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

Between 1960 and 1984, 20 selected patients with Paget's 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 Paget's 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 Paget's disease of the nipple without concomitant breast tumor.

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.

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.

Presentation of axillary lymphadenopathy without detectable breast primary (T0 N1b 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)

A preliminary comparative treatment planning study for radiotherapy of age-related maculopathy.

PURPOSE: We present a comparative planning of different approaches for external radiotherapy in age-related maculopathies. MATERIALS AND METHODS: Calculated dose distributions and dose-volume histograms for (a) bilateral irradiation with 6 MV photons, (b) a single lateral-oblique beam using either photons, electrons or protons and (c) an anterior circular proton beam. RESULTS: For lateral photon or electron beams the dose to the lens is usually lower than 10% of the dose to the macula. The entrance doses for bilateral photon beams are about 50% which increase up to 100% at the orbital bone. About 5 mm of optic nerves are irradiated at the maximal dose while the optic chiasma is spared. A single photon beam gives 50% of the dose to the fellow eye. The electron beam spares the fellow eye but gives a rather inhomogeneous dose to the target volume. For a lateral proton beam, 4 mm of optic nerve receives 90% of the dose, the skin dose is at least 70% of the dose to the macula and the lens and the fellow eye are spared. An anterior proton beam gives 90% of the dose to 1 mm of optic nerve and the 50% isodose approaches the periphery of the lens. CONCLUSION: Doses to the critical structures can be dramatically diminished for all the techniques by reducing the beam size, but only if very precise set-up techniques are used. Proton beams are an attractive solution, but the impact of such a choice on the use of proton facilities and on the national health system should be carefully evaluated, as well as the risk of radio-induced secondary neoplasias.

Fine-needle cytology of 292 palpable orbital and eyelid tumors.

Fine-needle cytology (FNC) of 292 palpable orbital and eyelid tumors was performed with a 25-gauge (0.5-mm), 3-cm needle and compared with the histopathologic findings in 286 cases. Among these 286 cases, a concordant diagnosis of malignancy and type was achieved in 249 cases (87%). False positive diagnoses were made in four cases (1.6%) and false negative diagnoses in five cases (1.8%). No complications were encountered. These results led to the conclusion that FNC is an accurate tool in the diagnosis of orbital and eyelid tumors, especially when sampling and interpretation are performed by an experienced pathologist.

Cytogenetic forms of retinoblastoma: their incidence in a survey of 66 patients.

Sixty-six retinoblastoma patients were investigated using high resolution banding techniques, sister chromatid exchange (SCE) studies, and esterase-D phenotype determination and dosage. Seven patients (in six families) were found to be carriers of a rearrangement of band 13q14 due to de novo deletions, apparently balanced de novo translocations, or parental insertions. The possible role of submicroscopic parental insertions is suggested to explain transmission of nonchromosomal forms through unaffected carriers.

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.

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.

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 cm(3)). 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.

Cytologic diagnosis of orbital and periorbital palpable tumors using fine-needle sampling without aspiration.

Sixty-two cases of orbital and periorbital palpable neoplasms were analyzed cytologically. The material was obtained by our technique of simply introducing a fine injection needle in the tumor mass without aspiration. Fifty-six of these tumors had a subsequent histologic diagnosis by surgical procedure or biopsy. Forty-nine of the 56 cytologic diagnoses (87%) were concordant with the histologic findings with regard to malignancy and its variety. In three other cases the diagnosis of malignancy was only achieved by surgical procedure or biopsy (5%). In two cases, there were false-malignant results (4%), one corresponding to a meningioma and the other related to a reactive lymphoid hyperplasia. There was one false-benign (2%) result in a case of non-Hodgkin's lymphoma. In one patient, the cytologic material was insufficient for diagnosis (2%). In six other cases, the initial cytologic examination was ultimately confirmed either by biochemical studies or by biopsies of nodal metastases. No orbital hemorrhage was observed after fine-needle sampling. This outpatient technique is highly accurate and permits diagnosis in a few minutes.

[The place and limitations of therapeutic regimens in the management of breast epitheliomas. 10 year results]. / Place et limites des thérapeutiques à visée conservatrice des épithéliomas mammaires Résultat à 10 ans.

Between 1960 and 1966, 258 carcinomas of the breast with a follow up of 10 years or more formed a group which had been treated conservatively. Two conservative approaches were used, either lumpectomy followed by irradiation, or irradiation, alone, surgery being reserved for failures. At 10 years the survival rate of 51 p. 100 with no sign of recurrence is comparable with the results of radical or modified mastectomy. Among those living with no sign of recurrence 61 p. 100 had retained their breast almost always with a satisfactory aesthetic result. The place of lumpectomy followed by irradiation is reserved for single lumps of small volume and unaccompanied by axillary lymph node enlargement.

[Carcinoma of the breast: diagnosis of sub-clinical bone metastases. Predictive value of isotope bone scan (author's transl)]. / Cancers du sein. Diagnostic des métastases infra-cliniques osseuses. Valeur prévisionnelle de la scintigraphie.

The possibility of drawing a distinction between two groups with or without bone metastases is of fundamental importance in the determintion of management. With this in mind, isotope bone scan using Tc 99 was performed routinely in 99 cases of locally advanced non-metastatic carcinoma of the breast. Amongst 121 "operable" (T1, T2, T3, N0, N1a) carcinomas, 4 (3%) had a positive scan. Of these 4 cases, 3 showed evidence of bone metastases within one year, in 3 of which the site was not the same as that predicted by the scan. Amongst 53 "inoperable" (T4, N0, N1, T., N2, N3) cases, 5 (10%) had a positive scan and 5 a doubtful scan. Amongst the 5 positive cases, within one year metastases were seen at the predicted site. In agreement with a large number of authors, it would thus appear that routine isotope bone scan has no role to play in the pretherapeutic assessment of so-called "operative" breast carcinomas.

[Basocellular epithelioma of the back with metastases of the axillary ganglia]. / Epithélioma basocellulaire du dos avec métastase ganglionnaire axillaire

In a 52-year old woman, basal cell carcinoma of the back skin recurs after excision and the axillary lymph nodes are involved. This case is to be added to the list of basal cell carcinomas with metastatic evolution. The histologic study of a series of sections allows to show the migration of neoplastic cells in the vessels. Though exceptional, the ability of the basal cell carcinomas to yield metastases must be taken into account.

[Prognostic factors in epitheliomas of the breast]. / Facteurs pronostiques des épithéliomas mammaires.

Prognostic factors in breast carcinoma were studied on material which consisted of 733 patients with a follow-up of over 5 years and on 361 with a follow-up of over 10 years. In the first part of the study the prognostic factors are related to the physical characteristics of the primary tumour such as its situation and size and its relationship to skin and deep tissues. Clinical examination of the axilla, studied in detail, has proved a reliable guide to prognosis. The second part deals with such factors as age, hormonal status, age at first pregnancy and parity. A critical analysis of the T.N.M. classification ends the study, with special reference to the prognostic factors which relate to the primary tumour.

[Isotopic bone examination in operable breast cancer]. / Exploration osseuse isotopique dans les cancers mammaires opérables.

In the pre-treatment work-up in breast carcinoma cases the bone scan findings could be of major interest. If the presence of occult metastases is discovered management may be modified accordingly. In a group involving 78 cases of breast carcinoma, classified as primary, operable, in three cases only scintigraphy revealed bone metastases before they produced clinical and radiological signs. In two of them there was agreement, in one disagreement over the findings. Moreover, in 5 cases a bone metastasis was revealed and immediately confirmed on a complete bone assessment.

[Conservative treatment of tumors of the retina at the Curie Institute. Long-term results of 129 cases treated with Stallard's disk and electrons]. / Traitement conservateur des tumeurs de la rétine à l'Institut Curie. Résultats à long terme de 129 cas traités par disque de Stallard et électrons.

The authors report a retrospective study of 129 children with retinoblastoma treated from 1963 to 1977 at the Institut Curie by enucleation of the worst eye and conservative irradiation of the other eye; this irradiation was performed either with Stallard plaque (19 cases) or with electrons (110 cases). In 8 familial cases, no enucleation has been performed. T.E.M. was used from 1964 to 1973 and iterative photocoagulation since 1968. With a 5 years follow up, 88 children (68%) are living NED, 6 are lost. There was 34 treatment failures (26%) and 1 death from second malignant tumor. At 10 and 15 years, the results are stable despite the occurrence of two other second primary tumors. Irradiation preserved 73/94 (78%) of the irradiated eyes. The technical aspects of the radiotherapy with electrons and both ocular and vital prognostic factors are discussed.

[Bone sarcoma and malignant tumors of the retina]. / Sarcomes osseux et tumeurs malignes de la rétine.

Secondary bone sarcomas are frequent among children who have been treated previously for a retinoblastoma. The main point is that these bone sarcoma occur almost always after a bilateral retinoblastoma and more often in the irradiated area; from these, the classical concept of "radiocancer" was generally admitted. However, since many authors reported bone sarcomas occurring in a different location from the irradiated area, radiotherapy cannot be by itself the causative factor of these secondary bone sarcomas. Therefore the genetical factor is probably one of the predisposing factor. The authors report 6 cases of bone sarcomas with a review of the literature of bone sarcomas occurring in the irradiated field or not, for children "cured" of retinoblastoma.

[Conservative treatment of tumors of the retina at the Curie Institute. 5-year ophthalmologic results of 129 cases treated with the Stallard disc and electrons]. / Traitement conservateur des tumeurs de la rétine à l'Institut Curie. Résultats ophtalmologiques à 5 ans de 129 cas traités par disque de Stallard et électrons.

The authors report a retrospective study of 129 children with retino-blastoma treated from 1963 to 1977 at the Institute Curie by enucleation of the worst eye and conservative irradiation of the other eye; this irradiation was performed either with Stallard plaque (19 cases) or with electrons (110 cases). In 8 familial cases no enucleation was performed. T.E.M. was used from 1964 to 1973 and iterative photocoagulation has been performed since 1968. Five years absolute NED survival rate was 68% (88/129 children). In these 88 children, 94 eyes were irradiated. Ophthalmological results were as follows: 21 eyes were enucleate secondarily (20/21 were tumoral); the attempt of ocular conservation was succeeded in 78% of the cases: 73 of the 94 irradiated eyes were cured; among these 73 cured eyes, 4 had complications and 15 had sequelae; the others 54 eyes were normal; only 5 eyes escaped ophthalmological survey; for the other 68 eyes vision was evaluated: 2 eyes (3%) were functional but vision could not be measured; 10 (14%) had less than 1/10 of visual acuity; 14 (19%) had vision at least equal to 1/10 but less than 5/10; 42 (57%) had 5/10 or more. 62% of all irradiated eyes (58/94) and 79% of conservated eyes (58/73) had "useful vision". Results are discussed and compared with these published by other teams; the authors try to determine elements of visual prognosis.