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Biomedical subjects

T J Kinsella

Publications and source records attributed to T J Kinsella.

At least 127 records · Page 7Linked to original sources
PubMed1990

Minimization of small bowel volume within treatment fields utilizing customized "belly boards".

Thirty consecutive patients with pelvic malignancies were evaluated prospectively for the impact of a novel bowel minimization device ("belly board") on the volume of small bowel included within a four field pelvic radiation plan. A customized polyurethane and styrofoam bowel immobilization mold was created for each patient in the prone position. Using contrast enhanced CT scanning on a dedicated radiation treatment planning scanner, we imaged the location of the small intestine in the supine position and the prone position aided by the "belly board". Custom in-house interactive image analysis software was developed to allow volumetric determination of small bowel within the treatment portals. The mean small bowel volume was reduced by 66% (299 cm3 to 102 cm3), comparing the standard supine position to the prone position assisted by the "belly board". In 13 patients without prior pelvic surgery, the small bowel volume reduction was a more dramatic 74% (334 cm3 to 88 cm3). All patients were found to benefit from this prone "belly board" setup regardless of body habitus, weight, and age. Compliance with the set-up including use of bladder distension was excellent. All patients completed their pelvic radiotherapy without requiring a treatment break. Weight loss at completion averaged less than 5%. Seventy-six percent of patients experienced little or no diarrhea. This technique is comfortable, inexpensive, highly reproducible, and permits maximal bowel displacement from standard pelvic radiotherapy fields.

Adult↗
PubMed1989

Are complications in intraoperative radiation therapy more frequent than in conventional treatment?

To evaluate whether intraoperative radiation therapy (IORT) results in higher complication rates than conventional radiotherapy, 119 patients were studied who entered four prospectively randomized clinical trials that compared IORT with conventional therapy. Malignant neoplasms included 33 gastric carcinomas, 35 retroperitoneal sarcomas, 22 resectable pancreatic cancers, and 29 unresectable pancreatic cancers. One hundred thirty-six complications developed among 66 patients who received conventional therapy, and 108 complications developed among 53 patients who received IORT. There was no statistical significance between treatment groups with respect to the overall incidence of complications. Analysis of types of complications by tumor type using Fisher's exact test revealed only one significant complication: an increased rate of sepsis among the patients with retroperitoneal sarcoma who received conventional therapy compared with their IORT cohorts. The overall complication rate associated with IORT was equivalent to conventional radiotherapy in the treatment of these malignant neoplasms and supported the use of IORT where clinically indicated.

Abdominal Neoplasms↗
PubMed1989

Intensive combined modality therapy of small round cell and undifferentiated sarcomas in children and young adults: local control and patterns of failure.

Seventy-five patients (ages 4-35 years) with the following small round cell tumors and undifferentiated sarcoma were treated at the National Cancer Institute: Ewing's sarcoma (n = 32), peripheral neuroepithelioma (n = 14), rhabdomyosarcoma (n = 24), undifferentiated sarcoma (n = 5). Most patients had poor prognostic features including 36 (48%) with metastatic disease, and 42 (56%) with central (truncal) tumors (22 in the pelvis). Treatment included 5 cycles of intensive induction chemotherapy with vincristine, cyclophosphamide and adriamycin, plus aggressive local radiation therapy using simulation and computerized treatment planning for all patients. Thereafter, complete clinical responses were consolidated with intensive chemotherapy, total body irradiation and autologous bone marrow transplantation. There were three local only failures, 10 local plus distant failures, 36 distant only failures, 3 treatment-related deaths, and one intercurrent death. Overall actuarial survival and event-free survival at 4 years are 49 and 29%, respectively. Actuarial freedom from local progression was seen in 74% of patients at 4 years, quite remarkable considering the bulk and location of most of these tumors. Without aggressive surgery, many of these high risk patients had satisfactory outcomes, but better systemic treatments are still needed.

Adolescent↗
PubMed1989

Treatment of sarcomas of the chest wall using intensive combined modality therapy.

As part of two sequential protocols using intensive combined modality treatment in pediatric and adolescent sarcomas, 31 consecutive patients with primary chest wall tumors were treated between November 1977 and March 1986. This group included 13 patients with peripheral neuroepithelioma (Askin's tumor), 11 patients with Ewing's sarcoma, 3 patients with rhabdomyosarcoma, and 4 patients with undifferentiated sarcomas. Following complete work-up, 17 patients presented with localized disease and 14 patients presented with metastases. Patients received intensive combined modality treatment with combination chemotherapy (vincristine, cyclophosphamide, Adriamycin, +/- actinomycin-D and DTIC) and high-dose conventionally fractionated radiation therapy to the primary (55-60 Gy) and non-pulmonary metastases (45-50 Gy). Radiation techniques used for the primary chest wall tumor varied with the clinical presentation. Patients achieving a complete response received either low-dose fractionated TBI (1.5 Gy/0.15 Gy fx/5 weeks) or high-dose TBI (8 Gy/4 Gy fx/2 days) and an intensive cycle of chemotherapy followed by autologous bone marrow transplantation. Twenty-five of 31 patients were judged to have a complete response (including 1 patient with complete resection). With minimum follow-up of 6 months and median follow-up of 36 months from completion of treatment, 14 patients remain disease-free with 2 additional patients alive in second remission after relapse. Patients with localized disease at presentation have improved disease-free survival and overall survival compared to patients with metastases at presentation. All 17 localized patients achieved a CR and 11 are NED compared to 8 of 14 metastatic patients achieving a CR and only 3 are NED. There have been 5 loco-regional recurrences with 3 "in-field" failures and 2 failures in the regional pleura. There were no treatment-related deaths and no clinically significant cases of pneumonitis. To date, 2 patients have significant treatment related morbidity, including 1 patient with scoliosis requiring surgery and 1 patient with acute leukemia developing 42 months after the start of therapy (presently in remission). We conclude that this intensive combined modality therapy results in a high CR rate and good local control with acceptable morbidity. Patients with metastatic disease at presentation remain a therapeutic challenge.

Adolescent↗
PubMed1989

Endobronchial irradiation for malignant airway obstruction.

An afterloading endobronchial irradiation (EBRT) technique using Iridium-192 (Ir-192), was piloted for malignant airway obstruction. Under bronchoscopic guidance, a catheter is threaded distal to the lesion. Orthogonal radiographs and computerized tomographic (CT) scans are obtained for dosimetry. Forty implants in 38 patients have been performed. Thirty-two patients had lung cancer; 23 had received prior irradiation and eight had prior chemotherapy. Eight patients underwent pre-endobronchial irradiation laser excision. Median implant duration was 50.5 hr; median dose at 1 and 2 cm from source center was 50 and 20 Gy, respectively. The procedure was well tolerated with four long-term complications (10.5%). Twelve of 38 patients are currently alive with a median survival of 5+ months and a range of 1 to 21+ months. Changes in performance status (PS), symptom resolution, radiographic demonstration of re-aeration of atelectatic lung, changes in pulmonary function (PFT), and post-endobronchial irradiation bronchoscopy were used to assess response. Seventy percent of the patients' remaining life was rendered symptom-free or improved. A 70% radiographic response was noted. Fourteen patients underwent post-endobronchial irradiation bronchoscopy with 12 complete responses. Endobronchial irradiation, therefore, appears to be a safe, effective technique to palliate malignant airway obstruction.

Airway Obstruction↗
PubMed1989

Iododeoxyuridine (IdUrd) incorporation into DNA of human hematopoietic cells, normal liver and hepatic metastases in man: as a radiosensitizer and as a marker for cell kinetic studies.

Iododeoxyuridine (IdUrd) was administered as a continuous infusion for 14 days to patients with glioblastoma and sarcoma, and for 3 days to patients with metastatic colorectal carcinoma. In the first group, the maximum incorporation of IdUrd into DNA was determined, taking granulocytes as parameter. In the second group, selective incorporation into DNA of normal liver and hepatic metastases of colorectal cancer was investigated. The highest dose of 675 mg/sq.m./day for 14 days produced IdUrd plasma concentrations of 1.8 +/- 0.3 microM, and a substitution of dThd by IdUrd in the range of 7.1-11.7%. Coadministration of fluorodeoxyuridine did not show significant enhancement of IdUrd-incorporation in granulocytes. Three-day intravenous infusions of IdUrd 1000 mg/sq.m./day produced 1.7-4.5% IdUrd-incorporation in hepatic metastases. Three-day intraarterial infusions (hepatic artery) produced 3.8-10.5% dThd-replacement, whereas, in 9/10 patients this was less than 1% in normal liver. In tumor tissue there was a trend towards FdUrd-modulated enhancement of IdUrd-incorporation, although there was considerable scatter. Cell kinetic studies revealed that IdUrd-incorporation in monocytes and granulocytes was very similar. In lymphocytes, a much lower fraction incorporated IdUrd. Liver tumor contained a considerably higher fraction of IdUrd-labeled cells, compared with normal liver. Potential doubling times for the tumors were estimated to be 10 days.

Cell Cycle↗
PubMed1989

Radiation induced thyroid neoplasms 1920 to 1987: a vanishing problem?

Radiation for benign diseases has been implicated as an etiologic factor in thyroid cancer. From 1930-60, over 2 million children may have been exposed to therapeutic radiation and it is estimated that up to 7% may develop thyroid cancer after a 5-40 year latency. Thyroid stimulating hormone, secondary to radio-induced hypothyroidism, has been implicated as causative in animals. Such data has led to expensive screening programs in high risk patients. Because of a decline in irradiation for benign diseases in children over the last 2 decades, we questioned whether the incidence of radiation induced thyroid neoplasms (RITN) was also decreasing. Twenty-six of 227 patients (11%) with thyroid malignancies seen at our institution from 1974-87 had a history of previous head and neck irradiation. These included 13 papillary, 3 follicular, and 7 mixed carcinomas as well as 2 lymphomas and 1 synovial cell sarcoma. None of these 26 patients had abnormal thyroid function tests at presentation. Mean latency from irradiation to the diagnosis of thyroid cancer was 25.4 years (6-55 year range). Compared to the reported increasing incidence of RITN from 1940-70, there appears to be a significant decrease since 1970. Based on our analysis, the use of expensive screening programs in high risk populations may no longer be warranted. Additionally, the routine use of thyroid replacement in previously irradiated chemically hypothyroid patients is not recommended.

Adolescent↗
PubMed1989

A phase I study of intraarterial iododeoxyuridine in patients with colorectal liver metastases.

Regional delivery of iododeoxyuridine (IdUrd) to patients with colorectal liver metastases was examined in a phase I study. The maximum-tolerated intraarterial (IA) dose (MTD) was 1,333 mg/m2/d administered continuously for 14 days. The dose-limiting toxicity was thrombocytopenia. Thrombocytopenia and leukopenia were correlated with the amount of IdUrd incorporated into DNA of peripheral granulocytes. In contrast to our experience with 5-fluorodeoxyuridine, there was no evidence of hepatobiliary toxicity. In 11 patients who received IA IdUrd alone, seven had a greater than or equal to 50% decrease in carcinoembryonic antigen (CEA) levels, with five having tumor volume reductions of 65%, 48%, 46%, 44%, and 27%. Thus, IA IdUrd alone has antitumor efficacy. Patients subsequently received IdUrd in combination with external beam radiation to a total dose of 2,400 cGy without acute local toxicity. In addition to these favorable clinical findings, we have previously shown that IdUrd is selectively incorporated into tumor DNA compared with normal liver in these patients. Further phase II evaluations of this approach are warranted.

Antineoplastic Agents↗
PubMed1989

Long-term follow-up of testicular function following radiation therapy for early-stage Hodgkin's disease.

Seventeen male patients with pathological staged I-IIIA1 Hodgkin's disease were followed prospectively for radiation damage to the testes from low-dose scattered irradiation. During conventionally fractionated radiation therapy, the testicular dose ranged from 6 to 70 cGy. Testicular function was measured in a prospective fashion by repeated analyses (every 6 to 12 months) of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. Patients were also followed by serial semen analyses and by a questionnaire on fertility. The follow-up period ranged from 3 to 7 years after completion of radiation therapy. In patients receiving greater than or equal to 20 cGy, there was a dose-dependent increase in serum FSH values following irradiation, with the maximum difference at 6 months compared with pretreatment levels. All patients showed a return to normal FSH values within 12 to 24 months following irradiation. No significant changes in LH and testosterone were observed in this patient group. Eight patients with a normal pretreatment semen analysis provided serial semen samples and two patients showed transient oligospermia with complete recovery by 18 months following treatment. Four patients have fathered normal offspring following radiation therapy. We conclude that low doses (greater than 20 cGy) of scatter irradiation during treatment for Hodgkin's disease can result in transient injury to the seminiferous tubule as manifested by elevations of FSH for 6 to 24 months following treatment. Below 20 cGy, FSH values remained in the normal range. No evidence of Leydig cell injury (using LH and testosterone) was seen in this dose range (up to 70 cGy). Thus, patients with early-stage Hodgkin's disease can be treated with radiation therapy with little to no risk of irreversible testicular injury. Radiation treatment techniques to shield the testes are discussed.

Adolescent↗
PubMed1989

Intraoperative radiation therapy-induced sarcomas in dogs.

In a canine model the tolerance of normal and surgically manipulated tissue to intraoperative radiotherapy (IORT) was investigated to provide guidelines for the clinical use of IORT in human cancer patients. A dose of 20 Gy IORT, with or without external beam radiotherapy, was generally well tolerated without significant increased treatment morbidity. Higher doses of IORT (over 30 Gy) have produced radiation-induced sarcomas in some animals followed over a long period. Therefore IORT should be used only in human cancer patients in well controlled studies, in which complications are well documented, and the possibility of radiation-induced malignancies in long-term survival should be considered.

Animals↗
PubMed1989

Effects of radiation therapy and chemotherapy on testicular function.

Chemotherapy and radiation therapy are commonly used alone or in combination in the curative management of many malignancies in adolescent and adult males. Over the last 15-20 years, the striking success in the treatment of some common cancers in reproductive males has led to increasing concern for damage to normal tissues, such as the testes, resulting from curative cancer treatment. Indeed, a major future goal for cancer treatment will be to improve on the complication-free cure rate. Inherent in achieving this goal is to understand the pathophysiology and clinical expression of testicular injury. Both chemotherapy and radiation therapy result in germ cell depletion with the development of oligo- to azoospermia and testicular atrophy. The type of drug (particularly the alkylating agents), duration of treatment, intensity of treatment, and drug combination are major variables in determining the extent and duration of testicular injury. Testicular injury with chemotherapy also appears to vary with the age of the patient at the time of treatment. Newer drug combinations are now being used which appear to have curative potential in tumors such as Hodgkin's disease and germ cell testicular cancer with less potential for testicular injury. The most accurate and complete information on radiation injury to the testes is derived from two studies of normal volunteers who received graded single doses directly to the testes. A clear dose-response relationship of clinical and histological testicular damage was found with gradual recovery occurring following doses of up to 600 cGy. While these two studies provide an important clinical data base, radiation therapy used in treating cancers involves multiple daily treatments, usually 25-35 delivered over several weeks. Additionally, direct testicular irradiation is seldom used clinically. Based on several recent studies of testicular injury following conventional radiation therapy, it appears that fractionated scatter irradiation may have a more profound effect than single dose irradiation and that recovery of normal testicular function may be delayed. Testicular injury from doses as low as 20 cGy is reflected principally in transient elevations in serum FSH levels. With higher radiation doses (greater than 200 cGy), Leydig cell dysfunction is also seen as evidenced by elevations in LH. Recently, testicular shields have been constructed which can reduce scatter dose to the testes by up to a factor of 10. Today, the routine use of a testicular shield and other technical innovations in the clinical use of radiation therapy should minimize the risk of significant testicular injury.

Antineoplastic Agents↗
PubMed1988

Fluorodeoxyuridine modulation of the incorporation of iododeoxyuridine into DNA of granulocytes: a phase I and clinical pharmacological study.

The amount of iododeoxyuridine (IdUrd) incorporated into DNA determines the degree of radiosensitization. Fluorodeoxyuridine (FdUrd) has been shown to biochemically modulate IdUrd incorporation into DNA in vitro and in vivo. In this Phase I study, these drugs were coadministered to patients during 14-day continuous i.v. infusion periods in order to investigate whether the incorporation of IdUrd into DNA in vivo could be increased without increasing the dose of IdUrd. IdUrd plasma concentrations and incorporation of IdUrd into DNA of granulocytes were measured by high-performance liquid chromatography. Up to 8.8% substitution of thymidine by IdUrd was observed. Even at 3.5 mg/m2/day FdUrd for 14 days (78% of the maximum-tolerated dose as a single agent), no clinically relevant enhancement of incorporation of IdUrd into DNA of granulocytes was observed. Also, no changes in plasma levels of IdUrd were observed with escalating doses of FdUrd. Toxicity patterns (stomatitis, diarrhea, and bone marrow depression) and isobologram analysis suggested that IdUrd and FdUrd had additive, rather than synergistic, effects.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Histopathological effects of intraoperative radiotherapy on pancreas and adjacent tissues: a postmortem analysis.

Intraoperative radiotherapy (IORT) has been utilized in the treatment of resectable and unresectable pancreatic carcinoma at the National Cancer Institute. Detailed autopsy analyses of the radiation effects on the pancreas and adjacent tissues were performed on 13 patients dying at various times following therapy. IORT can induce a progressive retroperitoneal fibrosis and fibrosis of the porta hepatis in patients with resectable pancreatic carcinoma. In unresectable pancreatic carcinoma, the major expression of intraoperative irradiation with external beam irradiation is a progressive fibrosis of the pancreas with vascular sclerosis, nerve degeneration, atrophy of acinar cells, and atypical changes in the ducts of the pancreas, as well as degenerative changes of the pancreatic tumor.

Adrenal Glands↗
PubMed1988

Tolerance of the canine bladder to intraoperative radiation therapy: an experimental study.

An experimental study of bladder tolerance to intraoperative radiotherapy (IORT) was designed using a large animal model (adult American Foxhounds, weight 25-30 kg) to access acute and late radiation effects. Dogs were subjected to laparotomy where the bladder was mobilized and IORT was delivered using a 5 cm circular cone through a cystotomy incision with 12 MeV electrons. The bladder trigone including both ureteral orifices and the proximal urethra was irradiated in groups of 3 dogs with doses of 0, 20, 25, 30, 35, and 40 Gy. Dogs were followed clinically with repeat urinalysis, intravenous pyelogram (IVP), and cystometrogram at 1 month and then Q6 months for up to 4 years. One dog from each dose group was sacrificed electively at 1 and 2 years, whereas the other dog is being followed clinically for a minimum of 4 years. Complete autopsies were performed with particular attention to genitourinary and pelvic structures. No clinically detectable acute toxicity resulted from IORT to the bladder. Three of 15 IORT dogs (1 each at 25, 35, and 40 Gy) showed obstruction of a ureteral orifice with 2 dogs dying of renal failure secondary to bilateral hydronephrosis within 1-2 years of treatment. The remaining 12 IORT dogs and 3 control dogs have normal repeat IVP's and renal function with up to 4 years of follow-up. Serial cystometry demonstrates no major loss of bladder contractility or volume. At autopsy, histological changes of mucosal thinning and telangiectasia with submucosal fibrosis were confined to the IORT field and appeared dose-related. However, the bladder epithelium remained intact at all doses. The ureterovesical junction in animals receiving 20 Gy showed mild fibrosis of the lamina propria and moderate chronic inflammation. Above 20 Gy, these histological changes at the U-V junction were more pronounced with gross stenosis in 3 animals as predicted by the IVP. We conclude that the bladder trigone will tolerate IORT to 20 Gy without major clinical sequellae. Above 20 Gy, progressive inflammation and fibrosis of the U-V junction resulted in obstructive hydronephrosis in three animals within 1-2 years of IORT. The bladder mucosa remained intact with doses to 40 Gy, although submucosal fibrosis and chronic inflammation were evident and appeared dose-related. However, bladder function as measured by cystometry showed essentially no change with follow-up to 4 years. From this large animal study, IORT for early-stage bladder carcinoma is technically feasible and deserves a careful clinical study.

Animals↗
PubMed1988

Surgery with intraoperative radiotherapy for sarcomas of the pelvic girdle: a pilot experience.

Sarcomas of the pelvic girdle represent difficult treatment problems. Many are not treatable for cure, and among the patients who are technically resectable, there is high risk for local tumor recurrence and distant spread. Intraoperative radiotherapy (IORT) has been used in conjunction with surgical resection in five patients with extensive sarcomas of the pelvic girdle. Patients underwent a hemipelvectomy and IORT (dose 20-30 Gy) to the sacral resection margin and surrounding soft tissues. Three patients developed pulmonary metastases within 3 months and eventually died from metastatic disease (8-38 months). Two patients have remained disease-free (43 and 53 months). Four patients (80%) have remained locally free of tumor with follow-ups of 8-53 months. The only treatment complication was late osteonecrosis of the coccyx which appeared 7 months after treatment. By contrast, six historical control patients with sarcomas of the pelvic girdle treated with resection alone showed a local control rate of only 27% over a 40-month follow-up. On the basis of this preliminary experience, it appears that IORT may substantially help to control local disease in patients with grossly resectable sarcomas of the bony pelvis.

Adolescent↗