Enamel Mineral Content Changes After Bleaching With High and Low Hydrogen Peroxide Concentrations: Colorimetric Spectrophotometry and Total Reflection X-ray Fluorescence Analyses.

The purpose of this study was to evaluate the calcium (Ca) and phosphorous (P) content in enamel bleached with high and low concentrations of hydrogen peroxide (HP) using Total Reflection X-Ray Fluorescence (TXRF) and colorimetric spectrophotometry (SPEC). Forty-eight sound human third molars were used. Their roots were embedded in polystyrene resin and immersed for seven days in an artificial saliva solution. Then they were distributed into six groups to receive the bleaching treatments. The agents of high HP concentration (for in-office use) evaluated were Whiteness HP Maxx/FGM (35% HP), Whiteness HP Blue/FGM (35% HP, 2% calcium gluconate), Pola Office+/SDI (37.5% HP, 5% potassium nitrate), and Opalescence Boost/Ultradent (38% HP, 1.1% ion fluoride, 3% potassium nitrate); these agents were applied to enamel in three sessions. The agents of low HP concentration (for home use) evaluated were Pola Day/SDI (9.5% HP) and White Class 10%/FGM (10% HP, potassium nitrate, calcium, fluoride), and these agents were applied for 14 days. Enamel microbiopsies were evaluated by TXRF and SPEC analysis before the bleaching treatment (baseline), during the treatment, and 14 days after the end of the treatment. For TXRF, the Kruskal-Wallis test showed that Ca and P were not influenced by agent (p>0.05). For SPEC, Pola Office+, Opalescence Boost, Pola Day, and White Class 10% caused a decrease of Ca over time; there was a significant decrease of P over time to Pola Office+ and White Class 10%. The Spearman test showed no correlation between the Ca (p=0.987; r2=-0.020) and P (p=0.728, r2=0.038) obtained by SPEC and TXRF. For TXRF and SPEC, changes in Ca and P during bleaching occurred independently of the HP concentration used.

Simultaneous superficial hyperthermia and external radiotherapy: report of thermal dosimetry and tolerance to treatment.

BACKGROUND: In vitro and animal studies indicate that a moderate temperature of 41 degrees C maintained for approximately 1 h will provide radiosensitization if radiation (RT) and hyperthermia (HT) are delivered simultaneously, but not with sequential treatment. A minimum tumour temperature of 41 degrees C is a more feasible goal than the goal of >42 degrees C needed for sequential treatment. METHODS AND MATERIALS: Forty-four patients with 47 recurrent superficial cancers received simultaneous external beam radiotherapy and superficial hyperthermia on successive IRB approved phase I/II studies. All lesions had failed previous therapy, 35 were previously irradiated (mean dose 52.7 Gy). Hyperthermia was delivered with 915 MHz microwave or 1-3.5 MHz ultrasound using commercially available applicators. The average dimensions of 19 lesions treated with microwave were 4.7 x 3.6 x 1.7 cm and the average dimensions of 28 lesions treated with ultrasound were 8.0 x 6.1 x 2.9 cm. The most common sites were chest wall (15 cases) and head and neck (21 cases). Temperatures were monitored at an average of six intratumoral locations using multisensor probes. The median number of hyperthermia treatments was three and the median radiation dose 30 Gy. Radiation dose per fraction was 4 Gy with hyperthermia and 2 Gy or 4 Gy (depending on protocol) on non-hyperthermia days. RESULTS: Six different measures of minimum monitored temperature and duration were found to be highly correlated with each other. There was nearly a one-to-one correspondence between minimum tumour time at or above 41 degrees C (Min t41) and minimum tumour Sapareto Dewey equivalent time at 42 degrees C (Min teq42). After four sessions 63% of cases had a per session average Sapareto Dewey equivalent time at 41 degrees C which exceeded 60 min in all monitored tumour locations. The complete and partial response rate in evaluable lesions were respectively 21/41 (51%) and 7/41 (17%) and were best correlated with site (chest wall showing best response). Toxicity consisted of 10/47 (21%) slow healing soft tissue ulcers which healed in all cases but required a median of 7 months. The most important predictors for chronic ulceration were cumulative radiation dose >80 Gy and complete response to treatment. CONCLUSIONS: Minimum tumour temperatures maintained for durations compatible in vitro with thermal radiosensitization (if RT and HT are delivered simultaneously) are clinically feasible and tolerable for broad but superficial lesions amenable to externally applied ultrasound or microwave hyperthermia. The current in-house protocol is evaluating the impact of more than four hyperthermia sessions on the overall thermal dose distribution and toxicity.

Superficial hyperthermia and irradiation for recurrent breast carcinoma of the chest wall: prognostic factors in 196 tumors.

PURPOSE: To correlate patient-, tumor-, and treatment-related factors with subsequent local tumor control. METHODS AND MATERIALS: From 1977 to 1990, 196 subcutaneous/superficial lesions (179 measurable, 17 microscopic) in 151 patients with recurrent breast carcinoma of the chest wall were treated with superficial 915-MHz microwave hyperthermia and irradiation. The definition of min t43 > or = 10 min is that all monitored tumor catheters had a minimum of 1 hyperthermia session with temperatures > 43 degrees C for at least 10 min. RESULTS: Factors correlating with local control on univariate analysis included length of survival (> or = 1 year vs. < 1 year) (p < 0.0001), specific absorption rate (SAR) (> or = 25% vs. < 25%) (p = 0.0001), minimum t43 > 10 min (p < 0.0001), tumor volume (p < 0.0001), tumor surface area (p < 0.0001), tumor depth (p = 0.0002), number of hyperthermia sessions (p = 0.0003), and current radiation dose (p = 0.0012). On multivariate analysis, the factors best correlated with ultimate local control were SAR (p < 0.001) and number of hyperthermia sessions (p = 0.003). CONCLUSIONS: Multivariate analysis supports the importance of adequate specific absorption rate (SAR) coverage as a better predictor of local control than tumor volume, surface area, or depth. The explanation is that SAR can be correlated with the tumor surface area and depth, depending on the hyperthermia applicator characteristics. It is recommended that future clinical trials stratify study lesions into either SAR > or = 25% or < 25% because this can be readily estimated prior to initiating treatment. It is also recommended that future clinical trials attempt to have adequate lengths of follow-up after therapy to assess the results in long-term survivors.

Adenocarcinoma of the prostate: innovations in management.

Adenocarcinoma of the prostate (CaP) in the Western world has become the most common noncutaneous human tumor. CaP is also the second most important cause of cancer deaths among the male population in the United States. Major progress was made in the past decade in better understanding this disease process, as well as in improved diagnostic accuracy. This improved diagnostic accuracy was due to wide application of prostate-specific antigen (PSA), use of transrectal ultrasound (TRUS), and greater awareness among clinicians of CaP. The use of PSA in clinical practice has resulted in a sharp increase in the number of patients diagnosed with capsule-confined tumors. The optimal treatment for capsule-confined CaP is in the process of being defined. Radical prostatectomy in the United States is currently the most commonly applied treatment for younger patients. Excellent treatment results with a 10-year actuarial survival > 80% are readily obtainable in properly selected patients. Nerve-sparing procedures helped reduce the high incidence of impotence that occurs in patients after radical retropubic prostatectomy. Radiotherapy remains the other curative treatment method in the management of CaP patients, with long-term survival rates similar to those reported in surgical series. Due to the problem of frequent preoperative tumor understaging, a routine use of postoperative irradiation to the prostatic fossa produces an excellent (> 95%) incidence of local tumor control. Management of patients with metastatic disease has undergone a considerable evolution with the development of modern hormonal management and treatment with strontium-89 to control intractable bone pain. Newer treatment methods such as hyperthermia are currently being investigated. Major efforts are directed toward the reduction of short- and long-term treatment toxicity associated with surgery, radiotherapy, and hormonal management, thus improving patient quality of life.

Phase III study of interstitial thermoradiotherapy compared with interstitial radiotherapy alone in the treatment of recurrent or persistent human tumors. A prospectively controlled randomized study by the Radiation Therapy Group.

PURPOSE: The objectives of this randomized trial were to determine if interstitial thermoradiotherapy (ITRT) improves tumor regression/control in accessible lesions in comparison with interstitial radiotherapy (IRT) alone and to assess the skin and soft tissue complications with either modality. METHODS AND MATERIALS: From January 1986 to June 1992, 184 patients with persistent or recurrent tumors after previous radiotherapy and/or surgery, which were amenable to interstitial radiotherapy, were accessioned to a protocol developed by the Radiation Therapy Oncology Group (RTOG). One hundred seventy-three cases were analyzed (87 patients in the IRT group and 86 in the ITRT arm). The two arms were well balanced regarding stratification criteria. Most tumors were in the head and neck (40% in the IRT group and 46% in the ITRT group), and pelvis (42% and 43%, respectively). Eighty-four percent of patients in both arms had prior radiation therapy (> or = 40 Gy); 50% and 40%, respectively, had prior surgery, and 34% in each arm had prior chemotherapy. The dose of radiation therapy administered was dependent on the previous radiation dose and did not exceed a total cumulative dose of 100 Gy. Hyperthermia was delivered in one or two sessions, either before or before and after interstitial implant. The intended goal of the hyperthermia was to maintain a minimal tumor temperature of 42.5 degrees C for 30 to 60 min. RESULTS: There was no difference in any of the study end points between the two arms. Complete response (CR) was 53% and 55% in both arms. Two-year survival was 34% and 35%, respectively. Complete response rate for persistent lesions was 69% and 63% in the two treatment arms as compared with 40% and 48% for recurrent lesions. A set of minimal adequacy criteria for the delivery of hyperthermia was developed. When these criteria were applied, only one patient had an adequate hyperthermia session. Acute Grade 3 and 4 toxicities were 12% for IRT and 22 % for ITRT. Late Grade 3 and 4 toxicities were 15% for IRT and 20% for ITRT. The difference was not significant. CONCLUSIONS: Interstitial hyperthermia, as applied in this randomized study, did not show any additional beneficial effects over interstitial radiotherapy alone. Delivery of hyperthermia remains a major obstacle (since only one patient met the basic minimum adequacy criteria as defined in this study). The benefit of hyperthermia in addition to radiation therapy still remains to be proven in properly randomized prospective clinical trials after substantial technical improvements in heat delivery and dosimetry are achieved.

Radiation therapy in the treatment of localized prostate cancer: an alternative to an emerging consensus.

Optimal treatment for patients with localized carcinoma of prostate is controversial. Radiation therapy is an established modality; reports indicate that results are comparable to those of radical prostatectomy. A retrospective review was carried out of 963 patients with carcinoma of the prostate treated with definitive irradiation (65 to 71 Gy in 6.5 to 7 weeks). Survival, incidence of local recurrence and distant metastases, and postirradiation PSA data were analyzed. Ten-year disease-free survival with external irradiation was 100% for clinical stage A1 (T1a), 69% for stage A2 (T1b,c), 57% for clinical stage B (T2), and 41% for stage C (T3). Initial PSA level closely correlated with probability of freedom from chemical failure (PSA elevation) after definitive irradiation in 317 patients with stage T1b,c and T2 tumors (96% and 89%, respectively, with initial PSA of < 10 ng/ml and 75% and 65% with higher PSA levels). Although modern irradiation techniques produce results comparable to those of radical prostatectomy in localized prostate carcinoma, we must continue to critically assess treatment policies, develop appropriately designed prospective clinical trials, and define optimal management of these patients.

Evaluation of 45 degrees C hyperthermia and irradiation. I. Studies in a murine rhabdomyosarcoma model.

This report describes biologic experiments using transplanted RIF-1 tumors (diameter 0.5 or 1 cm) in C3H/He inbred mice (12 to 20 per treatment group) to compare the results with heat alone (43 degrees C for 60 minutes or 45 degrees C for 15 minutes, twice weekly via radiofrequency electrodes), irradiation alone (400 cGy twice weekly for a total of 4,000 cGy with 140 kVp x-rays), or a combination of both therapies. Animals receiving combined treatment had significantly greater complete regression than those treated with either therapy alone. Tumor regrowth curves were equivalent for 43 degrees C or 45 degrees C following irradiation. In tumors 0.5 cm in diameter the overall tumor cure rates were 17% for 43 degrees C for 60 minutes and 25% for 45 degrees C for 15 minutes with heat alone and 8% with irradiation alone; the combination of irradiation and heat at both temperatures yielded comparable complete cure rates (75 and 67%). With 1-cm tumors the corresponding cure rates were 0% with heat alone (either temperature), 5% for irradiation alone, 33% for irradiation and 43 degrees C heat, and 64% for irradiation and 45 degrees C heat (p = .3). Approximately 20% of the animals in the various groups developed moist or dry desquamation in the area treated, whereas 40 to 66% exhibited moist desquamation. There was a slight increase in this sequela (73%) for mice that received irradiation and 45 degrees C compared with 50% in mice treated with 43 degrees C, but the difference was not statistically different (p = .54). Experimental studies demonstrated equivalent efficacy of 10 hyperthermia sessions at 43 degrees C or 45 degrees C combined with irradiation. Caution must be exercised in the clinical application of thermal iso-effect heat dose concepts until further clinical trials have been performed and there is a better understanding of the time-temperature relationship.

Evaluation of 45 degrees C hyperthermia and irradiation. II. A phase I clinical trial in humans by the Radiation Therapy Oncology Group.

This report describes the experience in 40 evaluable patients entered into a Radiation Therapy Oncology Group (RTOG) study to evaluate the feasibility of administering 45 degrees C for 15 minutes for superficial malignant lesions: 18 patients (45%) tolerated only 1 heat session at 45 degrees C; 7 (17.5%), 2 sessions; 4 (10%), 3 sessions; and 3 (7.5%) tolerated > or = 4 sessions. The overriding reason for discontinuing at 45 degrees C treatment was pain. Of the 40 evaluable patients, 22 (55%) had complete tumor regression, and 8 (20%) had partial regression. Tumors < or = 3 cm in diameter had significantly better complete tumor response than lesions > 3 cm (85% vs 41%) (p = .02). We conclude that 45 degrees C heating is difficult to use in patients chiefly because of pain; this may be due in part to inadequacy of currently available external hyperthermia equipment. Caution must be exercised in the application of thermal isoeffect heat dose concepts in clinical practice until further trials have been performed and a better understanding of the time-temperature relationship is established.

Radiation therapy in the management of cancer of the cervix.

Patients with stage IB or IIA carcinoma of the uterine cervix can be treated with comparable results using either radical surgery or definitive radiotherapy. The treatment of choice for stage IIB and III tumors is radiotherapy alone. Although the efficacy of adjuvant chemotherapy has not been documented, several trials are evaluating the potential use of combined chemotherapy and irradiation in bulky or extensive lesions. In most patients, radiotherapy consists of a combination of external-beam irradiation of the pelvis and two intracavitary radioactive source insertions. This article reviews the basic principles of management of patients with cervical cancer and describes the radiotherapy techniques employed.

Equilibrium temperature distributions in uniform phantoms for superficial microwave applicators: implications for temperature-based standards of applicator adequacy.

Equilibrium temperature distributions are computed using measured SAR distributions for five different superficial microwave (915 MHz) applicators. We assume a model with uniform conduction and blood flow. A Green's function approach is used to calculate equilibrium solutions which identically obey boundary conditions at the surface of the phantom and at infinite depth. The equilibrium solutions are categorized by surface temperature (TS), maximum allowed temperature (TM), and by a parameter (referred to as the diffusion length, lambda) which characterizes the contributions of thermal conduction relative to blood flow. The computed equilibrium temperature distribution at depths of 2 and 3 cm is strongly dependent on lambda and on TM. It is not strongly dependent on surface temperature for TS below 35 degrees C. In previous work we compared the SAR distribution with local control of 53 superficial tumours with over 1 year of follow-up. As an alternative to an SAR-based description of applicator adequacy we consider a temperature-based standard. Tumours are categorized by the minimum value of lambda that would allow full coverage of the tumour volume by the 42 degrees C contour, assuming a TM of 47.5 degrees C and a TS of 35 degrees C. Eighteen of 27 lesions (67%) were locally controlled for lambda less than 1 cm. The local control in 26 lesions with lambda greater than or equal to 1 cm was 31% (p = 0.016). The lesions with the best results were those with both good coverage in theory (lambda less than 1 cm) and with all monitored catheter tracks achieving at least one session with 30 min at or above 43 degrees C. We found that the temperature-based standard of applicator adequacy was not independent of an SAR-based standard, and in this cohort of patients either a minimum SAR criterion or a maximum diffusion length criterion would serve equally well as a screen for inappropriate applicators.

Combined hyperthermia and irradiation in the treatment of superficial tumors: results of a prospective randomized trial of hyperthermia fractionation (1/wk vs 2/wk).

From December 1984 to December 1989, 240 superficially located recurrent/metastatic malignant lesions (173 patients) were enrolled in a prospective randomized study of one versus two hyperthermia fractions per week. In the majority of patients, the dose of radiation therapy was less than 4000 cGy over 4 to 5 weeks. Stratification was by tumor size, site, and histology. The goal of the hyperthermia sessions were 42.5 degrees C for 45-60 min minimum intra-tumor measured temperature. Hyperthermia was given after radiation within 30-60 min. External applicators, both microwave (over 90% of treatments) and ultrasound, were used. Overall, complete response rate in 222 evaluable lesions was 56.3% (125/222) with a minimum follow-up of 6 months and a maximum follow-up of 52 months. The complete response rate for once a week versus twice a week hyperthermia group was 54.7% and 57.8%, respectively. The severe complication rate was 18% (41/222). There was no difference between the two treatment arms. Cox regression analyses were performed to study the prognostic significance of patient characteristics, tumor characteristics, and treatment parameters. Detailed analysis and results are presented.

Radiotherapy and breast reconstruction: clinical results and dosimetry.

Immediate or delayed reconstruction using implants or autologous tissue transfer is increasingly offered to women undergoing mastectomy for breast cancer. Some patients require radiotherapy for prevention of local/regional relapse, and some for post-surgical local/regional recurrence. Others with augmented breasts may opt for conservative surgery and irradiation. At Washington University, 70 breast cancers were irradiated in 66 patients following mastectomy with reconstruction (N = 61) or wide local excision of an augmented breast (N = 5). Two patients elected to have a second reconstruction after an unsatisfactory initial result. Thus, 72 breasts were evaluated after radiotherapy for tumor control, complications, cosmesis, and patient satisfaction. Locoregional failure occurred in only five patients, one following adjuvant radiotherapy after mastectomy with reconstruction and four following radiotherapy for recurrent breast cancer within a reconstructed breast. Grade 2 or 3 complications occurred in 34 patients (51%). The complication rate was highest in autologous tissue transfer reconstructions. Cosmetic results were evaluated good/excellent in 49% by physicians and 67% by patients. Immediate reconstructions had fewer good/excellent physician evaluations (32%) compared with reconstructions performed at least 6 weeks after radiotherapy (55%). Transverse rectus abdominis flaps had the best cosmesis scores, followed by permanent silicone prostheses, tissue expanders, latissimus dorsi, and gluteal flaps. Only 48% of patients would choose to have the same reconstructive procedure again. Phantom interface dosimetry with a parallel plate chamber and TLD measurements was performed. Radiotherapy and reconstruction are not incompatible, but careful consideration of their relative timing and technique appear to be important in optimizing cosmesis while minimizing complications.

Randomized phase III study comparing irradiation and hyperthermia with irradiation alone in superficial measurable tumors. Final report by the Radiation Therapy Oncology Group.

A total of 307 patients with superficial measurable tumors were registered on a Radiation Therapy Oncology Group (RTOG) protocol involving fractionated radiation therapy, either alone or followed immediately by hyperthermia (42.5 degrees C, 45-60 min). Overall complete response (CR) was observed in 30% of the lesions treated with radiotherapy (RT) and 32% of those receiving RT and heat. Response was found to be significantly related to both maximum tumor diameter (less than 3 or greater than or equal to 3 cm) and site/histology (breast/adenocarcinoma, head and neck/squamous, or other site/histologies). In tumors less than 3 cm in diameter in the breast, trunk, and extremities, a better CR rate was noted with irradiation and heat (62 and 67%) than with irradiation alone (40 and 0%). However, in the head and neck there was only minimal difference in CR with irradiation alone or combined with hyperthermia (50 vs 38%). In lesions less than 3 cm treated with irradiation and heat, there was improved local control. In lesions greater than 3 cm, there was no difference in local control between the two treatment arms. The higher response rate in patients with smaller lesions (less than 3 cm) may be explained by the fact that these tumors are easier to heat. Problems in correlating tumor response with quality of heating include less than optimal heating in larger lesions and the limited ability of current thermometry to map the temperature distribution in a tumor. Acute and late toxicities in both treatment arms were comparable, except for an overall 30% incidence of thermal blisters in the heated tumors.

Phase I/II study, combination of radiotherapy and hyperthermia in patients with deep-seated malignant tumors: report of a pilot study by the Radiation Therapy Oncology Group.

This is a report of a Phase I/II study activated in March 1984 and completed in October 1988 by the Radiation Therapy Oncology Group on the feasibility/toxicity of hyperthermia in patients with deep-seated malignant tumors. The main objective of this study was to evaluate the morbidity of regional hyperthermia (systemic and regional, acute and late effects); a secondary objective was to evaluate tumor response to combined irradiation and regional hyperthermia. A total of 54 patients with locally advanced abdominal or pelvic malignancy were accrued to this study; 42% were male and 58% female. Seventy-five of the patients had pelvic tumors and 25% abdominal tumors. Acute toxicities included grade 4 in three patients (1 cutaneous, 1 infection and 1 chemical peritonitis) one grade 3 (skin), and 12 grade 2 toxicities (6 skin and 6 gastrointestinal). With regard to late toxicities, grade 4 was noted in one patient (skin), grade 3 (GI) in one, and grade 2 (skin, peripheral neuropathy) in six patients. The prescribed course of hyperthermia was completed in 17 (32%) of patients. In 36 patients (68%) the course of hyperthermia was terminated, primarily because of patient discomfort. Tumor response was assessed by physical examination or radiological studies. Of 44 patients evaluable for response, there were 17 (39%) complete responses and 6 (14%) partial responders. Significant technical problems in heat delivery and thermometry remain.

Tumor control in long-term survivors following superficial hyperthermia.

Sixty tumors with a minimum of 1-year follow-up were treated with radiation and superficial microwave hyperthermia (915 MHz). The overall local control rate was 50% (30/60). The most important factor in outcome was appropriateness of the hyperthermia applicator. Tumors covered by at least the 25% iso-SAR contour achieved 65% local control versus 21% local control with less than 25% SAR coverage (p less than 0.01). Several measures of adequate minimum monitored tumor temperature and duration were considered. The measure best correlated with outcome was best single session time at or above 43 degrees C (t43). If each monitored tumor catheter achieved t43 greater than or equal to 30 minutes in at least one session, then tumor control was significantly (p less than 0.01) improved (63% with Min t43 greater than or equal to 30 versus 25% with Min t43 less than 30). Although there was considerable overlap between tumors with SAR greater than or equal to 25% and those achieving Min t43 greater than or equal to 30, a statistically significant (p = 0.02) difference could be demonstrated between the group meeting both the SAR and the minimum tumor time/duration standards as opposed to those meeting only one standard. The actuarial local progression-free survival for tumors most likely to have had adequate hyperthermia (defined as SAR greater than or equal to 25% and Min t43 greater than or equal to 30) and all other tumors did not begin to separate significantly until 8 to 12 months after treatment. Implications for future randomized studies are discussed.

Phase I/II study of definitive radiotherapy and chemotherapy (cisplatin and 5-fluorouracil) for advanced or recurrent gynecologic malignancies. Preliminary report.

Twenty-three patients with advanced gynecologic malignancy were treated with definitive irradiation and synchronous sensitizing chemotherapy (CT) consisting of cisplatin (CDDP), 50 mg/m2 i.v. rapid infusion, and a 5-day continuous infusion of 5-fluorouracil (5-FU), 750 mg/m2/day. A total of three cycles were administered every 3-4 weeks. Fifteen patients had primary cervical epidermoid carcinoma (three bulky stage IIB, one stage IIIA, ten stage IIIB, one stage IV), four had pelvic recurrences of carcinoma of the cervix, two had endometrial adenocarcinomas (stage IV), and two had vulvar epidermoid carcinoma (one stage III and one stage IV). Radiotherapy (RT) for implantable tumors consisted of 2,000 cGy whole pelvis, 3,000-4,000 cGy split field, and two intracavitary or interstitial insertions, resulting in a total dose of 7,500-8,000 cGy to point A. Three courses of CT were delivered simultaneously with irradiation of the central bulk of tumor: during the first week of whole pelvis RT and with each of the two brachytherapy procedures. Nonimplantable tumors were treated with protracted external beam RT (5,500 cGy tumor dose) and three courses of CT during weeks 1, 4, and 7 of RT. Twenty-one of 23 patients completed RT and 18 of 23 patients completed CT as planned, but half had delays in either RT or CT. Grade 2 or 3 late sequelae consisted of leg edema (one patient), proctosigmoiditis (one patient), bowel obstruction (one patient), vesicovaginal fistula (one patient), and pulmonary embolus (two--one fatal). The incidence of grade 2 and 3 sequelae were 18 and 22%, respectively. With 1-3 years of follow-up evaluation, 12 of 23 (52%) patients are free of disease, and 9 of 22 evaluable patients (41%) have had failure within the pelvis. We conclude that high-dose definitive RT can be delivered with synchronous CDDP and 5-FU at the doses given, with acceptable toxicity. Further study is required to evaluate the impact of radiosensitization on tumor control and late morbidity of therapy. Optimization of irradiation and drug doses as well as the best schedules that may enhance the interaction of these two modalities should be further investigated.

Physical predictors of adequate hyperthermia with the annular phased array.

One hundred and fifty-two hyperthermia sessions in 36 consecutive patients treated with the BSD 1000 annular phased array system (APAS) are reviewed with regard to physical predictors of quality of hyperthermia. Although central tumour temperatures exceeding 42 degrees C were momentarily obtained in 62% of the sessions, it frequently proved difficult to maintain the patient at temperature for prolonged periods of time. The time to reach target temperature was negatively associated with quality of hyperthermia. Thus, of 25 sessions which required over 25 min to attain a temperature of 42 degrees C, only one was adequate (defined as central tumour temperature greater than or equal to 42 degrees C maintained for at least 30 min) as opposed to 28/69 adequate sessions when 42 degrees C was reached in less than 25 min. Physical parameters measured in the first 3 min of the session found to be associated with adequate hyperthermia include an initial rate of temperature rise at the tumour site exceeding 0.4 degrees C/min achieved with a net forward power less than 1500 W. Only three of 57 sessions not meeting these criteria were adequate. Treatment policy recommendations and recommendations for future research are made.

Regional hyperthermia in the treatment of recurrent deep-seated tumors: preliminary analysis of phase I trial.

This is a preliminary report on a phase I pilot study of regional hyperthermia of advanced tumors, using annular phased array system (APAS) in combination with radiation therapy and/or chemotherapy. All patients were treated without anesthesia. In all hyperthermia sessions, physiological parameters such as blood pressure, cardiac rate, respiratory rate, and EKG were monitored throughout the treatment. Tumor temperature was monitored with intratumoral probe with an additional probe either in the esophagus or rectum for monitoring systemic temperature. Present reports are on analysis of the first 30 patients: a total of 139 treatment sessions were analyzed. The results indicate local discomfort, anxiety, systemic temperature elevation, and tachycardia were the predominant factors limiting the number of sessions, the duration of sessions, and the deposition of power, in 18, 6, 6, and 2 patients, respectively. The complications were rare. No injuries to visceral organs clearly attributed to the hyperthermia have been recorded.

Clinical trials with local (external and interstitial) irradiation and hyperthermia. Current and future perspectives.

There is a growing body of experience in the clinical use of either external or interstitial (local) hyperthermia. A great deal has been learned about the technical and prognostic factors that influence the efficacy of heat combined with irradiation. Despite some technologic advances, substantial limitations remain to the optimal delivery of heat and monitoring of the temperature throughout the treatment volume with localized techniques. Additional efforts to improve present equipment are paramount, and further studies should be encouraged to establish the optimal conditions for the delivery and temperature monitoring of local hyperthermia combined with irradiation or cytotoxic agents. It is possible to induce tumor regression and produce satisfactory palliative results in selected groups of patients with recurrent or advanced tumors. The clinical application of hyperthermia, particularly in previously irradiated patients, should be continued. Adequately designed clinical trials to amplify our understanding of this modality and its optimal clinical applications should be strongly supported.

Quality assurance problems in clinical hyperthermia and their impact on therapeutic outcome: a Report by the Radiation Therapy Oncology Group.

Since February 1981, 300 patients with superficial measurable tumors were randomized on an RTOG protocol (81-04) involving fractionated radiation therapy (4.00 Gy twice weekly for a total of 32.00 Gy), either alone or followed immediately by hyperthermia (42.5 degrees C, 60 min). This is a report of 218 eligible patients with single lesions: 107 treated with radiotherapy alone (RT), 111 with radiotherapy plus hyperthermia (RT + HT). Only 56% of the 24 tumors less than 3 cm and 36% of the 53 lesions larger than 3 cm received what was felt to be "adequate" therapy (greater than or equal to 29 Gy and 8 heating sessions). Overall complete response (CR) was observed in 28% of the patients treated with RT, and 32% of the patients receiving RT and heat. Response has been found in previous analyses of this and other RTOG studies to be significantly related to both maximum tumor diameter (less than 3 or greater than or equal to 3 cm) and site/histology (breast/adenocarcinoma, head and neck/squamous, or other site/histologies). In the head and neck tumors less than 3 cm in diameter there was no difference in CR with irradiation alone or combined with hyperthermia (46% vs 43%). However, in the breast, and trunk and extremities a better CR rate was noted with irradiation and heat (55% and 67%) than with irradiation alone (33% and 0). In lesions less than 3 cm treated with irradiation and heat the probability of remaining in response was 80% compared with 15% with irradiation alone. In lesions larger than 3 cm no difference in CR was observed in either treatment group. It has been hypothesized that the response rate is higher in patients with smaller lesions (less than 3 cm) and in breast/chest wall, trunk/extremity lesions because these tumors and anatomical sites are easier to heat adequately. Problems encountered in correlating tumor response with quality of heating include less than optimal heating in larger lesions and the limited ability of current thermometry to accurately represent the temperature distribution in a tumor. Furthermore, differences in equipment and treatment practices among institutions add to the variability in heat administration data collected. In addition, tumor response may be difficult to judge because of short survival of some patients and occasionally rapid tumor regression that may cause necrosis which may be misinterpreted as persistent tumor.(ABSTRACT TRUNCATED AT 400 WORDS)