Palliative treatments for lung cancer: What can the oncologist do? Neil Bayman Consultant Clinical Oncologist GM Cancer Palliative Care and Lung Cancer Education Event Manchester, 31 st January 2017
Most patients present with stage 4 disease The Christie NLCA NHS 2014 Foundation Trust
Palliative treatments for lung cancer: What can the oncologist do? Radiotherapy Systemic therapy
Palliative Radiotherapy
Case Study 63 yr old man Stage 4 NSCLC WHO PS 1 Pain in right hip Mobile No neurological signs What next?
Radiotherapy for bone pain Systematic review 25 randomised trials, > 5500 patients Response rate Any reduction in pain = 60% Complete response = 23% Overall and complete response rates 73% and 29% respectively when excluding patients not assessed at follow-up Chow, Clin The Oncol Christie (R Coll Radiol) NHS Foundation 2012 Trust
Systematic review of single vs multiple fraction radiotherapy for bone metastases n Single fraction Multiple fractions OR (95% CI) Overall 5617 60% 61% 0.98 (0.95- response 1.02) Complete 5263 23% 24% 0.97 (0.89- response 1.06) Re-irradiation 4632 20% 8% 2.60 (1.92-3.47) Pathological fracture Spinal cord compression 4279 3.3% 3% 1.10 (0.65-1.86) 2886 2.8% 1.9% 1.44 (0.90-2.30) Response rate assessments ranged from 3 weeks to 3 months Chow, Clin The Oncol Christie (R Coll Radiol) NHS Foundation 2012 Trust
Pain flare occurs in up to 40% patient following radiotherapy for bone pain Hird IJROP 2009 Dexamethasone (8mg d1-5) reduces risk of pain flare Chow, Lancet Oncol 2015
Guidelines Royal College of Radiologists For the initial therapy of pain from bone metastases, a single fraction of 8 Gy is recommended (Grade A) RCR Radiotherapy Dose-Fractionation 2016
Palliative RT for bone pain in last 3 months of life: Worthwhile or Futile? Prospective, population-based Canadian study Response rates 70% at 1 month 63% at 2 months Dennis, Clin Oncol (R Coll Radiol) 2011 Dutch bone metastases study 76% response rate overall 54-65% response rate in those dying < 3 months Meeuse, Cancer 2010
Palliative Radiotherapy Audit Christie 14 day mortality after RT = 5% 30 day mortality after RT = 18%
Palliative Radiotherapy Audit Christie
Metastatic Spinal Cord Compression
Metastatic Spinal Cord Compression (MSCC) > 4000 cases per year in UK Extradural compression or invasion from adjacent metastatic vertebra Reversible Venous obstruction and oedema MSCC Pain Immobility Loss of sphincter control Irreversible Direct compression arterial compression axonal fracture neuropraxia Oncological emergency treated with surgery or radiotherapy
Tokuhashi Score Validated score to predict prognosis after diagnosis MSCC Surgical selection tool Lung cancer poor prognostic factor
Metastatic Spinal Cord Compression: NICE guidance 1.5.1. Radiotherapy for painful spinal metastases Offer patients with spinal metastases causing non-mechanical spinal pain 8 Gy single fraction palliative radiotherapy even if they are completely paralysed. Patients with asymptomatic spinal metastases should not be offered radiotherapy with the intention of preventing MSCC except as part of a randomised controlled trial.
Metastatic Spinal Cord Compression: NICE guidance 1.5.5 Radiotherapy for the definitive treatment of MSCC Urgent access (within 24 hours) to radiotherapy 7 days a week Offer a fractionated rather than a single fraction regimen to patients with a good prognosis. Routine fractionated radiotherapy to all patients after surgery Offer urgent radiotherapy (within 24 hours) to all patients with MSCC who are not suitable for spinal surgery unless: they have had complete tetraplegia or paraplegia for more than 24 hours and their pain is well controlled; or their overall prognosis is judged to be too poor.
SCORAD III Phase III RCT Eligibility MSCC Prognosis > 8 weeks Histological diagnosis of malignancy Primary outcome Ambulation at 8 weeks
Palliative Radiotherapy for Brain Metastases
Median survival (weeks) Whole brain RT 9.2 Supportive care 8.5 No difference in QALY or OS
Palliative thoracic radiotherapy Erridge et al. Clin Oncol (R Coll Radiol) 2005
Systemic Therapy
Case Study 60 year old lady Vietnamese Never smoked No co-morbidities Keen ballroom dancer PS2 Fatigue Cough Dyspnoea Weight Loss
Where is it?
What is it?
Adenocarcinoma EGFR mutation Started 1 st line Gefitinib (tyrosine kinase inhibitor) Case 2 What is it?
1 st line Iressa vs chemotherapy in NSCLC with EGFR mutation N Engl J Med 2010;362:2380-8
October November December January
Case Symptoms resolved after 1 st cycle Toxicity - Mild skin reaction (acneform rash over face and dry skin) Restarted ballroom dancing Spent time visiting relatives and travelling with her husband in SE Asia. with several boxes of gefitinib.
Prevention of Skeletal Related Bisphosphonates Events (SRE) Zolendronic acid (4mg every 3w for 9 months) reduced risk of skeletal related events compared to placebo Increased time to first SRE NNT to prevent SRE at 9 months = 14 Denosumab Non-inferior to ZA in delaying time to first SLE Rosen JCO 2003 Henry JCO 2011 Improved OS compared to ZA on exploratory analysis (8.9 vs 7.7 months; hazard ratio [HR] 0.80, p=0.01) Palliation of bone pain??? Scagliotti JTO 2012
Take home messages Radiotherapy Very effective treatment for cancer induced bone pain and heamoptysis Metastatic spinal cord compression is an oncological emergency Does not improve QALY for patients with brain metastases (?young/good PS/controlled extracranial disease) Systemic therapy Can improve survival and offer holistic symptom relief Tissue for histological and molecular analysis is essential