A phase I-B trial of the radiosensitizer: etanidazole (SR-2508) with radiosurgery for the treatment of recurrent previously irradiated primary brain tumors or brain metastases (RTOG Study 95-02).

RTOG 95-02 assessed patient tolerance to hypoxic cell radiosensitizer, etanidazole (SR-2508), combined with radiosurgery. Patients had primary or metastatic brain tumors and previously localized or whole brain irradiation. The toxicity is reported in three groups of patients according to the tumor size. Etanidazole doses of 12g/m2 combined with radiosurgery were well tolerated.

Outcome analysis for stage IE and IIE thyroid lymphoma.

Previous reports have revealed modest results in the management of thyroid lymphoma with radiotherapy alone. This retrospective report evaluates the outcome of patients treated for thyroid lymphoma with radiotherapy alone and with combined modality therapy (chemotherapy and radiotherapy) at a single institution. Twenty-seven patients with stages IE and IIE non-Hodgkin's lymphoma of the thyroid gland were treated between 1960 and 1998 at Barnes-Jewish Hospital, of which 14 patients were stage IE and 13 patients were stage IIE. The median age at diagnosis was 67 years, and there were 21 females and 6 males evaluated. The median follow-up time was 38 months (range: 3-279 months). All patients had histologically proven non-Hodgkin's lymphoma, of which 22 patients (81%) were intermediate grade. Treatment consisted of radiotherapy alone in 19 patients and a combined modality therapy in 8 patients. The median radiation dose to the thyroid bed was 44 Gy, and most patients received a doxorubicin-containing regimen administered prior to radiotherapy. Patient, tumor, and treatment-related characteristics were evaluated using Cox regression analysis. Local-regional tumor control, disease-free survival (DFS), and overall survival (OS) were calculated using the Kaplan-Meier method. Four patients had local relapse in this series, with a crude local tumor control rate of 85%. No factor was determined to be significant for local tumor control. The actuarial 5-year DFS and OS for the entire cohort were 57%, and 56%, respectively. In terms of DFS, both age and stage were statistically significant. The 5-year actuarial DFS for patients less than age 65 years was 83% versus 37% for those more than this age (p = 0.024). Furthermore, the 5-year actuarial DFS for patients with stage I and II disease was 69% and 45%, respectively (p = 0.022). In multivariate analysis, age continued to be significant for DFS (p = 0.049). Overall survival analysis revealed age, local tumor control, and stage to be significant in univariate analysis. Multivariate analysis was further carried out using Cox proportional hazard model, and it revealed age (p = 0.006) and local tumor control (p = 0.007) to be significant. Primary thyroid gland lymphomas have a favorable outcome with appropriate therapy, but prognosis depends on both clinical stage and age at presentation. Because of the risk of both local-regional and distant failure, combined modality approaches that use chemotherapy with radiotherapy are warranted for intermediate- and high grade thyroid lymphoma.

Phase III randomized intergroup trial of subtotal lymphoid irradiation versus doxorubicin, vinblastine, and subtotal lymphoid irradiation for stage IA to IIA Hodgkin's disease.

PURPOSE: The management of early-stage Hodgkin's disease in the United States is controversial. To evaluate whether staging laparotomy could be safely avoided in early-stage Hodgkin's disease and whether chemotherapy should be a part of the treatment of nonlaparotomy staged patients, a phase III intergroup trial was performed. PATIENTS AND METHODS: Three hundred forty-eight patients with clinical stage IA to IIA supradiaphragmatic Hodgkin's disease were randomized without staging laparotomy to treatment with either subtotal lymphoid irradiation (STLI) or combined-modality therapy (CMT) consisting of three cycles of doxorubicin and vinblastine followed by STLI. RESULTS: The study was closed at the second, planned, interim analysis because of a markedly superior failure-free survival (FFS) rate for patients on the CMT arm (94%) compared with the STLI arm (81%). With a median follow-up of 3.3 years, 10 patients have experienced relapse or died on the chemoradiotherapy arm, compared with 34 on the radiotherapy arm (P <.001). Few deaths have occurred on either arm (three deaths on CMT and seven deaths on STLI). Treatment was well tolerated, with only one death on each arm attributed to treatment. CONCLUSION: These results demonstrate that it is possible to obtain a high FFS rate in a large group of stage IA to IIA patients without performing staging laparotomy and that three cycles of chemotherapy plus STLI provide a superior FFS compared with STLI alone. Extended follow-up is necessary to assess freedom from second relapse, overall survival, late toxicities, patterns of treatment failure, and quality of life.

The role of amifostine as a radioprotector.

Effective radiotherapy for patients with cancer should include maximal tumor cell killing with minimal injury to normal tissue. Radiation doses that can be delivered, without causing severe damage to surrounding normal tissues, can be insufficient to eradicate a tumor. Agents have been developed to protect normal tissue from the toxicities of radiation. The aminothiol amifostine (Ethyol) is the subject of extensive research as a protector. Several studies have demonstrated that amifostine protects normal tissues from both acute and late radiation damage without protecting the tumor. This article reviews the physicochemical basis of radiation therapy on biologic tissues and the mechanisms responsible for the protective effects of amifostine. The increasing body of biochemical, preclinical, and clinical data can justify the use of protectors such as amifostine with radiotherapy to provide improved therapeutic efficacy and quality of life for the patient. This article will review the current understanding of the nature of toxicity resulting from radiation therapy and the benefits that can be derived from using protection to increase the tolerance of normal tissue to radiation damage.

Breast cancer occurred after treatment for Hodgkin's disease: analysis of 133 cases.

PURPOSE: To assess the clinical and histological characteristics of breast cancer (BC) occurring after Hodgkin's disease (HD) and give possible therapies and prevention methods. MATERIALS AND METHODS: In a retrospective multicentric analysis, 117 women and two men treated for HD subsequently developed 133 BCs. The median age at diagnosis of HD was 24 years. The HD stages were stage I in 25 cases (21%), stage II in 70 cases (59%), stage III in 13 cases (11%), stage IV in six cases (5%) and not specified in five cases (4%). Radiotherapy (RT) was used alone in 74 patients (63%) and combined modalities with chemotherapy (CT) was used in 43 patients (37%). RESULTS: BC occurred after a median interval of 16 years. TNM classification (UICC, 1978) showed 15 T0 (11.3%), 44 T1 (33.1%), 36 T2 (27.1%), nine T3 (6.7%), 15 T4 (11.3%) and 14 Tx (10.5%). Ductal infiltrating carcinoma and ductal carcinoma in situ (DCIS) represented 81.2 and 11.3% of the cases, respectively. Among the infiltrating carcinoma, the axillary involvement rate was 50%. Seventy-four tumours were treated by mastectomy without (67) or with (ten) RT. Forty-four tumours had lumpectomy without (12) or with (32) RT. Another four received RT alone, and one CT alone. Sixteen patients (12%) developed isolated local recurrence. Thirty-nine patients (31.7%) developed metastases and 34 died; 38 are in complete remission whereas five died of intercurrent disease. The 5-year disease-specific survival rate was 65.1%. The 5-year disease-specific survival rates for the pN0, pN1-3 and pN>3 groups were 91, 66 and 15%, respectively (P<0.0001), and 100, 88, and 64% for the TIS, T1 and T2. For the T3 and T4, the survival rates decreased sharply to 32 and 23%, respectively. These secondary BC are of two types: a large number of aggressive tumours with a very unfavourable prognosis (especially in the case of pN>3 and/or T3T4), and many tumours with a 'slow spreading' such as DCIS and microinvasive lesions. These lesions developed especially in patients treated exclusively by RT. CONCLUSIONS: The young women and girls treated for HD should be carefully monitored in the long-term by clinical examination, mammography and ultrasonography. We suggest that a baseline mammography is performed 5-8 years after supradiaphragmatic irradiation (complete mantle or involved field) in patients who were treated before 30 years of age. Subsequent mammographies should be performed every 2 years or each year, depending on the characteristics of the breast tissue (e.g. density) and especially in the case of an association with other BC risk factors. This screening seems of importance due to excellent prognosis in our T(1S)T(1) groups, and the possibility of offering these young women a conservative treatment.

Can costs be measured and predicted by modeling within a cooperative clinical trials group? Economic methodologic pilot studies of the radiation therapy oncology group (RTOG) studies 90-03 and 91-04.

PURPOSE: To (1) measure radiation therapy costs for patients in randomized controlled clinical trials, (2) compare measured costs to modeling predictions, (3) examine cost distributions, and (4) assess feasibility of collecting economic data within a cooperative group. METHODS: The Radiation Therapy Oncology Group conducted economic pilot studies for two Phase III studies that compared fractionation patterns. Expected quantities of Current Procedural Terminology (CPT) codes and relative value units (RVU) were modeled. Institutions retrospectively provided procedure codes, quantities, and components, which were converted to RVUs used for Medicare payments. Cases were included if the radiation therapy quality control review judged them to have been treated per protocol or with minor variation. Cases were excluded if economic quality review found incomplete economic data. RESULTS: The median and mean RVUs were within the range predicted by the model for all arms of one study and above the predicted range for the other study. CONCLUSION: The model predicted resource use well for patients who completed treatment per protocol. Actual economic data can be collected for critical cost items. Some institutions experienced difficulty collecting retrospective data, and prospective collection of data is likely to allow wider participation in future Radiation Therapy Oncology Group economic studies.

Management of swallowing in supraglottic and extended supraglottic laryngectomy patients.

BACKGROUND: Aspiration of food and liquid following supraglottic and supracricoid laryngectomy has been documented and found to be the most frequent major postoperative complication that extends hospitalization. The advantages as well as disadvantages of discharging a patient with percutaneous endoscopic gastrostomy (PEG) placement and home therapy versus an aggressive in-hospital dysphagia management program remain controversial. The present investigation examines an aggressive in-patient postoperative dysphagia management program following decannulation. METHODS: Twenty-one patients participated in a four-part dysphagia management program following decannulation: patient education, indirect therapy, swallowing evaluation, and nutrition education. RESULTS: Eleven patients achieved functional swallowing goals prior to discharge with no reports of pneumonia or rehospitalization over a 3-month follow-up period. Six patients were discharged with a tracheostomy and duo tube; five of these patients were started on an oral diet the same day of decannulation. Four patients decannulated prior to discharge did not achieve functional swallowing. CONCLUSION: Certain patients can achieve functional swallowing goals prior to discharge and avoid the cost and surgical placement of a PEG. This group required an additional 2 to 3 days of hospitalization; however, the usual and customary charges for aggressive dysphagia management in this group were exceeded by charges for PEG placement and in-home therapy according to pricing guidelines for the hospital where these patients were treated. Specific patient profiles of those who were unsuccessful relate to extent of surgery, ie, supraglottic + base of tongue (SUPRA + BOT) and supraglottic + vocal fold (SUPRA + VF) resection, and non-compliance. Complicated patients often require longer rehabilitation and may benefit from a PEG at the time of surgery.

Effect of amifostine on patient assessed clinical benefit in irradiated head and neck cancer.

PURPOSE: To determine if head and neck (H/N) cancer patients receiving daily amifostine during radiation therapy (RT) experienced clinical benefit (improvement in their ability to carry out normal functions with reduced discomfort) compared to nonamifostine treated patients. METHODS AND MATERIALS: This was an open-label, multi-institutional randomized trial in 303 H/N cancer patients treated with RT +amifostine. Clinical benefit was measured using an 8-item validated Patient Benefit Questionnaire (PBQ) during and up to 11 months after RT. RESULTS: 301 patients completed one or more PBQ assessments. Amifostine patients had significantly better PBQ scores (p < 0.05) than controls. The improvement in PBQ scores was most significant during chronic xerostomia. CONCLUSIONS: Amifostine use results in improved Patient Benefit Questionnaire (PBQ) scores, which is indicative of improved oral toxicity related outcomes and improved clinical benefit. Less oral toxicity should lead to preservation of late dental and oral health, and improvements in activities such as diet, nutrition, and sleep.

Phase III randomized trial of amifostine as a radioprotector in head and neck cancer.

PURPOSE: Radiotherapy for head and neck cancer causes acute and chronic xerostomia and acute mucositis. Amifositine and its active metabolite, WR-1065, accumulate with high concentrations in the salivary glands. This randomized trial evaluated whether amifostine could ameliorate these side effects without compromising the effectiveness of radiotherapy in these patients. PATIENTS AND METHODS: Patients with previously untreated head and neck squamous cell carcinoma were eligible. Primary end points included the incidence of grade > or =2 acute xerostomia, grade > or =3 acute mucositis, and grade > or =2 late xerostomia and were based on the worst toxicity reported. Amifostine was administered (200 mg/m(2) intravenous) daily 15 to 30 minutes before irradiation. Radiotherapy was given once daily (1.8 to 2.0 Gy) to doses of 50 to 70 Gy. Whole saliva production was quantitated preradiotherapy and regularly during follow-up. Patients evaluated their symptoms through a questionnaire during and after treatment. Local-regional control was the primary antitumor efficacy end point. RESULTS: Nausea, vomiting, hypotension, and allergic reactions were the most common side effects. Fifty-three percent of the patients receiving amifostine had at least one episode of nausea and/or vomiting, but it only occurred with 233 (5%) of 4,314 doses. Amifostine reduced grade > or =2 acute xerostomia from 78% to 51% (P<.0001) and chronic xerostomia grade > or = 2 from 57% to 34% (P=.002). Median saliva production was greater with amifostine (0.26 g v 0.10 g, P=.04). Amifostine did not reduce mucositis. With and without amifostine, 2-year local-regional control, disease-free survival, and overall survival were 58% versus 63%, 53% versus 57%, and 71% versus 66%, respectively. CONCLUSION: Amifostine reduced acute and chronic xerostomia. Antitumor treatment efficacy was preserved.

Three-dimensional conformal therapy or standard irradiation in localized carcinoma of prostate: preliminary results of a nonrandomized comparison.

PURPOSE: We present preliminary results of a nonrandomized comparison of three-dimensional conformal radiation therapy (3D CRT) and standard radiation therapy (SRT) in localized carcinoma of the prostate in two groups of patients with comparable prognostic factors treated during the same period. METHODS AND MATERIALS: Between January 1992 and December 1997, 146 patients were treated with 3D CRT and 131 with SRT alone for clinical stage T1c or T2 histologically confirmed carcinoma of the prostate. None of these patients received hormonal therapy. Mean follow-up for all patients is 3 years (range, 1-6 years). For 3D CRT, 7 intersecting fields were used (Cerrobend blocking or multileaf collimation) to deliver 68-73.8 Gy to the prostate; 3D dose distributions and dose-volume histograms (DVHs) of the planning target volume, bladder, and rectum were obtained. SRT consisted of bilateral 120 degrees rotational arcs, with portals with 2-cm margins around the prostate to deliver 68-70 Gy to the prostate. The criterion for chemical disease-free survival was a postirradiation prostate-specific antigen (PSA) (Tandem-R, Hybritech) value following the American Society for Therapeutic Radiology and Oncology guidelines. Symptoms during treatment were quantitated weekly, and late effects were assessed every 4-6 months. RESULTS: DVHs showed a two-thirds reduction in normal bladder or rectum receiving 70 Gy or more with 3D CRT. Higher 5-year chemical disease-free survival was observed with 3D CRT (91% for T1c and 96% for T2 tumors) compared with SRT (53% and 58%, respectively). There was no statistically significant difference in chemical disease-free survival in patients with Gleason score of 4 or less (p = 0.83), but with Gleason score of 5-7, the 5-year survival rates were 96% with 3D CRT and 53% with SRT (p < or = 0.01). In 111 patients with pretreatment PSA of 10 ng/mL or less, treated with 3D CRT, the chemical disease-free rate was 96% vs. 65% in 94 patients treated with SRT (p < or = 0.01). In patients with PSA of 10. 1-20 ng/mL, the chemical disease-free survival rate for 26 patients treated with 3D CRT was 88% compared with 40% for 20 patients treated with SRT (p = 0.05). The corresponding values were 71% and 26%, respectively, for patients with PSA levels of greater than 20 ng/mL (p = 0.30). On multivariate analysis, the most important prognostic factors for chemical failure were pretreatment PSA (p = 0. 023), nadir PSA (p = 0.001), and 3D CRT technique (p = 0.033). Moderate dysuria and difficulty in urinating were reported by 2-5% of patients treated with 3D CRT in contrast to 6-9% of patients treated with SRT; moderate urinary frequency and nocturia were reported by 18-24% treated with 3D CRT and 18-27% of patients in the SRT group. The incidence of moderate loose stools/diarrhea, usually after the 4th week of treatment, was 3-5% in the 3D CRT patients and 8-19% in the SRT group. Late intestinal morbidity (proctitis, rectal bleeding) was very low (1.7%) in the 3D CRT group in contrast to the SRT patients (8%). CONCLUSION: Three-dimensional CRT spares more normal tissues, yields higher chemical disease-free survival, and results in less treatment morbidity than SRT in treatment of Stage T1-T2 prostate cancer. Longer follow-up is needed to confirm these preliminary observations.

The benefit of treatment intensification is age and histology-dependent in patients with locally advanced non-small cell lung cancer (NSCLC): a quality-adjusted survival analysis of radiation therapy oncology group (RTOG) chemoradiation studies.

PURPOSE: Currently, chemoradiation treatment strategies in locally advanced NSCLC are essentially the same irrespective of tumor histology or patient age. The purpose of this study is to analyze the impact of age, histology, Karnofsky performance status (KPS), and specific toxicities on the median survival time (MST) and quality-adjusted survival (QTime) for each treatment strategy. METHODS AND MATERIALS: Nine hundred seventy-nine patients with Stage II-IIIB inoperable NSCLC were enrolled on 6 prospective Phase II and III studies from 1983 to 1995. Treatment regimens ranged from standard RT (SRT) to 60 Gy, hyperfractionated RT (HRT) to 69.6 Gy, induction chemotherapy (ICT) of cisplatin (CIS) and vinblastine (VBL) followed by SRT, ICT + concurrent CT (CCT) + SRT, and CCT + HRT; CCT consisted of etoposide or VBL + CIS. Toxicities assessed were skin, mucous membrane, lung, esophagus, neurologic, hematologic, and upper GI. QTime was calculated by weighting the time spent with a specific toxicity, as well as local or distant tumor progression. Each toxicity was weighted with increasing severity as the toxicity increased in grade. RESULTS: As expected, patients with the worst KPS (50-70) had the lowest MST (7.8 months) and QTime (6.7 months). Patients <70 years had improved survival with more aggressive therapy (i.e., ICT + SRT or CCT + HRT), while patients > 70 years achieved the best QTime with standard RT (SRT) alone. In patients with squamous cell carcinoma, those treated with ICT + CCT + SRT had dramatically improved MST (25.7 months) and QTime (21.8 months) compared to the other treatment regimens (11.7-12.8 and 10.7-12 months, respectively). Patients with adenocarcinoma, however, generally manifested incrementally better MST and QTime as the therapies intensified. Within the concurrent chemoradiation arms, the upper GI and lung toxicities had the greatest impact on QTime. CONCLUSION: This quality-adjusted survival analysis suggests that there is a critical relationship between the type of histology and its optimal treatment, age and the ability to tolerate intensive therapy, and the need to reduce lung and upper GI toxicities.

Sequential chemotherapy (etoposide, vinblastine, and doxorubicin) and subtotal lymph node radiation for patients with localized Hodgkin disease and unfavorable prognostic features: A phase II Cancer and Leukemia Group B Study (9051).

BACKGROUND: The aim of this study was to evaluate a regimen of sequential chemotherapy and radiotherapy for patients with Hodgkin disease. METHODS: The Cancer and Leukemia Group B conducted a Phase II study of three cycles of etoposide, vinblastine, and doxorubicin (EVA) chemotherapy followed by subtotal lymph node radiation for patients with localized Hodgkin disease and unfavorable prognostic features. Fifty-nine patients were enrolled in the study. Fifty-three patients met all study eligibility criteria; 48 of them (91%) had mediastinal disease and 29 (55%) had bulky mediastinal disease. RESULTS: A complete response (CR) occurred in 35 of the patients (66%). Of all patients who had CR, 26% had the CR after the chemotherapy and before the radiation, and 74% after the chemotherapy and radiation. Twenty percent of the patients who had CR experienced disease progression; in these patients, the progression was outside the radiotherapy field in the lung and involved widespread disease. CONCLUSIONS: EVA offers a nonbleomycin-containing alternative for patients in whom preexisting pulmonary disease may be exacerbated by bleomycin and radiation therapy. EVA, as given in this study (in three cycles), was insufficient chemotherapy for patients who had disease in areas outside the radiation fields (occult disease).

American Society of Clinical Oncology clinical practice guidelines for the use of chemotherapy and radiotherapy protectants.

PURPOSE: Because toxicities associated with chemotherapy and radiotherapy can adversely affect short- and long-term patient quality of life, can limit the dose and duration of treatment, and may be life-threatening, specific agents designed to ameliorate or eliminate certain chemotherapy and radiotherapy toxicities have been developed. Variability in interpretation of the available data pertaining to the efficacy of the three United States Food and Drug Administration-approved agents that have potential chemotherapy- and radiotherapy-protectant activity-dexrazoxane, mesna, and amifostine-and questions about the role of these protectant agents in cancer care led to concern about the appropriate use of these agents. The American Society of Clinical Oncology sought to establish evidence-based, clinical practice guidelines for the use of dexrazoxane, mesna, and amifostine in patients who are not enrolled on clinical treatment trials. METHODS: A multidisciplinary Expert Panel reviewed the clinical data regarding the activity of dexrazoxane, mesna, and amifostine. A computerized literature search was performed using MEDLINE. In addition to reports collected by individual Panel members, all articles published in the English-speaking literature from June 1997 through December 1998 were collected for review by the Panel chairpersons, and appropriate articles were distributed to the entire Panel for review. Guidelines for use, levels of evidence, and grades of recommendation were reviewed and approved by the Panel. Outcomes considered in evaluating the benefit of a chemotherapy- or radiotherapy-protectant agent included amelioration of short- and long-term chemotherapy- or radiotherapy-related toxicities, risk of tumor protection by the agent, toxicity of the protectant agent itself, quality of life, and economic impact. To the extent that these data were available, the Panel placed the greatest value on lesser toxicity that did not carry a concomitant risk of tumor protection. RESULTS AND CONCLUSION: Mesna: (1) Mesna, dosed as detailed in these guidelines, is recommended to decrease the incidence of standard-dose ifosfamide-associated urothelial toxicity. (2) There is insufficient evidence on which to base a guideline for the use of mesna to prevent urothelial toxicity with ifosfamide doses that exceed 2.5 g/m(2)/d. (3) Either mesna or forced saline diuresis is recommended to decrease the incidence of urothelial toxicity associated with high-dose cyclophosphamide use in the stem-cell transplantation setting. Dexrazoxane: (1) The use of dexrazoxane is not routinely recommended for patients with metastatic breast cancer who receive initial doxorubicin-based chemotherapy. (2) The use of dexrazoxane may be considered for patients with metastatic breast cancer who have received a cumulative dosage of 300 mg/m(2) or greater of doxorubicin in the metastatic setting and who may benefit from continued doxorubicin-containing therapy. (3) The use of dexrazoxane in the adjuvant setting is not recommended outside of a clinical trial. (4) The use of dexrazoxane can be considered in adult patients who have received more than 300 mg/m(2) of doxorubicin-based therapy for tumors other than breast cancer, although caution should be used in settings in which doxorubicin-based therapy has been shown to improve survival because of concerns of tumor protection by dexrazoxane. (5) There is insufficient evidence to make a guideline for the use of dexrazoxane in the treatment of pediatric malignancies, with epirubicin-based regimens, or with high-dose anthracycline-containing regimens. Similarly, there is insufficient evidence on which to base a guideline for the use of dexrazoxane in patients with cardiac risk factors or underlying cardiac disease. (6) Patients receiving dexrazoxane should continue to be monitored for cardiac toxicity. Amifostine: (1) Amifostine may be considered for the reduction of nephrotoxicity in patients receiving cisplatin-based chemoth

Radioprotective effects of amifostine.

Effective radiotherapy for patients with cancer should include maximal tumor cell killing with minimal injury to normal tissue. However, current radiation doses that can be delivered without causing severe damage to surrounding normal tissues are often insufficient to eradicate a tumor. Recently, a number of agents have been developed to protect normal tissue from the harmful effects of antitumor therapies. The aminothiol amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) has been the subject of extensive research as a prospective protector. While this drug has been approved for use to reduce toxicities associated with cisplatin, several studies also have demonstrated that amifostine protects normal tissues from both acute and late radiation damage without protecting the tumor. Consequently, higher radiation doses could be used with less than or equal risk to surrounding normal tissues. This report reviews the physicochemical basis of radiation therapy on biologic tissues and the mechanisms responsible for the cytoprotective effects of amifostine. The increasing body of biochemical, preclinical, and clinical data could justify the use of protectors such as amifostine with radiotherapy to provide improved therapeutic efficacy and quality of life for the patient.

Irradiation with or without misonidazole for patients with stages IIIB and IVA carcinoma of the cervix: final results of RTOG 80-05. Radiation Therapy Oncology Group.

PURPOSE: The purpose of this study was to evaluate tumor response, progression-free survival, local tumor control, patterns of relapse, and toxicity in patients with Stages IIIb and IVa squamous cell carcinoma of the uterine cervix treated with irradiation or irradiation and misonidazole. This is a report of the final results of the study. METHODS: This study was a prospective randomized Phase III trial performed by the Radiation Therapy Oncology Group (RTOG). Between August 1980 and November 1984, 120 patients with Stages IIIb and IVa squamous cell carcinoma of the cervix were randomized to receive either standard irradiation or standard irradiation and misonidazole. Irradiation consisted of 46 Gy to the pelvis plus a 10 Gy parametrial boost followed by intracavitary brachytherapy or external irradiation boost to the primary tumor. Misonidazole was administered at 400 mg/m2 daily, 2-4 h before irradiation. Patients in the 2 treatment groups were evenly distributed by stage, Karnofsky Performance Status, and positive para-aortic lymph nodes. RESULTS: Sixty-one patients were treated with irradiation alone, and 59 patients received irradiation and misonidazole. Complete response in the pelvis occurred in 44 (75%) of those treated with irradiation and in 38 (64%) of those treated with irradiation and misonidazole. The progression-free survivals were 22% at 5 years for the control group, and 29% at 5 years for the misonidazole group. At the time of last follow-up, 18 patients in the control arm were free of disease, and in the experimental arm, 19 were free of disease. The patterns of failure for those treated with irradiation alone were local-only in 9 patients, distant-only in 8 patients, and local and distant in 11 patients. The patterns of failure for those receiving irradiation and misonidazole were local-only in 3 patients, distant-only in 8 patients, and local and distant in 8 patients. The maximum toxicity experienced per patient was grade 3 in 18%, grade 4 in 8%, and no grade 5 toxicity for those treated with irradiation alone compared to 8%, 2%, and 2%, respectively, for the experimental arm. CONCLUSION: There were no statistically significant differences in pelvic response, disease-free survivals, patterns of failure, or toxicity for the irradiation alone group or for the irradiation and misonidazole group as administered in this study for patients with Stages IIIb and IVa squamous cell carcinoma of the uterine cervix.

Physician resource utilization in radiation oncology: a model based on management of carcinoma of the prostate.

PURPOSE: To develop a methodology to estimate the comparative cost of physician time in treating patients with localized prostate cancer, using as an example two-dimensional (2D) vs. three-dimensional (3D) conformal irradiation techniques, and to illustrate how current cost-accounting techniques can be used to quantify the cost of physician time and effort of any treatment. METHODS AND MATERIALS: Activity-based costing, a recent innovation in accounting, widely recommended for estimating and managing the costs of specific activities, was used to derive physician resource utilization costs (actual cost of the physician services and related support services consumed). RESULTS: Patients treated with 3D conformal irradiation consume about 50% more physician time than patients receiving 2D conventional radiation therapy. The average professional reimbursement for the 3D conformal irradiation is only about 26% more than for the 2D treatment. Substantial variations in cost are found depending on the total available physician working hours. In an academic institution, a physician working 40 hours a week would have to spend an average of about 60% of available time on clinical services to break even on a 2D treatment process and over 74% of available time on clinical work to break even on a 3D treatment process. The same physician working 50 hours a week would have to spend an average of about 48% of available time on 2D clinical services and about 60% of available time on 3D clinical work to break even. Current Medicare reimbursement for 3D treatment falls short of actual costs, even if physicians work 100% of a 50-hour week. Medicare reimbursement for 2D barely allows the department to break even for 2D treatments. CONCLUSIONS: Costs based on estimates of resource use can be substantially under- or overestimated. A consistent language (method) is needed to obtain and describe the costs of radiation therapy. The methodology described here can help practitioners and researchers more accurately interpret actual cost information. Future use of such cost-estimation methodologies could provide consistent and comparable costs for negotiations with health care providers and help assess different treatment strategies.

When is a negative study not negative?

Results of Phase III randomized clinical trials can be categorized into three groups: positive, null, and negative. The jargon used in discussing results of comparative studies requires clarification because misclassification can result in incorrect interpretation. A positive result indicates that the experimental therapy(ies) is(are) superior to standard therapy. A null result indicates that no statistically significant difference between therapies was found; hence, standard therapy should not be replaced. A negative result indicates that the experimental therapy had a deleterious effect compared to standard therapy. This article presents a discussion of these categories and examples of each.

Cost benefit of emerging technology in localized carcinoma of the prostate.

PURPOSE: In a health care environment strongly concerned with cost containment, cost-benefit studies of new technology must include analyses of loco-regional tumor control, morbidity, impact on quality of life, and financial considerations. METHODS AND MATERIALS: This nonrandomized study analyzes 124 patients treated with three-dimensional conformal radiation therapy (3D CRT) and 153 with standard irradiation (SRT) between January 1992 and December 1995, for histologically proven adenocarcinoma of prostate, clinical Stage T1 or T2. Mean follow-up is 1.4 years. Three-dimensional CRT consisted of six or seven coplanar oblique and lateral and, in some patients, AP fields designed to treat the prostate with a 1 to 1.7 cm margin. SRT consisted of 120 degrees bilateral arc rotation. Total doses to prostate were 67 to 70 Gy when pelvic lymph nodes were irradiated or 68.4 to 73.8 Gy when prostatic volume only was treated; dose per fraction was 1.8 Gy. Patients were interviewed weekly for severity of 12 acute intestinal and urinary pelvic irradiation side effects (0 to 4+ grading). Time and effort for 3D RTP and daily treatment with 3D CRT and SRT were recorded. Dose-volume histograms (DVHs) were calculated for gross tumor volume, planning target volume, bladder, and rectum. Actual reimbursement to the hospital and university was determined for 41 3D CRT, 43 SRT, and 40 radical prostatectomy patients treated during the same period. RESULTS: Average treatment planning times (in minutes) were: 101 for 3D conformal therapy simulation, 66 for contouring of target volume and sensitive structures, 55 for virtual simulation, 39 for plan preparation and documentation, 65 for physical simulation, and 20 for approval of treatment plan. Daily mean treatment times were 19 min for 3D CRT with Cerrobend blocking, 16 with multileaf collimation, and 10 with bilateral arc rotation. Dosimetric analysis (DVHs) showed a reduction of 50% in volume of bladder or rectum receiving doses higher than 65 Gy. Acute side effects included dysuria, moderate difficulty in urinating, and nocturia in 25-39% of both SRT and CRT patients; loose stools or diarrhea in 5-12% of 3D CRT and 16-22% of SRT patients; moderate proctitis in 3% of 3D CRT and 12% of SRT patients (p = 0.01). Chemical disease-free survival (prostate-specific antigen < or =2 ng/ml) at 3 years was 90% with 3D CRT and 80% with SRT (p = 0.01). Average initial treatment reimbursements were $13,823 (3D CRT), $10,864 (SRT), and $12,250 (radical prostatectomy). Average total treatment reimbursement and projected cost of management of initial therapy failures per patients were $15,173, $16,264, and $16,405, respectively. CONCLUSIONS: Three-dimensional CRT irradiated less bladder and rectum volume than SRT; CRT initial reimbursement was 28% higher than SRT and 12% higher than radical prostatectomy. Because of projected better local tumor control, average total cost of treating a patient with 3D CRT or radical prostatectomy is equivalent to cost of SRT. Treatment morbidity was lower with 3D CRT. Our findings reflect an overall benefit with 3D CRT as a new promising technology in treatment of localized prostate cancer. Dose-escalation studies may enhance its efficacy and cost benefit.

The perception of sexual attractiveness: sex differences in variability.

Results of three independent studies supported predictions derived from evolutionary theory: Men's assessments of sexual attractiveness are determined more by objectively assessable physical attributes; women's assessments are more influenced by perceived ability and willingness to invest (e.g., partners' social status, potential interest in them). Consequently, women's assessments of potential partners' sexual attractiveness and coital acceptability vary more than men's assessments. The proposition that polygamous women's assessments of men's sexual attractiveness vary less than those of monogamous women (because the former allegedly are more influenced by target persons' physical attributes) was also tested. In Study 1 male college students showed more agreement than females in their rankings of the sexual attractiveness of opposite-sex target persons. Target persons' flesh and bodily display enhanced this sex difference. In Study 2 men exhibited less variance than did women in their ratings of target persons' acceptability for dating and sexual relations. Women who viewed models described as having low status showed more variability than did women in the high-status condition. In Study 3 women showed more variability than men did in their ratings of 20 opposite-sex celebrities' sexual attractiveness. Studies 2 and 3 included the Sociosexual Orientation Inventory (SOI)-a measure of polygamous attitudes and behavior. Women's SOI scores did not affect the variability of their assessments in either Study 2 or 3. In Study 3 men with low SOI scores showed less variability than did men with high SOI scores. Alternative explanations of the findings are examined. Theoretical and empirical implications are discussed.