An analysis of the late effects of radiotherapy in pediatric central nervous system tumors.

PURPOSE: The purpose of this study is to assess the long term results of all pediatric patients diagnosed with central nervous system (CNS) tumors treated with external beam radiotherapy either primarily or postoperatively. MATERIALS: Forty-seven pediatric patients with CNS tumors were treated between 1978 and 1989 with external beam radiotherapy to customized fields using cobalt 60, 4, 6, or 18 MV photons. Daily doses ranged from 1.5 to 2.0 Gray; total doses from 35 to 66 Gray. Ages ranged from one month to 18 years of age, with an average age of 8.2 years. Thirty-nine patients survived more than 12 months (range 36 to 178 months; median 62 months) and were included for analysis. Ten of 39 (25.6%) patients experienced Grade I to II complications and six patients had (15.7%) Grade III to IV complications for an overall incidence of 41%. The influence of field size, radiation dose, chemotherapy, age, and extent of surgical resection upon long-term complications were studied. CONCLUSION: Radiation therapy for pediatric CNS malignancies is associated with long-term complications. Significant long-term complications can be limited to an acceptable level of approximately 15%.

Retrospective analysis of patients with primary fallopian tube carcinoma treated at the University of Louisville.

Medical records of patients diagnosed with primary fallopian tube carcinoma between 1979 and 1989 were reviewed. Twenty-six patients were eligible; 8 patients were excluded after pathologic review, leaving 18 patients included in the study for this analysis. The median and mean age were 61 and 59 years, respectively, with a range of 39-80 years. There were three Stage I, five Stage II, seven Stage III, and three Stage IV patients. The most common presenting symptoms were abdominal/pelvic pain, abdominal distension, and vaginal discharge/bleeding. The primary site of the lesion was determined to be the right tube in 44% of the cases, the left tube in 39% of the patients, bilateral lesions in 11% of the patients, and indeterminate in 6%. Histologic grade was poorly differentiated (Grade III) in 13 patients, moderately differentiated (Grade II) in 4 patients, and well differentiated (Grade I) in one. No patient was correctly diagnosed preoperatively. Survival at 5 years of the entire group was 35% with a 3 year minimum followup. Corresponding disease free survival was 30%. Mean and median survival times were 74 and 37 months, respectively. The range of survival times was from 1 to 120 months. All Stage I patients, 80% (4/5) of Stage II, and 29% (2/7) of Stage III patients are alive without disease. None (0/3) of the Stage IV patients are alive. Treatment regimens consisted of intraperitoneal P-32, external beam radiotherapy, and/or chemotherapy. Radiotherapy was associated with a low incidence of treatment-related complications, the majority being gastrointestinal related. There was one chemotherapy-related death. These patients and their treatment outcomes add to the data base of numerous previous reports on fallopian tube carcinoma. Stage I and II patients fared excellently with primary surgical and adjuvant therapy. While the prognosis of Stage III and IV patients is much worse, significant levels of long term survival can be achieved with aggressive treatment.

Rhabdomyosarcoma in children--a ten year review.

PURPOSE: The purpose of this study is to retrospectively analyze all pediatric patients with Rhabdomyosarcoma (RMS) of various anatomic sites, treated in our department over a 10-year period, for treatment results. Anatomical site, group, and gender are individually analyzed as prognostic indicators of overall survival. MATERIALS AND METHODS: Sixteen rhabdomyosarcoma patients diagnosed by biopsy or surgical resection were reviewed. All patients were treated according to assigned IRS protocols except one. Age ranged from 1 to 19 years with a median age of 4 years. Ten patients were male and 6 were female, 14 were white and 2 black. Anatomic sites included six from the head and neck region, seven in the trunk and three in the extremities. Embryonal RMS was present in all but one which was classified as undifferentiated. All patients had surgery (biopsy-5, partial-1 or complete resection-10) and chemotherapy (VA, VAC, VAC plus Adriamycin, or VAC plus Adriamycin, CIS Platinum and VP-16). Ten patients received irradiation consisting of 3060 cGy to 5850 cGy using shrinking fields with 1.8 to 2.0 Gy/day/5 day/wk. RESULTS: Patients tolerated the treatment well and there were no late complications. Only one patient had a recurrence in the primary site with a median follow-up of 61 months (range 5-118 months) for the whole group. The 5-year disease free survival and actuarial survival for all patients treated were 73% and 87% respectively, with four patients developing metastasis and three of those dead of disease. CONCLUSION: This study represents a heterogeneous group of patients with RMS treated over a 10-year-period. The results correlate with those found in the most recent published IRS data for embryonal histology. From experience gained from earlier studies, newer IRS protocols have tailored treatment protocols to specific site with more intense therapy used for difficult treatment sites.

Wilms' tumor in an adult: a case report and review of the literature.

Wilms' tumor in an adult is extremely rare, with less than 250 cases reported in the world literature. Treatment guidelines for pediatric Wilms' tumor are well established; those for adults are not. This article presents the case of a 19-year-old male diagnosed with Wilms' tumor after complaints of hematuria. He was categorized as Stage IV after nephrectomy and received post-operative radiotherapy and chemotherapy consisting of Vincristine, Adriamycin, and Actinomycin-D. Two years later he was found to have metastases to brain and lungs. He was treated with radiotherapy and bone marrow transplantation, and died of septic shock. The literature regarding Wilms' tumor in adults is reviewed, and current therapy is discussed.

Chemical modification of normal tissue damage induced by photodynamic therapy.

One of the limitations of successful use of photodynamic therapy (PDT) employing porphyrins is the acute and long-term cutaneous photosensitivity. This paper describes results of experiments designed to test the effects of two radiation protective agents (WR-2721, 500 mg kg-1 or WR-3689, 700 mg kg-1) on murine skin damage induced by PDT. C3H mice were shaved and depilated three days prior to injection with the photosensitiser, Photofrin (5 or 10 mg kg-1). Twenty-four hours later, the mice were injected intraperitoneally with a protector 30 min prior to Argon dye laser (630 nm) exposure. The skin response was followed for two weeks post irradiation using an arbitrary response scale. A light dose response as well as a drug dose response was obtained. The results indicate that both protectors reduced the skin response to PDT, however WR-2721 was demonstrated to be the most effective. The effect of the protectors on vascular stasis after PDT was determined using a fluorescein dye exclusion assay. In mice treated with Photofrin (5 mg kg-1), and 630 nm light (180 J cm-2) pretreatment with either WR-2721 or WR-3689 resulted in significant protection of the vascular effects of PDT. These studies document the ability of the phosphorothioate class of radiation protective agents to reduce the effects of light on photosensitized skin. They do so in a drug dose-dependent fashion with maximum protection at the highest drug doses.

Radiation therapy for pituitary adenomas. A retrospective study of the University of Louisville experience.

A retrospective analysis of treatment outcome was performed on patients treated with radiation for pituitary adenomas at the University of Louisville from January 1988 to December 1992. The study population included 27 patients. Twenty received radiation as a component of their initial treatment while seven received radiation as part of their treatment for recurrent disease. Nineteen patients were treated with post-operative radiation, and eight were treated with radiation alone. Follow-up interval ranged from 1 month to 109 months, with a median of 28 months. All three patients with stage I disease were controlled with radiation alone (1/3) or combined surgery and postoperative radiation (2/3), whereas six of eight stage II patients had disease control following surgery and postoperative radiation. Both patients with stage III adenomas treated with radiation alone had local control, whereas local control was achieved in six of seven with post-operative radiation. Three of five patients with recurrent disease had local control with radiation alone, whereas both patients undergoing surgery and postoperative radiation had local control. This retrospective analysis supports previous findings that radiation therapy alone or combined with transphenoidal resection is effective in long-term control of pituitary adenomas. It further suggests that immediate radiation therapy may be superior to radiation for surgical or medical failures.

Results of irradiation in patients with high-grade gliomas evaluated by magnetic resonance imaging.

Evidence shows that most high-grade gliomas are a diffuse process. Prior studies reported a median survival with surgery and postoperative radiotherapy of 8.6 months for glioblastoma multiforme (GBM) and 36.2 months for anaplastic astrocytoma (AA). Since MRI delineated the glioma better than CT scan, using MRI-based radiotherapy treatment planning allows for more precise treatment volumes. We retrospectively reviewed the records of the first 36 patients with malignant glioma, who had a presurgery MRI-based radiotherapy treatment planning. These patients were diagnosed between January 1986 and February 1991. Minimum follow up was 14 months and median survival was 15.4 months for GBM (7-42 months) and 27.4 months for AA (7-53 months). We feel that the trend for increased median survival in GBM (15.4 vs 8.6 months) is partly due to better definition of the tumor volume by using MRI. Larger studies are needed to confirm this finding.

Radiation therapy for pancreatic cancer: a retrospective study of the University of Louisville experience.

Although multiple regimens and approaches have been used in attempts to treat pancreatic cancer, the 5-year disease-free survival is dismal. With an increase in incidence of pancreatic cancer over the past 35 years, researchers continue their efforts to find an effective treatment for this aggressive disease. Between January 1983 and January 1993, we treated 77 patients with radiotherapy for pancreatic cancer. Only 35 of these patients had localized adenocarcinoma and were treated for cure. In this group of 35 patients, 5 received < 4,000 cGy (mean survival of 5.6 months) and 30 received > or = 4,000 cGy (mean survival of 14.7 months). Twenty-four of these 30 received > or = 5,000 cGy, resulting in a mean survival of 15.4 months, and 17 of these 24 received > or = 6,000 cGy, with a mean survival of 15.7 months. Some palliation of symptoms was achieved in 57% of all patients. These results at the University of Louisville Brown Cancer Center are comparable to other published results, but the prognosis for patients with pancreatic cancer remains bleak.

Use of P-32 in stage III epithelial carcinoma of the ovary.

From 1982 through 1989, 56 patients with Stage III epithelial carcinoma of the ovary received intraperitoneal chromic phosphate following chemotherapy and second look (52 pts) or as the only postsurgical management (4 pts). Median follow-up was 48 months (range of 24 to 108 months). The 4 patients treated following primary surgery with P-32 without chemotherapy had microscopic abdominal disease (3 pts) or complete reduction of gross abdominal disease (1 pt), and their 5-year survival was 100%. Of the 52 patients treated with P-32 following PAC chemotherapy, 23 were pathologic negative, 15 had microscopic residual, and 14 had gross residual at second look. The 5-year survival following second look was 75% for negative, 48% for microscopic, and 32% for gross residual. There were 4 Grade 3 GI complications (7%). There were no complications in the 38 patients who received the P-32 within 12 hr of surgery. The use of P-32 as an adjuvant for Stage I and II epithelial carcinoma of ovary has been found to be effective in prior GOG trials. We have expanded the selection criteria in patients with Stage III carcinoma to include those who can be surgically reduced to microscopic residual at primary surgery or second look following chemo reduction. Because of multiple prognostic variables affecting survival in Stage III ovarian cancer, a randomized study with control arm would be necessary to draw firm conclusions regarding the effectiveness of P-32. The 5-year survival in this group of patients compares favorably to published reports.

Radioneurosurgery using the LINAC scalpel: technique, indications, and literature review.

Two available commercial units for radiosurgery are the modified linear accelerator (LINAC scalpel) and the gamma knife. Advantages of the LINAC scalpel over the gamma knife are its greater accuracy, the availability of a wide range of collimator sizes that allow for a more homogeneous field of radiation for large lesions, state-of-the-art computer software programs, and lower expense. Radiosurgery does not require an incision, is painless, and can be performed on an outpatient basis. It is ideally suited for the treatment of inaccessible, deep intracranial lesions that are radioresistant to conventional forms of radiotherapy, such as arteriovenous malformations, meningiomas, vestibular schwannomas, selected primary brain tumors, and cerebral metastases. Radiosurgery is an attractive treatment alternative to conventional neurosurgery for several intracranial lesions.

Irradiation in the management of anal cancer with literature review.

Sixteen patients with a diagnosis of anal cancer were treated from 1981 to 1990 with combination of surgery, irradiation, and chemotherapy. Median age was 56 years (range 42 to 78 years). There were 3 males and 13 females. Fourteen patients were white and 2 were black. The stage of the primary was: T1-4, T2-9, T3-3. Eleven patients had the tumor in anal canal and 5 patients at the anal verge. Twelve patients had squamous cell carcinoma and 4 had cloacogenic carcinoma. Four patients had planned abdomino perineal resection (APR) after pre-operative chemotherapy (mitomycin C-15 mgm/m2 day 1; 5-fluorouracil, 750 mgm/m2, 24 hour infusion, days 1 to 5, repeated q15 days), and irradiation (30 gy in 15 fractions in 3 weeks). One patient had wide excision of the primary site after the pre-op chemotherapy and irradiation. Ten of 11 patients received higher dose of irradiation (45 to 55 Gy in 4 1/2 to 5 1/2 weeks, 5 days/week) in combination with chemotherapy and anal sphincter conservation surgery. One patient refused chemotherapy and was treated with surgery and high dose irradiation. The median follow-up was 28 months (range 3-125 months). Fifteen patients (94%) had local control. Thirteen are NED from 3 to 125 months and 2 died of intercurrent disease without cancer at 3 and 14 months. One patient with local recurrence at 9 months had salvage surgery, but died of disease. Except for moderate diarrhea and perineal reactions, there were no major complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Phase I-II study of multiple daily fractions for palliation of advanced head and neck malignancies.

PURPOSE: To assess palliation of advance head and neck malignancies with the use of rapid hyper fractionation studies similar to the RTOG 85-02. MATERIALS AND METHODS: 37 patients with 39 lesions were entered into the non-randomized Phase I-II protocol, between 1984 and 1991. Previously untreated malignancies were present in 24 lesions, primary recurrent diseases in six patients, metastasis to the head and neck in five patients and skin primaries in the remaining two cases. At presentation 15 of 37 patients (or 17 of 39 lesions) were in operable due to poor medical status, eight patients were considered technically in operable due to extent of disease, 10 patients had distant metastasis and four patients refused surgery. The protocol uses twice a day fraction (370 cGy per fraction) for 2 consecutive days totalling 1,480 cGy per course. Three courses were given at 3-week intervals for a final tumor dose of 4,440 cGy in twelve fraction over 8-9 weeks. RESULTS: Eleven of 39 lesions had complete response; 19 lesions had partial response; 4 lesions had no response; 3 lesions progressed under treatment. Response could not be assessed in two patients. The average survival after completion of therapy was 4.5 months ranging from 2 weeks to 31 months. Palliation was achieved in 33 of 39 lesions. The acute reactions were minimal and no late or long term complications were noted. CONCLUSION: The absence of significant complications with reasonable response in the high rate of palliation suggests that this rapid hyper fractionation palliation study should be studied for further evaluation.

Imaging of radiation dose for stereotactic radiosurgery.

The distributions of radiation dose for stereotactic radiosurgery, using a modified linear accelerator (Philips SL-25 and SRS-200), have been studied by using three different dosimeters: (1) ferrous-agarose-xylenol orange (FAX) gels, (2) TLD, and (3) thick-emulsion GafChromic dye film. These dosimeters were loaded into a small volume of defect in a phantom head. A regular linac stereotactic radiosurgery treatment was then given to the phantom head for each type of dosimeter. The measured radiation dose and its distributions were found to be in good agreement with those calculated by the treatment planning computer.

Phase II trial of combination chemotherapy and irradiation in non-small-cell lung cancer, Radiation Therapy Oncology Group 88-04.

Encouraging results of several clinical trials utilizing combination chemotherapy and irradiation in unresectable non-small-cell lung cancer have been reported. A recent report from a cooperative group study suggested that preirradiation vinblastine and cisplatin improved survival over irradiation alone. In an attempt to enhance the possible effectiveness of combination chemotherapy and irradiation, the Radiation Therapy Oncology Group embarked on a Phase II trial utilizing preirradiation vinblastine (5 mg/m2 weekly x 5) and cisplatin (100 mg/m2) on days 1 and 29 prior to irradiation and on days 50, 71, and 92 during irradiation. The irradiation began on day 50 and consisted of 6300 cGy in 7 weeks. Between May 20, 1988 and May 1, 1989, 30 patients were entered on study. Seventy-two percent of patients had Karnofsky status greater than 90, and 76% had weight loss less than 5%. Forty-eight percent of the patients were younger than 60 years of age. Forty-five percent of the patients had Stage IIIA disease. Eighty-three percent of the patients received at least four courses of vinblastine, and 59% received at least four courses of cisplatin. Seventy-eight percent of the patients received at least 95% of the prescribed irradiation. The major toxicity was hematologic, and there were two fatal complications in the study group. The preliminary survival figures are encouraging. This combination of chemotherapy and irradiation appears to be tolerable and may merit further investigation.

Incidence of complications with mini vaginal culpostats in carcinoma of the uterine cervix.

Between 1980 and 1987, 298 patients with carcinoma of the uterine cervix were treated at the University of Louisville Department of Radiation Oncology. Of these, 197 (66.1%) were treated for cure by radiotherapy alone: 36 by external beam alone and 161 by external beam and tandem and ovoid applications. The F.I.G.O. staging of the 161 patients was 82 (50.1%) Stage IB, 9 (5.6%) Stage IIA, 40 (24.9%) Stage IIB, and 30 (18.6%) Stage III. The usual treatment was whole pelvis irradiation followed by two intracavitary applications using the Fletcher Suit Applicators of tandem and ovoids in 79/161 patients (49%), a 3-M Mini Applicator (Fletcher Suit Delcos Applicator) in 52/161 patients (32.3%), and a 3-M Mini Applicator with Caps in 30/161 patients (18.6%). The incidence of grade 3-4 gastrointestinal or genitourinary complications as defined by the RTOG was 19.3% (31/161). Various treatment parameters were analyzed to define possible contributing factors. Grade 3-4 complications were seen in 7.6% (6/79) of patients treated with the standard ovoid Fletcher system, 26.9% (14/52) treated with the mini-ovoid system, and 36.6% (11/30) treated with the mini-ovoid system with caps (p = .0006). Although trends were noted, neither the vaginal surface dose (VSD) from the ovoids nor the addition of the external beam dose to the VSD (total vaginal surface dose = TVSD) were significant independent variables (p = 0.19 and = 0.133, respectively). The TVSD was significant when comparisons were made between different ovoid systems (p = 0.05 for less than 12,000 cGy and p = 0.004 for greater than 12,000 cGy). In this study, the 3-M mini applicator was associated with a significant increase in grade 3-4 complications as compared to the Standard Fletcher Suit Applicator.

Glioblastoma multiforme in adults: results of treatment.

One hundred and thirty adult patients with brain tumors were treated in the Department of Radiation Oncology, Brown Cancer Center, University of Louisville School of Medicine from 1973 to 1980. Forty-one patients (39%) were diagnosed with glioblastoma multiforme. Forty-two percent of the patients were in the age group of 51-60 years. There were 24 males and 27 females. Forty-seven percent of the patients had partial resection, 27% had total excision and 26% had biopsy only. The radiation dose ranged from 4400 to 6600 rad with a median dose of 5500 rad. The median survival was 8.5 months, (range 3 to 120 months), 38% of patients survived one year or more and 10% survived 2 years or more. A detailed review of the current policy of treatment and of the ongoing clinical trials is done in this paper.

GYN implant orthogonal film holder.

An orthogonal film holder has been developed for the use of implants in the O.R. This film holder provides both AP and lateral films that are truly 90 degrees apart from each other. Placement of the GYN applicators must be checked before completion of the procedure. Traditionally, orthogonal films have been used for positioning and for the dose calculations. Therefore it is critical to have good quality radiographs. The AP film holder is placed beneath the patient and the lateral film holder slides into the side of the AP film holder, providing accurate placement and reproducibility in relation to each other. After the films have been approved, the lateral film holder bolts on top of the AP film holder. The system then looks like a briefcase and has a carrying handle for easy transportation and storage. This newly designed system has been used successfully and has proved its ease of use and accuracy.

Biteblock-head immobilizer system.

To accurately deliver high doses of radiation to the head and neck region one must be able to achieve three primary goals: reproduce the patient set-up or position, immobilize the patient, and most importantly, position the treatment field on the patient in the same exact location on a daily basis. Many patient positioning devices are available commercially but none address the concept of positioning the treatment field on the patient. The system presented in this paper accomplishes all 3 goals. Using a biteblock and a coordinate system, it has decreased the daily set-up time and improved the accuracy of the treatment field placement on the patient. Five hundred port films were reviewed retrospectively from previously treated patients who were treated without this new system (66% of those films were approved, and 34% needed some sort of adjustment). Using the new system the accuracy of 107 port films was determined (91% were approved, while only 9% needed any type of adjustment). This newly developed system provides the extra step, treatment accuracy, that no other device has done.

Medulloblastoma: results of treatment.

Fourteen patients with a diagnosis of medulloblastoma were treated in the Department of Radiation Oncology, University of Louisville School of Medicine from 1973 to 1979. The age of these patients ranged from 2 to 47 years with a median of 9 years. Twelve of them were 15 years or younger. All patients received craniospinal radiation after surgery, with a boost to the primary site by reduced field. The median dose to the primary was 4736 rads (range 3600 to 5600 rad). The median follow-up was 29.5 months. Six patients have died, and four of those six patients lived more than two years. Eight patients are alive to the last follow-up with a median survival of 29 months. Eight of 14 patients had local control and one patient developed distant metastasis. A brief review of the literature is done in this paper.

Primary gastric lymphoma and pseudolymphoma.

Eighteen patients with primary gastric lymphomas and two with pseudolymphomas treated at the University of Louisville affiliated hospitals were analyzed in order to develop a more precise understanding of these rare diseases. Abdominal pain and weight loss were the most common initial symptoms. Only one patient presented with an abdominal mass. Upper GI series were helpful but failed to show a definite abnormality in two of 18 cases. Endoscopic examinations in all 18 were compatible with malignancy on gross finding, but six out of 15 endoscopic biopsies were not conclusive. All four cases, which proved fatal in less than two years, showed serosal invasion and diffuse histological pattern. On the basis of our analysis, we suggest that in patients with abdominal pain and weight loss of more than two months duration an aggressive course of evaluation should include upper gastrointestinal x ray and repeated endoscopic biopsy. If symptoms persist, laparotomy and biopsy may be warranted even if endoscopic biopsy shows no neoplasm. Curative surgery is the treatment of choice, but radiation therapy should be added in patients with serosal involvement. Very careful histological assessment of pseudolymphomas is necessary, because they may contain malignant lymphoma.