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Syndiker innhold Journal of Thoracic Oncology - Current Issue
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A Milestone for the Journal of Thoracic Oncology

tir, 12/01/2015 - 06:00
No abstract available

Durable Clinical Response to Entrectinib in NTRK1-Rearranged Non-Small Cell Lung Cancer

tir, 12/01/2015 - 06:00
Introduction: Chromosomal rearrangements involving neurotrophic tyrosine kinase 1 (NTRK1) occur in a subset of non-small cell lung cancers (NSCLCs) and other solid tumor malignancies, leading to expression of an oncogenic TrkA fusion protein. Entrectinib (RXDX-101) is an orally available tyrosine kinase inhibitor, including TrkA. We sought to determine the frequency of NTRK1 rearrangements in NSCLC and to assess the clinical activity of entrectinib. Methods: We screened 1378 cases of NSCLC using anchored multiplex polymerase chain reaction (AMP). A patient with an NTRK1 gene rearrangement was enrolled onto a Phase 1 dose escalation study of entrectinib in adult patients with locally advanced or metastatic tumors (NCT02097810). We assessed safety and response to treatment. Results: We identified NTRK1 gene rearrangements at a frequency of 0.1% in this cohort. A patient with stage IV lung adenocrcinoma with an SQSTM1-NTRK1 fusion transcript expression was treated with entrectinib. Entrectinib was well tolerated, with no grade 3–4 adverse events. Within three weeks of starting on treatment, the patient reported resolution of prior dyspnea and pain. Restaging CT scans demonstrated a RECIST partial response (PR) and complete resolution of all brain metastases. This patient has continued on treatment for over 6 months with an ongoing PR. Conclusions: Entrectinib demonstrated significant anti-tumor activity in a patient with NSCLC harboring an SQSTM1-NTRK1 gene rearrangement, indicating that entrectinib may be an effective therapy for tumors with NTRK gene rearrangements, including those with central nervous system metastases.

The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for the Revision of the N Descriptors in the Forthcoming 8th Edition of the TNM Classification for Lung Cancer

tir, 12/01/2015 - 06:00
Introduction: Nodal status is considered to be one of the most reliable indicators of the prognosis in patients with lung cancer and thus is indispensable in determining the optimal therapeutic options. We sought to determine whether the current nodal (N) descriptors should be maintained or revised for the next edition (8th) of the International Lung Cancer Staging System. Methods: The new International Association for the Study of Lung Cancer lung cancer database was created from 94,708 patients diagnosed as having lung cancer between 1999 and 2010. Among these, 38,910 and 31,426 patients with non–small-cell lung carcinoma were available for an analysis of the clinical (c)N and pathological (p)N status, respectively. The anatomical location of lymph node involvement was defined by either the Naruke (for Japanese data) or American Thoracic Society (for non-Japanese data) nodal charts. Survival was calculated by the Kaplan–Meier method, and prognostic groups were assessed by a Cox regression analysis. Results: The current N0 to N3 descriptors for both the cN and pN status consistently separated prognostically distinct groups. The 5-year survival rates according to the cN and pN status were 60% and 75% (N0), 37% and 49% (N1), 23% and 36% (N2), and 9% and 20% (N3), respectively. The differences in survival between all neighboring nodal categories were highly significant for both the cN and pN status. With regard to pathological staging, additional analyses regarding the prognosis were performed by further dividing N1 into N1 at a single station (N1a) and N1 at multiple stations (N1b); N2 into N2 at a single station without N1 involvement (“skip” metastasis, N2a1), N2 at a single station with N1 involvement (N2a2), and N2 at multiple stations (N2b). The survival curves for N1b and N2a2 overlapped each other, and N2a1 had numerically a better prognosis than N1b, although the difference was not significant. Geographic difference in N-specific prognosis was observed for both c-settings and p-settings. This might have been because of the difference in the used nodal map, surgical technique, and pathologist’s handling of the resected specimen. Conclusions: Current N descriptors adequately predict the prognosis and therefore should be maintained in the forthcoming staging system. Furthermore, we recommend that physicians record the number of metastatic lymph nodes (or stations) and to further classify the N category using new descriptors, such as N1a, N1b, N2a, N2b, and N3, for further testing.

Clinical Trials Integrating Immunotherapy and Radiation for Non–Small-Cell Lung Cancer

tir, 12/01/2015 - 06:00
Methods of harnessing the immune system to treat cancer have been investigated for decades, but yielded little clinical progress. However, in recent years, novel drugs that allow immune recognition and destruction of tumor cells are emerging as potent cancer therapies. Building upon previous immunotherapy strategies that included therapeutic vaccines, recombinant cytokines, and other immunostimulatory agents, newer immunotherapy agents targeting immune checkpoints including programmed cell death 1, programmed cell death ligand-1, and cytotoxic T-lymphocyte-associated protein 4, among others, have garnered substantial enthusiasm after demonstrating clinical activity in a broad spectrum of tumor types. Trials evaluating immune checkpoint inhibitors in metastatic non–small-cell lung cancer (NSCLC) demonstrate robust and durable responses in a subset of patients. However, with overall response rates less than 20%, combinatorial strategies that extend the benefit of these agents to more patients are desirable. The integration of radiotherapy with immunotherapy is a conceptually promising strategy, as radiotherapy has potent immunomodulatory effects and may contribute not only to local control but may also augment systemic antitumor immune response. Preclinical data and case reports suggest the potential for robust clinical responses in metastatic NSCLC patients using this strategy, but prospective clinical trials evaluating the integration of radiation and immunotherapy are limited. The use of immunotherapy in nonmetastatic settings is also intriguing but understudied. We review the potential clinical settings of interest for the partnering of immunotherapy and radiation in NSCLC, including early stage, locally advanced, and metastatic disease, and review completed, accruing, and developing clinical trials.

A Prognostic Model to Predict Mortality among Non–Small-Cell Lung Cancer Patients in the U.S. Military Health System

tir, 12/01/2015 - 06:00
Introduction: Accurate prognosis assessment after non–small-cell lung cancer (NSCLC) diagnosis is an essential step for making effective clinical decisions. This study is aimed to develop a prediction model with routinely available variables to assess prognosis in patients with NSCLC in the U.S. Military Health System. Methods: We used the linked database from the Department of Defense’s Central Cancer Registry and the Military Health System Data Repository. The data set was randomly and equally split into a training set to guide model development and a testing set to validate the model prediction. Stepwise Cox regression was used to identify predictors of survival. Model performance was assessed by calculating area under the receiver operating curves and construction of calibration plots. A simple risk scoring system was developed to aid quick risk score calculation and risk estimation for NSCLC clinical management. Results: The study subjects were 5054 patients diagnosed with NSCLC between 1998 and 2007. Age, sex, tobacco use, tumor stage, histology, surgery, chemotherapy, peripheral vascular disease, cerebrovascular disease, and diabetes mellitus were identified as significant predictors of survival. Calibration showed high agreement between predicted and observed event rates. The area under the receiver operating curves reached 0.841, 0.849, 0.848, and 0.838 during 1, 2, 3, and 5 years, respectively. Conclusions: This is the first NSCLC prognosis model for quick risk assessment within the Military Health System. After external validation, the model can be translated into clinical use both as a web-based tool and through mobile applications easily accessible to physicians, patients, and researchers.

Soy Isoflavones Promote Radioprotection of Normal Lung Tissue by Inhibition of Radiation-Induced Activation of Macrophages and Neutrophils

tir, 12/01/2015 - 06:00
Introduction: Radiation therapy for lung cancer is limited by toxicity to normal lung tissue that results from an inflammatory process, leading to pneumonitis and fibrosis. Soy isoflavones mitigate inflammatory infiltrates and radiation-induced lung injury, but the cellular immune mediators involved in the radioprotective effect are unknown. Methods: Mice received a single dose of 10 Gy radiation delivered to the lungs and daily oral treatment of soy isoflavones. At different time points, mice were either processed to harvest bronchoalveolar lavage fluid for differential cell counting and lungs for flow cytometry or immunohistochemistry studies. Results: Combined soy and radiation led to a reduction in infiltration and activation of alveolar macrophages and neutrophils in both the bronchoalveolar and lung parenchyma compartments. Soy treatment protected F4/80+CD11c− interstitial macrophages, which are known to play an immunoregulatory role and are decreased by radiation. Furthermore, soy isoflavones reduced the levels of nitric oxide synthase 2 expression while increasing arginase-1 expression after radiation, suggesting a switch from proinflammatory M1 macrophage to an anti-inflammatory M2 macrophage phenotype. Soy also prevented the influx of activated neutrophils in lung caused by radiation. Conclusions: Soy isoflavones inhibit the infiltration and activation of macrophages and neutrophils induced by radiation in lungs. Soy isoflavones-mediated modulation of macrophage and neutrophil responses to radiation may contribute to a mechanism of resolution of radiation-induced chronic inflammation leading to radioprotection of lung tissue.

Impact of Concurrent PIK3CA Mutations on Response to EGFR Tyrosine Kinase Inhibition in EGFR-Mutant Lung Cancers and on Prognosis in Oncogene-Driven Lung Adenocarcinomas

tir, 12/01/2015 - 06:00
Introduction: In patients with epidermal growth factor receptor (EGFR)-mutant or KRAS-mutant lung adenocarcinomas, the prognostic impact of a concurrent PIK3CA mutation remains unclear. Although preclinical data suggest that sensitivity to EGFR tyrosine kinase inhibition (TKI) is decreased in EGFR-mutant lung cancers also harboring a PIK3CA mutation, this interaction has not been explored clinically. Methods: Patients with lung adenocarcinomas harboring a PIK3CA mutation concurrent with a separate driver mutation were identified through mutational hotspot testing, multiplex sizing assays, and fluorescence in situ hybridization. Overall survival and outcomes with EGFR TKI monotherapy (EGFR-mutant) were estimated using Kaplan–Meier methods and compared between double-mutant (EGFR-mutant or KRAS-mutant, concurrent PIK3CA-mutant) and single-mutant patients (EGFR-mutant or KRAS-mutant, PIK3CA wild-type) using log-rank tests. Results: In EGFR-mutant and KRAS-mutant lung cancers, a concurrent PIK3CA mutation was associated with a decrease in median overall survival: 18 versus 33 months (EGFR double mutant, n = 10 versus single mutant, n = 43, p = 0.006), and 9 versus 16 months (KRAS double mutant, n = 16 versus single mutant, n = 47, p = 0.020). In EGFR-mutant lung cancers, a concurrent PIK3CA mutation did not impact benefit from EGFR TKI monotherapy. Single versus double mutant: objective response rate, 83% (n = 29) versus 62% (n = 6, p = 0.80); median time to progression, 11 (n = 29) versus 8 months (n = 6, p = 0.84); and median duration of TKI therapy, 15 (n = 32) versus 15 months (n = 10, p = 0.65). Conclusion: A concurrent PIK3CA mutation is a poor prognostic factor in patients with advanced EGFR-mutant or KRAS-mutant lung adenocarcinomas. There was no evidence that clinical benefit from EGFR TKI monotherapy is affected by a concurrent PIK3CA mutation in EGFR-mutant lung cancers.

EGFR Mutation Impact on Definitive Concurrent Chemoradiation Therapy for Inoperable Stage III Adenocarcinoma

tir, 12/01/2015 - 06:00
Background: Concurrent chemoradiation therapy (CRT) is the current standard of care for patients with locally advanced lung adenocarcinoma; however, little has been reported about the impact of epidermal growth factor receptor (EGFR) mutation on CRT efficacy. Methods: From 2006 to 2013, we retrospectively screened 104 unresectable stage III adenocarcinoma patients who were examined for EGFR mutation status and received definitive concurrent CRT consisting of platinum doublet chemotherapy in first-line setting and compared the clinical outcomes and recurrence patterns according to mutation status. Results: Among 104 patients, EGFR mutation was detected in 29 (28%). The overall response rate did not differ between EGFR-mutant and wild-type patients (72.4% versus 72.0%, p = 0.607). The median progression-free survival in concurrent CRT was significantly shorter in EGFR-mutant patients than in wild-type patients (9.8 [95% confidence interval, CI: 7.6–19.0] versus 16.5 [95% CI: 11.8–19.9] months, p = 0.041). The 2-year recurrence-free survival rate was 7.7% and 28.1% in EGFR-mutant and wild-type patients, respectively (p = 0.028). Distant metastases were more frequently identified as the first recurrence site in EGFR-mutant patients than in wild-type patients (76% versus 40%, p = 0.001). The brain was the most often affected site in EGFR-mutant patients (35%). However, locoregional recurrence was less common in EGFR-mutant patients than in the wild-type population (14% versus 35%, p = 0.027). Overall survival was similar between EGFR-mutant and wild-type patients (51.1 [95% CI: 28.2–70.2] versus 42.9 [95% CI: 35.3 to not available] months, p = 0.637). Among the EGFR wild-type population who were examined for Kras mutation, Kras-mutant patients had significantly worse overall survival than Kras wild-type patients (21.6 versus 49.8 months, p = 0.024). Conclusion: Concurrent CRT resulted in shorter progression-free survival in EGFR-mutant stage III adenocarcinoma patients than in wild-type patients, mainly because of distant metastasis relapse, regardless of better local control. Because of these distinct biological features, a different strategy, including EGFR-tyrosine kinase inhibitors for EGFR-mutant locally advanced adenocarcinoma patients receiving definitive CRT may be needed.

Expression of PD-1 and Its Ligands, PD-L1 and PD-L2, in Smokers and Never Smokers with KRAS-Mutant Lung Cancer

tir, 12/01/2015 - 06:00
Introduction: Clinical responses to immune checkpoint blockade by anti-programmed cell death protein-1 (PD-1)/PD-L1 monoclonal antibodies in non–small-cell lung cancer (NSCLC) are associated with PD-L1 expression and smoking status. We aimed to determine the expression profile of PD-1 and its ligands, PD-L1 and PD-L2, in both smokers and never smokers patients with KRAS-mutant NSCLC. Methods: We retrospectively analyzed the clinical and molecular characteristics of 114 KRAS-mutant NSCLC patients (84 smokers and 30 never smokers) and their clinical tumor samples for the expression of PD-1, PD-L1, and PD-L2 by immunohistochemistry (IHC). We used murine monoclonal antibodies anti-PD-L1 (clone 9A11) and anti-PD-L2 (clone 9E5) to examine for tumor cell expression (0, negative; 1, weak; 2, moderate; 3, intense) and anti-PD-1 (clone EH33) for tumor-infiltrating lymphocytes. Results: PD-L1 expression was detected in 27 of 114 patients (24%; 95% confidence interval [CI], 16–33%) and associated with smoking status (current smokers, 44%; former smokers, 20%; never smokers, 13%; p = 0.03). Higher intensity of PD-L1 expression (IHC-2+/IHC-3+) was more frequently observed in smokers and associated with more pack-years. PD-L2 was positive in 54 of 114 patients (47%; 95% CI, 38–57%) and not related to smoking status. PD-1–positive tumor-infiltrating lymphocytes were present in 77 of 114 tumor specimens tested (68%; 95% CI, 59–77%) including 21 of 27 samples with PD-L1 expression and 39 of 54 samples with PD-L2–positive expression. We found that PD-L1 expression fades with the age of the specimens used for analyses decreasing beyond 3 years (p = 0.016). Conclusions: The expression of PD-1 and its ligands PD-L1 and PD-L2 is heterogeneous within KRAS-mutant NSCLC and suggests an inducible expression of PD-L1 by smoking.

Mechanisms of Acquired Resistance to AZD9291: A Mutation-Selective, Irreversible EGFR Inhibitor

tir, 12/01/2015 - 06:00
Introduction: AZD9291, a third-generation and mutation-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is active against patients with EGFRT790M-mutant non–small-cell lung cancer (NSCLC) who failed prior treatment with EGFR TKIs. However, acquired resistance to AZD9291 is inevitable. In this study, we identified the mechanisms of acquired resistance to AZD9291 in EGFRT790M-mutant NSCLC. Methods: Four NSCLC patients with both an EGFR exon 19 deletion and the EGFRT790M mutation after developing acquired resistance to first-generation EGFR TKIs received AZD9291 at doses of 20 to 80 mg/day in a phase I trial (NCT01802632). Paired tumor samples before and after treatment were obtained to evaluate EGFR modifications, alternative pathway activation, and histologic transformation. Genetic alterations were analyzed using Sanger sequencing, fluorescence in situ hybridization, real-time polymerase chain reaction, and targeted exome sequencing. Results: All four patients achieved a partial response (median duration of response, 9 months [range, 9–11 months]) and subsequently showed resistance to AZD9291. EGFRT790M-mutant clones depopulated AZD9291-resistant tumors to below 1% (baseline, 14%–36%) in three patients with progression: one with the loss of EGFRLREAT747del/T790M-double mutant clones and two accompanied by transformation to small-cell carcinoma and focal fibroblast growth factor receptor 1 (FGFR1) amplification, respectively. EGFRT790M-mutant clones remained and the EGFR ligand was overexpressed in one patient with focal progression to AZD9291. Conclusion: Acquired resistance mechanisms of AZD9291 in patients with EGFRT790M-mutant NSCLC who failed treatment with first-generation EGFR TKIs include the loss of EGFRT790M-mutant clones plus alternative pathway activation or histologic transformation and EGFR ligand–dependent activation.

Monotherapy Administration of Sorafenib in Patients With Non–Small Cell Lung Cancer (MISSION) Trial: A Phase III, Multicenter, Placebo-Controlled Trial of Sorafenib in Patients with Relapsed or Refractory Predominantly Nonsquamous Non–Small-Cell Lung Canc

tir, 12/01/2015 - 06:00
Introduction: Sorafenib monotherapy has shown benefits in phase II trials as third-/fourth-line treatment in patients with non–small-cell lung cancer (NSCLC). Methods: The phase III, multinational, double-blind, placebo-controlled Monotherapy admInistration of Sorafenib in patientS wIth nOn–small-cell luNg cancer (MISSION) trial randomized patients with advanced relapsed/refractory NSCLC, following two or three prior treatment regimens, to sorafenib 400 mg twice a day (n = 350) or matching placebo (n = 353) plus best supportive care. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS) and time to progression. Epidermal growth factor receptor and KRAS mutation status was analyzed in archival tumor and/or circulating tumor DNA from blood samples obtained during screening. Results: Median OS was similar in the sorafenib and placebo groups (8.2 versus 8.3 mo; hazard ratio [HR], 0.99; 95% confidence interval [CI], 0.84–1.17; p = 0.47). Median PFS (2.8 versus 1.4 mo; HR, 0.61; 95% CI, 0.51–0.72; p < 0.0001), and time to progression (2.9 versus 1.4 mo; HR, 0.54; 95% CI, 0.45–0.65; p < 0.0001) were significantly greater with sorafenib than with placebo. Among the 89 patients with epidermal growth factor receptor mutations, OS (13.9 versus 6.5 mo; HR, 0.48; 95% CI, 0.30–0.76; p = 0.002) and PFS (2.7 versus 1.4 mo; HR, 0.27; 95% CI, 0.16–0.46; p < 0.001) were significantly higher with sorafenib than placebo. PFS was significantly longer with sorafenib than placebo in patients with either wild-type or mutated KRAS, but OS was similar. Common drug-related adverse events were rash/desquamation, diarrhea, and fatigue, consistent with the safety profile of sorafenib. Conclusions: Third-/fourth-line sorafenib therapy did not significantly increase OS in patients with relapsed/refractory NSCLC, despite significantly increasing PFS.

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Non–Small-Cell Lung Cancer Patients with Leptomeningeal Carcinomatosis

tir, 12/01/2015 - 06:00
Background: Leptomeningeal carcinomatosis (LC) is a detrimental complication of patients with non–small-cell lung cancer (NSCLC). The effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) on the clinical outcome of these patients, particularly those with EGFR mutations, has not been studied yet. Methods: We searched the database for lung cancer patients diagnosed from 2003 to 2010 in one Asian medical center. NSCLC patients who also had LC diagnosed by either cytology or brain neuroimaging studies were identified. The treatments and clinical outcomes were reviewed. Results: Of 5526 lung cancer patients, we identified 212 (3.8%) NSCLC patients with LC. Most patients (88.7%) had adenocarcinoma histology, and 129 (60.9%) patients had been treated with at least one regimen of EGFR TKI before the diagnosis of LC. One hundred and twenty-four (58.5%) patients were treated with EGFR TKI, and 128 (60.4%) patients were treated with whole-brain radiation therapy (WBRT) after the diagnosis of LC. The median overall survival was 4.5 months (95% confidence interval, 3.5–7.3). Multivariate analysis suggested that EGFR TKI therapy, WBRT, and cytotoxic chemotherapy were independent predictors for longer survival. Mutational status of EGFR was evaluated in 101 patients, and 75 mutations (74.3%) were detected. Among the 75 patients with EGFR mutations, EGFR TKI therapy and cytotoxic chemotherapy after diagnosis of LC remained the independent factors predictive of extended survival in the multivariate analysis. Conclusions: Treatment of LC with EGFR TKI, cytotoxic chemotherapy, or WBRT in selected patients is associated with prolong survival period. These treatment options, especially EGFR TKIs, should be studied in patients with EGFR mutation-positive NSCLC and LC.

Changes in Pulmonary Function Following Image-Guided Stereotactic Lung Radiotherapy: Neither Lower Baseline Nor Post-SBRT Pulmonary Function Are Associated with Worse Overall Survival

tir, 12/01/2015 - 06:00
Purpose: To determine changes in pulmonary function brought about by lung stereotactic body radiation therapy (SBRT). Methods: One hundred and twenty-seven patients were treated with lung SBRT using 48 to 60Gy in four to five fractions on a prospective trial. We obtained pulmonary function tests (PFTs) at baseline, 6 weeks, 3 months, 6 months, 9 months, 12 months, and 24 months after SBRT. Group mean PFT parameter values are reported. Results: At baseline forced expiratory volume in 1 second (FEV1) was 1.5 l (67% predicted, range: 0.4–3.4 l), corrected diffusing capacity for carbon monoxide was 12.2 ml/min/mmHg (50.8% predicted, range: 3.3–27.2 ml/min/mmHg), and total lung capacity was 5.7 l (102.4% predicted, range: 3.1–9.1 l). At 12 months, there was decline in FEV1 (−4.1%; p = 0.01), corrected diffusing capacity for carbon monoxide (−5.2%; p = 0.027), forced vital capacity (−5.7%; p = 0.004), and total lung capacity (−3.6%; p = 0.039). Declines in FEV1 (−7.6%; p = 0.001) and forced vital capacity (−8.9%; p = 0.001) persisted at 24 months. Rates of pneumonitis were 3.1% and 0.8% for grades 2 and 3, respectively. There were no grade 3 PFT toxicities at 12 months. Lower PFTs at baseline and 1 year after SBRT did not predict for worse overall survival. Conclusions: As the largest cohort of patients with prospective follow-up PFT evaluation after lung SBRT, this supports the safety of SBRT in this population of predominantly medically inoperable patients. While statistically significant, nearly all declines in PFTs would be rated as a grade 1 on the Radiation Therapy Oncology Group scale, demonstrating safety. PFT declines were not associated with worse overall survival.

Utilization of Hyperfractionated Radiation in Small-Cell Lung Cancer and Its Impact on Survival

tir, 12/01/2015 - 06:00
Introduction: Twice-daily radiation with concurrent chemotherapy is recognized as the standard of care for the treatment of limited stage small-cell lung carcinoma (SCLC), but its utilization in this setting is unclear. The objective of this study was to analyze modern patterns of treatment for limited stage SCLC and the impact on survival utilizing the National Cancer Database. Methods: Between 1999 and 2012, there were 25,045 patients diagnosed with nonmetastatic SCLC who met the selection criteria, of whom 22,626 had survival data. Those receiving 45 Gy in 1.5 Gy fractions twice-daily (BID) were compared with those receiving 45 to 72 Gy in 1.8 or 2.0 Gy fractions. Overall survival was analyzed via Kaplan–Meier analysis and compared using the log-rank test. Multivariate Cox regression analysis was used to identify covariates associated with survival. Results: The utilization of BID radiation overall was 11.3%. Treatment at an academic center was associated with a higher likelihood of receiving BID treatment (odds ratio: 2.29, 95% confidence interval [CI]: 1.95–2.69; p < 0.001). Median survival was 22.1, 17.2, 18.3, 19.2, and 19.5 months for patients receiving 45 Gy BID, 45 Gy once-daily, 46 to 59.4 Gy once-daily, 60 to 61.2 Gy once-daily, and 62 to 72 Gy once-daily, respectively (p < 0.001 for all pairwise comparisons to BID). On multivariate analysis, treatment at an academic center (hazard ratio: 0.88, 95% CI: 0.83–0.93; p < 0.001) and receipt of BID radiation (hazard ratio: 0.92, 95% CI: 0.86–0.98; p = 0.008) were associated with improved survival. Conclusions: The adoption of BID radiation remains very limited, but is more commonly utilized in the academic setting. In this hospital-based study, BID fractionation was associated with improved survival over once-daily fractionation, even at doses ≥60 Gy.

Treatment Outcomes in Stage I Lung Cancer: A Comparison of Surgery and Stereotactic Body Radiation Therapy

tir, 12/01/2015 - 06:00
Introduction: The relative roles of surgery and stereotactic body radiation therapy in stage I non–small-cell lung cancer (NSCLC) are evolving particularly for marginally operable patients. Because there is limited prospective comparative data for these treatment modalities, we evaluated their relative use and outcomes at the population level using a national database. Methods: Patient variables and treatment-related outcomes were abstracted for patients with clinical stage I NSCLC from the National Cancer Database. Patients receiving surgery were compared with those undergoing stereotactic body radiation therapy (SBRT) in exploratory unmatched and subsequent propensity matched analyses. Results: Between 1998 and 2010, 117,618 patients underwent surgery or SBRT for clinical stage I NSCLC. Of these, 111,731 (95%) received surgery, whereas 5887 (5%) underwent SBRT. Patients in the surgery group were younger, more likely to be males, and had higher Charlson comorbidity scores. SBRT patients were more likely to have T1 (versus T2) tumors and receive treatment at academic centers. Thirty-day surgical mortality was 2596 of 109,485 (2.4%). Median overall survival favored the surgery group in both unmatched (68.4 versus 33.3 months, p < 0.001) and matched analysis based on patient characteristics (62.3 versus 33.1 months, p < 0.001). Disease-specific survival was unavailable from the data set. Conclusion: In a propensity matched comparison, patients selected for surgery have improved survival compared with SBRT. In the absence of information on cause of death and with limited variables to characterize comorbidity, it is not possible to assess the relative contribution of patient selection or better cancer control toward the improved survival. Rigorous prospective studies are needed to optimize patient selection for SBRT in the high-risk surgical population.

Role of CT and PET Imaging in Predicting Tumor Recurrence and Survival in Patients with Lung Adenocarcinoma: A Comparison with the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification

tir, 12/01/2015 - 06:00
Introduction: Recently, a new lung adenocarcinoma classification scheme was published. The prognostic value of this new classification has not been elaborated together with the value of imaging biomarkers including computed tomography (CT) and positron emission tomography (PET). Methods: We reviewed pathologic specimens and imaging characteristics of primary tumors from 723 consecutive patients who underwent surgical resection for lung adenocarcinoma. On pathology, the predominant histologic subtype and pattern group were quantified. Tumor-shadow disappearance ratio (TDR) on CT and maximum standardized uptake value (SUVmax) on PET were assessed. The relationships between those variables and survival (overall survival [OS] and disease-free survival) were analyzed by using Kaplan–Meier curves and Cox regression analyses. Results: The median follow-up period was 3.8 years. There were 137 patients (19%) with recurrence and 167 patients (23%) with metastasis after surgical resection. Among 723 patients, 35 patients (4.8%) had adenocarcinoma in situ, 34 patients (4.7%) had minimally invasive adenocarcinoma, 125 patients (17.3%) had lepidic predominant, 314 patients (43.4%) had acinar predominant, 65 patients (9.0%) had papillary predominant, 23 patients (3.2%) had micropapillary predominant, 113 patients (15.6%) had solid predominant, and 14 patients (1.9%) had variant adenocarcinomas. OS and disease-free survival rates were significantly different according to TDR on CT and SUVmax on PET, predominant subtypes, and pattern groups. On multivariate analysis, the SUVmax (p < 0.001), TDR (p = 0.038), and pattern group (p = 0.015) were independent predictors of OS. Conclusions: TDR on CT, SUVmax on PET, and the new histologic classification schemes appear to be promising parameters for the prognostic stratification of patients with lung adenocarcinomas, allowing for the triage of patients who necessitate further staging workup and adjuvant therapy.