Impact of concurrent antibody-drug conjugates and radiotherapy on symptomatic radiation necrosis in breast cancer patients with brain metastases: a multicenter retrospective study.

AIM: We aimed to investigate the impact of concurrent antibody-drug conjugates (ADC) and radiotherapy on symptomatic radiation necrosis (SRN) in breast cancer patients with brain metastases (BM). METHODS: This multicenter retrospective study uses four institutional data. Eligibility criteria were histologically proven breast cancer, diagnosed BM with gadolinium-enhanced MRI, a Karnofsky performance status of 60 or higher, and radiotherapy for all BM lesions between 2017 and 2022. Patients with leptomeningeal dissemination were excluded. Concurrent ADC was defined as using ADC within four weeks before or after radiotherapy. The cumulative incidence of SRN until December 2023 with death as a competing event was compared between the groups with and without concurrent ADC. Multivariable analysis was performed using the Fine-Gray model. RESULTS: Among the 168 patients enrolled, 48 (29%) received ADC, and 19 (11%) had concurrent ADC. Of all, 36% were HER2-positive, 62% had symptomatic BM, and 33% had previous BM radiation histories. In a median follow-up of 31 months, 18 SRNs (11%) were registered (11 in grade 2 and 7 in grade 3). The groups with and without concurrent ADC had 5 SRNs in 19 patients and 13 SRNs in 149, and the two-year cumulative incidence of SRN was 27% vs. 7% (P = 0.014). Concurrent ADC was associated with a higher risk of SRN on multivariable analysis (subdistribution hazard ratio, 3.0 [95% confidence interval: 1.1-8.3], P = 0.030). CONCLUSIONS: This study suggests that concurrent ADC and radiotherapy are associated with a higher risk of SRN in HER2-positive breast cancer patients.

Solid tumours showing oligoprogression to immune checkpoint inhibitors have the potential for abscopal effects.

PURPOSE: Given the uncertainty surrounding the abscopal effect (AE), it is imperative to identify promising treatment targets. In this study, we aimed to explore the incidence of AE when administering radiotherapy to patients with oligoprogressive solid tumours while they are undergoing treatment with immune checkpoint inhibitors (ICIs). MATERIALS AND METHODS: In this multicentre prospective observational study, oligoprogressive disease was defined as a < 20% increase in lesions compared to > 2 months before enrolment. We enrolled patients who requested radiotherapy during the ICI rest period between 2020 and 2023. AE was considered present if ≥ 1 non-irradiated lesion decreased by ≥ 30% before the next line of systemic therapy started. RESULTS: Twelve patients were included in this study; the common primary lesions were in the lungs (four patients) and kidneys (three patients). AEs were observed in six (50%) patients, with a median time to onset of 4 (range 2-9) months after radiotherapy. No significant predictors of AEs were identified. Patients in the AE group had a significantly better 1-year progression-free survival (PFS) rate than those in the non-AE group (p = 0.008). Two patients from the AE group were untreated and progression-free at the last follow-up. Four (33%) patients experienced grade 2 toxicity, with two cases attributed to radiotherapy and the other two to ICI treatment. No grade 3 or higher toxicities were observed in any category. CONCLUSION: Patients with oligoprogressive disease may be promising targets with potential for AEs. AEs can lead to improved PFS and, in rare cases, to a certain progression-free period without treatment. Irradiating solid tumours in patients with oligoprogressive disease during immune checkpoint inhibitor therapy may be a promising target with the potential for abscopal effects (AEs). AEs can lead to improved progression-free survival and, in rare cases, to a certain progression-free period without treatment.

Clinical Outcomes of Radiation Therapy for Angiosarcoma of the Scalp and Face: A Multi-Institutional Observational Study.

Angiosarcoma of the scalp and face (ASF) is a rare, aggressive tumor often treated with multimodal therapy, including radiation therapy (RT). This study assessed RT outcomes for ASF and identified prognostic factors. Data from 68 non-metastatic ASF patients undergoing RT with or without other therapies were analyzed. Median radiation dose was 66 Gy in 33 fractions (interquartile range (IQR) 60-70 Gy in 28-35 fractions). Local control (LC), progression-free survival (PFS), and overall survival (OS) rates were calculated using Kaplan-Meier analysis. Multivariate analyses and adverse event evaluation were conducted. Median patient age was 75 years (IQR 71-80 years), with a median follow-up of 17 months (IQR 11-42 months). One-/three-year LC rates were 57/37%, PFS rates were 44/22%, and OS rates were 81/44%. Multivariate analyses showed that an equivalent dose in a 2 Gy fraction (EQD2) >66 Gy correlated with improved LC (HR 2.35, 95% CI 1.03-5.32, p = 0.041). Combining chemotherapy (HR 2.43, 95% CI 1.08-5.46, p = 0.032) or surgery (HR 2.41, 95% CI 1.03-5.59, p = 0.041) improved PFS. No factors influenced OS. Late grade 3+ toxicities occurred in 1%, with one patient developing a grade 4 skin ulcer. These findings suggest that EQD2 > 66 Gy and combining chemotherapy or surgery can enhance LC or PFS in ASF. Further prospective studies are needed to determine the optimal treatment strategy for this rare malignancy, particularly in elderly patients.

Subpleural fibrotic interstitial lung abnormalities are implicated in non-small cell lung cancer radiotherapy outcomes.

BACKGROUND: The relationship between interstitial lung abnormalities (ILAs) and the outcomes of lung cancer radiotherapy is unclear. This study investigated whether specific ILA subtypes are risk factors for radiation pneumonitis (RP). PATIENTS AND METHODS: This retrospective study analysed patients with non-small cell lung cancer treated with radical-intent or salvage radiotherapy. Patients were categorised into normal (no abnormalities), ILA, and interstitial lung disease (ILD) groups. The ILA group was further subclassified into non-subpleural (NS), subpleural non-fibrotic (SNF), and subpleural fibrotic (SF) types. The Kaplan-Meier and Cox regression methods were used to determine RP and survival rates and compare these outcomes between groups, respectively. RESULTS: Overall, 175 patients (normal, n = 105; ILA-NS, n = 5; ILA-SNF, n = 28; ILA-SF, n = 31; ILD, n = 6) were enrolled. Grade ≥2 RP was observed in 71 (41%) patients. ILAs (hazard ratio [HR]: 2.33, p = 0.008), intensity-modulated radiotherapy (HR: 0.38, p = 0.03), and lung volume receiving 20 Gy (HR: 54.8, p = 0.03) contributed to the cumulative incidence of RP. Eight patients with grade 5 RP were in the ILA group, seven of whom had ILA-SF. Among radically treated patients, the ILA group had worse 2-year overall survival (OS) than the normal group (35.3% vs 54.6%, p = 0.005). Multivariate analysis revealed that the ILA-SF group contributed to poor OS (HR: 3.07, p =0.02). CONCLUSIONS: ILAs, particularly ILA-SF, may be important risk factors for RP, which can worsen prognosis. These findings may aid in making decisions regarding radiotherapy.

Daily irradiation versus irradiation at two- to three-day intervals in stereotactic radiotherapy for patients with 1-5 brain metastases: study protocol for a multicenter open-label randomized phase II trial.

BACKGROUND: Radiobiological daily changes within tumors are considered to be quite different between stereotactic radiotherapy (SRT) (e.g., 50 Gy in 4 fractions) and conventional radiotherapy (e.g., 60 Gy in 30 fractions). We aim to assess the optimal interval of irradiation in SRT and compare outcomes of daily irradiation with irradiation at two- to three-day intervals in SRT for patients with one to five brain metastases (BM). METHODS: This study is conducted as a multicenter open-label randomized phase II trial. Patients aged 20 or older with one to five BM, less than 3.0 cm diameter, and Karnofsky Performance Status ≥70 are eligible. A total of 70 eligible patients will be enrolled. After stratifying by the number of BMs (1, 2 vs. 3-5) and diameter of the largest tumor (< 2 cm vs. ≥ 2 cm), we randomly assigned patients (1:1) to receive daily irradiation (Arm 1), or irradiation at two- to three-day intervals (Arm 2). Both arms are performed with total dose of 27-30 Gy in 3 fractions. The primary endpoint is an intracranial local control rate, defined as intracranial local control at initially treated sites. We use a randomized phase II screening design with a two-sided α of 0∙20. The phase II trial is positive with p < 0.20. All analyses are intention to treat. This study is registered with the UMIN-clinical trials registry, number UMIN000048728. DISCUSSION: This study will provide an assessment of the impact of SRT interval on local control, survival, and toxicity for patients with 1-5 BM. The trial is ongoing and is recruiting now. TRIAL REGISTRATION: UMIN000048728. Date of registration: August 23, 2022. https://center6.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000055515 .

Pure ductal adenocarcinoma of the prostate protruding into the prostatic urethra: A case report of MRI findings and literature review.

Ductal adenocarcinoma of the prostate (DCa) is the histological variant of prostatic carcinoma. The macroscopic finding of DCa arising from primary duct by urethroscopy is papillary excrescences in the prostatic urethra. But the finding of MRI remains poorly understood, since there is no coherent report on the MRI finding of DCa arising from primary duct. We herein report a case of DCa arising from primary duct and forming papillary excrescences in the prostatic urethra. The patient was a male in his 70s and presented with gross hematuria a few days ago. Blood test showed elevated prostate specific antigen (PSA). Prostate MRI was performed. There were two lesions in the prostatic urethra and the right transition zone (TZ). On T 2-weighted image (T2WI), the lesion in the prostatic urethra was identifiable, but the lesion in the right TZ was difficult to identify. On diffusion-weighted image (DWI), both lesions showed hyperintense signal and could be identified, and there was continuity between them. Urethroscopy was performed, there was the lesion with papillary excrescences developing from the right dorsal side of prostatic urethra. Transurethral resection of the prostate was performed. The pathological diagnosis was DCa (pure type). A review of previous literature showed that DCa had a slightly hypointense signal on T2WI. It may be difficult to identify DCa in the TZ because DCa and the TZ show similar signals on T2WI. DWI may be useful to accurately assess DCa arising from primary duct.

Automatic one-click planning for hippocampal-avoidance whole-brain irradiation in RayStation.

This study aimed to verify the accuracy of auto-contouring and auto-dose optimization for hippocampal-avoidance whole-brain radiation therapy (HA-WBRT). Head computed tomography (CT) images of 15 patients were selected. The regions of interest, containing the brain, hippocampus, eyes, and lacrimal glands, were contoured manually and automatically on CT images. They were compared and evaluated for concordance rates using the Simpson coefficient. To verify the performance of dose optimization, auto-dose planning was compared with manual planning for 15 cases. All optimization plans were performed using the volumetric modulated arc therapy technique. The automatically contoured brain showed a very high concordance rate with the manually contoured brain; the Simpson coefficient was 0.990 ± 0.01. Contrastingly, the concordance rate of the hippocampal contour was low at 0.642 ± 0.15 (right) and 0.500 ± 0.16 (left); however, the rate improved to 0.871 ± 0.09 (right) and 0.852 ± 0.11 (left) with an additional 3-mm margin. For 2% of each planning target volume with the prescribed dose (D2%) and Dmean, there was no significant difference between the automatic and manual plans (35.50 Gy vs 35.23 Gy; p = 0.233 and 33.09 Gy vs 32.84 Gy; p = 0.073, respectively). The D98% was significantly better for the manual plan than for the automatic plan (25.49 Gy vs 26.11 Gy; p < 0.01). Dmax and D100% for the hippocampus did not show any significant difference between the automatic and manual plans (15.65, 16.09 Gy (right, left) vs 15.51, 15.80 Gy; p = 0.804, 0.233 and 8.08, 8.03 Gy vs 8.13, 8.01 Gy; p = 0.495, 1 respectively). The accuracy of auto-contouring for HA-WBRT can be guaranteed by providing an appropriate margin, and the precision of the auto-dose optimization was comparable to that of the manual plan.

Fully automated rigid image registration versus human registration in postoperative spine stereotactic body radiation therapy: a multicenter non-inferiority study.

To confirm the fully automated rigid image registration (A-RIR) accuracy in postoperative spine stereotactic body radiation therapy (SBRT), we conducted a multicenter non-inferiority study compared to the human rigid image registration (H-RIR). Twenty-eight metastatic cancer patients who underwent postoperative spine SBRT are enrolled-image registration (IR) of planning computed tomography (CT) and CT-myelogram for delineating the spinal cord. The adopted A-RIR workflow is a contour-focused algorithm performing a rigid registration by maximizing normalized mutual information (NMI) restricted to the data contained within the automatically extracted contour. Three radiation oncologists (ROs) from multicenters were prompted to review two blinded registrations and choose one for clinical use. Indistinguishable cases were allowed to vote equivalent, counted A-RIR side. A-RIR is considered non-inferior to H-RIR if the lower limit of the 95% confidence interval (CI) of A-RIR preferable/equivalent is greater than 0.45. We also evaluated the NMI improvement from the baseline and the translational/rotational errors between A-RIR and H-RIR. The A-RIR preferable/equivalent was selected in 21 patients (0.75, 95% CI: 0.55-0.89), demonstrating non-inferiority to H-RIR. The A-RIR's NMI improvement was greater than H-RIR in 24 patients: the mean value ± SD was 0.225 ± 0.115 in A-RIR and 0.196 ± 0.114 in H-RIR (P < 0.001). The absolute translational error was 0.38 ± 0.31 mm. The rotational error was -0.03 ± 0.20, 0.05 ± 0.19, -0.04 ± 0.20 degrees in axial, coronal, and sagittal planes (range: -0.66-0.52). In conclusion, A-RIR shows non-inferior to H-RIR in CT and CT-myelogram registration for postoperative spine SBRT planning.

Stereotactic body radiation therapy for Japanese patients with localized prostate cancer: 2-year results and predictive factors for acute genitourinary toxicities.

OBJECTIVE: We aimed to report the 2-year results of stereotactic body radiation therapy for prostate cancer and identify the clinical and dosimetric factors that predict acute genitourinary toxicities. METHODS: We retrospectively reviewed the medical records of patients with non-metastatic prostate cancer treated at Toyota Memorial Hospital between 2017 and 2020. The patients were treated with stereotactic body radiation therapy with a total dose of 36.25 Gy in five fractions on consecutive weekdays. While low-risk patients received radiotherapy alone, intermediate- to high-risk patients also received androgen deprivation therapy. RESULTS: We analysed a total of 104 patients, including 10, 60 and 34 low-, intermediate- and high-risk patients, respectively. The median follow-up duration was 2 years. We did not observe biochemical/clinical recurrence, distant metastasis or death from prostate cancer. One patient died of another cause. Grade 2 acute genitourinary toxicity was observed in 40 (38%) patients. Age (P = 0.021), genitourinary toxicity of grade ≥1 at baseline (P = 0.023) and bladder mean dose (P = 0.047) were significantly associated with the incidence of grade 2 acute genitourinary toxicity. The cut-off value of 65 years for age and 10.3 Gy for the bladder mean dose were considered the most appropriate. Grade 2 acute gastrointestinal toxicity was observed in five (5%) patients. None of the patients experienced grade ≥3 acute or late toxicity. CONCLUSIONS: Stereotactic body radiation therapy is feasible for Japanese patients with prostate cancer, with acceptable acute toxicity. Age, genitourinary toxicity at baseline and bladder mean dose predict grade 2 acute genitourinary toxicity.

Retrospective analysis of hypofractionated stereotactic radiotherapy for tumors larger than 2 cm.

Stereotactic radiosurgery for large brain metastases (BM) not amenable to surgical resection is associated with limited local control and neurotoxicity, while hypofractionated stereotactic radiotherapy (HFSRT) has emerged as a promising option. We retrospectively evaluated 61 patients with BM larger than 2 cm in the maximum diameter, who were treated with HFSRT (mainly 35 Gy/5 fractions) in our center between 2006-2016, focusing on the effect of BM size on outcomes. Eligible patients were divided according to the maximum BM diameter (group A [23 patients]: ≥3 cm, group B [22 patients]: <3 cm) to assess the relationship between tumor size and prognosis or safety. The primary outcome was the local control rate (LCR), and secondary outcomes were the response rate (RR), brain progression-free survival (BPFS), median survival time (MST), and radionecrosis (RN). Univariate and multivariate analyses for LCR were conducted using Cox's proportional hazards model. In the 45 eligible patients (58 lesions) enrolled in this study, the RR was 86.4% with an overall LCR of 64.7% at 12 months (67.1% for group A and 61.5% for group B [p = 0.45]). The median BPFS and MST were 11.6 and 14.2 months, respectively. Univariate analyses revealed that female patients and gynecological cancer patients had poorer LCR, but they were not significantly independent prognostic factors (p = 0.06, 0.09, respectively). Two patients (4.4%) experienced RN that was detected more than 4 years after HFSRT. We conclude that HFSRT is safe for large BM but further studies are needed to determine optimal doses and fractions.

Effects of dose-escalated radiotherapy in combination with long-term androgen deprivation on prostate cancer.

OBJECTIVE: We aimed to examine the effects of a dose escalation for prostate cancer patients receiving long-term androgen deprivation therapy (ADT). METHODS: A retrospective analysis of 605 patients treated with radiotherapy (RT) and long-term ADT (National Comprehensive Cancer Network criteria-defined intermediate-risk, minimum 10 months; high-risk and very-high-risk, minimum 20 months) was performed. The median ADT time was 31 months. Cox's proportional hazards models were used to compare biochemical disease-free survival (bDFS), clinical relapse-free survival (cRFS) and overall survival (OS) between the ≥70, <78 Gy group and 78 Gy group in a univariate analysis and to assess the effects of the dose escalation on bDFS in a multivariate analysis. RESULTS: After a median follow-up of 70 months, 5-year bDFS was significantly better in the 78 Gy group than in the ≥70, <78 Gy group [96 vs 83%; hazard ratio 3.6 (95% confidence interval 2.2-6.1); p < 0.001]. 5-year cRFS and OS were similar between the two groups. The multivariate analysis showed that RT dose was still an independent prognostic factor of bDFS (p = 0.005). CONCLUSION: The results of the present study suggest that dose escalations result in significant improvements in bDFS, even when used in combination with long-term ADT. A longer follow-up is needed to clarify the effects of dose escalations on cRFS and OS. Advances in knowledge: It remains unclear whether high-dose RT is necessary for improving the outcomes of patients receiving long-term ADT. The results suggest that dose escalations result in significant improvements in biochemical control.