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Biomedical subjects

G Marinello

Publications and source records attributed to G Marinello.

At least 19 recordsLinked to original sources

Radiotherapy in the management of mycosis fungoides: indications, results, prognosis. Twenty years experience.

PURPOSE: To determine the role of total skin electron beam therapy (TSEBT) and the prognosis of patients with mycosis fungoides. MATERIALS AND METHODS: From 1978 to 1996, 66 consecutive patients with mycosis fungoides received 30 Gy TSEBT delivered in 12 fractions over 40 days as treatment of their relapsed after topical or/and systemic therapy. All patients were staged as follows: stage A, superficial lesions covering less than 50% of the body surface; stage B, superficial lesions covering more than 50% of the body surface; Stage C. tumors involving the skin, lymph nodes and/or visceral organs. RESULTS: The median age was 50 years (ranging from 13-78 years). There were 39 males and 27 females. The minimum follow-up was 12 months (range 12-192 months). There were 24 (36%) stage A patients, 22 (33%) stage B patients, and 20 (30%) stage C patients. The overall survival at 5 years for our series was as follows: 93% for stage A; 79% for stage B, and 44% for stage C disease (P = 0.002). For the entire cohort, the complete remission rate was 65%, the progression-free survival (PFS) at 5 years and 10 years was 30 and 18% respectively. For the group A, PFS was 62% at 5 years and 46% at 10 years; for group B, PFS was 19% at 5 years. CONCLUSIONS: This study suggests that TSEBT gives good results for relapsed stage A disease. Total skin electron beam therapy combined with local fields irradiation or other local treatment (puvatherapy or topical nitrogen mustard) might further improve permanent complete response for stage B patients. The most advanced stages of mycosis fungoides are not controlled by TSEBT, but the radiation therapy offers good palliation results.

Adolescent

Lithium borate TLD for determining the backscatter factors for low-energy x rays: comparison with chamber-based and Monte Carlo derived values.

Recently, new backscatter factors for low-energy x rays derived from Monte Carlo calculations have been recommended in the UK code of practice for kilovoltage dosimetry published by (IPEMB). As these data, presented as a function of half-value layer, do not take account of the variation of the x-ray spectra for a given HVL, we have undertaken an experimental study in order to determine BSG for the beam qualities provided by a Darpac 2000 therapy unit. A RTL detector such as Li2B4O7:Cu and parallel-plate ion chambers specially designed for low-energy x-ray dosimetry have been used. The results obtained show very good agreement between the TLD and the Monte Carlo calculations, confirming values obtained by other authors with lithium borate TLD. On the contrary, the results obtained with plane-parallel ion chambers show discrepancies up to 9% that are discussed.

Borates

[Influence of irradiation on the risk of HIV virus transmission by bone allograft].

PURPOSE: The purpose of this study was to determine, when assuming the worst case scenario of bone contamination, the sterility assurance level in bone transplantation treated by irradiation and after donor screening. MATERIAL AND METHODS: The virus: We employed the HIV-1, LAV-1 as our reference strain, which has always been cultured on normal human cells (and has therefore never been in contact with cell lines). To test viral virulence, we used a very sensitive cell line: MT2 cell line, a T lymphoblastoid cell line which is HTLV-I positive and is sensitive to HIV-1/LAV-1 infection. It was maintained in RPMI 1640 culture medium containing 10 per cent heat-inactivated fetal calf serum (Boehringer Mannheim), 2 mM L-glutamine (Boehringer Mannheim) and 1 per cent antibiotics (PSN 100 x, Gibco). Cell concentration was 100,000 cells per milliliter. Irradiation was performed using an accelerator delivering electrons of 6.2 MeV providing several tens of kilograys in a few seconds. The dose delivered was checked by placing alanine dosimeters at the site of the HIV aliquots. Alanine is a solid amino acid which, when irradiated, gives rise to free radicals; these were counted using electron paramagnetic resonance (relative standard deviation of less than 1 per cent). RESULTS: 25 kilograys irradiation of 316,227 TCID50/ml at -80 degrees C led to a considerable titer reduction (3 logs) with 316 TCID50/ml remaining. According to the technique's sensitivity (100 TCID50/ml) and to the sensitivity with which the dose of irradiation can be measured (less than 1 per cent), the D10 value with "99 per cent confidence limits" was between 8.3 kilograys and 7.2 kilograys. Assuming the worst characteristics of irradiation, we have chosen 8.3 kilograys as the D10 value for -80 degrees C. DISCUSSION: Considering a mean level of contamination of 30 TCID50 per milliliter of plasma during the asympomatic phase of infection, the reduction of the transmission risk of HIV by a femoral head allograft was calculated in the best case to be only 5 per cent when performed at 25 kilograys. Irradiation cannot be considered as a process able to achieve sterility of the graft and has to be associated to an extensive screening. However irradiation associated with appropriate screening of donors decreases the risk of transmission of the disease under one out of one million in femoral allograft implantation.

Bone Transplantation

[Bone sterilization by radiation and the HIV virus].

An experimental study was performed to investigate the efficacy of irradiating HIV-contaminated allografts. Irradiation was achieved using an accelerator delivering 6.3 MeV electrons, and the viral strain was HIV-1/LAV-1. At an activity equivalent to 600.000 counts of reverse transcriptase activity per minute and per millilitre, irradiation permitted total inactivation of HIV. In the light of present data concerning plasma viremia in HIV-infected patients, this experiment suggested that irradiation minimizes as far as possible the risk of transmitting HIV infection through bone transplantation from a seronegative, contaminant donor. However, in view of the relative imprecision of viral sensitivity curves, irradiation does not authorize bone transplantation from a seropositive patient, even though the bone has been irradiated.

Animals

"PCL" a new automatic fast reader suitable for in vivo dosimetry.

The authors present a new automatic TLD reader specially designed for medical dosimetric applications, which allow considerable time-saving. The "PCL" reader is based on an isothermal heating kinetics and can be used with TL material of any nature and any shape (powder, microrods, pellets). Doses from 1 microGy to 10 Gy can be measured, or higher doses by interposing an optical absorber in front of the PM. The readout system is controlled by an IBM compatible personal computer. Results can be printed under the form defined by the users and then can be straightly stored in a patient sheet or an experience book. Tests performed with LiF chips TLD 100 and 700 (HARSHAW), Li2B4O7:Mn discs LiB (ALNOR), LiF powder PTL 717 (DESMARQUET) and Li2B4O7:Cu powder (CEN-FAR) are presented. They show a good reproducibility and interesting dosimetric properties.

Humans

Dosimetry of intraluminal brachytherapy.

Dose specification in intraluminal brachytherapy varies considerably in the literature. A terminology is proposed, inspired from the Paris System of interstitial brachytherapy, to define some dosimetric guidelines. The dose is specified in the central plane which is a plane perpendicular to the source and passing through its centre. The reference dose rate is calculated in this plane. The treated volume is the volume encompassed by the reference isodose. The hyperdose sleeve is the volume receiving a dose equal to or greater than twice the reference dose. A study of the dose distribution along a linear source of iridium-192 was undertaken. Results obtained, also valid for caesium-137 and cobalt-60, show that the radius of the hyperdose sleeve is relatively independent of the length of the source. It is approximately 0.6 times the distance between the source axis and the point of dose specification when the active length varies from 3 to 20 cm. Reporting not only the dose, but also the thickness of tissue covered by the reference isodose and the thickness of tissue included in the hyperdose sleeve, is recommended to assist in evaluation of the results of treatment and to facilitate the exchange of clinical information in intraluminal brachytherapy. Practical examples are given.

Brachytherapy

Conservative treatment for breast cancer: long-term results (15 years).

From 1961 to 1974, 245 patients with unilateral "operable" breast cancer (25% T1, 56% T2, 19% T3) were treated with breast conservation and irradiation at the Gustave Roussy Institute (1961-1969) or at the Henri Mondor Hospital (1970-1974). The minimum follow-up is 15 years. Most patients with T greater than 3 cm underwent radiation therapy with the tumor in place, while the greater part of patients with T less than 3 cm received radiation therapy after tumorectomy. The breast and draining lymph node areas received widefield telecobalt irradiation to 45 Gy. The dose to the tumor site was boosted using iridium-192 implantation. Additional irradiation was given to the internal mammary and lower axillary nodes using an electron beam. The 15 years NED survival rate was 63%, 51% and 26% for T1, T2 and T3 tumors, respectively. The NED survival for T less than or equal to 1 cm was 86%. The local recurrence rate was 8, 12 and 19% for T1, T2 and T3 tumors, respectively. Of the patients with local recurrence, 85% underwent surgical salvage. Complications were rare. Cosmetic results were satisfactory in most patients including the T3 group. The proportion of breasts conserved among patients living NED at 15 years, was 97, 88 and 93% for T1, T2 and T3 tumors, respectively. In 1980, after almost 20 years experience using breast conserving techniques, we modified our treatment policies in close collaboration with our surgical team, hel cbye extending the indications for tumorectomy and associating routine surgical exploration of the lower axilla.

Breast Neoplasms

Interstitial iridium 192 for cutaneous carcinoma of the external nose.

Several implantation techniques useful for nasal skin carcinoma have been developed at the Henri Mondor Hospital in Créteil, France and are described in detail. Iridium 192 wires, 0.3 mm in diameter, are afterloaded into either supple plastic tubes or rigid needles implanted according to the rules of the Paris system. Dosimetry is performed by computer, based on either direct measurements of active lengths and spacing, orthogonal films or a tomogram oriented in the central plane of the implant. According to a recent review by the European Curietherapy Group of 468 implants, the optimal dose is 60 Gy. The overall failure rate was 2.6%. Indications for implantation and choice of technique, based on tumor size, site, and gross morphology are discussed.

Brachytherapy

Iridium-192 curietherapy for T1 and T2 epidermoid carcinomas of the floor of mouth.

From 1970 to 1986, 117 patients with T1 (47) or T2 (70) epidermoid carcinomas of the floor of the mouth (SCC) were treated by iridium-192 implantation (192 Ir). The dose was prescribed according to the Paris System and varied over those years. Follow-up information was available on 116 patients. There were 46 T1N0, 47 T2N0, and 23 T2N1-3. Neck management varied for the 93 N0 patients consisting of surveillance (24 T1, 17 T2) or elective neck dissection (22 T1:all pN-, 30 T2: 20 pN-, 10 pN+). Cause specific survival rates were 94% for T1N0, 61.5% for T2N0, and 28% for T2N1-3 at 5 years. Primary local control was 93.5%, 74.5%, and 65%, respectively, and 98%, 79%, and 65% after salvage. Patients with gingival extension or a tumor size over 3 cm (T2b) had a local control of 50% (9/18) and 58% (15/26), respectively. Nodal control was 93.5% for Stage I, 85% for Stage II, and 48% for T2N1-3 patients. There was no difference in nodal control with regard to treatment policy for Stage I-II patients. There were few complications including three deaths: two from surgery and one from 192 Ir. Nodal status, tumor size defined as T1, T2a (less than or equal to 3 cm), T2b (greater than 3 cm), and gingival extension were the only independent prognostic factors. The management of T1N0 and T2N0 SCC by 192 Ir to a dose of 65 or 70 Gy, using the Paris System, is recommended for lesions 3 cm or less and without gingival extension.

Adult

Iridium 192 implantation of T1 and T2 carcinomas of the mobile tongue.

Between 1970 and 1986, 166 patients with T1 or T2 epidermoid carcinomas of the mobile tongue were treated by iridium 192 implantation (70 T1N0, 83 T2N0, 13 T1-2 N1-3). Five-year actuarial survival was 52% for T1N0, 44% for T2aN0, and 8% for or T1-2 N1-3. Cause specific survivals were 90%, 71%, and 46%, respectively. Local control was 87% for both T1N0 and T2N0, and 69% for T1-2 N1-3. Seven of 23 failures were salvaged by surgery, increasing local control to 96% for T1 and 90% for T2. Thirty-six patients developed a minor or moderate necrosis (16% T1, 28% T2). Half of these involved bone but only five required surgical intervention. Both local control (LC) and necrosis (nec) increased with increasing dose but improvement beyond 65 Gy is minimal (less than or equal to 60 Gy: LC = 78% nec = 13%; 65 Gy: LC = 90% nec = 29%; greater than or equal to 70 Gy: LC = 94% nec = 23%). For N0 patients, neck management consisted of surveillance (n = 78), elective neck dissection followed with external irradiation for pathologically positive nodes (n = 72), or irradiation (n = 3). Clinically positive nodes (13 patients) were managed by either neck dissection followed by external irradiation if pathologically positive (n = 10) or irradiation alone (n = 3). Regional control was 79% for N0 patients, improving to 88% after surgical salvage, and was 9/13 for N1-3 patients. We recommend that T1 and T2 carcinomas of the mobile tongue be treated by iridium 192 implantation to deliver 65 Gy. Mandibular necrosis should be reduced by using an intra-oral lead-lined dental mold.

Adult

Prognostic factors of local outcome for T1, T2 carcinomas of oral tongue treated by iridium 192 implantation.

The results of Iridium 192 implantation for 121 node negative T1 or T2 squamous carcinomas of mobile tongue were reviewed to look for predictors of local control and necrosis. Age, sex, total dose, dose rate, linear activity, and intersource spacing were examined. Minimum follow-up was 2 years but no patient with local recurrence or necrosis was excluded. There were 57 T1N0 tumors, 45 T2aN0 (2.1-3.0 cm), and 19 T2bN0 (3.1-4.0 cm). Local failures occurred in 14% of T1, 11% of T2a, and 26% of T2b. Univariate analysis showed that local control increased with increasing dose (55-60 Gy: 73%; 65-75 Gy: 92%, p = 0.005), whereas multivariate analysis revealed both sex and total dose to be significant. Radiation necrosis occurred in 17% of T1, 29% of T2a, and 47% of T2b (p = 0.034). Half were limited to soft tissue and the majority healed with conservative management. Univariate analysis showed that necrosis increased with increasing dose (55-60 Gy: 16%; 65-75 Gy: 33%, p = 0.037), as well as increasing dose rate, linear activity, and intersource spacing. With multivariate analysis only stage, dose rate, and spacing remained predictive of necrosis. Total dose was not adjusted for dose rate or tumor volume. This analysis suggests that within the therapeutic range of low dose rate brachytherapy, correction of total dose according to dose rate is unnecessary. We recommend 65 Gy. Lower dose rate (0.4-0.5 Gy/hr) and closer intersource spacing (12-14 mm) should be aimed for to minimize necrosis.

Adult

[Total cutaneous electron beam therapy of mycosis fungoides].

Electron beam irradiation of the entire skin surface was used to treat 25 patients with mycosis fungoides from 1977 to January 1988. A plexiglas screen was used to reduce the energy of the 8 MeV beam of a Sagittaire linear accelerator to 4 MeV. A total dose of 30 Gy was delivered in 12 fractions over days. This series includes 17 men and 8 women with a mean age of 44 years (range 13-78 years) and a mean follow-up of 34 months (range 6-92 months). The following-up staging system was used: stage A: superficial lesions covering less than 50 p. 100 of the body surface; stage B: superficial lesions covering more than 50 p. 100 of the body surface; stage C: tumors of the skin, lymph nodes and/or visceral organs, Sezary's syndrome. All stage A patients achieved complete remission. One developed recurrent disease in a very limited area 17 months after radiation therapy. No stage A patient died of mycosis fungoides. 6/9 stage B patients achieved complete remission; 4 of these developed recurrent disease localized to the skin 6 to 13 months after electron therapy. These recurrences were controlled by topical nitrogen mustard, puva therapy or localized irradiation. 1 patient showed no response and died of cutaneous mycosis fungoides. 5/10 stage C patients obtained complete remission but all relapsed within a mean period of 7 months. 4/5 of the patients not responding to electron therapy died of their disease and one is alive 16 months after completion of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Venocclusive disease of the liver after allogeneic bone marrow transplantation in man.

One hundred and fifty-one consecutive patients underwent allogeneic bone marrow transplantation (B.M.T.) following high-dose chemotherapy and single dose total body irradiation (T.B.I.) for hematologic malignancies between September 1980 and December 1985. All patients included in this study were treated using a 60 Co beam to deliver a prescribed dose of 10 Gy to the mid-plane of the abdomen. Total body irradiation was performed the day before B.M.T. The mean instantaneous dose-rate was 3.5 cGy/min (range: 2.6 to 4.7). The real dose received was measured using thermoluminescent dosimeters (lithium borate). The difference between the doses delivered to the liver and to the mid-plane of the abdomen did not exceed 5%. The mean real dose delivered to the reference point was 10 Gy (range 8.3 to 11.7). Ninety five per cent of the patients received a dose ranging from 9.1 Gy to 10.9 Gy. High-dose cyclophosphamide was given to 126 patients with a "standard-risk" of relapse (60 mg/kg on day 5 and 4 before B.M.T.). Chemotherapy was intensified by the addition of other drugs in 25 patients with "higher-risk" of relapse. We analyzed the effect of the following pretransplant characteristics on the subsequent posttransplant development of V.O.D.: age, sex, ASAT and/or ALAT before conditioning regimen, diagnosis and status of malignant disease, history of liver disease, interval between diagnosis of hematologic malignancy and B.M.T., conditioning regimen (i.e., classical or intensified) and dose delivered to the liver during T.B.I. Seventeen patients were classified as having clinical V.O.D. giving a prevalence of 11.2%. In the first 2 months following B.M.T., death occurred respectively in 9 of 17 (53%) and 23 of 134 (17%) patients with and without clinical V.O.D. Univariate analysis showed that four characteristics were significantly related to an increased prevalence of V.O.D.: sex (11/62 females vs 6/89 males; p less than 0.05); history of liver disease (7/28 vs 10/117 patients without antecedent; p less than 0.01); ASAT and/or ALAT levels greater than 1.5 upper normal limit (11/49 vs 6/102 patients with levels less than 1.5; p less than 0.01) and intensified conditioning regimen (6/25 vs 11/126 patients with classical regimen; p less than 0.05). The conditioning regimen and history of liver disease were highly correlated to transaminases levels. Only two factors, transaminases levels and female sex, remained significantly associated with V.O.D. after multivariate analysis.

Adolescent

Intracavitary irradiation of carcinomas of the uterus and cervix: the Créteil method.

The Créteil method is a logical and simple system for intracavitary therapy of cervical and uterine cancer. The system is based on the use of a plastic cervico-vaginal moulage loaded with 0.5 mm diameter iridium 192 wire sources. The dimensions of both the moulage and the sources correspond to the size of the cervix being treated according to precisely defined relationships. The dose is specified on a reference isodose of a "fixed" value enclosing the pear-shaped target volume whose dimensions depend on the geometry of the sources. Source geometry in turn, depends on the size of the cervix. Thus, the dimensions of the target volume can be accurately predicted at the time of the application. Furthermore, treatment can be performed in a single application, with all sources having the same linear reference air kerma rate (or activity). Radioprotective measures are simple but effective and the patient is not subjected to the restrictions imposed by attachment to an after-loading apparatus. Our clinical results for early Stage T1 and T2a cervical tumors show excellent local control without major treatment complications or long term sequelae.

Brachytherapy