M. Heinrich Seegenschmiedt

CONSENSUS GUIDELINES FOR RADIATION THERAPY OF BENIGN DISEASES: A MULTICENTER APPROACH IN GERMANY

PURPOSE To overcome the lack of written guidelines for radiation therapy (RT) of benign diseases, the German Working Group on Radiotherapy of Benign Diseases initiated a consensus process in 1999 to warrant continuous quality assurance and outcome research in this field. METHODS An expert panel was convened to define key issues and develop written guidelines for RT of benign diseases. Pertinent information and data from published literature were reviewed, and data of most importance were identified. In addition, a patterns of care study was conducted to obtain a nationwide survey on the current status and treatment standards. RESULTS From the data gathered, the expert panel prepared a first consensus statement that was open to propositions and comments from all participating institutions. After completion of the multicenter discussion, a final written consensus statement was compiled, discussed, and finally agreed on during a national conference of radiation therapists. For each individual nonmalignant disease, the accepted RT concepts were documented. Finally, specific evaluation tools and recommendations for follow-up examinations were defined. CONCLUSIONS For the first time, written consensus guidelines for RT of nonmalignant diseases have been developed by the interaction of all institutions involved. These guidelines may serve as a starting point for quality assessment, prospective clinical trials, and outcome research.

Radiation Therapy for Nonmalignant Diseases in Germany Current Concepts and Future Perspectives

Background:Radiotherapy (RT) of nonmalignant diseases has a long-standing tradition in Germany. Over the past decade significant theoretical and clinical progress has been made in this field to be internationally recognized as an important segment of clinical RT. This development is reflected in a national patterns-of-care study (PCS) conducted during the years 2001–2002.Material and Methods:In 2001 and 2002, a questionnaire was mailed to all RT facilities in Germany to assess equipment, patient accrual, RT indications, and treatment concepts. 146 of 180 institutions (81%) returned all requested data: 23 university hospitals (UNI), 95 community hospitals (COM), and 28 private institutions (PRIV). The specific diseases treated at each institution and the RT concepts were analyzed for frequencies and ratios between the different institution types. All data were compared to the first PCS in 1994–1996.Results:In 137 institutions (94%) 415 megavoltage units (mean 1.7; range 1–4), and in 78 institutions (53%) 112 orthovoltage units (mean 1.1; range 0–2) were available. A mean of 37,410 patients were treated per year in all institutions: 503 (1.3%) for inflammatory disorders, 23,752 (63.5%) for degenerative, 1,252 (3.3%) for hypertrophic, and 11,051 (29.5%) for functional, other and unspecified disorders. In comparison to the first PCS there was a significant increase of patients per year (from 20,082 to 37,410; +86.3%) in most nonmalignant diseases during the past 7–8 years. Most disorders were treated in accordance with the national consensus guidelines: the prescribed dose concepts (single and total doses) varied much less during the period 2001–2002 in comparison with the previous PCS in 1994–1996. Only five institutions (3.4%) received recommendations to change single or total doses and/or treatment delivery. Univariate analysis detected significant institutional differences in the use of RT for various disorders.Conclusion:RT is increasingly accepted in Germany as a reasonable treatment option for many nonmalignant diseases. The long-term perspective and research plan will have to include various updates of PCS, rewriting of consensus guidelines, introduction of registries for rare nonmalignant disorders, and clinical controlled studies even for so-called established indications, as international acceptance is based on the criteria of evidence-based medicine.Hintergrund:Die Radiotherapie (RT) nichtmaligner Erkrankungen hat eine lange Tradition in Deutschland. Im letzten Jahrzehnt wurden theoretische und klinische Fortschritte gemacht, die diesem Bereich der RT auch international eine erhebliche Bedeutung verschafft haben. Die positive Entwicklung stützt die jüngste Patterns-of-Care-Studie (PCS) der Jahre 2001–2002. Material und Methodik:Im Jahr 2001 und 2002 wurden anhand eines Fragebogens an allen deutschen strahlentherapeutischen Institutionen die technische Ausstattung, Patientenzuweisung, Indikationen und RT-Konzepte bei nichtmalignen Erkrankungen erfasst. 146 von 180 Institutionen (81%) machten vollständige Angaben: 23 Universitätskliniken (UNI), 95 Versorgungskrankenhäuser (COM) und 28 private Praxen (PRIV). Die einzelnen Krankheitsgruppen und Erkrankungen pro Institution und die RT-Konzepte wurden nach Häufigkeit und Verhältnis zwischen den Institutionen analysiert und mit der ersten PCS aus den Jahren 1994–1996 verglichen.Ergebnisse:In 137 Institutionen (94%) standen 415 Megavolt-Geräte (Mittel 1,7; Spanne 1–4) und in 78 Institutionen (53%) 112 Orthovolt-Geräte (Mittel 1,1; Spanne 0–2) zur Verfügung. Im Mittel wurden insgesamt 37 410 Patienten pro Jahr behandelt: 503 (1,3%) wegen entzündlicher, 23 752 (63,5%) wegen degenerativer, 1 252 (3,3%) wegen hyperproliferativer und 11 051 (29,5%) wegen funktioneller, anderer und nicht spezifizierter Erkrankungen. Im Vergleich zur ersten PCS vor 7–8 Jahren stieg die Patientenzahl pro Jahr signifikant an (von 20 082 auf 37 410; +86,3%). Die meisten Erkrankungen wurden gemäß den nationalen Konsensus-Leitlinien behandelt: Die Dosierungskonzepte (Einzel- und Gesamtdosis) schwankten im Zeitabschnitt 2001–2002 weit weniger als bei der vorherigen PCS von 1994–1996. Nur fünf Institutionen (3,4%) wurde aufgrund der eingereichten Daten eine Änderung der Einzel- und Gesamtdosis oder der Bestrahlungstechnik empfohlen. Es fanden sich univariat statistisch signifikante Unterschiede zwischen den einzelnen Institutionen und Krankheitsgruppen.Schlussfolgerung:Die RT wird in Deutschland zunehmend als Behandlungsoption für viele nichtmaligne Erkrankungen akzeptiert. Die langfristige Perspektive und Forschung auf diesem Gebiet müssen neben der Aktualisierung von PCS auch die Überarbeitung der Konsensus-Leitlinien, die Einführung von Registern für seltene Erkrankungen und die Durchführung kontrollierter Studien auch bei „etablierten Indikationen“ zum Ziel haben, da die internationale Akzeptanz allein auf den Kriterien der evidenzbasierten Medizin aufbaut.

RADIOTHERAPY IN PAINFUL HEEL SPURS (PLANTAR FASCIITIS)—RESULTS OF A NATIONAL PATTERNS OF CARE STUDY

PURPOSE After a general patterns of care study, the German Cooperative Group on Radiotherapy for Benign Diseases conducted a multicenter cohort study to analyze radiotherapy (RT) in painful heel spur syndrome (HSS). METHODS AND MATERIALS In 2001, a patterns of care study was conducted in all German RT institutions using a standardized structured questionnaire. Patient accrual, patient number, pretreatment, pain record, treatment indications, RT technique, and target volume concepts for painful HSS were assessed. In addition, the functional and subjective outcomes were evaluated. RESULTS Of the institutions, 146 (79.3%) returned the questionnaire: 10 (6.8%) reported no clinical experience with RT for HSS, and 136 (93.2%) treated 3621 patients annually, a median of 23 cases/institution. The indications for treatment were chronic or therapy refractory pain. The total dose ranged between 2.5 and 18.75 Gy (median 6), and single fractions ranged between 0.3 and 1. 5 Gy (median 1). Of the responding institutions, 44.9% applied two fractions and 37.5% three fractions weekly. RT was delivered with orthovoltage units (38.2%), linear accelerators (53.7%), (60)Co units (5.1%), or other treatment units (3%). Seventy-six institutions presented their retrospective clinical evaluation in a total of 7947 patients. Pain reduction for at least 3 months was reported in 70%, and persistent pain reduction was reported in 65% of the treated patients. In 19 institutions, a second RT series was applied for inadequate pain response or early pain recurrence. No radiogenic acute or chronic side effects were observed. CONCLUSION The study comprised the largest number of cases reported of RT for painful HSS. Despite variations in the daily RT practice, this national patterns of care study represents a very large number of painful and refractory HSS cases that were treated effectively with RT.

Radiotherapy for Symptomatic Vertebral Hemangiomas: Results of a Multicenter Study and Literature Review

PURPOSE The current study analyzes the potential role of radiotherapy (RT) in symptomatic vertebral hemangioma (SVH). METHODS AND MATERIALS Seven cooperating German institutions collected clinical information, treatment plans, and outcome data for all patients with SVH referred for local RT. RESULTS From 1969 to 2008, a total of 84 patients with 96 symptomatic lesions were irradiated for SVH. The primary indication for radiotherapy was pain (97.6%), and 28.6% of patients had additional neurological symptoms. RT was performed at a median total dose of 34 Gy, with a median single dose of 2.0 Gy. After receiving a median follow-up of 68 months, the overall patient response rate was 90.5%. Complete symptom remission occurred in 61.9% of patients, 28.6% of patients had partial pain relief, and 9.5% of patients had no pain relief. In 26.2% of patients, radiological signs of reossification were observed in long-term follow-up but not significantly correlated with pain relief. Most importantly, total doses of >/=34 Gy resulted in significantly greater symptomatic relief and control rate than total doses of <34 Gy. CONCLUSIONS This study consists of the largest database of cases reported so far using RT for SVH. RT is easy, safe, and effective for pain relief treatment for SVH. Total doses of at least 34 Gy give the best symptomatic response.

Radiation Therapy for Nonmalignant Diseases in Germany

Background:Radiotherapy (RT) of nonmalignant diseases has a long-standing tradition in Germany. Over the past decade significant theoretical and clinical progress has been made in this field to be internationally recognized as an important segment of clinical RT. This development is reflected in a national patterns-of-care study (PCS) conducted during the years 2001–2002.Material and Methods:In 2001 and 2002, a questionnaire was mailed to all RT facilities in Germany to assess equipment, patient accrual, RT indications, and treatment concepts. 146 of 180 institutions (81%) returned all requested data: 23 university hospitals (UNI), 95 community hospitals (COM), and 28 private institutions (PRIV). The specific diseases treated at each institution and the RT concepts were analyzed for frequencies and ratios between the different institution types. All data were compared to the first PCS in 1994–1996.Results:In 137 institutions (94%) 415 megavoltage units (mean 1.7; range 1–4), and in 78 institutions (53%) 112 orthovoltage units (mean 1.1; range 0–2) were available. A mean of 37,410 patients were treated per year in all institutions: 503 (1.3%) for inflammatory disorders, 23,752 (63.5%) for degenerative, 1,252 (3.3%) for hypertrophic, and 11,051 (29.5%) for functional, other and unspecified disorders. In comparison to the first PCS there was a significant increase of patients per year (from 20,082 to 37,410; +86.3%) in most nonmalignant diseases during the past 7–8 years. Most disorders were treated in accordance with the national consensus guidelines: the prescribed dose concepts (single and total doses) varied much less during the period 2001–2002 in comparison with the previous PCS in 1994–1996. Only five institutions (3.4%) received recommendations to change single or total doses and/or treatment delivery. Univariate analysis detected significant institutional differences in the use of RT for various disorders.Conclusion:RT is increasingly accepted in Germany as a reasonable treatment option for many nonmalignant diseases. The long-term perspective and research plan will have to include various updates of PCS, rewriting of consensus guidelines, introduction of registries for rare nonmalignant disorders, and clinical controlled studies even for so-called established indications, as international acceptance is based on the criteria of evidence-based medicine.Hintergrund:Die Radiotherapie (RT) nichtmaligner Erkrankungen hat eine lange Tradition in Deutschland. Im letzten Jahrzehnt wurden theoretische und klinische Fortschritte gemacht, die diesem Bereich der RT auch international eine erhebliche Bedeutung verschafft haben. Die positive Entwicklung stützt die jüngste Patterns-of-Care-Studie (PCS) der Jahre 2001–2002. Material und Methodik:Im Jahr 2001 und 2002 wurden anhand eines Fragebogens an allen deutschen strahlentherapeutischen Institutionen die technische Ausstattung, Patientenzuweisung, Indikationen und RT-Konzepte bei nichtmalignen Erkrankungen erfasst. 146 von 180 Institutionen (81%) machten vollständige Angaben: 23 Universitätskliniken (UNI), 95 Versorgungskrankenhäuser (COM) und 28 private Praxen (PRIV). Die einzelnen Krankheitsgruppen und Erkrankungen pro Institution und die RT-Konzepte wurden nach Häufigkeit und Verhältnis zwischen den Institutionen analysiert und mit der ersten PCS aus den Jahren 1994–1996 verglichen.Ergebnisse:In 137 Institutionen (94%) standen 415 Megavolt-Geräte (Mittel 1,7; Spanne 1–4) und in 78 Institutionen (53%) 112 Orthovolt-Geräte (Mittel 1,1; Spanne 0–2) zur Verfügung. Im Mittel wurden insgesamt 37 410 Patienten pro Jahr behandelt: 503 (1,3%) wegen entzündlicher, 23 752 (63,5%) wegen degenerativer, 1 252 (3,3%) wegen hyperproliferativer und 11 051 (29,5%) wegen funktioneller, anderer und nicht spezifizierter Erkrankungen. Im Vergleich zur ersten PCS vor 7–8 Jahren stieg die Patientenzahl pro Jahr signifikant an (von 20 082 auf 37 410; +86,3%). Die meisten Erkrankungen wurden gemäß den nationalen Konsensus-Leitlinien behandelt: Die Dosierungskonzepte (Einzel- und Gesamtdosis) schwankten im Zeitabschnitt 2001–2002 weit weniger als bei der vorherigen PCS von 1994–1996. Nur fünf Institutionen (3,4%) wurde aufgrund der eingereichten Daten eine Änderung der Einzel- und Gesamtdosis oder der Bestrahlungstechnik empfohlen. Es fanden sich univariat statistisch signifikante Unterschiede zwischen den einzelnen Institutionen und Krankheitsgruppen.Schlussfolgerung:Die RT wird in Deutschland zunehmend als Behandlungsoption für viele nichtmaligne Erkrankungen akzeptiert. Die langfristige Perspektive und Forschung auf diesem Gebiet müssen neben der Aktualisierung von PCS auch die Überarbeitung der Konsensus-Leitlinien, die Einführung von Registern für seltene Erkrankungen und die Durchführung kontrollierter Studien auch bei „etablierten Indikationen“ zum Ziel haben, da die internationale Akzeptanz allein auf den Kriterien der evidenzbasierten Medizin aufbaut.

Radiotherapy for prevention of disease progression in early-stage Dupuytren's contracture: Initial and long-term results

PURPOSE Radiotherapy (RT) was given to prevent disease progression in early-stage Dupuytrens contracture. Initial response, long-term outcome, and treatment toxicity were evaluated. METHODS Between 1982 and 1993, 96 patients (142 hands) received orthovoltage RT, which consisted of two courses with daily fractionation of 5 x 3 Gy (total dose 30 Gy) separated by a 6-week interval. The extent of disease was staged according to the classification of Tubiana et al.. Initial evaluation was performed 3 months after completion of RT; long-term outcome was analyzed at last follow-up (i.e., between February and April 1994). The mean follow-up was 6 +/- 2 (range 1-12) years. Fifty-seven patients with a minimum follow-up of 5 (median 7.5; mean 9.5-12) years were separately evaluated for long-term outcome (i.e., prevention of disease progression). Acute and late treatment toxicity was assessed using the Radiation Therapy Oncology Group/EORTC criteria. RESULTS According to stage, 130 cases (92%) remained stable at 3 months follow-up, 10 improved (7%), and 2 progressed (1%). An objective reduction of symptomatic cords and nodules was achieved in 107 cases (75%) at 3 months follow-up. Moreover, 87% of the patients reported a subjective relief of symptoms. In long-term follow-up, only 16 of 142 cases (11%) had progressed according to stage. In the group with minimum follow-up 5 years (n = 57), 44 patients (77%) experienced no disease progression, whereas 13 progressed (23%) inside [8 cases (14%)] or outside [5 cases (9%)] of the RT field. Most failures could have been avoided with appropriate choice of larger safety margins included in the treated portals; however, the failures outside were still amenable for another RT course. CONCLUSION Radiotherapy is effective to prevent disease progression for early-stage Dupuytrens contracture. Thus, it helps to avoid an otherwise necessary surgical procedure which is performed in adavanced stages of Dupuytrens contracture.

RADIATION THERAPY FOR TREATMENT OF PIGMENTED VILLONODULAR SYNOVITIS: RESULTS OF A NATIONAL PATTERNS OF CARE STUDY

PURPOSE The German Cooperative Group on Radiotherapy in Benign Diseases (GCG-BD) conducted a pattern-of-care study (PCS) to analyze the radiation therapy (RT) practice for pigmented villonodular synovitis (PVNS). METHODS AND MATERIALS In 2007, a structured questionnaire to assess the number of patients, the pretreatments, the RT indication, technique, target volume concepts, outcome data, and possible early or late toxicity was circulated to 227 institutions. RESULTS Until August 2008, a response was available from 189 institutions (83.2 %), of whom 19 (10.0 %) experienced RT for PVNS. Complete clinical information was available for 41 patients from 14 RT departments. Thirty patients (73.2 %) received postsurgical RT because of primary incomplete resection, 11 patients (26.8 %) as an adjunct after complete resections of recurrences or unclear resection status. The total doses ranged from 30 to 50 Gy (median, 36 Gy), the median single dose was 2.0 Gy. Local control was achieved 95.1%, and 82.9% had no or only slight functional impairment. The early and late toxicity was mild (<or=RTOG Grade II). CONCLUSIONS Radiation therapy is a safe and effective treatment for PVNS in the postoperative setting after incomplete resection, and also as a salvage option for treatment of recurrences it provides a high rate of local control.

Demographic, clinical and treatment related predictors for event-free probability following low-dose radiotherapy for painful heel spurs – a retrospective multicenter study of 502 patients

A total of 502 patients treated between 1990 and 2002 with low-dose radiotherapy (RT) for painful heel spurs were analysed for prognostic factors for long-term treatment success. The median follow-up was 26 months, ranging from 1 to 103 months. Events were defined as (1) slightly improved or unchanged pain after therapy, or (2) recurrent pain sensations during the follow-up period. Overall 8-year event-free probability was 60.9%. Event-free probabilities of patients with one/two series (414/88) were 69.7%/32.2% (p <0.001); >58/ ≤58 years (236/266), 81.3%/47.9% (p =0.001); high voltage/orthovoltage (341/161), 67.9%/60.6% (p =0.019); pain anamnesis ≤6 months/ >6 months (308/194), 76.3%/43.9% (p =0.001); single dose 0.5/1.0 Gy (100/401), 86.2%/55.1% (p =0.009); without/with prior treatment (121/381), 83.1%/54.9% (p =0.023); men/women (165/337), 61.2%/61.5% (p =0.059). The multivariate Cox regression analysis with inclusion of the number of treatment series, age, photon energy, pain history, single-dose and prior treatments revealed patients with only one treatment series (p <0.001), an age >58 years (p =0.011) and therapy with high voltage photons (p =0.050) to be significant prognostic factors for pain relief. Overall low-dose RT is a very effective treatment in painful heel spurs.

Low-dose radiotherapy for painful heel spur. Retrospective study of 117 patients

Purpose:Retrospective analysis of 117 patients treated between 1996 and 2000 with low-dose radiotherapy (RT) for painful heel spurs.Patients and Methods:71 women and 46 men were irradiated on 136 painful heel spurs in one (n = 104) or two radiation series (n = 13). The painful spurs were located either at the plantar (n = 94), dorsal (n = 5) or bilateral heel (n = 18). 82 patients had prior treatments, in 35 patients RT was the primary treatment. Low-dose RT was performed twice a week with one 6-MV photon field. Ten fractions of 0.5 Gy were applied to a total dose of 5 Gy. Evaluation was done on completion and during follow-up using the four-scale von Pannewitz score.Results:On completion of RT, 27 patients were free of pain, 40 were much improved, 31 reported slight improvement, and 19 experienced no change. After a mean follow-up of 20 months, 75 out of 100 patients were free of pain, twelve had marked and three some improvement. Ten patients reported no change of symptoms. Mean duration of pain before RT was 6 months. RT applied ≤ 6 months after the onset of clinical symptoms resulted in improvement in 94%. By contrast, an interval of > 6 months until the initiation of RT resulted in only 73% of patients with clinical improvement.Conclusion:Low-dose RT reveals a benefit in > 80% of the patients. RT should start during the first 6 months of symptoms. Prospective clinical studies with validated symptom scores should be conducted to assess optimal dose and fractionation scheme of RT.Ziel:Analyse der analgetischen Radiotherapie (RT) von 117 Patienten mit schmerzhaftem Fersensporn, die von 1996 bis 2000 behandelt wurden.Patienten und Methodik:71 Frauen und 46 Männer mit einem Altersmedian von 58 Jahren (30–84 Jahre) und 136 Fersenspornen (links n = 43, rechts n = 55, beide n = 19) wurden in einer (n = 104) oder zwei Serien (n = 13) bestrahlt. 94-mal lag ein plantarer, fünfmal ein dorsaler und 18-mal ein beidseitiger Fersensporn vor. 82 Patienten berichteten über vorher durchgeführte Therapien, bei 35 Patienten wurde die RT als erste Maßnahme eingesetzt. Die RT erfolgte zweimal pro Woche mit einem 6-MV-Photonen-Stehfeld mit 0,5 Gy Einzeldosis bis zu einer Gesamtdosis von 5,0 Gy. Die Therapieergebnisse wurden am Ende und aktuell nach dem Von-Pannewitz-Score bewertet (Tabelle 1).Ergebnisse:Direkt nach RT waren 27 Patienten schmerzfrei, 40 Patienten gaben eine wesentliche Besserung, 31 Patienten eine leichte Besserung sowie 19 Patienten keine Beeinflussung an (Tabelle 1). Mit einem medianen Follow-up von 20 Monaten (1–63 Monate) waren 03/2001 von 100 untersuchten Patienten 75 schmerzfrei, zwölf gaben eine wesentliche Besserung, drei eine Besserung und zehn keine Beeinflussung an (Tabelle 1). Bei einer medianen Schmerzdauer vor RT von 6 Monaten (1–60 Monate) führte der Beginn der RT im Intervall ≤ 6 Monate (n = 70) bei 94,2% zu einer Schmerzkontrolle, im Gegensatz dazu im Intervall > 6 Monate (n = 30) bei 72,8% (Abbildung 1).Schlussfolgerung:Die RT mit 6-MV-Photonen ist bei über 80% der behandelten Patienten langfristig erfolgreich. Die RT sollte innerhalb der ersten 6 Monate nach Symptombeginn erfolgen. Weitere prospektive Untersuchungen mit validierten Scores sollten durchgeführt werden.

Multivariate analysis of prognostic parameters using interstitial thermoradiotherapy (IHT-IRT): Tumor and treatment variables predict outcome

PURPOSE From January 1986 to October 1991, 90 patients with localized tumors were treated in a Phase I/II trial using low-dose 192Ir brachytherapy (IRT) plus interstitial 915 MHz microwave (MW) hyperthermia (IHT) and external beam radiotherapy (ERT). Tumors were classified as locally advanced primary (class 1: 27), recurrent (class 2: 40), metastatic (class 3: 10) and persistent (class 4: 13) lesions. The treatment sites included tumors of the head and neck (62), pelvis (26), and others (2). The mean cuboidal tumor volume was 63 cm3 (range: 8-288 cm3). Most recurrent and metastatic lesions (48) had received prior treatment including ERT. METHODS AND MATERIALS The treatment protocol prescribed two heating sessions (each 60 min) at 41-44 degrees C before and after IRT. One hundred sixty-one IHT sessions were evaluated. Invasive thermal data were recorded at an average of 18 sites throughout the implant volume. Several thermal variables were analyzed (e.g., averaged parameters: Tmaxav, Tmean, Tminav; index parameters: T10, T50, T90). The study was evaluated with a minimum follow up (FU) of one year. Median follow-up was 19 months. RESULTS At 3 months FU, a complete response (CR) was observed in 59 of 90 (66%) patients. At 12 months FU, local control (LC) was achieved in 54 of 84 (64%) evaluable patients. Ten patients developed a local and 14 a regional recurrence (REC) after achieving a CR and/or LC. At last FU, a total of 31 (34%) patients were still alive and 28 (31%) patients had relapse-free survival. For all 90 patients, the median overall survival was 20 months and the median relapse-free survival was 17 months. Overall and relapse-free survival was significantly longer for primary and persistent lesions as compared to recurrent and metastatic lesions (p = 0.002; p < 0.001). Totally 22 (24%) patients experienced acute or subacute side-effects (Grade 1: 12 patients; Grade 2: eight patients; Grade 3: two patients). CONCLUSION Univariate logistic regression analysis revealed significant dependencies of CR, LC and REC upon tumor parameters as well as radiation and thermal parameters. The overall and relapse free survival was associated with tumor and radiation parameters. The multivariate analysis revealed two independent predictors of CR: tumor volume and minimum tumor temperature variables. We conclude, that IHT-IRT is a safe and effective treatment. The results provide important implications for planning HT-RT studies and for defining quality assurance (QA) criteria and thermal performance standards in HT studies.