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Location: Marriott Marquis
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Main Session

SS 25 - Lung 1: Randomized Trials for Lung Cancer

244 - The Impact of Prophylactic Bisphosphonates on Radiation-Induced Rib Fractures and Chest Wall Pain in Peripheral Lung Tumor SBRT: A Randomized, Double-Blind, Placebo-Controlled Study

Monday, September 30, 2024
5:20 PM – 5:30 PM ET
Location: Room 207

    Presenter(s)

  • MF

    Michael Farris, MD

    Wake Forest University Medical Center
    Winston Salem, NC, United States

M. Farris1, R. T. Hughes2, H. D. Pacholke2,3, B. Levine4, P. J. Black2, N. Razavian2, J. D. Ververs2, J. Ponnatapura5, J. C. Farris6, S. Glynn2, K. E. Weaver7, G. J. Lesser8, S. Park2, J. Ruiz9, J. H. Heinzerling II10, and J. Willey2; 1Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, 2Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC, 3High Point Regional Hospital, High Point, NC, 4Wake forest, winston, NC, 5Department of Radiology, Wake Forest University School of Medicine, Winston Salem, NC, 6Department of Radiation Oncology, Bon Secours Health System, Greenville, SC, 7Department of Social Sciences and Health Policy, Wake Forest University School of Medicine, Winston Salem, NC, 8Department of Hematology and Oncology, Wake Forest University School of Medicine, Winston Salem, NC, 9Department of Internal Medicine, Section of Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, 10Levine Cancer Institute, Atrium Health and Southeast Radiation Oncology Group, Charlotte, NC

Purpose/Objective(s): Stereotactic body radiation therapy (SBRT) for peripheral lung tumors can result in high radiation doses to surrounding ribs. Preclinical studies have shown single fraction doses of 2-10 Gy increase osteoclast activity and lead to bone loss. We conducted randomized, double-blind, placebo-controlled trial to evaluate whether early suppression of osteoclast activity could mitigate SBRT-induced rib fractures. Materials/

Methods: Between July 2019 - Feb 2022, 84 patients enrolled. Eligible patients had lung tumors within 2 cm of chest wall and were randomized 1:1 to receive either a single dose of risedronate (150mg) or placebo delivered 7 to 21 days before SBRT (48-60 Gy in 3-10 fractions). Chest wall pain (CWP) graded using modified CTCAE v5 assessed every 3 months after SBRT up to 1 year. Following minimum period of 1 year post drug administration, thoracic radiologist assessed all accessible imaging follow-up for fracture incidence.
Results: 76 patients (38 placebo 38 risedronate) with 81 treated lung lesions included in this analysis with a median follow-up of 26.3 months with a maximum of 43.4 months. Follow-up was measured from end date of SBRT to date of last available CT chest or date fracture detection. Total of 25 patients (33%) developed rib fractures. Median (range) values for rib (dose in EQD2, a/b=3) and chest wall (3 cm thickness) structures are as follows: rib D0.03cc, 215 Gy (range, 52-373); rib D2cc, 101 (26-252); chest wall V30, 20 cc (0.5-314). There was no significant difference in fracture rates between risedronate and placebo groups - 13 risedronate group (34.2%) vs 12 in placebo arm (31.6%) (p = 0.2). Among those who fractured, the median time to the first fracture was 14.2 mo (95% CI 9.8 - 16.9 mo) [range 5.9 - 43.4 mo] with 9 patients developing fracture within 1 year from the end of SBRT. P</span>atients receiving risedronate had a significantly lower rate of grade 2+ CWP within 1 year post SBRT completion compared to patients who received placebo: 18% versus 42% respectively (P=0.045), Among patients who did not develop a detectable fracture, the rate of G2+ CWP was (12 % vs 34.6% p=0.06) favoring the risedronate arm, and similarly among those who did develop fractures, the incidence of G2+ CWP was 31% vs 58% (p = 0.17).
Conclusion: For patients receiving SBRT for peripheral lung tumors, the use of prophylactic risedronate, when compared to placebo, did not reduce the incidence of treatment-induced rib fractures. The use of risedronate, however, lowered the risk of G2+ CWP. The suggested protective impact of risedronate against G2 or higher CWP may point to a nerve and osteoclast cross talk mechanism contributing to the development of SBRT-induced CWP. Alternatively, risedronate may have partially reduced osteoclast activity, preventing the accumulation of microfractures that could have contributed to pain. Further investigations into the appropriate dose and type of antiresorptive agent to specifically counteract bone loss and prevent pain or fracture after thoracic SBRT are warranted