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Introduction: Prostate bed radiotherapy (RT) is a major affecter of patients’ long-term quality of life (QoL). To ensure the best possible outcome of these patients, dose constraints are key for optimal RT planning and delivery. However, establishing refined dose constraints requires access to patient-level data. Therefore, we aimed to provide such data on the relationship between OAR and gastrointestinal (GI) as well as genitourinary (GU) QoL outcomes of a homogenous patient cohort who received dose-intensified post-operative RT to the prostate bed. Furthermore, we aimed to conduct an exploratory analysis of the resulting data. Methods: Patients who were treated with prostate bed RT between 2010 and 2020 were inquired about their QoL based on the Expanded Prostate Cancer Index Composite (EPIC). Those (n = 99) who received volumetric arc therapy (VMAT) of at least 70 Gy to the prostate bed were included. Dose-volume histogram (DVH) parameters were gathered and correlated with the EPIC scores. Results: The median age at the time of prostate bed RT was 68.9 years, and patients were inquired about their QoL in the median 2.3 years after RT. The median pre-RT prostate-specific antigen (PSA) serum level was 0.35 ng/mL. The median duration between surgery and RT was 1.5 years. The median prescribed dose to the prostate bed was 72 Gy. A total of 61.6% received prostate bed RT only. For the bladder, the highest level of statistical correlation (p < 0.01) was seen for V10-20Gy, Dmean and Dmedian with urinary QoL. For bladder wall, the highest level of statistically significant correlation (p < 0.01) was seen for V5-25Gy, Dmean and Dmedian with urinary QoL. Penile bulb V70Gy was statistically significantly correlated with sexual QoL (p < 0.05). A larger rectal volume was significantly correlated with improved bowel QoL (p < 0.05). Sigmoid and urethral DVH parameters as well as the surgical approach were not statistically significantly correlated with QoL. Conclusion: Specific dose constraints for bladder volumes receiving low doses seem desirable for the further optimization of prostate bed RT. This may be particularly relevant in the context of the aspiration of establishing focal RT of prostate cancer and its local recurrences. Our comprehensive dataset may aid future researchers in achieving these goals.

Highlights • Intensification of chemoradiation with hyperthermia was feasible in nine patients with LAPC. • Only one grade three toxicity was reported and two tumours became resectable. • The 24 months median OS and 100% 1 year OS are superior to historical series., Introduction Driven by the current unsatisfactory outcomes for patients with locally advanced pancreatic cancer (LAPC), a biologically intensified clinical protocol was developed to explore the feasibility and efficacy of FOLFORINOX chemotherapy followed by deep hyperthermia concomitant with chemoradiation and subsequent FOLFORINOX chemotherapy in patients with LAPC. Methods Nine patients with LAPC were treated according to the HEATPAC Phase II trial protocol which consists of 4 cycles of FOLFORINOX chemotherapy followed by gemcitabine-based chemoradiation to 56 Gy combined with weekly deep hyperthermia and then a further 8 cycles of FOLFORINOX chemotherapy. Results One grade three related toxicity was reported and two tumours became resectable. The median overall survival was 24 months and 1 year overall survival was 100%. Conclusions Intensification of chemoradiation with deep hyperthermia was feasible in nine consecutive patients with LAPC.

The road of acceptance of oncologic thermotherapy/hyperthermia as a synergistic modality in combination with standard oncologic therapies is still bumpy [...]

Simple Summary Hyperthermia (HT) is a promising therapeutic option for multiple cancer entities as it has the potential to increase the cytotoxicity of radiotherapy (RT) and chemotherapy (CT). Thermometric parameters of HT are considered to have potential as predictive factors of treatment response. So far, only limited data about the prognostic and predictive role of thermometric parameters are available. In this review, we investigate the existing clinical evidence regarding the correlation of thermometric parameters and cancer response in clinical studies in which patients were treated with HT in combination with RT and/or CT. Some studies show that thermometric parameters correlate with treatment response, indicating their potential significance for treatment guidance. Thus, the establishment of specific thermometric parameters might pave the way towards a better standardization of HT treatment protocols. Abstract 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

• We conducted a Swiss survey on patterns of practice during COVID-19 pandemic. • Dedicated IT solutions were implemented in all radiation-oncology departments. • Upfront endocrine treatments for breast and prostate cancer were privileged. • Use of hypofractionation for breast, rectal cancer and palliation was increased.

Purpose In 2015, the United Nations proposed “The 2030 Agenda for Sustainable Development” goals, which envision reducing premature mortality from noncommunicable diseases by one third by 2030. Because >50% of patients with cancer require radiation therapy (RT), the existing gaps in RT infrastructure in low- and middle-income countries (LMICs) and additional requirements by 2030 were examined. Cost-effective strategies to address this challenge were explored. Methods and Materials Public domain databases of the United Nation organizations were accessed. RT requirements for 2030 were estimated according to the International Atomic Energy Agency recommendations. To explore a feasible cost-effective solution, a teleradiotherapy network (TRTNet) was conceived with 4 to 8 primary RT centers (PRTCs) (each with 1 teletherapy unit, US$2.05 million) linked to a secondary RT center (SRTC; 2 teletherapy units and 1 brachytherapy unit, US$5.05 million). Results Of the 137 LMICs, 51 (37.3%) presently lack RT facilities. The remaining 86 LMICs have 5084 teletherapy units (gap: –7741) and thus a mean access to RT of 33%. By 2030, an additional 12,133 teletherapy units would be required for 14.2 million patients with cancer. A TRTNet linked 4 to 8 PRTCs with 1 SRTC could yield a return of investment (ROI) between –181.1% and 757.6% depending on the TRTNet configuration, 2-year survival, gross national income per capita, and employment-population ratio of the individual LMICs. Sixty-five (47.4%) of these could be expected to attain a positive ROI (7.1% to 757.6%) with a 2-year survival of 50% and a TRTNet configuration of 1 SRTC and 8 PRTCs. Conclusion Optimized TRTNets through resource sharing could be a cost-effective and financially viable option to create RT infrastructure and facilitate capacity building toward realizing the 2030 Agenda for Sustainable Development goals in most LMICs. Low-income countries and some LMICs not expected to gain positive ROI should be considered for external financial assistance.

Purpose Hyperthermia inhibits the repair of irradiation-induced DNA damage and thereby could alter the α/β values of tumours. This study estimates the clinical α/βHTRT values from clinical trials of thermoradiotherapy (HTRT) vs radiotherapy (RT) in recurrent breast (RcBC), head and neck (III/IV) (LAHNC) and cervix cancers (IIB-IVA) (LACC). Methods Three recently published meta-analyses for HTRT vs RT in RcBC, LAHNC and LACC were evaluated for complete response (CR). Studies with specified RT dose (D), dose/fraction (d) and corresponding CRs were selected. Tumour biological effective dose (BED) for each study with RT (BEDRT) was computed assuming an α/βRT of 10 Gy. As outcomes were favourable with HTRT, thermoradiobiological BED (BEDHTRT) was calculated as a product of BEDRT and %CRHTRT/%CRRT. The α/βHTRT was estimated as Dd/(BEDHTRT – D). Results 12 trials with 864 patients were shortlisted – RcBC (3 studies, n = 259), LAHNC (5 studies, n = 338) and LACC (4 studies, n = 267). Overall risk difference of 0.28 favoured HTRT (p Conclusion Thermoradiobiological effects on the repair of RT induced DNA damage results in reduction in α/β values of tumours. This should be considered to effectively optimize HTRT dose-fractionation schedules in the clinic.

A 70-year old male with stage I large cell neuroendocrine carcinoma (LCNEC) of the lung underwent resection of a metachronous 5 cm brain metastasis and received postoperative hypofractionated stereotactic radiotherapy (hfSRT). Five sequential nodular leptomeningeal metastases up to 5.3 cm in diameter were diagnosed on MRI within 10 months and were treated with SRT. Currently the patient has no evidence of intracranial disease 24 months after last irradiation without chemotherapy or whole brain radiotherapy. This is the first report of sustained complete remission of multiple large leptomeningeal metastases achieved with hfSRT, highlighting this brain-sparing approach in selected patients with LCNEC lung cancer.

We present a simulation study investigating the feasibility of electrical impedance tomography (EIT) as a low cost, noninvasive technique for hyperthermia (HT) treatment monitoring and adaptation. Temperature rise in tissues leads to perfusion and tissue conductivity changes that can be reconstructed in 3D by EIT to noninvasively map temperature and perfusion. In this study, we developed reconstruction methods and investigated the achievable accuracy of EIT by simulating HT treatmentlike scenarios, using detailed anatomical models with heterogeneous conductivity distributions. The impact of the size and location of the heated region, the voltage measurement signal-to-noise ratio, and the reference model personalization and accuracy were studied. Results showed that by introducing an iterative reconstruction approach, combined with adaptive prior regions and tissue-dependent penalties, planning-based reference models, measurement-based reweighting, and physics-based constraints, it is possible to map conductivity-changes throughout the heated domain, with an accuracy of around 5% and cm-scale spatial resolution. An initial exploration of the use of multifrequency EIT to separate temperature and perfusion effects yielded promising results, indicating that temperature reconstruction accuracy can be in the order of 1 °C. Our results suggest that EIT can provide valuable real-time HT monitoring capabilities. Experimental confirmation in real-world conditions is the next step., Cancers, 13 (13), ISSN:2072-6694

Moderate hyperthermia at temperatures between 40 and 44°C is a multifaceted therapeutic modality. It is a potent radiosensitizer, interacts favorably with a host of chemotherapeutic agents, and, in combination with radiotherapy, enforces immunomodulation akin to "in situ tumor vaccination." By sensitizing hypoxic tumor cells and inhibiting repair of radiotherapy-induced DNA damage, the properties of hyperthermia delivered together with photons might provide a tumor-selective therapeutic advantage analogous to high linear energy transfer (LET) neutrons, but with less normal tissue toxicity. Furthermore, the high LET attributes of hyperthermia thermoradiobiologically are likely to enhance low LET protons; thus, proton thermoradiotherapy would mimic 12C ion therapy. Hyperthermia with radiotherapy and/or chemotherapy substantially improves therapeutic outcomes without enhancing normal tissue morbidities, yielding level I evidence reported in several randomized clinical trials, systematic reviews, and meta-analyses for various tumor sites. Technological advancements in hyperthermia delivery, advancements in hyperthermia treatment planning, online invasive and non-invasive MR-guided thermometry, and adherence to quality assurance guidelines have ensured safe and effective delivery of hyperthermia to the target region. Novel biological modeling permits integration of hyperthermia and radiotherapy treatment plans. Further, hyperthermia along with immune checkpoint inhibitors and DNA damage repair inhibitors could further augment the therapeutic efficacy resulting in synthetic lethality. Additionally, hyperthermia induced by magnetic nanoparticles coupled to selective payloads, namely, tumor-specific radiotheranostics (for both tumor imaging and radionuclide therapy), chemotherapeutic drugs, immunotherapeutic agents, and gene silencing, could provide a comprehensive tumor-specific theranostic modality akin to "magic (nano)bullets." To get a realistic overview of the strength (S), weakness (W), opportunities (O), and threats (T) of hyperthermia, a SWOT analysis has been undertaken. Additionally, a TOWS analysis categorizes future strategies to facilitate further integration of hyperthermia with the current treatment modalities. These could gainfully accomplish a safe, versatile, and cost-effective enhancement of the existing therapeutic armamentarium to improve outcomes in clinical oncology.

Treatment options in locally advanced cervix cancer (LACC) have evolved around radiation therapy (RT) and/or chemotherapy (CT), hypoxic cell sensitizers, immunomodulators (Imm), and locoregional moderate hyperthermia (HT). A systematic review and network meta-analysis was conducted to synthesize the evidence for efficacy and safety in terms of long-term locoregional control (LRC), overall survival (OS), and grade ≥3 acute morbidity (AM) and late morbidity (LM). Five databases were searched, and 6285 articles (1974-2018) were screened per the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Fifty-nine randomized trials in untreated LACC without surgical intervention were shortlisted. These used 13 different interventions: RT alone and/or neoadjuvant CT (NACT), adjuvant CT (ACT), concurrent chemoradiation therapy (CTRT) (weekly cisplatin [CDDP]/3-weekly CDDP/combination CT with CDDP/non-CDDP-based CT), hypoxic cell sensitizers, Imm, or HT. Odds ratios (ORs) using random effects network meta-analysis were estimated. Interventions for each endpoint were ranked according to their corresponding surface under cumulative ranking curve values. Of the 9894 patients evaluated, the total events reported for LRC, OS, AM, and LM were 5431 of 8197, 4482 of 7958, 1710 of 7183, and 441 of 6333, respectively. ORs and 95% credible intervals (CrIs) for the 2 best strategies were HT + RT versus CTRT + ACT (OR, 1.23; 95% CrI, 0.49-3.19) for LRC, CTRT (3-weekly CDDP) versus HTCTRT (OR, 1.14; 95% CrI, 0.35-3.65) for OS, RT + ACT versus RT (OR, 0.01; 95% CrI, 0.00-1.04) for AM, and NACT + RT + ACT versus RT + Imm (OR, 0.42; 95% CrI, 0.02-7.39) for LM. The 3 interventions with the highest cumulative surface under cumulative ranking curve values for all 4 endpoints were HTRT, HTCTRT, and CTRT (3-weekly CDDP). Articles with low risk of bias and those published during 2004 to 2018 also retained these interventions as the best. Two-step cluster analysis grouped these 3 modalities in a single distinctive cluster. HTRT, HTCTRT, and CTRT with 3-weekly CDDP were identified as therapeutic modalities with the best comprehensive impact on key clinical endpoints in LACC. This warrants a phase 3 randomized trial among these strategies for a head-to-head comparison and additional validation.

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.

Hyperthermia (HT) as an adjuvant to radiation therapy (RT) is a multimodality treatment method to enhance therapeutic efficacy in different tumours. High demands are placed on the hardware and treatment planning software to guarantee adequately planned and applied HT treatments. The aim of this prospective study was to determine the effectiveness and safety of the novel HT system in tumour-bearing dogs and cats in terms of local response and toxicity as well as to compare planned with actual achieved data during heating. A novel applicator with a flexible number of elements and integrated closed-loop temperature feedback control system, and a tool for patient-specific treatment planning were used in a combined thermoradiotherapy protocol. Good agreement between predictions from planning and clinical outcome was found in 7 of 8 cases. Effective HT treatments were planned and verified with the novel system and provided improved quality of life in all but 1 patient. This individualized treatment planning and controlled heat exposure allows adaptive, flexible and safe HT treatments in palliatively treated animal patients.

Background: Low dose radiotherapy (LDRT) is an effective treatment for therapy-resistant musculoskeletal disorders that is associated with only minimal toxicities and low costs [1]. As the population in many countries ages and such disorders result in significant impairment in quality of life and costs, there is now a wider international interest in LDRT for these conditions [2]. Numerous retrospective series describe the benefits of LDRT for non-malignant joint disorders, with response rates between 63-89% [3], but randomized and prospective data are scarce, [4, 5, 6]. Objectives: To prospectively evaluate pain, function and quality of life after low dose radiotherapy (LDRT) in patients with lateral and medial epicondylitis (LE and ME), finger osteoarthritis (OA) and plantar fasciitis (PlF). Methods: Patients over 40 years old were recruited to this single center trial. LDRT (8 x 0.5 Gy, 200 kV X-rays) was repeated once up to a total dose of 8.0 Gy. Pain scores (visual analogue scale=VAS), function tests and quality of life questionnaires were documented at 0, 2, 6, and 12 months. Results: 204 sites were treated. At 12 months after last LDRT (first or second course) compared with baseline prior to first LDRT: 39 LE sites reported pain reduction (median change in VAS) at rest (-2.5, p Conclusion: Patients with LE and ME, finger OA and PlF achieved sustained analgesia and an objective improvement in musculoskeletal function 12 months after completion of LDRT with 4-8 Gy. References: [1] Keilholz L et al. Radiotherapy for painful degenerative joint disorders. Indications, technique and clinical results. Strahlenther Onkol 1998;174:243-250. [2] Taylor RE et al.Radiotherapy for benign disease: Current evidence, benefits and risks. Clin Oncol 2015;27:433-435. [3] Seegenschmiedt MH et al. Radiotherapy for non-malignant disorders: State of the art and update of the evidence-based practice guidelines. Br J Radiol 2015;88:20150080. [4] Ott OJ et al. Radiotherapy for calcaneodynia. Results of a single center prospective randomized dose optimization trial. Strahlenther Onkol 2013;189:329-334. [5] Prokein B et al. Radiotherapy of painful heel spur with two fractionation regimens : Results of a randomized multicenter trial after 48 weeks’ follow-up. Strahlenther Onkol 2017;193:483-490. [6] Niewald M et al. German Cooperative Group on Radiotherapy for Benign Diseases of the German Society for Radiation O. Randomized, multicenter trial on the effect of radiation therapy on plantar fasciitis (painful heel spur) comparing a standard dose with a very low dose: Mature results after 12 months’ follow-up. Int J Radiat Oncol Biol Phys 2012;84:e455-462. Disclosure of Interests: None declared

Objective: Large inoperable sacral chordomas show unsatisfactory local control rates even when treated with high dose proton therapy (PT). The aim of this study is assessing feasibility and reporting early results of patients treated with PT and concomitant hyperthermia (HT). Methods: Patients had histologically proven unresectable sacral chordomas and received 70 Gy (relative biological effectiveness) in 2.5 Gy fractions with concomitant weekly HT. Toxicity was assessed according to CTCAE_v4. A volumetric tumor response analysis was performed. Results: Five patients were treated with the combined approach. Median baseline tumor volume was 735 cc (range, 369–1142). All patients completed PT and received a median of 5 HT sessions (range, 2–6). Median follow-up was 18 months (range, 9–26). The volumetric analysis showed an objective response of all tumors (median shrinkage 46%; range, 9–72). All patients experienced acute Grade 2–3 local pain. One patient presented with a late Grade 3 iliac fracture. Conclusion: Combining PT and HT in large inoperable sacral chordomas is feasible and causes acceptable toxicity. Volumetric analysis shows promising early results, warranting confirmation in the framework of a prospective trial. Advances in knowledge: This is an encouraging first report of the feasibility and early results of concomitant HT and PT in treating inoperable sacral chordoma.

The purpose of this study was to evaluate the present status of radiotherapy infrastructure and human resources in Switzerland and compute projections for 2020. The European Society of Therapeutic Radiation Oncology “Quantification of Radiation Therapy Infrastructure and Staffing” guidelines (ESTRO-QUARTS) and those of the International Atomic Energy Agency (IAEA) were applied to estimate the requirements for teleradiotherapy (TRT) units, radiation oncologists (RO), medical physicists (MP) and radiotherapy technologists (RTT). The databases used for computation of the present gap and additional requirements are (a) Global Cancer Incidence, Mortality and Prevalence (GLOBOCAN) for cancer incidence (b) the Directory of Radiotherapy Centres (DIRAC) of the IAEA for existing TRT units (c) human resources from the recent ESTRO “Health Economics in Radiation Oncology” (HERO) survey and (d) radiotherapy utilization (RTU) rates for each tumour site, published by the Ingham Institute for Applied Medical Research (IIAMR). In 2015, 30,999 of 45,903 cancer patients would have required radiotherapy. By 2020, this will have increased to 34,041 of 50,427 cancer patients. Switzerland presently has an adequate number of TRTs, but a deficit of 57 ROs, 14 MPs and 36 RTTs. By 2020, an additional 7 TRTs, 72 ROs, 22 MPs and 66 RTTs will be required. In addition, a realistic dynamic model for calculation of staff requirements due to anticipated changes in future radiotherapy practices has been proposed. This model could be tailor-made and individualized for any radiotherapy centre. A 9.8 % increase in radiotherapy requirements is expected for cancer patients over the next 5 years. The present study should assist the stakeholders and health planners in designing an appropriate strategy for meeting future radiotherapy needs for Switzerland.

To conduct a systematic review and meta-analysis to evaluate the outcome of hyperthermia (HT) and radiation therapy (RT) in locally recurrent breast cancers (LRBCs).A total of 708 abstracts were screened from 8 databases according to the PRISMA guidelines. Single-arm and 2-arm studies, treating LRBCs with HT and RT but without surgery (for local recurrence) or concurrent chemotherapy were considered. The evaluated endpoint was complete response (CR).Thirty-one full text articles, pertaining to 34 studies, were shortlisted for the meta-analysis. Eight were 2-arm (randomized, n=5; nonrandomized, n=3), whereas 26 were single-arm studies. In all, 627 patients were enrolled in 2-arm and 1483 in single-arm studies. Patients were treated with a median of 7 HT sessions, and an average temperature of 42.5°C was attained. Mean RT dose was 38.2 Gy (range, 26-60 Gy). Hyperthermia was most frequently applied after RT. In the 2-arm studies, a CR of 60.2% was achieved with RT + HT versus 38.1% with RT alone (odds ratio 2.64, 95% confidence interval [CI] 1.66-4.18, P.0001). Risk ratio and risk difference were 1.57 (95% CI 1.25-1.96, P.0001) and 0.22 (95% CI 0.11-0.33, P.0001), respectively. In 26 single-arm studies, RT + HT attained a CR of 63.4% (event rate 0.62, 95% CI 0.57-0.66). Moreover, 779 patients had been previously irradiated (696 from single-arm and 83 from 2-arm studies). A CR of 66.6% (event rate 0.64, 95% CI 0.58-0.70) was achieved with HT and reirradiation (mean ± SD dose: 36.7 ± 7.7 Gy). Mean acute and late grade 3/4 toxicities with RT + HT were 14.4% and 5.2%, respectively.Thermoradiation therapy enhances the likelihood of CR rates in LRBCs over RT alone by 22% with minimal acute and late morbidities. For even those previously irradiated, reirradiation with HT provides locoregional control in two-thirds of the patients. Thermoradiation therapy could therefore be considered as an effective and safe palliative treatment option for LRBCs.

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.

Globally, new cancer cases will rise by 57% within the next two decades, with the majority in the low- and middle-income countries (LMICs). Consequently, a steep increase of about 40% in cancer deaths is expected there, mainly because of lack of treatment facilities, especially radiotherapy. Radiotherapy is required for more than 50% of patients, but the capital cost for equipment often deters establishment of such facilities in LMICs. Presently, of the 139 LMICs, 55 do not even have a radiotherapy facility, whereas the remaining 84 have a deficit of 61.4% of their required radiotherapy units. Networking between centers could enhance the effectiveness and reach of existing radiotherapy in LMICs. A teleradiotherapy network could enable centers to share and optimally utilize their resources, both infrastructure and staffing. This could be in the form of a three-tier radiotherapy service consisting of primary, secondary, and tertiary radiotherapy centers interlinked through a network. The concept has been adopted in some LMICs and could also be used as a “service provider model,” thereby reducing the investments to set up such a network. Teleradiotherapy networks could be a part of the multipronged approach to address the enormous gap in radiotherapy services in a cost-effective manner and to support better accessibility to radiotherapy facilities, especially for LMICs.

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, ­T was the sole determinant of computed α/β (model R2: 0.98, p 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 ­T usage, which should be considered when planning future RT dose-fractionation schedules.

A systematic review and meta-analysis were conducted to evaluate the therapeutic outcomes of conventional radiation therapy (CRT) and hypofractionated radiation therapy (HRT) for localized or locally advanced prostate cancer (LLPCa).A total of 599 abstracts were extracted from 5 databases and screened in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Only phase III trials randomized between CRT and HRT in LLPCa with a minimum of 5 years of follow-up data were considered. The evaluated endpoints were biochemical failure, biochemical and/or clinical failure, overall mortality, prostate cancer-specific mortality, and both acute and late gastrointestinal (GI) and genitourinary (GU) (grade ≥2) toxicity.Ten trials from 9 studies, with a total of 8146 patients (CRT, 3520; HRT, 4626; 1 study compared 2 HRT schedules with a common CRT regimen), were included in the evaluation. No significant differences were found in the patient characteristics between the 2 arms. However, the RT parameters differed significantly between CRT and HRT (P.001 for all). The use of androgen deprivation therapy varied from 0% to 100% in both groups (mean ± standard deviation 43.3% ± 43.6% for CRT vs HRT; P=NS). The odds ratio, risk ratio, and risk difference (RD) between CRT and HRT for biochemical failure, biochemical and/or clinical failure, overall mortality, prostate cancer-specific mortality, acute GU toxicity, and late GU and GI toxicities were all nonsignificant. Nevertheless, the incidence of acute GI toxicity was 9.1% less with CRT (RD 0.091; odds ratio 1.687; risk ratio 1.470; P.001 for all). On subgroup analysis, the patient groups with ≤66.8% versus66.8% androgen deprivation therapy (RD 0.052 vs 0.136; P=.008) and76% versus ≥76% full seminal vesicles in the clinical target volume (RD 0.034 vs 0.108; P.001) were found to significantly influence the incidence of acute GI toxicity with HRT.HRT provides similar therapeutic outcomes to CRT in LLPCa, except for a significantly greater risk of acute GI toxicity. HRT enables a reduction in the overall treatment time and offers patient convenience. However, the variables contributing to an increased risk of acute GI toxicity require careful consideration.

Hyperthermia, i.e. thermal cancer therapy, is increasingly (re)gaining ground as a treatment option. Encouraging results from phase I, II, and III clinical trials and positive meta-analyses for com...

Summary Objectives To analyze the prognostic value of clinical tumor response during chemoradiation for locally advanced head and neck cancer. Patients and Methods The locoregional response at 50.4 Gy was assessed by physical examination (PE) in patients treated within the randomized trial SAKK 10/94 using hyperfractionated radiotherapy (RT), median total dose 74.4 Gy with or without cisplatin 20 mg/m2 chemotherapy on 5 consecutive days during weeks 1 and 5 or 6 of RT. Response was classified as a complete response (CR), complete response with uncertainty (Cru), partial response (PR), stable disease (SD), or progressive disease (PD). The primary endpoint was time to treatment failure (TTF) due to any cause. Secondary endpoints included locoregional-recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS). Univariate and multivariate Cox proportional hazards (PH) models were applied to analyze the associations between survival endpoints and clinical tumor response. Results A total of 136, 131 and 97 patients were evaluable for response at the primary tumor, lymph nodes and both sites combined, respectively. At 50.4 Gy 57/136 (42%), 46/131 (35%) and 21/97 (22%) patients had a good response (CR/Cru vs. PR/SD) at the primary tumor, the lymph nodes, and both sites combined, respectively. The median follow-up times were 11.4, 9.6 and 11.4 years for the three groups. Good responses were all significantly associated with improved TTF, LRRFS, DMFS and OS in univariate analysis whereas good response at the primary tumor and lymph nodes remained significantly associated with TTF and OS after multivariate Cox PH models. Conclusions Locoregional response at 50.4 Gy was identified as predictor of oncologic outcome. PE during treatment should not be underestimated in clinical practice.

Background Diffusion-weighted magnetic resonance imaging (MRI) is being increasingly applied in clinical practice, for example in neuronavigation and in modern radiation treatment planning. Quality assurance (QA) is therefore important to avoid clinical errors. Purpose To compare four analytical programs and a neuronavigation tool to evaluate our in-house diffusion-weighted imaging protocol in order to be able to implement diffusion tensor imaging (DTI) into clinical practice. Material and Methods A phantom containing crossing fibers was used for the QA. Fiber tracking and fractional anisotropy (FA) analyses were performed, and the geometrical resolution was verified using the phantom. Results FA results were reproducible within each program and no significant differences between programs were observed. Also, no significant differences in FA values were found when comparing the results between the four software programs. Geometrical resolution of the anatomical data-set was satisfactory; however the crossing of the fibers was not accurately represented by three of the four programs. Conclusion Phantom QA is necessary before using DTI for novel procedures to identify the uncertainties associated with DTI data. It is important to remember that the results are software-dependent and that representation of the tracts may vary between software products. We therefore recommend caution with regard to the application of fiber tracking results intraoperatively when dealing with abnormal fiber tract anatomy.

The efficacy of concurrent chemoradiotherapy (CTRT) in locally advanced cervix cancer (LACC, stages IIB-IVA) is contentious. This is due to the variable extent of therapeutic benefit reported in different randomized clinical trials and meta-analyses that usually include all stages of cervix cancer. A systematic review and meta-analysis was therefore conducted to evaluate the efficacy of concurrent CTRT over radiotherapy (RT) alone, predominantly in LACC for the key endpoints; complete response (CR), long-term loco-regional control (LRC), overall survival (OS), grade III/IV acute and late toxicities. Six databases namely - PubMed, EMBASE, SCOPUS, Web of Science, Google Scholar and Cochrane library were explored and supplemented by hand-searching. Only prospective randomized trials conducted in LACC between concurrent CTRT and RT alone with no surgical interventions were included. Fourteen English language articles from 1788 citations were shortlisted for the final analysis. Of the 2445 patients evaluated (CTRT: n=1217; RT: n=1228), 95.7% had LACC and 96% had a squamous cell histology. Eight studies used cisplatin alone, 4 had cisplatin-based combination chemotherapy (CT) while 2 used mitomycin-C, either alone or in combination. CTRT improved the CR (+10.2%, p=0.027), LRC (+8.4%, p

OBJECTIVES: To conduct a central pathology review within a randomized clinical trial on salvage radiation therapy (RT) in the presence of biochemical recurrence after prostatectomy to assess whether this results in shifts of histopathological prognostic factors such as the Gleason Score. PATIENTS AND METHODS: A total of 350 patients were randomized and specimens of 279 (80%) of the patients were centrally reviewed by a dedicated genitourinary pathologist. The Gleason Score, tumor classification and resection margin status were reassessed and compared with the local pathology reports. Agreement was assessed using contingency tables and Cohen's Kappa. Additionally, the association between other histopathological features (e.g. largest diameter of carcinoma) with rapid biochemical progression (up to 6 months after salvage RT) was investigated. RESULTS: There was good concordance between central pathology review and local pathologists for seminal vesicle invasion [pT3b: 91%; k=0.95 (95% CI 0.89, 1.00)], for extraprostatic extension [pT3a/b: 94%; k=0.82 (95% CI 0.75, 0.89)], and for positive surgical margin status [87%; k=0.7 (95% CI 0.62, 0.79)]. Agreement was lower for Gleason score [78%; k=0.61 (95% CI 0.52, 0.70)]. The median largest diameter of carcinoma was 16 mm (range, 3-38 mm). A total of 49 patients (18%) experienced rapid biochemical progression after salvage RT. Largest diameter of carcinoma [odds ratio (OR): 2.04 (95% Confidence interval (CI): 1.30, 3.20); p = 0.002], resection margin status [OR: 0.36 (95% CI: 0.18, 0.72); p = 0.004] and Gleason score [OR: 1.55 (95% CI: 1.00, 2.42); p = 0.05] remained associated with rapid progression after salvage RT after backward selection. CONCLUSION: The results of the central pathology analyses reveal concordant results for seminal vesicle invasion, extraprostatic extension, positive surgical margin but lower agreement for Gleason Score. Largest diameter of carcinoma was found to be a potential prognostic factor for rapid biochemical progression after salvage RT. This article is protected by copyright. All rights reserved.

A systematic review with conventional and network meta-analyses (NMA) was conducted to examine the outcomes of loco-regional hyperthermia (HT) with radiotherapy (RT) and/or chemotherapy (CT) in locally advanced cervix cancer, IIB-IVA (LACC).A total of 217 abstracts were screened from five databases and reported as per PRISMA guidelines. Only randomised trials with HT and RT ± CT were considered. The outcomes evaluated were complete response (CR), long-term loco-regional control (LRC), patients alive, acute and late grade III/IV toxicities.Eight articles were finally retained. Six randomised trials with HTRT (n = 215) vs. RT (n = 212) were subjected to meta-analysis. The risk difference for achieving CR and LRC was greater by 22% (p .001) and 23% (p .001), respectively, with HTRT compared to RT. A non-significant survival advantage of 8.4% with HTRT was noted with no differences in acute or late toxicities. The only HTCTRT vs. RT trial documented a CR of 83.3% vs. 46.7% (risk difference: 36.7%, p = .001). No other end points were reported. Bayesian NMA, incorporating 13 studies (n = 1000 patients) for CR and 12 studies for patients alive (n = 807 patients), comparing HTCTRT, HTRT, CTRT and RT alone, was conducted. The pairwise comparison of various groups showed that HTRTCT was the best option for both CR and patient survival. This was also evident on ranking treatment modalities based on the "surface under cumulative ranking" values.In LACC, HTRT demonstrates a therapeutic advantage over RT without significant acute or late morbidities. On NMA, HTCTRT appears promising, but needs further confirmation through prospective randomised trials.

The aim of this study was to evaluate the outcomes of loco-regional hyperthermia (HT) with radiotherapy (RT) and/or chemotherapy (CT) in elderly patients with muscle-invasive bladder cancers (MIBC).Twenty consecutive MIBC patients were treated with HTRT (n = 8) or HTCTRT (n = 12) following transurethral resection of their bladder tumours. Weekly HT was administered prior to RT to a mean temperature of 40.6-42.7 °C for 60 min. A mean RT dose of 54.6 Gy (SD ± 4.2) was delivered. Single-agent cisplatin (n = 2) or carboplatin (n = 10) was used in HTCTRT patients.The median age was 81 years. HTRT patients received a mean RT dose of 51.0 Gy compared to 57.1 Gy with HTCTRT (p 0.001) in a shorter overall treatment time (OTT) (30.8 ± 6.9 versus 43.9 ± 4.0 days, p 0.001). All HTRT patients had long-term local disease control, while 41.6% of HTCTRT recurred during follow-up. None of the HTRT patients experienced grade III/IV acute and late toxicities, while these were evident in two and one HTCTRT patients respectively. Taken together, the 3-year bladder preservation, local disease-free survival, cause-specific survival and overall survival were 86.6%, 60.7%, 55% and 39.5% respectively. Even though the mean biological effective dose (BED) for both groups was similar (57.8 Gy15), the thermo-radiobiological BED estimated from HT-induced reduction of α/β was significantly higher for HTRT patients (91 ± 4.4 versus 85.8 ± 4.3 Gy3, p = 0.018).Thermal radiosensitisation with consequent reduction in α/β results in a higher thermo-radiobiological BED with a relatively higher RT dose/fraction and shorter OTT. This translates into a favourable outcome in elderly MIBC patients. Any benefit of CT in these patients needs further investigation.