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CNS metastases are the most common cause of malignant brain tumours in adults. Historically, patients with brain metastases have been excluded from most clinical trials, but their inclusion is now becoming more common. The medical literature is difficult to interpret because of substantial variation in the response and progression criteria used across clinical trials. The Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group is an international, multidisciplinary effort to develop standard response and progression criteria for use in clinical trials of treatment for brain metastases. Previous efforts have focused on aspects of trial design, such as patient population, variations in existing response and progression criteria, and challenges when incorporating neurological, neuro-cognitive, and quality-of-life endpoints into trials of patients with brain metastases. Here, we present our recommendations for standard response and progression criteria for the assessment of brain metastases in clinical trials. The proposed criteria will hopefully facilitate the development of novel approaches to this difficult problem by providing more uniformity in the assessment of CNS metastases across trials.

Background: Agents targeting programmed death-1 receptor (PD-1) and its ligand (PD-L1) are showing promising results in non-small-cell lung cancer (NSCLC). It is unknown whether PD-1/PD-L1 are differently expressed in oncogene-addicted NSCLC. Methods: We analysed a cohort of 125 NSCLC patients, including 56 EGFR mutated, 29 KRAS mutated, 10 ALK translocated and 30 EGFR/KRAS/ALK wild type. PD-L1 and PD-1 expression were assessed by immunohistochemistry. All cases with moderate or strong staining (2+/3+) in >5% of tumour cells were considered as positive. Results: PD-1 positive (+) was significantly associated with current smoking status ( P =0.02) and with the presence of KRAS mutations ( P =0.006), whereas PD-L1+ was significantly associated to adenocarcinoma histology ( P =0.005) and with presence of EGFR mutations ( P =0.001). In patients treated with EGFR tyrosine kinase inhibitors ( N =95), sensitivity to gefitinib or erlotinib was higher in PD-L1+ vs PD-L1 negative in terms of the response rate (RR: P =0.01) time to progression (TTP: P <0.0001) and survival (OS: P =0.09), with no difference in PD1+ vs PD-1 negative. In the subset of 54 EGFR mutated patients, TTP was significantly longer in PD-L1+ than in PD-L1 negative ( P =0.01). Conclusions: PD-1 and PD-L1 are differentially expressed in oncogene-addicted NSCLC supporting further investigation of specific checkpoint inhibitors in combination with targeted therapies.

Machine- and patient-specific quality assurance (QA) is essential to ensure the safety and accuracy of radiotherapy. QA methods have become complex, especially in high-precision radiotherapy such as intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), and various recommendations have been reported by AAPM Task Groups. With the widespread use of IMRT and VMAT, there is an emerging demand for increased operational efficiency. Artificial intelligence (AI) technology is quickly growing in various fields owing to advancements in computers and technology. In the radiotherapy treatment process, AI has led to the development of various techniques for automated segmentation and planning, thereby significantly enhancing treatment efficiency. Many new applications using AI have been reported for machine- and patient-specific QA, such as predicting machine beam data or gamma passing rates for IMRT or VMAT plans. Additionally, these applied technologies are being developed for multicenter studies. In the current review article, AI application techniques in machine- and patient-specific QA have been organized and future directions are discussed. This review presents the learning process and the latest knowledge on machine- and patient-specific QA. Moreover, it contributes to the understanding of the current status and discusses the future directions of machine- and patient-specific QA.

The postoperative hypofractionated intensity-modulated radiation therapy (POHIM-RT) trial is a phase II study to evaluate toxicity following hypofractionated intensity modulated radiation therapy (IMRT) for cervical cancer. This study describes the results of a benchmark procedure for RT quality assurance of the POHIM-RT trial. Six participating institutions were provided computed tomography for RT planning and an IMRT plan for a sample and were instructed to delineate volumes, create a treatment plan and quality assurance (QA) plan, and submit the results of all procedures. The inter-institutional agreements on RT volume and plan results were evaluated using the kappa value and dice similarity coefficients. The simultaneous truth and performance level estimation (STAPLE) method was employed to generate a consensus target volume. The treatment volumes, organs-at-risk volumes, and results of the RT plan and QA reported by the institutions were acceptable and adhered well to the protocol. In terms of clinical target volume (CTV) delineation, there were differences between the institutions, particularly in vaginal cuff and paracolpium subsites. Consensus CTV was generated from the collected CTVs with the STAPLE method. The participating institutions showed considerable agreement regarding volume, dose and QA results. To improve CTV agreement in CTV, we provided feedback with images of the consensus target volume and detailed written guidelines for specific subsites that were the most heterogeneous.

This study aimed to evaluate the recent trends in single-fraction conventional radiotherapy (CRT) as palliative treatment in Japan, using data from the National Database published by the Ministry of Health, Labor, and Welfare. Data from fiscal year (FY) 2014 to FY2022, specifically related to the utilization of single-fraction CRT, were analyzed. Multi-fraction CRT, stereotactic body radiotherapy (SBRT), intensity-modulated radiotherapy (IMRT), and brachytherapy were excluded. The primary outcome was the cumulative and annual number of single-fraction CRT courses. Additionally, quarterly course data from FY2019 to FY2022, the period for which monthly data were available, were assessed to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on single-fraction CRT utilization. Of the total 2 315 607 radiotherapy courses, we identified 33 221 single-fraction CRT courses after excluding multi-fraction CRT (n = 1 835 650), SBRT (n = 33 935), IMRT (n = 332 827), and brachytherapy (n = 113 195). The annual number of single-fraction CRT courses increased from 1730 in FY2014 to 5642 in FY2022, with an average annual growth rate of 0.28 (range: −0.07 to 0.65). Outpatient courses significantly increased, particularly from FY2019 onward, surpassing inpatient courses in FY2022 (2914 vs 2728). The highest annual increase was observed in FY2020, particularly from April to December, although this upward trend did not persist in 2021. In conclusion, single-fraction CRT has exhibited a consistent upward trend, highlighting its expanding role in palliative radiotherapy. Although the COVID-19 pandemic temporarily accelerated this trend, its impact has already subsided, with growth rates returning to pre-pandemic levels.

Dynamic WaveArc (DWA) is a technique used for continuous, non-coplanar volumetric-modulated arc therapy on the Vero4DRT platform. This study aimed to evaluate the application of single-isocenter DWA (SI-DWA) for treating multiple brain metastases by comparing dose distribution and irradiation time with multi-isocenter DWA (MI-DWA) through retrospective treatment planning. Treatment plans were developed for SI-DWA and MI-DWA in 14 cases with 3–5 brain metastases. Parameters assessed included target dose indices, such as conformity index (CI) of the planning target volume (PTV), volumes of normal brain excluding gross tumor volumes (GTVs) receiving a single dose equivalent of 14 Gy (V14), V30%, V20%, V10%, volumes of normal brain, including GTVs receiving a single dose equivalent of 12 Gy (V12), D2% for other organs at risk, and beam-on time. SI-DWA showed inferior CI, V14, and V12 values for lesions with PTV volumes <1 cc, whereas it performed equivalently to MI-DWA for lesions with PTV volumes ≥1 cc. SI-DWA resulted in higher volumes of normal brain receiving low doses compared to MI-DWA. SI-DWA exhibited significantly shorter beam-on times than MI-DWA. In conclusion, SI-DWA is an effective method for treating multiple brain metastases with PTV volumes ≥1 cc, offering an index of radiation-induced brain necrosis comparable with MI-DWA while allowing for shorter irradiation times.