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Purpose: To investigate the treatment outcomes of extracranial oligometastatic colorectal cancer (CRC) patients treated with stereotactic body radiotherapy (SBRT)., Materials and Methods: The clinical data of 388 extra-cranial oligometastatic CRC (≤ 5 lesions) patients and 463 lesions treated with SBRT at 19 cancer institutions were retrospectively analyzed. The prognostic factors predicting overall survival (OS), progression-free survival (PFS), and local control (LC) were assessed in uni- and multivariable analyses., Results: The median age was 62 years (range, 29-92 years). The majority of the patients (90.5%) received surgery and systemic treatment for their primary tumor, had ≤ 2 metastasis (83.3%), had single organ involvement (90.3%), and staged using flouro-deoxyglucose positron emission tomography (FDG-PET/CT) (76%). The median fraction and total radiation doses were 10 Gy (range: 6-34 Gy) and 50 Gy (range: 8-64 Gy), respectively, delivered in a median of 4 fractions (range: 1-8). The median follow-up time for the entire cohort was 30.7 months (interquartile range: 27.0-34.3 months). The 3‑year OS, PFS, and LC rates were 64.0%, 42.3%, and 72.7%, respectively. The 3‑year LC rate was significantly higher in patients receiving BED 10  ≥ 100 Gy than those receiving BED 10  < 100 Gy (76.0% vs. 67.3%; p = 0.04). The 3‑year PFS and OS rates were higher in patients receiving BED 10  ≥ 100 Gy than those receiving BED 10  < 100 Gy (33.2% vs. 25.2%; p = 0.03; 53.7% vs.  44.8%; p = 0.02). Single metastasis and complete response after SBRT were independent prognostic factors for survival in multivariable analysis., Conclusions: In this multi-center study, we demonstrated that SBRT is an effective treatment option of metastatic lesions in oligometastatic CRC patients by providing promising LC rates. Higher SBRT doses beyond BED 10  ≥ 100 Gy were associated with improved LC and survival. LC of treated lesion and lower tumor burden after SBRT were associated with better outcomes., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

High-activity radioactive iodine (RAI) therapy for metastatic thyroid cancer (TC) requires isolation to minimize radiation exposure to third parties, thus posing challenges for patients needing hands-on care. There are limited data on the approach to high-activity RAI treatment in paraplegic patients. We report a state-of-the-art multidisciplinary approach to the management of bedbound patients, covering necessary radiation safety measures that lead to radiation exposure levels as low as reasonably achievable. Given the limited literature resources on standardized approaches, we provide a practical example of the safe and successful treatment of a woman with BRAFV600E -mutant tall-cell-variant papillary TC and pulmonary metastases, who underwent dabrafenib redifferentiation before RAI therapy. The patient was 69 y old and had become paraplegic because of a motor-vehicle accident. Since caring for a paraplegic patient with neurogenic bowel and bladder dysfunction poses radiation safety challenges, a multidisciplinary team comprising endocrinologists, nuclear medicine physicians, radiation safety specialists, and the nursing department developed a radiation mitigation strategy to ensure patient and staff safety during RAI therapy. The proposed standardized approach includes thorough monitoring of radiation levels in the workplace, providing additional protective equipment for workers who handle radioactive materials or are in direct patient contact, and implementing strict guidelines for safely disposing of radioactive waste such as urine collected in lead-lined containers. This approach requires enhanced training, role preparation, and practice; use of physical therapy equipment to increase the exposure distance; and estimation of the safe exposure time for caregivers based on dosimetry. The effective and safe treatment of metastatic TC in paraplegic patients can be successfully implemented with a comprehensive radiation mitigation strategy and thorough surveying of personnel for contamination., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective. Proton therapy is a limited resource and is typically not available to metastatic cancer patients. Combined proton-photon therapy (CPPT), where most fractions are delivered with photons and only few with protons, represents an approach to distribute proton resources over a larger patient population. In this study, we consider stereotactic radiotherapy of multiple brain or liver metastases, and develop an approach to optimally take advantage of a single proton fraction by optimizing the proton and photon dose contributions to each individual metastasis. Approach. CPPT treatments must balance two competing goals: (1) deliver a larger dose in the proton fractions to reduce integral dose, and (2) fractionate the dose in the normal tissue between metastases, which requires using the photon fractions. Such CPPT treatments are generated by simultaneously optimizing intensity modulated proton therapy (IMPT) and intensity modulated radiotherapy (IMRT) plans based on their cumulative biologically effective dose (BED α / β ). The dose contributions of the proton and photon fractions to each individual metastasis are handled as additional optimization variables in the optimization problem. The method is demonstrated for two patients with 29 and 30 brain metastases, and two patients with 4 and 3 liver metastases. Main results. Optimized CPPT plans increase the proton dose contribution to most of the metastases, while using photons to fractionate the dose around metastases which are large or located close to critical structures. On average, the optimized CPPT plans reduce the mean brain BED 2 by 29% and the mean liver BED 4 by 42% compared to IMRT-only plans. Thereby, the CPPT plans approach the dosimetric quality of IMPT-only plans, for which the mean brain BED 2 and mean liver BED 4 are reduced by 28% and 58%, respectively, compared to IMRT-only plans. Significance. CPPT with optimized proton and photon dose contributions to individual metastases may benefit selected metastatic cancer patients without tying up major proton resources., (Creative Commons Attribution license.)

Purpose: We conducted a single-center, single-arm study (NCT03129412) to prospectively analyze the long-term outcomes of newly diagnosed patients with oligometastatic nasopharyngeal carcinoma (NPC) who received radical radiotherapy and local treatment of metastases., Patients and Methods: Patients who reached disease controll after platinum-based palliative chemotherapy continued to receive radical radiotherapy for the nasopharyngeal region and neck. Appropriate local treatments were selected to treat the metastatic lesions. The primary endpoint of this study was overall survival (OS) and the secondary endpoint was progression-free survival (PFS)., Results: Fifty-one patients were included in the final analysis. During a median follow-up of 60 months, the median OS and PFS were 53.87 and 24.23 months, respectively. The 1-year, 3-year, and 5-year PFS and OS rates were 76.5 %, 38.1 %, and 31.8 % and 98 %, 75.4 %, 45.6 %, respectively. Both single and multivariate analysis indicated that maintenance therapy after radiotherapy could significantly increase PFS (36.43 vs. 16.1 months, P = 0.005). The OS of patients with single organ metastasis was significantly better than that of patients with double organ metastasis (P = 0.001). In addition, the number of metastatic organs also significantly affected PFS in the multifactor analysis., Conclusion: Patients with newly diagnosed oligometastatic NPC can achieve long-term survival after receiving radical radiotherapy to the primary site and local treatment for metastases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: The management of oligometastatic prostate cancer, defined by its few metastatic sites, poses distinct clinical dilemmas. Debates persist regarding the most effective treatment approach, with both cytoreductive surgery and radiotherapy being key contenders. The purpose of this research is to thoroughly evaluate and compare the effectiveness of these two treatments in managing patients with oligometastatic prostate cancer., Methods: A comprehensive search of the literature was carried out to find pertinent publications that compared the results of radiation and cytoreductive surgery for oligometastatic prostate cancer. A meta-analysis was conducted in order to evaluate both short-term and long-term survival. Furthermore, utilizing institutional patient data, a retrospective cohort research was conducted to offer practical insights into the relative performances of the two treatment regimens., Results: Five relevant studies' worth of data were included for this meta-analysis, which included 1425 patients with oligometastatic prostate cancer. The outcomes showed that, in comparison to radiation, cytoreductive surgery was linked to a substantially better cancer-specific survival (CSS) [hazard ratio (HR): 0.70, 95% (CI): 0.59-0.81, P <0.001] and overall survival (OS) [HR, 0.80; 95% (CI), 0.77-0.82; P <0.01]. The two therapy groups' Progression-Free Survival (PFS) and Castration-Resistant Prostate Cancer-Free Survival (CRPCFS), however, did not differ significantly (HR: 0.56, 95% CI: 0.17-1.06; HR: 0.67, 95% CI: 0.26-1.02, respectively). Out of the 102 patients who were recruited in the retrospective cohort research, 36 had cytoreductive surgery (CRP), 36 had radiation therapy (primary lesion), and 30 had radiation therapy (metastatic lesion). The follow-up time was 46.3 months (18.6-60.0) on average. The enhanced OS in the CRP group [OS interquartile range (IQR): 45-60 months] in comparison to the radiation group (OS IQR: 39.0-59.0 months and 25.8-55.0 months, respectively) was further supported by the cohort research. Furthermore, CRP had a better OS than both radiation (primary region) and radiotherapy (metastatic region), with the latter two therapeutic methods having similar OS., Conclusion: This meta-analysis and retrospective research provide valuable insights into the comparative efficacy of cytoreductive surgery and radiotherapy for oligometastatic prostate cancer. While short-term survival (PFS, CRPCFS) was similar between the two groups, cytoreductive surgery exhibited superior CSS and OS. Adverse event rates were manageable in both modalities. These findings contribute to informed treatment decision-making for clinicians managing oligometastatic prostate cancer patients. Further prospective studies and randomized controlled trials are essential to corroborate these results and guide personalized therapeutic approaches for this distinct subset of patients., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The effectiveness of single-fraction 8-Gy radiotherapy for painful bone metastases has been verified in numerous randomized controlled trials. However, few reports have described the effectiveness of single-fraction 8-Gy radiotherapy in painful tumors other than bone metastases. We conducted a retrospective analysis to evaluate the pain response to single-fraction 8-Gy radiotherapy in painful non-bone-metastasis tumors. We included patients who had received single-fraction 8-Gy radiotherapy for such tumors between January 2017 and December 2022, excluding those with brain metastases, hematological tumors and those who received re-irradiation. Pain response assessment was based on the best responses documented in the medical records and conducted by two radiation oncologists. A total of 36 eligible patients were included in this study. The irradiation sites included primary lesions in eight patients, lymph node metastases in eight, muscle metastases in seven, pleural dissemination in four, skin/subcutaneous metastases in four and other sites in five. Pain response was assessed in 24 patients after radiotherapy. Pain response rate was 88% in evaluable patients; 21 of the 24 patients experienced response. The median assessment date for pain response was 37 days (range: 8-156 days) after radiotherapy. Re-irradiation was performed in four patients (11%). Single-fraction 8-Gy radiotherapy seemed to be a promising treatment option for painful non-bone-metastasis tumors and warrants further investigation., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Introduction: Treatment of recurrent oligometastatic gynecologic malignancy may involve targeted surgery, thermal ablation, or CT-guided high-dose-rate interstitial brachytherapy ablation (CT-HDR-IBTA). The purpose of this study was to describe the safety and efficacy of CT-HDR-IBTA for oligometastatic gynecologic malignancies., Methods: With institutional review board approval (IRB) approval and compliance with the Health Insurance Portability and Accountability Act of 1996 (HIPAA) compliance, we searched our database to assemble a single-arm study cohort of all patients with oligometastatic gynecologic cancers who underwent CT-HDR-IBTA from 2012-2022 with follow-up. The electronic record was reviewed to determine relevant clinicopathological variables including patient demographics, prior treatments, clinical course, local control, and local and distant recurrence with follow-up imaging., Results: The study cohort comprised 37 lesions in 34 patients treated with CT-HDR-IBTA for recurrent oligometastatic uterine (n = 17), cervix (n = 1), or ovarian cancer (n = 16) with an average lesion size of 2.5 cm with an average patient age of 61.4 years. Each lesion was treated with an average radiation dose of 23.8 Gy in 1.8 fractions and a median follow-up time of 24.0 months. The primary efficacy of CT HDR ITBA was 73% with a median progression-free survival of 8.0 months (95% CI 3.6-12.8 months) and with 58% of patients still alive at 43 months with median overall survival not reached. The rate of Grade 1 adverse events was 22% without any Grade 2, 3 or 4 events., Conclusions: CT HDR IBTA was safe and effective for treating oligometastatic gynecologic cancers in a heavily pretreated cohort., Competing Interests: Declaration of Competing Interest The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Oligometastatic disease (OMD) is a metastatic stage that could benefit maximally from local therapies. Patients in this state have a better prognosis relative to those with disseminated metastases. Stereotactic radiotherapy provides a non-invasive ablative tool for primary malignant tumors and metastases., Materials and Methods: We searched our register for patients with oligometastatic or recurrent head and neck cancer (OMD/R-HNC) who received stereotactic radiotherapy to manage their OMD/R. We evaluated the survival outcomes and prognostic factors that affected the survival of those patients., Results: In all, 31 patients with 48 lesions met the inclusion criteria for the analysis. The lesions comprised various metastatic sites, with the majority being pulmonary (37 lesions). Squamous cell cancer was the most common histology (26 patients). The median overall survival (mOS) was 33 months, with a progression-free survival (PFS) of 9.6 months. Eight patients received subsequent stereotactic radiotherapy after disease progression. The local control (LC) rates were 91.3, 87.7, and 83% at 6, 12, and 36 months. Patients with the de novo OMD who received stereotactic radiotherapy as their initial treatment had a median systemic treatment-free survival of 23.9 months. In univariate analysis, a trend for better OS was observed in patients with p16-positive squamous cell tumors; patients who progressed within 150 days after diagnosis had a significantly lower OS. De novo OMD showed significantly better PFS compared to induced OMD. Multivariate analyses identified p16-positive squamous cell cancer, metachronous OMD and a longer time to progression as positive predictors of OS, while de novo OMD was the only positive predictor for PFS. Treatment-related toxicities were generally mild, with two cases of grade 3 dysphagia reported., Conclusion: Stereotactic radiotherapy demonstrated favorable outcomes in patients with OMD/R-HNC with limited toxicities. Further studies are warranted to validate these findings and optimize treatment strategies for this patient population., (© 2023. The Author(s).)

Purpose: Local ablative therapy, such as radiotherapy or surgery, plays a key role in treatment of patients with oligometastatic disease. Stereotactic ablative body radiotherapy (SABR) comes to the fore as a safe and effective treatment for patients with a limited number of metastases, even those located in hard-to-reach body sites. Many researchers have suggested that metastatsis-directed therapy could improve long-term progression-free survival (PFS) and overall survival (OS) in patients with oligometastases., Patients and Methods: This was a retrospective, single-arm, observational study conducted between July 2015 and February 2022. In our institute, 60 patients with controlled primary tumors and one to five metastases were treated with SABR. Prescribed radiation doses ranged from 12 to 60 Gy administered in one to seven fractions. We aimed to determine whether metastatic-directed therapy using SABR for all oligometastases affects OS and PFS and whether the primary tumor or metastatic site influences OS/PFS., Results: The most common primary malignancy types were prostate (n = 14), colorectal (n = 10), lung (n = 7), and breast cancers (n = 6). The median follow-up was 30 months, ranging from 9 to 79. The 1-, 3-, and 5-year PFS and OS rates were 54.9%, 37.0%, and 37.0% and 98.3%, 84.4%, and 73.8%, respectively, and the median time to first progression was 15 (range, 2-32) months. Twenty-four (40%) patients had no recurrence. In our analysis, primary tumor site was not an independent prognostic factor. The metastatic site may influence on patient outcome in cases of localized bone and liver metastases., Conclusion: In our retrospective analysis, SABR was associated with favorable levels of PFS and OS in patients with oligometastases. The limitations of our study were lacking high-level evidence, and randomized studies to compare SABR and palliative standard of care are mandatory.

Objective: We aimed to evaluate recent trends in characteristics and treatments among patients with brain metastases in clinical practice., Methods: All newly diagnosed patients with brain metastases during 2016-2021 at a single cancer center were enrolled. We collected the detailed features of each patient and estimated the number of candidates considered to meet the following criteria used in common clinical trials: Karnofsky performance status ≥ 70 and mutated non-small cell lung cancer, breast cancer or melanoma. The brain metastases treatments were classified as follows: (i) stereotactic radiosurgery, (ii) stereotactic radiosurgery and systemic therapy, (iii) whole-brain radiotherapy, (iv) whole-brain radiotherapy and systemic therapy, (v) surgery, (vi) immune checkpoint inhibitor or targeted therapy, (vii) cytotoxic agents and (ix) palliative care. Overall survival and intracranial progression-free survival were estimated from brain metastases diagnosis to death or intracranial progression., Results: A total of 800 brain metastases patients were analyzed; 597 (74.6%) underwent radiotherapy, and 422 (52.7%) underwent systemic therapy. In addition, 250 (31.3%) patients were considered candidates for common clinical trials. Compared to 2016, the later years tended to shift from whole-brain radiotherapy to stereotactic radiosurgery (whole-brain radiotherapy: 35.7-29.1% and stereotactic radiosurgery: 33.4-42.8%) and from cytotoxic agents to immune checkpoint inhibitor/targeted therapy (cytotoxic agents: 10.1-5.0 and immune checkpoint inhibitor/targeted therapy: 7.8-10.9%). There was also an increase in the proportion of systemic therapy combined with radiation therapy (from 26.4 to 36.5%). The median overall survival and progression-free survival were 12.7 and 5.3 months, respectively., Conclusions: This study revealed the diversity of brain metastases patient characteristics, recent changes in treatment selection and the percentage of candidates in clinical trials., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Japanese national oncological experts convened to evaluate the efficacy and safety of particle beam therapy (PT) for pulmonary, liver and lymph node oligometastases (P-OM, L-OM and LN-OM, respectively) and to conduct a statistically comparative analysis of the local control (LC) rate and overall survival (OS) rate of PT versus those of X-ray stereotactic body radiotherapy (X-SBRT) and X-ray intensity-modulated radiotherapy (X-IMRT). They conducted [1] an analysis of the efficacy and safety of metastasis-directed therapy with PT for P-OM, L-OM and LN-OM using a Japanese nationwide multi-institutional cohort study data set; [2] a systematic review of X-ray high-precision radiotherapy (i.e. X-SBRT/X-IMRT) and PT for P-OM, L-OM and LN-OM; and [3] a statistical comparison between LC and OS of the cohort data set in PT and that of the extracted historical data set in X-SBRT/X-IMRT from the preceding systematic review. Safety was evaluated as the incidence of grade ≥ 3 adverse events, while statistical comparisons of LC and OS were conducted by estimating the incidence rate ratios (IRR) for local progression and mortality, respectively. This study demonstrated that PT provided durable LC (3-year LC rate: 72.8-83.2%) with acceptable OS (3-year OS rate: 38.5-68.1%) and risk of severe toxicity incidence of 0.8-3.5% in radical metastasis-directed therapy for P-OM, L-OM and LN-OM. Compared to LC with X-SBRT or X-IMRT, LC with PT was potentially superior for P-OM; superior for L-OM; and equivalent for LN-OM. In particular, this study demonstrated that PT may be a new treatment option for L-OM tumors measuring > 5 cm., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

What Is This Summary About?: Few life-prolonging treatment options are available for patients with metastatic castration-resistant prostate cancer (mCRPC). This article provides an overview of the current systemic treatments available for mCRPC and reviews studies that investigate the optimal timing for the use of radium-223. The aim is to illustrate possible systemic treatment sequences to maximize benefit from radium-223 therapy., What Is Metastatic Castration-Resistant Prostate Cancer & How Is It Treated?: Prostate cancer is called mCRPC when it spreads to organs outside of the prostate (such as the lymph nodes, bones, liver, or lungs) and no longer responds to hormonal therapy. There are several treatment options available for mCRPC, such as abiraterone, enzalutamide, radium-223, docetaxel, cabazitaxel, olaparib, rucaparib, sipuleucel-T, and 177Lu-PSMA. It is important to understand the risks and benefits associated with each treatment and whether current use may have an impact on future treatment options, including eligibility in certain clinical trials. Maintaining bone health is also an important part of prostate cancer care., What Is Radium-223?: Radium-223 is a radioactive molecule that releases strong radiation within a very small range around itself. It mainly travels to the bone where the prostate cancer has spread and kills the cancer cells in that area. Results from a clinical study named ALSYMPCA showed that men who received radium-223 lived longer in addition to having less bone pain. The most common side effects of radium-223 are nausea, vomiting, and diarrhea. Radium-223 minimally suppresses the bone marrow, which means that it slightly reduces the levels of red and white blood cells.

Background and Purpose: The use of SBRT for the treatment of oligometastatic prostate cancer is increasing rapidly. While consensus guidelines are available for non-spinal bone metastases practice continues to vary widely. The aim of this study is to look at inter-observer variability in the contouring of prostate cancer non-spinal bone metastases with different imaging modalities., Materials and Methods: 15 metastases from 13 patients treated at our centre were selected. 4 observers independently contoured clinical target volumes (CTV) on planning CT alone, planning CT with MRI fusion, planning CT with PET-CT fusion and planning CT with both MRI and PET-CT fusion combined. The mean inter-observer agreement on each modality was compared by measuring the delineated volume, generalized conformity index (CIgen), and the distance of the centre of mass (dCOM), calculated per metastasis and imaging modality., Results: Mean CTV volume delineated on planning CT with MRI and PET-CT fusion combined was significantly larger compared to other imaging modalities (p = 0.0001). CIgen showed marked variation between modalities with the highest agreement between planning CT + PET-CT (mean CIgen 0.55, range 0.32-0.73) and planning CT + MRI + PET-CT (mean CIgen 0.59, range 0.34-0.73). dCOM showed small variations between imaging modalities but a significantly shorter distance found on planning CT + PET-CT when compared with planning CT + PET-CT + MRI combined (p = 0.03)., Conclusions: Highest consistency in CTV delineation between observers was seen with planning CT + PET-CT and planning CT + PET-CT + MRI combined., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.)

Purpose: In patients with extracranial oligometastatic disease, distant failure (DF) after local ablative therapies is common. Prognostic scores to guide salvage treatment decision making are currently lacking. Analogous to brain metastasis velocity, we propose distant metastasis velocity (DMV) as a prognostic score for overall survival (OS) and widespread failure-free survival (WFFS) after DF following metastasis-directed stereotactic body radiation therapy (SBRT)., Methods and Materials: Patients with ≤5 metastases from solid organ malignancies treated with SBRT to all lesions at our institution from 2014 to 2019 were screened, and patients who developed DF were included in this retrospective analysis. DMV was defined as metastases per month, determined at DF, and transformed into a 3-level categorical variable with cut points that minimized the log-rank P value for OS. Simple and multiple linear regression was used to predict DMV based on different patient and treatment variables. The association of DMV and other variables with OS was studied by univariable and multivariable Cox regression., Results: Three hundred eighty-five patients were screened, of which 303 developed DF and were included. The median DMV was 0.7 metastases per month. Patients with <0.5, 0.5 to 1.5, and >1.5 metastases per month were classified as low, intermediate, and high DMV, and had a median OS of 37.1, 26.7, and 16.8 months, respectively (P < .0001). On multivariable analysis, DMV was a strong independent predictor of OS, with a hazard ratio of 0.31 for low (P < .001) compared with high DMV. Lower DMV was significantly associated with longer WFFS (P = .04). The cumulative metastases volume at baseline (regression coefficient β = 0.03, P = .04) and oligoprogressive/-persistent disease (β = 1.91, P = .10) predicted higher DMV., Conclusions: DMV is a novel metric strongly associated with OS and WFFS after DF following SBRT in patients with oligometastatic disease and should be evaluated for decision making about the optimal multimodality salvage treatment strategy. The prognostic value of DMV should be validated in prospective studies., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Prostate cancer ranges from localized, low risk to metastatic, morbid disease. Although radiation therapy (RT) is commonly incorporated in the treatment of early disease or for palliation of symptomatic lesions, its role in extending survival in metastatic disease is less well-established. Here, we review the available evidence surrounding localized RT in the presence of oligometastatic disease and metastasis-directed therapy in both hormone-sensitive and hormone-resistant prostate cancer. We further outline potential future incorporation of RT as an immune-sensitizing therapy and the importance of highly sensitive imaging modalities in considering RT in metastatic disease., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this critical review is to provide an overview of the role and outcomes associated with the use of local therapy for patients with oligometastatic gastrointestinal cancers., Methods and Materials: A review of clinical data was performed to describe outcomes associated with the use of systemic therapy and/or locoregional therapies for patients with oligometastatic gastrointestinal cancers including esophagus, gastric, liver, biliary, pancreas, colorectal, and anal canal., Results: This review describes outcomes associated with current first line systemic therapy and oligometastasis directed locoregional therapy for patients with gastrointestinal cancers. Available data suggest that for well-selected patients among each gastrointestinal disease subsite, the use of local therapy is associated with favorable disease control and possible survival benefit., Conclusions: These data emphasize the importance of multidisciplinary collaboration and consideration of radiation therapy for patients with oligometastatic gastrointestinal cancers to improve locoregional control and progression-free survival. Multiple trials are ongoing to determine whether metastasis-directed radiation therapy improves overall survival., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The survival benefit of primary external beam radiation therapy (EBRT) has never been formally tested in elderly men who were newly diagnosed with metastatic prostate cancer (mPCa). We hypothesized that elderly patients may not benefit of EBRT to the extent as younger newly diagnosed mPCa patients, due to shorter life expectancy., Methods: We relied on Surveillance, Epidemiology and End Results (2004-2016) to identify elderly newly diagnosed mPCa patients, aged >75 years. Kaplan-Meier, univariable and multivariable Cox regression models, as well as Competing Risks Regression models tested the effect of EBRT versus no EBRT on overall mortality (OM) and cancer-specific mortality (CSM)., Results: Of 6556 patients, 1105 received EBRT (16.9%). M1b stage was predominant in both EBRT (n = 823; 74.5%) and no EBRT (n = 3908; 71.7%, p = 0.06) groups, followed by M1c (n = 211; 19.1% vs. n = 1042; 19.1%, p = 1) and M1a (n = 29; 2.6% vs. n = 268; 4.9%, p < 0.01). Median overall survival (OS) was 23 months for EBRT and 23 months for no EBRT (hazard ratio [HR]: 0.97, p = 0.6). Similarly, median cancer-specific survival (CSS) was 29 months for EBRT versus 30 months for no EBRT (HR: 1.04, p = 0.4). After additional multivariable adjustment, EBRT was not associated with lower OM or lower CSM in the entire cohort, as well as after stratification for M1b and M1c substages., Conclusions: In elderly men who were newly diagnosed with mPCa, EBRT does not affect OS or CSS. In consequence, our findings question the added value of local EBRT in elderly newly diagnosed mPCa patients., (© 2021 The Authors. The Prostate published by Wiley Periodicals LLC.)

First cycle dosimetry calculation of 177 Lu-DOTATOC (single activity:1.59-3.49 GBq) was carried out in eight patients with advanced neuroendocrine tumors (NETs) who underwent whole-body planar (0.5, 24, 48, 72 h) and SPECT/CT scans (24 h). Focal uptake of 177 Lu-DOTATOC was found in primary and metastatic tumors. Organs with the highest absorbed doses per injected activity were tumors (1.293 ± 0.862 mGy/MBq) and spleen (0.461 ± 0.408 mGy/MBq), while low absorbed doses were observed in kidneys (0.384 ± 0.112 mGy/MBq) and bone marrow (0.0297 ± 0.0123 mGy/MBq). 177 Lu-DOTATOC is safe, well-tolerated and appropriate in Chinese NETs patients for PRRT., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose: Stereotaxic radiotherapy is performed regularly for the irradiation of non-spine bone metastases, but its place is not well understood., Materials and Methods: This article in stereotaxic radiotherapy of non-spine bones oligometastases presents the current scientific data relating to the indications, to virtual simulation, to the delineation of target volumes, to the total dose and fractionation, to the efficacy and tolerance., Results: Oligometastatic patients are classified into 4 categories: oligorecurrences, oligometastasis, oligopersistence, oligoprogression. The prognosis will be evaluated according to the following characteristics: primary tumor, quantitative characteristics, kinetics, qualitative characteristics. The delineation of GTV includes extensions to the soft tissue and bone marrow with the aid of MRI and PET. The CTV corresponds to a margin of 2 to 5mm and the PTV to a margin of 2mm. The most widely used irradiation schemes are: 1 single fraction of 18 to 24Gy/1 fr; 24Gy/2 fr; 27 to 30Gy/3 fr; 30 to 35Gy/5 fr. Stereotaxis provides 90% local control at 1 year and good pain control. The side effects are not very marked., Conclusion: Stereotaxic radiotherapy is feasible, non-invasive, minimally toxic and effective with good local control and good pain relief. The main issue remains selecting the patients most likely to benefit from it., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background: The use of stereotactic radiotherapy (SBRT) for oligometastases is supported by several literature studies, but in the setting of gynecological malignancies, this scenario remains quite unexplored. This study reports a preliminary assessment of clinical outcomes in a cohort of 40 patients with oligometastatic gynecological neoplasms., Methods: Radiotherapy was delivered in 3-10 fractions with VMAT-IGRT technique. Toxicity was retrospectively collected according to CTCAE v4.0. Data were retrospectively collected and analyzed. Univariate and multivariate analyses were performed for assessing any potential predictive factor for clinical outcomes., Results: A total of 63 oligometastases were treated from December 2014 to February 2021. Median age was 63 years (range 30-89). Most frequent primary tumors were ovarian cancer in 42.5% and endometrium cancer in 42.5%. With a median follow-up of 27 months (range 6-69), no local failures were observed, our progression-free survival rates were 43.6% and 23% at one and 2 years, respectively, while 1 and 2-year overall survival rates were both 70%. No acute or late G ≥ 2 adverse events were observed., Conclusions: In our experience, SBRT for oligometastatic gynecological malignancies resulted in promising results in terms of clinical outcomes, with excellent local control and no evidence of severe toxicity, highlighting the effectiveness of this therapeutic option. Prospective studies to further explore this approach in this setting are advocated., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Stereotactic radiotherapy is an ever more common technique, regardless of the location treated. However, spinal stereotactic radiotherapy requires a particular technicality in order to ensure its proper realization. There is now a large literature defining the type of imaging to be used, the dose to be delivered and the delineation of target volumes. This technique can achieve a significant local control and an interesting analgesic efficiency. However, its place in relation to conventional radiotherapy remains limited because it requires MRI imaging and a significantly longer patient management during the treatment fraction. In this context, it is currently mainly restricted to oligometastatic patients or for re-irradiations., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: A Benchmark Case (BC) was performed as part of the quality assurance process of the randomized phase 2 GORTEC 2014-14 OMET study, testing the possibility of multisite stereotactic radiation therapy (SBRT) alone in oligometastatic head and neck squamous cell carcinoma (HNSCC) as an alternative to systemic treatment and SBRT., Material and Methods: Compliance of the investigating centers with the prescription, delineation, planning and evaluation recommendations available in the research protocol was assessed. In addition, classical dosimetric analysis was supplemented by quantitative geometric analysis using conformation indices., Results: Twenty centers participated in the BC analysis. Among them, four major deviations (MaD) were reported in two centers. Two (10%) centers in MaD had omitted the satellite tumor nodule and secondarily validated after revision. Their respective DICE indexes were 0.37 and 0 and use of extracranial SBRT devices suboptimal There were significant residual heterogeneities between participating centers, including those with a similar SBRT equipment, with impact of plan quality using standard indicators and geometric indices., Conclusion: A priori QA using a BC conditioning the participation of the clinical investigation centers showed deviations from good SBRT practice and led to the exclusion of one out of the twenty participating centers. The majority of centers have demonstrated rigorous compliance with the research protocol. The use of quality indexes adds a complementary approach to improve assessment of plan quality., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

The abscopal effect has been mentioned since 1953. The increase in knowledge about the immune system and the development of immunotherapies support its potential therapeutic interest. While it is accepted that radiotherapy induces an immune response, demonstrating its systemic impact is not easy. The preclinical basis is solid but its clinical validation pending. Radiotherapy rarely induces tumor reduction at a distance from the beams, probably due to its immunosuppressive effect. This is why a synergy between radiotherapy and systemic treatments targeting these immunosuppressive mechanisms was observed. Several parameters can modulate the induction of the abscopal effect. Among these, the fractionation of the dose seems to be determining with currently a pre-eminence of hypofractionated stereotaxis. On the other hand, even if the choice of more immunogenic targets (liver, lung) should be favoured, the optimal number of lesions to be irradiated remains to be defined as well as the minimum volume allowing sufficient release of tumor antigens. The impact of radiation-induced lymphopenia on radiotherapy/immunotherapy efficacy needs to be assessed more precisely, as does the effect of radiotherapy techniques on them. Finally, the choice of immunotherapy(ies) and the combination regimen with radiotherapy remain under discussion. A sequential scheme appears to provide less toxicities but the concomitant would lead to a better response. The study of these different parameters should allow us to deliver optimized radiotherapy/immunotherapy(ies) combinations to our metastatic patients in order to benefit as many people as possible from this abscopal effect., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

The constantly increasing life expectancy is raising the issue of treating oncological older patients, who were traditionally candidates to best supportive care or palliative treatments. Several literature data support SBRT in the treatment of the oligometastatic patient as a potentially curable therapeutic option. However, data on older patients are lacking. This study presents the outcomes of a cohort of 61 oligometastatic patients over the age of 80 years who received SBRT, that was proposed to all patients with a minimum Karnofsky Performance Status ≥ 70 and a life expectancy of at least 6 months, with up to five oligometastatic lesions. Radiotherapy was delivered in 3-10 fractions with VMAT-IGRT technique. Toxicity was retrospectively collected according to CTCAE v4.0. Data were retrospectively collected and analyzed. Univariate and multivariate analysis were performed for assessing any potential predictive factor for clinical outcomes. A total of 90 oligometastases were treated in 61 patients with median age 82 years (range, 80-90). The most frequent histology was colorectal cancer (27% of cases). Median follow-up was 20 months (range, 2-63). Local control rates at 1- and 2-years were 98.8% and 88.2%, with colorectal histology being associated with worse LC rates (p = 0.014) at univariate analysis. Progression-free survival rates at 1- and 2-years were 48.6% and 30.5%. Oligorecurrent lesions and single oligometastases were associated with better PFS rates (respectively, p = 0.04 and p = 0.011). Overall survival rates were 75% and 60.5%, polymetastatic spread being predictive of worse survival outcomes at multivariate analysis (p = 0.012). No G2 or higher adverse events were recorded. Our study supports the role of SBRT for the treatment of elderly oligometastatic patients, highlighting the possibility to further explore this therapeutic option in the management of older oncological patients., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Patients with osteoblastic metastases from high risk osteosarcoma continue to have a poor prognosis after progression from standard-of-care multi-agent chemotherapy. In a first-in-human dose escalation trial of bone targeted Radium 223 dichloride alpha-particle therapy in 18 patients with advanced osteosarcoma only 1 patient responded based on conventional Response Evaluation Criteria in Solid Tumors (RECIST). Na 18 F PET response Criteria in Solid Tumors(NAFCIST), based on Sodium fluoride-18 (Na 18 F) positron emission tomography (PET)-CT was developed to better evaluate bone specific response. To further appreciate the spatial and temporal heterogeneity of the partial or mixed responses, a radiomics method was developed. Analyses were performed with 18 F-sodium fluoride positron emission tomography imaging studies before and after alpha-particle therapy. Radioactive 18 F - -atom concentrations were measured in soft-tissues, in approximately 1000 concentration data points for 18 F - per 1 cm 3 metastatic tumor. Data was analyzed from the SUV intensity values, the histogram of intensities and entropy values. Radiomics may inform intra-tumoral and inter-tumoral heterogeneity in response of bone forming osteosarcoma to alpha particle therapy. Each patient (and each tumor) represents an "N of 1" case and warrants in depth analysis individually., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: [ 177 Lu]Lu-prostate-specific membrane antigen (PSMA)-617 has emerged as a promising radiopharmaceutical for targeting PSMA in metastatic castrate-resistant prostate carcinoma (mCRPC). We have optimized the radiolabeling protocol for a multidose formulation (27-28.8 GBq equivalent to 6-7 patient-doses) of [ 177 Lu]Lu-PSMA-617 using [ 177 Lu]Lu 3+ produced via 176 Lu(n,γ) 177 Lu route with moderate specific activity (0.66-0.81 GBq/μg). Methods: [ 177 Lu]Lu-PSMA-617 was synthesized using moderate specific activity [ 177 Lu]LuCl 3 (0.74 GBq/μg) with PSMA-617 having metal-to-ligand molar ratio ∼1: 2.5 in CH 3 COONH 4 buffer (0.1 M) containing gentisic acid at pH 4.0-4.5. Human prostate carcinoma cell line LNCaP cell (high PSMA expression) was used for in vitro cell-binding studies and generating tumor xenograft models in nude mice for tissue biodistribution studies. Several batches of the present formulation have been clinically administered in mCRPC patients (single patient dose: 4.44-5.55 GBq per cycle). Results: In this study we report a consistent and reproducible protocol for multidose formulations of [ 177 Lu]Lu-PSMA-617 for adopting in a hospital radiopharmacy setting. Although the radiochemical yield of [ 177 Lu]Lu-PSMA-617 was found to be 97.30% ± 1.03%, the radiochemical purity was 98.24% ± 0.50% ( n  = 19). In vitro and serum stability of [ 177 Lu]Lu-PSMA-617 was retained up to 72 and 120 h after radiolabeling and upon storage at -20°C with a radioactive concentration between 0.37 and 0.74 GBq/mL upon using stabilizer concentration as low as 43-48 μg/mCi. Preclinical cell-binding studies of [ 177 Lu]Lu-PSMA-617 revealed specific binding with LNCaP cells of 17.4% ± 2.4%. The uptake in LnCaP xenografted tumor (nude mice) was 7.5 ± 2.6% ID/g for ∼1.5-2.0 cm 3 tumor volume at 24-h post-injection. Post-therapy (24 h) SPECT image of mCRPC patients with prior orchidectomy and various hormone therapy showed specific localization of [ 177 Lu]Lu-PSMA-617 in the tumor region. Conclusions: Formulation of a ready-to-use multidose formulation of [ 177 Lu]Lu-PSMA-617 was successfully achieved and the procedure was optimized for routine preparation at a hospital radiopharmacy set-up. High degree of localization of [ 177 Lu]Lu-PSMA-617 in post-therapy SPECT scan and the post-therapeutic response confirms its therapeutic efficacy. Clinical Trials.gov ID: RPC/51/Minutes/Final dated 16th October, 2019.

Background: Thyrotropin alfa (rhTSH) is not currently approved by the Food and Drug Administration or European Medicines Agency for the preparation of radioactive iodine therapy (RAIT) in patients with distant metastatic papillary thyroid cancer (PTC). There are only a few studies comparing rhTSH with levothyroxine withdrawal (LTW) in this context. Our main aim was to compare the two methods of RAIT preparation in terms of avidity and structural/biochemical response in distant metastatic PTC. We also intended to evaluate whether the two methods of RAIT preparation represented independent prognostic factors for progression-free survival (PFS) and disease-specific survival (DSS) in this subset of patients. Methods: We performed a retrospective analysis of all patients with PTC treated with RAIT for distant metastatic disease between 2006 and 2018. We included 95 PTC patients-27 (28.4%) had LTW and 68 (71.6%) had rhTSH for RAIT. Results: The two groups presented similar clinicopathological characteristics, except for median age at PTC diagnosis, which was higher in the rhTSH group ( p  = 0.001), but the median age at first RAIT for distant metastatic disease was not different between the two methods of preparation, 63 years old (interquartile range [IQR] 23) in the LTW group versus 70 (IQR 26.75), p  = 0.06. Avidity was similar between the two groups ( p  = 0.973). Median estimate PFS ( p  = 0.076) and DSS ( p  = 0.084) were also similar between LTW and rhTSH. Regarding RAIT-related side effects, only 1 (3.7%) patient and 5 (7.4%) patients in the LTW and rhTSH groups, respectively, reported sialadenitis ( p  = 0.670). Conclusions: There were no differences between the two methods of RAIT preparation regarding avidity and clinical response. rhTSH may be used as an alternative method of preparation for RAIT in patients with known distant lesions, as it presents similar clinical outcomes to LTW and a good safety profile.

Purpose: RENORT is a novel data mining application developed to extract relevant clinical data from oncology information systems (OIS; ARIA and Mosaiq) used in radiation oncology (RO)., Methods/patients: We used RENORT to extract demographic and clinical data from the OIS of all patients treated at the RO Department at the General Hospital of Valencia during the year 2019., Results: A total of 1158 treatments were performed. The female/male ratio was 39.3%/60.7%, with a mean age of 66 years. The mean waiting time between the treatment decision/proposal to the first visit was 10.1 days. Mean duration of the treatment preparation process was 21 days. Most patients (90.4%) completed treatment within the prescribed time ± 7 days. The most common sites/treatment types were: metastatic/palliative treatments (n = 300; 25.9%), breast (209; 18.0%), genitourinary (195; 16.8%), digestive (116; 10.0%), thoracic (104; 9.0%), head and neck (62; 5.4%), and skin cancer (51; 4.4%). The distribution according to treatment intent was as follows: palliative (n = 266; 23.0%), adjuvant curative (335; 28.9%), radical without adjuvant treatment (229; 19.8%), radical with concomitant treatment (188; 16.2%), curative neoadjuvant (70; 6.0%), salvage radiotherapy (61; 5.3%); and reirradiation (9; 0.8%). The most common treatment techniques were IMRT/VMAT with IGRT (n = 468; 40.4%), 3D-CRT with IGRT (421; 36.4%), SBRT (127; 11.0%), 2DRT (57; 4.9%), and SFRT (56; 4.8%). A mean of 15.9 fractions were administered per treatment. Hypofractionated schemes were used in 100% of radical intent breast and prostate cancer treatments., Conclusions: The RENORT application facilitates data retrieval from oncology information systems to allow for a comprehensive determination of the real role of radiotherapy in the treatment of cancer patients. This application is valuable to identify patterns of care and to assess treatment efficacy.

Purpose: Neuroblastoma (NB) is the most common extracranial solid malignancy during childhood. Despite a multimodal treatment approach, the prognosis of patients with metastatic NB is not satisfactory. Although radiotherapy (RT) has become an integral part of treatment of the primary tumor, the role of RT in osteomedullary lesions is not well defined. A retrospective analysis was conducted to evaluate the impact of RT for metastatic sites in children with high-risk NB., Methods: All patients with stage 4 NB from the prospective, multicenter NB trials NB97 and NB2004 who received RT to metastatic sites during frontline treatment were included in this retrospective analysis., Results: A total of 18 children were irradiated with a median dose of 36 Gray (Gy; range 20-45 Gy) to one or more (range 1-3) osteomedullary metastases with or without concomitant RT to the primary tumor site. The median follow-up time was 149 months (range 55-220) in survivors. At 5 years, local relapse-free survival (LRFS) at irradiated metastatic sites and metastases-free survival (MFS) at distant, non-irradiated site rates were 51.4 and 39.9%, respectively. The estimated overall survival (OS) rate at 5 years was 49.4%. No high-grade acute or late toxicity and no secondary malignancy was reported., Conclusion: RT to metastases is feasible for patients with stage 4 NB. However, an impact of RT to residual metastatic sites on outcome was not found. Studies with larger cohorts or prospective trials would be desirable in order to elucidate the role of RT for metastases., (© 2020. The Author(s).)

Oligometastatic prostate cancer is a subtype of metastatic disease that generally is defined by the presence of 5 or fewer metastatic lesions. Metastatic prostate cancer currently is treated with androgen deprivation therapy and additional systemic therapy, such as novel antiandrogen medications or chemotherapy. The management of metastatic prostate cancer is evolving, however, with the notion that some patients with low-burden metastatic disease may benefit from both local and systemic therapy. Local therapy of the prostate in the setting of oligometastatic prostate cancer is a new concept. Evidence from retrospective studies suggests that cytoreductive therapy, including radical prostatectomy, can improve overall survival in these patients. Ongoing randomized trials are comparing cytoreductive therapy with standard-of-care treatment options. Local therapy in the form of radiation has also been investigated in phase 2 randomized trials. In this review, we discuss the biological and clinical rationales for local therapy, review the current evidence for local therapy, and compare the clinical designs of various ongoing trials.

Objective: Being able to predict a patient's life expectancy can help doctors and patients prioritize treatments and supportive care. For predicting life expectancy, physicians have been shown to outperform traditional models that use only a few predictor variables. It is possible that a machine learning model that uses many predictor variables and diverse data sources from the electronic medical record can improve on physicians' performance. For patients with metastatic cancer, we compared accuracy of life expectancy predictions by the treating physician, a machine learning model, and a traditional model., Materials and Methods: A machine learning model was trained using 14 600 metastatic cancer patients' data to predict each patient's distribution of survival time. Data sources included note text, laboratory values, and vital signs. From 2015-2016, 899 patients receiving radiotherapy for metastatic cancer were enrolled in a study in which their radiation oncologist estimated life expectancy. Survival predictions were also made by the machine learning model and a traditional model using only performance status. Performance was assessed with area under the curve for 1-year survival and calibration plots., Results: The radiotherapy study included 1190 treatment courses in 899 patients. A total of 879 treatment courses in 685 patients were included in this analysis. Median overall survival was 11.7 months. Physicians, machine learning model, and traditional model had area under the curve for 1-year survival of 0.72 (95% CI 0.63-0.81), 0.77 (0.73-0.81), and 0.68 (0.65-0.71), respectively., Conclusions: The machine learning model's predictions were more accurate than those of the treating physician or a traditional model., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background/aim: The aim of this study was to identify prognostic factors for brain metastases treated with Gamma knife radiosurgery., Patients and Methods: Multivariate Cox proportional hazards regression analyses were conducted for patients who received treatment between June 2013 and March 2018., Results: A total of 131 consecutive patients were included. The median follow-up period was 16.0 months (range=1.5-61.5 months). Brain metastases [hazard ratio (HR)=0.42, 95%CI=0.27-0.67, p<0.001], history of systemic therapy (HR=2.23, 95%CI=1.28-3.89, p=0.005), and active extracranial disease (HR=2.49, 95%CI=1.30-4.76, p=0.006) were independent predictors of overall survival. Number of brain metastases (HR=0.39, 95%CI=0.26-0.59, p<0.001) and history of systemic therapy (HR=1.90, 95%CI=1.17-3.08, p=0.005) were independent predictors of intracranial progression-free survival., Conclusion: The number of brain metastases and the history of systemic therapy are associated with patient overall survival and intracranial progression-free survival., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To assess the impact of the width of multileaf collimator (MLC) on dose distributions on HyperArc fractionated stereotactic irradiation for multiple (5-10) brain metastases., Patients and Methods: Twenty-one HyperArc (HA) plans were generated using the high definition (HD) MLC (2.5 mm) to deliver 30-35 Gy in 3-5 fractions (HA-HD). The HyperArc plans using Millennium (ML) MLC (5 mm) were retrospectively generated (HA-ML) using the same planning parameters with HA-HD. Dosimetric parameters between the planning target volume (PTV) and organs at risk (OARs) were compared., Results: The conformity index was significantly higher (p<0.0001) in the HA-HD plans (0.95±0.04) than that in the HA-ML plans (0.92±0.06). The HA-HD provided significantly lower (p<0.0001) gradient index (5.6±2.5) than HA-ML (6.2±3.5). For the brainstem and retina (right), a statistically significant difference (p<0.05) was observed between the HA-HD (12.8±10.9 and 2.8±1.7 Gy, for brainstem and retina, respectively) and HA-ML (13.6±11.1 and 3.0±1.8 Gy) plans. For the brain tissue, the HA-HD plans statistically significantly reduced dosimetric parameters (p<0.0001) in all evaluated dose range (V 6Gy -V 28Gy )., Conclusion: The narrower MLC provided significantly higher conformity, steeper dose gradient, and better normal tissue sparing., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: In the treatment of patients with metastatic cancer, the current paradigm states that metastasis-directed therapy does not prolong life. This paradigm forms the basis of clinical trial null hypotheses, where trials are built to test the null hypothesis that patients garner no overall survival benefit from targeting metastatic lesions. However, with advancing imaging technology and increasingly precise techniques for targeting lesions, a much larger proportion of metastatic disease can be treated. As a result, the life-extending benefit of targeting metastatic disease is becoming increasingly clear., Methods and Materials: In this work, we suggest shifting this qualitative null hypothesis and describe a mathematical model that can be used to frame a new, quantitative null. We begin with a very simple formulation of tumor growth, an exponential function, and illustrate how the same intervention (removing a given number of cells from the tumor) at different times affects survival. Additionally, we postulate where recent clinical trials fit into this parameter space and discuss the implications of clinical trial design in changing these quantitative parameters., Results: Our model shows that although any amount of cell kill will extend survival, in many cases the extent is so small as to be unnoticeable in a clinical context or is outweighed by factors related to toxicity and treatment time., Conclusions: Recasting the null in these quantitative terms will allow trialists to design trials specifically to increase understanding of the circumstances (patient selection, disease burden, tumor growth kinetics) that can lead to improved overall survival when targeting metastatic lesions, rather than whether targeting metastases extends survival for patients with (oligo-) metastatic disease., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Metastasis-directed therapy (MDT) utilizing stereotactic body radiotherapy (SBRT) for oligoprogressive lesions could provide a delay in next-line systemic treatment (NEST) change while undergoing androgen receptor-targeted agents (ARTA) treatment. We evaluated prognostic factors for prostate cancer-specific survival (PCSS) and progression-free survival (PFS) to characterize patients receiving treatment with ARTA who may benefit from MDT for oligoprogressive lesions. The impact of MDT on delaying NEST and the predictive factors for NEST-free survival (NEST-FS) were also assessed., Materials and Methods: The clinical data of 54 metastatic castration-resistant prostate cancer patients with 126 oligoprogressive lesions receiving abiraterone (1 g/day) or enzalutamide (160 mg/day) before or after systemic chemotherapy were analyzed. A median of three lesions (range: 1-5) were treated with MDT. The primary endpoints were PCSS and PFS. The secondary endpoints were time to switch to NEST and NEST-FS., Results: The median follow-up time was 19.1 months. Univariate analysis showed that the number of oligoprogressive lesions treated with SBRT and the time between the start of ARTA treatment and oligoprogression were significant prognostic factors for PCSS, and the timing of ARTA treatment (before or after chemotherapy) and the prostate-specific antigen (PSA) response after MDT were significant prognostic factors for PFS. Multivariate analysis showed that early MDT for oligoprogressive lesions delivered less than 6 months after the beginning of ARTA and higher PSA levels after MDT were significant predictors of worse PCSS and PFS. The median total duration of ARTA treatment was 13.8 months. The median time between the start of ARTA treatment and the start of MDT for oligoprogressive lesions was 5.2 months, and MDT extended the ARTA treatment by 8.6 months on average. Thirty-two (59.3%) patients continued ARTA treatment after MDT. ARTA treatment after chemotherapy, early oligoprogression requiring MDT, and lower radiation doses for MDT were independent predictors of NEST-FS in multivariate analysis., Conclusions: MDT for oligoprogressive lesions is effective and may provide several benefits compared to switching from ARTA treatment to NEST. Patients with early progression while on ARTAs and inadequate PSA responses after MDT have a greater risk of rapid disease progression and poor survival, which necessitates intensified treatment., (© 2021 Wiley Periodicals LLC.)

Importance: Increased prostate-specific antigen (PSA) levels after treatment (PSA failure) may have different associations with outcomes for men with locally advanced vs localized prostate cancer., Objective: To evaluate whether the association between PSA failure and death may be different in locally advanced vs localized prostate cancer., Design, Setting, and Participants: This multicenter cohort study included patients from 2 randomized clinical trials. The Dana-Farber Cancer Institute (DFCI) 95-096 trial randomized 206 men with localized prostate cancer from December 1, 1995, to April 15, 2001, whereas the European Organisation for Research and Treatment of Cancer (EORTC) 22961 trial randomized 970 men with locally advanced prostate cancer from October 30, 1997, to May 1, 2002. Data were analyzed from January 1, 2020, to October 31, 2020., Interventions: The DFCI 95-096 trial randomized men to 0 vs 6 months of androgen deprivation therapy (ADT) with external beam radiotherapy; the EORTC 22961 trial randomized men to 6 vs 36 months of ADT with external beam radiotherapy., Main Outcomes and Measures: For each trial, the PSA doubling time (time to doubling of PSA levels) associated with PSA failure was evaluated. The risk of all-cause mortality associated with PSA failure (nadir plus 2 definition) was evaluated after adjustment of baseline covariates and treatment., Results: This analysis included a total of 1173 men (206 from DFCI 95-096 and 967 with available tumor stage from EORTC 22961; median age, 70.0 [interquartile range (IQR), 65.0-74.0 years). For DFCI 95-096, 161 men died (30 [18.6%] due to prostate cancer) at a median follow-up of 18.2 (IQR, 17.3-18.8) years. Among the 108 men with PSA failure, the median PSA doubling time was 13.0 (IQR, 7.4-31.1) months. For EORTC 22961, 230 men died (75 [32.6%] due to prostate cancer) at a median follow-up of 6.4 (IQR, 6.3-6.6) years. Among 290 men who experienced PSA failure, the median PSA doubling time was 5.0 (IQR, 2.9-8.9) months. Compared with DFCI 95-096, PSA failure was associated with a higher risk of all-cause mortality in EORTC 22961 (adjusted hazard ratios, 3.98 [95% CI, 2.92-5.44]; P < .001 vs 1.51 [95% CI, 1.03-2.23]; P = .04)., Conclusions and Relevance: The association of PSA failure with outcomes may differ between locally advanced and localized prostate cancer. This finding supports the study of treatment intensification with the use of novel antiandrogen agents in addition to ADT at the time of PSA failure after treatment for locally advanced disease., Trial Registration: ClinicalTrials.gov Identifiers: NCT00116220 and NCT00003026.

Introduction: Recently major efforts have been made to define the oligometastatic setting, but for head and neck cancer (HNC) limited data are available. We aimed to evaluate outcome of oligometastatic HNC treated with Stereotactic body radiotherapy (SBRT) as metastasis-directed therapy., Materials and Methods: We analyzed patients treated with SBRT on a maximum of five oligometastases from HNC, in up to two organs. Concomitant treatment was allowed. End points were toxicity, local control of treated metastases (LC), progression-free survival (PFS) and overall survival (OS)., Results: 48 consecutive patients and 71 lesions were treated. With a follow-up of 20.2 months, most common primary tumors were larynx (29.2%) and salivary glands (29.2%), while common site of metastases was lung (59.1%). Median dose was 48 Gy (21-75) in 3-8 fractions. Treatment was well tolerated, with two patients reporting mild pain and nausea. LC rates at 1 and 2 years were 83.1% and 70.2%. Previous local therapy (HR 4.97; p = 0.002), oligoprogression (HR 4.07; p = 0.031) and untreated metastases (HR 4.19; p = 0.027) were associated with worse LC. PFS at 1 and 2 years were 42.2% and 20.0%. Increasing age (HR 1.03; p = 0.010), non-adenoid cystic carcinoma (HR 2.57; p = 0.034) and non-lung metastases (HR 2.20; p = 0.025) were associated with worse PFS. One- and 2-years OS were 81.0% and 67.1%. Worse performance status (HR 2.91; p = 0.049), non-salivary primary (HR 19.9; p = 0.005), non-lung metastases (HR 2.96; p = 0.040) were correlated with inferior OS., Conclusions: SBRT can be considered a safe metastasis-directed therapy in oligometastatic HNC. Efficacy of the treatment seems to be higher when administered upfront in the management of metastatic disease; however, selection of patients need to be improved due to the relevant risk of appearance of new metastatic site after SBRT.

Background: Metastatic prostate carcinoma has poor prognoses with a median survival period ranging from 2 to 5 years with existing therapeutic challenges. Currently, peptide receptor radionuclide therapy is permitted as a treatment method for metastatic prostate carcinoma patients. Therefore, it is crucial to comprehend the efficiency and safety of peptide receptor radionuclide therapy among this patient population. This study aims to analyse the efficacy of peptide receptor radionuclide therapy when used to treat metastatic prostate carcinoma patients., Methods: This research will perform a methodological search in the following electronic databases to find related randomized controlled trials: Cochrane Library, EMBASE, PubMed, Web of Science, Scopus, China National Knowledge Infrastructure (CNKI), WanFang database, and Chinese BioMedical Literature. All the databases are searched from their inauguration till November 2020. Two independent authors will screen and select literature for review. The two authors will independently utilize the Cochrane Risk of Bias tool to assess the bias risk in studies. This study also plans to conduct subgroup and sensitivity analyses to evaluate the robustness in the results. Statistical analyses will be conducted with the RevMan 5.3 software., Results: A high-quality synthesis of existing evidence related to peptide receptor radionuclide therapy in the treatment of metastatic prostate carcinoma will be presented in this study., Conclusion: Our findings will provide evidence to judge whether peptide receptor radionuclide treatment is efficient for metastatic prostate carcinoma patients., Ethics and Dissemination: An ethics approval is not required because the data of the present study are primarily obtained from published studies.OSF registration number: December 1, 2020.osf.io/3psx7. (https://osf.io/3psx7/)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The Stereotactic Ablative Radiation therapy for Comprehensive Treatment of Oligometastatic Tumors phase 2 randomized clinical trial found that stereotactic ablative radiation therapy (SABR) improved outcomes among cancer patients with oligometastatic disease. Yet, the cost of SABR along with the large number of patients with oligometastatic disease raises the important question of value. This study sought to evaluate the cost-effectiveness of the addition of SABR compared with standard therapy alone among cancer patients with oligometastatic disease., Methods and Materials: We constructed a Markov model to simulate treatment with stereotactic ablative radiation therapy or standard therapy among patients with oligometastatic cancers. The model derived transition probabilities from Stereotactic Ablative Radiation therapy for Comprehensive Treatment of Oligometastatic Tumors clinical trial data to estimate risks of toxicity, disease progression and survival. Health care costs and health utilities were estimated from the literature. Probabilistic and one-way sensitivity analyses evaluate model uncertainty. Cost-effectiveness was estimated from both the health care sector and societal perspectives with an incremental cost-effectiveness ratio (ICER) defined as dollars per quality-adjusted life year (QALY). An ICER less than $100,000/QALY was considered cost-effective. One-way and probabilistic sensitivity analyses were used to examine model uncertainty., Results: The addition of SABR increased total costs by $54,260 (health care sector perspective) or $72,799 (societal perspective) and improved effectiveness by 1.88 QALYs compared with standard therapy, leading to an ICER of $28,906/QALY (health care sector perspective) or $38,783/QALY (societal perspective). The model was modestly sensitive to assumptions about tumor progression, although the model was not sensitive to assumptions about survival or cost of treatment. Probabilistic sensitivity analyses demonstrated that SABR was the cost-effective treatment option 99.8% (health care sector perspective) or 98.7% (societal perspective) of the time., Conclusions: The addition of SABR increased costs and improved quality adjusted survival, overall leading to a cost-effective treatment strategy for patients with oligometastatic cancer., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT) has demonstrated efficacy and tolerability with a dose-response effect in phase I/II trials in men with metastatic castration-resistant prostate cancer (mCRPC). The need for positive PSMA imaging before PSMA-TRT to select patients is largely practiced, but its utility is not proven. Given target heterogeneity, developing a biomarker to identify the optimal patient population remains an unmet need. The aim of this study was to assess PSMA uptake by imaging and response to PSMA-TRT., Methods: We performed an analysis of men with mCRPC enrolled in sequential prospective phase I/II trials of PSMA-TRT. Each patient had baseline PSMA imaging by planar 111 In and/or 177 Lu SPECT (N = 171) or 68 Ga-PSMA-11 PET/CT (N = 44), but the results were not used to include/exclude treatment. Semiquantitative imaging scores (IS) on a 0-4 scale were assigned based on PSMA uptake in tumors compared to liver uptake. We compared the ≥50% PSA decline response proportions between low (0-1) and high (2-4) PSMA IS using the χ 2 -test. We used multivariable logistic regression analysis to understand the relationship between independent and dependent variables, including IS, radionuclide activity (dose) administered, CALGB (Halabi) prognostic risk score, prior taxane use., Results: 215 men with progressive mCRPC received PSMA-TRT as follows: 177 Lu-J591 (n = 137), 177 Lu-PSMA-617 (n = 44), 90 Y-J591 (n = 28), 177 Lu-J591 +  177 Lu-PSMA-617 (n = 6). High PSMA expression (IS 2-4) was found in 160 (74.4%) patients and was significantly associated with more frequent ≥ 50% PSA reduction (26.2 vs. 7.3%, p = .006). On multivariate logistic regression analysis, higher IS was associated with a ≥50% decrease in PSA, even after accounting for CALGB (Halabi) prognostic score, the dose administered, and previous taxane use (OR, 4.72; 95% CI, 1.71-16.85; p = .006). Patients with low PSMA expression (N = 55, 24.7%) were less likely to respond. Thirteen of 26 (50%) with no PSMA uptake (IS = 0) had post-PSMA-TRT PSA decline with 2 (7.7%) having ≥ 50% PSA declines., Conclusion: Collectively, the data provide evidence in favor of the hypothesis that patients with high PSMA uptake and high administered radionuclide dose correlate with a higher chance of response., (© 2021 Wiley Periodicals LLC.)

Importance: Prostate radiotherapy (RT) improves survival in men with low-burden metastatic prostate cancer. However, owing to the dichotomized nature of metastatic burden criteria, it is not clear how this benefit varies with bone metastasis counts and metastatic site., Objective: To evaluate the association of bone metastasis count and location with survival benefit from prostate RT., Design, Setting, and Participants: This exploratory analysis of treatment outcomes based on metastatic site and extent as determined by conventional imaging (computed tomography/magnetic resonance imaging and bone scan) evaluated patients with newly diagnosed metastatic prostate cancer randomized within the STAMPEDE trial's metastasis M1 RT comparison. The association of baseline bone metastasis counts with overall survival (OS) and failure-free survival (FFS) was assessed using a multivariable fractional polynomial interaction procedure. Further analysis was conducted in subgroups., Interventions: Patients were randomized to receive either standard of care (androgen deprivation therapy with or without docetaxel) or standard of care and prostate RT., Main Outcomes and Measures: The primary outcomes were OS and FFS., Results: A total of 1939 of 2061 men were included (median [interquartile range] age, 68 [63-73] years); 1732 (89%) had bone metastases. Bone metastasis counts were associated with OS and FFS benefit from prostate RT. Survival benefit decreased continuously as the number of bone metastases increased, with benefit most pronounced up to 3 bone metastases. A plot of estimated treatment effect indicated that the upper 95% CI crossed the line of equivalence (hazard ratio [HR], 1) above 3 bone metastases without a detectable change point. Further analysis based on subgroups showed that the magnitude of benefit from the addition of prostate RT was greater in patients with low metastatic burden with only nonregional lymph nodes (M1a) or 3 or fewer bone metastases without visceral metastasis (HR for OS, 0.62; 95% CI, 0.46-0.83; HR for FFS, 0.57; 95% CI, 0.47-0.70) than among patients with 4 or more bone metastases or any visceral/other metastasis (HR for OS, 1.08; 95% CI, 0.91-1.28; interaction P = .003; HR for FFS, 0.87; 95% CI, 0.76-0.99; interaction P = .002)., Conclusions and Relevance: In this exploratory analysis of a randomized clinical trial, bone metastasis count and metastasis location based on conventional imaging were associated with OS and FFS benefit from prostate RT in M1 disease., Trial Registration: ClinicalTrials.gov Identifier: NCT00268476; ISRCTN.com Identifier: ISRCTN78818544.

Purpose: The phase 2 randomized study SABR-COMET demonstrated that in patients with controlled primary tumors and 1 to 5 oligometastatic lesions, SABR was associated with improved progression-free survival (PFS) compared with standard of care (SoC), but with higher costs and treatment-related toxicities. The aim of this study was to assess the cost-effectiveness of SABR versus SoC in this setting., Methods and Materials: A Markov model was constructed to perform a cost-utility analysis from the Canadian health care system perspective. Utility values and transition probabilities were derived from individual-level data from the SABR-COMET trial. One-way, 2-way, and probabilistic sensitivity analyses were performed. Costs were expressed in 2018 CAD. A separate analysis based on US payer's perspective was performed. An incremental cost-effectiveness ratio (ICER) at a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY) was used., Results: In the base case scenario, SABR was cost-effective at an ICER of $37,157 per QALY gained. This finding was most sensitive to the number of metastatic lesions treated with SABR (ICER: $28,066 per QALY for 2, increasing to $64,429 per QALY for 5), difference in chemotherapy use (ICER: $27,173-$53,738 per QALY), and PFS hazard ratio (HR) between strategies (ICER: $31,548-$53,273 per QALY). Probabilistic sensitivity analysis revealed that SABR was cost-effective in 97% of all iterations. Two-way sensitivity analysis demonstrated a nonlinear relationship between the number of lesions and the PFS HR. To maintain cost-effectiveness for each additional metastasis, the HR must decrease by approximately 0.047. The US cost analysis yielded similar results, with an ICER of $54,564 (2018 USD per QALY) for SABR., Conclusions: SABR is cost-effective for patients with 1 to 5 oligometastatic lesions compared with SoC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Fewer attendances for radiation therapy results in increased efficiency and less foot traffic within a radiation therapy department. We investigated outcomes after single-fraction (SF) stereotactic body radiation therapy (SBRT) in patients with oligometastatic disease., Methods and Materials: Between February 2010 and June 2019, patients who received SF SBRT to 1 to 5 sites of oligometastatic disease were included in this retrospective study. The primary objective was to describe patterns of first failure after SBRT. Secondary objectives included overall survival (OS), progression-free survival (PFS), high-grade treatment-related toxicity (Common Terminology Criteria for Adverse Events grade ≥3), and freedom from systemic therapy (FFST)., Results: In total, 371 patients with 494 extracranial oligometastases received SF SBRT ranging from 16 Gy to 28 Gy. The most common primary malignancies were prostate (n = 107), lung (n = 63), kidney (n = 52), gastrointestinal (n = 51), and breast cancers (n = 42). The median follow-up was 3.1 years. The 1-, 3-, and 5-year OS was 93%, 69%, and 55%, respectively; PFS was 48%, 19%, and 14%, respectively; and FFST was 70%, 43%, and 35%, respectively. Twelve patients (3%) developed grade 3 to 4 treatment-related toxicity, with no grade 5 toxicity. As the first site of failure, the cumulative incidence of local failure (irrespective of other failures) at 1, 3 and 5 years was 4%, 8%, and 8%, respectively; locoregional relapse at the primary was 10%, 18%, and 18%, respectively; and distant failure was 45%, 66%, and 70%, respectively., Conclusions: SF SBRT is safe and effective, and a significant proportion of patients remain FFST for several years after therapy. This approach could be considered in resource-constrained or bundled-payment environments. Locoregional failure of the primary site is the second most common pattern of failure, suggesting a role for optimization of primary control during metastasis-directed therapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Lutetium 177 ( 177 Lu) - DOTATATE is a form of peptide receptor radionuclide therapy (PRRT) utilized in the treatment of neuroendocrine tumors. Data on 177 Lu-DOTATATE-induced thyroid dysfunction is limited., Case Description: A 29-year-old male with SDHB  positive metastatic paraganglioma enrolled under the 177 Lu-DOTATATE trial (NCT03206060) underwent thyroid function test (TFT) evaluation comprised of thyroid stimulating hormone (TSH) and free thyroxine (FT4) immunoassay measurements per protocol prior to 177 Lu-DOTATATE therapy. The TSH was suppressed [<0.01 µIU/ml (0.27-4.2 µIU/ml)], and FT4 was normal [1.3 ng/dl (0.9-1.7 ng/dl)]. The TSH receptor antibody and thyroid stimulating immunoglobulin index were undetectable [<1 IU/L (≤1.75 IU/L), and <1 (≤1.3) respectively], while the anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies were elevated [605 IU/ml (0.0-34.9 IU/ml), and 178 IU/ml (0.0-40.0 IU/ml) respectively]. Mass spectrometry on a stored (-80°C) plasma sample obtained one-month pre-PRRT revealed elevated total triiodothyronine (TT3) [235 ng/dl (65-193 ng/dl)] and FT4 [3.9 ng/dl (1.2-2.9 ng/dl)] levels. The patient was diagnosed with Hashimoto's thyrotoxicosis. However, the patient was asymptomatic. One month after the first dose of 200mCi 177 Lu-DOTATATE, the patient noted fatigue and a 2.6 Kg weight gain. The TSH (73.04 µIU/ml), anti-TPO antibodies (>1,000 IU/ml), and anti-Tg antibodies (668 IU/ml) had substantially increased, with reductions in FT4 (0.3 ng/dl) and TT3 [54 ng/dl (87-169 ng/dl)]. Diagnostic gallium 68 - DOTATATE positron emission tomography-computed tomography performed prior to 177 Lu-DOTATATE treatment revealed diffuse thyroid uptake. Post-therapy single-photon emission computed tomography also revealed diffuse uptake of  177 Lu-DOTATATE in the thyroid gland. Levothyroxine therapy was initiated, and the patient's symptoms resolved., Summary: We report, for the first time, a patient with asymptomatic primary hyperthyroidism who rapidly developed symptomatic primary hypothyroidism 1 month after 177 Lu-DOTATATE therapy, accompanied by marked changes in TFTs and thyroid auto-antibody titers, with functional imaging evidence of diffuse uptake of 177 Lu-DOTATATE in the thyroid gland., Conclusions: Thyroid dysfunction can be associated with PRRT. Thyroid uptake patterns on pre-treatment diagnostic somatostatin analog scans might predict individual susceptibility to PRRT-associated TFT disruption. Therefore, periodic evaluation of TFTs should be considered in patients receiving PRRT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gubbi, Al-Jundi, Del Rivero, Jha, Knue, Zou, Turkbey, Carrasquillo, Lin, Pacak, Klubo-Gwiezdzinska and Lin.)

Aims: Bladder cancer represents the most common type of urothelial carcinoma, with a median overall survival of 12.5-15 months in the case of metastatic disease. We evaluated the role of stereotactic body radiation therapy (SBRT) in the management oligometastatic urothelial cancer., Materials and Methods: Data on patients with a maximum of five metastases were collected from three institutions. Concomitant systemic therapy was allowed. End points were the local control of treated metastases, distant progression-free survival (PFS), overall PFS and overall survival., Results: Data for 82 lesions and 61 patients were included. The primary tumour was located in the bladder in 82% of patients, followed by kidney pelvis (11.5%). The most common treated site was lung (40.2%). Twenty-nine (47.5%) and 14 (23%) patients received systemic therapy before and during SBRT, respectively. The median BED10 value was 78.7 Gy. The median follow-up was 17.2 months. Rates of local control at 1 and 2 years were 92% and 88.9%, respectively, with correlation with systemic therapy before SBRT (hazard ratio 2.62, P = 0.034). Overall PFS at 1 and 2 years was 47.9% and 38.1%, respectively. The number of metastases was a predictive factor (hazard ratio 2.65, P = 0.008). The median overall survival was 25.6 months. Total dose (hazard ratio 0.93, P = 0.003) and BED10 (hazard ratio 0.97, P = 0.006) were correlated with overall survival. No grade ≥2 adverse events were reported., Conclusions: SBRT represents an effective and safe treatment in metastatic urothelial carcinoma. Prospective randomised trials are necessary to better evaluate the benefit on delaying the onset of new systemic therapies., (Copyright © 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Introduction:  To evaluate the clinical therapeutic response of PSMA targeted radioligand therapy with 177 Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer. The current study analyzed disease-related quality of life (QoL) in patients undergoing PSMA therapy with a special focus on the association with simultaneous PSA response., Methods:  Thirty patients (age range 50-87 years, median 73.5 years) undergoing 177 Lu-PSMA-617 therapy from 2014 to 2016 at our institution were included in this pilot study. Health-related QoL was assessed by EORTC QLQ-C30 questionnaire filled in at baseline and two months after initializing the PSMA-therapy. The treatment response was evaluated under three categories with regard to changes in (a) global health status and other functional scales, (b) disease-related symptoms, and (c) effects of PSA values., Results:  Most patients underwent three treatment cycles (n = 12); at least 2 cycles (n = 6) or at most 8 cycles (n = 1) were performed. Out of 30 cases, PSA response after the first cycle was observed in 73 % (n = 22). Compared to baseline, QoL was significantly improved at 2-month follow-up revealing increase in global health status (p = 0.025), role functioning (p = 0.017) and emotional functioning (0.010), and decrease in pain (p = 0.033). Global health status variation can be explained up to 20.5 % by response in PSA (p = 0.012), this improved with PSA reduction., Conclusion:  PSMA radioligand therapy seems to be an effective treatment option of metastatic castration-resistant prostate cancer patients as it improves their QoL in terms of increasing global health and mitigation of disease-related pain., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

This study was aimed at assessing the feasibility and toxicity of using stereotactic body radiation therapy (SBRT) for reirradiation of spinal metastatic tumors. We conducted a retrospective review, from our institutional database, of the data of patients who received reirradiation, with overlap of some prescribed isodose lines to the vertebra from the initial radiation therapy, between 2007 and 2019. We identified 40 patients with spinal metastatic tumors, of whom 2 had 2 metastatic vertebral lesions each, totaling up to 42 target lesions. The median dose to spinal cord at the initial radiation therapy was 30 Gy. SBRT based on the intensity-modulated radiation therapy (IMRT) technique was used for reirradiation to spare the spinal cord. All patients received a prescription dose of 25 Gy in 5 fractions to the planning target volume (PTV). Among the 40 cases who had pain, pain relief was obtained in 24 (60%) after reirradiation. Neurologic improvement was obtained in 8 of 15 cases (53%). The adverse events were evaluated using the Common Terminology Criteria for Adverse Events Version 5.0. Reirradiation was well-tolerated, with only 2 patients experiencing adverse events ≥grade 2 in severity, including 1 patient with grade 3 pain, and another patient with grade 3 spinal fracture. None of the patients developed radiation myelopathy. Our data demonstrated that reirradiation of spinal metastasis using SBRT provided effective pain relief and neurologic improvement, with minimal toxicity., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objective: To assess the efficacy and safety of stereotactic body radiation therapy (SBRT) for oligometastatic gynecologic malignancies., Method: A comprehensive search of the PubMed, Medline, and EMBASE databases was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. "Oligometastatic" was defined as a limited number of uncontrolled/untreated metastatic lesions (typically ≤ 5), including regional nodal metastases. Primary outcomes were response rate (complete response or partial response), local control of oligometastatic lesions, and toxicity., Results: Of 716 screened records, 17 studies (13 full length articles, 4 conference abstracts) were selected and analyzed as 16 unique studies. A total of 667 patients were treated with ~1071 metastatic lesions identified. Primary sites included ovarian (57.6%), cervical (27.1%), uterine (11.1%), vaginal (0.4%), vulvar (0.3%), and other/unspecified (3.4%). Most patients (65.4%) presented with a single metastatic lesion. Metastatic lesion sites included the abdomen (44.2%), pelvis (18.8%), thorax (15.5%), neck (4.6%), central nervous system (4.3%), bone (1.6%), and other/unspecified (11%). Of the lesions, 64% were nodal. Response rate (among 8 studies) ranged from 49% to 97%, with 7/8 studies reporting > 75% response rate. Local control ranged from 71% to 100%, with 14/16 studies reporting ≥ 80% local control. No grade ≥ 3 toxicities were observed in 9/16 (56%) studies. Median progression-free survival (PFS) (among 10 studies) ranged from 3.3 months to 21.7 months. Disease progression most commonly occurred outside of the SBRT radiation field (79% to 100% of failures)., Conclusions: SBRT for oligometastatic gynecologic malignancies is associated with favorable response and local control rates but a high rate of out-of-field progression and heterogeneous PFS. Additional study into rational combinations of SBRT and systemic therapy appears warranted to further improve patient outcomes., Competing Interests: Declaration of Competing Interest S.K. Jabbour has research funding from Merck and Nestle, outside of the submitted work. The remaining authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Since its discovery in the late 19 th century, radiotherapy has been one of the most important medical treatments in oncology. Recently, fasting or short-term starvation (STS) in cancer patients undergoing chemotherapy has been studied to determine its potential for enhancing the therapeutic index and for preventing side- effects, but no data are available in the radiotherapy setting. We thus decided to investigate the effects in vitro of STS in combination with radiotherapy in metastatic cancer cells and non-cancer cells., Methods: Cells were incubated in short-term starvation medium (STS medium, 0·5 g/L glucose + 1% FBS) or in control medium (CM medium, 1 g/L glucose + 10 % FBS) for 24 h and then treated with single high-dose radiation. A plexiglass custom-built phantom was used to irradiate cells. DNA damage was evaluated using alkaline comet assay and theCometAnalyser software. The cell surviving fraction was assessed by clonogenic assay., Finding: STS followed by single high-dose radiation significantly increased DNA damage in metastatic cancer cell lines but not in normal cells. Furthermore, STS reduced the surviving fraction of irradiated tumor cells, indicating a good radio-sensitizing effect on metastatic cell lines. This effect was not observed in non-tumor cells., Interpretation: Our results suggest that STS may alter cellular processes, enhancing the efficacy of radiotherapy in metastatic cancer cellsin vitro. Interestingly, STS has radioprotective effect on the survival of healthy cells., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Androgen deprivation therapy (ADT) remains the standard therapy for patients with oligometastatic prostate cancer (OMPC). Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT)-based stereotactic body radiotherapy (SBRT) is emerging as an alternative option to postpone starting ADT and its associated side effects including the development of drug resistance. The aim of this study was to determine progression free-survival (PFS) and treatment failure free-survival (TFFS) after PSMA-PET/CT-based SBRT in OMPC patients. The efficacy and safety of single fraction radiosurgery (SFRS) and ADT delay were investigated., Methods: Patients with ≤5 metastases from OMPC, with/without ADT treated with PSMA-PET/CT-based SBRT were retrospectively analyzed. PFS and TFFS were primary endpoints. Secondary endpoints were local control (LC), overall survival (OS) and ADT-free survival (ADTFS)., Results: Fifty patients with a total of 75 metastases detected by PSMA-PET/CT were analyzed. At the time of SBRT, 70% of patients were castration-sensitive. Overall, 80% of metastases were treated with SFRS (median dose 20 Gy, range: 16-25). After median follow-up of 34 months (range: 5-70) median PFS and TFFS were 12 months (range: 2-63) and 14 months (range: 2-70), respectively. Thirty-two (64%) patients had repeat oligometastatic disease. Twenty-four (48%) patients with progression underwent second SBRT course. Two-year LC after SFRS was 96%. Grade 1 and 2 toxicity occurred in 3 (6%) and 1 (2%) patients, respectively. ADTFS and OS rates at 2-years were 60.5% and 100%, respectively. In multivariate analysis, TFFS significantly improved in patients with time to first metastasis (TTM) >36 months (p = 0.01) and PSA before SBRT ≤1 ng/ml (p = 0.03)., Conclusion: For patients with OMPC, SBRT might be used as an alternative to ADT. This way, the start/escalation of palliative ADT and its side effects can be deferred. Metastases treated with PSMA-PET/CT-based SFRS reached excellent LC with minimal toxicity. Low PSA levels and longer TTM predict elongated TFFS., Competing Interests: The authors have declared that no competing interests exist.