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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.

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.

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.

Purpose To propose a roadmap and explore the cost implications of establishing a teleradiotherapy network to provide comprehensive cancer care and capacity building in countries without access to radiation therapy. Methods and Materials Ten low-income sub-Saharan countries with no current radiation therapy facilities were evaluated. A basic/secondary radiation therapy center (SRTC) with 2 teletherapy, 1 brachytherapy, 1 simulator, and a treatment planning facility was envisaged at a cost of 5 million US dollars (USD 5M). This could be networked with 1 to 4 primary radiation therapy centers (PRTC) with 1 teletherapy unit, each costing USD 2M. The numbers of PRTCs and SRTCs for each country were computed on the basis of cancer incidence, assuming that a PRTC and SRTC could respectively treat 450 and 900 patients annually. Results An estimated 71,215 patients in these countries will need radiation therapy in 2020. Stepwise establishment of a network with 99 PRTCs and 28 SRTCs would result in 155 teletherapy units and 96% access to radiation therapy. A total of 310 radiation oncologists, 155 medical physicists, and 465 radiation therapy technologists would be needed. Capacity building could be undertaken through telementoring by networking to various international institutions and professional societies. Total infrastructure costs would be approximately USD 860.88M, only 0.94% of the average annual gross domestic product of these 10 countries. A total of 1.04 million patients could receive radiation therapy during the 15-year lifespan of a teletherapy unit for an investment of USD 826.69 per patient. For the entire population of 218.32 million, this equates to USD 4.11 per inhabitant. Conclusion A teleradiotherapy network could be a cost-contained innovative health care strategy to provide effective comprehensive cancer care through resource sharing and capacity building. The network could also be expanded to include other allied specialties. The proposal calls for active coordination between all national and international organizations backed up by strong geopolitical commitment and action from all stakeholders.

A systematic review and meta-analysis was conducted to evaluate the outcome of controlled clinical trials in head and neck cancers (HNCs) using hyperthermia and radiotherapy versus radiotherapy alone.A total of 498 abstracts were screened from four databases and hand searched as per the PRISMA guidelines. Only two-arm studies treating HNCs with either radiotherapy alone, or hyperthermia and radiotherapy without concurrent chemotherapy or surgery were considered. The evaluated end point was complete response (CR).Following a detailed screening of the titles, abstracts and full text papers, six articles fulfilling the above eligibility criteria were considered. In total 451 clinical cases from six studies were included in the meta-analysis. Five of six trials were randomised. The overall CR with radiotherapy alone was 39.6% (92/232) and varied between 31.3% and 46.9% across the six trials. With thermoradiotherapy, the overall CR reported was 62.5% (137/219), (range 33.9-83.3%). The odds ratio was 2.92 (95% CI: 1.58-5.42, p = 0.001); the risk ratio was 1.61 (95% CI: 1.32-1.97, p 0.0001) and the risk difference was 0.25 (95% CI: 0.12-0.39, p 0.0001), all in favour of combined treatment with hyperthermia and radiotherapy over radiotherapy alone. Acute and late grade III/IV toxicities were reported to be similar in both the groups.Hyperthermia along with radiotherapy enhances the likelihood of CR in HNCs by around 25% compared to radiotherapy alone with no significant additional acute and late morbidities. This level I evidence should justify the integration of hyperthermia into the multimodality therapy of HNCs.

The economic viability of establishing a state-funded radiation therapy (RT) infrastructure in low- and middle-income countries (LMICs) in accordance with the World Bank definition has been assessed through computation of a return on investment (ROI).Of the 139 LMICs, 100 were evaluated according to their RT facilities, gross national income (GNI) per capita, and employment/population ratio. The assumption was an investment of US$5 million for a basic RT center able to treat 1000 patients annually. The national breakeven points and percentage of ROI (%ROI) were calculated according to the GNI per capita and patient survival rates of 10% to 50% at 2 years. It was assumed that 50% of these patients would be of working age and that, if employed and able to work after treatment, they would contribute to the country's GNI for at least 2 years. The cumulative GNI after attaining the breakeven point until the end of the 15-year lifespan of the teletherapy unit was calculated to estimate the %ROI. The recurring and overhead costs were assumed to vary from 5.5% to 15% of the capital investment.The %ROI was dependent on the GNI per capita, employment/population ratio and 2-year patient survival (all P.001). Accordingly, none of the low-income countries would attain an ROI. If 50% of the patients survived for 2 years, the %ROI in the lower-middle and upper-middle income countries could range from 0% to 159.9% and 11.2% to 844.7%, respectively. Patient user fees to offset recurring and overhead costs could vary from "nil" to US$750, depending on state subsidies.Countries with a greater GNI per capita, higher employment/population ratio, and better survival could achieve a faster breakeven point, resulting in a higher %ROI. Additional factors such as user fees have also been considered. These can be tailored to the patient's ability to pay to cover the recurring costs. Certain pragmatic steps that could be undertaken to address these issues are discussed in the present study.

QUESTIONS UNDER STUDY The aim of this retrospective analysis was to evaluate the safety and efficacy of local hyperthermia (HT) and reirradiation (ReRT) in the management of preirradiated locoregional recurrent breast cancers at Kantonsspital Aarau, Switzerland. METHODS Twenty-four previously irradiated patients who had developed locoregional recurrences in the chest wall or breast, with or without regional lymph node involvement, were reirradiated to a mean dose of 36.8 Gy (range 20-50 Gy) delivered at a mean dose per fraction of 2.33 Gy (range 1.8-4.0 Gy). All patients received local HT at 41 to 43 °C, once or twice a week prior to radiotherapy. Online thermometry was carried out during the hyperthermia sessions. RESULTS An overall objective response rate of 91.7% (22/24) with a complete response in 66.7% (16/24) of patients and partial response in 25% (6/24) of patients was observed. Post-thermoradiotherapy follow-up ranged from 1 to 38 months (median 10 months). The 3-year actuarial local control rate was 59.7%. More patients who attained complete response had sustained locoregional control until their death or last follow-up when compared with those who were partial or non-responders (median local disease-free survival for complete responders not reached; for partial and non-responders 4 months; p