Complete pathologic response to short-course neoadjuvant alectinib in mediastinal node positive (N2) ALK rearranged lung cancer.

OBJECTIVES: Neoadjuvant therapy prior to surgical resection for locally advanced lung cancer has evolved to incorporate systemic cytotoxic chemotherapy +/- immunotherapy +/- radiotherapy. The role of neoadjuvant precision therapies remains understudied. MATERIALS AND METHODS: We report cases with major and complete pathologic responses to off-label neoadjuvant alectinib. RESULTS: A case with stage IIIA (cT1b cN2 cM0) EML4-ALK variant 3a/b lung adenocarcinoma received 6 weeks of alectinib followed by R0 left upper lobectomy with complete pathological response (ypT0 ypN0). Another case with stage IIIA (cT3 cN2 cM0) EML4-ALK variant 2 received 12 weeks of alectinib followed by R0 right middle lobectomy with a major pathologic response (ypT1a ypN0) but systemic recurrence 12 months post-operatively. CONCLUSION: Ongoing clinical trials are evaluating the role of both neoadjuvant and adjuvant ALK-directed therapy. Our cases support the completion of ongoing trials (ALINA: NCT03456076 and ALNEO: NCT05015010), and highlight the ability of second generation ALK inhibitors to induce major and complete pathologic responses in the neoadjuvant setting plus the likely role of long-term adjuvant kinase inhibitor therapy to prevent radiographic/clinical recurrence.

Patterns of care for non-small-cell lung cancer at an academic institution affiliated with a national cancer institute-designated cancer center.

PURPOSE: Evidence-based treatment guidelines for non-small-cell lung cancer (NSCLC) exist to improve the quality of care for patients with this disease. However, how often evidence-based decisions are used for care of NSCLC is poorly understood. PATIENTS AND METHODS: We examined patterns of care and rate of adherence to evidence-based guidelines for 185 new NSCLC patients seen between 2007 and 2009. Evidence-based care status was determined for 150 patients. RESULTS: Eighty-one percent of the patients were white, the mean age was 66 years, 49% were women, 11% were never smokers, 83% had Eastern Cooperative Oncology Group performance status 0 to 1, 49.7% of tumors were adenocarcinomas, 57.1% of never smokers had tumors genotyped (EGFR, ALK, KRAS), and 13.3% participated in clinical trials. The rate of evidence-based treatment adherence was 94.1% (16 of 17), 100% (21 of 21) and 100% (36 of 36) in patients with stages I, II, and III NSCLC, respectively. Stage IV disease, with adherence of 76.3% (58 of 76), was correlated with a higher rate of nonadherence when compared with stages I-III (odds ratio 16.33; 95% CI, 1.94 to 137.73). In patients with stage IV disease, the rate of evidence-based adherence was 95% (72 of 76) for first-line therapy, 95.2% (40 of 42) for second-line therapy, and only 33.3% (6 of 18) for third-line therapy (P < .001). There was no significant correlation between evidence-based adherence status and the patient's age, sex, performance status, smoking history, ethnicity, or the treating physician. CONCLUSION: These data point toward the need for improved evidence-based use of resources in the third-line setting of stage IV NSCLC.

Expanded prostate cancer index composite for clinical practice: development and validation of a practical health related quality of life instrument for use in the routine clinical care of patients with prostate cancer.

PURPOSE: Measuring the health related quality of life of patients with prostate cancer in routine clinical practice is hindered by the lack of instruments enabling efficient, real-time, point of care scoring of multiple health related quality of life domains. Thus, we developed an instrument for this purpose. MATERIALS AND METHODS: The Expanded Prostate Cancer Index Composite for Clinical Practice is a 1-page, 16-item questionnaire that we constructed to measure urinary incontinence, urinary irritation, and the bowel, sexual and hormonal health related quality of life domains. We eliminated conceptually overlapping items from the 3-page Expanded Prostate Cancer Index Composite-26 and revised the questionnaire format to mirror the AUA symptom index, thereby enabling practitioners to calculate health related quality of life scores at the point of care. We administered the Expanded Prostate Cancer Index Composite for Clinical Practice to a new cohort of patients with prostate cancer in community based and academic oncology, radiation, and urology practices to evaluate instrument validity as well as ease of use in clinical practice. RESULTS: A total of 175 treated and 132 untreated subjects with prostate cancer completed the Expanded Prostate Cancer Index Composite for Clinical Practice. The domain scores of the Expanded Prostate Cancer Index Composite for Clinical Practice correlated highly with the respective domain scores from longer versions of the Expanded Prostate Cancer Index Composite (r≥0.93 for all domains). The Expanded Prostate Cancer Index Composite for Clinical Practice showed high internal consistency (Cronbach's α 0.64-0.84) and sensitivity to prostate cancer treatment related effects (p<0.05 in each of 5 health related quality of life domains). Patients completed the Expanded Prostate Cancer Index Composite for Clinical Practice efficiently (96% in less than 10 minutes and with 11% missing items). It was deemed very convenient by clinicians in 87% of routine clinical encounters and clinicians accurately scored completed questionnaires 94% of the time. CONCLUSIONS: The Expanded Prostate Cancer Index Composite for Clinical Practice is a valid instrument that enables patient reported, health related quality of life to be measured efficiently and accurately at the point of care, and thereby facilitates improved emphasis and management of patient reported outcomes.