P. Schlienger

Treatment of liver metastases from uveal melanoma by combined surgery—chemotherapy

AIMS To investigate sporadic results demonstrating prolonged survival after surgical resection and/or intraarterial chemotherapy (IACH) for liver metastases from uveal melanoma. METHODS From December 1992 to March 1997 every patient with liver metastases from uveal melanoma was enrolled in a prospective study including: (1) aggressive surgical approach removing as much liver disease as possible; (2) implantation of an intraaterial catheter; (3) intraarterial chemotherapy for 6 months. 75 patients were enrolled: 38 men, 37 women, mean age 51 years (range: 18-72), mean time from initial diagnosis of uveal melanoma to liver metastases 37 months (ranged: 1-168). RESULTS Disseminated disease in both lobes was present in all but one patient. Macroscopically curative surgery was possible in 27.5%. Significant tumour reduction was performed in 49.3% and a simple biopsy was possible in 23.2%. Eight patients did not receive chemotherapy and died soon after. IACH included Fotemustine and/or DTIC-Platinum for 4-9 cycles. Overall median survival was 9 months; very similar to non-operated historical controls. In the 61 patients receiving complete treatment surgery plus chemotherapy, median survival improved to 10 months. When curative resection was possible, survival increased to 22 months (P < 0.001). CONCLUSIONS Aggressive surgical resection, when possible, appears to be the best method of improving survival of liver metastases from uveal melanoma. New drug combinations are also required to improve survival.

Role of chemotherapy alone or in combination with hyperthermia in the primary treatment of intraocular retinoblastoma: preliminary results

BACKGROUND The efficacy of the etoposide-carboplatin combination in extraocular retinoblastoma is well known. This drug combination is therefore used in intraocular retinoblastoma, as primary reduction chemotherapy, before local treatment. The use of carboplatin in combination with diode laser hyperthermia as local treatment (thermochemotherapy) has been recently described as a conservative approach avoiding external beam radiotherapy in posterior pole tumours. METHODS All patients were reviewed, who were treated for retinoblastoma at the Institut Curie between June 1994 and October 1995, in whom treatment included either reduction chemotherapy or thermochemotherapy or both modalities successively. 23 patients presenting with unilateral (three) or bilateral (20) intraocular retinoblastoma received neoadjuvant chemotherapy consisting of two courses of etoposide 150 mg/m2/day and carboplatin 200 mg/m2/day for 3 days. 15 patients (17 eyes), eight of whom had already received neoadjuvant chemotherapy, were treated by thermochemotherapy. RESULTS Neoadjuvant chemotherapy: overall, seven eyes in seven patients could be treated conservatively, avoiding external beam irradiation, with a median follow up of 14 months. Thermochemotherapy: external beam irradiation was avoided for 14 of the 17 eyes treated. CONCLUSION Integration of neoadjuvant chemotherapy and combined treatment with carboplatin and diode laser, into the therapeutic armamentarium for retinoblastoma allows use of more aggressive treatments such as enucleation and external beam radiation.

Osteosarcoma following retinoblastoma: Age at onset and latency period

In order to assess the role of genetic predisposition in the induction of radiation-induced tumors, we performed statistical analysis on data from the literature and from our own Institute with regard to the age at onset and the latency period of osteosarcoma as the second primary tumor for retinoblastoma with or without subsequent radiotherapy. In retinoblastoma survivors who subsequently developed osteosarcoma, the age at onset of retinoblastoma was young (average of 12 months) in both unilateral and bilateral forms. This suggests that all or almost all of the patients were genetically predisposed by a mutation of one allele of the RB1 gene. For retinoblastoma patients, osteosarcomas occurred 1.2 years earlier inside than outside the radiation field. The latency period between radiotherapy and osteosarcoma onset was 1.3 years shorter inside than outside the radiation field. Interestingly, a bimodal distribution of latency periods was observed for osteosarcomas arising inside, but not outside the radiation field: 40% occurred after a short latency, while the latency of the remaining 60% was comparable to that of osteosarcoma occurring outside the radiation field. This suggests that different mechanisms may be involved in radiocarcinogenesis. A radiation-induced mutation of the second RB1 allele may be the cause of osteosarcomas occurring after a short delay, while other genes may be affected in those occurring after a longer delay.

Paget's disease of the nipple without detectable breast tumor: conservative management with radiation therapy.

Between 1960 and 1984, 20 selected patients with Pagets disease of the breast confined to the nipple were treated conservatively with radiotherapy alone (17/20 pts) or limited surgery and radiotherapy (3/20 pts). Median follow-up was 7.5 years. No patients died of breast disease. Three patients had recurrence in the treated breast, and were treated by mastectomy. All recurrences were located in the nipple or areola and were all Pagets disease, without associated intraductal or invasive carcinoma. No axillary node recurrences occurred. The actuarial 7-year probability of living free of disease with breast preserved was 81%. Among the 15 patients who had a minimum follow-up of 3 years, without recurrence, 12 (80%) had a good cosmetic result. These results suggest that radiation therapy could be an effective alternative to radical surgery in the treatment of patients with Pagets disease of the nipple without concomitant breast tumor.

Presentation of axillary lymphadenopathy without detectable breast primary (T0 Nib breast cancer): experience at Institut Curie

Between 1960 and 1985, 31 patients presented to Institut Curie with isolated axillary lymphadenopathy, of probable metastatic origin from the breast, but without clinical or radiological evidence of a breast tumor and no other primary tumor. The mean age was 54.6 years (range 39-79 years). Histological diagnosis was obtained by axillary surgery (22 cases), drill biopsy (6 cases), and cytology (3 cases). All slides were reviewed for the present study. Treatment consisted of axillary surgery followed by radiotherapy in 22 patients, radiotherapy followed by axillary surgery in 6 patients, radiotherapy followed by modified radical mastectomy in one patient, and radiotherapy alone in 2 patients. Systemic adjuvant treatment was given to 11/31 patients. The median follow-up was 9 years (range 2-26 years). Eight recurrences have appeared. Four patients recurred in the breast only (mean time to relapse: 112 months, range 63-162 months). The four other patients recurred both in breast and/or axilla (mean time to relapse: 23 months, range 7-46 months). Nine patients have developed distant metastases, of whom three also had locoregional recurrence. Among the 11 patients who had had systemic treatment, 5/11 had recurrence or metastases. The overall 5 and 10 year actuarial survival rates were 76 and 71%, respectively. The metastasis-free 5 and 10 year actuarial survival rates were 73 and 71%, respectively. Axillary metastases without clinical or radiological evidence of a primary breast tumor represents a discrete clinical entity, the prognosis of which appears to be better than that of clinical invasive breast cancer with associated lymph node involvement.(ABSTRACT TRUNCATED AT 250 WORDS)

External radiotherapy for carcinoma of the eyelid: Report of 850 cases treated

PURPOSE We report a retrospective series of 850 patients treated by external irradiation for carcinoma of the eyelid at Institut Curie and we compare our results with other techniques: brachytherapy and surgery. METHODS AND MATERIALS Eight hundred fifty patients were treated by external radiotherapy for carcinoma of the eyelid. None of these patients have been previously treated. All the patients were classified according to the TNM classification of (UICC). We distinguished five histological types and five clinical groups according to the site of the skin tumor. Three modalities of external radiotherapy were used: contact therapy, conventional radiotherapy, and electrontherapy. We reviewed the clinical files of the 850 patients who went regularly at follow-up visits. RESULTS We report the 5-year survival results--alive with no evidence of disease: 72%; alive with progression: 2%; died from tumor progression: 0.5%; died from intercurrent disease: 19.5%; and lost to follow-up: 5%. The 5-year local control rate was 97.5%. We observed 45 failures--lymph node, metastatic, and local--and emphasize this last group by presenting the results of treatment of these local failures. We studied the complications of treatment: 2.3% of corneal complications, 2% of cataracts, and 1.4% of serious ocular complications. CONCLUSIONS Our results concerning local failures and loss of the eye are comparable to those reported for other techniques involving brachytherapy or surgery. Overall, external radiotherapy is a safe and effective treatment, as it ensures a high local control rate and provides perfectly satisfactory functional and esthetic results. It seemed particularly useful to report this series in that few publications are available on this subject that, nevertheless, constitutes a topical issue.

Second non-ocular tumours in survivors of bilateral retinoblastoma: A 30-year follow-up

The authors have reviewed a series of 80 patients treated at the Curie Institute before 1965 for bilateral retinoblastoma. They present their cases of second non-ocular tumours in these patients and discuss their results and the possible factors influencing the percentage of second tumours in these patients.

Intraocular inflammation after proton beam irradiation for uveal melanoma

AIM To describe the inflammatory reaction that can occur following proton beam irradiation of uveal melanomas based on a large series of patients and to try to determine the risk factors for this reaction. METHODS Data from a cohort of patients with uveal melanoma treated by proton beam irradiation between 1991 and 1994 were analysed. The presence of inflammation was recorded and evaluated. Kaplan-Meier estimates and statistical analysis of general and tumour related risk factors were performed. RESULTS 28% of patients treated during this period presented with ocular inflammation (median follow up 62 months). Risks factors were essentially tumour related and were correlated with larger lesions (height > 5 mm, diameter > 12 mm, volume > 0.4 cm3). Multivariate analysis identified initial tumour height and irradiation of a large volume of the eye as the two most important risk factors. Ocular inflammation usually consisted of mild anterior uveitis, resolving rapidly after topical steroids and cycloplegics. The incidence of inflammation after proton beam irradiation of melanomas seems higher than previously reported and is related to larger lesions. Evidence of inflammation associated with uveal melanoma has been described and seems to be associated with tumour necrosis (spontaneous or after irradiation). The appearance of transient inflammation during the follow up of these patients may be related to the release of inflammatory cytokines during tumour necrosis. CONCLUSION Inflammation following proton beam irradiation is not unusual. It is correlated with larger initial tumours and may be related to tumour necrosis.

Medullary breast carcinoma: The role of radiotherapy as primary treatment

The results are reported of a selected series of 41 patients with medullary carcinoma of the breast, treated with primary radiotherapy with (24 patients) or without (17 patients) adjuvant chemotherapy. Complete responses to radiotherapy occurred with moderate doses (67% of the patients had a complete response after a dose of 55-60 Gy) and were increased by the addition of an irradiation boost. The 6-year actuarial free of local recurrence survival, metastase-free survival and survival rates were 86, 83, and 83%, respectively. The 6-year actuarial probability of living with breast preserved was 72%. Recurrences and survivals were not influenced by the tumor size or clinical axillary node status. Adjuvant chemotherapy had no effect on the rate of recurrence or survival.

Nonocular second primary tumors after retinoblastoma: retrospective study of 111 patients treated by electron beam radiotherapy with or without TEM.

The objective of this study was to assess the role of various clinical and treatment factors involved in the long-term incidence of nonocular second primary tumors following retinoblastoma. The study was based on 111 patients treated between 1963 and 1977 according to the same radiotherapy protocol (electron beam radiotherapy) alone or in combination with triethylene melamine (TEM). Various statistical methods were used to obtain the actuarial survival curve, the cumulative incidence of second primary tumors, and comparisons of patient groups and subgroups. The 5-, 10-, 20-, and 30-year survival rates were 75%, 70%, 63%, and 55% with a follow-up of 23 to 35 years. The study reports the various parameters concerning 111 children and 17 second primary tumors: sex, age at treatment, histology of the retinoblastoma and second primary tumors, site of second tumors (anatomic and compared with irradiation field), radiation dose, time to onset, and chemotherapy with or without TEM. The results are discussed and compared with the data reported in the literature. Electron beam radiotherapy at a dose of 45 Gy does not eliminate the risk of nonocular second primary tumors. TEM also does not modify survival or the overall incidence of second primary tumors, but significantly increases the risk of second primary tumors outside the irradiation field.