Palliative Radiation Therapy for Bone Metastases in Neuroendocrine Neoplasms

Abstract

Purpose Bone metastases are reported in 10% to 12% of patients with neuroendocrine neoplasms (NENs) and can lead to pain and skeletal-related events (SREs), resulting in diminished quality of life and functional status. In other solid tumors with bone metastases, radiation therapy (RT) is an established treatment approach for SREs, yet few data are available in NENs historically considered to be radioresistant. We hypothesize that RT is effective for pain and other SREs in NENs and aimed to delineate any differences in pain palliation and time until progression of pain between different fractionation and dosing schedules of RT. Methods and Materials We retrospectively reviewed 686 records of patients with NENs treated at the institution between 2011 and 2018 and identified 28 (4.1%) patients treated with RT for 61 cases of SREs. The primary endpoint was change in patient reported pain scores after RT. Results All 28 patients experienced bone pain. Nineteen sites were treated with a single fraction (doses of 800-1800 cGy) and 42 sites with fractionated regimens (doses of 900-3750 cGy over 3-15 fractions). In 55 of 61 cases (90%), patients experienced improvement in pain after RT. The median time to recurrence or progression of pain was 3.5 months. Significant differences were found between primary site and change in performance status ( P = .024), sex, and reported magnitude of pain score decrease after RT ( P = .025). There were no differences in the time to the progression of pain, change in performance status, and degree of improvement in pain based on age, chemotherapy received during RT, or radiation site. Outcomes were similar for patients who received single-fraction versus fractionated regimens ( P = .545) and between those receiving palliative versus ablative RT regimens ( P = .812). Conclusions Although the majority of cases in this NEN cohort benefited from RT, additional studies on the use of RT in the treatment of painful bone metastases are warranted.

Stereotactic Ablative Radiotherapy for the Management of Liver Metastases from Neuroendocrine Neoplasms: A Preliminary Study

“…Historically, radiation has not been considered, likely due to initial experience using outdated techniques and dose/fractionation tailored for widespread metastatic disease [27]. Contemporary studies utilizing modern radiation techniques have demonstrated radiographic and clinical response to primary and metastatic disease [16, 28, 29]. Radiobiological models utilize the alpha/beta ratio to determine the response of tumors to varied dose/fraction radiation schemes; most rapidly growing histologies will have an alpha/beta value of ∼10, while slower growing tumors will have a lower value and thus be more responsive to high-dose per fraction treatment [30].…”

Bone Metastases in Neuroendocrine Tumors: Molecular Pathogenesis and Implications in Clinical Practice

“…Bone-directed therapies include radiotherapy, orthopedic surgery, bisphosphonates (administered either orally or intravenously), and denosumab. Both radiotherapy and surgery are often used to prevent or treat SREs in patients with NET [11], and bone pain relief has been described in up to 90% of patients treated with radiotherapy [61]. In a study of 45 NET patients receiving palliative external beam radiotherapy, skeletal metastases represented the 75% of target lesions, and the median symptom-free survival was 4 months [62].…”

Bone Metastases in Neuroendocrine Neoplasms: From Pathogenesis to Clinical Management

“…Several studies have shown bone pain to be the most common symptom, reported in 42.4%–100% of patients with metastatic GEP- and BP-NENs [10,12,13,41,63]. Bone pain could frequently be disproportionate to the degree of bone involvement and could impair performance status, affecting patients’ work, motility, and sleep [6].…”

“…External beam radiation therapy (EBRT) and/or surgery are often required both to prevent and to treat SREs [64,90,91]. A recent study showed that EBRT was able to relieve bone pain in 90% of treated BMs in NEN patients, independent from single-fraction vs. fractionated regimens, primary tumor site, chemotherapy received during RT, or radiation site [63]. In addition, among loco-regional therapies, thermal ablation techniques (radiofrequency-ablation/cryotherapy) must be mentioned.…”