Preliminary survivorship report on combined intraoperative radiation and hyperthermia treatments for unresectable pancreatic adenocarcinoma.

Five patients with unresectable pancreatic adenocarcinoma were treated with simultaneous intraoperative radiotherapy and intraoperative hyperthermia. Postoperative survivorship averaged 15.8 months, which compares favorably to a previous study in which 19 patients receiving intraoperative radiotherapy without intraoperative hyperthermia survived an average of 6.05 months. Three of the five patients following the experimental protocol of intraoperative radiotherapy and intraoperative hyperthermia with additional external beam radiotherapy are still alive, which may result in average postoperative survivorship exceeding 15.8 months.

Iodine-131 treatment of hyperthyroidism in a patient on dialysis for chronic renal failure.

A 7- to 8-cm diffuse toxic goiter with associated symptoms of hyperthyroidism developed in a 38-year-old black female undergoing regular hemodialysis for renal failure. Our treatment of choice was an ablative dose of radioactive iodine in the form of sodium iodide (Na-131I). To our knowledge, this is only the 4th documented case of hyperthyroidism in a patient with renal failure. Detailed monitoring of 131I radioactivity in the blood, thyroid gland and the dialysate demonstrated that there was no radiation hazard to personnel involved in the patient management.

Induction chemotherapy for advanced head and neck cancer: modification of response to chemotherapy by antiemetics.

Forty Stage IV head and neck cancer patients were entered on a multimodality trial of induction chemotherapy (cisplatin + infusional 5-fluorouracil), surgery, and radiation. During chemotherapy, the patients of Group A (the first 19 patients) were medicated with metoclopramide. The patients of Group B (the next 21 patients) were medicated with droperidol. The groups were comparable. The response rate (complete + partial) was 32% for Group A and 52% for Group B (p = 0.16). Primary site (p = 0.08) and surgical margin (p = 0.005) clearance of tumor were better in Group B. Nodal disease responded poorly to chemotherapy in both groups. Tumor necrosis (p = 0.006) and granulation tissue (p = 0.07) were reduced in surgical specimens after chemotherapy in Group B. The drugs were well tolerated with reversible toxicity; nausea/vomiting (p = 0.01) and weight loss (p = 0.07) after chemotherapy, were increased in Group B. The 2-year survival was 26% for Group A and 62% for Group B (p = 0.027). The median survival was 15 months for Group A and 33 months for Group B (p = 0.05). Progression-free survival improved in Group B (p greater than 0.17). These improvements in response and survival did not appear to reflect changes in surgical or radiotherapy management, but may have reflected an uninhibited effect of cisplatin in Group B. It is theorized that the metabisulfite formulated with metoclopramide altered the pharmacokinetics or pharmacodynamics of cisplatin. This resulted in the poor response to chemotherapy and poor survival in Group A. An analysis of a randomized trial comparing metoclopramide (formulated with metabisulfite) versus a control antiemetic can confirm the data presented in this pilot study. Overall, our patients survived as well as others in comparable multimodality studies in Europe and the United States.

The application of preoperative radiation therapy for unresectable malignancies.

Preoperative radiation therapy is one of the major indications for the use of ionizing radiation in the treatment of malignant disease. The preoperative application of radiation treatment is given with the intention of reducing the size of bulky cancers, thus converting unresectable tumors into resectable ones. Other benefits are reduction in the risk of locoregional recurrence and in the risk of blood-borne dissemination of malignant cells promoted during surgical resection.This paper presents and discusses three cases of unresectable intrapelvic tumors initially treated by radiation therapy with the primary goal of palliation. These three cases included rectal, cecal, and uterine carcinoma. In each case, a preoperative radiation dose of 4500 to 5000 cGy was delivered. Evaluations during and after the completion of the radiation treatments revealed that the tumor responded remarkably well to the treatment, which encouraged the surgical intervention; at surgery, minimal tumor was found. These three patients are alive to date without apparent evidence of disease.

Intraoperative radiotherapy for patients with carcinoma of the pancreas. The Howard University Hospital experience, 1978-1986.

During the period from 1978 to 1986, 106 patients were diagnosed with carcinoma of the pancreas; 30 of these patients were excluded from this study. Of the remaining 76 patients, 40 did not receive intraoperative radiotherapy (IORT) and were used as the nonrandomized control group for the 36 patients who did receive IORT after histologic confirmation of carcinoma of the pancreas. The records of 35 patients were available for review. The group receiving IORT ranged in ages from 43 to 89 years (20 males and 15 females). Seventeen patients had distant metastatic disease. The primary was located in the head of the pancreas in 32 and the body in three. No patient in this group had a curative resection. All patients were treated by a combination of biliary and gastric bypass prior to or concurrent with IORT. IORT was begun only after obtaining a histologic diagnosis and prior to the completion of any anastomosis. Necrotizing pancreatitis occurred in the treated group. There was no statistically significant difference in the survival of the nonrandomized control and treated groups.

The first simultaneous intraoperative hyperthermia and radiotherapy procedure: dog experiment and technique.

The Department of Radiation Therapy of Howard University Hospital was the first to revive (1976) the use of intraoperative radiotherapy, or direct view irradiation, using electron beam (IORTe(-)) in the United States. Since that time, this pioneering effort has gained both national and international acceptance. Now, many leading centers employ this investigational treatment modality. Recently, a new mode of cancer therapy has been gaining acceptance, namely hyperthermia (the treatment of cancer by heat). Hyperthermia has been shown, both experimentally and clinically, to improve the rate of local control (thermal enchancement ratio [TER]) when combined with radiation therapy in the treatment of cancer. Maximal TER has been observed with simultaneous or immediate application of radiation and hyperthermia for both tumor and normal tissues. Therefore, to achieve maximum therapeutic gain, selective, intraoperative, simultaneous heating and irradiation of the tumor with mechanical retraction of the normal and sensitive structures from the treatment field seems a promising alternative.There have been no published reports, to the authors' knowledge, on the combination of simultaneous IORTe(-) with intraoperative hyperthermia (IOHT). To employ this combination in human subjects, several questions must be answered first using animal models, including the technical and practical feasibility, the toxicity and morbidity, as well as the pathologic changes that may arise. The technical aspects of the first animal case, using a mongrel dog, applying simultaneous IORTe(-) and IOHT are presented.

Use of interstitial hyperthermia to produce homogeneous heat distribution patterns.

The preliminary experience of the use of a prototype hyperthermia unit (Astro 200) for tumor regression in Howard University Hospital's Department of Radiotherapy is described. The purpose of this study was to produce homogeneous heat distribution patterns within a 5-cm cylinder in the middle of a phantom (ground beef) using radio frequency conducted through electrodes implanted in the medium. Homogeneous heat distribution was achieved by finding the optimal spatial distribution of electrodes within the phantom and by sequencing the radio frequency in the electrodes. Monitored observation revealed a steady state homogeneous temperature of 42.5 °C within a 4-cm diameter. There was a temperature difference of 0.5 °C within 1 cm of the periphery.Heat in the clinical range of 42 to 43 °C has caused tumor regression, and was found to be most effective when combined with another modality of radiation. At Howard University Hospital, hyperthermia is used in conjunction with conventional modalities-surgery, radiotherapy, and chemotherapy-in the treatment of tumors.

The use of intraoperative radiotherapy and external beam therapy in the management of desmoid tumors.

Desmoid tumors are rare nonencapsulated benign lesions that invade the musculoaponeurotic tissues of the body. Such tumors infiltrate insidiously, and attempts to remove them frequently fail, usually leaving residual tumor. The use of adjuvant radiotherapy to decrease the recurrence rate in partially resected extra-abdominal desmoids has been reported by several authors. The role of irradiation in the management of desmoid tumors is illustrated in a case that combined surgery, intraoperative radiotherapy, and postoperative external beam radiotherapy in the management of this lesion.

Anesthesia in intraoperative radiotherapy patients.

Intraoperative radiotherapy (IOR) is a relatively new modality for the treatment of carcinoma. This modality necessitates a multidisciplinary approach among the surgeon, anesthesiologist, radiotherapist, pathologist, and other members of the surgical support team. In addition to appropriate IOR and surgical techniques, the role of the anesthesiologist is crucial in determining patient outcome. Specifically, the degree of preoperative preparation has a direct correlation with a successful postoperative course. Patients considered for surgery are grouped in terms of: (1) primary tumor with no metastasis and/or unresectable loco-regional disease; (2) clinical and investigational evidence of tumor with no proven malignancy; and (3) those with known metastasis but in otherwise good general condition.The primary surgical goal is to localize the tumor, obtain a frozen-section biopsy, and evaluate for resectability at the same time as the radiotherapist evaluates whether IOR is indicated. Thus many facets come together to make the IOR procedures feasible and safe. The 148 patients treated at Howard University Hospital, uneventfully, should serve to justify intraoperative radiotherapy as both a practical and safe tool in the treatment of malignancy.

Treatment of a Down's syndrome patient for hyperthyroidism with radioactive iodine.

A Down's syndrome patient was hospitalized for evaluation of vomiting, abdominal pain, and a history of weight loss. A subsequent workup revealed that she had hyperthyroidism. The treatment of choice was radioactive iodine therapy. The patient had a history of consistent nausea and incontinence for urine and feces. Special problems posed by the patient and radiation safety are discussed.

Intraoperative radiotherapy for intracranial malignancies. A pilot study.

Intraoperative radiotherapy (IOR) or "direct view" irradiation permits the delivery of a single exposure of high-energy electrons to a surgically exposed tumor. Surgical exposure permits physical retraction of normal uninvolved tissues away from the IOR beam as well as the accurate assessment of the target volume. IOR represents a "supplement" or "boost" dose to conventional fractionated external beam irradiation that is administered postoperatively. This pilot study represents the clinical experience in the US using IOR for brain tumors. At Howard University Hospital, Washington, DC, 12 patients underwent surgical resection or decompression and 1500 cGy were delivered to the tumor bed intraoperatively. After surgical recovery, 5000 cGy in 25 fractions were delivered to the whole brain and an additional 500 cGy cone-down boost were delivered to the tumor bed. This protocol was best tolerated when the cranial vault was decompressed. Two patients with meningioma are without evidence apparently NED at 8, 11, 12, and 15 months, respectively. A fifth patient died at 8 months NED from an accident. Three glioma patients died with disease at 3, 13, and 15 months, respectively. Two additional patients died 30 days after surgery. Indications, techniques, and clinical findings are presented.

Intraoperative radiotherapy in childhood malignant astrocytoma.

A 12-year-old black male patient with glioblastoma multiforme was treated with intraoperative radiotherapy followed by conventional external beam radiation and chemotherapy. The authors' clinical experience with these therapeutic measures is discussed.

Intraoperative radiation in the treatment of advanced cervical cancer.

Nineteen patients with invasive cervical cancer were treated with intraoperative radiation and most of the patients subsequently received conventional external radiation therapy and intracavitary applications. The technique, resulting complications, and survival of the patients are discussed.

Internal mammary implantation: the need for revival of a simple technique.

Available statistics on breast cancer indicate a high frequency of positive internal mammary nodes, which is associated with decreased five-year survival rates. The close proximity of the majority of internal mammary nodes (87 percent within 1 cm) to the internal mammary vessels makes them easily accessible to high-dose intravascular continuous irradiation by afterloading radioactive ribbons (iridium 192) in the internal mammary vessels that are surgically exposed. This is a simple technique that can be carried out at the time of mastectomy or as a separate procedure, either as a primary radiation modality, for post-XRT recurrence, or as a boost in combination with conventional parasternal radiation therapy. The step-by-step technique, indications, need for revival, and future implications are presented.

Intraluminal radiation for esophageal cancer: a Howard University technique.

The objective of radiotherapeutic management in esophageal cancer is to accomplish maximum tumor sterilization with minimal normal tissue damage. This sincere effort is most often countered by the differential in tumor dose response vs normal tissue tolerance. Intraluminal isotope radiation, with its inherent advantage of rapid dose falloff, spares the lungs, the spinal cord, and other vital structures, yet yields adequately high doses to esophageal tumor. Though in existence since the turn of the century, the method of intracavitary radium bougie application dropped out of favor due to technical difficulties imposed by the size of the radium source and radiation exposure to the personnel involved. The authors describe a simple "iridium 192 afterloading intraluminal technique" that eliminates technical problems and reduces radiation exposure considerably.