Improving outcomes for the lung cancer patient with impaired lung function

Abstract

Lung function impairment is common amongst patients with lung cancers. Identifying the patients that are most likely to benefit from anti-cancers therapies, without suffering significant toxicities, is central to improving their outcomes. Radiotherapy Method: A retrospective review with survival and regression analyses to establish associated factors related to pneumonitis, relapse and survival from 208 SBRT treatments. Results: Median overall survival 2.6 years (2.3-3.3). Mediastinal staging associated with risk of pneumonitis (OR: 11.79 (2.66-52.26) p=0.001). No association between lung function parameters and risk of pneumonitis. Low TLCO associated with worse overall survival (HR:0.98 (0.97-0.99) p=0.010). Increased tumour size associated with shorter time to relapse (HR:1.05 (1.02-1.08) p=0.001). Conclusion: Low TLCO is a poor prognostic marker for patients undergoing SBRT for early stage NSCLC. Radiotherapy/Immunotherapy combination Part A Method: A phase 1b/II study to assess the safety of adjuvant nivolumab (240mg every 2 weeks) commencing within 24 hours of the final fraction of SBRT. Results: After a minimum of 3 months follow up of the first 5 recruited patients, no episodes of grade 3 pneumonitis were observed. Based on this, the trial has been expanded to include recruitment of patients of ECOG performance status 2. Conclusion: Early data suggests unacceptable lung toxicity is not seen with adjuvant nivolumab following SBRT Part B Method: NanoString analysis of RNA from macrodissected NSCLC biopsies including the tumour microenvironment. Results: Successful immunogenomic profiling from 12 degraded NSCLC biopsies. Tendency for lower expression of MCIB and IFN in biopsies from patients who went on to respond to combination radiotherapy/immunotherapy treatment. Conclusion: The immune makeup of the tumour microenvironment may help to predict responses to combination immunotherapy and radiotherapy treatment regimens. Chemotherapy Method: A retrospective analysis of 52 patients to establish the patient factors associated with tolerability and outcome from second-line docetaxel for NSCLC. Results: FEV1 was the factor most associated with overall survival (HR:0.96 (0.93-0.99=0.009). Patients with an FEV1 less than 50% predicted had significantly worse survival (HR:0.15 (0.04-0.57) p=0.005) and were also more likely to discontinue treatment due to toxicity (p=0.023). Conclusion: An FEV1 less than 50% predicted is a poor marker in patients being considered for docetaxel chemotherapy for advanced NSCLC. Symptom control Method: An open label, randomised, controlled trial comparing the effect of adding optimal inhaled therapies to best supportive care alone in 64 patients with co-existing untreated COPD and lung cancer. Results: Inhaled therapies led to an increase in the proportion of patients achieving a minimum 2-point improvement in VAS breathlessness after 4 weeks. Response rate in those receiving inhaled therapies was 53% (35-71) compared to 26% (12-45) in the group that received BSC alone (p=0.027). Conclusion: Spirometry performed in the lung cancer clinic can identify undiagnosed COPD and treating this with inhaled therapies improves breathlessness.