Search

Simple Summary: We evaluated the repurposing of a class of non-cancer drugs, phosphodiesterase inhibitors, to increase the potency of an anti-folate chemotherapy drug against non-small-cell lung cancer. We showed that this approach represents a double-edged strategy. While the use of phosphodiesterase inhibitors potentiated the killing of lung cancer cells by combination low-dose anti-folate chemotherapy, in half of the tumors evaluated, the benefit was lost when using higher doses of chemotherapy. Phosphosidesterases (PDEs) are key regulators of cyclic nucleotide signaling, controlling many hallmarks of cancer and playing a role in resistance to chemotherapy in non-small-cell lung cancer (NSCLC). We evaluated the anti-tumor activity of the anti-folate agent pemetrexed (PMX), alone or combined with biochemical inhibitors of PDE5, 8, 9, or 10, against squamous and non-squamous NCSLC cells. Genomic alterations to PDE genes (PDEmut) or PDE biochemical inhibition (PDEi) can sensitize NSCLC to PMX in vitro (observed in 50% NSCLC evaluated). The synergistic activity of PDEi with PMX required microdosing of the anti-folate drug. As single agents, none of the PDEis evaluated have anti-tumor activity. PDE biochemical inhibitors, targeting either cAMP or cGMP signaling (or both), resulted in significant cross-modulation of downstream pathways. The use of PDEi may present a new strategy to overcome PMX resistance of PDEwt NSCLC tumors but comes with important caveats, including the use of subtherapeutic PMX doses. [ABSTRACT FROM AUTHOR]

Background: A recently overall survival (OS) analysis from the AURA3 trial indicated that osimertinib improves median OS versus platinum-pemetrexed for patients with previously treated epidermal growth factor receptor (EGFR) T790M advanced non-small cell lung cancer (NSCLC). Here, we assessed the costeffectiveness of second-line osimertinib versus platinum-pemetrexed, from the perspectives of the United States payer and the Chinese health care system. Methods: A Markov model was constructed to compare the costs and health outcomes of osimertinib versus platinum-pemetrexed in second-line treatment of EGFR T790M advanced NSCLC. Life years (LYs), quality adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs) were calculated. One-way and probabilistic sensitivity analyses assessed the robustness of the model. Costeffectiveness was examined in the intention-to-treat (ITT) population and central nervous system (CNS) metastases population. Results: In the United States, compared with platinum-pemetrexed, osimertinib yielded additional effectiveness of 0.43 QALYs and -0.12 QALYs, with incremental costs of $67,588 and $16,465 in the ITT population and CNS metastases population, respectively. The ICERs of osimertinib over platinumpemetrexed were $159,126/QALY and $-130,830/QALY, respectively. The probability of osimertinib being cost-effective was 37% and 5.76%, respectively, at the willingness-to-pay (WTP) threshold of $150,000/QALY. In China, osimertinib showed incremental effectiveness of 0.34 QALYs and -0.14 QALYs, with incremental costs of $1,663 and $-505, resulting in ICERs of $4,950/QALY and $3,754/QALY in the ITT population and CNS metastases population, respectively. At the WTP threshold of $37,489/QALY, there was a 100% and 26% likelihood that osimertinib was cost-effective in the ITT population and CNS metastases population. Conclusion: In the United States, second-line osimertinib treatment for EGFR T790M advanced NSCLC is not cost-effective compared to platinumpemetrexed under the current WTP threshold. When the osimertinib price reduces, the economic outcome may become favorable. In China, assuming a WTP threshold of $37,489/QALY, osimertinib is the dominant treatment strategy compared with platinum-pemetrexed in the ITT population and provides cost savings for CNS metastases patients. [ABSTRACT FROM AUTHOR]

Aim: Assess factors associated with EGFR TKI initiation among patients with metastatic non-small-cell lung cancer (mNSCLC). Patients & methods: Medicare Part D patients diagnosed with non-squamous mNSCLC and starting an EGFR TKI within 1 year of diagnosis were selected from the Surveillance, Epidemiology and End Results (SEER)-Medicare database. Associations between patient characteristics and time from diagnosis to treatment initiation (time-to-treatment [TTT]) were analyzed. Results: Among the sample (n = 890), the patients who were younger, African-American or from rural communities had significantly longer TTT. Patients who did not receive surgery, who were Asian and those with brain metastases had significantly shorter TTT. Conclusion: Patient demographics and clinical characteristics may affect timeliness of EGFR TKI treatment for mNSCLC. Future research should examine potential barriers to treatment. [ABSTRACT FROM AUTHOR]

Lung cancer is the second most common cancer in both men and women and is the leading cause of cancer death in the United States. The development of drug resistance to commonly used chemotherapeutics in non-small-cell lung cancer (NSCLC) poses significant health risks and there is a dire need to improve patient outcomes. In this study, we report the use of RNA nanotechnology to display ligand on exosome that was loaded with small interfering RNA (siRNA) for NSCLC regression in animal trials. Cholesterol was used to anchor the ligand targeting epidermal growth factor receptor on exosomes that were loaded with siRNA to silence the antiapoptotic factor survivin. The cytosolic delivery of siRNA overcame the problem of endosome trapping, leading to potent gene knockdown, chemotherapy sensitization, and tumor regression, thus achieving a favorable IC50 of 20 nmol/kg siRNA encapsulated by exosome particles in the in vivo gene knockdown assessment. [ABSTRACT FROM AUTHOR]

Rationale: Because of improvements in screening, there is an increasing number of patients with early-stage non-small-cell lung cancer (NSCLC) who are making treatment decisions.Objectives: Among patients with suspected stage I NSCLC, we evaluated longitudinal patient-centered outcomes (PCOs) and the association of changes in PCOs with treatment modality, stereotactic body radiotherapy (SBRT) compared with surgical resection.Methods: We conducted a multisite, prospective, observational cohort study at seven medical institutions. We evaluated minimum clinically important differences of PCOs at four time points (during treatment, 4-6 wk after treatment, 6 mo after treatment, and 12 mo after treatment) compared with pretreatment values using validated instruments. We used adjusted linear mixed models to examine whether the association between treatment and European Organization for Research and Treatment of Cancer global and physical quality-of-life (QOL) scales differed over time.Results: We included 127 individuals with stage I NSCLC (53 surgery, 74 SBRT). At 12 months, approximately 30% of patients remaining in each group demonstrated a clinical deterioration on global QOL from baseline. There was a significant difference in slopes between treatment groups on global QOL (-12.86; 95% confidence interval [CI], -13.34 to -12.37) and physical QOL (-28.71; 95% CI, -29.13 to -28.29) between baseline and during treatment, with the steeper decline observed among those who underwent surgery. Differences in slopes between treatment groups were not significant at all other time points.Conclusions: Approximately 30% of patients with stage I NSCLC have a clinically significant decrease in QOL 1 year after SBRT or surgical resection. Surgical resection was associated with steeper declines in QOL immediately after treatment compared with SBRT; however, these declines were not lasting and resolved within a year for most patients. Our results may facilitate treatment option discussions for patients receiving treatment for early-stage NSCLC. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant therapy (NT) will be increasingly used for patients with non-small cell lung cancer (NSCLC), particularly given the recent approval of neoadjuvant chemoimmunotherapy. Several barriers may prevent the uptake of NT and should be identified and addressed. We queried the National Cancer Database (NCDB) to determine predictors of the use of NT., Methods: Using the NCDB (2006-2019), we identified 80,707 patients who underwent surgery for clinical stage II and III NSCLC. Sociodemographic and clinical factors were reviewed, and univariable and multivariable analyses were performed to identify associations with the uptake of NT. In propensity score-matched groups, survival was determined using the Kaplan-Meier method., Results: Among 80,707 eligible patients, 17,262 (21.4%) received NT. Clinical stage and node positivity were associated with receipt of NT. On multivariable analysis, factors associated with lower rates of NT included black race (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.67-0.90), Charlson Comorbidity Index ≥2 (OR, 0.75; 95% CI, 0.67-0.85), Medicaid/Medicare insurance (OR, 0.82; 95% CI, 0.75-0.90), lower income level (OR, 0.79; 95% CI, 0.71-0.87), and treatment at a community center (OR, 0.81; 95% CI, 0.67-0.96). In an exploratory analysis, those patients who received NT had longer 5-year overall survival compared with those who did not (48.3% vs 46.0%; P < .001)., Conclusions: Rates of NT are relatively low for patients with clinical stage II/III NSCLC treated prior to recent chemoimmunotherapy trials. Socioeconomic barriers to the uptake of NT include race, insurance status, income, and area of residence. As NT becomes more widely offered, accessibility for vulnerable populations must be assured., Competing Interests: Conflict of Interest Statement Dr Stiles reports consulting fees and research support from Medtronic, AstraZeneca, Genentech, Pfizer, Arcus Biosciences, Bristol Myers Squib, BMS Foundation, Gala Therapeutics, and the Lung Cancer Research Foundation. Dr Chudgar reports consulting fees from AstraZeneca. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Published by Elsevier Inc.)

Background: Racial and socioeconomic disparities in receipt of care for non-small-cell lung cancer (NSCLC) are well described. However, no previous studies have evaluated the association between mortgage denial rates and receipt of timely and guideline-concordant care for NSCLC and patient outcomes., Methods: We identified individuals ≥18 years diagnosed with NSCLC between 2014 and 2019 from the National Cancer Database. Using the Home Mortgage Disclosure Act database, we calculated the proportion of denied home loans to total loans at the zip-code level and categorized them into quintiles. Our outcomes included receipt of guideline-concordant care based on clinical and pathologic stage at diagnosis and the National Comprehensive Cancer Network guidelines, time from surgery to chemotherapy initiation, and overall survival., Results: Of the 629,288 individuals diagnosed with NSCLC (median age 69; IQR 61-76 years, 49.1% female), 47.8% did not receive guideline-concordant care. Residing in areas with higher mortgage denial rates and lower income was associated with worse guideline-concordant care overall (aRR = 1.28; 95% CI = 1.25-1.32) and for each cancer treatment modality, worse receipt of timely chemotherapy (aHR = 1.14; 95% CI = 1.11-1.17) and worse overall survival (aHR = 1.21; 95% CI = 1.19-1.22), compared with residing in areas with the lowest mortgage denial rate and highest income., Conclusions: Area-level mortgage denial rate was associated with worse receipt of timely and guideline-concordant NSCLC care and survival. This highlights the critical need to understand and address systemic practices, such as mortgage denial, that limit access to resources and are associated with worse access to quality cancer care and outcomes., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Brigatinib, a next‐generation anaplastic lymphoma kinase (ALK) inhibitor, received accelerated approval in the United States for the treatment of patients with metastatic ALK+ non–small‐cell lung cancer who have progressed on or are intolerant to crizotinib. A clinical study was conducted to assess the effect of food on brigatinib pharmacokinetics (PK). Healthy subjects received a single oral dose of brigatinib 180 mg (2 × 90‐mg tablets) after a 10‐hour fast or after a high‐fat meal in a 2‐period, 2‐sequence crossover study. Plasma samples for PK characterization were collected over 168 hours postdose. Twenty‐four subjects were enrolled (mean age 44 years; 58% male), with 21 included in the PK‐evaluable population. Brigatinib peak concentration was reduced by 13% under fed (high‐fat meal) versus fasted conditions, with no effect on area under the concentration‐time curve. The median time to peak concentration of brigatinib was longer under fed conditions (5 hours) than in fasted conditions (2 hours). Treatment‐emergent adverse events were similar under fasted (48%) and fed (46%) conditions and were of mild intensity. Consumption of a high‐fat meal decreased the rate of brigatinib oral absorption but had no impact on the extent of absorption, thereby supporting brigatinib administration without regard to meals. These recommendations are reflected in the US prescribing information for brigatinib. [ABSTRACT FROM AUTHOR]

• EXPRESS evaluated real-world prevalence of PD-L1 expression in advanced NSCLC. • The PD-L1 IHC 22C3 pharmDx assay was used, with local testing across 18 countries. • Testing failure rate was low with PD-L1 evaluation across a large number of sites. • The prevalence of PD-L1 expression was similar across geographic regions. • 53% of patients without EGFR/ALK aberrations had PD-L1 TPS ≥ 1% and 27% had TPS ≥ 50%. : Tumor programmed death ligand 1 (PD-L1) expression is associated with improved clinical benefit from immunotherapies targeting the PD-1 pathway. We conducted a global, multicenter, retrospective observational study to determine real-world prevalence of tumor PD-L1 expression in patients with NSCLC. : Patients ≥18 years with histologically confirmed stage IIIB/IV NSCLC and a tumor tissue block (≤5 years old) obtained before treatment were identified in 45 centers across 18 countries. Tumor samples from eligible patients were selected consecutively, when possible. PD-L1 expression was evaluated at each center using the PD-L1 IHC 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA). : Of 2617 patients who met inclusion criteria, 2368 (90%) had PD-L1 data; 530 (22%) patients had PD-L1 TPS ≥ 50%, 1232 (52%) had PD-L1 TPS ≥ 1%, and 1136 (48%) had PD-L1 TPS < 1%. The most common reason for not having PD-L1 data (n = 249) was insufficient tumor cells (<100) on the slide (n = 170 [6%]). Percentages of patients with PD-L1 TPS ≥ 50% and TPS ≥ 1%, respectively were: 22%/52% in Europe; 22%/53% in Asia Pacific; 21%/47% in the Americas, and 24%/55% in other countries. Prevalence of EGFR mutations (19%) and ALK alterations (3%) was consistent with prior reports from metastatic NSCLC studies. Among 1064 patients negative for both EGFR mutation and ALK alteration, the percentage with PD-L1 TPS ≥ 50% and TPS ≥ 1%, respectively, were 27% and 53%. : This is the largest real-world study in advanced NSCLC to date evaluating PD-L1 tumor expression using the 22C3 pharmDx kit. Testing failure rate was low with local evaluation of PD-L1 TPS across a large number of centers. Prevalence of PD-L1 TPS ≥ 50% and TPS ≥ 1% among patients with stage IIIB/IV NSCLC was similar across geographic regions and broadly consistent with central testing results from clinical trial screening populations. [ABSTRACT FROM AUTHOR]

Aim: This cohort study evaluated the association between immune checkpoint inhibitors (ICIs)-induced immune-related adverse events (irAEs) and mortality as well as ICI discontinuation among older adults with NSCLC. Methods: 2007-2019 Surveillance, Epidemiology and End Results-Medicare linked database was used and survival analysis with time-varying exposure of irAEs was applied to estimate the associations. Results & conclusion: A total of 8,175 individuals were included, with 46.8% of whom developed an irAE. Cox regression models showed the occurrence of any irAEs was associated with increased risk of mortality (HR: 1.73, 95% CI: 1.63-1.82) and treatment discontinuation (HR: 1.87, 95% CI: 1.78-1.97). Some variability was observed in the effect on the two outcomes depending on the type of irAE.

Background: Immune checkpoint inhibitor (ICI) treatment has been linked to a variety of immune-related adverse events (irAEs), which can affect any organ system. The incidence and risk factors of irAEs have not been adequately evaluated among older adults with NSCLC., Methods: A cohort study was conducted using 1999-2019 SEER-Medicare data among beneficiaries aged ≥65 years with a diagnosis of NSCLC who received nivolumab, pembrolizumab, or atezolizumab. Incident irAEs were identified post-ICI initiation. Demographic, cancer-related characteristics, and clinical history risk factors of irAEs were evaluated with competing events considered., Results: A total of 8175 older NSCLC patients were included (with 46.8% experiencing irAEs). Pneumonitis (16.5%), hypothyroidism (10.5%), arrhythmia (11.18%), and acute kidney injury (AKI) (5.8%) were the most common irAEs. The median time to first irAE was 82 days (IQR: 29-182 days). The earliest onset of irAE occurrence was for hematologic irAEs, while the latest were gastrointestinal, dermatologic, and musculoskeletal irAEs. Fine-Gray regression modeling revealed significantly greater hazards of irAE occurrence in patients who received pembrolizumab at index, did not have CNS metastases, had a history of autoimmune disorder, and had chemotherapy in combination with ICI. Race, socioeconomic status, previous radiation therapy, and comorbidity burden were found to be associated with the occurrence of certain type of irAEs., Conclusion: A significant proportion of older patients with NSCLC develop an irAE after receiving ICI treatment. Factors related to cancer and treatment as well as demographics contribute to the increased risk of irAEs. Close monitoring and prediction of irAE among older patients receiving ICI is warranted., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Aim: To quantify the economic burden of early-stage non-small-cell lung cancer (NSCLC) among patients with and without adjuvant therapy. Methods: All-cause and NSCLC-related healthcare resource utilization and medical costs were assessed among patients with resected stage IB-IIIA NSCLC in the SEER-Medicare database (1 January 2011-31 December 2019), from NSCLC diagnosis to death, end of continuous enrollment, or end of data availability (whichever occurred first). Results: Patients receiving adjuvant therapy had the lowest mean NSCLC-related medical costs (adjuvant [n = 1776]: $3738; neoadjuvant [n = 56]: $5793; both [n = 47]: $4818; surgery alone [n = 3478]: $4892, per-person-per-month), driven by lower NSCLC-related hospitalization rates. Conclusion: Post-surgical management of early-stage NSCLC was associated with high economic burden. Adjuvant therapy was associated with numerically lower medical costs over surgical resection alone.

Objectives: Non-small-cell lung cancer mortality has declined at a faster rate than incidence due to multiple factors, including changes in smoking behaviour, early detection which shifts diagnosis, and novel therapies. Limited resources require that we quantify the contribution of early detection versus novel therapies in improving lung cancer survival outcomes., Methods: Non-small-cell lung cancer patients from the Surveillance, Epidemiology, and End Results-Medicare data were queried and divided into: (i) stage IV diagnosed in 2015 (n = 3774) and (ii) stage I-III diagnosed in 2010-2012 (n = 15 817). Multivariable Cox-proportional hazards models were performed to assess the independent association of immunotherapy or diagnosis at stage I/II versus III with survival., Results: Patients treated with immunotherapy had significantly better survival than those who did not (HRadj: 0.49, 95% confidence interval: 0.43-0.56), as did those diagnosed at stage I/II versus stage III (HRadj: 0.36, 95% confidence interval: 0.35-0.37). Patients on immunotherapy had a 10.7-month longer survival than those who were not. Stage I/II patients had an average survival benefit of 34 months, compared to stage III. If 25%% of stage IV patients not on immunotherapy received it, there would be a gain of 22 292 person-years survival per 100 000 diagnoses. A switch of only 25% from stage III to stage I/II would correspond to 70 833 person-years survival per 100 000 diagnoses., Conclusions: In this cohort study, earlier stage at diagnosis contributed to life expectancy by almost 3 years, while gains from immunotherapy would contribute ½ year of survival. Given the relative affordability of early detection, risk reduction through increased screening should be optimized., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: This study investigated real-world treatment patterns and overall survival (OS) in early non-small-cell lung cancer patients and the association between OS and time-to-adjuvant-treatment. Materials & methods: This retrospective study using Surveillance, Epidemiology and End Results data linked with Medicare claims included resected early non-small-cell lung cancer patients between 2010 and 2015. Unadjusted OS analyses used Kaplan-Meier curves; adjusted OS analyses used extended Cox proportional hazards models. Results: Only 54-71% of stage II-IIIA patients received any adjuvant treatment. Adjusted risk of death was higher when starting treatment outside 6-8 weeks after surgery (p < 0.05). Conclusion: Improved systemic therapy in the adjuvant chemotherapy setting is needed.

Background We compared cardiac outcomes for surgery-eligible patients with stage III non-small-cell lung cancer treated adjuvantly or neoadjuvantly with chemotherapy versus chemo-radiation therapy in the Surveillance, Epidemiology and End Results-Medicare database. Methods and Results Patients were age 66+, had stage IIIA/B resectable non-small-cell lung cancer diagnosed between 2007 and 2015, and received adjuvant or neoadjuvant chemotherapy or chemo-radiation within 121 days of diagnosis. Patients having chemo-radiation and chemotherapy only were propensity-score matched and followed from day 121 to first cardiac outcome, noncardiac death, radiation initiation by patients who received chemotherapy only, fee-for-service enrollment interruption, or December 31, 2016. Cause-specific hazard ratios (HRs) and competing risks subdistribution HRs were estimated. The primary outcome was the first of these severe cardiac events: acute myocardial infarction, other hospitalized ischemic heart disease, hospitalized heart failure, percutaneous coronary intervention/coronary artery bypass graft, cardiac death, or urgent/inpatient care for pericardial disease, conduction abnormality, valve disorder, or ischemic heart disease. With median follow-up of 13 months, 70 of 682 patients who received chemo-radiation (10.26%) and 43 of 682 matched patients who received chemotherapy only (6.30%) developed a severe cardiac event ( P =0.008) with median time to first event 5.45 months. Chemo-radiation increased the rate of severe cardiac events (cause-specific HR: 1.62 [95% CI, 1.11-2.37] and subdistribution HR: 1.41 [95% CI, 0.97-2.04]). Cancer severity appeared greater among patients who received chemo-radiation (noncardiac death cause-specific HR, 2.53 [95% CI, 1.93-3.33] and subdistribution HR, 2.52 [95% CI, 1.90-3.33]). Conclusions Adding radiation therapy to chemotherapy is associated with an increased risk of severe cardiac events among patients with resectable stage III non-small-cell lung cancer for whom survival benefit of radiation therapy is unclear.

Abstract: Introduction: The identification of somatic genomic aberrations in non-small-cell lung cancer (NSCLC) is part of evidence-based practice guidelines for care of patients with NSCLC. We sought to establish the frequency and correlates with these changes in routine patient–tumor sample pairs. Methods: Clinicopathologic data and tumor genotype were retrospectively compiled and analyzed from an overall cohort of 381 patient–tumor samples. Results: Of these patients, 75.9% self-reported White race, 13.1% Asian, 6.5% Black, 27.8% were never-smokers, 54.9% former-smokers and 17.3% current-smokers. The frequency of EGFR mutations was 23.9% (86/359), KRAS mutations 34.2% (71/207) and ALK FISH positivity 9.1% (23/252) in tumor samples, and almost all had mutually exclusive results for these oncogenes. In tumors from White, Black and Asian patients, the frequencies of EGFR mutations were 18.4%, 18.2% and 62%, respectively; of ALK FISH positivity 7.81%, 0% and 14.8%, respectively; and of KRAS mutations 41.6%, 20% and 0%. These patterns changed significant with increasing pack-year history of smoking. In White patients, the frequencies of EGFR mutations and ALK FISH positivity decreased with increasing pack-year cohorts; while the frequencies of KRAS mutations increased. Interestingly, in Asian patients the frequencies of EGFR mutations were similar in never smokers and in the cohorts with less than 45pack-year histories of smoking and only decreased in the 45pack-year plus cohort. Conclusions: The frequencies of somatic EGFR, KRAS, and ALK gene abnormalities using routine lung cancer tissue samples from our United States-based academic medical practice reflect the diverse ethnicity (with a higher frequency of EGFR mutations in Asian patients) and smoking patterns (with an inverse correlation between EGFR mutation and ALK rearrangement) of our tested population. These results may help other medical practices appreciate the expected results from introduction of routine tumor genotyping techniques into their day-to-day care of NSCLC. [Copyright &y& Elsevier]

Introduction As angiogenic pathways have become important targets for inhibition of tumor growth, we examined the concept of dual pathway blockade by small-molecule tyrosine kinase inhibitors targeting vascular endothelial and epidermal growth factor receptors. Methods Escalating doses of pazopanib (400-800 mg once daily [QD]) plus erlotinib (100-150 mg QD) doses were evaluated in cohorts of 3-6 adults with advanced solid tumors. Twelve additional patients were enrolled in an expansion cohort to confirm the maximum tolerated dose (MTD). Results The MTD, defined during assessment of 20 patients, was pazopanib 600 mg plus erlotinib 150 mg. Two dose-limiting toxicities, rash and elevated liver enzymes, occurred at pazopanib 800 mg and erlotinib 150 mg. Overall, 30 % and 27 % of patients required dose interruption of pazopanib or erlotinib, respectively; 15 % of patients required a dose reduction of erlotinib to manage toxicities. The most common adverse events in patients treated with any dose regimen of pazopanib plus erlotinib ( N = 33) were diarrhea, rash, nausea, and decreased appetite. The adverse-event profile of the combination did not appear to differ from that of each compound administered alone. Coadministration of pazopanib 600 mg QD and erlotinib 150 mg QD did not consistently affect the pharmacokinetics of either compound relative to that observed for either compound administered alone. Of 26 patients evaluated for efficacy, 3 (12 %; all non-small-cell lung cancer) had partial response and 10 (38 %) had stable disease. Conclusions Concomitant administration of pazopanib 600 mg and erlotinib 150 mg is feasible, with a manageable toxicity profile. These results support further clinical development of the pazopanib-erlotinib combination. [ABSTRACT FROM AUTHOR]

Introduction: Lung cancer is the leading cause of cancer-related death in Europe and the US. Isolated metastases to skeletal muscle and the mandible are very uncommon.Case Presentation: This report presents two cases. Case 1 concerns a 45-year-old Caucasian woman affected by muscle metastasis of the right thigh from non-small-cell lung cancer. Case 2 concerns a 61-year-old Caucasian man affected by mandible metastasis from non-small-cell lung cancer. Both metastases were detected by diagnostic imaging studies. Both patients were treated with radiation therapy with palliative and antalgic intent.Conclusion: Radiation therapy was effective and well tolerated in both cases. Both our patients are alive, with follow-up of 18 months and five months, respectively. [ABSTRACT FROM AUTHOR]

Abstract: Background: This is a phase II randomized study to evaluate the efficacy and safety of bortezomib and pemetrexed alone or in combination, in patients with previously treated advanced non-small-cell lung cancer (NSCLC). The primary end point was assessment of response rate. Methods: A total of 155 patients were randomized (1:1:1) to pemetrexed (500mg/m2) on day 1 plus bortezomib (1.6mg/m2) on days 1 and 8 (Arm A) or pemetrexed (500mg/m2) on day 1 (Arm B) or bortezomib (1.6mg/m2) on days 1 and 8 (Arm C) of a 21 day cycle. Response rate was assessed by investigators using Response Evaluation Criteria In Solid Tumors (RECIST) criteria and toxicity assessed by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading system. Results: Response rate was 7% in Arm A, 4% in Arm B, and 0% in Arm C; disease control rates were 73%, 62%, and 43%, respectively. Median overall survival was 8.6 months in Arm A, 12.7 months in Arm B, and 7.8 months in Arm C; time to progression was 4.0 months, 2.9 months, and 1.4 months, respectively. Most common reported adverse events ≥grade 3 were neutropenia (19%), thrombocytopenia (15%), and dyspnea (13%) in Arm A, neutropenia (10%) in Arm B, and dyspnea (13%) and fatigue (10%) in Arm C. Conclusion: In previously treated NSCLC the addition of bortezomib to pemetrexed was well tolerated but offered no statistically significant response or survival advantage versus pemetrexed alone, while bortezomib alone showed no clinically significant activity. [Copyright &y& Elsevier]

Purpose: To compare the survival of postresection recurrent vs. newly diagnosed non–small-cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy. Methods and Materials: The study population consisted of 661 consecutive patients with NSCLC registered in the radiation oncology databases at two medical centers in the United States between 1992 and 2004. Of the 661 patients, 54 had postresection recurrent NSCLC and 607 had newly diagnosed NSCLC. Kaplan-Meier and Cox regression models were used for the survival analyses. Results: The distribution of relevant clinical factors between these two groups was similar. The median survival time and 5-year overall survival rates were 19.8 months (95% confidence interval [CI], 13.9–25.7) and 14.8% (95% confidence interval, 5.4–24.2%) vs. 12.2 months (95% CI, 10.8–13.6) and 11.0% (95% CI, 8.5–13.5%) for recurrent vs. newly diagnosed patients, respectively (p = .037). For Stage I-III patients, no significant difference was observed in the 5-year overall survival (p = .297) or progression-free survival (p = .935) between recurrent and newly diagnosed patients. For the 46 patients with Stage I-III recurrent disease, multivariate analysis showed that chemotherapy was a significant prognostic factor for 5-year progression-free survival (hazard ratio, 0.45; 95% CI, 0.224–0.914; p = .027). Conclusion: Our institutional data have shown that patients with postresection recurrent NSCLC achieved survival comparable to that of newly diagnosed NSCLC patients when they were both treated with radiotherapy or chemoradiotherapy. These findings suggest that patients with postresection recurrent NSCLC should be treated as aggressively as those with newly diagnosed disease. [Copyright &y& Elsevier]

PURPOSE: Complex radiotherapy (RT) planning is increasingly common in the treatment of lung cancer though it remains unclear if these treatments are associated with better outcomes. We evaluated the association between the complexity of RT planning simulation with survival among elderly Stage IIIB non-small cell lung cancer (NSCLC) patients. METHODS: We included all patients aged >65 years with histologically confirmed Stage IIIB NSCLC diagnosed between 1992 and 2002 receiving chemotherapy and RT from the Surveillance, Epidemiology, and End Results registry linked to Medicare claims. Patients were divided into simple, intermediate, and complex RT planning groups using Medicare physician codes. Kaplan-Meier curves and Cox regression were used to compare overall and lung cancer-specific survival rates across groups. RESULTS: We identified 1,733 patients: 148 (8%), 1,138 (66%), and 447 (26%) were classified as having received simple, intermediate and complex RT planning, respectively. Baseline characteristics were similar across groups. Increasing complexity of RT planning was significantly associated with better overall survival (p=0.0002). Multivariate analyses showed that intermediate (HR: 0.75, 95% CI: 0.62 to 0.91) and complex planning (HR: 0.69, 95% CI: 0.55 to 0.86) were associated with better overall survival compared to simple RT planning. Similar results were observed for lung cancer-specific survival analyses. Toxicities were comparable across groups. CONCLUSIONS: The use of more complex RT planning and simulation methods is associated with better survival in elderly patients with Stage IIIB NSCLC. Although these results should be further validated in prospective clinical trials, this data suggests that complex planning may improve the outcomes of these patients. [ABSTRACT FROM AUTHOR]

Purpose: To present issues to be considered in, and make proposals for, image-based brachytherapy for cervical cancer.Methods and materials: The Image-Guided Brachytherapy Working Group, consisting of representatives from the Gynecology Oncology Group (GOG), Radiologic Physics Center (RPC), American Brachytherapy Society (ABS), American College of Radiology (ACR), American College of Radiology Imaging Network (ACRIN), American Association of Physicists in Medicine (AAPM), Radiation Therapy Oncology Group (RTOG), and American Society for Therapeutic Radiology and Oncology (ASTRO), proposed guidelines for image-based brachytherapy for cervical cancer. This report was based on their aggregate clinical experience and a review of the literature. It reflects only the personal opinions of the authors and is not meant to be an endorsement from any of the above organizations.Results: The Group recommended T2-weighted MRI using a pelvic surface coil with MRI-compatible brachytherapy applicators in place for image-based intracavitary brachytherapy for cervical cancer. Imaging must be performed with the patient in the treatment position, with all other treatment conditions duplicated as closely as possible. Future use of positron emission tomography or positron emission tomography/CT may obviate the need for special applicators. The group proposed the following terminology for image-based brachytherapy. The GTV(I) is defined as the gross tumor volume as defined through imaging, GTV is defined as the GTV(I) plus any clinically visualized or palpable tumor extensions, and GTV + cx is defined as the GTV plus the entire cervix. The dose–volume histograms (DVH) of the GTV, GTV(I), GTV + cx should be performed, and the dose to 100%, 95%, or 90% of the GTV (D100, D95, and D90, respectively) and the percentage of the GTV covered by Point A dose (V100) should be reported. Similarly, the DVH of the bladder and rectum wall should be performed, and the maximal dose at any point within the bladder and rectal wall should be reported, along with the maximal dose to a contiguous 1, 2, and 5 cm3 volume of the bladder and rectum, respectively. In addition, the dose at the International Commission on Radiation Units and Measurements reference point for the bladder and rectum should be reported. The Group thought that the current dose prescription method in use for cervical cancer brachytherapy (i.e., to prescribe to Point A in most institutions) should not be changed as yet, because image-based dosimetry is not ready for routine practice. The Group proposes that for research purposes, individual centers and cooperative groups (e.g., GOG, RTOG, ACRIN) collect image-based dosimetry information and perform DVHs and correlate these data with the clinical outcome to determine which of the above parameters are relevant. The Group encourages external funding for image-based dosimetry and recommends that brachytherapy manufacturers develop image-compatible applicators.Conclusion: Although current institutional brachytherapy prescription for cervical cancer should continue, image-based data collection and analysis are needed to optimize cervical cancer brachytherapy. Proposals are made for research in image-based brachytherapy for cervical cancer. [Copyright &y& Elsevier]

Lung cancer is the leading cause of cancer-related death in the United States, accounting for over 30% of cancer deaths in men and 25% in women. Small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) are uniformly aggressive tumors, with rates of regional or distant metastases at diagnosis as high as 70%. Because the majority of these tumors are unresectable, patients with relatively good performance status receive platinum-based chemotherapy. Although no treatment consensus exists, currently recommended regimens for SCLC include PE (cisplatin and etoposide), CAV (cyclophosphamide, doxorubicin, and vincristine), CAE (cyclophosphamide, doxorubicin, and etoposide), and CAVE (cyclophosphamide, doxorubicin, vincristine, and etoposide). Of these, the PE regimen has been widely accepted in the United States, although CE (carboplatin and etoposide) provides better tolerability. For NSCLC, standard chemotherapy regimens have included platinum-based therapy (cisplatin and a vinca alkaloid or PE). Data from recent studies suggest that the addition of paclitaxel to platinum modestly improves tumor response and survival in NSCLC. Although SCLC and NSCLC are both responsive to first-line chemotherapy, most patients relapse and die from their disease, with 5-year survival rates of approximately 15%. Given the disappointing survival rates associated with SCLC and NSCLC, the introduction of new cytotoxic agents has been eagerly anticipated. Evidence of improved response and extended survival is mounting for various combinations of established regimens (e.g., PE) with newer drugs exhibiting novel mechanisms of action and single-agent antitumor activity, such as gemcitabine, paclitaxel, docetaxel, vinorelbine, and topotecan. This article reviews the current standards of care in SCLC and NSCLC, and introduces the potential role of newer agents given in combination with standard chemotherapy.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Geographic and socioeconomic factors impact patient treatment choices for certain cancers. Whether they impact treatment in older adults with lung cancer is unknown. We investigated geographic differences in treatment for stage I non-small-cell lung cancer (NSCLC) in older adults in the United States., Methods: Using the Surveillance, Epidemiology and End Results Database 18th submission, a cohort of stage I NSCLC patients ≥60-years-old was created. Treatment differences (surgery or radiation alone) by geographic location and socioeconomic factors were analyzed., Results: Forty-three thousand three hundred and eighty-seven stage I NSCLC patients were analyzed. Demographics and socioeconomic factors varied across all 13 states (p < 0.001). Surgery was the most common treatment in all states (range 58.6% in AK to 86.5% in CT) (all p < 0.001). Our multivariable analysis found older individuals had higher odds of getting radiation as compared to surgery (odds ratio [OR]: 1.22 for 65-69 years-old to OR: 8.95 for 85+ years-old; p < 0.001). Multiple states (LA, HI, IA, MI, WA, NM) were associated with increased odds of radiation use (vs. surgery alone) (all p < 0.05). People with lower education level (OR: 0.98) and median income (OR: 0.99) and non-Black race (OR: 0.52 for "other" to OR: 0.68 for "White" race with respect to Black race) were associated with lower odds of radiation (p < 0.05)., Conclusions: Our study identified treatment differences for stage I NSCLC patients in the United States related to demographics, socioeconomic factors, and geographic location., (© 2022 Wiley Periodicals LLC.)

Aim: To evaluate the cost-effectiveness of nivolumab plus ipilimumab (NI) in the first-line treatment of patients with advanced non-small-cell lung cancer from a US-payer perspective. Materials & methods: We developed a Markov model to evaluate the cost and effectiveness of NI versus chemotherapy as first-line treatment of NSCLC. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were estimated. Results: NI provided an additional 0.715 QALYs compared with chemotherapy in all population. The corresponding ICER of NI was $180,307 per QALY gained. However, the ICER decreased to $143,434 per QALY in the programmed death ligand 1 expression level <1% population. Conclusion: From a US-payer perspective, NI is estimated to be cost-effective in the first-line setting for advanced NSCLC patients with programmed death ligand 1 expression level <1%.

Objectives: Primary lung adenosquamous carcinoma (ASC) is a rare cancer subtype and has a poor prognosis. The prognostic factors for resected early-stage ASC remain unclear. We aimed to develop a nomogram to predict lung cancer-specific survival (LCSS) of patients undergoing surgical resection for stage I-II ASC., Methods: Data of patients undergoing resection for stage I-II ASC and diagnosed between 2004-2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. All the included patients were randomized at a 7:3 ratio into a training and a validation cohort. We selected and integrated significant prognostic factors based on competing for risk regression to build a nomogram. The performance of the nomogram was evaluated using Harrell's concordance index (C-index) and calibration plots., Results: A total of 988 patients (530 men and 458 women) undergoing surgical resection for stage I-II ASC were identified and randomized into a training (692, 70%) cohort and a validation cohort (296, 30%). The baseline characteristics were similar in the training and validation cohorts. Age, T stage, N stage, and the number of examined lymph nodes were independent prognostic factors for LCSS and were used in the nomogram. The calibration plots showed that the 3- and 5-year LCSS probabilities were consistent between the nomogram prediction and the actual observation. The C-index of the nomogram was 0.671 (95%CI: 0.618-0.724) and 0.635 (95%CI: 0.557-0.713) in the training cohort and validation cohort, respectively. We developed a risk classification system based on the nomogram to stratify patients into high- and low-risk of cancer-specific death groups. Patients with a similar risk shared similar prognostic prediction regardless of the stage category and patients with the same risk shared similar prognoses despite the different stage category., Conclusions: We developed a competing risk nomogram to reliably predict cancer-specific survival of patients undergoing surgical resection for stage I-II ASC. The nomogram might be a useful tool to identify patients undergoing surgical resection for ASC who could be suitable candidates for adjuvant chemotherapy., (© 2020 Wiley Periodicals, Inc.)

Objectives: We sought to identify the risk factors associated with mortality post-video-assisted thoracoscopic surgery (VATS) lobectomy over a 2-year period., Methods: Analysis was performed using a sample from an institutionally maintained database. All lobectomies for non-small-cell lung cancer from April 2014 to March 2018 started with VATS approach and with a complete follow-up were included (n = 732). Several clinical variables were screened using the Cox univariate analysis for their association with 2-year survival. Those with a P-value <0.1 were included in a Cox proportional hazard model., Results: After multivariable analysis, the following variables showed significant association with 2-year survival: age >75 [hazard ratio (HR) 1.527, P = 0.043], carbon monoxide lung diffusion capacity <70 (HR 1.474, P = 0.061), body mass index (BMI) <18.5 (HR 2.628, P = 0.012), American Society of Anesthesiologist Physical Status >2 (HR 1.518, P = 0.047), performance status >1 (HR 1.822, P = 0.032) and male gender (HR 2.700, P < 0.001). A score of 2 was assigned to the male gender and BMI <18.5, with all other variables assigned a score of 1. Each patient was scored and placed into their risk class. A Kaplan-Meier estimate for 2-year survival was calculated for each class. These were collapsed into the following 3 classes of risk based on their similar 2-year survival: class A (score 0) 97%, 95% CI 88-99, class B (score 1-3) 84%, 95% CI 80-88, class C (score > 3) 66%, 95% CI 57-74., Conclusion: Our scoring system can serve as an adjunct to a clinician's experience in risk-stratifying patients during multidisciplinary tumour board discussion and the shared decision-making process., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aim: To estimate the real-world incidence and timing of radiation pneumonitis following chemoradiotherapy for Stage III non-small-cell lung cancer and compare costs between patients with and without radiation pneumonitis. Methods: Retrospective analysis using the Symphony Health Integrated Dataverse. Results: Pneumonitis incidence was 12.4% with a 177-day mean time to onset. Patients with versus without pneumonitis were more frequently admitted to the hospital (33.8 vs 19.2%, p < 0.0001) and seen in the emergency room (51.9 vs 35.8%, p < 0.0001) and had higher mean total healthcare costs (US$4251 vs US$3969 per-patient per-month; p = 0.0163). Conclusion: Although pneumonitis significantly increased healthcare resource utilization and costs in chemoradiotherapy-treated Stage III non-small-cell lung cancer, the per-patient per-month differential was <10%. Such financial assessments are critical for cost-benefit analysis.

Background: There is wide interest in developing prognostic models in non-small-cell lung cancer (NSCLC) due to the heterogeneity of the disease. Models developed at other healthcare institutions may not be directly applicable for patients treated at the Department of Veterans Affairs (VA). External validation of a candidate prognostic model among VA patients would be crucial before it can be implemented to aid clinical decision-making., Methods: A prognostic model for mortality developed in the Military Health System (MHS) was applied to data from the VA Precision Oncology Data Repository (VA-PODR), which is available to researchers inside and outside the VA at the Veterans Precision Oncology Data Commons (VPODC). Measures of discrimination and calibration were calculated for the MHS model. The MHS model was also refitted in VA-PODR data using the same risk factors to compare the effect of specific factors and predictive performance when the model is developed using VA data., Results: Time-dependent AUC of the MHS prognostic model was 0.788, 0.806, 0.780, and 0.779 for predicting survival at 1, 2, 3, and 5 years following diagnosis, respectively. Significant discrepancies were found between predicted and observed rates of survival, particularly for later years. When the model is refit in VA-PODR data, it achieved cross-validated AUCs of 0.739, 0.773, 0.769, and 0.807 at the same time points, and discrepancies between predicted and observed survival were reduced., Conclusions: Validation of the MHS prognostic model in VA-PODR demonstrates that its discrimination remains strong when applied to VA patients. Nevertheless, further calibration to VA data may be needed to improve its risk estimation performance. This study highlights the utility of VA-PODR and the VPODC as a national resource for developing analytic tools that are well adapted to the Veteran population., (Published by Elsevier Inc.)

Objectives: Adjuvant chemotherapy is routinely offered post-surgical resection for early stage non-small-cell lung cancer (NSCLC) ≥4 cm; however, its role following definitive stereotactic body radiotherapy (SBRT) has not been well defined. We investigated the association between receipt of adjuvant chemotherapy post-SBRT and overall survival (OS) for patients with T1-T3N0M0 NSCLC in the National Cancer Database (NCDB)., Materials and Methods: The NCDB was queried for patients with T1-T3N0M0 NSCLC treated with definitive SBRT from 2004 to 2014. The association between non-randomized receipt of adjuvant chemotherapy and OS was analyzed for all patients (n = 24,011) and a propensity-matched cohort (n = 608) using Kaplan-Meier methods and Cox proportional hazard models. A subset analysis was performed for patients with tumors ≥4 cm (n = 2,323)., Results: There were 24,011 patients in the cohort with a median follow-up of 32.5 months. Of these, 322 (1.3%) received adjuvant chemotherapy. Three-year OS was 41.3% with adjuvant chemotherapy compared to 50.6% without adjuvant chemotherapy (p = 0.001). On multivariate analysis, adjuvant chemotherapy was independently associated with higher overall mortality (hazard ratio:1.22, 95% confidence interval:1.06-1.40, p = 0.005). For tumors ≥4 cm, 3-year OS was 38.2% with adjuvant chemotherapy (n = 80) compared to 33.0% without adjuvant chemotherapy (p = 0.81). After propensity-score matching, there was a persistent association between lower OS and adjuvant chemotherapy with those receiving adjuvant chemotherapy (n = 322) having 3-year OS of 41.3% compared to 60.9% without adjuvant chemotherapy (p < 0.0001)., Conclusion: Adjuvant chemotherapy following definitive SBRT for T1-3N0M0 NSCLC is associated with lower OS and is not associated with a survival benefit for patients with tumors ≥4 cm., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Women with lung cancer have better survival than men. The reasons are unknown, but estrogen is hypothesized to improve survival. Our objective was to examine the association between estrogen monotherapy and cancer-specific and overall survival in elderly women with non-small cell lung cancer (NSCLC)., Materials and Methods: We used the SEER-Medicare database to identify women ≥65 years old who were diagnosed with stage III or IV NSCLC. Estrogen monotherapy (EM) was defined as at least one estrogen claim without any progesterone claims 6 months prior to diagnosis. To assess cancer-specific survival and overall survival, we used Kaplan-Meier and multivariate Cox modeling with propensity score adjustments. As an exploratory analysis, we also examined the effect of combined estrogen and progesterone hormonal therapy on survival using Cox modeling., Results: We identified 6958 women in our initial cohort: 283 used EM (4%) and 6675 (96%) did not. The median follow-up time was 46.5 months in the EM patients and 49.5 months in the non-EM patients. In a Kaplan-Meier analysis, median overall survival was 8.2 months in patients who receive EM and 6.2 months in those who did not (p = 0.004). In our 1:4 propensity-matched cohort, median follow-up was 46.5 in the EM group and 50.6 in the non-EM group; median overall survival was 8.0 months in the EM group and 6.4 months in the non-EM group (p = 0.02). In a multivariate Cox regression of the matched cohort, EM was significantly associated with overall survival (HR 0.84; 95% CI 0.73 - 0.97). All results were similar for cancer-specific survival. In our exploratory analysis, combined Estrogen-Progesterone did significantly impact overall survival (HR 0.84; 95% CI 0.71-0.99, p = 0.04) but did not appear to effect cancer-specific survival (HR 0.91; 95% CI 0.77-1.09, p = 0.30)., Conclusion: EM was associated with a significant improvement in cancer-specific survival and overall survival in women with late stage NSCLC., (Copyright © 2019. Published by Elsevier B.V.)

The first biosimilar of bevacizumab was approved by the US FDA; other potential biosimilars of bevacizumab are in late-stage clinical development. Their availability offers opportunity for increased patient access across a number of oncologic indications. The regulatory pathway for biosimilar approval relies on the totality of evidence that includes a comprehensive analytical assessment, and a clinical comparability study in a relevant disease patient population. Extrapolation of indications for a biosimilar to other eligible indications held by the originator, in the absence of direct clinical comparison, frequently forms part of the regulatory judgment. Herein, we consider the evidence required to demonstrate biosimilarity for bevacizumab biosimilars, with particular focus on the rationale for extrapolation across oncologic indications.

Objectives: To determine whether there are differences in survival associated with different treatment modalities among patients with lymph node-negative, very large non-small-cell lung cancers (NSCLCs)., Methods: The National Cancer DataBase was used to identify patients diagnosed with NSCLCs >7 cm (T3) without lymph node involvement (N0) or metastatic disease (M0) from 1999 to 2006. Surgical therapy included surgery alone, neoadjuvant chemoradiation therapy or chemotherapy, surgery followed by adjuvant chemoradiation therapy or chemotherapy and surgery followed by postoperative radiation therapy (PORT). The 5-year overall survival (OS) was estimated by the Kaplan-Meier method and comparisons were made using log-rank tests and Cox regression models., Results: Of the 2296 patients identified with cT3N0M0 disease, 45% underwent surgical therapy. The 5-year OS rate was 38%. Across the different treatment regimens, there was a significant difference in 5-year OS. Neither neoadjuvant chemoradiation therapy or chemotherapy nor adjuvant chemoradiation therapy was associated with improved 5-year OS. The use of adjuvant chemotherapy was associated with improved OS relative to surgery alone [hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.54-0.91, P = 0.008]. PORT alone was associated with a detrimental effect on 5-year OS relative to surgery alone [HR 2.04; 95% CI 1.38-3.03, P < 0.001]., Conclusions: Large T3N0 NSCLCs appear to be optimally treated with surgical resection followed by adjuvant chemotherapy., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: The role of adjuvant chemotherapy for non-small-cell lung cancer (NSCLC) stage I patients with tumors size ≥4 cm is not well established in the elderly., Patients and Methods: We identified 3289 patients with stage I NSCLC (T2N0M0 and tumor size ≥4 cm) who underwent lobectomy from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database diagnosed from 1992 to 2009. Overall survival and rates of serious adverse events (defined as those requiring admission to hospital) were compared between patients treated with resection alone, platinum-based adjuvant chemotherapy, or postoperative radiation (PORT) with or without adjuvant chemotherapy. Propensity scores for receiving each treatment were calculated and survival analyses were conducted using inverse probability weights based on the propensity score., Results: Overall, 84% patients were treated with resection alone, 9% received platinum-based adjuvant chemotherapy, and 7% underwent PORT with or without adjuvant chemotherapy. Adjusted analysis showed that adjuvant chemotherapy [hazard ratio (HR), 0.82; 95% confidence interval (CI) 0.68-0.98] was associated with improved survival compared with resection alone. Conversely, the use of PORT with or without adjuvant chemotherapy (HR 1.91; 95% CI 1.64-2.23) was associated with worse outcomes. Patients receiving adjuvant chemotherapy had more serious adverse events compared with those treated with resection alone, with neutropenia (odds ratio, 21.2; 95% CI 5.8-76.6) being most significant. No significant difference was observed in rates of fever, cytopenias, nausea, and renal dysfunction., Conclusions: Platinum-based adjuvant chemotherapy is associated with reduced mortality and increased serious adverse events in elderly patients with stage I NSCLC and tumor size ≥4 cm., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Racial disparities in outcomes of non-small-cell lung cancer (NSCLC) patients in the United States are well documented. A retrospective analysis of patients in the Veterans Affairs Central Cancer Registry was conducted to determine whether similar disparities exist in a population with a single-payer, accessible health care system., Patients and Methods: Demographic data of patients diagnosed with NSCLC between January 1995 and February 2009 were analyzed using Kruskal-Wallis test or the χ(2) test. Multivariate Cox proportional hazards regression analysis was used to compare survival among races., Results: Of the 82,414 patients, 98% were male, 82% had a smoking history, and 81% were Caucasian. Caucasian individuals had better prognostic features compared with African-American individuals (stage I/II [24% vs. 21%]; Grade I/II [21% vs. 17%]). A larger proportion of Caucasian compared with African-American individuals received stage-appropriate treatment (surgery for stage I [48% vs. 41%; P < .001]; chemotherapy for stage IV [18% vs. 16%; P = .003]). African-American individuals had a lower risk of mortality compared with Caucasian individuals (hazard ratio, 0.94; 95% confidence interval, 0.92-0.96)., Conclusion: Although African-American patients had a higher stage and grade of NSCLC, they had a better overall survival than Caucasian patients. In a single-payer system with accessible health care, previously described racial differences in lung cancer outcomes were not observed., (Published by Elsevier Inc.)

Radiation therapy plays a potential curative role in the treatment of patients with non-small-cell lung cancer with locoregional disease who are not surgical candidates and a palliative role for patients with metastatic disease. Stereotactic body radiation therapy is a relatively new technique in patients with early-stage non-small-cell lung cancer. A trial from RTOG(®) reported >97% local control at 3 years. For patients with locally advanced disease, thoracic radiation to a dose of 60 Gy remains the standard of care. Sequential chemotherapy or radiation alone can be used for patients with poor performance status who cannot tolerate more aggressive approaches. Chemotherapy should be used for patients with metastatic disease. Radiation therapy is useful for palliation of symptomatic tumors, and a dose of approximately 30 Gy is commonly used. Endobronchial brachytherapy is useful for patients with symptomatic endobronchial tumors. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment., (Copyright © 2013 American College of Radiology. Published by Elsevier Inc. All rights reserved.)