Lung Cancer Screening, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology.

Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. Early detection of lung cancer is an important opportunity for decreasing mortality. Data support using low-dose computed tomography (LDCT) of the chest to screen select patients who are at high risk for lung cancer. Lung screening is covered under the Affordable Care Act for individuals with high-risk factors. The Centers for Medicare & Medicaid Services (CMS) covers annual screening LDCT for appropriate Medicare beneficiaries at high risk for lung cancer if they also receive counseling and participate in shared decision-making before screening. The complete version of the NCCN Guidelines for Lung Cancer Screening provides recommendations for initial and subsequent LDCT screening and provides more detail about LDCT screening. This manuscript focuses on identifying patients at high risk for lung cancer who are candidates for LDCT of the chest and on evaluating initial screening findings.

Age-related changes in nanoparticle albumin-bound paclitaxel pharmacokinetics and pharmacodynamics: influence of chronological versus functional age.

PURPOSE: This study evaluated age-related changes in pharmacokinetic and pharmacodynamic parameters of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in patients with metastatic breast cancer. METHODS: Forty patients received nab-paclitaxel (100 mg/m(2) weekly for 3 weeks followed by a 1-week break) as first- or second-line chemotherapy. Blood samples were collected for analysis, and response was assessed every two cycles. Planned statistical analyses included linear regression to examine the relationship between age and pharmacokinetic variables (ln clearance [CL] and ln area under the curve [AUC]) and two-sided two-sample t tests to evaluate age differences in pharmacodynamic variables. The association between chemotherapy toxicity risk scores and pharmacokinetic and pharmacodynamic variables including grade ≥ 3 toxicity were examined post hoc. RESULTS: Of 40 patients enrolled, 39 (98%) were evaluable (mean age: 60 years; range: 30-81 years). A partial response was achieved in 31%, and 38% had stable disease. There was a borderline positive association between age and 24-hour ln AUC (slope = 0.011; SE = 0.006; p = .055). Grade 3 toxicity was experienced by 26% (8% hematologic, 18% nonhematologic). There were no differences in age based on the presence of grade 3 toxicity (p = .75), dose reductions (p = .38), or dose omissions (p = .15). A significant association was noted between chemotherapy toxicity risk score category and presence of grade 3 toxicity (toxicity rate by risk score category: low, 5 of 30 patients; medium, 3 of 6 patients; high, 2 of 3 patients; p = .041). CONCLUSION: A borderline significant relationship exists between age and 24-hour AUC, but no differences were noted for pharmacodynamic variables (grade 3 toxicity, dose reductions, or dose omissions) based on age. There is an association between toxicity risk score and grade ≥ 3 chemotherapy toxicity and pharmacokinetic variables. The treatment is well tolerated across all age groups.

A phase II study of vorinostat and rituximab for treatment of newly diagnosed and relapsed/refractory indolent non-Hodgkin lymphoma.

This study examines the activity and tolerability of a regimen combining vorinostat and rituximab in patients with indolent B-cell non-Hodgkin lymphoma. A total of 28 patients with newly diagnosed or relapsed/refractory follicular, marginal zone, or mantle cell lymphoma, with 4 or less prior therapies were eligible for this open-label phase II study. Oral vorinostat 200 mg was administered twice daily on days 1-14 along with 375 mg/m(2) of intravenous rituximab on day 1 of a 21-day cycle, continuing until disease progression or unacceptable toxicity. Primary end point was objective response rate, with secondary end points of progression-free survival, time to progression, duration of response, safety, and tolerability. Median follow up was 25.6 months and median number of vorinostat cycles was 11.5. Overall response rate was 46% for all patients, 67% for previously untreated, and 41% for relapsed/refractory patients. Median progression-free survival was 29.2 months for all patients, 18.8 months for previously treated patients, and not reached for untreated patients. The regimen was well tolerated over long treatment periods with the most common grade 3/4 adverse events being asymptomatic thrombosis, neutropenia, thrombocytopenia, lymphopenia, and fatigue. The vorinostat/rituximab combination exhibits activity in indolent B-cell non-Hodgkin lymphoma with an acceptable safety profile and durable responses. Re-treatment was effective in 2 of 3 relapsing responders. This phase II clinical trial was registered at clinicaltrials.gov identifier: 00720876.

Lung cancer screening, version 1.2015: featured updates to the NCCN guidelines.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Lung Cancer Screening provide recommendations for selecting individuals for lung cancer screening, and for evaluation and follow-up of nodules found during screening, and are intended to assist with clinical and shared decision-making. These NCCN Guidelines Insights focus on the major updates to the 2015 NCCN Guidelines for Lung Cancer Screening, which include a revision to the recommendation from category 2B to 2A for one of the high-risk groups eligible for lung cancer screening. For low-dose CT of the lung, the recommended slice width was revised in the table on "Low-Dose Computed Tomography Acquisition, Storage, Interpretation, and Nodule Reporting."

Change in Apparent Diffusion Coefficient Is Associated With Local Failure After Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer: A Prospective Clinical Trial.

PURPOSE: Response assessment with computed tomography after stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC) is challenging because myriad anatomic changes can occur after treatment. Diffusion-weighted magnetic resonance imaging (MRI) may provide additional data to guide therapy response. The primary objective was to evaluate the effect of SBRT on the mean apparent diffusion coefficient (ADC). METHODS AND MATERIALS: This is a prospective clinical study of patients with NSCLC who received SBRT to the primary lung lesion. Patients underwent MRI scans before and at 1 month after completion of SBRT. MRI consisted of T1- and T2-weighted sequences, along with postcontrast, dynamic-contrast, and diffusion-weighted sequences with construction of ADC maps. Two blinded radiologists generated the ADC. SBRT was given over 5 fractions. RESULTS: A total of 13 patients were enrolled. Twelve patients were eligible for analysis. An average increase of 50% and 46% in mean single-plane ADC was observed after treatment by readers 1 and 2, respectively (P < .01, both reviewers). There was good interobserver agreement of single-plane ADC values between the 2 radiologists (Pearson correlation of 0.85 [baseline] and 0.89 [1-month post-SBRT], P < .001 for both). There was also a significant 18% increase in mean volumetric ADC on the 1-month scan (Wilcoxon P = .02). Two patients developed a local failure after SBRT, 1 at 6 months and the other at 34 months. Using a threshold of volumetric ADC increase of greater than 40%, 2 of 2 patients demonstrated local failure compared with 0 of 10 patients below this limit. CONCLUSIONS: A statistically significant increase in ADC was observed 1 month after treatment. An ADC increase of 40% at 1 month was associated with a higher rate of local failure. This pilot study provides impetus for studying ADC as a radiomic biomarker in patients receiving lung SBRT for NSCLC.

A Phase II Trial of Older Adults With Metastatic Breast Cancer Receiving nab-Paclitaxel: Melding the Fields of Geriatrics and Oncology.

INTRODUCTION: Phase II clinical trials including geriatric assessment (GA) measures are critical for improving the evidence base for older adults with cancer. We assessed the efficacy and tolerability of nab-paclitaxel in older adults with metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients aged ≥ 65 years with MBC and ≤ 1 previous line of chemotherapy received 100 mg of nab-paclitaxel on days 1, 8, and 15 of a 28-day cycle. A GA was completed pre-chemotherapy, and the validated Cancer and Aging Research Group (CARG) chemotherapy toxicity risk score was calculated. Relationships between tolerability (number of courses, hospitalizations, dose reductions, and toxicity) and risk score were assessed using general linear models, Student t tests, and the Fisher test. Response rate and progression-free survival were evaluated using the Kaplan-Meier method. RESULTS: Forty patients (mean age, 73 years; range, 65-87 years) were included. The median number of cycles was 6, 75% (n = 30) of patients had ≥ 1 dose hold, and 50% (n = 20) had ≥ 1 dose reduction. Fifty-eight percent (n = 23) had treatment-related ≥ grade 3 toxicities, and 30% (n = 12) were hospitalized owing to toxicity. Thirty-five percent (n = 14) responded, and the median progression-free survival was 6.5 months (95% confidence interval, 5.5 months to undefined). Patients with intermediate/high toxicity risk scores had higher risk of grade ≥ 3 toxicity than those with low risk scores (odds ratio, 5.8; 95% confidence interval, 1.3-33.1; P = .01). A higher mean risk score was associated with higher likelihood of dose reductions and hospitalizations. CONCLUSIONS: Among older adults with MBC receiving weekly nab-paclitaxel, more than one-half experienced ≥ grade 3 chemotherapy toxicity. However, a GA-based risk score could predict treatment tolerability.

Is there a role for PET in the evaluation of subcentimeter pulmonary nodules?

There are little published data available at this time to determine the appropriate role of positron emission tomography (PET) in the evaluation of subcentimeter pulmonary nodules. The sensitivity for malignancy is lower in these smaller lesions, while one would expect the specificity to be higher. Given that the resolution of current generation PET scanners is only 5 to 6 mm, one will be very unlikely to gain useful information from PET for a lesion below 5 mm. For lesions 5 to 10 mm in size, useful information might be gained from PET in those deemed intermediate risk by CT criteria, but this remains to be established. A positive PET in a small, intermediate risk lesion might push one toward biopsy/excision, though a negative PET in such a lesion must be considered to provide no information whatsoever. Even with advances in PET technologies in the future, we feel it is unlikely that PET will evolve a major role in the evaluation of the subcentimeter nodule.

Augmented meaningful use criteria to identify patients eligible for lung cancer screening.

BACKGROUND: Lung cancer screening (LCS) with low-dose-radiation (low-dose computed tomography [LDCT]) saves lives. Despite recent US Preventive Services Task Force (USPTF) draft endorsement of LCS, a minority of eligible patients get screened. Meaningful use is a set of standards for electronic health records (EHR) established by the Centers for Medicare and Medicaid Services and includes reporting of smoking status. We sought to improve rates of LCS among patients treated at our institution by identifying eligible patients using augmented smoking-related meaningful use criteria. METHODS: We launched an LCS program at our institution, a National Comprehensive Cancer Network (NCCN) cancer center, in January 2013. We developed a "tobacco screen," administered by clinic staff to all adult outpatients every 6 months and entered into the EHR. This contained smoking-related meaningful use criteria as well as a pack-year calculation and quit date if applicable. Weekly electronic reports of patients who met eligibility criteria for LCS were generated, and EHR review excluded patients who had had chest computed tomography (CT) within 12 months or who were undergoing cancer treatment. We then contacted eligible patients to review eligibility for LCS and communicated with the primary treating physician regarding the plan for LCS. RESULTS: During the first 3 months of the program, 4 patients were enrolled, 2 by physician referral and 2 by self-referral. We then began to use the tobacco screen reports and identified 418 patients potentially eligible for LCS. Over the next 7 months, we enrolled a total of 110 patients. Fifty-eight (53%) were identified from the tobacco screen, 32 (29%) were self-referred, and 20 (18%) were physician referrals. Three stage I lung cancers were detected and treated. The tobacco screen was easily implemented by clinic staff and took a median time of 2 minutes to enter for current and former smokers. Lack of response to attempts at telephone contact and objection to paying out-of-pocket costs were the most common reasons for failing to screen eligible patients. CONCLUSIONS: Use of augmented meaningful use criteria containing detailed tobacco exposure history is feasible and allows for identification of patients eligible for LCS in a medical center. Barriers to LCS include lack of insurance coverage and lack of systematic referral of patients at high risk.

Phase II study of vorinostat for treatment of relapsed or refractory indolent non-Hodgkin's lymphoma and mantle cell lymphoma.

PURPOSE: We performed a phase II study of oral vorinostat, a histone and protein deacetylase inhibitor, to examine its efficacy and tolerability in patients with relapsed/refractory indolent lymphoma. PATIENTS AND METHODS: In this open label phase II study (NCT00253630), patients with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL), with ≤ 4 prior therapies were eligible. Oral vorinostat was administered at a dose of 200 mg twice daily on days 1 through 14 of a 21-day cycle until progression or unacceptable toxicity. The primary end point was objective response rate (ORR), with secondary end points of progression-free survival (PFS), time to progression, duration of response, safety, and tolerability. RESULTS: All 35 eligible patients were evaluable for response. The median number of vorinostat cycles received was nine. ORR was 29% (five complete responses [CR] and five partial responses [PR]). For 17 patients with FL, ORR was 47% (four CR, four PR). There were two of nine responders with MZL (one CR, one PR), and no formal responders among the nine patients with MCL, although one patient maintained stable disease for 26 months. Median PFS was 15.6 months for patients with FL, 5.9 months for MCL, and 18.8 months for MZL. The drug was well-tolerated over long periods of treatment, with the most common grade 3 adverse events being thrombocytopenia, anemia, leucopenia, and fatigue. CONCLUSION: Oral vorinostat is a promising agent in FL and MZL, with an acceptable safety profile. Further studies in combination with other active agents in this setting are warranted.