This retrospective cohort study was conducted on patients with painful non-bone tumors who underwent palliative radiotherapy at our institution between September 2018 and September 2022. This study was approved by our institutional review board, and all participants provided informed consent with an opt-out form that stated that participants were included unless they explicitly decided to exclude themselves. Patients who (1) were diagnosed with painful non-bone lesions, (2) experienced pain related to the targeted tumor, and (3) underwent palliative radiotherapy for pain relief were included. Palliative radiotherapy is defined as radiotherapy aimed at relieving the symptoms related to specific lesions. However, this study did not include patients who underwent palliative radiotherapy for non-bone lesions to relieve symptoms other than pain, such as gastrointestinal stenosis or bleeding. The intended target non-bone lesions for this study were primary tumor lesions, lymph node metastases, hematogenous metastases other than bone metastases, and other lesions (including pleural/peritoneal/meningeal dissemination). Herein, palliative radiotherapy for non-bone lesions was performed at our institution using the three-dimensional conformal radiation method. Therefore, this study did not include data on intensity-modulated radiation therapy, volumetrically modulated arch therapy, or stereotactic body radiation therapy. Patient follow-up for this study ended on May 30, 2023, and those who were alive or lost to follow-up at this time were censored.

Figure 1 presents a consort diagram of the study process. We identified 142 patients with painful non-bone lesions among the 420 enrolled patients. Thirty patients were unable to assess their pain response because they were lost to follow-up after radiotherapy. After excluding these 30 non-evaluable patients, 112 evaluable patients were included in the analysis.

Consort diagram of this study

We collected data on patient and tumor characteristics, radiation dose and fractionation schedule, worst pain scores, analgesic medication use, imaging findings, adverse events, and survival. Pain scores were determined based on the patient’s self-reported worst pain experienced in the past 3 days, rated using the Numeric Rating Scale (NRS); the scores ranged from 0 to 10, with higher scores indicating more severe pain [15]. Patients with an NRS score of 0 were excluded. Analgesic medication use was recorded as the daily oral morphine equivalent dose (OMED) calculated based on the National Comprehensive Cancer Network guidelines [16].

The pain response was assessed using the ICPRE criteria [17]. Overall response (OR) included complete response (CR) and partial response (PR). CR was defined as a pain score of 0 at the treated site with no concomitant increase in analgesic intake. PR was defined as a pain reduction of 2 or more without an analgesic increase or an analgesic reduction of 25% or more from baseline without an increase in the severity of pain. Pain progression (PP) was defined as an increase in pain score of 2 or more above the baseline with stable OMED or an increase of 25% or more in OMED compared with the baseline with a stable pain score or a pain score of 1 point above the baseline. Indeterminate response (IR) was defined as a response other than CR, PR, or PP.

The primary endpoint was the pain response rate in evaluable patients, defined as the proportion of the overall response based on pain scores and analgesic medication use within 4 months of radiotherapy. The secondary endpoints were adverse events, survival rates, and pain recurrence. Pain recurrence was defined as PP occurring after a pain response, but the baseline pain score for determining PP was changed to the minimum score after the pain response.

All the explanatory variables were treated as categorical variables: Eastern Cooperative Oncology Group Performance Status (0–1 vs. 2–4), NRS (2–6 vs. 7–10), age (< 66 vs. ≥ 66), sex (female vs. male), OMED (< 60 mg vs. ≥ 60 mg), radiation dose (≥ 40 Gy10 BED10 vs. < 40 Gy10 BED10), and the history of radiotherapy (yes vs. no). In addition, the target lesions were classified as primary tumor lesions, lymph node metastases, non-bone hematogenous metastases, or others. To explore the factors affecting the pain response, univariate and multivariate logistic regression analyses were performed using the above covariates as explanatory variables. Variables with a P-value < 0.05 after a univariate analysis were selected for inclusion in the multivariate model.

Survival curves were estimated using the Kaplan–Meier method, and the differences between groups were compared using the log-rank test. Statistical significance was set at a P-value of < 0.05. All statistical analyses were performed using the R statistical software version 4.2.2 (The R Foundation for Statistical Computing, Vienna, Austria).