[Home-based infusion therapy--a feasible approach for chronically ill patients? A new path to provide superior patient care exemplified for Fabry's disease]. / Infusionsbehandlung in häuslicher Umgebung--ein praktikabler Ansatz für chronisch Kranke? Neue Wege der Versorgung am Beispiel des Morbus Fabry.

BACKGROUND: As there are scarce data from Germany addressing home-based infusion therapy in chronically ill patients, a study on transferring infusion therapy from in-patient-treatment to home care, exemplified for Fabry's disease, was conducted. METHODS: A total of 69 patients on enzyme replacement infusion therapy (ERT with agalsidase alfa every two weeks) were enrolled in the open, non-controlled, multicentre, non-interventional observational study. After uneventful ERT in a hospital setting, intravenous treatment was administered at home by a specially-trained nurse. Primary outcome measure was change in patient satisfaction measured by an eleven-item Likert scale. RESULTS: The in-home observation period lasted between 96 und 401 days (median 180; IQR 166-184). Patient satisfaction increased significantly with home-based therapy (p = 0.001). A quality of life analysis (SF-36) demonstrated significant improvements in role-physical (p = 0.003), bodily pain (p = 0.032), vitality (p < 0.001), social functioning (p = 0.020), role-emotional (p = 0.007), mental well-being (p = 0.007) and mental sum score (p = 0.002). Home infusions turned out to be safe and were well tolerated. CONCLUSION: Chronically ill patients with need for regular infusion therapy may benefit from a home care setting. Home-based infusion therapy as exemplified by agalsidase alfa ERT in Fabry's disease is a viable option for patients who received uneventful infusions within the hospital.

Adjuvant vs. neoadjuvant radiochemotherapy for locally advanced rectal cancer: the German trial CAO/ARO/AIO-94.

AIM: The standard treatment for patients with clinically resectable rectal cancer is surgery. Postoperative radiochemotherapy (RCT) is recommended for advanced disease (pT3/4 or pN+). In recent years, encouraging results of pre-operative radiotherapy have been reported. This prospective randomized phase-III-trial (CAO/ARO/AIO-94) compares the efficacy of neoadjuvant RCT to standard postoperative RCT. We report on the design of the study and first results with regard to toxicity of RCT and postoperative morbidity. PATIENTS AND METHODS: Patients with locally advanced operable rectal cancer (uT3/4 or uN+, Mason CS III/IV) were randomly assigned to pre or postoperative RCT: A total dose of 50.4 Gy (single dose 1.8 Gy) was applied to the tumour and the pelvic lymph nodes. 5-FU (1000 mg/m2/d) was administered concomitantly in the 1th and 5th week of radiation as 120 h-continuous infusion. Four additional cycles of 5-FU-chemotherapy (500 mg/m2/d, i.v.-bolus) were applied. RCT was identical in both arms except for a small-volume boost of 5.4 Gy postoperatively. The time interval between RCT and surgery was 4-6 weeks in both arms. Techniques of surgery were standardized and included total mesorectal excision. Primary endpoints of the study are 5-year survival and local and distant control. Secondary endpoints include the rate of curative (R0) resection and sphincter saving procedures, toxicity of RCT, surgical complications and quality of life. RESULTS: As of July 2002, 805 patients were randomized from 26 participating institutions. Acute toxicity (WHO) of RCT was low, with less than 15% of patients experiencing grade 3 or higher toxicity: The principal toxicity was diarrhea, with 12% in the postoperative RCT-arm and 11% in the pre-operative RCT-arm having grade 3-, and 1% in either arm having grade 4-diarrhea. Erythema, nausea and leukopenia were the next common toxicities, with less than 3% of patients in either arm suffering grade 3 or greater leukopenia or nausea. Postoperative complication rates were similar in both arms, with 12% (postop. RCT) and 12% (pre-op. RCT) of patients, respectively, suffering from anastomotic leakage, 3% (postop. RCT) and 3% (pre-op. RCT) from postoperative bleeding, and 6% (postop. RCT) and 4% (pre-op. RCT) from delayed wound healing. CONCLUSION: The patient accrual to the trial is satisfactory. Neoadjuvant RCT is well tolerated and bears no higher risk for postoperative morbidity.

Regular intake of non-opioid analgesics is associated with an increased risk of restless legs syndrome in patients maintained on antidepressants.

OBJECTIVE: To evaluate prevalence and risk factors of restless legs syndrome (RLS) in secondary-care patients maintained on tricyclic and serotonin reuptake inhibiting antidepressants. METHOD: A total of 243 subjects with affective and anxiety disorders were interviewed for symptoms of RLS before and after at least 6 months of antidepressant pharmacotherapy within a naturalistic study. Logistic regression analysis was applied to adjust for the effects of age, gender, comorbidities, and the most frequent co-medications. RESULTS: The overall prevalence of RLS was 27%. In the RLS-affected patients, regular use or overuse of non-opioid analgesics frequently combined with caffeine was the major risk factor which significantly correlated with psychiatric and medical comorbidity. In a subsample of 172 patients who had seldom taken analgesics the prevalence of RLS was 9%, which corresponds with its prevalence in the general population. CONCLUSION: Neither antidepressants nor neuroleptics but non-opioid analgesics appear to be a major risk factor of RLS. Their regular use should be considered in studies of RLS-patients on psychotropic or other drugs. In this sample of secondary-care patients, ICD-10 classified depression or anxiety per se did not appear to be a risk factor of RLS.

Adjuvant versus neoadjuvant radiochemotherapy for locally advanced rectal cancer. A progress report of a phase-III randomized trial (protocol CAO/ARO/AIO-94).

AIM: The standard treatment for patients with clinically resectable rectal cancer is surgery. Postoperative radiochemotherapy is recommended for patients with advanced disease (pT3/4 or pN+). In recent years, encouraging results of preoperative radiotherapy have been reported. This prospective randomized phase-III trial (CAO/ARO/AIO-94) compares the efficacy of neoadjuvant radiochemotherapy to standard postoperative radiochemotherapy. We report on the design of the study and first results with regard to toxicity of radiochemotherapy and postoperative morbidity. PATIENTS AND METHODS: Patients with locally advanced operable rectal cancer (uT3/4 or uN+, Mason CS III/IV) were randomly assigned to pre- or postoperative radiochemotherapy: A total dose of 50.4 Gy (single dose 1.8 Gy) was applied to the tumor and the pelvic lymph nodes. 5-FU (1,000 mg/m2/d) was administered concomitantly in the first and fifth week of radiation as 120-h continuous infusion. Four additional cycles of 5-FU chemotherapy (500 mg/m2/d, i.v. bolus) were applied. Radiochemotherapy was identical in both arms except for a small-volume boost of 5.4 Gy in the postoperative setting. Time interval between radiochemotherapy and surgery was 4-6 weeks in both arms. Techniques of surgery were standardized and included total mesorectal excision. In addition, stratification according to surgeons involved has been provided for. Primary endpoints of the study are 5-year overall-survival, local and distant control, secondary endpoints include rate of curative (R0) resections and sphincter saving procedures, toxicity of radiochemotherapy, surgical complications and quality of life. RESULTS: As of 15th November 2000, 628 patients were randomized from 26 participating institutions: 310 patients were randomized to postoperative radiochemotherapy, 318 patients to preoperative radiochemotherapy. Acute toxicity (WHO) of radiochemotherapy was low, with less than 15% of patients experiencing Grade 3 or higher toxicity: The principal toxicity was diarrhea, with 12% in the postoperative radiochemotherapy arm and 10% in the preoperative radiochemotherapy arm having Grade-3, and 1% in either arm having Grade-4 diarrhea. Erythema, nausea and leukopenia were the next common toxicities, with less than 3% of patients in either arm suffering Grade 3 or greater leukopenia or nausea. Postoperative complication rates were similar in both arms, with 12% (postoperative radiochemotherapy) and 13% (preoperative radiochemotherapy) of patients, respectively, suffering from anastomotic leakage, 4% (postoperative radiochemotherapy) and 3% (preoperative radiochemotherapy) from postoperative bleeding, and 6% (postoperative radiochemotherapy) and 5% (preoperative radiochemotherapy) from delayed wound healing. CONCLUSION: The patient accrual of our trial is satisfactory, neoadjuvant radiochemotherapy is well tolerated and bears no higher risk for postoperative morbidity.

Efficacy of 'functional relaxation' in comparison to terbutaline and a 'placebo relaxation' method in patients with acute asthma. A randomized, prospective, placebo-controlled, crossover experimental investigation.

BACKGROUND: 'Functional relaxation' (FR) according to Marianne Fuchs is a body-oriented psychotherapy that involves teaching the patient a type of relaxation techniques aimed at maintaining equilibrium of the nervous system. METHODS: In order to determine whether the practice of elementary parts of this therapy has an immediate beneficial effect on pulmonary function, a randomized, single-blind, prospective crossover study was done with 21 asthmatics with acute bronchoconstriction. On 3 consecutive days they were given either (1) a 5-min verbal standard instruction in elementary exercises of FR (eFR), which they were to practice during subsequent bodyplethysmographic measurement or (2) inhalative terbutaline (IT), a beta(2)-sympathomimetic drug, or (3) an unspecific 'placebo relaxation' technique (PRT), so that all subjects tried all 3 treatments in random order. Spirometric variables were assessed. RESULTS: There was a significant decrease in specific airway resistance with eFR, which, though not as pronounced as with IT, was significantly greater than with PRT. This study shows that clinically relevant effects can be achieved for patients with asthma through mind-body interaction, which can be triggered by reproducible procedures. CONCLUSION: Further development of the FR approach could lead to a nonpharmacological and effective supplementary treatment for asthma, which is in high demand by many patients.

CEA and CA 19-9 measurement as a monitoring parameter in metastatic colorectal cancer (CRC) under palliative first-line chemotherapy with weekly 24-hour infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA).

BACKGROUND: There have been contradictory reports on the benefit of CEA and CA 19-9 measurements in patients with metastatic colorectal cancer using palliative chemotherapy. The object of this study was to examine the diagnostic accuracy of monitoring of palliative chemotherapy by means of CEA and CA 19-9. PATIENTS AND METHODS: The tumour markers CEA and CA 19-9 were subjected to serial measurement in patients with metastatic colorectal cancer (n = 90) using palliative first-line chemotherapy with weekly 24-hour infusion of high-dose 5-FU with FA and were compared with objective response according to WHO criteria. 85 patients could be evaluated. 43 patients (51%) initially had elevated CEA (> or = 10 ng/ml) and 33 patients (39%) elevated CA19-9 (> or = 50 IE/ml). In 24 patients (28%), both markers were initially increased. With CEA positive patients, 143 cycles of chemotherapy were carried out, which showed the following response in the various cycles: 21 episodes with progressions (ePD), 69 episodes with no change (eNC), 53 episodes with partial/complete remission (ePR/eCR). With CA 19-9 positive patients, 100 cycles of chemotherapy were carried out with the following results: 21 episodes with progressions (ePD), 48 episodes with eNC, and 31 episodes with ePR/eCR. RESULTS: A CEA rise by at least 50% differentiated between ePD versus eNC/ePR/eCR with a sensitivity of 76% and specificity of 90%. With CEA decreases of at least 30% in 99% of these patient episodes (78 of 79), a tumour progression could be excluded. Patients with an initial drop in CEA after the first cycle of chemotherapy of at least 50% of the initial level had a significantly higher probability of achieving an ePR/eCR in further therapy (relative risk 2.9; P = 0.002). With an CA 19-9 increase of at least 30%, a sensitivity progression of 62% and a specifity of 90% could be calculated. A CA 19-9 decrease of at least 60% excludes a progression in 95% of the patient episodes. CONCLUSIONS: A CEA or CA 19-9 rise is only conditionally appropriate for recording progressions. A progression however, can be excluded with falling levels with high diagnostic accuracy, in which CEA offers a greater degree of certainty than CA 19-9. With a drop in CEA 79 of 143 (= 55%) of the CT scans could be saved, in which case 78 of 79 patient episodes (99%) were correctly assessed as 'no progression'. In patients with an increased CEA and CA 19-9 the CEA determination is sufficient for the further monitoring. A confirmation of these results by multicenter trials can result in a considerable decrease of monitoring costs for palliative treatment.

Impact of surgery on survival in palliative patients with metastatic colorectal cancer after first line treatment with weekly 24-hour infusion of high-dose 5-fluorouracil and folinic acid.

BACKGROUND: In palliative first-line treatment of colorectal cancer, the secondary resection of distant metastases after downstaging has constantly gained in importance. The objective of this prospective study was to examine the tumor response rate, the toxicity, the median survival time and the prognostic impact of metastatic resection after downstaging of consecutively enrolled patients with primary nonresectable colorectal cancer treated with once weekly 24-hour (24-h) infusion of high-dose 5-fluorouracil (5-FU) and folinic acid. PATIENTS AND METHODS: Between January 1995 and July 1997, 53 consecutive patients with primary nonresectable metastases were recruited for a prospective phase II study. The patients received in out-patient care 500 mg/m2 folinic acid in the form of a 1-2-hour infusion followed by 2600 mg/m2 5-FU administered as a 24-h infusion once weekly. One treatment cycle comprised six weekly infusions followed by a two week rest. Three cycles were administered, and in the event of complete remission (CR) or partial remission (PR) and good tolerability, a fourth cycle was undertaken. Thereafter, the possibility of performing a curative metastatic resection was investigated. RESULTS: Of the 53 patients treated, 7 showed a CR (13%), 15 patients a PR (28%), 26 patients stable disease (SD) (49%), and 5 patients progressive disease (PD) (10%). As the main symptom of toxicity, diarrhea (CTC grade 3 + 4) was observed in 11 patients (21%), followed by leucocytopenia (CTC grade 3 + 4) in 2 patients (4%), and the hand-foot syndrome in 1 patient (2%). The median survival time was 17 months with a median follow-up of 41 months (range: 28-59 months). In 9 patients (17%), a secondary metastatic resection was considered; in 6 patients (11%) curative resection was performed, and 4 patients (8%) showed no evidence of disease for at least three years. CONCLUSION: In this phase II study, we have been able to show prospectively that, after downstaging by palliative treatment using a weekly 24-h infusion of high-dose 5-FU and folinic acid, secondary curative metastatic resection was technically feasible in 11% of the patients. For some of these patients, long-term survival is therefore possible. Secondary metastatic resection should be carried out in close interdisciplinary cooperation, and should be further investigated in prospective phase III studies.

Functional relaxation as a somatopsychotherapeutic intervention: a prospective controlled study.

CONTEXT: Functional relaxation is based on concentration on body perception while moving the joints of the skeleton smoothly and simultaneously breathing out. Case reports have shown that patients with headaches can profit from functional relaxation. OBJECTIVE: To examine whether patients with chronic tension headaches (International Headache Society diagnosis) who use functional relaxation as a complementary treatment will report less pain than before they learned this technique. DESIGN: Randomized, prospective, single-blind, controlled trial. Standardized elements of functional relaxation were compared to a placebo-relaxation technique, a simple isotomic exercise of the hand. SETTING: Primary care, ambulatory private practice. PARTICIPANTS: Twelve matched pairs were chosen according to age, sex, and initial pain intensity. This poststratification was performed on patients, who kept a complete pain diary covering 60 days before and 60 days after the introduction to the therapy. After a 45-minute introduction in small groups, the patients were told to do the exercises as often as possible for the following 2 months. MAIN OUTCOME MEASURES: Pain diary. RESULTS: In the functional-relaxation group, a significant reduction was found in the sum of total pain hours and in high- and medium-intensive pain (Wilcoxon signed rank test). CONCLUSIONS: This study supports the concept that this psychosomatic therapy can bring relief from tension headaches. This procedure can be viewed as an easy-to-learn relaxation technique to be used either prophylactic or complementary to pharmaceutical treatment.

Influence of optic disc size on neuroretinal rim shape in healthy eyes.

PURPOSE: To evaluate the influence of optic disc size on segmental neuroretinal rim area in healthy eyes. PATIENTS AND METHODS: The study included 193 eyes of 193 healthy patients with physiologic disc cupping. On 15 degrees color stereophotographic optic disc diapositives, optic disc area and neuroretinal rim area were morphometrically determined in 36 radial optic disc segments each measuring 10 degrees. RESULTS: The correlations of segmental rim area to disc area were significantly strongest (P < 0.01) and the regression lines were steepest in the inferior disc region, and the values were lowest in the temporal disc region. Complementary to the rim data, the correlations of segmental cup area to disc area were significantly strongest (P < 0.01) and the regression lines were steepest in the temporal disc region, and the values were lowest in the inferior disc region. In comparison with neuroretinal rim area, cup area was significantly (P < 0.01) more strongly correlated with disc area and the regression line was steeper in the whole optic disc and in each disc segment. The regional distribution of the widest rim part and smallest rim part was independent of disc size. CONCLUSIONS: The increase of rim area and cup area with increasing disc size differs between various disc regions. Because cup area increases more than rim area with increasing disc size, correction for disc size may be more important for segmental cup area than for segmental rim area. The rim shape with respect to the location of the smallest or broadest rim part is independent of disc size.

Concomitant radiochemotherapy with 5-FU and cisplatin for invasive bladder cancer. Acute toxicity and first results.

PURPOSE: To evaluate acute toxicity and efficacy of simultaneous radiochemotherapy for invasive urothelial cancer of the bladder. PATIENTS AND METHODS: From September 1993 to July 1997, 61 patients with invasive bladder cancer were treated with a transurethral resection (TURB) followed by radiochemotherapy (RCT). Twenty-five received a combination of 5-FU and cisplatin. The prescribed doses were 600 mg/m2 5-FU daily as continuous infusion over 5 days each in the 1st and 5th treatment week and 20 mg/m2 cisplatin daily at the same days as a short infusion. The pelvis was irradiated with 54 Gy, the bladder with 59.4 Gy and the paraaortic nodes in 7 cases with 45 Gy, respectively. Six to 8 weeks after RCT a second TURB was performed for reasons of restaging. RESULTS: Twenty out of 25 patients received at least 80% of the prescribed chemotherapy, in 13 cases the full dose could be given. Gastrointestinal toxicity of Grade I and II occurred in 10 cases, 1 patient developed severe diarrhea (Grade VI). After the 1st course of chemotherapy 7 patients had leuko- or thrombopenia of Grade III. One patient had a leucopenia of Grade IV. After the 2nd course 4 patients developed Grade III leuko- and thrombopenia, 1 of Grade IV. Two Grade II anemia were found. All more severe toxicities and necessary dose reductions were related to radiation of the paraaortic nodes. No life threatening infections, bleedings or cardiotoxicity was found. Restaging TURBs resulted in 22 complete remissions, 1 patient had a de-novo-carcinoma (Tis) at this time, 2 were non-responders (8%). After a median follow-up of 38 months 20 patients are alive (80%). CONCLUSIONS: 1. If irradiation of paraaortic nodes is necessary, 5-FU should not be applied, because the gastrointestinal toxicity is too extensive. In all other cases side effects are tolerable and can be managed by supportive care. 2. The first results are promising and should be evaluated in a prospective study.

[The acute toxicity of the simultaneous radiochemotherapy of rectal carcinoma]. / Akuttoxizität der simultanen Radiochemotherapie des Rektumkarzinoms.

AIM: We retrospectively examined the acute toxicity of (neo-)adjuvant combined treatment for rectal cancer in an attempt to evaluate potential factors that influence the severity of toxic side effects. PATIENTS AND METHOD: Between 1987 and 1995, 120 patients with rectal cancer (73 patients with primary tumor, 47 with recurrent disease) received chemoradiation for rectal cancer. Fifty-six patients received preoperative chemoradiation, 64 patients were treated postoperatively. Radiation was given by 4-field box technique with 6 to 10 MV-photons. Daily fraction size was 1.8 Gy, total dose 50.4 Gy (range: 41.4 to 56 Gy) +/- 5.4 Gy (range: 3.6 to 19.8 Gy) local boost in selected cases, specified to the ICRU reference point. During the first and fifth week of radiation 5-FU at a dose of 1000 m2/d for 120 hours was administered by continuous infusion. Toxicity was recorded following (modified) WHO-criteria. RESULTS: Acute grade 3 toxicity occurred mainly as diarrhea (33%), perineal skin reaction (37%), and leukopenia (10%). Extension of the treatment volume including paraaortic lymph nodes (L3) led to a significant increase of grade 3-diarrhea (68% vs. 25%, p = 0.0003) and grade 3-leukopenia (18% vs. 8%, p = 0.03). After abdominoperineal resection less patients suffered from grade 3-diarrhea (8% vs. 47% after sphincter preserving procedures, p = 0.0006), whereas severe perineal erythema occurred more frequently (56% vs. 29%, p = 0.02). Women had significantly more toxic side effects (grade 3-diarrhea: 39% vs. 16% in men, p = 0.04; grade 2 to 3-nausea/emesis: 21% vs. 8% in men, p = 0.018; grade 2 to 3-leukopenia 53% vs. 31% in men, p = 0.02). After preoperative chemoradiation a significant reduction of grade 3-diarrhea (11% vs 29%, p = 0.03) and grade 3-erythema (16% vs. 41%, p = 0.04) was noted. CONCLUSION: Treatment volume, type of surgery, sex and sequence of treatment modalities are the most important factors that influence the severity of toxic side effects. Individual adjustment of 5-FU dosage by monitoring its systemic clearance (which is lower in women) could help to avoid toxic side effects. The reduced acute toxicity of the preoperative approach provides a further argument in favor of the neoadjuvant chemoradiation for rectal cancer.

'Functional relaxation' reduces acute airway obstruction in asthmatics as effectively as inhaled terbutaline.

BACKGROUND: 'Functional relaxation' (German: 'Funktionelle Entspannung') has been developed since 1944 by the German physiotherapist M. Fuchs. It is based on concentrating on body perception while moving the joints of the skeleton smoothly and at the same time breathing out. This procedure induces a physical and emotional relaxation in many cases. The aim of the study was to compare the efficiency of standardized elements of a somatopsychotherapy (eFE) and a standardized bronchodilatative test using terbutaline (IT). METHODS: Seventeen asthmatic patients with acute airway obstruction had either IT or eFE on 2 consecutive days. Airway resistance (R(aw)) was measured before and after IT and eFE. It was used for statistical evaluation as it is independent of the patient's will. RESULTS: Although both therapies lead to a significant mean decrease in R(aw) (p < 0.01), the comparison revealed no superiority of one over the other (ANOVA on repeated measurements, p > 0.78). CONCLUSIONS: This study supports the benefit of psychosomatic therapy in the relief of asthma and the procedure can be used as an easy-to-learn relaxation technique to be used during acute asthmatic airway obstruction.

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.