Tan, Angelina D.

Background: Although 50% to 90% of patients who receive epidermal growth factor receptor (EGFR) inhibitors develop a rash, options for rash prevention or palliation remain limited. This issue is particularly important from a palliative care standpoint because these agents are prescribed only to patients with incurable cancer. Here, we report (1) gene expression profiling of skin biopsies from patients with an EGFR inhibitor–induced rash and (2) a randomized, placebo-controlled feasibility trial with the antiandrogen, spironolactone. Both investigations were undertaken to begin to explore the hypothesis that androgens mediate EGFR inhibitor–induced rash and that antiandrogens palliate it. Methods/Results: First, 4 skin biopsies from patients with EGFR inhibitor–induced rash (3 men and 1 woman) were subject to gene expression microarray profiling. A public data set of normal skin gene expression (Gene Expression Omnibus, GSE22998) served as a reference. Sixty percent of commonly interrogated androgen receptor genes (207 of 308 between the 2 data sets) were differentially expressed ( P < .05) in the rash samples. Second, in a 17-patient double-blinded, placebo-controlled trial with topical spironolactone applied to the face, although the primary feasibility end point was not achieved, patients in the spironolactone arm received more doses of EGFR inhibitor, and anecdotal photographic evidence suggested salutatory effects of spironolactone on rash. Conclusions: Epidermal growth factor receptor inhibitor–induced rash appears to be androgen-mediated; antiandrogen therapy merits further study for rash prevention/palliation.

32 Background: The link between patient concerns and clinical systems delivery is often suboptimal. We developed a case management system for palliative care which transforms the patient’s greatest concerns into actionable clinical pathways. Methods: The system collects patients’ single greatest and second greatest concern plus Quality of Life (QOL) data (pain, fatigue and overall QOL single-items scored 0-10 with 10 representing worst pain/fatigue, or best QOL) and produces a report to guide the physician and patient. The system presents ten “buttons” in a xylophone-like grid: Personal Relationships, Monitoring Health, Emotional Health, Money, Health Behaviors, Medication Troubles, Care Access, Work Worries, Physical Health and Care Planning. We performed a quality improvement study at Mayo Clinic sites. Results: 409 patients participated in at least one survey from 11/04/2015 to 9/22/2016 (620 total surveys). The most common Main Concern was Physical Health 265/620 (43%) followed by Monitoring Health (17%), Medication (8%), and Emotional Health, Money, and Health Behaviors (7% each), Personal Relationships (6%). Future Care Planning, Work, and Care Access/Coordination were rarely chosen ( < 5%). The most common Second greatest concern was Health Behaviors 73/409 (18%) followed by Physical Health (17%). 93/122 (67%) patients changed their greatest concern from baseline to subsequent visits. The mean QOL, fatigue and pain at baseline were 4.8, 6.0 and 4.8 respectively, indicating substantial clinically significant deficits. Post baseline mean scores improved by a maximum of 0.8, 1.1, and 0.9 points respectively, representing clinically meaningful effects. On average it took 8 minutes for patients to use the system. Conclusions: The system was quick and easy to utilize. The personal impact concerns (physical/emotional health, medications) were most often cited as the greatest concern, while care issues were de-emphasized by patients. Patients and physicians praised the system for making visits more efficient and raising issues that otherwise might not have been addressed. This system has the potential to improve patient well-being and clinical outcomes, as well as to reduce burden on clinicians and optimize case management activities.

AbstractThis analysis was performed to create a scoring system to estimate the survival of patients with non‐small cell lung cancer (NSCLC). Data from 1274NSCLCpatients were analyzed to create and validate a scoring system. Univariate (UV) and multivariate (MV) Cox models were used to evaluate the prognostic importance of each baseline factor. Prognostic factors that were significant on bothUVandMVanalyses were used to develop the score. These included quality of life, age, performance status, primary tumor diameter, nodal status, distant metastases, and smoking cessation. The score for each factor was determined by dividing the 5‐year survival rate (%) by 10 and summing these scores to form a total score.MVmodels and the score were validated using bootstrapping with 1000 iterations from the original samples. The score for each prognostic factor ranged from 1 to 7 points with higher scores reflective of better survival. Total scores (sum of the scores from each independent prognostic factor) of 32–37 correlated with a 5‐year survival of 8.3% (95%CI = 0–17.1%), 38–43 correlated with a 5‐year survival of 20% (95%CI = 13–27%), 44–47 correlated with a 5‐year survival of 48.3% (95%CI = 41.5–55.2%), 48–49 correlated to a 5‐year survival of 72.1% (95%CI = 65.6–78.6%), and 50–52 correlated to a 5‐year survival of 84.7% (95%CI = 79.6–89.8%). The bootstrap method confirmed the reliability of the score. Prognostic factors significantly associated with survival on bothUVandMVanalyses were used to construct a valid scoring system that can be used to predict survival ofNSCLCpatients. Optimally, this score could be used when counseling patients, and designing future trials.

BACKGROUNDThis study evaluated the 2‐year overall survival rate, adverse event rate, local control rate, and impact on pulmonary function tests for medically inoperable patients with stage IA non–small cell lung cancer (NSCLC) undergoing computed tomography (CT)–guided radiofrequency ablation (RFA) in a prospective, multicenter trial.METHODSFifty‐four patients (25 men and 29 women) with a median age of 76 years (range, 60‐89 years) were enrolled from 16 US centers; 51 patients were eligible for evaluation (they had biopsy‐proven stage IA NSCLC and were deemed medically inoperable by a board‐certified thoracic surgeon). Pulmonary function tests were performed within the 60 days before RFA and 3 and 24 months after RFA. Adverse events were recorded and categorized. Patients were followed with CT and fludeoxyglucose positron emission tomography. Local control rate and recurrence patterns were analyzed.RESULTSThe overall survival rate was 86.3% at 1 year and 69.8% at 2 years. The local tumor recurrence–free rate was 68.9% at 1 year and 59.8% at 2 years and was worse for tumors > 2 cm. In the 19 patients with local recurrence, 11 were re‐treated with RFA, 9 underwent radiation, and 3 underwent chemotherapy. There were 21 grade 3 adverse events, 2 grade 4 adverse events, and 1 grade 5 adverse event in 12 patients within the first 90 days after RFA. None of the grade 4 or 5 adverse events were attributable to RFA. There was no significant change in the forced expiratory volume in the first second of expiration or the diffusing capacity of lung for carbon monoxide after RFA. A tumor size less than 2.0 cm and a performance status of 0 or 1 were associated with statistically significant improved survival of 83% and 78%, respectively, at 2 years.CONCLUSIONSRFA is a single, minimally invasive procedure that is well tolerated in medically inoperable patients, does not adversely affect pulmonary function tests, and provides a 2‐year overall survival rate that is comparable to the rate reported after stereotactic body radiotherapy in similar patients. Cancer 2015;121:3435–43. © 2015 American Cancer Society.

Purpose A major concern with sublobar resection (SR) for non–small-cell lung cancer (NSCLC) is high local recurrence (LR). Adjuvant brachytherapy may reduce LR This multicenter randomized trial compares SR to SR with brachytherapy (SRB). Patients and Methods High-risk operable patients with NSCLC ≤ 3 cm were randomly assigned to SR or SRB. The primary end point was time to LR, where LR included recurrence at the staple line (local progression), in the primary tumor lobe away from the staple line, and in ipsilateral hilar nodes. The trial was designed to have a 90% power to detect a hazard ratio (HR) of 0.315 in favor of SRB, using a one-sided type I error rate of 0.05 with a sample size of 100 eligible patients in each arm. Results Two hundred twenty-four patients were randomly assigned; 222 patients were evaluable for intent-to-treat analysis. Median age was 71 years (range, 49 to 87 years). No differences were found in baseline characteristics. Median follow-up time was 4.38 years (range, 0.04 to 5.59 years). There was no difference in time to LR (HR, 1.01; 95% CI, 0.51 to 1.98; log-rank P = .98) or in the types of LR. Local progression occurred in only 17 (7.7%) of 222 patients. In patients with potentially compromised margins (margin < 1 cm, margin-to-tumor ratio < 1, positive staple line cytology, wedge resection, nodule size > 2.0 cm), SRB did not reduce LR, although trends favored the SRB arm. This was most marked in 14 patients with positive staple line cytology (HR, 0.22; P = .24). Three-year overall survival rates were similar for patients in the SR (71%) and SRB (71%) arms (P = .97). Conclusion Brachytherapy did not reduce LR after SR. This finding may have been related to closer attention to parenchymal margins by surgeons participating in this study.