Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil.

PURPOSE: To compare sequential methotrexate (M) and fluorouracil (F) (M-->F) with surgery (National Surgical Adjuvant Breast and Bowel Project [NSABP] B-13) and cyclophosphamide (C), M, and F with M-->F (NSABP B-19), in patients with estrogen receptor (ER)-negative tumors and negative axillary nodes. PATIENTS AND METHODS: A total of 760 patients were randomized to B-13; 1,095 patients with the same eligibility requirements were randomized to B-19. Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were determined using life-table estimates. RESULTS: A significant benefit in overall DFS (74% v 59%; P < .001) was demonstrated at 8 years in all B-13 patients who received M-->F (69% v 56% [P = .006] in those or= 50 years). A survival advantage was evident in older patients (89% v 80%; P = .03). In B-19, through 5 years, an overall DFS advantage (82% v 73%; P < .001) and a borderline survival advantage (88% v 85%; P = .06) were evident with CMF. The DFS (84% v 72%; P < .001) and survival (89% v 84%; P = .04) benefits from CMF were greater in women aged F or CMF after lumpectomy and breast irradiation resulted in a low probability of ipsilateral breast tumor recurrence (IBTR). In B-13, the frequency of IBTR was 2.6% following M-->F versus 13.4% in women treated by lumpectomy; it was 0.6% following CMF in B-19. Toxicity >or= grade 3 was more frequent among CMF patients in B-19. The age-related difference in CMF benefit was not related to amount of drug received. CONCLUSION: M-->F and CMF are effective for node-negative patients with ER-negative tumors. The incidence of local-regional or distant metastases and IBTR decreased after either therapy. The benefit from either therapy was evident in all patients, but the CMF advantage was greater in those F may be used in patients with medical problems that would preclude CMF administration.

Breast conservation radiation therapy technique for women with large breasts.

A technique is presented for the conservative irradiation of women with huge (size "EE") breasts. Patients are treated in a modified lateral decubitus position with an immobilization device. The technique is easily reproducible and allows favorable cosmetic outcome. The isodose plots for treatment with this technique are compared to treatment in standard fashion. We feel that this reproducible technique offers breast conserving therapy to women with large breasts, without poor cosmesis.

A technique for delivery of total body irradiation for bone marrow transplantation in adults and adolescents.

With the increasing use of bone marrow transplantation for cancer, total body irradiation is becoming a more commonplace procedure in many of the larger centers across the country. The technical difficulties in delivering homogenous doses of radiation to the whole body are significant and involve many factors such as creation of a homogeneous, "flat" beam of radiation, and dealing with variations in patient thickness and tissue homogeneity, particularly in the lung. In addition, techniques must be used to safely and efficiently deal with patients who are usually very ill and require long treatment times. Although there is often an advantage in terms of dosimetry to using an AP/PA treatment technique, many institutions use parallel opposed lateral beams because of equipment and facility limitations. A technique has been devised that enables total body irradation to be given by an AP/PA technique using equipment available in many radiotherapy departments. Patients are supported in an upright position during treatment by means of a modified harness attached to the ceiling of the treatment room. Lung compensators are fixed to individually fitted "vests," allowing the patient moderate amounts of movement during treatment while maintaining the position of the compensator relative to the lungs. Thermoluminiscent dosimeter (TLD) dose measurements in a phantom indicate that this system can deliver accurate and homogeneous doses to lung tissue, while allowing a good degree of patient comfort and safety during the long treatment times that are required.

The distribution of power and heat produced by interstitial microwave antenna arrays: I. Comparative phantom and canine studies.

To adequately plan and administer localized hyperthermia with interstitial microwave antennas, the thermal distribution patterns generated by such antennas must be characterized. This study evaluated the performance of single node 915 MHz antennas operating either alone or as a 2 cm square array of four parallel antennas using both muscle-equivalent phantoms and canine thigh muscle. Two types of measurements were compared. Specific absorption rate (SAR), where temperature increases resulting from short duration microwave pulses were used to define power distribution, and temperature gradients during simulated hyperthermia treatments. SAR measurements in phantoms were comparable to those obtained in non-perfused canine muscle demonstrating the usefulness of the phantom for these measurements. For a single antenna there was a rapid decrease in power radially which resulted in a steep thermal gradient at distances within 0.5 cm. However, the power generated by a four-antenna array was highest along its central axis and declined to approximately 50% near the antennas at the array periphery. Along the central axis of the array power decreased most rapidly distal to the antenna nodes. The distribution of temperature measured during simulated hyperthermia treatments in phantoms paralleled the SAR distribution and was comparable to the temperature gradient observed in perfused canine muscle, suggesting that phantoms could be used to predict temperature distributions in resting muscle tissue.

The distribution of power and heat produced by interstitial microwave antenna arrays: II. The role of antenna spacing and insertion depth.

The distribution of power and temperature generated by 915 MHz interstitial microwave antenna arrays was studied in static muscle-equivalent phantoms and both perfused and non-perfused canine thigh muscle. These arrays, which would form the geometric basis of larger volume implants, consisted of four parallel antennas oriented such that transverse to their long axes they formed the corners of a square. Arrays with 2 and 3 cm sides were compared at various depths of insertion where the nodes for all four antennas were coincident at the same depth. The position relative to the antenna nodes of the maximum power and highest temperature within the array volume varied with the depth of insertion of the antennas. Though power dropped rapidly distal to the nodes at all depths, a shift in the location of the maximum power proximal to the nodes resulted in an increase in the effective heating volume at certain insertion depths. For 2 cm array spacing the highest power and temperature were measured along the central axis of the array at all insertion depths. However, arrays using 3 cm spacing generated their maximum power adjacent to the antennas with only 50% of this level occurring along the central axis. When the temperature produced by 3 cm arrays was measured in phantoms midway through simulated 30-minute hyperthermia treatments, the effect of thermal conduction on the temperature distribution was evident. Though power was only 50% centrally, the highest temperatures occurred there. This same pattern of central heating occurred in perfused canine muscle demonstrating the importance of conductive and convective heat redistribution in reducing thermal gradients within the array volume.

Therapeutic responses of spontaneous canine malignancies to combinations of radiotherapy and hyperthermia.

The goals of this ongoing Phase III study of adjuvant local hyperthermia with radiotherapy were to evaluate how tumor control and normal tissue complications were related to patient and treatment variables. Canine veterinary patients with localized malignancies were stratified by histology and anatomic site and randomized into three groups. All patients received radiotherapy (60CO) in 3.5 Gy fractions given Mon-Wed-Fri to 14 treatments (49 Gy). One group received radiotherapy alone while the others also received microwave-induced hyperthermia (44 degrees C) for 30 minutes once each week. Hyperthermia followed radiotherapy and was given to one group immediately and delayed 4-5 hours in the other. Adjuvant hyperthermia resulted in a significant (p less than .05) increase in complete response rate, reduction in the frequency of non-responders, and increased persistent local control relative to radiotherapy alone. Hyperthermia increased the complete response rate regardless of histology, site, or volume and with the current sample size control was significantly (p less than .05) greater for sarcomas, tumors of the trunk and extremities, and those with volumes less than 10 cc. Quantitative clinical assessment of the acute response of skin and oral mucosa indicated that hyperthermia significantly enhanced these acute reactions, which required roughly twice the healing time observed with radiotherapy alone. Quantitative histologic scoring of changes seen between pre- and post-therapy skin biopsies indicated that a treatment induced decline in the frequency of dermal blood vessels, sebaceous glands, and hair follicles was enhanced by adjuvant hyperthermia, particularly in the late response evaluation interval. The probability of tumor control and adverse normal tissue responses correlated with several measures of thermal dose. Thermal doses in excess of 120 equivalent minutes at 43 degrees C correlated positively with increased skin reactions and negatively with the complete response rate, and these trends were usually evident during the animals' first treatment.

Rhabdomyosarcoma in children. A clinicopathologic study of 35 patients.

Thirty-five patients with rhabdomyosarcoma were treated at the Children's Hospital Medical Center from 1953 to 1973. Factors important in diagnosis and prognosis included age, sex, site, stage of tumor, and specific pathologic type. Effects that surgery, radiation, and chemotherapy had on survivals were also analyzed. Survivals ranged from 2 to 20 years. The rates were 86% for Stage I disease; 40% for Stage II disease, and 0 for the more advanced lesions. A useful prognostic indicator was found in pathologic subgroupings. Survivals for the myxoid spindle-cell variant were 80% for all stages. For the partial maturation series with moderately well-differentiated rhabdomyoblasts, survival was 10% for all stages. For a combination of the above two types, survival was 40% for all stages. The alveolar types had no survivors, although these patients seemed to live longer with their disease.

Bilateral synchronous breast cancer: mode of detection and comparison of histologic features between the 2 breasts.

BACKGROUND: Bilateral synchronous breast cancer is uncommon (accounting for 1.0%-2.6% of all patients with breast cancer), and most physicians do not accumulate a large personal experience of patients with this disease. We reviewed our experience with patients with bilateral synchronous breast cancer, focusing on the mode of detection and histologic features in the 2 breasts. METHODS: The charts of patients who were treated at this institution for bilateral synchronous breast cancer during the 15-year period of 1984 through 1999 were reviewed. Information regarding age, mode of detection, histopathologic features, treatment, and overall survival were analyzed. RESULTS: During the study period, 51 patients (all women) were treated at our institution for bilateral synchronous breast cancer. This comprised 2.1% of all patients (n = 2382 patients) treated for breast cancer during the same period of time. The first cancer was detected by palpation in 81% and by mammography in 14%. The corresponding figures for the contralateral cancer were 24% and 54%, respectively. The histologic type of cancer was identical in the 2 breasts in 29 patients (57%) and was different between the 2 breasts in 22 patients (43%). The overall 10-year survival rate was 63%. CONCLUSIONS: Bilateral synchronous breast cancer is often detected by mammography and is frequently of the same histologic type as the index cancer. A better awareness of the risk for this disease may help detect bilateral breast cancer earlier.

Radiation therapy in prostate cancer: whole pelvis with prostate boost or small field to prostate?

The purpose of this retrospective study is to identify prostate cancer patients who would benefit from pelvic nodes irradiation (whole pelvis) as opposed to the small-field irradiation to the prostate only. Between 1975 and 1983, 126 patients were treated by whole pelvis (4,600-5,000 cGY) with prostate boost (2,000 cGY) radiation (WP + P). Median follow-up was six years and six months. Comparison was made with historic control of 116 patients irradiated at the same institutions between 1971 and 1977 by small field to the prostate (P) to a dose of 7,000-7,500 cGY. There was a significant five-year survival improvement in the current WP + P radiation in Stage C (72% vs 40%, p = 0.0004) and Stage B (92% vs 70%, p = 0.025) but not in Stage A2 patients. However, WP + P radiation significantly improved disease-free survival (DFS) in only well and moderately but not in poorly differentiated carcinoma with a combined well and moderately differentiated five-year DFS of 63 percent compared with the 45 percent in P radiation (p = 0.0228). Local tumor control was significantly improved in WP + P radiation in only Stage C cancers with their local recurrence rate 16 percent as compared with the 34 percent in P radiation (p = 0.0172). Although acute radiation reactions were more frequent in WP + P than P radiation (61% vs 41%, p = 0.0022), chronic radiation morbidity in both series were similar. Thus, whole pelvis with prostate boost radiation should be utilized in Stage B and Stage C cancers as this has shown to increase the survival of the patient without increasing chronic radiation morbidity.

Comparison of whole pelvis versus small-field radiation therapy for carcinoma of prostate.

One hundred thirty-six patients with adenocarcinoma of the prostate gland Stage A2 (12 patients), Stages B1 and B2 (26), Stage C (64), and Stages D1 and D2 (34 patients) were evaluated clinically and treated in a similar fashion at three hospitals. Megavoltage radiation therapy units were employed to deliver 4,600-5,000 cGy to the whole pelvis, and the prostatic area was treated for an additional 2,000 cGy (boost). Local recurrence was infrequent (8/136 = 6%), and the five-year actuarial survival and disease-free survival rates were 85 and 42 per cent, respectively. Adverse clinical parameters included poor histologic differentiation, age younger than sixty years, and diagnosis by transurethral resection of the prostate rather than needle biopsy in Stage C patients. Severe acute reactions occurred in only 2 patients, and only 2 patients were hospitalized for severe chronic (late) reactions. Whole pelvis radiation yielded a statistically significant improved five-year survival and three-year disease-free survival for similarly evaluated patients for Stage C but not for Stages A and B when compared with 116 patients treated with small-volume radiation (prostate area), previously reported from these three hospitals.

Specific absorption rates in simulated tissue media for a 10 x 10 cm 915-MHz waveguide applicator.

The use of hyperthermia in combination with radiotherapy is currently being investigated at many cancer treatment facilities. Several different types of heating modalities are presently being used and for each of these systems it is important to determine the power distributions of their hyperthermia applicators in tissue-equivalent phantoms. This information will be used for treatment planning, routine quality assurance, and acceptance testing as well as for comparison between these various modalities and systems. This report describes the power distribution characteristics of the Clini-Therm 10 x 10 cm 915-MHz waveguide applicator measured within muscle tissue phantom materials arranged in several clinically relevant treatment configurations. The net increase in temperature that resulted from 20-s pulses of microwave power was measured at various points within each phantom by the system's implantable fiberoptic temperature sensors. From these temperature measurements the distribution of power was calculated as specific absorption rates (SAR). The results are displayed as two-dimensional ISO-SAR maps which relate power levels throughout the irradiated volume to those obtained on the central axis of the applicator. When the applicator was in direct contact with the muscle phantom the highest SAR measured was 2 cm lateral to its central axis along the muscle surface. On the central axis approximately 50% of the power was attenuated by each centimeter of muscle material. The introduction of either fat, bone, or a water-filled pad between the applicator and the muscle altered the pattern of power distribution within the irradiated volume without substantially altering the relative distribution of power along the central axis.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiation-associated gliomas: a report of four cases and analysis of postradiation tumors of the central nervous system.

Four cases of radiation-associated gliomas are described. All patients were white men, irradiated in childhood for craniopharyngioma, anaplastic ependymoma, retinoblastoma of the orbit, and Burkitt's lymphoma, respectively. The dose ranged from 1800 to 5900 rads, and the latency period was 5 to 25 years. All primary and secondary tumors were verified histologically, and no evidence of persistence of the primary tumors was found. All secondary tumors arose in the fields of irradiation. Ninety-six cases of radiation-induced tumors of the central nervous system have been reported in the literature to date. Twenty-four were gliomas and occurred mainly in young men.

Malignant thymoma with metastases to the gastrointestinal tract and ovary: a case report and literature review.

This is the first clinical case report of a thoracic invasive thymoma metastatic to the ovary with disease noted in the entire abdomen including the pelvis 5 1/2 years after initial diagnosis. The involved areas of metastases include the distal ileum, peritoneal and serosal surfaces (including the surface of the distal colon, bladder, and pelvis), and the surface of the right ovary. The patient survived 13 years after her initial diagnosis and 7 1/2 years after discovery of her metastases. Thymomas are rare tumors but comprise the most common primary tumor of the anterior mediastinum. Extrathoracic metastases of malignant thymomas are also rare, and the literature reports that the most common sites for metastases are the liver, lung, lymph nodes, and bone. Extrathoracic disease is associated with a poor prognosis. The average time of survival after the diagnosis of metastases is 1.5 years.

Safety of radiating jejunal interposition grafts in head and neck cancer.

The safety of high-dose postoperative radiation therapy to a jejunal graft has not been established in the literature. The purpose of the present study is to review the effect of postoperative radiation on swallow function in patients who have received a jejunal interposition graft as part of their reconstruction after cancer resection. Charts of patients undergoing hypopharyngeal resections for cancers with placement of jejunal interposition grafts who received postoperative radiation therapy were reviewed. Swallow function was determined from records of patients' subjective characterization of their swallow function, records of weights at each visit, use of gastrostomy tube, need for jejunal dilatation and review of barium swallows. Seventeen patients were identified who had undergone resection of cancers with jejunal interpositions and postoperative radiation therapy. Four patients never regained adequate swallow function postoperatively to allow G-tube removal. The remaining thirteen patients had their G-tubes removed, generally several months after resection, and were able to obtain adequate nutrition orally to maintain or increase their weights. The present series suggests that a segment of jejunum transferred into the neck after laryngopharyngoesophagectomy can be irradiated to high dose with generally acceptable morbidity.

The reirradiation of recurrent bronchogenic carcinoma with external beam irradiation.

Symptomatic local failure following thoracic irradiation for bronchogenic carcinoma presents a clinical challenge to the Radiation Oncologist. We retrospectively evaluated the efficiency of reirradiation with external beam radiation of 30 patients. The median dose of initial irradiation was 6,000 cGy in 6 weeks. The median time following initial irradiation to recurrence was 12 months. The median dose of retreatment was 3,030 cGy in 3 weeks. Of the symptomatic patients, 88% and 70% subjectively responded to initial irradiation and to reirradiation, respectively. Retreatment toxicity included radiation esophagitis (6 patients), dry desquamation (4 patients), and symptomatic radiation pneumonitis (1 patient). Based on this study, doses of external beam radiation in the range of 2,000-3,000 cGy in 2 to 3 weeks appear safe and effective in reirradiating recurrent bronchogenic carcinoma.

Concurrent radiotherapy and chemotherapy for locally advanced non-small-cell cancer of the lung. Report of a clinical trial and review of the literature.

A prospective nonrandomized phase II study was begun in 1985 using concurrent split-course radiation and chemotherapy in the treatment of locally advanced non-small-cell cancer of the lung. Patients were treated with 3,000 cGy of radiation in 15 fractions to the chest, together with 100 mg/m2 cisplatin on day 1 and 1,000 mg/m2/day 5-fluorouracil infusion on days 1-4. The radiation and chemotherapy were then repeated after a 1-week break. Twenty-one patients were treated, with five patients having a complete response and nine patients having a partial response for an overall response rate of 67%. With a minimum of 24 months follow-up, five patients remain alive. Median survival for the entire group is 11.6 months. The toxicity of the treatment regimen was acceptable. These results do not differ significantly from survivals of similar patients treated with radiation alone, including a series from our own institution. The literature on concurrent chemotherapy and radiation is reviewed and possible future approaches to this tumor are discussed.

Management of radiation-induced moist skin desquamation using hydrocolloid dressing.

Moist skin desquamation has been of concern to radiation oncologists, nurses and patients since the inception of this mode of therapy. As radiation treatment machines became more sophisticated, severe reactions became less of a problem. However, with the increasing use of chemotherapy and radiation as combined modalities, moist skin reaction is occurring with greater frequency. A noncomparative study of 20 patients using a hydrocolloid occlusive dressing (Duoderm) was initiated. The purpose of the study was to determine whether moist occlusive healing would be beneficial. The dressing was evaluated on the basis of healing time, safety, wound temperature, bacterial growth, and comfort. Data were collected using photographs, bacterial cultures, temperature probes, and patient evaluations. Eighteen patients completed the study. All patients' skin reactions healed. There were no wound infections evident. Mean healing time was 12 days, with mean wound temperature relative to body core -0.8 degree C on day 1 and -1.2 degrees C on the healed site. Patient results on comfort were: 8 of 18 excellent, 7 of 18 good, 3 of 18 fair, and 0 of 18 poor. The results of this study indicate that a hydrocolloid occlusive dressing can be effective in the healing process of moist skin reaction that is due to radiation therapy.

Imaging of irradiated liver with Tc-99m-sulfur colloid and Tc-99m-IDA.

In three cases, irradiated regions of liver failed to concentrate Tc-99m-sulfur colloid. In two of these three, imaging with Tc-99m-acetanilide iminodiacetic acid (IDA) agents within five days showed near normal hepatic uptake of this hepatobiliary imaging agent. The hepatic parenchymal cells may be imaged with Tc-99m-IDA in some irradiated regions of liver, despite loss of reticuloendothelial cell function.