The influence of smoking on radiation-induced bystander signal production in esophageal cancer patients.

The relevance of radiation-induced bystander effects in humans is unclear. Much of the existing data relate to cell lines but the effect of bystander signals in complex human tissues is unclear. A phase II clinical study was untaken, where blood sera from 60 patients along with 15 cancer-free volunteers were used to detect whether measurable bystander factor(s) could be found in the blood following high dose rate (HDR) brachytherapy. Overall, there was no significant change in bystander signal production (measured in a human keratinocyte reporter system) before and after one treatment fraction of HDR brachytherapy (p>0.05). Further assessment of patient characteristics and environmental modifiable factors including smoking were also analyzed. Similar to previously published data, samples taken from smokers produced weaker signals compared to non-smokers (p<0.05). Although the number of non-smoking subjects was low, there was a clear decrease in cloning efficiency observed in keratinocyte cultures for these patients that requires further study. This study found that samples taken from smokers do not produce bystander signals, whereas samples taken from non-smokers can produce such signals following HDR brachytherapy. These findings highlight the importance of studying the interactions of multiple stressors including environmental modifiers with radiation, since some factors such as smoking may elicit protection in tumor cells which could counteract the effectiveness of radiation therapy.

2D∕3D registration algorithm for lung brachytherapy.

PURPOSE: A 2D∕3D registration algorithm is proposed for registering orthogonal x-ray images with a diagnostic CT volume for high dose rate (HDR) lung brachytherapy. METHODS: The algorithm utilizes a rigid registration model based on a pixel∕voxel intensity matching approach. To achieve accurate registration, a robust similarity measure combining normalized mutual information, image gradient, and intensity difference was developed. The algorithm was validated using a simple body and anthropomorphic phantoms. Transfer catheters were placed inside the phantoms to simulate the unique image features observed during treatment. The algorithm sensitivity to various degrees of initial misregistration and to the presence of foreign objects, such as ECG leads, was evaluated. RESULTS: The mean registration error was 2.2 and 1.9 mm for the simple body and anthropomorphic phantoms, respectively. The error was comparable to the interoperator catheter digitization error of 1.6 mm. Preliminary analysis of data acquired from four patients indicated a mean registration error of 4.2 mm. CONCLUSIONS: Results obtained using the proposed algorithm are clinically acceptable especially considering the complications normally encountered when imaging during lung HDR brachytherapy.

Angiosarcomas--clinical profile, pathology and management.

Files of 8 patients with primary angiosarcomas treated in the Department of Radiation Oncology at the University of the Witwatersrand from 1982 to 1995 were identified. None of these patients had received prior radiotherapy or chemotherapy which would have predisposed them to the formation of an angiosarcoma. Slides of 6 patients were reviewed. Five of the 6 were confirmed as having angiosarcomas, while 1 patient was found to have a peripheral neuro-epithelial tumour. Four patients had angiosarcomas of the breast, while there was 1 patient each with angiosarcoma of the skin, intestine and brain. Complete excision was the primary modality of management whenever possible. Postoperative radiotherapy was given in cases of incomplete excision, patient refusal of radical surgery or gross tumour. Four patients died within 4 months of diagnosis. Three patients are alive (2 with no evidence of disease) 22-96 months after diagnosis. In 1 patient follow-up details were not available as he did not return for treatment. Angiosarcomas are aggressive malignant tumours arising from the endothelial cells. Complete surgical excision is the treatment of choice in the management of this aggressive disease, which has a poor prognosis.

Fractionated high dose rate intraluminal brachytherapy in palliation of advanced esophageal cancer.

PURPOSE: To optimize the dose of fractionated brachytherapy for palliation of advanced esophageal cancer. METHODS AND MATERIALS: One hundred and seventy-two patients with advanced esophageal cancer were randomized to receive 12 Gy/2 fractions (group A); 16 Gy/2 fractions (group B), and 18 Gy/3 fractions (group C) by high dose rate intraluminal brachytherapy (HDRILBT). Treatment was given weekly and dose prescribed at 1 cm from the source axis. Patients were followed up monthly and assessed for dysphagia relief and development of complications. RESULTS: Twenty-two patients died before completing treatment due to advanced disease and poor general condition. The overall survival was 19.4% at the end of 12 months for the whole group (A--9.8%, B--22.46%, C--35.32%; p > 0.05). The dysphagia-free survival was 28.9% at 12 months for the whole group (A--10.8%, B--25.43%, C--38.95%; p > 0.05). Forty-three patients developed fibrotic strictures needing dilatation (A--5 of 35, B--15 of 60, C--23 of 55; p = 0.032). Twenty-seven patients had persistent luminal disease (A--11, B--6, C--10), 15 of which progressed to fistulae (A--7, B--2, C--6; p = 0.032). There was no effect of age, sex, race, histology, performance status, previous dilation, presenting dysphagia score, presenting weight, grade, tumor length, and stage on overall survival, dysphagia-free, and complication-free survival (p > 0.05). On a multivariate analysis, brachytherapy dose (p = 0.002) and tumor length (p = 0.0209) were found to have a significant effect on overall survival; brachytherapy dose was the only factor that had an impact on local tumor control (p = 0.0005), while tumor length was the only factor that had an effect on dysphagia-free survival (p = 0.0475). When compared to other forms of palliation currently available (bypass surgery, laser, chemotherapy, intubation, external radiotherapy), fractionated brachytherapy gave the best results with a median survival of 6.2 months. CONCLUSIONS: Fractionated brachytherapy is the best modality for palliation of advanced esophageal cancer. It offers the best palliation to patient when compared to all other modalities currently available. The optimal brachytherapy dose ranges between 16 Gy in two fractions and 18 Gy in three fractions given a week apart.

Adenoid cystic carcinoma of the salivary glands: a review of 10 years.

A retrospective analysis was performed of 50 patients with adenoid cystic carcinoma who were seen in the Department of Radiation Oncology, University of Witwatersrand, Johannesburg, South Africa, in the past 10 years. There were 25 men and 25 women with a mean age of 52 years (age range, 21 to 88 years). Five patients had metastatic disease, and 17 had neural invasion. Thirty-four patients had surgery (11, complete; 23, microscopic residual). Sixteen patients had radiotherapy as initial management. The disease-free survival was 26%, overall survival was 29%, and local control was 30% at 10 years. Most recurrences occurred in the first 3 years. Nine patients had metastasis following treatment. The mean survival after metastasis was 15 months. Seven prognostic variables were analyzed using the log-rank test. There was no impact of age, site, type of salivary gland (major vs. minor), tumor stage, node positivity, or neural invasion on disease-free survival, overall survival, or local control. Extent of surgical resection (complete vs. microscopic residual) had a significant impact on disease-free survival and local control (P < 0.05) but no impact on overall survival (P > 0.05) because of the slow-growing nature of these tumors. Similarly, patients who had microscopic residual after surgery and were treated with radiotherapy did better than those who had biopsy and radiotherapy, although this was not significant statistically (P > 0.05). Thus, whenever possible, every attempt must be made to remove all microscopic tumor by surgery. Addition of postoperative radiotherapy with high-energy photons did not improve the locoregional control or survival in our series. There is a place for neutrons in the treatment of adenoid cystic carcinomas in advanced cases of inoperable or recurrent tumors, as a review of literature shows.

Primary gastrointestinal lymphoma--disease spectrum and management: a 15-year review from north India.

OBJECTIVE: To analyze retrospectively the disease spectrum and outcome of primary gastrointestinal lymphoma (PGIL) in a tertiary referral center in north India. MATERIAL: Seventy five patients presenting with PGIL between January 1971 and December 1985 were evaluated. RESULTS: The 49 males and 26 females were aged 3.5-69 years (mean 34) at presentation. Abdominal pain, weight loss and vomiting were cardinal symptoms at presentation; the stomach was the most common site of involvement. Histologically, a majority of patients were classified as having diffuse poorly-differentiated lymphocytic lymphoma (46.7%) and diffuse histiocytic type (30.7%). Twenty seven (36%) patients had stage I disease, 31 (40%) stage II, 11 (14.7%) stage III, and 6 (8%) stage IV. At laparotomy, primary resection and anastomosis was carried out in 66 patients, while only biopsies were taken in nine. Forty eight patients received adjuvant radiation with or without chemotherapy. The mean follow-up was 3.9 years (range 1-14). The 5-year actuarial survival was 34%, 25% and 16% for stages I, II, and higher-stage disease, respectively. The survival was significantly better (p < 0.01) for gastric location (44%) compared to other sites (24%). CONCLUSION: PGIL was more common in the 3rd and 4th decades of life, with the stomach being the predominant site of involvement. Survival was better among patients with stages I and II disease, and gastric location of lesion.

Symmetrical multifocal liposarcoma.

Multiple liposarcomas are extremely rare. We report on a patient with liposarcoma of the right lower limb who had undergone surgery and radiotherapy 4 years previously for a liposarcoma in the left lower limb. An outline of the management is discussed and a short review of available literature is given.

Role of radiotherapy in stage III invasive thymomas.

Twenty-five patients with malignant invasive stage III thymomas who underwent biopsy for tissue diagnosis were treated with primary radiotherapy (mean dose 46.36 Gy, range 32.4-58 Gy). These patients were followed up for a period of 10 years and survival/failure analysis was performed. Five prognostic variables were compared using the log rank test. There was no difference in survival between ages less than 50 and more than 50 years, presence or absence of myasthenia gravis, sex, histology and race. The mean follow-up was 39 months (range 1-86 months). The 5-year disease-free survival was 81% overall survival 72% and local failure rate 13%. Most local failures occurred in the first 3 months. Six patients died after a course of radiotherapy (2 intrathoracic relapse, 1 disseminated disease, 1 local failure and distant metastasis, 2 causes not related to disease). Hilar fibrosis was seen in 4 patients who are asymptomatic. No other complications were recorded. Radical external beam radiotherapy alone can give good results in malignant stage III invasive thymomas.

Hepatoprotection with Glycosmis pentaphylla (Retz).

Effects of extracts of leaf (250, 500 and 750 mg/kg body wt) and stem bark (100, 200 and 400 mg/kg body wt) of G. pentaphylla were studied on CCl4 (1 mg/kg body wt) induced hepatic injury in albino rats. Parameters studied were plasma ALAT, ASAT, ALP, total bilirubin and tissue histopathology. Recovery of hepatic tissue was indicated with the highest dose (750 mg/kg body wt) of leaf extract. The therapeutic dose range was devoid of toxic effects. Toxicity of leaf extract was observed histopathologically at and above 2.5g/kg body wt.

Adenoid cystic carcinoma of the trachea. A report of 2 cases.

Two cases of adenoid cystic carcinomas arising from the trachea are presented. Epidemiology, presenting features, available therapeutic options and a review of the literature are discussed.

Radiotherapy for stage I and II testicular seminoma after orchidectomy.

A retrospective study was undertaken to evaluate the effect of irradiation on 65 patients with stage I, or II testicular seminomas treated at Hillbrow Hospital with irradiation following orchidectomy. Forty-seven patients presented with stage 1 and 9 with stage II disease. All patients received infradiaphragmatic irradiation. In addition 4 patients with stage II disease received prophylactic supradiaphragmatic irradiation. The 5-year overall and disease-free survival rate for all stages and for stage I and II compared favourably with other reports in the literature. The irradiation was well tolerated and severe long-term toxicity was rare. Seminomas were uncommon in black patients, of whom only 3 were seen in the 12-year period of this study.

Palliation of carcinoma of the oesophagus with brachytherapy and the Didcott dilator.

Forty-one patients with oesophageal cancer who developed strictures after high dose rate intraluminal brachytherapy were dilated using a slow continuous dilator (Didcott dilator). After dilatation, all patients were evaluated monthly for relief of dysphagia. At the end of the 1st month, 41 patients were evaluable: 28 had no dysphagia while 13 had improvement; at the end of the 2nd month, 40 were evaluable, 26 had no dysphagia while 14 had improvement; at the end of the 3rd month, 34 patients were evaluable, 24 had no dysphagia while 10 had improved. Three patients developed worsening of dysphagia owing to tumour recurrence among 32 patients who were evaluable at the end of the 4th month. Five patients developed worsening of dysphagia among the 26 patients who were evaluable at the 5th month due to tumour. These patients were dilated with the Didcott dilator and were treated with further brachytherapy. At the end of the 6th month, 14 patients were evaluable; seven had no dysphagia, while seven had improvement over their presenting dysphagia scores. Slow continuous dilatation using the Didcott dilator is very effective in the dilatation of strictures after high dose rate intraluminal brachytherapy. Dilatation is prolonged and sustained and a single dilatation is usually enough to maintain patency.

Toxicity in patients with testicular seminoma treated with radiotherapy. Different dose levels and treatment fields.

The aim of this study was to evaluate the acute and late effects of irradiation in 56 patients with stage I and II testicular seminomas. A retrospective study of patients' records was performed paying attention to the acute and late toxicity of radiation in relation to treatment fields and radiation doses. Treatment groups were compared using the chi squared-test. Mild to moderate nausea and/or vomiting was seen in 66% of patients and occurred equally independent of the treatment volume or radiation dose. Increased bowel frequency was seen in 59% and was more common when a larger treatment volume was used. Skin reactions increased with increase in treatment volume and dose (p = 0.046). Severe late complications were recorded in two patients (myocardial damage-1/4 at risk, duodenal ulcer-1/56 at risk). These could not be attributed solely to the irradiation as other contributing factors might play a role. Overall the data suggest that the risk of major posttreatment morbidity is minimal for patients with testicular seminoma treated with postoperative radiotherapy.

Three dimensional conformal radiation therapy in pediatric parameningeal rhabdomyosarcomas.

PURPOSE: We evaluated the utility of three dimensional (3D) treatment planning in the management of children with parameningeal head and neck rhabdomyosarcomas. METHODS AND MATERIALS: Five children with parameningeal rhabdomyosarcoma were referred for treatment at our radiation oncology center from May 1990 through January 1993. Each patient was evaluated, staged, and treated according to the Intergroup Rhabdomyosarcoma Study. Patients were immobilized and underwent a computed tomography scan with contrast in the treatment position. Tumor and normal tissues were identified with assistance from a diagnostic radiologist and defined in each slice. The patients were then planned and treated with the assistance of a 3D treatment planning system. A second plan was then devised by another physician without the benefit of the 3D volumetric display. The target volumes designed with the 3D system and the two-dimensional (2D) method were then compared. The dosimetric coverage to tumor, tumor plus margin, and normal tissues was also compared with the two methods of treatment planning. RESULTS: The apparent size of the gross tumor volume was underestimated with the conventional 2D planning method relative to the 3D method. When margin was added around the gross tumor to account for microscopic extension of disease in the 2D method, the expected area of coverage improved relative to the 3D method. In each circumstance, the minimum dose that covered the gross tumor was substantially less with the 2D method than with the 3D method. The inadequate dosimetric coverage was especially pronounced when the necessary margin to account for subclinical disease was added. In each case, the 2D plans would have delivered substantial dose to adjacent normal tissues and organs, resulting in a higher incidence of significant complications. CONCLUSIONS: 3D conformal radiation therapy has a demonstrated advantage in the treatment of sarcomas of the head and neck. The improved dosimetric coverage of the tumor and its margin for subclinical extensions may result in improvement in local control of these tumors. In addition, lowering of radiation dose to adjacent critical structures may help lower the incidence of adverse late effects in children.

Carotid body tumour--a case for radiotherapy?

Carotid body tumours are rare tumours in the head and neck region. Treatment has been surgery with little or no role for radiotherapy. We describe 5 patients with carotid body tumours seen in our department in the last 10 years. Two patients were treated with postoperative radiotherapy after incomplete surgery, 2 had inoperable tumours and were treated with radiotherapy alone, and 1 had a complete excision and required follow-up only. In the 4 patients who received radiotherapy, the disease was stable in 1 patient at 1,1 years and progressive in 2 at 0,6 and 5,6 years respectively; 1 patient did not complete treatment. The patient who had surgery alone for a small tumour was free of disease at 1 year. Small carotid body tumours should be treated with surgery alone. When the tumour is large or the patient is older we propose radiotherapy as initial treatment because of the high morbidity of surgery. A review of the literature and the results with radiotherapy alone in varying doses support this view.

Jugulotympanic paragangliomas.

Eleven patients with glomus jugulotympanicum tumours were seen in our department between January 1983 and December 1993. Nine patients received a full course of radiotherapy with doses ranging from 35 to 54 Gy. Four patients were available for assessment after 48 months. All were alive and asymptomatic at the time of writing. In 4 other patients, pain had improved although cranial nerve function had not at the last follow-up (1-9 months). One patient died 1 month after treatment. Radiotherapy can provide long-term local control and survival in the treatment of glomus jugulotympanicum tumours. The details of clinical presentation, follow-up and the methods of investigation are presented together with a review of the literature.

Von Recklinghausen's disease associated with a primary malignant schwannoma of the breast.

A case of a primary malignant schwannoma of the breast is reported. This case and the review of the literature illustrate the problems of diagnosing and treating this rare malignancy.