Long-term assessment of efficacy with a novel Thoracic Survivorship Program for patients with lung cancer.

OBJECTIVE: We developed a novel, nurse practitioner-run Thoracic Survivorship Program to aid in long-term follow-up. Patients with non-small cell lung cancer who were disease-free at least 1 year after resection could be referred to the Thoracic Survivorship Program by their surgeon. Our objectives were to summarize follow-up compliance and assess long-term outcomes between Thoracic Survivorship Program enrollment and non-Thoracic Survivorship Program. METHODS: Patients who underwent R0 resection for stages I to IIIA between 2006 and 2016 were stratified by enrollment in Thoracic Survivorship Program versus surgeon only follow-up (non-Thoracic Survivorship Program). Follow-up included 6-month chest computed tomography scans for 2 years and then annually. Lack of follow-up compliance was defined by 2 or more consecutive delayed annual computed tomography scans/visits ± 90 days. Relationships between Thoracic Survivorship Program and second primary non--small cell lung cancers, extrathoracic cancers, and survival were quantified using multivariable Cox proportional hazards regression with time-varying covariate reflecting timing of enrollment. RESULTS: A total of 1162 of 3940 patients (29.5%) were enrolled in the Thoracic Survivorship Program. The median time to enrollment was 2.3 years; 3279 of 3940 (83%) had complete computed tomography scan data, and 60 of 3279 (1.8%) had 2 or more delayed scans; 323 of 9082 (3.6%) non-Thoracic Survivorship Program visits were noncompliant versus 132 of 4823 (2.7%) of Thoracic Survivorship Program visits (P = .009); 136 of 1146 Thoracic Survivorship Program patients developed second primary non-small cell lung cancer, and 69 of 1123 developed extrathoracic cancer, whereas 322 of 2794 of non-Thoracic Survivorship Program patients developed second primary non-small cell lung cancer and 225 of 2817 patients developed extrathoracic cancer. In multivariable analyses, Thoracic Survivorship Program enrollment was associated with improved disease-free survival (hazard ratio, 0.57; 95% confidence interval, 0.48-0.67; P < .001). CONCLUSIONS: Our novel nurse practitioner-run Thoracic Survivorship Program is associated with high patient compliance and outcomes not different from those seen with physician-based follow-up. These results have important implications for health care resource allocation and costs.

Trial of a 5-day dosing regimen of temozolomide in patients with relapsed small cell lung cancers with assessment of methylguanine-DNA methyltransferase.

OBJECTIVES: Small cell lung cancers (SCLCs) are characterized by aberrantly methylated O(6)-methyl-guanine-DNA methyltransferase (MGMT). Epigenetic silencing of MGMT is associated with loss of MGMT activity and improved sensitivity to alkylating agents in glioblastomas. We have reported the activity of temozolomide, a non-classical alkylating agent, in patients with relapsed sensitive or refractory SCLCs, given at 75 mg/m2/day for 21 of 28 days. However, prolonged myelosuppression was noted. We therefore evaluated a 5-day dosing schedule of temozolomide and examined MGMT as a predictive biomarker for temozolomide treatment in SCLC. MATERIALS AND METHODS: Patients with sensitive or refractory SCLCs and progression after one or two prior chemotherapy regimens received temozolomide 200 mg/m2/day for 5 consecutive days in 28-day cycles. The primary endpoint was tolerability. We also assessed MGMT promoter methylation status by PCR and MGMT expression by immunohistochemistry in tumor specimens. RESULTS: Of 25 patients enrolled, 5 experienced grade 3 or 4 toxicity (anemia, thrombocytopenia, neutropenia, and constipation). The partial response rate was 12% [95% CI: 3-31%], with partial responses in 2 refractory patients. We were able to obtain tumor samples for more than half of patients for MGMT testing. CONCLUSION: Temozolomide 200 mg/m2/day for 5 days in 28-day cycles is tolerable and active in patients with relapsed SCLCs. No treatment-limiting prolonged cytopenias were observed, making this our preferred schedule for further studies. Acquisition of archived biospecimens is feasible and necessary in order to continue evaluating the role of MGMT as a predictive biomarker in SCLCs.

Harnessing technology to improve clinical trials: study of real-time informatics to collect data, toxicities, image response assessments, and patient-reported outcomes in a phase II clinical trial.

PURPOSE: In clinical trials, traditional monitoring methods, paper documentation, and outdated collection systems lead to inaccuracies of study information and inefficiencies in the process. Integrated electronic systems offer an opportunity to collect data in real time. PATIENTS AND METHODS: We created a computer software system to collect 13 patient-reported symptomatic adverse events and patient-reported Karnofsky performance status, semi-automated RECIST measurements, and laboratory data, and we made this information available to investigators in real time at the point of care during a phase II lung cancer trial. We assessed data completeness within 48 hours of each visit. Clinician satisfaction was measured. RESULTS: Forty-four patients were enrolled, for 721 total visits. At each visit, patient-reported outcomes (PROs) reflecting toxicity and disease-related symptoms were completed using a dedicated wireless laptop. All PROs were distributed in batch throughout the system within 24 hours of the visit, and abnormal laboratory data were available for review within a median of 6 hours from the time of sample collection. Manual attribution of laboratory toxicities took a median of 1 day from the time they were accessible online. Semi-automated RECIST measurements were available to clinicians online within a median of 2 days from the time of imaging. All clinicians and 88% of data managers felt there was greater accuracy using this system. CONCLUSION: Existing data management systems can be harnessed to enable real-time collection and review of clinical information during trials. This approach facilitates reporting of information closer to the time of events, and improves efficiency, and the ability to make earlier clinical decisions.

Phase II trial of temozolomide in patients with relapsed sensitive or refractory small cell lung cancer, with assessment of methylguanine-DNA methyltransferase as a potential biomarker.

PURPOSE: This phase II study was conducted to assess the efficacy of temozolomide in patients with relapsed small cell lung cancer (SCLC). EXPERIMENTAL DESIGN: Patients with disease progression after one or two prior chemotherapy regimens received temozolomide at 75 mg/m(2)/d for 21 days of a 28-day cycle. The primary endpoint was the overall response rate [ORR; complete response (CR) plus partial response (PR)], which was evaluated separately in sensitive and refractory cohorts. In the available tissue, we assessed O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status by PCR and MGMT expression by immunohistochemistry. RESULTS: Sixty-four patients were accrued: 48 patients in the sensitive cohort and 16 in the refractory group. One CR and 10 PRs were noted in sensitive patients [ORR, 23%; 95% confidence interval (CI), 12%-37%]. Two PRs were seen in the refractory cohort (ORR, 13%; 95% CI, 2%-38%). As second- and third-line treatment, the ORR was 22% (95% CI, 9%-40%) and 19% (95% CI, 7%-36%), respectively. Among patients with target brain lesions, 38% had a CR or PR (95% CI, 14%-68%). Grade ≥3 thrombocytopenia and neutropenia were observed in nine patients (14%). A greater number of cases with methylated MGMT had a response compared to those with unmethylated MGMT (38% vs. 7%; P = 0.08). CONCLUSION: Temozolomide has activity in relapsed SCLC, particularly for brain metastases. Response to temozolomide may correlate with MGMT methylation in SCLC.