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Gamma knife radiosurgery of radiation-induced intracranial tumors: local control, outcomes, and complications.

PURPOSE: To determine local control (LC) and complication rates for patients who underwent radiosurgery for radiation-induced intracranial tumors. METHODS AND MATERIALS: Review of a prospectively maintained database (2,714 patients) identified 16 patients (20 tumors) with radiation-induced tumors treated with radiosurgery between 1990 and 2004. Tumor types included typical meningioma (n=17), atypical meningioma (n=2), and schwannoma (n=1). Median patient age at radiosurgery was 47.5 years (range, 27-70 years). The median tumor margin dose was 16 Gy (range, 12-20 Gy). Median follow-up was 40.2 months (range, 10.8-146.2 months). Time-to-event outcomes were calculated with Kaplan-Meier estimates. RESULTS: Three-year and 5-year LC rates were 100%. Three-year and 5-year overall survival rates were 92% and 80%, respectively. Cause-specific survival rates at 3 and 5 years were 100%. Three patients died: 1 had in-field progression 65.1 months after radiosurgery and later died of the tumor, 1 died of progression of a preexisting brain malignancy, and 1 died of an unrelated cause. One patient had increased seizure activity that correlated with development of edema seen on neuroimaging. CONCLUSIONS: LC, survival, and complication rates in our series are comparable to those in previous reports of radiosurgery for intracranial meningiomas. Also, LC rates with radiosurgery are at least comparable to those of surgical series for radiation-induced meningiomas. Radiosurgery is a safe and effective treatment option for radiation-induced intracranial tumors, most of which are typical meningiomas.

Adult↗

Pulsed ultrasound measurements of depth and regression of basal cell carcinomas after photodynamic therapy: relationship to probability of 1-year local control.

BACKGROUND: The regression of clinical basal cell carcinoma (BCC) after photodynamic therapy (PDT) is poorly understood, but is potentially important when, as is increasingly the case, a second treatment is contemplated. High-frequency pulsed ultrasound provides noninvasive information on skin and lesion thickness. OBJECTIVES: To relate pulsed ultrasound measurements before and after PDT to the probability of local control of BCC by PDT. METHODS: Skin thickness and lesion thickness were measured by 20-MHz pulsed ultrasound in 181 patients diagnosed as having BCC. Maximal lesion thickness was determined by repeatedly sampling the BCCs. Measurements were made immediately prior to PDT with aminolaevulinic acid plus 630 nm visible light, and then at 1, 6 and 12 months. RESULTS: Skin thickness in individual patients did not vary with time in this study (mean +/- SD 2.3 +/- 0.6 mm; P = 0.8). In contrast, BCC mean +/- SD maximal thickness 4-6 weeks after PDT was significantly smaller than pretreatment (0.6 +/- 0.8 mm vs. 1.3 +/- 0.8 mm; P < 0.001). The overall probability of 1-year local control fell from 85% when only BCCs </= 1.5 mm thick were considered, to 75% when BCCs up to 3 mm were included. CONCLUSIONS: Ultrasound measurement of maximal pretreatment BCC thickness strongly predicts the probability of local control, defined clinically, at 1 year after a single PDT treatment. The degree of regression at 4-6 weeks is additionally predictive.

Aged↗

Mucosal melanoma of the head and neck: the impact of local control on survival.

The management for mucosal melanoma of the head and neck is controversial in view of the poor prognosis. Thirty-five patients seen from 1955 to 1991 were analyzed retrospectively. Almost all (34/35) presented with localized disease. Primary treatments included radical surgery (15), local resection (11), radiation therapy (6), or systemic treatment (2). While the rate of local recurrence was high (27/34), only 5 patients developed distant disease before local relapse. Furthermore, only 5/21 achieved successful local salvage. Patients with their disease controlled locally had significantly longer survival than those with persistent local disease (P = .0001). The 5-year disease-specific survival was 45%. The authors conclude that mucosal melanoma of the head and neck is not necessarily incurable. When local control is achieved, survival rate is significantly improved. Aggressive local treatments should be initiated at presentation of this disease.

Actuarial Analysis↗

Local control of murine subglottis development.

OBJECTIVE: To determine if subglottic development is at least partially under local control and to determine which tissue layer(s) is predominantly responsible. DESIGN: The suglottises of 12 day-3 CD1 mice were grown in whole organ culture. The 12 subglottises were divided into 3 individual groups: +++, -++, and ---. Group+++ had all tissue layers of the subglottis intact: luminal epithelium, cricoid cartilage, inner and outer perichondrium. Group-++ had all layers intact with the exception of luminal epithelium. Group--- had all layers removed (luminal epithelium, inner and outer perichondrium) resulting in cricoid cartilage-only rings. All rings were grown in basic medium without the use of growth factors or serum for 15 days. Measurements of the rings were taken before and after organ culture growth. RESULTS: Group+++ was the only group that experienced growth. Only luminal growth was statistically significant although all rings experienced growth in both the luminal and external diameter. Group-++ did not experience any growth. Group--- lost structural integrity with collapse of the ring and did not experience growth of any dimension of the cartilage. CONCLUSIONS: Growth of the subglottis is under local control but may have additional influences from the outside that were not investigated here. Removal of just the epithelium stunts growth of the entire ring, but preferentially the lumen more so than the external diameter. Removal of all tissue layers around the cricoid cartilage results in a structural collapse of the ring, suggesting that the cartilage in this age group is dependent on surrounding tissues for structural integrity.

Animals↗

The effect of dose on local control of prostate cancer.

Three patterns of care outcome surveys in prostate cancer totalling 1516 patients had been combined and analyzed for the effect of dose on infield recurrence. There are significant dose effects observed in the overall data (1516 patients, p = .003), Stage B cancers (725 patients, p = .004) and Stage C cancers (624 patients, p = .059). No dose effect was observed for Stage A cancers (168 patients, p = .217) within the dose range observed (5500 cGy to greater than 7000 cGy). For patients with Stage B cancer one may conclude that dose between 6000 cGy and 6999 cGy is appropriate. Patients treated to less than 6000 cGy show a highly significant increase in local failure. Patients treated to greater than 7000 cGy do not show a demonstrable improvement in local control, but do show an increase in complications. Patients with Stage C cancer appear to require dose that is equal or greater than 7000 cGy to obtain the best local control, and the potential increased morbidity of these high doses appears to be justified in this stage of the disease. Patients who have been given hormonal therapy more than 1 month prior to radiation therapy show an increase in local failure rate for all stages of cancer. This is presumed to be the selection of poor risk patients for adjuvant hormonal treatment or by referring non-responding hormone treated patients for radiation therapy. Histologic grade exerts a major influence on local failure for patients with Stage C disease (p = less than .001), identifying an important stratification point for prospective clinical trials and a sub-group for which it is important to develop strategies for improving local control. The policy of treating all stages of prostate cancer with the same dose is not supported by these data.

Dose-Response Relationship, Radiation↗

Prognostic factors for local control in nasopharyngeal cancer (NPC): analysis by multivariate proportional hazard models.

Despite the development of meticulous radiation therapy techniques, the local control of the nasopharyngeal cancer (NPC) remains unsatisfactory. We examined retrospectively the clinicopathologic factors which have impact upon local recurrence-free survival (LRFS) of the 67 patients with NPC who had been irradiated greater than or equal to 40 Gy with curative intent from 1975 through 1988. Three-year LRFS rate was 63%. T stage, histology, the presence of accompanying lymphocytic infiltration, and the properness of radiation therapy had influence upon LRFS with a statistical significance. Multivariate proportional hazard models showed that T stage and pathology retained significance. Radiation therapy properness emerged as a third factor when only the patients irradiated greater than or equal to 60 Gy were included in the analysis. From these results, three groups with low, moderate, and high risk of shortened LRFS could be separated. This risk classification could contribute to the stratification criteria of future study for the improvement of local control by new modalities.

Adult↗

Impact of overall treatment time on local control of anal cancer treated with radiochemotherapy.

Between 1987 and 2000, 111 patients with epidermoid anal cancer (T1-T4 Nx M0) were assigned to primary simultaneous radiochemotherapy (RCT) with a radiation dose of 45 Gy, performed either as a split course with 2-Gy single fractions (schedule A, 1987-1996, n = 65 patients) or continuously with fractions of 1.8 Gy (schedule B, 1996-2000; n = 38 patients). The chemotherapy consisted of continuous infusions of 5-fluorouracil (5-FU; 800/1,000 mg/m(2)/day, on 4/5 consecutive days, during weeks 1 and 5) together with one (schedule A) or two (schedule B) short infusions of mitomycin C (10 mg/m(2)) during the first course of 5-FU. Associations between clinical outcome and various prognostic factors were assessed in 103 patients who completed these schedules. For both patient groups combined, 5-year local control rate was 67% and 5-year survival rate 71%. Advanced tumor stage, size, and nodal status significantly decreased the 5-year local control rate as well as the overall treatment time (OTT) >41 days (58% for OTT >41 days vs. 79% for OTT < or =41 days; p = 0.04). However, we did not find a correlation with the prescribed radiotherapy schedule (A or B). In conclusion, in patients with anal carcinomas treated with RCT with a radiation dose of 45 Gy, the predominant determinant of local control is the resulting OTT and not the administration schedule (split course or continuous radiotherapy).

Adult↗

Thoracic radiotherapy variables: influence on local control in small cell lung cancer limited disease.

In limited small cell lung cancer (LSCLC), the high local failure rate of chemotherapy by itself (60-100%) and with the addition of external beam radiotherapy (approximately 30%) has led to investigation of methods to improve local control. To that end, we integrated Platinum 60 mg/m2, d. 1, 22 and Etoposide 120 mg/m2, d. 4, 6, & 8; 25, 27 & 29 with concurrent twice-daily 150 cGy (total dose: 4500 cGy). Of 32 consecutively referred patients, 4 with variant histology, 31 were evaluable for toxicity, response, and survival. Two of 4 variant histology patients responded, and 27 of 27 pure small cell responded, p = 0.005. CT scans were inaccurate at forecasting survival. Of 17/32 patients considered "positive," 59% of these were survivors; of those considered "negative," 47% were survivors, p = N.S. Radiation portals were volumetrically conservative; the supraclavicular fossa was included infrequently and the contralateral hilum not at all. Local failure occurred in only 1/27 patients (4%). All four variant patients failed locally, p = 0.001. With a median follow-up of 43 months, the actuarial disease-free survival remains nearly 50%. Variant histology is more predictive of local control than the physical factors of dose or volume.

Antineoplastic Combined Chemotherapy Protocols↗

CT number distribution and its association with local control and as a marker of lung tumor response to radiation.

An early noninvasive indicator of tumor response to therapy and the ability to predict clinical outcome may potentially enhance disease management. Currently, however, tumor response to therapy is often delayed, potentially compromising disease management. We examined the computed tomography (CT) number or Hounsfield unit distribution to follow lung tumor response to radiation treatment. To help interpret the results, we examined whether the CT number distribution follows a simple two-component model. The CT number distribution was derived from a CT-simulator for 11 patients with lung cancer before and after the initial radiation treatment (1-1.5 months, average 3,407 cGy). Clinical outcomes were followed in 8 patients who received 5,580-6,660 cGy. All patients were scanned serially, using identical radiation imaging parameters (voltage, current, scan time, and slice thickness) in a CT-simulator. The lung tumors were digitally contoured, and software windows were applied to avoid inclusion of lung tissue in the analysis. Histograms and statistical analysis of the CT numbers for the tumor were generated. Radiation-induced CT number or Hounsfield unit (HU) shifts exceeding a threshold (13 HU) in lung tumors were associated with (P=0.04) local control (> or = 10 months). Initial lung tumor size (below 100 cm3) was less well-associated with local control (P=0.26). The change in standard deviation of the CT numbers (derived from the more careful contouring and using software windows) induced by radiation treatment correlated with the change in average CT number (R2=0.71). The change in standard deviation did not correlate with a change in tumor volume (R2=0.02). Radiation treatments reduced the average CT number (P < 0.001). In summary, radiation reduces the CT number and this reduction may be associated with local control at 10 months. A two-component model is consistent with lung tumor number distribution and its response to radiation.

Adult↗

Improved local control of nasopharyngeal carcinoma after intracavitary brachytherapy boost.

In 1976 we began using intracavitary cesium boost technique as a portion of comprehensive treatment of primary T2 and T3 nasopharyngeal carcinoma. At first, we offered this procedure sporadically to patients with T1 lesions. For the past 10 years, intracavitary boost has been offered to all patients except those with T4 lesions. The radiation therapy program consists of external beam dose of 60-64 Gy, either once daily (q.d.) or twice daily (b.i.d.) schedule, followed by 10-15 Gy boost to mucosal surface by intracavitary implant, making a total of approximately 75 Gy. This article presents the experience at the Massachusetts General Hospital with 146 patients with T1-3 carcinoma of the nasopharynx irradiated from 1970 through 1988. Seventy-six patients were treated with intracavitary boost and 70 patients were treated up to 65-70 Gy by external beam alone. The overall 5-year actuarial local control rate for the T1 lesions was 93% after radiation therapy and intracavitary boost as compared with 54% without brachytherapy boost (p value = 0.057). For the T1-2 lesions, the corresponding local rates after external radiation therapy and brachytherapy boost and after external beam irradiation without boost were 90 and 59%, respectively, with p = 0.001. For the T3 lesions, the rates were 100 and 64%, respectively, with p = 0.090. The reason for improved local control is unclear and may be due to a somewhat higher mucosal dose to the nasopharynx. Hopefully, the improved beneficial local control effects may be reflected in improved patient survival. However, such data require a controlled randomized clinical trial for confirmation.

Brachytherapy↗

Immediate postoperative radiotherapy in residual nonfunctioning pituitary adenoma: beneficial effect on local control without additional negative impact on pituitary function and life expectancy.

PURPOSE: To demonstrate the benefit of immediate postoperative radiotherapy in residual nonfunctioning pituitary adenoma (NFA) in perspective to the need for hormonal substitution and life expectancy. METHODS AND MATERIALS: Retrospective cohort analysis of 122 patients, operated for NFA between 1979 and 1998. Recurrence was defined as regrowth on computed tomography or magnetic resonance imaging. The occurrence of hormonal deficiencies was defined as the starting date of hormonal substitution therapy. RESULTS: Seventy-six patients had residual NFA after surgery and received immediate postoperative radiotherapy (Group 1); three patients developed a recurrence, resulting in a 95% local control rate at 10 years. Twenty-eight patients had residual NFA after surgery, but were followed by a wait-and-see policy (Group 2). Sixteen developed a recurrence, resulting in a local control rate of 49% at 5 years and 22% at 10 years (p < 0.001 compared with Group 1). There were no differences between Group 1 and 2 regarding the need for substitution with thyroid hormone, glucocorticoids, and sex hormones before first surgery, directly after surgery and at end of follow-up. There were no differences in hormone substitution free survival between Group 1 and Group 2 during the study period after first surgery. Life expectancy was similar in Group 1 and 2, and their median life expectancy did not differ from median life expectancy in the general population. CONCLUSIONS: Immediate postoperative radiotherapy provides a marked improvement of local control among patients with residual NFA compared with surgery alone, without an additional deleterious effect on pituitary function and life expectancy.

Adenoma↗

Effect on local control and survival of electron beam intraoperative irradiation for resectable pancreatic adenocarcinoma.

PURPOSE: To assess the impact on local control and survival of intraoperative radiotherapy (IORT) in resectable pancreatic adenocarcinoma. METHODS AND MATERIALS: The outcome of 127 patients surgically treated with curative intent combined with IORT was compared with the therapeutic results of 76 patients treated with surgery as exclusive treatment. RESULTS: Operative mortality and morbidity were similar in IORT and no-IORT patients. In 49 patients with locally limited disease (Stage I-II; LLD), IORT (n = 30) reduced the local failure rate and significantly prolonged time to local failure (TTLF), time to failure (TTF), and overall survival (OS) with respect to surgery alone (n = 19). The multivariate analyses, stratifying patients by age, tumor grade, resection margins, chemotherapy, and external-beam radiotherapy use, confirmed the independent impact of IORT on outcome. In patients with locally advanced disease (Stage III-IVA; LAD), IORT had an impact on local failure rate and on TTLF when combined with beam energies of greater than 6 MeV, whereas no effect on TTF and OS was observed. CONCLUSION: IORT did not increase operative mortality and morbidity and achieved a significant improvement in local control and outcome in patients with LLD. In patients with LAD, beam energies greater than 6 MeV prolonged TTLF.

Adenocarcinoma↗

Influence of bone invasion and extent of mandibular resection on local control of cancers of the oral cavity and oropharynx.

The aim of this paper was to evaluate the influence of bone invasion on treatment outcome among patients with cancers of the oral cavity and oropharynx and to determine whether or not outcome was influenced by the extent of mandibular resection. A review of 127 prospectively documented patients who were treated with marginal or segmental resection for oral (n = 110) and oropharyngeal (n = 17) cancers was undertaken. There were 97 males and 30 females with a median age of 61 years. Clinical T stages were: T1 17 patients, T2 33, T3 22, T4 55. Median followup was 4 years. A total of 94 patients underwent marginal resections and 33 underwent segmental resections. Histological bone invasion was present in 17 patients (16%) in the marginal resection group and 21 patients (64%) in the segmental group (P<0.05). Soft tissue surgical margins were positive in 11 patients (12%) in the marginal group and in seven patients (21%) in the segmental group (P=not significant). Local control did not correlate significantly with T stage, the extent of mandibular resection or the presence of histological bone invasion, but was significantly influenced by positive soft tissue margins (P<0.01). Among patients with bone invasion, the local control rate was higher following segmental resection when compared to marginal resections (87% vs 75%) but this was not statistically significant. Survival was significantly influenced by positive soft tissue margins but not bone invasion or the type of resection. We conclude that bone invasion alone did not predict for local control or survival rates among patients with oral and oropharyngeal cancers. Involved soft tissue margins were highly predictive of local recurrence and decreased survival. Conservative resection of the mandible is safe as long as marginal mandibulectomy does not lead to compromise of soft tissue margins. Segmental resection should be reserved for patients extensive bone invasion or those with limited invasion in a thin atrophic mandible.

Adult↗

Local control of veins: biomechanical, metabolic, and humoral aspects.

The incidence of vein diseases (varicosity, thrombophlebitis, phlebosclerosis, orthostatic intolerance) is extremely high. In several countries it may exceed that of the arterial pathology by an order of magnitude. In the last decades, this recognition and the rapid accumulation of experimental data have resulted in a progressive reevaluation of the physiological significance of the venous system, which had been rather neglected earlier by scientists. The major aim of this review is to provide a critical survey of recent selected literature related to different physiological functions of the venous system as well as to biomechanical, metabolic, and humoral (ionic, hormonal) aspects of the local venous control. Local neural control mechanisms, including effects of catecholamines and other transmitters, are regarded to be beyond the scope of this work. At present, the synthesis of information available in the literature meets certain difficulties, because occasionally poorly defined methodological techniques and physiological parameters have been applied. On the other hand, a significant part of works dealing with venous physiology is excellent and inspirational. We have good reason to believe that the fast accumulation of reliable scientific data on this very important field will soon reach a new critical level, then an even more effective integration of knowledge will be possible.

Animals↗

Radiotherapy for solitary extramedullary plasmacytoma in the head-and-neck region: A dose greater than 45 Gy to the target volume improves the local control.

PURPOSE: Our aim was to determine the dose to the clinical target volume (CTV) required for solitary extramedullary plasmacytoma (EMP) in the head and neck (HN). METHODS AND MATERIALS: Seventeen patients (15 Stage I and 2 Stage II) were treated for HN EMP at our institution between 1979 and 2003. The mean International Commission on Radiation Units (ICRU) dose prescribed to the CTV was 52.6 Gy (range, 40-65 Gy) over 24 fractions (range: 20-30). The Stage II patients received neck irradiation doses of 40 and 60 Gy. A mean dose of 36.4 Gy was used for 5 Stage I patients who received elective neck irradiation. Dose administrated to the CTV was evaluated from dosimetric data or from planning films when dosimetric data were not available. Two groups of patients were distinguished: CTV covered with a dose greater than 40 Gy and CTV covered with a dose greater than 45 Gy. RESULTS: The 5-year local control was 72.8%. It was 100% for patients who received dose to the CTV > or = [DOSAGE ERROR CORRECTED] 45 Gy vs. 50% for dose to the CTV <45 Gy (p = 0.034). The prognostic factor for 5-year disease-specific survival (81.6%) was local control (p = 0.058). The prognostic factors for disease-free survival (64.1%) were monoclonal immunoglobulin secretion (p = 0.008) and a CTV dose > or = 45 Gy (p = 0.056) CONCLUSIONS: Local control of EMP in the HN seems to be improved when the dose to the CTV is > or = [DOSAGE ERROR CORRECTED] 45 Gy. A minimum dose of 45 Gy should be recommended to the CTV.

Adult↗

Can pretreatment CT predict local control of T2 glottic carcinomas treated with radiation therapy alone?

PURPOSE: To determine whether pretreatment CT can predict local control of T2 squamous cell carcinoma of the glottic larynx treated with radiation therapy alone. METHODS: Pretreatment CT studies were retrospectively evaluated by two head and neck radiologists in 28 patients with T2 squamous cell carcinoma of the glottic larynx treated with definitive radiation therapy. All patients were followed for a minimum of 2 years. A tumor score was calculated based on the CT findings of tumor involvement of the following areas: the anterior commissure, the contralateral true vocal cord, the arytenoid face, the interarytenoid region, the laryngeal ventricle, the paraglottic space at the true and false vocal cord levels, and the subglottic region. Tumor volumes based on pretreatment CT were measured in each patient using a computer digitizer. Statistical analysis was performed using the independent sample t test, Wilcoxon's rank sum test, and Fisher's Exact Test. RESULTS: There was no statistically significant relationship between tumor volume or tumor score and outcome of the T2 glottic tumors treated with definitive radiation therapy in this series. The overall local control rate was 82%. There were no treatment complications that resulted in loss of laryngeal function. CONCLUSIONS: Like low-volume supraglottic and T3 glottic carcinomas, T2 glottic squamous cell carcinoma is likely (82%) to be controlled with definitive radiation therapy. Failure to control the primary tumor is attributable to factors other than volume, which may not be detectable on CT, such as tumor-host biological factors. Pretreatment CT, however, is beneficial for detecting submucosal spread across the ventricle and subglottic extension, which might contraindicate vertical hemilaryngectomy and might not be apparent on endoscopic examination.

Carcinoma, Squamous Cell↗

Radiosurgery for brain metastasis: impact of CTV on local control.

PURPOSE: The purpose of the present analysis was to assess whether adding a 1 mm margin to the gross tumour volume (GTV) improves the control rate of brain metastasis treated with radiosurgery (RS). PATIENTS AND METHODS: All the patients had one or two brain metastases, 30 mm or less in diameter, and only one isocentre was used for RS. There were 23 females and 38 males. The median age was 54 years (34-76). The median Karnofsky performance status was 80 (60-100). At the time of RS, 23 patients had no evidence of extracranial disease and 38 had a progressive systemic disease. Thirty-eight patients were treated up-front with only RS. Twenty-three patients were treated for relapse or progression more than 2 months after whole brain radiotherapy. From January 1994 to July 1995, clinical target volume (CTV) was equal to GTV without any margin (33 metastases). From August 1995 to August 2000, CTV was defined as GTV plus a 1 mm margin (45 metastases). A dose of 20Gy was prescribed to the isocentre and 14Gy at the margin of CTV. RESULTS: The median follow-up was 10.5 months (1-45). The mean minimum dose delivered to GTV was 14.6Gy in the group without a margin and 16.8Gy in the group with a 1 mm margin (P<0.0001). The response of 11 metastases was never assessed because patients died before the first follow-up. Ten metastases recurred, eight in the group treated without a margin and two in the group treated with a 1 mm margin (P=0.01). Two-year local control rates were 50.7+/-12.7% and 89.7+/-7.4% (P=0.008), respectively. Univariate analysis showed that the treatment group (P=0.008) and the tumour volume (P=0.009) were prognostic factors for local control. In multivariate analysis, only the treatment group with a 1 mm margin was an independent prognostic factor for local control (P=0.04, RR: 5.8, 95% CI [1.08-31.13]). There were no significant differences, either in overall survival rate or in early and late side effects, between the two groups. CONCLUSION: Adding a 1 mm margin to the GTV in patients treated with RS significantly improves the probability of metastasis control without increasing the side effects.

Adenocarcinoma↗

Thermal dose is related to duration of local control in canine sarcomas treated with thermoradiotherapy.

PURPOSE: To test that prospective delivery of higher thermal dose is associated with longer tumor control duration. EXPERIMENTAL DESIGN: 122 dogs with a heatable soft tissue sarcoma were randomized to receive a low (2-5 CEM43 degrees CT90) or high (20-50 CEM43 degrees CT90) thermal dose in combination with radiotherapy. Most dogs (90%) received four to six hyperthermia treatments over 5 weeks. RESULTS: In the primary analysis, median (95% confidence interval) duration of local control in the low-dose group was 1.2 (0.7-2.1) years versus 1.9 (1.4-3.2) years in the high-dose group (log-rank P = 0.28). The probability (95% confidence interval) of tumor control at 1 year in the low-dose versus high-dose groups was 0.57 (0.43-0.70) versus 0.74 (0.62-0.86), respectively. Using multivariable procedure, thermal dose group (P = 0.023), total duration of heating (P = 0.008), tumor volume (P = 0.041), and tumor grade (P = 0.027) were significantly related to duration of local tumor control. When correcting for volume, grade, and duration of heating, dogs in the low-dose group were 2.3 times as likely to experience local failure. CONCLUSIONS: Thermal dose is directly related to local control duration in irradiated canine sarcomas. Longer heating being associated with shorter local tumor control was unexpected. However, the effect of thermal dose on tumor control was stronger than for heating duration. The heating duration effect is possibly mediated through deleterious effects on tumor oxygenation. These results are the first to show the value of prospectively controlled thermal dose in achieving local tumor control with thermoradiotherapy, and they establish a paradigm for prescribing thermoradiotherapy and writing a thermal prescription.

Animals↗