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Background: The purpose of this randomised study was to determine whether dose‐intensified stereotactic body radiotherapy (SBRT) for painful vertebral metastases results in increased rates of pain improvement compared with conventional external beam radiotherapy (cEBRT) (control) 6 months after treatment. Methods: This randomized, controlled phase 3 trial was conducted between November 2016 and January 2023, when it was stopped early. Patients were eligible if they were aged 18 years or older; had one or two painful, stable, or potentially unstable vertebral metastases; and had a life expectancy of 1 year or longer according to the investigator's estimates. Patients received 48.5 grays (Gy) in 10 fractions (with epidural involvement) or 40 Gy in five fractions (without epidural involvement) in the SBRT group and 30 Gy in 10 fractions or 20 Gy in five fractions in the cEBRT group, respectively. The primary end point was an improvement in the pain score at the treated site by at least 2 points (on a visual analog scale from 0 to 10 points) at 6‐month follow‐up. Data were analyzed on an intention‐to‐treat and per‐protocol basis. Results: Of 214 patients who were screened for eligibility, 63 were randomized 1:1 between SBRT (33 patients with 36 metastases) and cEBRT (30 patients with 31 metastases). The median age of all patients was 66 years, and 40 patients were men (63.5%). In the intention‐to‐treat analysis, the 6‐month proportion of patients who had metastases with pain reduction by 2 or more points was significantly higher in the SBRT group versus the control group (69.4% vs. 41.9%, respectively; two‐sided p =.02). Changes in opioid medication intake relative to baseline were nonsignificant between the groups. No differences were observed in vertebral compression fracture or adverse event rates between the groups. Conclusions: Dose‐intensified SBRT improved pain score more effectively than cEBRT at 6 months. In this randomized clinical trial that included 63 patients with 67 painful vertebral metastases, the proportion of those who had metastases with pain improvement at 6‐month follow‐up was 69% in the stereotactic body radiotherapy group versus 42% in the conventional external beam radiotherapy group: a significant difference. Changes in opioid medication intake relative to baseline between the groups were not significant, and dose‐intensified stereotactic body radiotherapy was not associated with increased risks of adverse events. [ABSTRACT FROM AUTHOR]

Background: Chemoradiation therapy (CRT) is the treatment of choice for locally advanced non-small cell lung cancer (LA-NSCLC). Several clinical trials that combine programmed cell death 1 (PD1) axis inhibitors with radiotherapy are in development for patients with LA-NSCLC. However, the effect of CRT on tumor cells programmed cell death ligand-1 (PD-L1) expression is unknown. Methods: In this multicentric retrospective study, we analyzed paired NSCLC specimens that had been obtained pre- and post-CRT. PD-L1 expression on tumor cells was studied by immunohistochemistry. The purpose of this study was to evaluate the feasibility, risk of complications, and clinical relevance of performing re-biopsy after CRT in patients with PD-L1 negative LA-NSCLC. Results: Overall, 31 patients from 6 centers with PD-L1 negative LA-NSCLC were analyzed. The percentage of tumor cells with PD-L1 expression significantly increased between pre- and post-CRT specimens in 14 patients (45%). Nine patients had unchanged PD-L1 expression after CRT, in five patients the rebiopsy material was insufficient for PD-L1 analysis and in two patients no tumor cells at rebiopsy were found. The post-rebiopsy complication rate was very low (6%). All patients with positive PD-L1 re-biopsy received Durvalumab maintenance after CRT, except one patient who had a long hospitalization for tuberculosis reactivation. Median PFS of patients with unchanged or increased PD-L1 expression was 10 and 16.9 months, respectively. Conclusion: CRT administration can induce PD-L1 expression in a considerable fraction of PD-L1 negative patients at baseline, allowing them receiving the maintenance Durvalumab in Europe. Hence, after a definitive CRT, PD-L1 redetermination should be considered in patients with LANSCLC PD-L1 negative, to have a better selection of maintenance Durvalumab candidates. [ABSTRACT FROM AUTHOR]

Aim: stereotactic ablative radiotherapy (SABR) has been shown to increase survival in oligometastatic patients. Few studies actually depicted the oligometastatic disease (OMD) evolution after SABR. There is few evidence on which patient will remain disease-free after SABR and which will develop rapidly a polymetastatic disease (PMD) therefore apart from the number of active metastases, there are no clues on which proven factor should be taken into account for prescribing local treatment in OMD. The aim of the present preliminary study based on a large retrospective database is to identify predictive factors of polymetastatic evolution in lung oligometastatic colorectal cancer patients to tailor SABR prescription. Methods: the study involved 23 centers, and was approved by the Ethical Committee (Prot. Negrar 2019- ZT). The data of 367 lung oligometastatic patients were reported. Primary end-point was the time to the polymetastatic conversion (tPMC), defined as the first occurrence of >5 simultaneous new metastases after SABR. Additionally, oligometastases number and cumulative gross tumor volume (GTV) were used as combined predictive factors of tPMC. Oligometastases number was stratified as 1, 2-3, and 4-5; cumulative GTV was dichotomized to the median value of 15.6 cc. The 6 groups are reported in table 1. Results: the median tPMC in the overall population was 26.1 months. The median tPMC stratified for the 6 groups is reported in table 1 (p=0.00). After data checking we were able to classify patients according to their median tPMC in 4 risk classes: low risk (group 1+3), favorable intermediate (group 2), unfavorable intermediate (group 4), high risk (group 5+6). The median tPMC for the 4 risk classes was: 34.6, 19.3, 12, and 6.7 months, respectively (figure 1; p=0.00). Conclusion: the present study identified predictive factors of polymetastatic evolution after SABR in lung oligometastatic colorectal cancer. The results demonstrated that the sole numerical number is not enough to define the OMD since patients identified as oligometastatic from a numerical point of view might rapidly progress to the PMD when the cumulative tumor volume is high. A tailored approach in SABR prescription should be pursued considering the expected disease evolution after SABR, with the aim to avoid unnecessary treatment and side effect in those at high risk of polymetastatic spread, and maximize local treatment in those with a favorable disease evolution. [ABSTRACT FROM AUTHOR]

Recently, the development of targeted therapy approaches such as those based on tyrosine kinase inhibitor (TKI) greatly improved the clinical outcomes of patients affected by oncogene addicted advanced non-small cell lung cancer (NSCLC). Similarly, the improvement of radiation therapy techniques has permitted to deliver high radiation doses to a limited number of metastatic target lesions (oligopersistent or oligoprogressive), with limited high-dose normal tissue exposure that leads to low severe toxicity rates. The aim of this narrative review was to provide an overview of the currently established definition of oligometastatic and oligoprogressive disease, to define first line and subsequent lines targeted therapies and the role of consolidative non-invasive local ablative treatments (LATs) in these settings. The potential benefit of local treatment (LT) such as radiotherapy (RT) or surgery might be represented by an overall reduction of switching to subsequent systemic treatments lowering the risk of further systemic dissemination. Further randomized clinical trials will clarify the role of LT and their correct timing in relation to systemic targeted therapies., Competing Interests: MT received speakers’ and consultants’ fee from Astra-Zeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda, Pierre Fabre, Amgen, Merck, Sanofi. MT received institutional research grants from Astra-Zeneca, Boehringer Ingelheim. A Bruni reported travel grants from AstraZeneca, MSD, Ipsen. Other authors have nothing to disclose., (© The Author(s) 2024.)

Earlier treatment intensification with systemic potent androgen receptor inhibition has been shown to improve clinical outcomes in metastatic hormone sensitive prostate cancer. Nonetheless, oligometastatic patients may benefit from local treatment approaches such as stereotactic body radiotherapy (SBRT). Aiming to explore the benefit of SBRT in this scenario, we designed this trial to specifically test the hypothesis that SBRT will improve clinical outcomes in select population affected by metachronous oligometastatic HSPC treated with androgen deprivation therapy + apalutamide. Enrolled patients will be randomized to receive the standard systemic treatment alone or in combination with SBRT on all metastatic sites of disease. Here we report the protocol design and an overview of the ongoing trials testing different integration strategies between RT and systemic therapies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: Stereotactic ablative radiotherapy (SABR) showed increasing survival in oligometastatic patients. Few studies actually depicted oligometastatic disease (OMD) evolution and which patient will remain disease-free and which will rapidly develop a polymetastatic disease (PMD) after SABR. Therefore, apart from the number of active metastases, there are no clues on which proven factor should be considered for prescribing local treatment in OMD. The study aims to identify predictive factors of polymetastatic evolution in lung oligometastatic colorectal cancer patients., Methods: This international Ethical Committee approved trial (Prot. Negrar 2019-ZT) involved 23 Centers and 450 lung oligometastatic patients. Primary end-point was time to the polymetastatic conversion (tPMC). Additionally, oligometastases number and cumulative gross tumor volume (cumGTV) were used as combined predictive factors of tPMC. Oligometastases number was stratified as 1, 2-3, and 4-5; cumGTV was dichotomized to the value of 10 cc., Results: The median tPMC in the overall population was 26 months. Population was classified in the following tPMC risk classes: low-risk (1-3 oligometastases and cumGTV ≤ 10 cc) with median tPMC of 35.1 months; intermediate-risk (1-3 oligometastases and cumGTV > 10 cc), with median tPMC of 13.9 months, and high-risk (4-5 oligometastases, any cumGTV) with median tPMC of 9.4 months (p = 0.000)., Conclusion: The present study identified predictive factors of polymetastatic evolution after SABR in lung oligometastatic colorectal cancer. The results demonstrated that the sole metastases number is not sufficient to define the OMD since patients defined oligometastatic from a numerical point of view might rapidly progress to PMD when the cumulative tumor volume is high. A tailored approach in SABR prescription should be pursued considering the expected disease evolution after SABR, with the aim to avoid unnecessary treatment and toxicity in those at high risk of polymetastatic spread, and maximize local treatment in those with a favorable disease evolution., Competing Interests: 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., (© 2022 The Authors.)

Purpose: Lattice radiation therapy (LRT) is an innovative type of spatially fractionated radiation therapy. It aims to increase large tumors control probability by administering ablative doses without an increased toxicity. Considering the rising number of positive clinical experiences, the objective of this work is to evaluate LRT safety and efficacy., Method: Reports about LRT clinical experience were identified with a systematic review conducted on four different databases (namely, Medline, Embase, Scopus, and Cochrane Library) through the August 2022. Only LRT clinical reports published in English and with the access to the full manuscript text were considered as eligible. The 2020 update version PRISMA statement was followed., Results: Data extraction was performed from 12 eligible records encompassing 7 case reports, 1 case series, and 4 clinical studies. 81 patients (84 lesions) with a large lesion ranging from 63.2 cc to 3713.5 cc were subjected to exclusive, hybrid, and metabolism guided LRT. Excluding two very severe toxicity with a questionable relation with LRT, available clinical experience seem to confirm LRT safety. When a complete response was not achieved 3-6 months after LRT, a median lesion reduction approximately ≥50 % was registered., Conclusion: This systematic review appear to suggest LRT safety, especially for exclusive LRT. The very low level of evidence and the studies heterogeneity preclude drawing definitive conclusions on LRT efficacy, even though an interesting trend in terms of lesions reduction has been described., Competing Interests: 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., (© 2022 The Author(s).)

Simple Summary: Although radiotherapy plays a fundamental role in the management of intermediate/high/very high-risk non-metastatic prostatic cancer (IHR-nmPca), there is still no consensus on the optimal treatment strategy in this setting. Remarkably, the role of elective nodal irradiation (ENI) is still highly controversial. The PROspective multicenter observational study on Elective Pelvic nodes Irradiation (PRO-EPI) was designed to provide "real life" data regarding the patterns of care for IHR-nmPca. Forty-three Italian Radiation Oncology centers participated in the PROspective multicenter observational study on Elective Pelvic nodes Irradiation (PRO-EPI) project, with 1029 patients enrolled. In this preliminary analysis, we longitudinally evaluated the impact of Elective Nodal Irradiation (ENI) and radiotherapy features on toxicity and quality of life (QoL). Six months follow-up data were available for 913 patients and 12 months data for 762 patients. Elective Nodal Irradiation was given to 506 patients (48.9%). Volumetric Intensity-Modulated Radiation Therapy (IMRT) was adopted in more than 77% of patients and Image-Guided Radiation Therapy (IGRT) in 84.4%. Androgen deprivation therapy (ADT) was administered to the majority of patients (68.3%), and it was associated to ENI in 408 cases (81.1%). Toxicity was mostly mild and reversible and IGRT resulted in a significant reduction of rectal toxicity, although a non-significant trend toward increased urinary toxicity was observed. No statistically significant differences in QoL and toxicity were seen in patients treated with or without ENI. The adoption of IGRT is widespread and increasing and could reduce treatment toxicity. ENI is not yet the standard treatment, but it is performed in a growing fraction of cases and not resulting into an increase in toxicity or in a deterioration of QoL. Further analyses are needed to clarify the long-term toxicity profile and the impact of ENI on survival., 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 © 2022 Guerini, Noale, Mortellaro, Lisi, Bruni, Santini, Muto, Ferrera, Cossali, Morelli, PRO-EPI study group, Magrini, Spiazzi and Buglione.)