Hyperthermia (HT) is a cancer treatment modality which targets malignant tissues by heating to 40–43 °C. In addition to its direct antitumor effects, HT potently sensitizes the tumor to radiotherapy (RT) and chemotherapy (CT), thereby enabling complete eradication of some tumor entities as shown in randomized clinical trials. Despite the proven efficacy of HT in combination with classic cancer treatments, there are limited international standards for the delivery of HT in the clinical setting. Consequently, there is a large variability in reported data on thermometric parameters, including the temperature obtained from multiple reference points, heating duration, thermal dose, time interval, and sequence between HT and other treatment modalities. Evidence from some clinical trials indicates that thermal dose, which correlates with heating time and temperature achieved, could be used as a predictive marker for treatment efficacy in future studies. Similarly, other thermometric parameters when chosen optimally are associated with increased antitumor efficacy. This review summarizes the existing clinical evidence for the prognostic and predictive role of the most important thermometric parameters to guide the combined treatment of RT and CT with HT. In conclusion, we call for the standardization of thermometric parameters and stress the importance for their validation in future prospective clinical studies.

Despite its reputation as a radioresistant tumour, there is evidence to support a role for radiotherapy in patients with melanoma and we summarise current clinical practice. Melanoma is a highly immunogenic tumour and in this era of immunotherapy, there is renewed interest in the potential of irradiation, not only as an adjuvant and palliative treatment, but also as an immune stimulant. It has long been known that radiation causes not only DNA strand breaks, apoptosis, and necrosis, but also immunogenic modulation and cell death through the induction of dendritic cells, cell adhesion molecules, death receptors, and tumour-associated antigens, effectively transforming the tumour into an individualised vaccine. This immune response can be enhanced by the application of clinical hyperthermia as evidenced by randomised trial data in patients with melanoma. The large fraction sizes used in cranial radiosurgery and stereotactic body radiotherapy are more immunogenic than conventional fractionation, which provides additional radiobiological justification for these techniques in this disease entity. Given the immune priming effect of radiotherapy, there is a strong but complex biological rationale and an increasing body of evidence for synergy in combination with immune checkpoint inhibitors, which are now first-line therapy in patients with recurrent or metastatic melanoma. There is great potential to increase local control and abscopal effects by combining radiotherapy with both immunotherapy and hyperthermia, and a combination of all three modalities is suggested as the next important trial in this refractory disease.

Background: The objective benefits of low dose radiotherapy (LDRT) for non-malignant joint disorders are controversial. This study evaluated changes in pain, quality of life (QoL) and function after LDRT for epicondylitis, plantar fasciitis, and finger osteoarthritis. Materials and Methods: Patients over 40 years old with epicondylitis, plantar fasciitis, and finger osteoarthritis were had pain following at least 6 months of conservative therapy. Patients received 0.5 Gy LDRT twice weekly for 4 weeks repeated once after 8 weeks in patients who failed to achieve complete pain relief. Patients assessed their pain according to the visual analog scale. Handgrip strength was measured with an isometric dynamometer and the fast self-paced walking test was used in patients with plantar fasciitis. QoL was evaluated according to the EQ-5D and HAQ-DI questionnaires. Results: Outcomes for 157 patients (204 sites) were documented at 2, 6, and 12 months after last LDRT. Pain reduction at rest (p < 0.001), during activity (p < 0.001) and increase in handgrip strength (extension p < 0.001, flexion p = 0.002) were highly significant for patients with lateral epicondylitis. Patients with medial epicondylitis reported pain relief at rest (p = 0.041) and during activity (p = 0.041) and significant increase in handgrip strength (p = 0.022). Patients with plantar fasciitis reported pain reduction at rest (p < 0.001), during activity (p < 0.001) and faster walking times (p < 0.001). A trend toward improved QoL was observed. Patients with finger osteoarthritis reported significant pain relief during activity (p < 0.001) and a gain in handgrip strength (p = 0.004), with a trend to both pain relief at rest (p = 0.056) and stronger pinch grip (p = 0.099). Conclusions: LDRT achieved significant pain relief at rest and during activity and a corresponding objective improvement in handgrip strength in patients with epicondylitis. Pain relief at rest, during activity and improvement in walking time were demonstrated in patients with plantar fasciitis. LDRT achieved pain relief during activity, and handgrip strength was improved in patients with finger osteoarthritis. No significant effect was seen on quality of life measures for these conditions. The observed benefits were maintained 12 months after LDRT for all 3 indications and we recommend this low cost, safe intervention for patients over 40 who have failed prior conservative therapy.

Background: The α/β values for prostate cancer (PCa) are usually assumed to be low (1.0–1.8 Gy). This study estimated the α/β values of PCa from phase III randomized trials of conventional (CRT) versus hypofractionated (HRT) external beam radiotherapy (RT), reported as isoeffective in terms of their 5-year biochemical (BF) or biochemical and/or clinical failure (BCF) rates. Material and methods: The α/β for each trial was estimated from the equivalent biological effective doses using the linear-quadratic model for each of their HRT and CRT schedules. The cumulative outcomes of these trials were evaluated by meta-analysis for odds ratio (OR), risk ratio (RR) and risk difference (RD). Results: Eight trials from seven studies, randomized 6993 patients between CRT (n = 2941) and HRT (n = 4052). RT treatment varied between the two treatment groups in terms of dose/fraction, total dose, overall treatment time and %patients on androgen deprivation therapy (ADT). Differences in OR, RR, and RD for both BF and BCF were nonsignificant. The computed α/β ranged from 1.3 to 11.1 Gy (4.9 ± 3.9 Gy; 95% CI: 1.6–8.2). On multivariate regression, %ADT was the sole determinant of computed α/β (model R²: 0.98, p < .001). Conclusions: Clinically estimated α/β for PCa from isoeffective randomized trials using known variables in the linear-quadratic expression ranged between 1.3 and 11.1 Gy. The estimated α/β values were inversely related to %ADT usage, which should be considered when planning future RT dose-fractionation schedules.

Objectives: To summarize the available literature on using machine learning (ML) for the detection and segmentation of benign tumors of the central nervous system (CNS) and to assess the adherence of published ML/diagnostic accuracy studies to best practice. Methods: The MEDLINE database was searched for the use of ML in patients with any benign tumor of the CNS, and the records were screened according to PRISMA guidelines. Results: Eleven retrospective studies focusing on meningioma (n = 4), vestibular schwannoma (n = 4), pituitary adenoma (n = 2) and spinal schwannoma (n = 1) were included. The majority of studies attempted segmentation. Links to repositories containing code were provided in two manuscripts, and no manuscripts shared imaging data. Only one study used an external test set, which raises the question as to whether some of the good performances that have been reported were caused by overfitting and may not generalize to data from other institutions. Conclusions: Using ML for detecting and segmenting benign brain tumors is still in its infancy. Stronger adherence to ML best practices could facilitate easier comparisons between studies and contribute to the development of models that are more likely to one day be used in clinical practice.

Background: 90% of glioblastomas (GBM) relapse within two years of diagnosis. In contrast to the initial setting, there is no standard management for recurrent disease and options include hypofractionated stereotactic re-irradiation (re-mHSRT). The aims of this study were to investigate re-mHSRT practice in Swiss neuro-oncology centres. Methods: A survey of 18 questions regarding re-irradiation for GBM was created and distributed electronically (SurveyMonkey, USA) to 11 radiation oncologists in Switzerland specialising in brain tumours. We evaluated the clinical outcomes of a multicentre series of patients treated with an established re-mHSRT schedule to benchmark these against the literature and investigated the radiological patterns of relapse after re-mHSRT. Results: 8 of 11 (73%) radiation oncologists responded to the survey and re-irradiation practice was heterogeneous. The 10 × 3.5 Gy schedule (RTOG 1205, BRIOChe trials) was used by 5/8 respondents and 47/50 patients with recurrent GBM treated with re-mHSRT with this schedule in daily practice were included in the analysis. The median time to re-mHSRT following completion of adjuvant RT was 23.3 (7-224) months. The median PTV at re-mHSRT was 22.0 cm³ (0.9–190). Combined CTV + PTV margins ranged from 0 to 10 mm and median prescription isodose was 80% (67–100). 14/47 (30%) patients received temozolomide and four (8.5%) continued bevacizumab concomitantly. On multivariable analysis, concomitant systemic therapy predicted for progression-free survival (PFS), HR 2.87 (95% CI 1-03-7.96), p = 0.042. Median PFS following re-mHSRT was 6.6 (0.2–92.5) months and 26/47 patients (55%) received subsequent systemic therapy. The median overall survival (OS) following recurrence was 11.8 months (1.5–92.5), similar to the 10.8 months in the literature with the same schedule. The six-month OS rate was 37/47 (79%), which compares well with the 73% reported in a meta-analysis of 50 publications employing various schedules. In a subgroup analysis of 36/47 (79%) patients with MR follow-up after re-mHSRT, 8/36 (22%) had no radiological evidence of tumour progression at a median follow-up of 9.4 months. 21/28 (75%) radiological relapses were in-field, two were marginal and five were out of field. Conclusions: Re-mHSRT with 10 × 3.5 Gy can achieve local control in selected patients with recurrent GBM.