Factors influencing outcome following radio-chemotherapy for oesophageal cancer. The Trans Tasman Radiation Oncology Group (TROG)

BACKGROUND AND PURPOSES: To define new directions, the Trans Tasman Radiation Oncology Group (TROG) has conducted a detailed analysis of its unrandomised experience with radio-chemotherapy in oesophageal cancer. METHODS AND PATIENTS: Since 1984, 373 patients with oesophageal cancer have been treated on three prospective, but unrandomised, protocols involving radiation with concurrent cisplatin and infusional fluorouracil. Centres in Australia and New Zealand have contributed patients. Reasons for case selection have been examined in detail and prognostic models have been examined in the light of biases exposed. RESULTS: Cause specific survival in 92 patients treated pre-operatively with 35 Gy, infusional fluorouracil and cisplatin was 25.5 +/- 6.0% at 5 years and similar to the 5 year expectations of 169 patients treated with 60 Gy and two courses of the same chemotherapy (23.8 +/- 4.7%). Analysis of failure in these groups suggests that local relapse precedes the development of metastases and competes as a cause for ultimate failure. Although patients treated surgically were less likely to relapse locally, survival was no better because more developed metastases. Some of the 112 patients treated "palliatively" with 30-35 Gy concurrent with chemotherapy without surgery have become long-term survivors with 5 year survival figure in this group 7.7 +/- 3.4%. Apart from variables related to disease stage and performance status at presentation, tumour site emerged as a strong predictor of outcome. Prognosis worsens the nearer the tumour is to the stomach. In addition, indications of a radiation dose response relationship emerged. CONCLUSIONS: Concurrent radio-chemotherapy protocols can improve outcome in patients fit enough to tolerate these approaches. New strategies remain necessary, however.

Mucosal regeneration during radiotherapy. Trans Tasman Radiation Oncology Group (TROG).

BACKGROUND AND PURPOSE: Regeneration of the aerodigestive mucosa is known to occur during conventionally fractionated radiotherapy. The circumstances surrounding its time of onset and magnitude are not well understood, however. MATERIAL AND METHODS: Mucosal reactions were observed in 100 patients undergoing conventionally fractionated treatment at 2 Gy/day over 7 weeks and 88 receiving accelerated treatment at 1.8 Gy twice daily over 3 1/2 weeks on the Trans Tasman Radiation Oncology Group head and neck cancer trials. Similar observations in 61 patients treated palliatively at dose rates between 0.8 and 240 Gy/h using ten 3.0-4.2 Gy fractions over 2 weeks are compared. RESULTS: Several findings emerged from these studies: 1. Reactions evolved more quickly at oropharyngeal sites than in the hypopharynx. 2. Reactions at both sites evolved more rapidly at greater rates of dose accumulation. 3. The timing of reactions suggested the presence of a strong regenerative mucosal response that started before the manifestation of "patchy' (grade II) mucosal reactions. 4. The regenerative response was strong enough to "make good' damage accumulated at a rate of 2 Gy/day in over a third of cases. 5. The linear quadratic model without time correction failed to provide an adequate prediction of the frequency or intensity of mucosal reactions produced by any of the regimes. A simple model of the regenerative response is presented. CONCLUSIONS: This study suggests that the timing and magnitude of the regenerative response vary between sites and individuals but are linked to the amount of epithelial cellular depletion occurring during treatment.

The misuse of mammography in the management of breast cancer.

In the six years from 1979 to 1985, a total of 735 women were referred to the Department of Radiation Oncology, Westmead Hospital, for the management of primary breast cancer. Of these, 218 had undergone mammography after the discovery of their breast tumour. In 95 of those patients with breast cancer the mammogram had failed to define the carcinoma. For almost 50% of the patients with a negative result of a mammogram, the negative report result had, in our opinion, led to a delay in definitive management and to the re-presentation of those patients at a later date with a disease of poorer prognosis. A false-negative result of a mammogram was particularly likely to be obtained in young premenopausal women with small tumours. When these women finally presented with breast cancer, the tumour was larger, and the prevalences of pathological involvement of the axillary nodes and of locally advanced disease were significantly greater. The misuse of mammography as a diagnostic tool in patients with symptomatic disease is dangerous in that it has a significant false-negative rate which carries with it the serious risk of postponing a biopsy.

The misuse of mammography in the management of breast cancer revisited.

A second study of the use of mammography as a diagnostic procedure in women with breast symptoms is reported. In a two-year period during which 468 patients with a new diagnosis of breast cancer were seen, 238 women had undergone mammography before referral to the Department of Radiation Oncology, Westmead Hospital. For 73 (30.7%) patients the mammographic report was falsely negative. Among those 73 patients with a falsely negative mammographic report, 40 women experienced a mean treatment delay of 12.7 months (range, three to 60 months). A negative mammographic result was significantly (P less than 0.001) more likely to be obtained in younger women. When the women with an initially negative mammographic result represented, they did so with disease of a more advanced stage. This, we contend, is related to the delay in their definitive treatment as caused by the first falsely negative mammographic report. Theoretical calculations are presented; under varying conditions of sensitivity and specificity, these show that, even with the addition of specialist opinion, significant proportions of patients with breast cancer will have a mammographic result which is falsely reassuring. The identification of these subsets depends on histological or cytological examination of the tumour. This is a decision that best is made, in our opinion, by a specialist in breast-cancer management.

Gorham's syndrome: a usually fatal cause of pleural effusion treated successfully with radiotherapy.

A 21 year old man presented with a right sided pleural effusion. Destruction of the 11th and 12th right ribs and adjacent vertebral bodies was noted on computed tomographic scanning. An open rib biopsy revealed the histopathological changes of Gorham's syndrome. In view of the progressive vertebral destruction and inevitable spinal cord compromise, he was treated with high dose radiotherapy. The process was arrested and he remains well with no signs of recurrence after four years. Pleural effusion and vertebral destruction complicating Gorham's syndrome carry a poor prognosis but, in this case, high dose radiotherapy has been effective in controlling both the effusion and the progressive bony destruction.

The management of oesophageal carcinoma: radiotherapy or surgery? Cost considerations.

A cost comparison has been made between two treatment modalities used with curative intent for carcinoma of the oesophagus, for 144 patients seen between December 1979 and December 1985. Forty-two patients were selected for radical oesophagectomy. In this paper these are compared with 50 patients who underwent radical radiotherapy. The median survival of both groups was identical (12 months). The remaining 52 patients underwent a variety of palliative procedures and are not considered further. Components of management were identified and costed on the basis of direct resource use by the hospital. Surgically treated patients on average cost $A13,638 in 1987 dollars, whereas those treated by radiotherapy cost $A3533. The major factors accounting for this cost difference were the necessary perioperative intensive management in the surgical group, the inevitable perioperative complications and the subsequent prolonged hospitalization of a proportion of patients. The cost of the management of the complications of radiation therapy are included but were not a major factor in overall costs for the irradiated group. This cost differential must influence the continuation of current strategies in which radical surgery, rather than irradiation, is the selected routine curative approach for oesophageal cancer particularly in the absence of evidence of higher survival.

Preliminary results of combined chemotherapy and radiotherapy for non-AIDS primary central nervous system lymphoma. Trans-Tasman Radiation Oncology Group (TROG).

OBJECTIVES: To assess the results and toxicity of a regimen of combined chemotherapy and radiotherapy for patients with non-AIDS-related primary central nervous system lymphoma. DESIGN: Prospective assessment of patients treated with intravenous methotrexate followed by cranial irradiation between 1 January 1991 and 31 July 1995. PATIENTS AND SETTING: Patients attending nine Australian and New Zealand centres who were eligible and gave informed consent. MAIN OUTCOME MEASURES: Probability of survival at two years, and acute toxicity. RESULTS: Twenty-four patients were treated. Their probability of survival at two years was 70% (95% confidence interval [CI], 45%-95%). The acute toxicity of the regimen was minimal in most cases, but one patient died of treatment-related neutropenia and subsequent sepsis. Two patients showed progression of pre-existing short term memory disturbance, without evidence of recurrent lymphoma. CONCLUSIONS: Combined-modality therapy improves survival in patients with non-AIDS-related primary central nervous system lymphoma, at least in the short term, relative to radiotherapy alone. The combined regimen resulted in only moderate treatment-related morbidity. Longer follow-up is required for a more accurate estimate of late effects and long-term survival prospects.