Comparative effectiveness of stereotactic radiosurgery versus whole-brain radiation therapy for patients with brain metastases from breast or non-small cell lung cancer.

BACKGROUND: The optimal treatment for patients with brain metastases remains controversial as the use of stereotactic radiosurgery (SRS) alone, replacing whole-brain radiation therapy (WBRT), has increased. This study determined the patterns of care at multiple institutions before 2010 and examined whether or not survival was different between patients treated with SRS and patients treated with WBRT. METHODS: This study examined the overall survival of patients treated with radiation therapy for brain metastases from non-small cell lung cancer (NSCLC; initially diagnosed in 2007-2009) or breast cancer (initially diagnosed in 1997-2009) at 5 centers. Propensity score analyses were performed to adjust for confounding factors such as the number of metastases, the extent of extracranial metastases, and the treatment center. RESULTS: Overall, 27.8% of 400 NSCLC patients and 13.4% of 387 breast cancer patients underwent SRS alone for the treatment of brain metastases. Few patients with more than 3 brain metastases or lesions ≥ 4 cm in size underwent SRS. Patients with fewer than 4 brain metastases less than 4 cm in size (n = 189 for NSCLC and n = 117 for breast cancer) who were treated with SRS had longer survival (adjusted hazard ratio [HR] for NSCLC, 0.58; 95% confidence Interval [CI], 0.38-0.87; P = .01; adjusted HR for breast cancer, 0.54; 95% CI, 0.33-0.91; P = .02) than those treated with WBRT. CONCLUSIONS: Patients treated for fewer than 4 brain metastases from NSCLC or breast cancer with SRS alone had longer survival than those treated with WBRT in this multi-institutional, retrospective study, even after adjustments for the propensity to undergo SRS. Cancer 2016;122:2091-100. © 2016 American Cancer Society.

NCCN Guidelines Insights: Malignant Pleural Mesothelioma, Version 3.2016.

These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Malignant Pleural Mesothelioma (MPM). These NCCN Guidelines Insights discuss systemic therapy regimens and surgical controversies for MPM. The NCCN panel recommends cisplatin/pemetrexed (category 1) for patients with MPM. The NCCN panel also now recommends bevacizumab/cisplatin/pemetrexed as a first-line therapy option for patients with unresectable MPM who are candidates for bevacizumab. The complete version of the NCCN Guidelines for MPM, available at NCCN.org, addresses all aspects of management for MPM including diagnosis, evaluation, staging, treatment, surveillance, and therapy for recurrence and metastasis; NCCN Guidelines are intended to assist with clinical decision-making.

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 4.2016.

These NCCN Guidelines Insights focus on recent updates in the 2016 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC; Versions 1-4). These NCCN Guidelines Insights will discuss new immunotherapeutic agents, such as nivolumab and pembrolizumab, for patients with metastatic NSCLC. For the 2016 update, the NCCN panel recommends immune checkpoint inhibitors as preferred agents (in the absence of contraindications) for second-line and beyond (subsequent) therapy in patients with metastatic NSCLC (both squamous and nonsquamous histologies). Nivolumab and pembrolizumab are preferred based on improved overall survival rates, higher response rates, longer duration of response, and fewer adverse events when compared with docetaxel therapy.

Non-Small Cell Lung Cancer, Version 6.2015.

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC). Appropriate targeted therapy is very effective in patients with advanced NSCLC who have specific genetic alterations. Therefore, it is important to test tumor tissue from patients with advanced NSCLC to determine whether they have genetic alterations that make them candidates for specific targeted therapies. These NCCN Guidelines Insights describe the different testing methods currently available for determining whether patients have genetic alterations in the 2 most commonly actionable genetic alterations, notably anaplastic lymphoma kinase (ALK) gene rearrangements and sensitizing epidermal growth factor receptor (EGFR) mutations.

Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint.

Improvements in outcomes for patients with resectable lung cancers have plateaued. Clinical trials of resectable non-small-cell lung cancers with overall survival as the primary endpoint require a decade or longer to complete, are expensive, and limit innovation. A surrogate for survival, such as pathological response to neoadjuvant chemotherapy, has the potential to improve the efficiency of trials and expedite advances. 10% or less residual viable tumour after neoadjuvant chemotherapy, termed here major pathological response, meets criteria for a surrogate; major pathological response strongly associates with improved survival, is reflective of treatment effect, and captures the magnitude of the treatment benefit on survival. We support the incorporation of major pathological response as a surrogate endpoint for survival in future neoadjuvant trials of resectable lung cancers. Additional prospective studies are needed to confirm the validity and reproducibility of major pathological response within individual histological and molecular subgroups and with new drugs.

Non-small cell lung cancer, version 1.2015.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) focuses on the principles of radiation therapy (RT), which include the following: (1) general principles for early-stage, locally advanced, and advanced/metastatic NSCLC; (2) target volumes, prescription doses, and normal tissue dose constraints for early-stage, locally advanced, and advanced/palliative RT; and (3) RT simulation, planning, and delivery. Treatment recommendations should be made by a multidisciplinary team, including board-certified radiation oncologists who perform lung cancer RT as a prominent part of their practice.

Smoking status and survival in the national comprehensive cancer network non-small cell lung cancer cohort.

BACKGROUND: The objectives of this study were to evaluate survival among current smokers, former smokers, and never smokers who are diagnosed with non-small cell lung cancer (NSCLC). METHODS: The study included patients who participated in the National Comprehensive Cancer Network's NSCLC Database Project. Current, former, and never smokers were compared with respect to overall survival by fitting Cox regression models. RESULTS: Data from 4200 patients were examined, including 618 never smokers, 1483 current smokers, 380 former smokers who quit 1 to 12 months before diagnosis, and 1719 former smokers who quit >12 months before diagnosis. Among patients with stage I, II, and III disease, only never smokers had better survival than current smokers (hazard ratio, 0.47 [95% confidence interval, 0.26-0.85] vs 0.51 [95% confidence interval, 0.38-0.68], respectively). Among patients with stage IV disease, the impact of smoking depended on age: Among younger patients (aged ≤55 years), being a never smoker and a former smoker for ≥12 months increased survival. After age 85 years, smoking status did not have a significant impact on overall survival. CONCLUSIONS: Patients who were smoking at the time of diagnosis had worse survival compared with never smokers. Among younger patients with stage IV disease, current smokers also had worse survival compared with former smokers who quit >12 months before diagnosis. It is likely that tumor biology plays a major role in the differences observed; however, to improve survival, it is prudent to encourage all smokers to quit smoking if they are diagnosed with NSCLC.

Thymomas and thymic carcinomas: Clinical Practice Guidelines in Oncology.

Masses in the anterior mediastinum can be neoplasms (eg, thymomas, thymic carcinomas, or lung metastases) or non-neoplastic conditions (eg, intrathoracic goiter). Thymomas are the most common primary tumor in the anterior mediastinum, although they are rare. Thymic carcinomas are very rare. Thymomas and thymic carcinomas originate in the thymus. Although thymomas can spread locally, they are much less invasive than thymic carcinomas. Patients with thymomas have 5-year survival rates of approximately 78%. However, 5-year survival rates for thymic carcinomas are only approximately 40%. These guidelines outline the evaluation, treatment, and management of these mediastinal tumors.

Non-small cell lung cancer, version 2.2013.

These NCCN Guidelines Insights focus on the diagnostic evaluation of suspected lung cancer. This topic was the subject of a major update in the 2013 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer. The NCCN Guidelines Insights focus on the major updates in the NCCN Guidelines and discuss the new updates in greater detail.

Longitudinal associations between caregiver burden and patient and spouse distress in couples coping with lung cancer.

PURPOSE: While spouses play a vital role in the care of cancer patients, caregiving exerts a physical and psychological toll. Caregiving burden may not only compromise spouses' quality of life but also the quality of care and support they are able to provide. Consequently, spousal caregiving burden may also negatively impact patients' psychological adjustment. However, the effect of caregiving burden on patients' psychological distress is unknown. Thus, this 6-month longitudinal study examined the associations between caregiving burden and distress in both lung cancer patients and their spouses. METHODS: Patients and their spouses individually completed questionnaires within 1 month of treatment initiation (baseline) and at 3- and 6-month follow-up. Distress was measured with the Brief Symptom Inventory and caregiving burden with the Caregiver Reaction Assessment. RESULTS: Multilevel modeling of data from 158 couples revealed that baseline spouses' reports of caregiving-related health problems were significantly associated with 3-month (p < 0.001) and 6-month (p = 0.01) follow-up distress in both patients and spouses even when controlling for baseline distress and dyadic adjustment. Furthermore, there was evidence that baseline spouses' reports of schedule disruption (p = 0.05) predicted 3-month patients' distress and baseline spouses' reports of financial strain (p < 0.05) and lack of support (p < 0.10) predicted their own distress at 6 month. CONCLUSION: Caregiving burden is problematic for both patients and spouses. Couples in which spouses report caregiving-related health problems may be at particular high risk of long-term elevated distress. Targets of future couple-focused interventions such as self-care and use of social support are discussed.

First-line systemic therapy practice patterns and concordance with NCCN guidelines for patients diagnosed with metastatic NSCLC treated at NCCN institutions.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) allow many systemic therapy options for patients with metastatic non-small cell lung cancer (NSCLC). This analysis uses the NCCN NSCLC Outcomes Database to report on first-line therapy practice patterns and concordance with NCCN Guidelines. The analysis was limited to patients diagnosed with metastatic NSCLC between September 2006 and November 2009 at 1 of 8 participating NCCN Member Institutions. Patient characteristics, regimens used, and guidelines concordance were analyzed. Institutional variation and changes in practice over time were also measured. A total of 1717 patients were included in the analysis. Of these, 1375 (80%) were treated with systemic therapy, most often in the form of a carboplatin-based doublet (51%) or carboplatin-based doublet with targeted therapy (17%). Overall, 76% of patients received care that was concordant with NCCN Guidelines. Among patients with good performance status (n = 167), the most common reasons for not receiving first-line therapy were that therapy was not recommended (39%) or death occurred before treatment (33%). The most common reason for receiving nonconcordant drug therapy was the administration of pemetrexed or erlotinib before its incorporation into the NCCN Guidelines for first-line therapy (53%). Most patients in this cohort received care that was concordant with NCCN Guidelines. The NSCLC Outcomes Database is a valuable resource for evaluating practice patterns and concordance with NCCN Guidelines among patients with NSCLC.

Non-small cell lung cancer.

Most patients with non-small cell lung cancer (NSCLC) are diagnosed with advanced cancer. These guidelines only include information about stage IV NSCLC. Patients with widespread metastatic disease (stage IV) are candidates for systemic therapy, clinical trials, and/or palliative treatment. The goal is to identify patients with metastatic disease before initiating aggressive treatment, thus sparing these patients from unnecessary futile treatment. If metastatic disease is discovered during surgery, then extensive surgery is often aborted. Decisions about treatment should be based on multidisciplinary discussion.

Association of Medicaid Insurance With Survival Among Patients With Small Cell Lung Cancer.

Importance: Small cell lung cancer (SCLC) is an aggressive neoplasm requiring rapid access to subspecialized multidisciplinary care. For this reason, insurance coverage such as Medicaid may be associated with oncologic outcomes in this disproportionately economically vulnerable population. With Medicaid expansion under the Affordable Care Act, it is important to understand outcomes associated with Medicaid coverage among patients with SCLC. Objective: To determine the association of Medicaid coverage with survival compared with other insurance statuses. Design, Setting, and Participants: This cohort study included adult patients with limited-stage (LS) and extensive-stage (ES) SCLC in the US National Cancer Database from 2004 to 2013. Data were analyzed in January 2019. Main Outcomes and Measures: Patients were analyzed with respect to insurance status. Associations of insurance status with survival were interrogated with univariate analyses, multivariable analyses, and propensity score matching. Results: A total of 181 784 patients with SCLC (93 131 [51.2%] female; median [interquartile range] age; 67 [60-75] years for patients with LS-SCLC and 68 [60-75] years for patients with ES-SCLC) were identified, of whom 70 247 (38.6%) had LS-SCLC and 109 479 (60.2%) had ES-SCLC. On univariate analyses of patients with LS-SCLC, Medicaid coverage was not associated with a survival advantage compared with being uninsured (hazard ratio, 1.02; 95% CI, 0.96-1.08; P = .49). Likewise, on multivariable analyses of patients with ES-SCLC, compared with being uninsured, Medicaid coverage was not associated with a survival advantage (hazard ratio, 1.00; 95% CI, 0.96-1.03; P = .78). After propensity score matching, median survival was similar between the uninsured and Medicaid groups both among patients with LS-SCLC (14.4 vs 14.1 months; hazard ratio, 1.05; 95% CI, 0.98-1.12; P = .17) and those with ES-SCLC (6.3 vs 6.4 months; hazard ratio, 1.00; 95% CI, 0.96-1.04; P = .92). Conclusions and Relevance: Despite of billions of dollars in annual federal and state spending, Medicaid was not associated with improved survival in patients with SCLC compared with being uninsured in the US National Cancer Database. These findings suggest that there are substantial outcome inequalities for SCLC relevant to the policy debate on the Medicaid expansion under the Affordable Care Act.

Uncommon EGFR mutations in advanced non-small cell lung cancer.

Molecular profiling in advanced non-small cell lung cancer (NSCLC) has allowed for the detection of actionable mutations, which has revolutionized the treatment paradigm in this highly fatal disease. Mutations involving the epidermal growth factor receptor (EGFR) gene are most common and the 'classical mutations', exon 19 deletions and the point mutation L858R at exon 21, predict response to EGFR tyrosine kinase inhibitors (TKIs). The 'uncommon' EGFR mutations account for 10-18% of all EGFR mutations and primarily consist of exon 20 insertions, exon 18 point mutations and complex mutations. Improved detection techniques have broadened the spectrum of reported aberrations within the 'uncommon group' but response to TKIs is variable and not fully elucidated. This review provides an overview of the biology and incidence of uncommon EGFR mutations and summarizes reported outcomes when treated with EGFR-TKIs.

Adjuvant chemotherapy in completely resected non-small-cell lung cancer.

Surgery alone has long been the standard treatment for patients with operable non-small-cell lung cancer (NSCLC). However, despite complete resection, 5-year survival rates have been disappointing, with about 50% of patients eventually suffering relapse and death from disease. Randomized trials conducted in the 1980s hinted at a survival benefit for postoperative cisplatin-based regimens, but they were underpowered. A meta-analysis published in 1995 found a nonsignificant 13% reduction in the risk of death associated with cisplatin-based chemotherapy, with an increase of survival of 5% at 5 years. This led to renewed interest in adjuvant chemotherapy in resected NSCLC. Thousands of patients have been included in a new generation of randomized trials in the last 10 years. Most of these recent studies have now been reported and several have demonstrated a clear survival advantage for patients treated with platin-based adjuvant therapy. These results also suggest a greater benefit with modern two-drug regimens. In view of the most recent data, postoperative platin-based chemotherapy can now be considered the standard of care for completely resected NSCLC patients with good performance status.

Asian ethnicity as a predictor of response in patients with non-small-cell lung cancer treated with gefitinib on an expanded access program.

BACKGROUND: The primary objective of this retrospective study was to investigate the potential role of East Asian ethnicity or origin in predicting response to gefitinib in advanced-stage non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A chart review was done of all patients treated with gefitinib at M. D. Anderson Cancer Center on the Expanded Access Program. RESULTS: There were 223 patients with advanced-stage NSCLC who were enrolled. Of these, 182 received >or= 1 dose, and 160 were evaluable for response. The partial response rate was 8.8%, and the stable disease rate was 26.3%. Median time to progression was 2.5 months, and median survival was 6.8 months. The 1- and 2-year survival rates were 35.3% and 12.4%, respectively. Partial responses were seen in 7 of 12 patients (58.3%) of East Asian origin compared with 7 of 131 patients who were white (5.3%). This difference was statistically significant when controlling for histology, smoking status, hemoglobin, and diarrhea. Never smoking and diarrhea were also independent predictors of response. CONCLUSION: For the first time, in a multivariate analysis, we observed a positive relationship between East Asian origin and response to gefitinib. These findings might help determine which patients will likely benefit from gefitinib.

Variation in Definitive Therapy for Localized Non-Small Cell Lung Cancer Among National Comprehensive Cancer Network Institutions.

PURPOSE: This study determined practice patterns in the staging and treatment of patients with stage I non-small cell lung cancer (NSCLC) among National Comprehensive Cancer Network (NCCN) member institutions. Secondary aims were to determine trends in the use of definitive therapy, predictors of treatment type, and acute adverse events associated with primary modalities of treatment. METHODS AND MATERIALS: Data from the National Comprehensive Cancer Network Oncology Outcomes Database from 2007 to 2011 for US patients with stage I NSCLC were used. Main outcome measures included patterns of care, predictors of treatment, acute morbidity, and acute mortality. RESULTS: Seventy-nine percent of patients received surgery, 16% received definitive radiation therapy (RT), and 3% were not treated. Seventy-four percent of the RT patients received stereotactic body RT (SBRT), and the remainder received nonstereotactic RT (NSRT). Among participating NCCN member institutions, the number of surgeries-to-RT course ratios varied between 1.6 and 34.7 (P<.01), and the SBRT-to-NSRT ratio varied between 0 and 13 (P=.01). Significant variations were also observed in staging practices, with brain imaging 0.33 (0.25-0.43) times as likely and mediastinoscopy 31.26 (21.84-44.76) times more likely for surgical patients than for RT patients. Toxicity rates for surgical and for SBRT patients were similar, although the rates were double for NSRT patients. CONCLUSIONS: The variations in treatment observed among NCCN institutions reflects the lack of level I evidence directing the use of surgery or SBRT for stage I NSCLC. In this setting, research of patient and physician preferences may help to guide future decision making.

Integrated computed tomography-positron emission tomography in patients with potentially resectable malignant pleural mesothelioma: Staging implications.

BACKGROUND: Integrated computed tomography-positron emission tomography imaging with coregistration of anatomic and functional imaging data may improve the accuracy of malignant pleural mesothelioma staging. We evaluate the use of integrated computed tomography-positron emission tomography in patients with malignant pleural mesothelioma who are being considered for extrapleural pneumonectomy. METHODS: Twenty-nine patients with malignant pleural mesothelioma who were judged to be candidates for extrapleural pneumonectomy after clinical and conventional radiologic evaluation underwent whole-body integrated computed tomography-positron emission tomography and pathologic staging. Two reviewers blinded to the results of clinical and pathologic staging retrospectively evaluated computed tomography, positron emission tomography, and coregistered computed tomography-positron emission tomography images. Staging was performed according to the International Mesothelioma Interest Group TNM staging system. Histopathology and/or results of further radiologic evaluation or follow-up served as the reference standard. RESULTS: Integrated computed tomography-positron emission tomography provided additional information in 11 of 29 patients that precluded extrapleural pneumonectomy. The overall tumor stage was correctly classified in 21 of 29 patients. The tumor stage was correctly determined in 15 of 24 patients, 6 of whom had T4 (nonresectable) disease. The node stage was accurately determined in 6 of 17 patients. Extrathoracic metastases not identified by routine clinical and conventional radiologic evaluation were detected in 7 of 29 patients and were found to be diffuse (n = 2) or solitary (n = 5). CONCLUSIONS: Integrated computed tomography-positron emission tomography increases the accuracy of malignant pleural mesothelioma staging and is important in determining the appropriate therapy in patients being considered for extrapleural pneumonectomy.

A phase I study of topotecan/paclitaxel alternating with etoposide/cisplatin and thoracic irradiation in patients with limited small cell lung cancer.

PURPOSE: Topotecan and paclitaxel are promising cytotoxic drugs with novel mechanisms of action relative to other chemotherapies used in the treatment of small cell lung cancer (SCLC). In an effort to integrate paclitaxel and topotecan into the treatment of limited disease (LD) SCLC, we conducted a Phase I study of these agents administered as initial induction therapy. EXPERIMENTAL DESIGN: Escalating doses of topotecan (0.8-1.4 mg/m(2) d1-5) and paclitaxel (110-175 mg/m(2) d1) were administered i.v. every 21 days for two cycles to determine the maximum tolerated dose (MTD) in patients with LD SCLC. This was followed by two cycles of etoposide (120 mg/m(2) d1-3) and cisplatin (60 mg/m(2) d1) with thoracic radiotherapy. The first 5 subjects received 1.8 Gy once daily x 25 fractions, while subsequent subjects received 1.5 Gy twice daily x 30 fractions. Two additional cycles of chemotherapy (topotecan and paclitaxel, followed by etoposide and cisplatin) were given. RESULTS: Common toxicities included grade >/=3 neutropenia in 67% of courses of topotecan and paclitaxel and grade >/=2 esophagitis in 71% of patients. The MTD was based on toxicity during the first two cycles of chemotherapy and defined after accrual of 18 patients to four dose levels. Two of three patients developed grade 3 nonhematological toxicity (pneumonia) at the fourth dose level. Thus, the third dose level (topotecan 1.2 mg/m(2), paclitaxel 160 mg/m(2)) was defined as the MTD recommended for Phase II studies. One subject died suddenly on day 2 of cycle 1 without autopsy confirmation of the etiology. A second subject died during cycle 3 due to thrombocytopenia, gastrointestinal bleeding, and respiratory failure. Response rates after induction of topotecan and paclitaxel: 16 of 18 (88.8%) partial response, 1 of 18 (5.5%) complete response. Response rates after completion of therapy: 10 of 18 (55.5%) partial response, 7 of 18 (38.8%) complete response. CONCLUSIONS: Induction topotecan and paclitaxel before chemoradiotherapy in patients with LD SCLC is feasible and results in expected toxicities. The outcome of a recently closed Cancer and Leukemia Group B Phase II study of similar design (CLB-39808) should help determine whether or not this approach warrants testing in a randomized setting.