[Pilot study of conformal intensity modulated radiation therapy for localized prostate cancer].

PURPOSE: - To report our experience on treatment planning and acute toxicity in 16 patients suffering from clinically localized prostate cancer treated with high-dose intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: - Between March 2001 and October 2002, 16 patients with clinically localized prostate cancer were treated with IMRT. Treatment planning included an inverse-planning approach, and the desired beam intensity profiles were delivered by dynamic multileaf collimation. All patients received the entire treatment course with IMRT to a prescribed dose of 78 Gy. All IMRT treatment plans were compared with a theoretical conventional three-dimensional conformal radiation therapy (3D-CRT). Acute lower gastro-intestinal (GI) and genito-urinary (GU) toxicity was evaluated in all patients and graded according to the Common Toxicity Criteria for Adverse Events version 3.0 (CTCAE v. 3.0). A relationship between dose volume and clinical toxicity was evaluated. RESULTS: - Ninety-five percent of the PTV2 received more than 76 Gy using IMRT or 3D-CRT with no difference between both methods. The dose-volume histogram mean obtained for the PTV2 was not different between IMRT and 3D-CRT. IMRT improved homogeneity of the delivered dose to the PTV2 as compared with 3D-CRT (7.5 vs 9%, respectively). Ninety-five percent of the PTV1 received 5 Gy more using IMRT with protection of the bladder and the rectum walls. The benefit was considered below 75 and 70 Gy for the wall of the bladder and the rectum, respectively. Grade 2 GI and GU toxicity was observed in four (25%) and five (31%) patients, respectively. No grade 3 toxicity was observed. There was a trend towards a relationship between the mean rectal dose and acute rectal toxicity but without statistical significant difference (P =0.09). CONCLUSION: - Dose escalation with IMRT is feasible with no grade 3 or higher acute GI or GU toxicity. Examination of a larger cohort and longer-term follow-up are warranted in the future.

[Cancer of the breast: the return of lymphoscintigraphy?]. / Cancer du sein: le retour de la lymphoscintigraphie?

Lymphoscintigraphy, after arousing great hope in the past in the field of breast cancer, has now been abandoned. The inability of this examination to predict the metastatic status of the nodes, and progress in therapeutic concepts have led to abandoning this technique. However, certain problems encountered by regional irradiation programmes and the work concerning sentinel node detection may bring this technique back into the spotlight. Lymphoscintigraphy may make it possible to adopt an individual approach, case by case, of the lymphatic drainage basins in breast tumors, thus enabling certain patients to benefit from regional irradiation when it would not have been traditionally recommended for this irradiation. Another aspect concerns the problem of the volumes irradiated. Work carried out with lymphoscintigraphy has enabled internal mammary chain nodes to be precisely located. Theses studies show the necessity of adapting the irradiation field to each individual case, but the clinical impact is limited, in the end, by the low recurrence rate in the internal mammary chain area. However, the new techniques of computer merging of scintigraphic and scanner images could enable the spatial position of the nodes in the upper axillary and supraclavicular regions to be determined. This would have, a priori, much wider clinical impact. Lymphoscintigraphic detection of the sentinel node is another field of major interest, but this technique is in competition with staining techniques. This procedure leads to a large reduction in morbidity of axillary surgery in 70% of patients. The use of techniques for detecting micrometastases in the sentinel node opens prospects in terms of prognosis. The qualities of differents radiotracers and different injection sites possible are also discussed.

2-Mercapto-propylamine: radiopharmacology in mice, pharmacokinetic studies in mice and in rats, mutagenicity and differential distribution between tissues and EMT6 tumour in mice.

Radiopharmacological studies conducted with 2-mercapto-propylamine (2MPA), a methylated derivative of cysteamine, indicated a good efficiency in whole body irradiated mice as observed over a period of 9 months. Its efficacy was also checked for supralethal irradiations of restricted body parts: in the brain and the rectum. The diffusion of 14C-labelled 2MPA was assessed by an autoradiographic study and measurement of its distribution in the main organs in mice. 2MPA penetrated the blood brain barrier but concentrated preferentially in the liver, kidney and skin. Fixation on plasmatic proteins was much lower in rats than in mice but urinary and faecal eliminations were of the same order for the two species. An important biliary excretion of 2MPA or its metabolites in rats combined with their lack in the faeces underlies an entero-hepatic cycle. A differential diffusion of 2MPA between normal tissues in mice and EMT6 tumours was clearly revealed by autoradiographic observations. The ability of 2MPA to trap 2,2'-diphenyl 1-picryl hydrazyl, an organic free radical, was checked by in vitro studies. Its performance indicated that 2MPA acted at least as a free radical scavenger. Ames test demonstrated that 2MPA whatever the dose employed was not a mutagenic agent. Pharmacological and pharmacokinetical observations provided a better understanding of the activity of this drug.

The radioprotective power of 2-isopropyl 5-methyl 1,3-thiazolane.

The adequate conditions of radioprotective treatment with 2-isopropyl 5-methyl 1,3-thiazolane were established for mice. Protection is maximum with a unique intraperitoneal injection of LD 50/2, 3 hours prior to the irradiation. The rate of radiation dose reduction is therefore 1.75. Survival rate of whole body irradiated mice with supralethal doses were determined for 11 months. The long term survival of the animals fully proved good prevention of radio-induced damages. In vitro pharmacological studies show the ability of the major metabolite of the compound to trap organic radicals.

Mice's brain radioprotection: comparative efficacy of a series of aminothiols and aminothiol precursors.

A serie of radioprotective aminothiols was checked upon irradiation of the mice's brain. Cysteamine protects efficiently the brain as soon as 15 minutes after its administration. Among the tested aminothiols, it was the most effective compound. 2-isopropyl 1,3-thiazolane, rapidly hydrolysed, delivers a large amount of cysteamine in the brain and was nearly as potent as exogenous cysteamine. The other thiazolanes which delivered only progressively cysteamine or 2-mercaptopropylamine during a long period of time showed lesser efficacy. WR 2721 which did not penetrate the brain exhibited only a feeble radioprotection. The imperviousness to straight active aminothiols may be compensated by the diffusion of their precursors across the blood brain barrier and by their speed of hydrolysis, yielding active aminothiols during a short period of time between their administration and the irradiation.

Mice's rectum radioprotection: comparative efficacy of a series of aminothiols and aminothiol precursors.

In mice, in a test of rectal gamma irradiation, cysteamine and cysteine are poor radioprotectors relative to thiazolanes or WR 2721. Among the tested prodrugs, 2-isopropyl 1,3-thiazolane was nearly as efficient as WR 2721 as soon as 15 minutes after its administration. The guarantee of radioprotection is the effective presence of the active aminothiols in the intracellular room during the irradiation. In this study, enterocytes of the rectal mucous membrane were not sufficiently permeable to exogenous cysteine or cysteamine. The cell imperviousness to these straight active aminothiols was compensated by the diffusion of their precursors across the membrane.

Laser heating of thermoluminescent plates: application to intraoperative radiotherapy.

A new system of radiation dose mapping based on laser heating of thermoluminescent dosimetric plates (TLDP) has been developed. Application of this technique to intraoperative radiotherapy (IORT) has been investigated. Preliminary results show that TLDP are a possible alternative to radiological films and ionization chambers since they provide some advantages such as 2D dose measurements with digital storage, large dynamic dose range, and easy processing.

Radiation therapy of cervical cancer with dosimetric prevention of late pelvic complications.

Two successive series of invasive carcinoma of the cervix (268 and 307 patients) were treated by radiation alone between 1973 and 1977 and 1978 and 1985. The main difference between these periods was the method used to determine the definitive dose delivered by intracavitary therapy. The treatment in all cases consisted of external and intracavitary radiotherapy. Computerized dosimetry was performed in all patients with determination of dose rate, maximum and mean cumulated doses at the reference points of the rectum and bladder. The tolerance doses to the rectum and bladder previously established and represented graphically were used prospectively for the patients from 1978 to 1985, permitting better coordination of the two treatments. The graph takes into account the fractionated tolerance to external irradiation and intracavitary radiotherapy. The systematic use of this method yielded results at six years for all stages which were comparable from one series to another. Parallel to this, the improvement in the number and gravity of the complications was significant, especially for grade 2 complications (P = 0.001) and, to a lesser degree, for grade 3 and 4 complications (P = 0.04). In conclusion, the respect of tolerance doses to the critical organs close to the principal tumoral volume represents an effective method for optimizing radiotherapeutic treatment for cervical cancer.

A quantified approach to the analysis and prevention of urinary complications in radiotherapeutic treatment of cancer of the cervix.

This paper is the report of a dosimetric study of 79 urinary complications after radical radiation treatment (1975-1979) of 624 cervical uterine tumors. Treatment consisted of external irradiation (25 MeV linear accelerator) and intracavitary irradiation (Fletcher-Suit-Delclos applicator). Dosimetric-computerized studies were expressed as the maximum bladder dose on the trigone, as proposed by the I.C.R.U. Bladder doses were actually studied as a function of intracavitary irradiation and intracavitary + external irradiation. The results show a significant difference in patients with and without complications based on the dose reaching the bladder. The relative contribution of external therapy and intracavitary irradiation and their value can serve as one of the primary indicators for predicting complications. These values should be determined before placement of intracavitary sources. We found that the dose to the critical organs cannot be defined as a single number. These results argue in favor of adapting individual patient therapy based on rectal and bladder dosimetry and may be adjustable to all treatment modalities.

Analysis of the results of irradiation in the treatment of tonsillar region carcinomas.

Five year follow-up data are presented for 215 patients with carcinomas of the tonsillar region, all of whom were treated by radiation therapy alone. Data are analyzed retrospectively to determine the factors associated with prognosis. As in many reports in the literature, prognostic factors regarding survival of the patients were: the initial tumor site (tumor extension to the base of the tongue was considered to be a bad prognosis factor); the initial tumor size and lymph node involvement (9.4% 5 year survival for T3N3 vs 73.7% 5 year survival for T1N0 cases); and histological type of differentiation (better prognosis for well differentiated carcinomas than for poorly differentiated tumors). Studies on the biological and volumetric data (the NSD value and target volume were calculated for each case) allowed a statistical and critical correlation between therapeutic results and physical characteristics of the radiation treatment.

Cancer of the uterine cervix: dosimetric guidelines for prevention of late rectal and rectosigmoid complications as a result of radiotherapeutic treatment.

This paper is the report of a dosimetric study of 41 rectal and rectosigmoid complications after radiotherapeutic treatment (1974-1978) of 287 cervical uterine tumors. Treatment consisted of external irradiation (25 MeV linear accelerator) and intracavitary irradiation (Fletcher-Suit applicator) at different doses depending on tumor stage. Dosimetric measurements were expressed as the maximum rectal dose and mean rectal dose on the anterior surface of the rectum, as proposed by the Groupe Européen de Curiethérapie. Rectal doses were also studied as a function of intracavitary irradiation and intracavitary + external irradiation (maximum rectal and mean cumulative doses for each). The results show a significant difference in the state of the patients with and without complications, based on the dose reaching the rectum. The maximum and the mean cumulative rectal doses serve as one of the primary indicators for predicting complications. These values should therefore be determined before placement of intracavitary sources or, at the latest, before the second intracavitary application. We have shown that there is no fixed threshold dose, but that it varies from one region to another, depending on level of external irradiation. Our results argue in favor of adapting individual patient therapy based on simple precautions, which are adjustable to all treatment modalities. This method could lead to complete elimination of late rectal and rectosigmoid complications arising from radiotherapeutic treatment of cervical uterine cancer.