DISCUSSION
tumor, confusion, painful bone metastases, pain, lung cancer, radioresistant malignancy, kidney, colon, and cervix
TUMOR, METASTASIS, DISEASE, LUNG CANCER, REMISSION, PRIMARY TUMOR, METASTASES, BONE METASTASES
Based on multiple clinical trials, meta‐analysis and guidelines, “simple”, high dose, single fraction radiotherapy is considered an effective, short‐term regimen that enables quick and long‐lasting pain relief. It can significantly improve a patient's performance status and quality of life, with no delay in other oncological treatment and reduce the use of analgesics. It does, however result in higher re‐irradiation rate than with multi‐fractionation regimen and it is generally suitable for patients with uncomplicated bone metastases. With the use of modern techniques such as IMRT, Rapid Arc, SBRT, etc. the additional confusion was made in the treatment of patients with painful bone metastases regarding both optimal technique selection and the optimal tumor dose. Ultimately, with the COVID‐19 outbreak, radiation oncologists were challenged to quickly adjust the approach to these patients reintroducing fast regimen. But did we rush?In the clinical practice as well as in most of the studies, palliative radiotherapy of painful bone metastases is usually seen as a single entity, although it is a very heterogeneous group of patients, the primary site of disease and histopathological diagnoses, as well as localization of metastases on the skeleton.In our study, the VAS scale was used to assess pain, and the response to radiotherapy was defined according to the recommendations of the radiotherapy consensus panel. Regardless of the applied pain assessment scale, in response to therapy, the definition of a complete response is the same everywhere—the complete absence of pain. The definition of a partial response, however, varies between studies but is defined as a reduction in pain by 1 category on a 4‐ or 5‐category scale, or by 2 points on the VAS. In this way, the studies are methodologically consistent, and our study fully corresponds to this system for assessing pain intensity. Also, in most studies, pain intensity was recorded 1, 2, 3, 4, 8, 12, and 24 weeks after irradiation, with which our study is in full agreement. Another important finding was that patient's compliance to telephone interview and patient reported outcome was 100% and we found it non‐challenging whatsoever. True, we did not have electronic patient‐reported outcome measures developed for that particular scenario.The assessment of the patient's performance was based on the ECOG performance scale. In most previous studies, the inclusion criterion was Karnofsky performance scale (KPS) ˃40 (PS3), while in the study by Foro Arnalot et al., out of the 160 patients included, as many as 131 patients had KPS ≥70 (PS2).In the entire group of 64 patients, 53 of them (83%) responded to radiotherapy. Of those 53 patients, 19 (36%) achieved a complete response, that is, complete absence of pain, of which 13 maintained a complete response without pain progression until the end of follow‐up. In 34 patients of our group (64%), a partial response to radiotherapy was recorded with a median difference in pain intensity of 4 points on the VAS (rank 3–6), which correlates with other series (average pain reduction—3.5 points on VAS).In the meta‐analysis by Wu et al., which included eight clinical trials, the total response to a single shoot was 62%, while complete remission was recorded in 33% of patients.In the group of patients who responded to radiotherapy, the average time to reach the maximum response was 25 days (range 2–93 days), that is, an average of 3 eeks (0–13 weeks). The average time until pain progression was 34 days (1–69 days), that is, the response duration was an average of 1 month. In the Foro Arnalot study,Gaze et al. recorded a duration of response of 13.5 weeks, and Linden et al. of 18 weeks,In the available literature, there are very few comments regarding the patients who did not respond to radiation. In 11 patients of our study (17%), no reduction of pain was recorded, although six patients achieved stabilization of pain by the end of the study, which did not increase further. In these patients, there was no increase in the use of analgesics. These patients were women, predominantly elderly (median 72 years) and all had radioresistant malignancy (kidney, colon, and cervix). In five patients of this group, a rapid progression of pain after irradiation was noted.Therefore, it is of great clinical importance to distinguish the group of patients who would benefit from radiotherapy compared to those who will not respond to it. Based on our results, no statistically significant difference was observed in the response to therapy depending on the age of the patient, performance status, primary origin of the tumor, histological type of the tumor, as well as depending on the location of the metastasis (bone) that was irradiated. There was no statistically significant difference in the time to pain progression, nor in the level of response to radiotherapy by any of the mentioned parameters. Even by separating the group of patients who had a response to radiotherapy (53 of them), no statistically significant difference was observed in the time to reach the maximum response according to any parameter. Several large‐world studies have analyzed the potential influence of pre‐therapeutic prognostic and predictive factors such as the patient's age, sex, and histology of the primary tumor and localization of metastases. None of these studies showed that any of these factors influenced response to therapy or survival.Overall survival in our entire group of patients was an average of 12 weeks (range 1–18 weeks), that is, 3 months. By the end of the study, 26 patients had died (41%), while almost two‐thirds (38 of them) were still alive (61%). In a retrospective study by Liu et al., 537 patients previously irradiated for painful bone metastases were examined. Median survival from irradiation was 6 months, which is longer than in our series. However, in this study, a significantly larger number of patients were in good performance status, in contrast to our study. Among other things, this study also concluded that patients with KPS below 80% have significantly worse survival. The worst survival was recorded in the gastrointestinal cohort, as well as in the lungs (4 months), which is correlated with our results, considering that in our study, patients with lung cancer were the most represented.The whole paradigm in the palliative approach was challenged during COVID‐19 pandemic, favoring quick, but non‐inferior radiotherapy regimens.