A Single-center Experience of Radiotherapy in Pediatric Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Chest Wall.

AIM: To evaluate the treatment results, prognostic parameters, and treatment-related toxicity in patients with Ewing sarcoma (ES)/primitive neuroectodermal tumor (PNET) of the chest wall who underwent surgery, chemotherapy, and radiotherapy (RT) in a tertiary referral center. METHODS: The data of 24 patients under 18 years of age with a histologic diagnosis of ES/PNET in the chest wall that received RT in our department between February 2003 and July 2020 were retrospectively evaluated. RT was applied to the primary site±whole involved chest wall and to the whole lung in patients with lung metastasis. RESULTS: The median age was 8.5 years (range: 1.5 to 17 y), 15 (63%) patients were female and 9 were male (37%). The tumor localization was extrathoracic in 18 (75%) and intrathoracic in 6 (25%) patients. Mediastinal lymph node and distant metastasis (DM) was present in 5 (21%) and 4 (16%) cases at diagnosis, respectively. The median follow-up after RT was 47 months (range: 11 to 162 mo). The 2-year and 5-year overall survival, event-free survival, local recurrence-free survival, and pleural recurrence-free survival were 83% and 48%, 48% and 42%, 74% and 48%, and 61% and 52%, respectively. The overall local control rate was 83% and the pleural control rate was 67%. RT was well tolerated, with 1 case of grade 3 acute dermatitis and 1 case of grade 3 subacute radiation pneumonitis. Late toxicity was observed in 3 (13%) cases. CONCLUSION: Long-term survival can be achieved with extended-field RT even in patients with ES/PNET of the chest wall with DM. The low toxicity rates allow us to draw the conclusion that RT with modern techniques is an effective and safe treatment modality for these patients.

Clinical effectiveness of combined whole body hyperthermia and external beam radiation therapy (EBRT) versus EBRT alone in patients with painful bony metastases: A phase III clinical trial study.

PURPOSE: To evaluate the response rate, pain relief duration, and time it took for pain to decline or resolve after radiation therapy (RT) with or without fever-range Whole Body Hyperthermia (WBH) in bony metastatic patients with mainly primary tumor of prostate and breast cancer leading to bone pain. MATERIALS & METHODS: Bony metastatic patients with pain score ≥4 on the Brief Pain Inventory (BPI) underwent RT of 30 Gy in 10 fractions in combination with WBH with nursing care under medical supervision versus RT-alone. WBH application time was 3-4 h in three fractions with at least 48-h intervals. All patients were stratified primary site, breast or prostate cancer vs others, BPI score, and exclusion criteria. The primary endpoint was complete response (CR) (BPI equal to zero with no increase of analgesics) within two months of follow-up. RESULTS: Based on this study, the RT-alone group showed the worst pain. The study was terminated after the enrollment of a total of 61 patients, 5 years after the first enrollment (April 2016 to February 2021). Finally, the CR rate in RT + WBH revealed the most significant difference with RT-alone, 47.4% versus 5.3% respectively within 2 months post-treatment (P-value <0.05). The time of complete pain relief was 10 days for RT + WBH, while the endpoint was not reached during the RT-alone arm. Pain progression or stable disease was observed in half of the patients in RT-alone group within 4 weeks after treatment. However, this score was near zero in RT + WBHT patients in two months post-treatment. CONCLUSIONS: WBH plus RT showed significant increases in pain relief and shorter response time in comparison with RT-alone for patients with bone metastatic lesions.

FLASH radiotherapy for the treatment of symptomatic bone metastases in the thorax (FAST-02): protocol for a prospective study of a novel radiotherapy approach.

BACKGROUND: FLASH therapy is a treatment technique in which radiation is delivered at ultra-high dose rates (≥ 40 Gy/s). The first-in-human FAST-01 clinical trial demonstrated the clinical feasibility of proton FLASH in the treatment of extremity bone metastases. The objectives of this investigation are to assess the toxicities of treatment and pain relief in study participants with painful thoracic bone metastases treated with FLASH radiotherapy, as well as workflow metrics in a clinical setting. METHODS: This single-arm clinical trial is being conducted under an FDA investigational device exemption (IDE) approved for 10 patients with 1-3 painful bone metastases in the thorax, excluding bone metastases in the spine. Treatment will be 8 Gy in a single fraction administered at ≥ 40 Gy/s on a FLASH-enabled proton therapy system delivering a single transmission proton beam. Primary study endpoints are efficacy (pain relief) and safety. Patient questionnaires evaluating pain flare at the treatment site will be completed for 10 consecutive days post-RT. Pain response and adverse events (AEs) will be evaluated on the day of treatment and on day 7, day 15, months 1, 2, 3, 6, 9, and 12, and every 6 months thereafter. The outcomes for clinical workflow feasibility are the occurrence of any device issues as well as time on the treatment table. DISCUSSION: This prospective clinical trial will provide clinical data for evaluating the efficacy and safety of proton FLASH for palliation of bony metastases in the thorax. Positive findings will support the further exploration of FLASH radiation for other clinical indications including patient populations treated with curative intent. REGISTRATION: ClinicalTrials.gov NCT05524064.

Advancements in the development of radiopharmaceuticals for nuclear medicine applications in the treatment of bone metastases.

Bone metastases are a painful and complex condition that overwhelmingly impacts the prognosis and quality of life of cancer patients. Over the years, nuclear medicine has made remarkable progress in the diagnosis and management of bone metastases. This review aims to provide a comprehensive overview of the recent advancements in nuclear medicine for the diagnosis and management of bone metastases. Furthermore, the review explores the role of targeted radiopharmaceuticals in nuclear medicine for bone metastases, focusing on radiolabeled molecules that are designed to selectively target biomarkers associated with bone metastases, including osteocytes, osteoblasts, and metastatic cells. The applications of radionuclide-based therapies, such as strontium-89 (Sr-89) and radium-223 (Ra-223), are also discussed. This review also highlights the potential of theranostic approaches for bone metastases, enabling personalized treatment strategies based on individual patient characteristics. Importantly, the clinical applications and outcomes of nuclear medicine in osseous metastatic disease are discussed. This includes the assessment of treatment response, predictive and prognostic value of imaging biomarkers, and the impact of nuclear medicine on patient management and outcomes. The review identifies current challenges and future perspectives on the role of nuclear medicine in treating bone metastases. It addresses limitations in imaging resolution, radiotracer availability, radiation safety, and the need for standardized protocols. The review concludes by emphasizing the need for further research and advancements in imaging technology, radiopharmaceutical development, and integration of nuclear medicine with other treatment modalities. In summary, advancements in nuclear medicine have significantly improved the diagnosis and management of osseous metastatic disease and future developements in the integration of innovative imaging modalities, targeted radiopharmaceuticals, radionuclide production, theranostic approaches, and advanced image analysis techniques hold great promise in improving patient outcomes and enhancing personalized care for individuals with bone metastases.

Stereotactic Body and Conventional Radiotherapy for Painful Bone Metastases: A Systematic Review and Meta-Analysis.

Importance: Conventional external beam radiotherapy (cEBRT) and stereotactic body radiotherapy (SBRT) are commonly used treatment options for relieving metastatic bone pain. The effectiveness of SBRT compared with cEBRT in pain relief has been a subject of debate, and conflicting results have been reported. Objective: To compare the effectiveness associated with SBRT vs cEBRT for relieving metastatic bone pain. Data Sources: A structured search was performed in the PubMed, Embase, and Cochrane databases on June 5, 2023. Additionally, results were added from a new randomized clinical trial (RCT) and additional unpublished data from an already published RCT. Study Selection: Comparative studies reporting pain response after SBRT vs cEBRT in patients with painful bone metastases. Data Extraction and Synthesis: Two independent reviewers extracted data from eligible studies. Data were extracted for the intention-to-treat (ITT) and per-protocol (PP) populations. The study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: Overall and complete pain response at 1, 3, and 6 months after radiotherapy, according to the study's definition. Relative risk ratios (RRs) with 95% CIs were calculated for each study. A random-effects model using a restricted maximum likelihood estimator was applied for meta-analysis. Results: There were 18 studies with 1685 patients included in the systematic review and 8 RCTs with 1090 patients were included in the meta-analysis. In 7 RCTs, overall pain response was defined according to the International Consensus on Palliative Radiotherapy Endpoints in clinical trials (ICPRE). The complete pain response was reported in 6 RCTs, all defined according to the ICPRE. The ITT meta-analyses showed that the overall pain response rates did not differ between cEBRT and SBRT at 1 (RR, 1.14; 95% CI, 0.99-1.30), 3 (RR, 1.19; 95% CI, 0.96-1.47), or 6 (RR, 1.22; 95% CI, 0.96-1.54) months. However, SBRT was associated with a higher complete pain response at 1 (RR, 1.43; 95% CI, 1.02-2.01), 3 (RR, 1.80; 95% CI, 1.16-2.78), and 6 (RR, 2.47; 95% CI, 1.24-4.91) months after radiotherapy. The PP meta-analyses showed comparable results. Conclusions and Relevance: In this systematic review and meta-analysis, patients with painful bone metastases experienced similar overall pain response after SBRT compared with cEBRT. More patients had complete pain alleviation after SBRT, suggesting that selected subgroups will benefit from SBRT.

Cytotoxicity Enhancement in Osteosarcoma with Multifunctional I-131 Radiotherapeutic Nanoparticles: In Vitro Three-Dimensional Spheroid Model and Release Kinetics Modeling.

This novel radiolabeled chitosan nanoparticle, facilitated with curcumin, increased doxorubicin cytotoxicity and radiosensitivity to MG-63 osteosarcoma cells in a three-dimensional model. Delivery of the anti-epidermal growth factor receptor (EGFR) targeted carboxymethyl chitosan nanoparticles, directly labeled with Na131I (ICED-N), achieved deep tumor penetration in a three-dimensional model. Of three kinetic models, the Higuchi model more closely matched the experimental curve and release profiles. The anti-EGFR targeting resulted in a 513-fold greater targeting efficacy to MG-63 (EGFR+) cells than the control fibroblast (EGFR-) cells. The curcumin-enhanced ICED-N (4 × 0.925 MBq) fractionated-dose regime achieved an 18.3-fold increase in cell cytotoxicity compared to the single-dose (1 × 3.70 MBq) doxorubicin-loaded nanoparticle, and a 13.6-fold increase in cell cytotoxicity compared to the single-dose Na131I nanoparticle. Moreover, the ICED-N fractionated dose increased cells in the G2/M phase 8.78-fold, indicating the cell cycle arrest in the G2/M phase is associated with DNA fragmentation, and the intracellular damage is unable to be repaired. Overall, the results indicate that the fractionated dose was more efficacious than a single dose, and curcumin substantially increased doxorubicin cytotoxicity and amplified osteosarcoma cell radiosensitivity to Na131I.

The radiopharmaceutical radium-223 has immunomodulatory effects in patients and facilitates anti-programmed death receptor-1 therapy in murine models of bone metastatic prostate cancer.

BACKGROUND & PURPOSE: Radium-223 (Ra223) improves survival in metastatic prostate cancer (mPC), but its impact on systemic immunity is unclear, and biomarkers of response are lacking. We examined markers of immunomodulatory activity during standard clinical Ra223 and studied the impact of Ra223 on response to immune checkpoint inhibition (ICI) in preclinical models. MATERIALS & METHODS: We conducted a single-arm biomarker study of Ra223 in 22 bone mPC patients. We measured circulating immune cell subsets and a panel of cytokines before and during Ra223 therapy and correlated them with overall survival (OS). Using two murine mPC models-orthotopic PtenSmad4-null and TRAMP-C1 grafts in syngeneic immunocompetent mice-we tested the efficacy of combining Ra223 with ICI. RESULTS: Above-median level of IL-6 at baseline was associated with a median OS of 358 versus 947 days for below levels; p = 0.044, from the log-rank test. Baseline PlGF and PSA inversely correlated with OS (p = 0.018 and p = 0.037, respectively, from the Cox model). Ra223 treatment was associated with a mild decrease in some peripheral immune cell populations and a shift in the proportion of MDSCs from granulocytic to myeloid. In mice, Ra223 increased the proliferation of CD8+ and CD4+ helper T cells without leading to CD8+ T cell exhaustion in the mPC lesions. In one of the models, combining Ra223 and anti-PD-1 antibody significantly prolonged survival, which correlated with increased CD8+ T cell infiltration in tumor tissue. CONCLUSION: The inflammatory cytokine IL-6 and the angiogenic biomarker PlGF at baseline were promising outcome biomarkers after standard Ra223 treatment. In mouse models, Ra223 increased intratumoral CD8+ T cell infiltration and proliferation and could improve OS when combined with anti-PD-1 ICI.

Metastatic castration resistant prostate cancer patients' experience with Radium-223 treatment in Japan.

Aim: We aimed to determine Japanese metastatic castration resistant prostate cancer (CRPC) patients' Ra-223 treatment experience. Patients & methods: Patients answered the Cancer Therapy Satisfaction Questionnaire (CTSQ domains: Satisfaction with Therapy [SWT], Expectations of Therapy [ET], Feelings about Side Effects [FSE]), the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) and the FACT-Bone Pain (FACT-BP) Questionnaire at baseline, during (vists 3 and 5) and after treatment (end of observation; EOO). Results: Data from 72 patients were included. Baseline median CTSQ scores SWT: 66.1 (IQR19.7), ET: 75.0 (IQR45), and FSE 68.8 (IQR 34.4) were unchanged during vists 3 and 5, but the SWT (-3.57 [IQR17.9]) and ET (-5.0 [IQR30]) decreased while FSE was unchanged (0.0 [IQR31.25]) at EOO. The median MAX-PC (18.0 [IQR 49]) score was unchanged (0.0, IQR 6) while the median FACT BP (54.0 [IQR13]) score decreased by -1.0 (IQR 8) at EOO. Conclusion: Japanese metastatic castration resistant prostate cancer patients' experience is stable during Ra-223 treatment.

What is this study about? We wanted to know the treatment experience with Radium-223 (Ra-223) among Japanese prostate cancer patients. Ra-223 is a radioactive molecule used for the treatment of metastatic castration resistant prostate cancer. We asked patients to answer different questionnaires on treatment satisfaction, anxiety and quality of life before, during, and after treatment with Ra-223. What were the results? Based on the patients' answers to our questionnaires, treatment satisfaction, anxiety and quality of life remain stable while the patients undergo treatment with Ra-223, but in some aspects may decline after treatment. What do the results mean? The results mean that patients' experience during Ra-223 treatment is stable but patients should share any concerns they have about their treatment with their doctors.

Micellar solution of [223Ra]RaCl2: Reaching renal excretion, potent efficacy in osteoblastic osteosarcoma in PDX model, biochemistry alterations and pharmacokinetics.

Despite the successful use of the radiopharmaceutical radium-223 dichloride ([223Ra]RaCl2) for targeted alpha therapy of castration-resistant prostate cancer patients with bone metastases, some short-term side effects, such as diarrhea and vomiting, have been documented, causing patient discomfort. Hence, we prepared a nanosized micellar solution of [223Ra]RaCl2 and evaluated its biodistribution, pharmacokinetics, and induced biochemical changes in healthy mice up to 96 h after intraperitoneal administration as an alternative to overcome the previous limitations. In addition, we evaluated the bone specificity of micellar [223Ra]RaCl2 in patient-derived xenografts in the osteosarcoma model. The biodistribution studies revealed the high bone-targeting properties of the micellar [223Ra]RaCl2. Interestingly, the liver uptake remained significantly low (%ID/g = 0.1-0.02) from 24 to 96 h after administration. In addition, the micellar [223Ra]RaCl2 exhibited a significantly higher uptake in left (%ID/g = 0.85-0.23) and right (%ID/g = 0.76-0.24) kidneys than in small (%ID/g = 0.43-0.06) and large intestines (%ID/g = 0.24-0.09) over time, suggesting its excretion pathway is primarily through the kidneys into the urine, in contrast to the non-micellar [223Ra]RaCl2. The micellar [223Ra]RaCl2 also had low distribution volume (0.055 ± 0.003 L) and longer elimination half-life (28 ± 12 days). This nanosystem was unable to change the enzymatic activities of alanine aminotransferase, aspartate aminotransferase, gamma GT, glucose, and liquiform lipase in the treated mice. Finally, microscopic examination of the animals' osteosarcoma tumors treated with micellar [223Ra]RaCl2 indicated regression of the tumor, with large areas of necrosis. In contrast, in the control group, we observed tumor cellularity and cell anaplasia, mitotic figures and formation of neoplastic extracellular bone matrix, which are typical features of osteosarcoma. Therefore, our findings demonstrated the efficiency and safety of nanosized micellar formulations to minimize the gastrointestinal excretion pathway of the clinical radiopharmaceutical [223Ra]RaCl2, in addition to promoting regression of the osteosarcoma. Further studies must be performed to assess dose-response outcomes and organ/tissue dosimetry for clinical translation.

Dynamic Responses of Circulating T Cells After Stereotactic Body Radiation Therapy for Bone Metastasis in Patients With Breast Cancer.

PURPOSE: Preclinical studies have shown that radiation therapy modulates antitumor immune responses. However, circulating T-cell responses after radiation therapy in patients with cancer have been poorly characterized. This study aims to explore the changes in circulating T cells after stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Peripheral blood samples of 30 patients with breast cancer who underwent SBRT for bone metastasis were analyzed using multicolor flow cytometry. Phenotypes of PD-1+ CD8+ T cells and regulatory T (TREG) cells were examined. Additionally, plasma protein levels were analyzed using a bead-based immunoassay. RESULTS: Circulating PD-1+ CD8+ T cells, which are enriched for tumor-specific clonotypes, were activated at 1 week after SBRT. However, circulating TREG cells were also activated after SBRT; this pattern was also evident among effector Foxp3hiCD45RA- TREG cells. We observed no difference in T-cell responses according to the fraction size and number. Notably, activation of TREG cells was more prominent in patients who experienced greater activation of PD-1+ CD8+ T cells. Plasma level changes in TGF-ß1, soluble CTLA-4, and soluble 4-1BB at 1 week after SBRT were associated with PD-1+ CD8+ T-cell responses. Activation of TREG cells at 1 week after SBRT was associated with worse progression-free survival. Clinical factors including molecular subtype were not associated with the T-cell responses. CONCLUSIONS: SBRT induced activation of both potentially tumor-specific CD8+ T cells and TREG cells, which were tightly associated with each other. These results may support the use of TREG cell-modulating strategies with SBRT to improve the antitumor immune response.

Breaking barriers: Stereotactic ablative proton and photon radiation therapy for renal cell carcinoma with extensive metastases: A case report.

Patients with advanced renal cancer (RCC) often have limited success with systemic therapy due to tumor heterogeneity. However, stereotactic ablative radiotherapy (SABR) has been shown to have a beneficial therapeutic effect for oligometastatic disease when used early. Despite this, current guidelines recommend the use of tyrosine kinase inhibitors (TKIs) as the first-line therapeutic agent for patients with recurrent or metastatic kidney cancer. Additionally, there is limited data on the combination of systemic treatment and SABR for extensive metastatic RCC due to concerns about high toxicity. Proton therapy offers a promising treatment option as it emits energy at a specific depth, generating high target doses while minimizing damage to normal tissue. This allows for precise treatment of various tumor lesions. In this case report, we describe a high-risk 65-year-old male with extensive pleural and thoracic lymph node metastases and 2 bone metastases of clear cell renal cancer. While the targeted therapy and immunotherapy effectively treated the bone metastases, it was not effective in treating the chest metastases, including the pleural and lymph node metastases. Thus, the patient received full-coverage radiotherapy with photon for primary renal tumor and intensity-modulated proton therapy (IMPT) for thoracic metastases. The patient showed no evidence of disease for 1 year after the initial radiotherapy, and no severe SABR-related adverse effects were observed until now. The combination of targeted therapy and immunotherapy with full-coverage radiotherapy may be a promising treatment option for selected patients with extensive metastatic renal cancer, especially as proton therapy allows for more precise control of the beam and minimal damage to normal tissue. This case has motivated us to investigate the potential advantages of administering proton therapy concurrently with systemic therapy in the management of metastatic renal cell carcinoma patients.

Therapeutic efficacy of an alpha-particle emitter labeled anti-GD2 humanized antibody against osteosarcoma-a proof of concept study.

PURPOSE: Current treatments for osteosarcoma (OS) have a poor prognosis, particularly for patients with metastasis and recurrence, underscoring an urgent need for new targeted therapies to improve survival. Targeted alpha-particle therapy selectively delivers cytotoxic payloads to tumors with radiolabeled molecules that recognize tumor-associated antigens. We have recently demonstrated the potential of an FDA approved, humanized anti-GD2 antibody, hu3F8, as a targeted delivery vector for radiopharmaceutical imaging of OS. The current study aims to advance this system for alpha-particle therapy of OS. METHODS: The hu3F8 antibody was radiolabeled with actinium-225, and the safety and therapeutic efficacy of the [225Ac]Ac-DOTA-hu3F8 were evaluated in both orthotopic murine xenografts of OS and spontaneously occurring OS in canines. RESULTS: Significant antitumor activity was proven in both cases, leading to improved overall survival. In the murine xenograft's case, tumor growth was delayed by 16-18 days compared to the untreated cohort as demonstrated by bioluminescence imaging. The results were further validated with magnetic resonance imaging at 33 days after treatment, and microcomputed tomography and planar microradiography post-mortem. Histological evaluations revealed radiation-induced renal toxicity, manifested as epithelial cell karyomegaly and suggestive polyploidy in the kidneys, suggesting rapid recovery of renal function after radiation damage. Treatment of the two canine patients delayed the progression of metastatic spread, with an overall survival time of 211 and 437 days and survival beyond documented metastasis of 111 and 84 days, respectively. CONCLUSION: This study highlights the potential of hu3F8-based alpha-particle therapy as a promising treatment strategy for OS.

Beyond Average: α-Particle Distribution and Dose Heterogeneity in Bone Metastatic Prostate Cancer.

α-particle emitters are emerging as a potent modality for disseminated cancer therapy because of their high linear energy transfer and localized absorbed dose profile. Despite great interest and pharmaceutical development, there is scant information on the distribution of these agents at the scale of the α-particle pathlength. We sought to determine the distribution of clinically approved [223Ra]RaCl2 in bone metastatic castration-resistant prostate cancer at this resolution, for the first time to our knowledge, to inform activity distribution and dose at the near-cell scale. Methods: Biopsy specimens and blood were collected from 7 patients 24 h after administration. 223Ra activity in each sample was recorded, and the microstructure of biopsy specimens was analyzed by micro-CT. Quantitative autoradiography and histopathology were segmented and registered with an automated procedure. Activity distributions by tissue compartment and dosimetry calculations based on the MIRD formalism were performed. Results: We revealed the activity distribution differences across and within patient samples at the macro- and microscopic scales. Microdistribution analysis confirmed localized high-activity regions in a background of low-activity tissue. We evaluated heterogeneous α-particle emission distribution concentrated at bone-tissue interfaces and calculated spatially nonuniform absorbed-dose profiles. Conclusion: Primary patient data of radiopharmaceutical therapy distribution at the small scale revealed that 223Ra uptake is nonuniform. Dose estimates present both opportunities and challenges to enhance patient outcomes and are a first step toward personalized treatment approaches and improved understanding of α-particle radiopharmaceutical therapies.

A potential biomarker of radiosensitivity in metastatic hormone sensitive prostate cancer patients treated with combination external beam radiotherapy and radium-223.

PURPOSE: The ADRRAD trial reported the safety and feasibility of the combination of external beam radiotherapy and radium-223 in the treatment of de novo bone metastatic prostate. This study aimed to determine if any biomarkers predictive of response to these treatments could be identified. EXPERIMENTAL DESIGN: 30 patients with newly diagnosed bone metastatic hormone sensitive prostate cancer were recruited to the ADRRAD trial. Blood samples were taken pre-treatment, before cycles 2 to 6 of radium-223, and 8 weeks and 6 months after treatment. Mononuclear cells were isolated and DNA damage was assessed at all timepoints. RESULTS: DNA damage was increased in all patients during treatment, with bigger increases in foci observed in patients who relapsed late compared to those who relapsed early. Increases in DNA damage during the radium-223 only cycles of treatment were specifically related to response in these patients. Analysis of hematology counts also showed bigger decreases in red blood cell and hemoglobin counts in patients who experienced later biochemical relapse. CONCLUSIONS: While some patients responded to this combination treatment, others relapsed within one year of treatment initiation. This study identifies a biomarker based approach that may be useful in predicting which patients will respond to treatment, by monitoring both increases in DNA damage above baseline levels in circulating lymphocytes and decreases in red blood cell and hemoglobin counts during treatment.

Short-term pain control after palliative radiotherapy for uncomplicated bone metastases: a prospective cohort study.

This study aimed at evaluating the efficacy of different radiotherapy (RT) fractionation regimens in managing uncomplicated painful bone metastases (BM) and identifying predictive factors for pain control. Patients with 1 to 4 symptomatic BM from any primary solid tumors and a life expectancy exceeding 3 months were included in the study and received palliative RT, with SBRT restricted in the context of oligometastatic disease or in patients with good prognosis. Pain analysis using the Brief Pain Inventory (BPI) tool was conducted at baseline, 1 and 3 months after RT. Analgesic intake was recorded as morphine-equivalent doses (OME). Pain response was assessed using the International Consensus on Palliative Radiotherapy Endpoint (ICPRE). Multivariate logistic regression analyzed patient-related, tumor-related, and treatment-related factors predicting BM pain control at 3 months post-RT. From Feb 2022 to Feb 2023, 44 patients with 65 symptomatic BM were investigated. Breast (32%) and lung (24%) tumors were the most common primary tumors. Treatment plans included 3DCRT (60%) and VMAT (40%), with a median biological effective dose for tumors (BED) of 29 Gy [14-108]. All patients completed the 3-month follow-up. Pain response rates were 62% at 1 month and 60% at 3 months. Responders had better PS ECOG scores (67%; P = 0.008) and received active systemic therapies (67%: P = 0.036). Non-responders had lower pretreatment BPI (mean: 13.7 vs. 58.2; P = 0.032), with significantly higher values after 1 month (mean: 9.1 vs. 5.3, P = 0.033). Baseline BPI (OR: 1.17; 95% CI: 1.032-1.327; P = 0.014) and BPI at 1 month (OR: 0.83; 95% CI: 0.698-0.976; P = 0.025) were independent predictors of pain response at 3 months. Our findings show that palliative RT ensured short-term pain control in patients with BM, regardless of tumor type and dose-fractionation regimen. A larger sample size and a longer follow-up could potentially identify which patients are likely to benefit most from RT, and which fractionation might be indicated for achieving a durable pain relief. A multidisciplinary approach is paramount to provide a better care to BM patients.