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Biomedical subjects

F A Gibbs

Publications and source records attributed to F A Gibbs.

At least 37 records · Page 2Linked to original sources

Regional hyperthermia for advanced tumors: a clinical study of 353 patients.

A Phase I study using deep regional hyperthermia (HT) with an annular phased array was conducted in 14 U.S. medical centers from 1980 through 1986. There were 353 patients whose average age was 57 years. All patients had advanced recurrent or persistent tumors. Prior frequently complex, multimodality anti-cancer therapy was received by 71% of the patients. Gastrointestinal adenocarcinoma was present in 146 (41%) patients, genitourinary tumors in 86 (24%), soft tissue sarcomas in 46 (13%), malignant melanoma in 21 (6%) and 15% had other tumors. The sites treated included: pelvis 55%, abdomen 21%, liver 14%, thorax 6%, and other sites 3%. All patients received deep regional HT with an average frequency of 55 MHz. A total of 1412 HT treatments was administered to these 353 patients with an aim to increase the temperature in the volume of interest to greater than 42 degrees C for greater than or equal to 30 minutes. Thermal dose (TD in equivalent minutes at 42.5 degrees C) was less than 50 in 104 (29%), greater than or equal to 50 less than 100 in 30 (11%), greater than or equal to 100 in 26 (7%), and greater than 200 in 34 (10%). The remaining 150 (42%) patients had TD = 0. In addition to HT, 260 (74%) received radiotherapy (RT). RT was given at 180 or 200 cGy daily with an average total dose of 33.4 Gy. A total of 42 (12%) patients were given chemotherapy (CT) with HT, and 15 (4%) CT + HT + RT/HT alone was given to 47 (13%) patients. Complete response (CR) was obtained in 35 (10%) and partial response (PR) in 59 (17%) patients. CR was 12% in patients who received RT, vs 2% in those who did not receive it, p = 0.003. Radiation dose was an important factor influencing response, p less than 0.001. Thermal dose was not an important parameter influencing tumor response. A duration of CR ranged from 4 to 73 weeks with an average duration of 31 weeks and the median duration of 28 weeks. The overall 2-year survival was 13% with the median survival of 42 weeks. Patients with CR and PR had a 2 year survival of 41%, and a median survival of 71 weeks. This compared with 8% 2-year survival and 24 weeks median survival in patients who did not have CR or PR, p less than 0.001. Of the patients presenting with significant pain, 62% had complete or partial pain relief.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Psychomotor-variant type of paroxysmal cerebral dysrhythmia.

Psychomotor-variant is a rare clinico-electroencephalographic entity, characterized by a great variety of thalamic, hypothalamic and limbic symptoms and by a specific electrographic finding during light sleep, i.e. discharges of notch-topped 6 per second waves, chiefly in the temporal areas. It is rare, occurring among only one percent of patients with epilepsy or a question of epilepsy. Sixty-eight percent of patients with psychomotor-variant disorder improved symptomatically if treated with anti-epileptic medication.

Adolescent↗

RIF-1 tumor treatment in anesthetized mice with minimal effects on blood flow and hypoxia.

The injectable anesthetic etomidate and a clip that facilitates hyperthermia by water bath immersion (the "Gibbs clip") were evaluated for their suitability with subcutaneous flank RIF-1 tumors in C3H/HeJ mice. For tumors between 100 and 250 mg (mean, 160 mg), etomidate at 40 mg kg-1 ip did not significantly increase the radiobiologic hypoxic fraction (RHF); as calculated from an in vitro assay after treatment in vivo the RHF increased from 0.06 (95% C.I.:0.03-0.13) to 0.08 (0.04-0.16). In contrast, for larger tumors (270-650 mg; mean, 400 mg) etomidate increased the RHF from 0.08 (0.04-0.17) to 0.28 (0.14-0.60). Holding 250-mg-or-less tumors 3-mm laterally away from the flank in an X-ray jig did not significantly reduce tumor blood flow as inferred from the clearance rates of Xe, but the RHF of 0.15 (0.08-0.26) was significantly (P less than 0.05) greater than the RHF in unanesthetized mice, although not the RHF in anesthetized mice. The Gibbs clip, which folded skin around a tumor to enhance thermal conduction from a water bath, did not impair the increase in tumor blood flow in response to the cardiovascular arousal associated with exposure to a hyperthermic stimulus. Intratumor temperature was within 0.25 degrees C of bath temperature 3 min after the tumor and clip were immersed, but only when rectal temperatures were at 37 degrees C or above; tumor blood flow increased intratumor temperature gradients by 0.10 degrees C for each 1.5 degrees C that the body temperature was below 37 degrees C.

Anesthesia↗

Assay of premorbid murine jejunal fibrosis based on mechanical changes after X irradiation and hyperthermia.

Preparative surgery immobilized 15 mm of functional jejunum against the peritoneal surface of the ventral abdominal wall in C3H/HeJ mice. The surgery allowed subsequent treatments with single fractions of 44 degrees C hyperthermia and X irradiation to be selective to this portion of small intestine. With each doubling of time since treatment, 1 through 70 weeks, a sample of mice was killed and specimens of their intestines were excised and radially stretched in a tensile-testing apparatus that measured tension as a continuous function of circumference. Preconditioning with repeated cycles of stretch and relaxation before specimens were irreversibly stretched enabled measurement of the limit collagen placed on the extensibility of the intestinal wall by physiologic forces and the stiffness of the intestinal collagen once that limit was exceeded. Both kinds of measurements made possible dose-response characterization of radiation fibrosis for treatments that killed no mice. Response increased linearly with X-ray dose above a threshold. After X rays alone the threshold remained constant at 9.7 +/- 0.6 Gy for the assays at 1 through 8 weeks and subsequently decreased to about 6 Gy by 35 weeks. With adjuvant hyperthermia of 15 min at 44 degrees C beginning 10 min after X irradiation, the threshold of approximately 5 Gy at 2-4 weeks decreased to about 2 Gy by 17 weeks; the thermal enhancement ratio as calculated from slope-ratio analysis of the dose-response curves was 1.50 +/- 0.08 at 2-4 weeks post-treatment and 1.96 +/- 0.05 at 17-70 weeks post-treatment. Up to 20 min at 44 degrees C by itself was without effect. From comparisons of these data with results of crypt microcolony assays, it was concluded that intestinal fibrosis was both a chronic sequela of acute mucosal injury and a late effect of X irradiation. Adjuvant hyperthermia both hastened the expression of the late effect and increased its severity beyond that predicted from the acute injury.

Animals↗

Electroencephalographic study of head injury in childhood.

A careful study of head injury in childhood shows that 14 and 6 per second positive spikes are not normal. They are a delayed reaction to mild injury and are more characteristic of slight injury than of severe injury, but they are common during recovery among patients with severe injury.

Brain Injuries↗

Regional hyperthermia for clinically advanced deep-seated pelvic malignancy.

Forty-three patients with deep-seated pelvic malignancy have been treated at the University of Utah on a pilot protocol involving regional hyperthermia (HT) produced by the BSD-1000 HT system and the annular phased array applicator (AA) usually driven at 60 MHz. Acute toxicity consisted primarily of pain within the AA aperture (74%), pain outside the aperture (33%), and bladder spasm (26%) or systemic stress (25%). Systemic stress only infrequently was power limiting. The most common power-limiting factors were pain (33%) and excessive heating of normal tissues (23%). In 9 patients (21%), there was no power-limiting factor. Treatment-related complications were uncommon and consisted of superficial second degree burns (3 patients), small bowel obstruction (1 patient), and rectal fistula (1 patient), all of which resolved with supportive nonsurgical therapy. Detailed thermal mapping and thermal dosimetry were performed on 36 patients. Thermal dosimetry parameters were all rather disappointing; however, the protocol prioritized the prevention of complications, and patients with acute toxicity or other power-limiting factors were not pushed to achieve high thermal doses. A logistic regression analysis was performed to determine if any factors were correlated with response (PR + CR). "Concurrent radiation dose" and "number of satisfactory heat treatments" were highly and independently correlated with response (p = 0.002). Responders (median survival = 10 months) survived significantly longer (p = 0.0014) than nonresponders (median survival = 4 months). Four of the responders are alive and currently without evidence of disease.

Humans↗

Abdominal regional hyperthermia with an annular phased array.

Twenty-eight patients with advanced upper-abdominal malignancy were treated at the University of Utah on a pilot protocol involving regional hyperthermia (HT) produced by the BSD-1000 HT system and the annular phased array applicator (AA), usually driven at 60 MHz. Eighty-two percent of the patients had widespread metastatic disease, and the mean tumor burden was 2,900 cc. Seventy-nine percent of the patients received concurrent radiotherapy. Acute toxicity consisted primarily of pain within the AA aperture (43%), systemic stress (43%), and nausea or vomiting (29%). Systemic stress was the most frequent power-limiting factor (46%). There were two treatment-related complications: sciatic neuritis from intramuscular injection (one) and pleural effusion from thermometry probe placement (one). Detailed thermal mapping and thermal dosimetry were performed on 26 patients. The mean thermal dosimetry parameters were quite low. Concurrent radiation doses were also quite low (mean, 1,500 rad) to avoid toxicity of sensitive organ systems within the abdomen. The objective response rate was only 18%, all partial, but 43% of the patients achieved effective symptomatic palliation. The five objective responders did survive significantly (P = .02) longer than the 23 nonresponders.

Abdominal Neoplasms↗

Merkel cell carcinoma: combined surgery and radiation therapy.

Merkel cell carcinoma, first reported as "trabecular carcinoma" by Toker in 1972, is a dangerous, often fatal primary skin tumor. The current authors report eight patients, only one of whom is considered to have a totally successful clinical outcome. Two patients died and one was preterminal with widespread disease in 10 to 20 months. Two others had recurrence or metastases within a year, and two patients died early of intercurrent disease after first developing regional lymph node involvement. Review of 139 patients reported in the literature indicates local recurrence in 30 per cent, regional lymph node metastases in 50 per cent, and death from neoplasm in 18 per of the cases. All patients in the present series received radiation therapy with encouraging response. The tumor was quite radiosensitive, and in only one instance was there recurrence within an irradiated field. Wide surgical excision with prompt postoperative irradiation to the local site and regional lymphatics is the therapy of choice in early lesions. Regional lymphadenectomy is recommended whenever nodal involvement is suspected. Currently, an aggressive combined surgical and radio-therapeutic approach to this dangerous neoplasm appears warranted, although further data may show that early and routine use of radiotherapy in Merkel cell carcinoma could obviate the necessity for extensive operative procedures.

Adenocarcinoma↗

Electron arc therapy: physical measurement and treatment planning techniques.

An electron beam arc therapy technique has been developed for the treatment of the post-mastectomy chest wall using a clinical linear accelerator modified for arc therapy. The effects on the dose distribution of primary X ray collimators, secondary cerrobend blocks attached to the accelerator accessory tray, and tertiary cerrobend casting of the treatment area on the patient's thorax have been investigated. Multiple electron energies within the same arc, variable rad per degree, and variable shaped secondary and tertiary applicators have been employed to optimize dose uniformity across the treated surface. A computerized treatment planning program has been developed to aid in visualization and optimization of dose distributions. A simple technique to estimate the width variation in the secondary collimator necessary to compensate for radial patient thickness changes in the cephalocaudad direction is described. Electron beam energies of 6 MeV, 9 MeV, 12 MeV, 15 MeV, and 18 MeV have been studied. The physical measurements needed to implement this technique are described, and a comparison of electron arc therapy dose distributions with other standard treatment techniques is presented.

Breast Neoplasms↗

Practical thermal dosimetry.

A relatively simple means of thermal dose documentation is presented. It has the advantage of greatly condensing the vast amount of data collected during a course of hyperthermia treatments. The formulation incorporates both temporal and spatial temperature transients and is applicable when comparing hyperthermia devices and in quality control for prospective hyperthermia treatment protocols.

Humans↗

A comparison of deep regional hyperthermia from an annular array and a concentric coil in the same patients.

Twenty-two patients with advanced pelvic or abdominal malignancy (or both) were treated on successive occasions with hyperthermia produced by an annular array (AA) (60-80 MHz, 500-1800 W forward power) and a concentric coil (CC) (13.56 MHz, 350-1000 W forward power). Both devices were compared with respect to acute toxicity and power limitations. There was no power limiting factor in pelvic heating in 7/14 patients treated with the AA, however 13/14 experienced power limiting sacrococcygeal pain with the CC. The 9 patients who underwent abdominal heating had a variety of power limitations with both devices. Thermal mapping was performed in 23 treatments with the AA and in 19 with the CC. Composite thermal maps of patients with similar thermometry sites show that heating patterns produced by the CC were predictable from theory and static phantom measurements. The AA achieved broader regional heating, particularly at depth, but heating patterns were less predictable. Spatial thermal dose (TD) analysis revealed higher minimum tumor TDs and more favorable mean tumor/normal tissue TD ratios with the AA than with the CC. We conclude that the AA is superior to the CC for pelvic treatment and that both devices have limitations in abdominal treatment.

Abdominal Neoplasms↗

Hyperthermia in the treatment of cancer. Perspectives on its promise and its problems.

The potential for the use of hyperthermia in the treatment of cancer is based on a strong and compelling biologic rationale. In the laboratory it has been shown in quantitative assays both in vitro and in vivo that (1) hyperthermia is cytotoxic to tumor cells as a function of time at temperatures above 42 degrees C; (2) cytotoxicity is relatively high for radioresistant S-phase cells and for cells that are nutritionally deprived and acidotic, conditions one might expect in regions of tumors containing large numbers of radioresistant hypoxic cells; and (3) heat is a radiosensitizer and a chemosensitizer. Clinical study is hampered by less than optimal physical heating methods and the need for invasive thermometry. Ultrasonic and electromagnetic approaches each have limitations and advantages. In spite of technical limitations, efficacy has been shown for superficial tumor sites treated by local hyperthermia and Phase I studies are underway investigating the more complicated problem of deep regional hyperthermia. Although whole body hyperthermia has the attractive capability of treating metastatic as well as more localized cancer, it is toxic therapy and its role in treatment remains undefined. Research advances in equipment design and treatment optimization are needed; however, there are studies underway utilizing existing methods and rationale which should further clarify the potential clinical usefulness of regional hyperthermia in combined modality approaches to cancer therapy.

Animals↗

Electron arc therapy: clinical experience with chest wall irradiation.

In order to overcome the technical problems commonly encountered in fixed field photon and electron beam chest wall irradiation, we have treated the chest wall in 22 breast cancer patients with a moving electron beam that rotates about the patient's thorax. This paper discusses the clinical results of chest wall treatment by electron arc therapy. Twenty-one patients were treated following mastectomy, 16 electively because of high risk for local failure, and 5 because of local recurrence. One patient with advanced local-regional disease was treated primarily. During a median follow-up period of 24 months there has been one chest failure in one of the patients treated for local recurrence. No major complications were observed in skin, lung, soft tissue or esophagus, even in the 7 patients recently or concomitantly treated with multiagent cytotoxic chemotherapy. In 3 patients, small areas of telangiectasia developed in the region of abutment of the electron arc field to a photon field used to irradiate the supraclavicular nodal area. We conclude that the technique as applied to these patients is safe and efficacious. In certain clinical settings it has advantage over standard, fixed field approaches to treat the chest wall.

Breast Neoplasms↗

Regional hyperthermia in the treatment of clinically advanced, deep seated malignancy: results of a pilot study employing an annular array applicator.

From October 1980 through December 1982, 46 patients were entered into a pilot study at the University of Utah Medical Center to assess the feasibility and safety of heating deep-seated, advanced, pelvic and abdominal malignancies with an annular array of electromagnetic wave (EMW) applicators. The patients, most of whom were heavily pretreated, were treated on a protocol in which most of the patients received combined hyperthermia and low dose X ray therapy. Discomforting local symptoms were the predominant treatment related acute side effects in 28 patients with pelvic disease, while systemic hyperthermia and associated symptoms were the predominant side effects in 18 patients with abdominal disease. Minor subacute toxicity was minimal and no serious treatment related, chronic toxicity was observed. The treatments of 22 patients with sufficiently detailed thermometry were analyzed at arbitrary index temperatures of 41 degrees C and 43 degrees C. Objective response rates in 22 evaluable patients were 67% and 9% for pelvic and abdominal sites respectively.

Abdominal Neoplasms↗