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.

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.

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.

Radiation therapy of esophageal cancer: role of high dose rate brachytherapy.

Fifty untreated cases of squamous cell carcinoma arising from the middle one-third of the esophagus, with no apparent extraesophageal spread on a computed tomography (CT) scan and with a Karnofsky performance status of over 70, were treated by external beam irradiation to a dose of 3500 cGy/15 fractions/3 weeks. Twenty-five patients (Group A) received treatment with further external beam irradiation to a dose of 2000 cGy/10 fractions/2 weeks. Another group of 25 patients (Group B) received treatment with high dose rate intracavitary irradiation to a dose of 1200 cGy delivered in two sessions of 600 cGy each a week apart. All patients were assessed symptomatically, endoscopically, and radiologically every 3 months. There was marked difference at the end of 1 year in relief of dysphagia (37.5% in Group A vs. 70.6% in Group B), local control (25% in group A vs. 70.6% in group B) although the results were statistically insignificant (p greater than 0.05) and actuarial survival (44% in group A vs. 78% in group B) which was, however, significant statistically (z = 2.83). The cumulative radiation effect (CRE) by external beam irradiation was 1729 reu and by external beam and intracavitary irradiation 1741 reu, but the biological dose effect was better with external beam and intracavitary irradiation. Eight percent of patients treated by external beam and intracavitary irradiation had strictures in contrast to 4% treated by external beam irradiation alone. Moderate doses of external beam and intracavitary irradiation can give a better local response than external beam irradiation alone for the same biological dose in the treatment of esophageal carcinoma.

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.

Fertility in patients treated with radiotherapy following orchidectomy for testicular seminoma.

This study evaluated the effect of paraaortic and ipsilateral pelvic node irradiation on the fertility of a group of 50 patients with Stage I and II testicular seminoma. Eleven patients were infertile before the start of treatment, and another 23 were unable or unwilling to father a child after radiotherapy. From the remaining 16 patients, 11 pregnancies resulted. It has been shown that fertility can be preserved if the dose to the remaining testis can be reduced to less than 2 Gy. No genetic abnormalities were seen in the offspring of any patient.

Changes in target volume during radiotherapy treatment of invasive bladder carcinoma.

Ninety patients with stage T3 Nx Mo carcinoma of the urinary bladder were treated with radical megavoltage external beam radiotherapy. Planning for treatment was undertaken on a treatment planning system utilizing CT scan slices to define the target volume and patient outline. All patients underwent a second CT scan half way through their course of treatment to assess any change in target volume and the continued adequacy of the original treatment plan. Seventy-two patients (80%) had no spatial shift in target volume, but, of the 18 patients with such a shift, treatment plans were changed in seven. The majority of patients had no delay in continuing their treatment after replanning, but one patient had a gap of 5 days before restarting treatment. An analysis of the factors possibly associated with a change in target volume showed that a primary tumour at the bladder base, rather than elsewhere in the bladder, was the single most important criterion for predicting target volume changes. There was no correlation between the size of the initial tumour, or the size of the prostate gland in male patients, and the occurrence of a shift in volume outside the initial target volume. Some method of regularly assessing the continued relevance of the target volume may be needed in this group of patients to improve the precision of treatment and also improve results.

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.

Evaluation of radical treatment of carcinoma esophagus using a combination of external beam and intracavitary irradiation.

Twenty five patients with squamous cell carcinoma arising from the middle third of the esophagus were treated radically, with external radiation, to a dose of 55-60 Gy. All patients had lesions less than 6 cm in length with no extra-esophageal spread on computed tomography scan. Eleven of these patients received additional intracavitary radiation to a dose of 12 Gy, 1 cm from the source axis in two sessions of 6 Gy each, a week apart. There was no significant difference in the relief of dysphagia and survival among these receiving and those not receiving intracavitary radiation. Addition of intracavitary radiation to radical external radiation was associated with significant complications like stricture and fistulae formation, which accounted for the poor results.

High dose rate intracavitary therapy in advanced carcinoma esophagus.

Nine patients with advanced squamous cell carcinoma of the middle third of the esophagus were treated by high dose rate intracavitary therapy. The dose delivered was 12 Gy in two sessions at 1 cm from the center of the source. All nine patients were alive after 9 months. Six months after treatment, 4 patients had strictures which were dilated. At the end of nine months, 6 patients had dysphagia, four of whom had strictures and two had recurrence which was treated by further intracavitary irradiation. Intracavitary radiation using high dose rate, remote controlled afterloader has a significant role in palliation in patients with advanced esophageal carcinoma and avoids intubation.

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.

Metastatic tumour of the iris: a rare presentation.

Metastasis to the iris is less frequent than that to the ciliary body and choroid. This might be the presenting feature. We report a 40 years male patient, a chronic smoker, who presented with pain, redenss and photophobia in the right eye. On detailed examination and investigations it turned out to be a case of primary squamous cell carcinoma of the bronchus metastasising to the iris. The presentation, difficulty in the diagnosis and management is discussed with review of the relavent literature.

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.

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.

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.

Initial experience with telebrachytherapy treatment in palliation of advanced oesophageal cancer.

Ten patients with advanced metastatic squamous cell carcinoma of the middle third of the oesophagus were treated with palliative external radiotherapy and intraluminal brachytherapy. All patients had long lesions, 8-15 cm in length, and narrow lumens that did not allow the passage of a guidewire for dilatation. Improvement in dysphagia by more than 2 grades was seen in 9 of 10 patients. This finding was correlated with an increase in the size of the oesophageal lumen at the end of 6 weeks following treatment by barium swallow. No complications of treatment were noted in any patient. Low doses of external beam radiotherapy and high-dose-rate intraluminal brachytherapy can provide quick and effective palliation in advanced metastatic oesophageal carcinoma.

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.

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.