Ian Firth

Determinants of Outcome in Melanoma Patients With Cerebral Metastases

PURPOSE To analyze prognostic factors, effects of treatment, and survival for patients with cerebral metastases from melanoma. PATIENTS AND METHODS All melanoma patients with cerebral metastases treated at the Sydney Melanoma Unit between 1952 and 2000 were identified. From 1985 to 2000, patients were diagnosed and treated using consistent modern techniques and this cohort was analyzed in detail. Multivariate analysis of prognostic factors for survival was performed. RESULTS A total of 1137 patients with cerebral metastases were identified; 686 were treated between 1985 and 2000. For these 686 patients, the median time from primary diagnosis to cerebral metastasis was 3.1 years (range, 0 to 41 years). A total of 646 patients (94%) have died as a result of melanoma. The median survival from the time of diagnosis of cerebral metastasis was 4.1 months (range, 0 to 17.2 years). Treatment was as follows: surgery and postoperative radiotherapy, 158 patients; surgery alone, 47 patients; radiotherapy alone, 236 patients; and supportive care alone, 210 patients. Median survival according to treatment received for these four groups was 8.9, 8.7, 3.4, and 2.1 months, respectively; the differences between surgery and nonsurgery groups were statistically significant. On multivariate analysis, significant factors associated with improved survival were surgical treatment (P <.0001), no concurrent extracerebral metastases (P <.0001), younger age (P =.0007), and longer disease-free interval (P =.036). Prognostic factors analysis confirmed the important influence of patient selection on treatment received. CONCLUSION This large series documents the characteristics of patients who developed cerebral metastases from melanoma. Median survival was dependent on treatment, which in turn was dependent on patient selection.

Cerebral metastases from malignant melanoma

A retrospective study was undertaken of factors affecting survival in 129 patients with cerebral metastases from malignant melanoma referred to the Department of Radiation Oncology from June 1982 to January 1990. Their ages ranged from 19 to 83 years and the time interval from diagnosis of the primary tumour to development of cerebral metastases ranged from one month to 17 years. Cerebral metastases were apparently solitary in 59 (46%) and multiple in 70 (54%) patients respectively. Craniotomy with resection of tumour was performed in 49 patients, of whom 24 had a solitary cerebral metastasis as the only evidence of disease. Most patients (94%) received a course of radiotherapy. Median survival of the whole group after detection of cerebral metastases was 5 months (range less than 1-87+). Univariate analysis indicated that a solitary cerebral metastasis, absence of extracranial disease and tumour resection predicted improved survival, but only surgical intervention was of independent prognostic significance in a multivariate analysis. The effect of cranial irradiation on survival could not be assessed, but the dose of radiation did not influence survival. Of the 10 patients who survived for more than 2 years, eight had total resection of a solitary cerebral metastasis.

Locally advanced melanoma

High rates of locoregional recurrence have been reported from surgical series of locally advanced melanoma. In this study, the outcomes of patients treated with surgery and postoperative hypofractionated radiation therapy were reviewed to assess local recurrence and survival.

Accelerated hyperfractionated radiotherapy for locally advanced cervix cancer.

PURPOSE A phase II trial was designed to evaluate the toxicity and outcome of patients with locally advanced cervix cancer treated with accelerated hyperfractionated radiotherapy (AHFX). METHODS AND MATERIALS In this prospective trial, AHFX doses of 1.25 Gy were administered twice daily at least 6 hours apart to a total pelvic dose of 57.5 Gy. A booster dose was then administered via either low-dose rate brachytherapy or external beam therapy to a smaller volume. All patients were accrued and treated at Peter MacCallum Cancer Institute (PMCI) between 1986 until April 1991. RESULTS Sixty-one eligible patients were enrolled in this protocol; 2 (3.2%) had Stage IIB; 42 (68.9%) had Stage III; 8 (13.1%) had Stage IV and 9 (14.8%) had recurrent cervical cancer. Fifty-two patients (85%) completed the planned external beam without a treatment break. Thirty patients had acute toxicity that required regular medication. One patient died of acute treatment related toxicity. Fifty-five patients received booster therapy: 45 with intrauterine brachytherapy, 6 with interstitial brachtherapy, and 4 with external beam. The median follow-up of surviving patients was 6 years. Overall 5-year survival is 27% and 5-year relapse free survival is 36%. Nineteen patients died with pelvic disease and the actuarial local control rate was 66%. There were 8 severe late complications observed in 7 patients. Seven required surgical intervention (an actuarial rate of 27%). Five patients also required total hip replacement. CONCLUSIONS The local control rate was favorable compared with other series that have used standard fractionation, although overall survival remained similar. The severe late complication rate was high for this protocol and higher than similar protocols reported in the literature.

Radiation treatment in recurrent squamous cell cancer of the vulva

PURPOSE To evaluate the treatment and outcome of recurrent vulvar cancer. METHODS AND MATERIALS In a retrospective review of 26 women referred to the department of radiation oncology between 1982 and 1995, patient records were analyzed with respect to the findings at original surgery, the time to locoregional recurrence, the location of the recurrence, and the subsequent management and outcome. RESULTS Sixteen recurrences were managed with a combination of surgery and radiotherapy, and the remainder with radiation treatment, combined with chemotherapy in some cases. The overall survival for the entire cohort at 5 years was 22%. The 5-year survival for those with recurrence confined to the vulva (n = 13) was 46%, compared with 0% for those women with a recurrence located or extending beyond the vulva (p = 0.002). The local control rate was 34.6%. CONCLUSION Our results confirm the poor overall prognosis for this condition. In particular, they highlight the importance of the location of the recurrence as a prognostic indicator. Based on this review, we conclude that radiotherapy fields should encompass the region at risk if the intent is curative. Finally, low-dose palliation for groin node recurrence is ineffectual.

Locally Advanced Cervix Cancer: Chemotherapy Prior to Definitive Surgery or Radiotherapy. A Single Institutional Experience

Primary or neoadjuvant chemotherapy prior to definitive local therapy has potential advantages for locally advanced cervix cancer. It can downstage a cancer and allow definitive local therapy to be technically possible (surgery), or potentially more effective (radiotherapy). It can also eradicate subclinical systemic metastases. This report reviews a single institutions experience of neoadjuvant chemotherapy prior to definitive local therapy for cervix cancer over a 13-year period. One hundred and six patients were treated with this intent. The patients were analysed for their response to chemotherapy, treatment received, survival, relapse and toxicity. The chemotherapy was feasible and the majority of patients had a complete or partial response (58.5%). Eight patients did not proceed to local treatment. Forty-six patients had definitive surgery and 52 had definitive radiotherapy. The 5-year overall survival was 27% and the majority of patients died with disease. The first site of relapse was usually in the pelvis (46.2%). Late complications that required ongoing medical therapy (n=6) or surgical intervention (n=2) were recorded in eight patients (7.5%). On univariate analysis stage (P=0.04), tumour size (P=0.01), lymph node status (P=0.003), response to chemotherapy (P=0.045) and treatment (P=0.003) were all significant predictors of survival. On multivariate analysis, tumour size (P < 0.0001) and nodal status (P=0.02) were significant predictors of survival. Despite the impressive responses to chemotherapy of advanced cervix cancer, there is evidence from randomized trials that it does not improve or compromise survival prior to radiotherapy. As its role prior to surgery remains unclear, it should not be used in this setting outside a prospective randomized trial.