Joseph Sia

Background: The FET-PET in Glioblastoma (FIG) study (TROG 18.06) assessed the impact of adding FET-PET to MRI on radiotherapy gross tumor volume delineation in newly diagnosed glioblastoma. Methods: This multicenter prospective phase 2 study evaluated participants with newly diagnosed glioblastoma IDH-wildtype undergoing postoperative MRI and FET-PET imaging before adjuvant radiotherapy, delivered according to standard MRI-based planning. The FET-PET-positive biological tumor volume (BTV) was used to derive the Hybrid (FET-PET+MRI) gross tumor volume (Hybrid-GTV). Primary outcomes were: (1) BTV excluded from the GTV defined on MRI alone (MR-GTV); (2) Hybrid-GTV excluded from the MR-GTV with both comparisons analyzed by non-overlap volume (cm3 and %), dosimetry (D98 and V95), and spatial similarity metrics; (3) clinically meaningful change in GTV non-overlap percentage volume with the addition of FET-PET. Results: There were 172 participants recruited, n = 140 evaluable. Median BTV was 23.1 cm3, median MR-GTV was 32.1 cm3, and median Hybrid-GTV was 46.0 cm3. Hybrid-GTV was significantly larger than the MR-GTV (P < .001), with a larger Hybrid-GTV observed in 83% of cases. Comparing BTV to MR-GTV, median non-overlap volume was 10.1 cm3 and non-overlap percentage volume 53.5%. Comparing Hybrid-GTV to MR-GTV, median non-overlap volume was 14.9 cm3 and non-overlap percentage volume 33.9%. D98 and V95 were lower for the Hybrid-GTV than for the MR-GTV, suggesting lower dose coverage. Applying a > 20% non-overlap percentage volume threshold, 76% of participants had a meaningful change in GTV with the addition of FET-PET. Conclusion: FET-PET differed significantly from MRI-based GTV delineation, with its incorporation leading to a clinically meaningful change in GTV in the majority of participants.

Purpose Radiation necrosis (RN) is a potentially debilitating complication of stereotactic radiosurgery (SRS) for brain metastases (BrM). Bevacizumab, a monoclonal antibody against vascular endothelial growth factor A, is increasingly used for treating symptomatic RN. This multi-institutional retrospective study examines its longitudinal efficacy, toxicity, and steroid-sparing effect in BrM patients with SRS-induced RN over an extended follow-up. Methods BrM patients from two Australian health networks who received bevacizumab between 2018 and 2023 for SRS-induced RN were identified. Patient characteristics, symptomatic and radiological responses, steroid use, and toxicities were recorded. Time-to-events and associations with outcomes were analysed with Kaplan-Meier and Cox methods. Results 26 patients were analysed over a median follow-up of 21.2 months. The most common bevacizumab schedule was 7.5 mg/kg 3-weekly for a median of 3 cycles. Symptomatic responses were detectable 1-week post-commencement, improving headache and neurological deficits in 60% and 80% of patients by 6 months. 88% had radiological improvement by a median of 7 weeks. 71% of those on steroids could cease steroids over a median of 1.9 month. 19% developed recurrent, symptomatic RN 9.5–28.5 months after bevacizumab cessation. 75% of those re-treated with bevacizumab for recurrent RN gained further symptomatic improvement. Grade 2 + toxicity rate was 24% (venous thromboembolism: 12%; hypertension: 8%; intra-tumoural haemorrhage: 4%). Conclusion Bevacizumab is an effective treatment for symptomatic, steroid-dependent SRS-induced RN but is associated with moderate rates of Grade 2–3 toxicities and recurrent, symptomatic RN after its cessation. Bevacizumab rechallenge remains useful for recurrent RN. Multi-disciplinary input and careful surveillance remain critical for its use in BrM patients.

Purpose: Pre-operative stereotactic radiosurgery (SRS) for brain metastases (BrM), an emerging alternative to post-operative SRS, is typically performed 1–2 days before resection. However, a longer period of the irradiated tumour in situ may confer anti-tumour immunological benefits. We conducted the first clinical trial to evaluate the feasibility of planned delayed resection after pre-operative SRS. Methods: In this single-arm trial, patients with suspected BrM suitable for pre-operative SRS and surgery were eligible. The primary endpoint was feasibility of resection 7–21 days after SRS, with a pre-defined feasibility threshold of 66% receiving this. Secondary endpoints included 6-month adverse events (AE) and local control (LC) rates. Tumour volume change was assessed from SRS- and neurosurgery-planning MRI’s. Result: 78 patients were screened and the target accrual of 15 patients was met. Common reasons for pre-operative SRS ineligibility were lack of existing cancer diagnosis (44%) and tumour size/peri-tumoural oedema (18%). Two patients declined resection after SRS. The median SRS-to-surgery interval was 8 days (range 0–15). Nine tumours in 8 patients (56%) received delayed resection. Reasons for earlier resection were predominantly non-medical. There were no Grade > 2 AE. The 6-month BrM LC was 100%. At a median follow-up of 13.8 months, the only BrM local failure after SRS and resection occurred with a 0-day SRS-to-surgery interval. No histopathological diagnosis issues were encountered with delayed resection. An increased SRS-to-surgery interval correlated with greater tumour shrinkage. Conclusions: The pre-defined feasibility threshold for delayed resection was not met, but more than half of patients received delayed resection without safety concerns. Trial registration number: ACTRN12622001372774 (Registered 26/10/2022).

Background: Desmoid tumors (DT) are rare, locally aggressive neoplasms that affect a young population and have a tendency for recurrence. There is sparse contemporary real‐world data to guide practice for DT. Here, we report on a large cohort of DT patients, describing patterns of care and clinical outcomes.Methods: Data on DT patients first seen between 2010 and 2021 were extracted from a prospective database and supplemented with a retrospective review of hospital records. Trends in treatment use were analyzed using the Cochran‐Armitage test. Time‐to‐next intervention (TTNI) was estimated with the Kaplan–Meier method. Imaging response was categorized using the RECIST v1.1 criteria.Results: A total of 135 patients, 265 treatment episodes were analyzed. Median follow‐up was 4.3 years. The common tumor sites were abdominal wall (27%), upper limb (20%), lower limb (16%), and intra‐abdominal (15%). Over time, the proportion of patients receiving no upfront treatment was stable (2010–2013: 31%, 2014–2017: 35%, 2018–2021: 29%; p = 0.5), but there was increasing first‐line use of NSAID/tamoxifen (7%, 41%, 47%; p < 0.001), and decreasing first‐line use of radiotherapy (35%, 14%, 4%; p < 0.001) and surgery (28%, 8%, 18%; p < 0.05). At 5 years, the proportion not requiring treatment switch was highest following surgery (72%), radiotherapy (66%), and no upfront therapy (52%). 12% and 5% of patients without treatment achieved partial and complete imaging responses at 2 years.Conclusion: We highlight the heterogeneity and trends in DT management over a 12‐year period, affirming the role of active surveillance, radiotherapy, and surgery in selected patients. Medical therapies are evolving and may significantly influence the DT management paradigm.

Differentiating between radiation necrosis and true tumour progression after radiotherapy is challenging due to overlapping imaging appearances. This review outlines useful techniques and imaging features for making this distinction, as well as potential pitfalls. Both radiation necrosis and true tumour progression commonly manifest as peripherally enhancing lesions on post‐contrast T1‐weighted imaging, but the enhancing rim should be thin in radiation necrosis, while more discrete nodular enhancement suggests active tumour. Other features on post‐contrast MRI that suggest radiation necrosis include enhancing lesions across anatomical boundaries, clustering of enhancing lesions and a change in lesion shape. Central diffusion restriction corresponding to the central necrotic area favours radiation necrosis, but there are potential pitfalls to be aware of, including hypercellular tumours, coagulative necrosis due to bevacizumab and intra‐lesional haemorrhage. Radiation necrosis typically results in small, clustered foci of magnetic susceptibility on susceptibility‐sensitive sequences, and the absence of such foci should raise concern for active tumour. When uncertainty remains, ancillary techniques such as MR perfusion and amino acid PET can improve confidence. Atypical appearances of radiation necrosis can occur, for example, cystic radiation necrosis or radiation necrosis occurring after radiotherapy to adjacent structures. It is also important for the radiologist to be aware of additional factors that may increase the likelihood of either radiation necrosis or tumour necrosis or influence patient management.

Background: Whether stereotactic radiosurgery (SRS) and immune checkpoint blockade (ICB) for brain metastases (BrM) have a time window for synergistic efficacy and toxicity is unclear. We examined this question in a large, contemporary cohort of patients who received concurrent SRS and ICB. Methods: Patients who received SRS for intact BrM within 1 month before to 6 months after an ICB cycle at a single center from 2018 to 2023 were included if they had no prior whole-brain radiotherapy or SRS to the same BrM. Intracranial progression-free survival (icPFS), local control (LC), distant brain control (DBC), overall survival (OS), and radionecrosis were analyzed by Kaplan–Meier and log-rank methods. Cox regression was used for uni/multivariable analysis (UVA/MVA). Results: A total of 419 BrM, 170 treatment episodes, and 134 patients were analyzed. In total, 43% and 40% of patients had melanoma and non-small cell lung cancer. A shorter SRS-ICB interval significantly correlated with improved icPFS, LC, and OS, but not DBC. This was true when analyzed as either a categorical or continuous factor. On MVA, SRS-ICB interval outperformed all factors including histology, ICB type, and de novo BrM status in predicting icPFS (P = .030), LC (P = .042), and OS (P = .033). In the absence of corticosteroids, pre-SRS lymphocyte counts correlated with improved LC (P = .02). Radionecrosis was not associated with SRS-ICB interval, but with BrM size and number of ICB cycles received prior to SRS. Conclusion: Delivering SRS closer to ICB cycles was associated with improved icPFS, LC, and OS without affecting radionecrosis rates. This may present a therapeutic opportunity to improve BrM outcomes.

Purpose: Shorter hypofractionated radiation therapy (HF-RT) schedules may have radiobiological, patient convenience and healthcare resource advantages over conventionally fractionated radiation therapy (CF-RT) in glioblastoma (GBM). We report outcomes of young, fit GBM patients treated with HF-RT and CF-RT during the COVID-19 pandemic, and a meta-analysis of HF-RT literature in this patient subgroup. Methods: Hospital records of patients with IDH-wildtype GBM treated with HF-RT (50 Gy/20 fractions) and CF-RT (60 Gy/30 fractions) between January 2020 and September 2021 were reviewed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Univariable analysis was performed using Cox regression analysis. A systematic search and meta-analysis of studies from January 2000 to January 2022 was performed. Results: 41 patients were treated (HF-RT:15, CF-RT:26). For both HF-RT and CF-RT groups, median age was 58 years and 80–90% were ECOG 0–1. There were more methylated tumours in the HF-RT group. All patients received concurrent/adjuvant temozolomide. At 19.2 months median follow-up, median OS was 19.8 months and not-reached for HF-RT and CF-RT (p = 0.5), and median PFS was 7.7 and 5.8 months, respectively (p = 0.8). HF-RT or CF-RT did not influence OS/PFS on univariable analysis. Grade 3 radionecrosis rate was 6.7% and 7.7%, respectively. 15 of 1135 studies screened from a systematic search were eligible for meta-analysis. For studies involving temozolomide, pooled median OS and PFS with HF-RT were 17.5 and 9.9 months (927 and 862 patients). Studies using shortened HF-RT schedules reported 0–2% Grade 3 radionecrosis rates. Conclusion: HF-RT may offer equivalent outcomes and reduce treatment burden compared to CF-RT in young, fit GBM patients.