Thyroid dysfunction after mantle irradiation of Hodgkin's disease patients.

Thyroid dysfunction can develop in patients with Hodgkin's disease who are treated with mantle irradiation. During the period 1970-89, the records of 320 patients who received mantle irradiation and who had thyroid function tests (TFT) were retrospectively reviewed. The median age was 30 years (range, 7-69 years). The median mantle and thyroid dose was 36 Gy (range, 30-40 Gy) and 39.8 Gy (range, 32-65 Gy), respectively. Overall thyroid dysfunction was present in 39% of the patients. Clinical hypothyroidism was seen in 10% and biochemical hypothyroidism was noted in 25%. Hyperthyroidism was found in 4% of patients. Thyroid nodules had developed in six patients (2%), of which those in four patients were malignant. Age, sex, histological subtype, stage of disease, dose, lymphangiogram and treatment with chemotherapy were not significant factors in the development of thyroid dysfunction. The narrow dose range prevented adequate analysis of dose effect. The results indicate that the incidence of thyroid abnormalities is high enough to warrant regular TFT assessment with pre-irradiation levels and follow-up testing for life because the development of abnormalities can occur many years later. Thyroid examination should form part of the routine follow-up examination and any abnormality should be promptly investigated.

Radiotherapy for early infradiaphragmatic Hodgkin's disease: the Australasian experience.

PURPOSE: To review the Australasian results of Stage I and IIA Infradiaphragmatic Hodgkin's Disease (IHD) treated solely by irradiation. METHODS AND MATERIALS: Eligible patients had IHD only and were treated by irradiation with curative intent over the period of 1969 to 1988. Ten radiation oncology centres from within Australia and New Zealand were surveyed for patient, tumour and treatment variables. Disease free rates, survival and complications were analysed. RESULTS: 106 patients with IHD were studied. The average potential follow up was 9.4 years. The male to female ratio was 3.3:1. The median age was 37.5 years. Histological subgroups were as follows; lymphocyte predominant 43%, mixed cellularity 21%, lymphocyte depleted 5%, nodular sclerosing 27% and unclassifiable 4%. Fifty nine patients had laparotomy of which 22 (37%) were positive for tumour. Nine laparotomies were performed for diagnosis and the remainder for staging. One patient was up-staged by laparotomy and three were down-staged. Sixty-eight patients presented with inguinal disease alone, five with abdominal disease alone, 19 with two sites of involvement and 12 with inguinal, pelvic and abdominal disease. In two patients the site was unknown. There was no correlation between site of involvement, age, sex or histological subtype. Forty seven cases were clinically staged (CS) as follows: CS IA-23, CS IIA-24. The other 59 were pathologically staged (PS) as follows: PS IA-37, PS IB-1, PS IIA-21. Treatment consisted of involved field alone (16), inverted Y (68), inverted Y and spleen (13), para-aortic irradiation only (3), or total nodal irradiation (6). Mean dose was 37 Gy. There were 30 recurrences to give an acturial 10-year disease-free rate of 70%. In multivariate analysis lower number of tumour sites, lymphocyte predominant histology and higher dose were all significantly correlated with higher disease free rates. Eight patients died of Hodgkin's disease and 19 of other causes. The 10-year overall survival rate was 71%. Older age and higher number of disease sites were significantly correlated with shorter survival. Fourteen of 30 relapses may have been avoidable by the use of total nodal irradiation. In particular ten of 21 patients with abdominal disease relapsed in nodal sites which would have been covered by total nodal irradiation. CONCLUSIONS: The rate of control in IHD could perhaps be improved by avoiding involved field irradiation or by aggressive therapy with total nodal irradiation or combined modality chemo-irradiation in Stage II disease. Staging laparotomy does not appear to be indicated.

Radiation treatment of superior sulcus lung carcinoma.

The survival of patients with superior sulcus lung carcinoma and the effects of treatment were reviewed. From a prospective database of 4123 consecutive new patients with lung carcinoma, 131 (3.2%) cases of superior sulcus lung carcinoma were identified. Seventy-four patients were planned to receive radiation with palliative intent, 53 radical radiotherapy and one was observed only. The remaining three patients, with small-cell carcinoma, were treated with chemotherapy with or without radiotherapy. Of the 53 radically treated patients, nine were treated with pre-operative radiation prior to intended radical resection. Analysis was carried out on the effect on survival of performance status, nodal involvement, weight loss, vertebral body or rib involvement, treatment intent and radical combined modality treatment compared with radical radiation alone. The estimated median survival for the whole group was 7.6 months; for those treated radically it was 18.3 months, while for the palliatively treated patients it was 3.7 months. Radically treated patients with no initial nodal involvement had an estimated median survival of 22 months, while radically treated patients with nodal involvement had an estimated median survival of 8.4 months (P = 0.003). There were no statistically significant differences in survival between radically treated patients grouped according to initial weight loss, performance status, or vertebral body and rib involvement. Patients treated with pre-operative radiation did not survive significantly longer than patients treated with radiation alone, although the numbers are small.

Radiation therapy for early stage Hodgkin's disease: Australasian patterns of care. Australasian Radiation Oncology Lymphoma Group.

PURPOSE: Analysis of treatment outcome for Stage I-IIA supradiaphragmatic Hodgkin's disease treated solely by irradiation in Australia and New Zealand. METHODS AND MATERIALS: Patients with supradiaphragmatic Hodgkin's disease only who were treated by irradiation alone with curative intent between 1969 to 1988 were retrospectively reviewed. Ten radiation oncology departments in Australia and New Zealand contributed patient data to the study. Patient, tumor, and treatment variables were recorded. Disease-free interval, survival, and complications were analyzed. RESULTS: Eight hundred and twenty patients were reviewed. The median age was 29 years. There were 437 men and 383 women. The distribution of 310 clinically staged patients was 170 stage IA, 5 IB, and 135 IIA. Five hundred and ten patients received laparotomies, and pathologic staging was as follows: IA 214, IB 13, IIA 283. The 10-year actuarial disease-free rate was 69% and overall survival rate was 79%. Increasing age, male sex, higher number of involved sites, the use of involved field irradiation, no staging laparotomy, and earlier year of treatment were significantly associated with an increased risk of relapse and lower survival. Actuarial 10-year survival following recurrence was 48%. Acute complications requiring interruption to treatment occurred in 46 patients (6%), but < 1% had their treatment permanently suspended. Actuarial complication rates at 10 years were: cardiac 2%, pulmonary 3% and thyroid 5%. There were 44 second malignancies including 10 non-Hodgkin's lymphomas, 3 leukemias, 7 lung, and 6 breast cancers. Mean delay to the development of a second cancer was 6 years. The 10-year actuarial rate of second malignancy was 5%. CONCLUSIONS: The Australasian experience of early stage Hodgkin's disease is consistent with the results in the published literature and confirms that irradiation produces a high cure rate with minimal toxicity.

A phase III study of accelerated radiotherapy with and without carboplatin in nonsmall cell lung cancer: an interim toxicity analysis of the first 100 patients.

PURPOSE: In 1989 we initiated a multicenter randomized trial to determine if accelerated radiotherapy with or without concurrent carboplatin improves local control and survival in patients with limited nonsmall cell lung cancer. This interim analysis was performed on the first 100 patients to determine whether the toxicity of the four treatment arms is acceptable. METHODS AND MATERIALS: One hundred patients with limited nonsmall cell lung cancer have been randomized to receive one of four treatments: arm I, radiotherapy 60 Gray (Gy) in 30 fractions in 6 weeks; arm II, accelerated radiotherapy 60 Gy in 30 fractions in 3 weeks; arm III, radiotherapy as in arm I plus carboplatin 350 mg/m2 during weeks 1 and 5 of radiotherapy; arm IV, radiotherapy as in arm II plus carboplatin 350 mg/m2 during week 1. Survival was measured for the group as a whole and treatment-related toxicities in the four arms were compared. RESULTS: The estimated median survival for all 100 patients was 17.1 months with 33% estimated survival at 2 years. The major toxicities were hematologic and esophageal. Patients receiving carboplatin had more neutropenia (p < 0.0001) and thrombocytopenia (p = 0.002) than patients receiving radiotherapy alone, and this was most marked in patients on arm III. Both carboplatin and accelerated radiotherapy separately caused more severe esophagitis when compared to conventional radiotherapy alone (p = 0.011 and p = 0.0017, respectively). Esophagitis was more prolonged in patients having accelerated radiotherapy (p < 0.0001, median duration 3.2 months compared with 1.4 months for patients receiving conventional fractionation). Six patients (23%) treated on arm II have required dilatation of esophageal stricture, one dying with a laryngo-esophageal fistula. CONCLUSION: In patients receiving radiotherapy for unresectable lung cancer, overall treatment time can be halved and carboplatin administered concurrently with increased but acceptable esophageal and hematologic toxicity.

Lymphocyte predominant Hodgkin's disease: a clinicopathologic comparative study of histologic and immunophenotypic subtypes.

PURPOSE: To compare the clinicopathologic features of the histologic and immunophenotypic subgroups of lymphocyte predominant Hodgkin's disease. METHODS AND MATERIALS: A retrospective review of 64 patients with lymphocyte predominant Hodgkin's disease treated at the Peter MacCallum Cancer Institute, Melbourne, was performed. Nodular and diffuse histological subtypes were confirmed by review of hematoxylin and eosin paraffin sections. Immunophenotyping with monoclonal antibodies L26 (B-cell origin) and Leu M1 (Hodgkin's phenotype) were available in 36 patients. RESULTS: The estimated freedom from progression and estimated overall survival at 10 years was 74% standard error (SE 5.8%) and 85% (SE 5.2%), non-Hodgkin's respectively. There were no significant differences in freedom from progression or overall survival when nodular and diffuse histology were compared. Similarly the presence of B-cell markers did not influence prognosis. There was only one case of secondary non-Hodgkin's lymphoma. CONCLUSION: Our results are consistent with major reported series displaying no differences between any of the subgroups of lymphocyte predominant Hodgkin's disease.

Radiation and carboplatin combined-modality therapy in non-small cell lung cancer.

Previously untreated patients with stages I to IV, N0-3, M0 unresectable non-small cell lung cancer were randomized to arm I (conventional radiotherapy [RT], 60 Gy in 30 fractions over 6 weeks), arm II (accelerated RT, 60 Gy in 30 fractions over 3 weeks), arm III (conventional RT, as in arm I, plus carboplatin 70 mg/m2/d on days 1 to 5 during treatment weeks 1 and 5), or arm IV (accelerated RT, as in arm II, plus carboplatin 70 mg/m2/d on days 1 to 5 of week 1 only). An intensive analysis of toxicity in the first 92 patients entered revealed significantly more neutropenia (P < .0001) and thrombocytopenia (P = .004) in the combined-modality arms. Esophagitis was worse on arms II, III, and IV, but was more prolonged in the accelerated RT arms. Overall, however, the treatment on all study arms was well tolerated.

Longer survival with higher doses of thoracic radiotherapy in patients with limited non-small cell lung cancer.

PURPOSE: To determine if there is an effect of thoracic radiotherapy dose on survival in patients with non small cell lung cancer localised to the primary site and regional lymph nodes. METHODS AND MATERIALS: Nine hundred and forty-one previously untreated patients with limited non small cell lung cancer presenting at Peter MacCallum Cancer Institute during 1984-1989 inclusive, were planned to receive radiotherapy using one of three schedules: 20 Gy in five fractions; 30 or 36 Gy in 10 or 12 fractions; and 60 Gy in 30 fractions. The survival of patients in each of the groups was analysed to determine if there was an effect of dose on survival, before and after adjusting for the major prognostic factors, performance status and weight loss. RESULTS: The survival of patients planned to receive 60 Gy was significantly better than for patients planned to receive lower doses (p < 0.0001) with median survival increasing from 6.1 to 9.2 and 14.5 months for the 20 Gy, 30 or 36 Gy and 60 Gy groups, respectively. After adjusting for the effect of performance status and weight loss, death rates relative to the 20 Gy group were 79% (95% confidence interval: 67-93%) for patients planned to receive 30 or 36 Gy and 53% (95% confidence interval: 44-65%) for patients planned to receive 60 Gy. CONCLUSION: These data support the hypothesis that the increased survival in patients with limited non small cell lung cancer treated with higher dose radiotherapy is not due purely to patient selection.

Concurrent radiotherapy and carboplatin in non small-cell lung cancer: a pilot study using conventional and accelerated fractionation.

Thirteen patients with unresectable non small cell lung cancer were treated with radical radiotherapy and carboplatin administered concurrently. The first 6 patients were treated to a total dose of 60 Gy in 30 fractions in 6 weeks, with carboplatin 70 mg/m2/day on days 1 to 5 during weeks 1 and 5 of radiotherapy. The remaining 7 patients were given 60 Gy in 30 fractions in 3 weeks, treating twice a day (accelerated fractionation). Carboplatin was given as above but only during week 1 of radiotherapy. Twelve patients completed radiotherapy without interruption but 2 patients developed WHO grade 3 neutropenia. Major toxicity was oesophagitis, one patient requiring nasogastric feeding. Average duration of dysphagia (any grade) in the accelerated fractionation group was 21 weeks. Four patients achieved good partial responses even though initial tumour volume was large. We conclude that this treatment is associated with increased but acceptable early mucosal toxicity.

Treatment of clinical stage I Hodgkin's disease by local radiation therapy alone. A United Kingdom Childrens Cancer Study Group study.

The UKCCSG study of the treatment of Hodgkin's disease between January 1982 and January 1988 accrued 209 patients. Of these, 59 had clinical Stage I disease. These 59 patients were treated with radiation therapy alone to sites of initial involvement. In case of relapse, combination chemotherapy was used. With a median follow-up of 3 years, 50 patients are alive with no evidence of disease after radiation therapy alone. Nine patients have relapsed between 5 and 55 months (median time to relapse, 18 months). Eight patients have been successfully treated with combination chemotherapy and are alive with no evidence of disease (one of these patients having had two relapses). One patient has died after widespread relapse. Of the 59 Stage I disease patients, 85% are relapse free after single-modality treatment. Overall survival is 98%. Long-term complications are minimal at this stage but long-term follow-up is essential.

Hypofractionation reduces the therapeutic ratio in early glottic carcinoma.

From 1969-1985 two types of fractionation schedules with similar time, dose, and fractionation factor (TDF) values were used to treat 197 patients with Tis, T1, and T2 squamous cell carcinoma of the vocal cord. One hundred and thirty-one patients were treated with conventional daily 2.0 Gy fractions, and 66 patients were treated once per week with large (5.5-6.6 Gy) fractions (hypofractionated group); both groups were treated over a period of approximately 6 weeks. The local failure and complication rates for patients completing treatment in the two groups were compared; a patient was regarded as having suffered a serious complication of treatment if laryngectomy or tracheostomy had to be performed in the absence of active disease, or if antibiotics and/or corticosteroids had to be prescribed for laryngeal oedema and/or necrosis. In patients with Tis and T1 disease, the failure rate was worse in the hypofractionated group than in the conventionally treated group (p = 0.06). In the smaller group of T2 patients, no significant difference was found in the failure rates between the hypo- and conventionally fractionated groups. Complication rates were similar in Tis/T1 and T2 patients, but significantly higher in the hypofractionated group (p less than 0.001). Neither stage nor fractionation schedule had an effect on survival, but laryngectomy/tracheostomy free survival was significantly worse in Tis/T1 patients receiving hypofractionated treatment, (p = 0.008) although not in T2 patients. These results indicate that in Tis/T1 glottic cancer, hypofractionation of radiotherapy produces a reduction in the therapeutic ratio.