Change in amount smoked and readiness to quit among patients undergoing lung cancer screening.

BACKGROUND: There is mixed evidence regarding whether undergoing computed tomography lung cancer screening (LCS) can serve as a "teachable moment" that impacts smoking behavior and attitudes. The study aim was to assess whether the standard procedures of undergoing LCS and receiving free and low-cost evidence-based cessation resources impacted short-term smoking-related outcomes. METHODS: Participants were smokers (N=87) who were registered to undergo lung screening and were enrolled in a cessation intervention trial. We conducted two phone interviews, both preceding trial randomization: the first interview was conducted prior to lung screening, and the second interview followed lung screening (median =12.5 days post-screening) and participants' receipt of their screening results. The interviews assessed demographic characteristics, interest in evidence-based cessation intervention methods, and tobacco-related characteristics, including cigarettes per day and readiness to quit. Participants received minimal evidence-based cessation resources following the pre-lung screening interview. RESULTS: Participants were 60.3 years old, 56.3% female, and reported a median of 40 pack-years. Participants were interested in using several evidence-based strategies, including counseling from a healthcare provider (76.7%) and receiving nicotine replacement therapy (69.8%). Pre-lung screening, 25.3% smoked ≤10 cigarettes per day, and 29.9% were ready to quit in the next 30 days. We conducted two McNemar binomial distribution tests to assess change from pre- to post-screening. At the post-lung screening assessment, approximately three-quarters reported no change on these variables. However, 23.3% reported smoking fewer cigarettes per day, whereas 4.7% reported smoking more cigarettes per day (McNemar P=0.002), and 17.2% reported increased readiness to quit, whereas 6.9% reported decreased readiness to quit (McNemar P=0.078). CONCLUSIONS: Following receipt of cessation resources and completion of lung screening, most participants reported no change in smoking outcomes. However, there was a significant reduction in cigarettes per day, and there was a trend for increased readiness to quit. This setting may provide a potential "teachable moment" and an opportunity to assist smokers with quitting. However, more proactive and intensive interventions will be necessary to capitalize on these changes and to support abstinence in the long-term.

Genomic Profiling of Advanced Non-Small Cell Lung Cancer in Community Settings: Gaps and Opportunities.

BACKGROUND: National guidelines have advocated broad molecular profiling as a part of the standard diagnostic evaluation for advanced non-small cell lung cancer (NSCLC), with the goal of identifying driver mutations for which effective therapies or clinical trials are available. However, adherence to genomic testing guidelines could present challenges to community oncologists. PATIENTS AND METHODS: We performed a retrospective review of genomic testing patterns in patients with nonsquamous NSCLC treated by 89 oncologists at 15 sites throughout New Jersey and Maryland from January 2013 to December 2015. RESULTS: A total of 814 patients (89% with stage IV; 11% with stage IIIB) were identified in the COTA Inc database. Of the 814 patients, 479 (59%) met the guideline recommendations for EGFR (epidermal growth factor receptor) and ALK (anaplastic lymphoma kinase) biomarker testing; 63 (8%) underwent comprehensive genomic profiling for all 4 major types of alterations (point mutations, indels, fusions, and copy number amplifications). Gender, age, race, site of care (referral vs. community center), and practice size did not influence comprehensive genomic profiling frequency. Active smokers and patients who died within 30 days were tested less frequently (P < .05). Among those not tested for EGFR and ALK, 52% received chemotherapy without documented reasons for no testing, 32% did not receive antineoplastic therapy, and 13% had insufficient tissue for genotyping. CONCLUSION: Genomic testing presents multiple logistical challenges for the community-based oncologist, including coordination of sample handling, long turnaround times, test reimbursement, access to targeted therapies, insufficient tissue, and patient harm from the repeat biopsies necessary if the tissue sample is insufficient. Opportunities exist for improvement in guideline adherence, possibly through new technologies such as "liquid biopsies," which obviates the need tissue biopsy samples in select settings.

Preliminary evaluation of a telephone-based smoking cessation intervention in the lung cancer screening setting: A randomized clinical trial.

Incorporating effective smoking cessation interventions into lung cancer screening (LCS) programs will be essential to realizing the full benefit of screening. We conducted a pilot randomized trial to determine the feasibility and efficacy of a telephone-counseling (TC) smoking cessation intervention vs. usual care (UC) in the LCS setting. In collaboration with 3 geographically diverse LCS programs, we enrolled current smokers (61.5% participation rate) who were: registered to undergo LCS, 50-77 years old, and had a 20+ pack-year smoking history. Eligibility was not based on readiness to quit. Participants completed pre-LCS (T0) and post-LCS (T1) telephone assessments, were randomized to TC (N=46) vs. UC (N=46), and completed a final 3-month telephone assessment (T2). Both study arms received a list of evidence-based cessation resources. TC participants also received up to 6 brief counseling calls with a trained cessation counselor. Counseling calls incorporated motivational interviewing and utilized the screening result as a motivator for quitting. The outcome was biochemically verified 7-day point prevalence cessation at 3-months post-randomization. Participants (56.5% female) were 60.2 (SD=5.4) years old and reported 47.1 (SD=22.2) pack years; 30% were ready to stop smoking in the next 30 days. TC participants completed an average of 4.4 (SD=2.3) sessions. Using intent-to-treat analyses, biochemically verified quit rates were 17.4% (TC) vs. 4.3% (UC), p<.05. This study provides preliminary evidence that telephone-based cessation counseling is feasible and efficacious in the LCS setting. As millions of current smokers are now eligible for lung cancer screening, this setting represents an important opportunity to exert a large public health impact on cessation among smokers who are at very high risk for multiple tobacco-related diseases. If this evidence-based, brief, and scalable intervention is replicated, TC could help to improve the overall cost-effectiveness of LCS. TRIAL REGISTRATION: NCT02267096, https://clinicaltrials.gov.

A multicenter phase II study of ganetespib monotherapy in patients with genotypically defined advanced non-small cell lung cancer.

PURPOSE: Ganetespib is a novel inhibitor of the heat shock protein 90 (Hsp90), a chaperone protein critical to tumor growth and proliferation. In this phase II study, we evaluated the activity and tolerability of ganetespib in previously treated patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Patients were enrolled into cohort A (mutant EGFR), B (mutant KRAS), or C (no EGFR or KRAS mutations). Patients were treated with 200 mg/m(2) ganetespib by intravenous infusion once weekly for 3 weeks followed by 1 week of rest, until disease progression. The primary endpoint was progression-free survival (PFS) at 16 weeks. Secondary endpoints included objective response (ORR), duration of treatment, tolerability, median PFS, overall survival (OS), and correlative studies. RESULTS: Ninety-nine patients with a median of 2 prior systemic therapies were enrolled; 98 were assigned to cohort A (n = 15), B (n = 17), or C (n = 66), with PFS rates at 16 weeks of 13.3%, 5.9%, and 19.7%, respectively. Four patients (4%) achieved partial response (PR); all had disease that harbored anaplastic lymphoma kinase (ALK) gene rearrangement, retrospectively detected by FISH (n = 1) or PCR-based assays (n = 3), in crizotinib-naïve patients enrolled to cohort C. Eight patients (8.1%) experienced treatment-related serious adverse events (AE); 2 of these (cardiac arrest and renal failure) resulted in death. The most common AEs were diarrhea, fatigue, nausea, and anorexia. CONCLUSIONS: Ganetespib monotherapy showed a manageable side effect profile as well as clinical activity in heavily pretreated patients with advanced NSCLCs, particularly in patients with tumors harboring ALK gene rearrangement.

A randomized phase II trial of first-line treatment with gemcitabine, erlotinib, or gemcitabine and erlotinib in elderly patients (age ≥70 years) with stage IIIB/IV non-small cell lung cancer.

INTRODUCTION: Single-agent gemcitabine is a standard of care for elderly patients with advanced non-small cell lung cancer, but novel therapies are needed for this patient population. METHODS: We performed a noncomparative randomized phase II trial of gemcitabine, erlotinib, or the combination in elderly patients (age ≥70 years) with stage IIIB or IV non-small cell lung cancer. Patients were randomized to arms: A (gemcitabine 1200 mg/m on days 1 and 8 every 21 days), B (erlotinib 150 mg daily), or C (gemcitabine 1000 mg/m on days 1 and 8 every 21 days and erlotinib 100 mg daily). Arms B and C were considered investigational; the primary objective was 6-month progression-free survival. RESULTS: Between March 2006 and May 2010, 146 eligible patients received protocol therapy. The majority of the patients (82%) had stage IV disease, 64% reported adenocarcinoma histology, 90% reported current or previous tobacco use, and 28% had a performance status of 2. The 6-month progression-free survival rate observed in arms A, B, and C was 22% (95% confidence interval [CI] 11-35), 24% (95% CI 13-36), and 25% (95% CI 15-38), respectively; the median overall survival observed was 6.8 months (95% CI 4.8-8.5), 5.8 months (95% CI 3.0-8.3), and 5.6 months (95% CI 3.5-8.4), respectively. The rate of grade ≥3 hematological and nonhematological toxicity observed was similar in all three arms. The best overall health-related quality of life response did not differ between treatment arms. CONCLUSIONS: Erlotinib or erlotinib and gemcitabine do not warrant further investigation in an unselected elderly patient population.

The feasibility of adjuvant carboplatin and docetaxel in patients with curatively resected non-small cell lung cancer.

INTRODUCTION: Adjuvant cisplatin-based chemotherapy improves overall survival; however, chemotherapy compliance has been difficult. Carboplatin (C) is better tolerated than cisplatin, and carboplatin-based adjuvant therapy may have better chemotherapy compliance. METHODS: The primary end point of this multicenter phase II trial was the feasibility of delivering carboplatin and docetaxel (C/D). An "adequate exposure" was defined as receiving four cycles of C/D within 12 weeks of initiating adjuvant therapy. A sample size of 72 patients provided 88% power to detect a true adequate exposure of rate of at least 80%. Patients with resected non-small cell lung cancer, a good functional status, and preserved organ function were eligible. Adjuvant therapy was initiated between 2 and 8 weeks after surgery, and consisted of four cycles C (area under the curve = 6), and D 75 mg/m every 3 weeks. RESULTS: Seventy-two patients were treated, and the patient demographics were: median age 65 years (range 47-84), gender male/female 67%/33%, stage I (40%), II (36%) IIIA (22%) and IIIB (1%), and the two most common histologies were: adenocarcinoma (44%), and squamous cell carcinoma (42%). Fifty-seven patients (79%) received four cycles within 12 weeks, and 15 (21%) of patients did not complete four cycles for the following reasons: adverse events (n = 5), patient refusal (n = 5), disease progression during active therapy (n = 3), and intercurrent illness (n = 2). No treatment related deaths were observed and the primary toxicities were hematologic (grade 4 neutropenia 42% and febrile neutropenia 11% of patients). Twenty-six patients (36%) received growth colony stimulating factor (G-CSF) supportive therapy during their treatment, and G-CSF supportive therapy was used in 21.6% of all cycles. CONCLUSIONS: C/D has an acceptable toxicity profile with the use of G-CSF supportive therapy and the majority of patients completed four cycles of therapy within 12 weeks.

Suppression of the human vestibulo-ocular reflex by visual fixation or forced convergence in the dark, with a model interpretation.

Six normal humans experienced yaw axis steps of velocity at 120 degrees /s in the dark. During the post-rotary period, subjects either had a null-task (do nothing); an ocular motor task (forced convergence: crossing the eyes); or a visual task (fixating a head-stationary target against a background of 10 degrees light/dark bars). Tasks started at 3 s post-rotation, and lasted either 2, 5, 10, or 15 s. Ocular motor and visual tasks were tested on different days. Five repetitions of each task duration were recorded for each subject. A mean VOR gain of 0.52 was observed, which did not vary with experimental conditions. Both convergence and fixation markedly suppressed nystagmus; in fact, the VORs obtained with the two different tasks are superficially similar in appearance. However, mean null-task time-constants were 9.4 s for convergence days, but 8.4 s for fixation days, and there was a small but significant reduction in overall null-task VOR amplitude on fixation days. Also, post-convergence slow-phase velocities were slightly enhanced, while post-fixation velocities were significantly reduced. The time-constant of velocity storage was found to be 10.1 s for convergence responses and 8.2 s for fixation responses. These differences can be understood in terms of modifications in central velocity storage during visual fixation which do not occur with convergence. The mean fixation data were analyzed in the context of a VOR model well-established for monkey data. With appropriate choice of parameters, this model accurately reproduces most features of the human data. An estimate for the human cupula time-constant of 3.3 s is obtained. Compared with the monkey, fixation suppression is greater and post-fixation velocity reduction less. Retinal slip alone accounts well for this; "velocity dumping" by an integrator shunt must be slight if present at all. The model correctly represents the post-fixation VOR for all durations of fixation.