngeal cancer includes surgery or concurrent chemoradiation (CRT). Although CRT has become more common in recent years, to the authors' knowledge, the effectiveness of complete CRT in improving survival over surgery has not been studied.The authors examined patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare claims-linked data set with locoregional laryngeal cancer who were diagnosed between 1997 and 2007. Multivariate Cox proportional hazard analyses were conducted to compare overall and cause-specific 5-year survival rates between treatment modalities, adjusting for patient sociodemographic and clinical characteristics. A propensity score-matched subcohort also was used to compare survival.Of the 3212 patients in the study cohort, 42% underwent surgery and 18% underwent CRT. Only approximately one-quarter of patients who were treated with CRT completed the courses. In adjusted analyses, the authors were unable to reject the null hypothesis of no difference in 5-year all-cause or cause-specific mortality risk between patients treated with surgery and patients undergoing complete CRT (hazards ratio, 1.25 [95% confidence interval, 0.91-1.71; P = .16] and hazard ratio, 1.41 [95% confidence interval, 0.9-2.2; P = .14], respectively). Older age, not currently married, Medicaid eligibility, and prior cancer history were found to be associated with a higher risk of mortality (P.05).Patients with advanced laryngeal cancer who underwent complete CRT were found to have overall and cause-specific survival rates similar to those of patients undergoing surgery. However, a substantial percentage of patients who initiated CRT did not complete the course. Although CRT provides organ preservation, the benefits and trade-offs of CRT and total laryngectomy should be discussed fully with patients. The importance of completing the full course of CRT should be emphasized. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2845-2856. © 2016 American Cancer Society.

Stereotactic body radiation therapy (SBRT) has demonstrated high rates of local control with low morbidity and has now emerged as the standard of care for medically inoperable, early stage non-small cell lung cancer (NSCLC). However, the impact of lung SBRT on survival in the elderly population is less clear given competing comorbid conditions. An analysis of the National Cancer Data Base (NCDB) was undertaken to determine whether definitive SBRT improves survival relative to observation alone patients ages 70 years and older.The NCDB, a retrospective national database that captures approximately 70% of all patients treated for cancer, was queried for patients aged 70 years or older with early stage (T1-T3N0M0) NSCLC from 2003 to 2006. Overall survival was compared between patients who received stereotactic body radiotherapy alone and those who received no treatment. An extended Cox proportional hazards model was applied to estimate the treatment effect of SBRT.In total, 3147 patients met the selection criteria for this analysis. SBRT was delivered to 258 patients (8.2%), and 2889 patients (91.8%) received no treatment. There was no significant difference in the distribution of Charlson/Deyo comorbidity index scores between the 2 groups (P = .076). Multivariable analysis revealed improved overall survival with SBRT compared with observation for the entire cohort (hazard ratio, 0.64; P .001).SBRT is associated with improved survival in elderly patients with early stage NSCLC who have concurrent comorbid conditions compared with observation alone. The current data support the use of SBRT for the treatment of elderly patients with early stage NSCLC who have limiting comorbid conditions.

The benefit of combined chemoradiation in elderly patients with human papillomavirus (HPV)-positive locally advanced oropharyngeal squamous cell carcinoma (SCC) must be balanced with the potential for higher toxicity rates. We performed a retrospective review of our institutional experience.Patients 70 years or older with p16-positive oropharyngeal SCC treated with definitive chemoradiation from 2005 to 2013 were evaluated. Overall survival (OS), disease-free survival (DFS), and locoregional failure-free survival were calculated.Twenty-one eligible patients had a follow-up of 22.4 months. Estimated 5-year OS, DFS, and locoregional failure-free survival were 76.0%, 40%, and 95%, respectively. There was 1 death from acute toxicity, and 50% had unplanned hospitalizations. Sixty percent had late toxicity, and 6-month feeding tube dependence was 25%.Elderly patients with HPV-positive locally advanced SCC of the oropharynx treated with definitive chemoradiation had good OS but high rates of acute and long-term toxicity. © 2015 Wiley Periodicals, Inc. Head Neck 38: 846-851, 2015.

The purpose of this study was to determine if lymph node ratio is associated with locoregional recurrence for patients with oral cavity or laryngeal cancer treated with initial surgical management.The study included 350 patients with oral cavity (73%) or laryngeal cancer (27%) who underwent initial surgery. All analyses were multivariable, adjusting for primary site, pathologic prognostic factors, and adjuvant therapy.Lymph node ratio was significantly associated with locoregional recurrence, in which each 1% increase in lymph node ratio had an adjusted hazard ratio (HR) for locoregional recurrence of 1.02 (95% confidence interval [CI], 1.002-1.042; p = .05). Lymph node ratio was also associated with OS, in which each 1% increase in lymph node ratio had an adjusted HR for death of 1.028 (95% CI, 1.012-1.045; p = .001).Adjusting for pathologic factors and adjuvant therapy, lymph node ratio was found to be an independent prognostic factor for locoregional recurrence and overall survival (OS). Patients with lymph node ratio ≥20% are at high risk of locoregional recurrence and death, and may be considered for adjuvant chemoradiation.