Long Term Outcomes of Conventional Palliative Radiotherapy in Bone Metastases of Lung Cancer: A Prospective Study

Abstract

Bone metastases (BM) are highly prevalent in metastatic lung cancer (LC) leading to consequential morbidity and a decline in quality of life. The identification of oncogenes mutation and introduction of targeted therapy has prolonged the survival and therefore evaluation of long-term pain response rates, durability and re-irradiation (Re-RT) with conventional radiotherapy (RT) is crucial, especially in LMIC where penetration of stereotactic body radiotherapy for BM is poor. This prospective observational study included consecutive patients with histologically proven LC with radiologically confirmed BM. The primary objective was to evaluate the pain response rates in lung cancer patients with bone metastases treated with palliative RT. Palliative RT to BM was delivered using a conventional/conformal technique. The International Bone Metastases Consensus response criteria using Numeric Pain Rating Scale (NPRS) and Oral Morphine Equivalent Dose (OMED) was used to evaluate the pain response at 12, 24, and 52 weeks. Assuming the worst-case scenario, pain progression-free survival (PPFS) was calculated from the date of baseline assessment to the date of pain progression (PP) or death using Kaplan-Meier survival analysis. Known prognostic factors were evaluated using Cox regression analysis. From June 2020 to August 2022, 250 patients of NSCLC (94%) were accrued. The majority were male (66%), smokers (35%), lytic lesions (75%) and in the axial skeleton (82%). The oncogenic mutation was seen in 123 (49%) patients. At baseline, the mean OMED was 20mg/day (SD-21), and the mean pain score was 6 (SD-2.3). The majority (66%) received an 8 Gy single fraction with only 3% treated with SBRT. In evaluable patients, the CR and PR rates at 12 (n-161) and 24 weeks (n-121) were 34%, 40%, and 44%, 35% respectively. The indeterminate response rate (IRR) at 3 and 6 months were 18% while the rate of PP was 6%. On multivariate analysis, negative oncogene mutation {HR-0.34 (CI 0.22- 0.50), p<0.0001} and soft tissue mass {HR-0.46 (CI 0.31- 0.68) p<0.0001} were significant prognostic factors for pain progression. Of 71 evaluable patients at 1 year, 56% had a complete response with an ORR of 87%. In patients with oncogene mutation, the CR rates at 12 (n-101), 24 (n-77), and 52 weeks were 40%, 47%, and 60% with an ORR of 86%. PP is observed in less than 4%. Pain response was significantly more durable than mutation negative (8 vs 3 months, p-0.003). Re-RT rate was overall 11% (n = 27) and 8.2% in oncogene mutation patients. Re-RT rate with single-fraction was 8% and 3% with fractionated RT. The median time to Re-RT was 9.7 weeks. The PPFS was 70% and 60% at 12 and 24 weeks, respectively. This prospective study in an LC-specific population demonstrated excellent CR and PR rates with conventional RT. Durable pain relief with modest Re-RT rates with single fraction, particularly in oncogene mutation compels us to evaluate the role of SBRT for BM, especially in LMIC in a randomized setting.