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On 2 July 2021, Kronenfeld et al. [...].

Simple Summary This retrospective study reports on 10 patients with radiation-associated angiosarcoma of the breast and chest wall treated during the past decade. In this rare disease local control is highly dependent on the extent of surgery. Further treatment options are urgently needed. Re-iradiation in combination with localized hyperthermia should be considered for adjuvant and definitive treatment of nonresectable radiation-associated angiosarcomas. The presented hypofractionated re-irradiation schedule with 5 × 4 Gy once per week immediately following wIRA-hyperthermia is a promising option to further reduce the radiation dose recommended so far. This could reduce side effects without compromising local control. Abstract Background: Radiation-associated angiosarcoma of the breast (RAASB) is a rare, challenging disease, with surgery being the accepted basic therapeutic approach. In contrast, the role of adjuvant and systemic therapies is a subject of some controversy. Local recurrence rates reported in the literature are mostly heterogeneous and are highly dependent on the extent of surgery. In cases of locally recurrent or unresectable RAASB, prognosis is very poor. Methods: We retrospectively report on 10 consecutive RAASB patients, most of them presenting with locally recurrent or unresectable RAASB, which were treated with thermography-controlled water-filtered infrared-A (wIRA) superficial hyperthermia (HT) immediately followed by re-irradiation (re-RT). Patients with RAASB were graded based on their tumor extent before onset of radiotherapy (RT). Results: We recorded a local control (LC) rate dependent on tumor extent ranging from a high LC rate of 100% (two of two patients) in the adjuvant setting with an R0 or R2 resection to a limited LC rate of 33% (one of three patients) in patients with inoperable, macroscopic tumor lesions. Conclusion: Combined HT and re-RT should be considered as an option (a) for adjuvant treatment of RAASB, especially in cases with positive resection margins and after surgery of local recurrence (LR), and (b) for definitive treatment of unresectable RAASB.

Effective tumor control in patients suffering from unresectable locally recurrent breast cancer (LRBC) in pre-irradiated areas can be achieved by re-irradiation combined with superficial hyperthermia. Using this combined modality, total re-irradiation dose and toxicity can be significantly reduced compared to conventionally fractionated treatment schedules with total doses of 60&ndash, 66 Gy. Applying contact-free, thermography-controlled water-filtered infrared-A superficial hyperthermia, immediately followed by hypofractionated re-irradiation, consisting of 4&thinsp, Gy once per week up to a total dose of 20&thinsp, Gy, resulted in high overall response rates even in large-sized tumors. Comparability of clinical data between different combined Hyperthermia (HT)/Radiotherapy (RT) treatment schedules is impeded by the highly individual characteristics of this disease. Tumor size, ranging from microscopic disease and small lesions to large-sized cancer en cuirasse, is described as one of the most important prognostic factors. However, in clinical studies and analyses of LRBC, tumor size has so far been reported in a very heterogeneous way. Therefore, we suggest a novel, simple and feasible size classification (rClasses 0&ndash, IV). Applying this classification for the evaluation of 201 patients with pre-irradiated LRBC allowed for a stratification into distinct prognostic groups.

On 2 July 2021, Kronenfeld et al. [...]

Evaluation of the efficacy and toxicity of a new setup of thermographically controlled water-filtered infra-red-A (wIRA) superficial hyperthermia (HT) combined with hypofractionated re-irradiation (re-RT) to treat large-sized breast cancer recurrences.Records of 73 heavily pre-irradiated patients with 103 treatment regions, treated from September 2009 to July 2015 were retrospectively analysed. Sixty-four patients with macroscopic disease were treated with 94 regions including 46 patients with lymphangiosis carcinomatosa. Hypofractionated RT consisted of 4 Gy once per week up to a total dose of 20 Gy delivered within 1-4 min after wIRA-HT. Heating of tumour nodules and diffusely spreading cancer lesions was performed under real-time thermographic temperature monitoring, maintaining the maximum skin temperature in the ROI between 42 °C and 43 °C, achieving intratumoural temperatures up to a depth of 2 cm between 39.5 °C and 42 °C. Seventeen patients received re-re-irradiation (re-re-RT) using the same HT/RT-treatment schedule.Response rates in patients with macroscopic disease: 61% CR, 33% PR, 5% NC and 1% PD. Local control throughout life time after CR of macroscopic disease: 59%. All nine patients with microscopic disease had CR and local control throughout lifetime. Only grade 1 toxicities were observed.Application of thermographically controlled wIRA-HT combined with extremely low-dose re-irradiation provides good local control throughout lifetime of heavily pre-treated breast cancer recurrences. The twin wIRA radiator provides a sufficiently homogeneous heat deposition for the treatment of larger areas. The time lag between HT and re-RT is substantially reduced. The possibility of re-re-RT opens new therapeutic options for the future.

Thermography-controlled, water-filtered infrared-A (wIRA) is a novel, effective and approved heating technique listed in the ESHO quality assurance guidelines for superficial hyperthermia clinical trials (2017). In order to assess the special features and the potential of wIRA-hyperthermia (wIRA-HT), detailed and updated information about its physical and photobiological background is presented. wIRA allows for (a) application of high irradiances without skin pain and acute grade 2-4 skin toxicities, (b) prolonged, therapeutically relevant exposure times using high irradiances (150-200 mW/cm

We intend to analyse retrospectively whether the time interval (‘‘gap duration’’ /GD) between preoperative radiotherapy and surgery in locally advanced rectal cancer (LARC) has an impact on overall survival (OS), cancer specific survival (CSS), disease free survival (DFS) and local control (LC). Two hundred seventy nine patients with LARC were entered in Trial 93-01 (hyperfractionated accelerated radiotherapy 41.6 Gy/26 Fx BID) shortly followed by surgery. From these 250 patients are fully assessable. The median GD of 5 days was used as a discriminator. The median follow-up for all patients was 39 months. GD � /5 days was a significant discriminator for actuarial 5-years OS (69% vs 47%, p /0.002), CSS (82% vs 57%, p /0.0007), DFS (62% vs 41%, p /0.0003) but not for LC (93% vs 90%, p /non-significant). In multivariate analysis, the following factors independently predict outcome; for OS: age, GD, circumferential margin (CM) and nodal stage (ypN); for CSS: GD, ypN and vascular invasion (VI); for DFS: CEA, distance to anal verge, GD, ypN and VI; for LC: CM only. Gap duration predicts survival outcome but not local control. The patients submitted to surgery after a median delay of more than 5 days had a significantly better outcome. Surgery is the mainstay of treatment in rectal cancer [19]. The incidence of local recurrence should be well below 15% provided surgery is performed according to the now well accepted surgical standard, which is a total (TME) or a partial mesorectal excision with sharp dissection. Nevertheless, preoperative radiotherapy yields a significant better local control and in some trials a positive impact on survival [1015]. In the randomized trials, in which a clear benefit in favour of 5 times 5 Gy has been reported, the interval between the end of radiotherapy and surgery is very short. In the Swedish rectal cancer trial (SRCT) the patients are submitted to surgery immediately after the weekend [15]. In the Dutch ColoRectal Cancer Group trial (DCRCG), the overall treatment time between the start of the radiotherapy and the surgery has to be within 10 days [13]. Therefore, in these trials the analysis of the impact of the timing of surgery after the end of radiotherapy is difficult to perform. In Trial 93-01, a prospective non-randomized phase II trial on hyperfractionated accelerated radiotherapy (HART) in locally advanced resectable rectal cancer (LARC), there is a variation of the GD. Therefore, we are able to analyze the importance of the GD on patient’s outcome.

Purpose To determine whether the application of two courses of cisplatin simultaneously with hyperfractionated radiotherapy improves the outcome in locally advanced and/or node-positive nonmetastatic carcinomas of the head and neck, compared with hyperfractionated radiotherapy alone. Patients and Methods From July 1994 to July 2000, 224 patients with squamous cell carcinomas of the head and neck (excluding nasopharynx and paranasal sinus) were randomly assigned to hyperfractionated radiotherapy (median dose, 74.4 Gy; 1.2 Gy twice daily) or the same radiotherapy combined with two cycles of concomitant cisplatin (20 mg/m2 on 5 days of weeks 1 and 5). The primary end point was time to any treatment failure; secondary end points were locoregional failure, metastatic relapse, overall survival, and late toxicity. Results There was no difference in radiotherapy between both treatment arms (74.4 Gy in 44 days). The full cisplatin dose was applied in 93% and 71% of patients during the first and second treatment cycles, respectively. Acute toxicity was similar in both arms. Median time to any treatment failure was not significantly different between treatment arms (19 months for combined treatment and 16 months for radiotherapy only, respectively) and the failure-free rate at 2.5 years was 45% and 33%, respectively. Locoregional control and distant disease–free survival were significantly improved with cisplatin (log-rank test, P = .039 and .011, respectively). The difference in overall survival did not reach significance (log-rank test, P = .147). Late toxicity was comparable in both treatment groups. Conclusion The therapeutic index of hyperfractionated radiotherapy is improved by concomitant cisplatin.

Mit einer exakt ausgefuhrten totalen mesorektalen Exzision (TME) konnen in der Behandlung des Rektumkarzinoms allein durch die chirurgische Technik sehr gute Resultate errecht werden, wie aus der neueren Literatur hervorgeht. Dennoch bleiben der alleinigen Chirurgie anatomische und tumorbiologische Grenzen gesetzt, welche der Einsatz adjuventer Masnahmen rechtfertigen. In unseren Handen hath sich die praoperative hyperfraktionierte akzelerierte Radiotherapie mit 41,6 Gy, TME und postoperative Chemotherapie mit 5-FU als Therapieschema zur lokoregionaren Beherrschung der Erkrankung bewahrt, zumal in einer durchschnittlichen Nachbeobachtungszeit von zweieinhalb Jahren einzig bei einem von 50 Patienten ein Kokalrezidiv aufgetreten ist, was einer Lokalrezidivrate von 2% entspricht. Problematisch bleibt aber weiterhin die Fernmetastasierung, in unseren Fallen bei 12% der initial RO-resezierten Patienten und ausschlieslich in Form von Lebermetastasen, welche Ziel weiterer Studien zur systemischen Behandlung des Leidens sein sollte.

BACKGROUND AND PURPOSE: Radiotherapy (RT) is well accepted for therapy-refractory palmo-plantar eczema or psoriasis, despite of lacking evidence regarding beneficial long term effects. Furthermore, the optimal irradiation dose is unknown. We evaluated the outcome of RT with two different RT single/total dose (SD/TD) treatment policies. PATIENTS AND METHODS: 28 consecutive patients with therapy-refractory eczema (n = 22) or psoriasis (n = 6) of palms and/or soles were irradiated twice a week either with a D(max) SD of 1 Gy (6/98-5/03; median TD: 12 Gy) or 0.5 Gy (6/03-7/04; median TD: 5 Gy). Median age was 52 years (27-71), median follow-up 20 months (4-76). Totally 88 regions were treated, 49 with 1 Gy, 39 with 0.5 Gy SD. Eight different symptoms were scored from 0 (absent) -3 (severe), giving a possible sum score of 0-24. Patients' rating of RT result was also documented (worse/stable/better/complete remission). RESULTS: The sum score was 15 (6-23) before RT, 2 (0-16) at the end of RT, and 1 (0-21) at last follow-up, respectively. The improvement was highly significant in both treatment regimens. Better or complete remission by the patients were reported in 44 and 39 (= 83 out of 88) localisations, that was often stable during the follow-up. 5 (6%) regions in 3 (11%) patients didn't benefit from RT. CONCLUSION: RT reveals excellent results in palmo-plantar eczema or psoriasis. We recommend a SD of 0.5 Gy twice a week up to a TD of 4-5 Gy.

Background and purpose: We aim to report on local control in a phase II trial on preoperative hyperfractionated and accelerated radiotherapy schedule (HART) in locally advanced resectable rectal cancer (LARC). This fractionation schedule was designed to keep the overall treatment time (OTT) as short as possible. Patients and methods: This is a prospective trial on patients with UICC stages II and III rectal cancer. The patients were submitted to a total dose of 41.6 Gy, delivered in 2.5 weeks at 1.6 Gy per fraction twice a day with a 6-h interfraction interval. Surgery was performed within 1 week after the end of irradiation. Adjuvant chemotherapy was delivered in a subset of patients. Results: Two hundred and seventy nine patients were entered and 250 are fully assessable, with a median follow-up of 39 months. The 5-years actuarial local control (LC) rate is 91.7%. The overall survival (OS) is 59.6%. The freedom from disease relapse (FDR) is 71.5%. Downstaging was observed in 38% of the tumors. Conclusion: The actuarial LC at 5 years is 91.7%, although we are dealing with stages II–III LARC, mainly located in the lower rectum (median distanceZ5 cm). The pattern of failure is dominated by distant metastases and treatment intensification will obviously require a systemic approach. q 2006 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 79 (2006) 52–58.

In this study factors are analyzed that may potentially influence the site of failure in pediatric medulloblastoma. Patient-related, disease-related, and treatment-related variables are analyzed with a special focus on radiotherapy time-dose and technical factors.Eighty-six children and adolescents with a diagnosis of medulloblastoma were treated in Switzerland during the period 1972-1991. Postoperative megavoltage radiotherapy was delivered to all patients. Simulation and portal films of the whole-brain irradiation (WBI) fields were retrospectively reviewed in 77 patients. The distance from the field margin to the cribiform plate and to the floor of the temporal fossa was carefully assessed and correlated with supratentorial failure-free survival. In 19 children the spine was treated with high-energy electron beams, the remainder with megavoltage photons. Simulation and port films of the posterior fossa fields were also reviewed in 72 patients. The field size and the field limits were evaluated and correlated with posterior fossa failure-free survival.In 36 patients (47%) the WBI margins were judged to miss the inferior portion of the frontal and temporal lobes. Twelve patients failed in the supratentorial region and 9 of these patients belonged to the group of 36 children in whom the inferior portion of the brain had been underdosed. On multivariate analysis only field correctness was retained as being significantly correlated with supratentorial failure-free survival (p = 0.049). Neither the total dose to the spinal theca nor the treatment technique (electron vs. photon beams) were significantly correlated with outcome. Posterior fossa failure-free survival was not influenced by total dose, overall treatment time, field size, or field margin correctness. Overall survival was not influenced by any of the radiotherapy-related technical factors.A correlation between WBI field correctness and supratentorial failure-free survival was observed. Treatment protocols should be considered that limit supratentorial irradiation mainly to subsites at highest risk of relapse. Optimized conformal therapy or proton beam therapy may help to reach this goal. Treating the spine with electron beams was not deletereous. A significant correlation between local control and other technical factors was not observed, including those relating to posterior fossa treatment. The use of small conformal tumor bed boost fields may be prefered to the larger posterior fossa fields usually considered as the standard treatment approach.

Purpose The combination of hyperthermia (HT) with radio(chemo)therapy or chemotherapy (CT) is an established treatment strategy for specific indications. Its application in routine clinical practice in Europe depends on regulatory and local conditions. We conducted a survey among European clinical centers to determine current practice of HT. Methods A questionnaire with 22 questions was sent to 24 European HT centers. The questions were divided into two main categories. The first category assessed how many patients are treated with HT in combination with radio(chemo)therapy or CT for specific indications per year. The second category addressed which hyperthermia parameters are recorded. Analysis was performed using descriptive methods. Results The response rate was 71% (17/24) and 16 centers were included in this evaluation. Annually, these 16 centers treat approximately 637 patients using HT in combination with radio(chemo)therapy or CT. On average, 34% (range: 3–100%) of patients are treated in clinical study protocols. Temperature readings and the time interval between HT and radio(chemo)therapy or CT are recorded in 13 (81%) and 9 (56%) centers, respectively. The thermal dose quality parameter “cumulative equivalent minutes at 43 °C” (CEM43°C) is only evaluated in five (31%) centers for each HT session. With regard to treatment sequence, 8 (50%) centers administer HT before radio(chemo)therapy and the other 8 in the reverse order. Conclusion There is a significant heterogeneity among European HT centers as to the indications treated and the recording of thermometric parameters. More evidence from clinical studies is necessary to achieve standardization of HT practice.

Background: Moderate hyperthermia is a potent and evidence-based radiosensitizer. Several indications are reimbursed for the combination of deep hyperthermia with radiotherapy (dHT+RT). We evaluated the current practice of dHT+RT in Switzerland. Methods: All indications presented to the national hyperthermia tumor board for dHT between January 2017 and June 2021 were evaluated and treatment schedules were analyzed using descriptive statistics. Results: Of 183 patients presented at the hyperthermia tumor board, 71.6% were accepted and 54.1% (99/183) finally received dHT. The most commonly reimbursed dHT indications were “local recurrence and compression” (20%), rectal (14.7%) and bladder (13.7%) cancer, respectively. For 25.3% of patients, an individual request for insurance cover was necessary. 47.4% of patients were treated with curative intent; 36.8% were in-house patients and 63.2% were referred from other hospitals. Conclusions: Approximately two thirds of patients were referred for dHT+RT from external hospitals, indicating a general demand for dHT in Switzerland. The patterns of care were diverse with respect to treatment indication. To the best of our knowledge, this study shows for the first time the pattern of care in a national cohort treated with dHT+RT. This insight will serve as the basis for a national strategy to evaluate and expand the evidence for dHT., Cancers, 14 (5)