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dc.contributor.authorWalder, D
dc.date.accessioned2021-09-10T13:35:21Z
dc.date.available2023-03-31T00:00:00Z
dc.date.issued2021-03-31
dc.identifier.citation2021en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4805
dc.description.abstractLung 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.en_US
dc.language.isoengen_US
dc.subjectTheses, Doctoralen_US
dc.subjectLung Cancer - Therapyen_US
dc.titleImproving outcomes for the lung cancer patient with impaired lung functionen_US
dc.typeThesis
rioxxterms.versionAOen_US
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden_US
rioxxterms.licenseref.startdate2021-03-31
rioxxterms.typeThesisen_US
pubs.notes24 monthsen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Treatment of thoracic tumours
pubs.embargo.terms24 monthsen_US
pubs.embargo.date2023-03-31T00:00:00Z
icr.researchteamTreatment of thoracic tumours
dc.contributor.icrauthorWalder, Daviden_US


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