Intraoperative radiation therapy at the National Cancer Institute: technical innovations and dosimetry.

The technical complexity of intraoperative radiotherapy (IORT) requires modification of the standard physical and dosimetric methods used in external electron beam therapy. At the National Cancer Institute, a number of technical innovations have been integrated into ongoing clinical studies of IORT. These include: (1) an electron beam applicator system that is significantly different from other IORT systems and includes customized "squircle" applicators; (2) peripheral dose shields; (3) a modified surgical table replacing the standard radiation treatment couch; and (4) routine use of multiple IORT fields that necessitates field matching.

Hepatic irradiation in the management of metastatic hormone-secreting tumors.

Three patients with extensive liver metastases from hormone-secreting tumors were treated with external beam radiation therapy to palliate signs and symptoms of tumor mass and/or hormone secretion. These patients experienced an objective response of 3, 14, and 24 months duration, respectively, as measured by plasma hormone levels and/or computed tomography (CT) scanning. Using conventional fractionation, a dose of 2400 to 3000 rad was delivered without significant acute or late toxicity.

The role of radiation therapy in the treatment of small cell lung cancer.

Patients with small cell lung cancer (SCLC) are candidates for aggressive therapy because of their potential for long-term survival, especially patients with limited-stage disease. Although no treatment protocol can be considered "standard", the best results in limited-stage SCLC appear to be produced by a combination of chemotherapy and thoracic irradiation. Ongoing protocols testing the efficacy of thoracic irradiation should be able to settle question of the optimal treatment approach in limited-stage SCLC over the next 1 to 2 years.

A randomized, prospective trial of adjuvant chemotherapy in adults with soft tissue sarcomas of the head and neck, breast, and trunk.

Since 1977, 31 patients were entered in a randomized, prospective study testing the efficacy of adjuvant chemotherapy after aggressive local treatment of high-grade sarcomas of the head, neck, breast, and trunk (excluding retroperitoneal sarcomas). All patients had complete resection of gross tumor and underwent postoperative radiotherapy (6000-6300 rads over 7-8 weeks). Seventeen patients received adjuvant chemotherapy consisting of doxorubicin (less than or equal to 550 mg/m2), cyclophosphamide (less than or equal to 5500 mg/m2), and methotrexate (less than or equal to 1000 mg/kg).

Results of multimodality therapy of resectable soft-tissue sarcomas of the retroperitoneum.

Thirty-seven patients with resectable retroperitoneal sarcomas were studied prospectively to determine the efficacy of aggressive multimodality treatments. No patients was lost to follow-up, which ranged from 11 to 85 months (median 29 months). All patients received radiotherapy and some received postoperative chemotherapy (doxorubicin, cyclophosphamide, and high-dose methotrexate).

Patterns of recurrence in patients with high-grade soft-tissue sarcomas.

From July 1975 to December 1982, 563 patients were referred to the Surgery Branch of the National Cancer Institute with the diagnosis of soft-tissue sarcoma. Three hundred and seven of these patients had fully resectable, localized high-grade soft-tissue sarcomas and were treated at the National Cancer Institute using standard protocols with surgery alone, or in combination with chemotherapy and/or radiotherapy. An aggressive surgical approach was undertaken in the management of patients who subsequently developed recurrent disease.

Peripheral dose to the testes: the design and clinical use of a practical and effective gonadal shield.

A simple and practical gonadal shield has been developed for use near megavoltage radiation fields. The lead shield encloses only the testes, allowing its use with nearly any radiation field that does not include the testes. The dose to the testes with and without the shield has been measured extensively both in phantoms and on patients.

The imaging revolution and radiation oncology: use of CT, ultrasound, and NMR for localization, treatment planning and treatment delivery.

The explosion of new imaging technologies such as X ray computed tomography (CT), ultrasound (US), positron emission tomography (PET), and nuclear magnetic resonance imaging (NMR) has forced a major change in radiation therapy treatment planning philosophy and procedures. Modern computer technology has been wedded to these new imaging modalities, making possible sophisticated radiation therapy treatment planning using both the detailed anatomical and density information that is made available by CT and the other imaging modalities. This has forced a revolution in the way treatments are planned, with the result that actual beam configurations are typically both more complex and more carefully tailored to the desired target volume.

Continuous intravenous infusions of bromodeoxyuridine as a clinical radiosensitizer.

Twelve patients were treated with continuous intravenous (24-hour) infusions of bromodeoxyuridine (BUdR) at 650 or 1,000 mg/m2/d for up to two weeks. Myelosuppression, especially thrombocytopenia, was the major systemic toxicity and limited the infusion period to nine to 14 days. However, bone marrow recovery occurred within seven to ten days, allowing for a second infusion in most patients.

A comparison of computed tomography and radionuclide scanning for detection of brain metastases in small cell lung cancer.

Neurologic history and examination, radionuclide brain scans (RN), and computed tomographic brain scans (CT) were performed at diagnosis and sequentially in 153 consecutive patients with small cell lung cancer (SCLC) to assess the sensitivity and accuracy of these screening methods and to determine whether the early detection of brain metastases influences survival. CT scans (sensitivity, 98%; positive predictive accuracy, 98%) were superior to RN scans (sensitivity, 71%; positive predictive accuracy, 86%) in patients with or without neurologic signs or symptoms. However, CT scans were positive in only 6% of asymptomatic patients at diagnosis and 13% of asymptomatic patients after systemic therapy.

Differing sensitivity to fluorescent light in Chinese hamster cells containing equally incorporated quantities of BUdR versus IUdR.

Chinese hamster V79 cells that had incorporated approximately equal levels of either BUdR or IUdR into their DNA were found to be equal sensitizers to X rays. However, BUdR-substituted cells were much more sensitive to fluorescent light than IUdR-substituted cells, both on a cell survival basis and by the initial number of single strand DNA breaks induced. Since a major toxicity to the use of BUdR clinically has been light-induced skin rash, these data indicate that the use of IUdR clinically might cause less untoward toxicity but yet provide the same radiosensitization as BUdR.

Soft tissue sarcoma: functional outcome after wide local excision and radiation therapy.

Functional outcome was evaluated in 40 patients with a diagnosis of soft tissue sarcoma (STS), who had received wide local surgical excision and postoperative radiation therapy. All patients were two or more years postsurgical excision, and 1.75 or more years postradiation.

The use of halogenated thymidine analogs as clinical radiosensitizers: rationale, current status, and future prospects: non-hypoxic cell sensitizers.

The halogenated pyrimidine analogs, bromodeoxyuridine (BUdR) and iododeoxyuridine (IUdR) have been recognized as potential clinical radiosensitizers for over two decades. In vivo and in vitro experimental studies document that radiosensitization is directly dependent on the amount of thymidine replacement in DNA by these analogs. Early clinical studies in Japan using selective intra-arterial infusions of BUdR and conventional fractionated radiation suggested improved survival in patients with primary brain tumors, although there were significant catheter-related complications.

Second malignant neoplasms complicating Hodgkin's disease: the National Cancer Institute experience.

The medical records of all patients treated for Hodgkin's disease during the years 1964-1981 were reviewed. Four hundred seventy-three previously untreated patients were analyzed. Thirty-four subsequent second malignant neoplasms were observed in 33 patients among those treated for Hodgkin's disease.

In vitro radiation studies on Ewing's sarcoma cell lines and human bone marrow: application to the clinical use of total body irradiation (TBI).

Patients with Ewing's sarcoma who present with a central axis or proximal extremity primary and/or with metastatic disease have a poor prognosis despite aggressive combination chemotherapy and local irradiation. In this high risk group of patients, total body irradiation (TBI) has been proposed as a systemic adjuvant. To aid in the design of a clinical TBI protocol, we have studied the in vitro radiation response of two established cell lines of Ewing's sarcoma and human bone marrow CFUc.

Radiation therapy of esophageal cancer.

Radiation therapy has been used extensively in the management of patients with cancer of the esophagus. It has demonstrated an ability to cure a small minority of patients. Cure is likely to be limited to patients who have lesions less than 5 cm in length and have minimal, if any, involvement of lymph nodes.

Illusion and reality: practical pitfalls in interpreting clinical trials.

This paper has attempted to review for the reader some of the common problem areas in the interpretation of results of cancer treatment. The intention has been to point out potential pitfalls in interpretation so that the reader can comprehend the literature with more insight and criticalness . The plethora of journals and ongoing investigations indicates a greater need for critical understanding on the part of readers.

Pharmacological evaluation of intravenous delivery of 5-bromodeoxyuridine to patients with brain tumors.

Previously, 5-bromodeoxyuridine (BrdUrd) has been shown to be an effective radiosensitizing agent in rapidly dividing cells. As part of a Phase I/II study to evaluate BrdUrd as a radiosensitizer in gliomas, the pharmacology was studied in eight patients. BrdUrd was infused using an i.

Small cell lung cancer 1973-1983: early progress and recent obstacles.

The recognition that the vast majority of patients with small cell lung cancer have distant metastatic disease at the time of diagnosis led to the use of systemic chemotherapy and consequent major improvements in survival in the early to mid-1970's. In the past five years, however, the pace of therapeutic advances has slowed. Recently evaluated treatment strategies, including more intensive induction chemotherapy, "late intensive" therapy of responding patients, alternation of chemotherapeutic regimens, integration of chest irradiation with drug therapy, large field irradiation, and reappraisal of the value of surgical resection, are discussed in this review.

The grading of soft tissue sarcomas. Results of a clinicohistopathologic correlation in a series of 163 cases.

A multidisciplinary study of 163 patients treated at the NCI for soft tissue sarcomas allowed the correlation of a number of histologic features (histologic type, mitosis, necrosis, pleomorphism, cellularity, and matrix) of the primary lesion to time to recurrence and overall survival of the patients. The results of the stratified analyses show that necrosis is the single best histopathologic parameter to predict the time to recurrence (P = 0.025) and the overall survival of the patients (P = 0.

Clinical experience with intravenous misonidazole for carcinoma of the esophagus: results in attempting radiosensitization of each fraction of exposure.

By using intravenous misonidazole, a hypoxic cell radiosensitizer, we attempted to test the hypothesis of hypoxia as the basis of the relatively poor results seen with radiation therapy in the treatment of carcinoma of the thoracic esophagus. As the peripheral neuropathy of misonidazole was well recognized, we felt that an adequate dose of misonidazole could be given approximately ten times before peripheral neuropathy would necessitate its discontinuation. Because of a desire to maximize any possible effects of radiosensitization, it was decided to administer misonidazole with each fraction of radiation, attempting to deliver curative radiation therapy with only ten fractions of radiation.

Intensive combined modality therapy including low-dose TBI in high-risk Ewing's Sarcoma Patients.

Twenty-four high-risk Ewing's sarcoma patients were treatedf on an intensive combined modality protocol including low-dose fractionated total body irradiation (TBI) and autologous bone marrow infusion (ABMI). Twenty patients (83%) achieved a complete clinical response to the primary and/or metastatic sites following induction therapy. The median disease-free interval was 18 months, and nine patients remain disease-free with a follow-up of 22 to 72 months.