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The use of heavy particles in the treatment of cancer is increasing remarkably, whether with external radiation or using a vector such as an antibody in radioimmunotherapy. Recent pre-clinical and clinical developments of alpha-radioimmunotherapy have provided more interesting information in parallel of the use of high Linear Energy Transfer (LET) external irradiation. This review aims at presenting recent advances of this therapeutic approach, and at detailing the biological specificities of this kind of radiation.

The radiosensitizing properties of gemcitabine in relation to low Linear Energy Transfer (LET) particles (Cobalt 60) and high-LET particles (alpha-RIT (213)Bi-radiolabeled CHX-DTPA-B-B4) were analyzed. Three multiple myeloma cell lines (LP1, RPMI 8226, U266) were irradiated with or without 10 nM gemcitabine 24 h prior to radiation. Gemcitabine led to radiosensitization of LP1 and U266 cells with low-LET (Radiation Enhancement Ratio: 1.55 and 1.49, respectively) but did not radiosensitize any cell line when combined with high-LET.

The methodology and choice of criteria and indexes used for a common evaluation of helical tomotherapy by 3 French centres are described. After a selection of clinical indications and definition of the general purpose are successively described the criteria and index selected for: 1) description of volumes and adaptation for on board imaging; 2) dose prescription and constraints related to IMRT; 3) intercomparaison of volumes and doses and potential dosimetric gain with this new equipment.

Objective: In Europe, until recently the standard treatment for locally advanced rectal cancer was preoperative radiotherapy (RT). The objective of this study was to evaluate the influence on survival of intervals between diagnosis and treatment., Patients and Methods: The influence on survival of intervals between diagnosis and surgery (Dg-Surg), diagnosis and initiation of RT (Dg-Rad), and completion of RT and surgery (Rad-Surg) was evaluated in a retrospective series of patients treated with preoperative RT. Between 1991 and 1998, 102 patients received treatment with preoperative RT without concomitant chemotherapy at the René Gauducheau Cancer Center. Patients generally received 45 Gy (80%) in 25 fractions over 35 days for T2-T3-T4 N0-N1 M0 rectal adenocarcinoma located mainly (62.7%) in the lower third of the rectum (< or = 5 cm from anal margin). Thirty-five pN1 patients were treated with postoperative chemotherapy. Differences between survival were assessed by the log-rank test, and prognostic factors by the Cox test., Results: Median time was 14.7 weeks for Dg-Surg, 4.6 weeks for Dg-Rad and 5.1 weeks for Rad-Surg. Median follow-up from diagnosis was 57.4 months. Five-year local relapse-free survival was 83.9%, metastasis-free survival 64% and overall survival 60.8%. No factor was predictive of tumour response to RT. Log-rank and multivariate analysis showed that overall survival was significantly influenced by lower-third tumours, pT, pN and Dg-Surg (poorer survival when > or = 16 weeks: OR = 2.59, P = 0.005). Metastasis-free survival correlated significantly with Dg-Surg (> or = 16 weeks: OR = 2.05, P = 0.05)., Conclusion: An interval of more than 16 weeks between diagnosis and surgery may reduce overall survival of patients treated with preoperative RT for locally advanced rectal cancer. Surgery should be performed shortly after completion of RT for patients with no possibility of sphincter preservation, or a minimal risk of morbidity from an abdominoperineal excision.

We relate 2 cases reports about rectal cancer and pregnancy. This association is rare but is a real problem of management because diagnosis is done latly and it mate have incompatibility between treatments and pregnancy. A medical bibliography has been done, to define the best medical procedure in function of the disease staging and the pregnancy term. It shows that a multi disciplinary decision must be done, which take into consideration the choice of the obstetricals, pediatricians, surgeons, and oncologists, but also the patient's choice.

Incidence of malignant pleural mesothelioma will rise until 2030-2040 because the elapsed time between exposure and diagnostic is up to several decades. Prognosis remains very poor with median survival less than one year and five-year survival not exceeding 5%. As compared to 1999, standart treatment adds chemotherapy with cisplatin and pemetrexed to local radiotherapy for prevention of local seeding after invasive diagnostic procedures. Despite various growth factors and their receptors are involved in malignant mesothelioma, first clinical trials of targeted therapies reported poor results. Multimodality therapy with extrapleural pneumonectomy and radiation therapy (+/-chemotherapy) can be of benefit in subgroups of patients but it cannot be recommended in a routine approach. As compared to bronchial carcinoma, inclusion of patients in clinical trials (using intensity-modulated radiation therapy) is the only way to somewhat improve results.

Background: Using a specific monoclonal antibody (MAb), B-B4, coupled to bismuth-213 ((213)Bi) by a chelating agent (CITC-DTPA), the feasibility of alpha-radioimmunotherapy (RIT) for multiple myeloma (MM) has been demonstrated previously., Methods: In this study, the two MAbs tested, MA5 and B-B4, target the epithelial antigens Muc-1 and syndecan-1, respectively, which are both expressed by MM cell lines. Antibody characterization was evaluated by flow cytometric analysis of normal and tumoral hematopoeitic cells of MM patients as well as immunohistochemical tests of normal, nonhematopoetic tissues. Radiobiologic effects were evaluated for (213)Bi- and iodine-131 ((131)I)--labeled antibodies. We assessed in vitro mortality (thymidine incorporation, MTT, and clonogenic assays) and cell cycle modifications with propidium iodide staining. These tests were performed on MM cell lines until 120 hours postirradiation at several time points, using radiolabeled antibody concentrations ranging from 0.5 to 20 nM and specific activities ranging from 240 to 1200 MBq/mg of MAb., Results: MA5 stained all MM cells in only 50% of patients, whereas B-B4 recognized all MM cells in all patients. B-B4 principally showed hepatic, pulmonary, and duodenal staining, whereas MA5 marked renal and pulmonary tissues. RIT with (213)Bi-B-B4 induced specific mortality and G(2)/M phase cell cycle arrest, which depended on the concentrations and specific activity. For (213)Bi-MA5, this arrest appeared at concentrations above 10 nM, an amount fivefold higher than that required with B-B4. This difference was also found in thymidine incorporation assays. Furthermore, with (213)Bi-B-B4, the arrest at the G(2)/M phase appeared quickly, within 24 hours after irradiation, and affected up to 60% of the cells (for 20 nM of (213)Bi-B-B4 at 1,200 MBq/mg). Conversly, (131)I-B-B4 had a very limited effect on cell mortality and did not induce any cell cycle arrest., Conclusions: The results of this study show that B-B4 might be the more effective therapeutic antibody and suggest that alpha-RIT might be more suitable than beta-RIT for treating single-cell tumor models. Thus, these findings set the stage for the beginning of clinical trials using alpha-emitter--radiolabeled B-B4, with special attention paid to hepatic, pulmonary, and intestinal side effects., (Copyright 2002 American Cancer Society.)

Purpose: To evaluate the efficacy of total abdominopelvic (TAI) and total body irradiation (TBI) in heavily pretreated follicular non-Hodgkin's lymphoma (NHL)., Patients and Methods: From 1983 to 1998, 34 patients received TAI (n = 22) or TBI (n = 12). All had Stage III or IV, Class B, C, D NHL in the working formulation and failed after receiving 1-5 regimens of chemotherapy. TAI was given at 20 Gy over a 3-week period. TBI was delivered in two successive half-body irradiations of 15 Gy over a 2-week period with a 4-week interval between each., Results: Mean follow-up from TAI or TBI was 120 months (range, 6-180). Seventy-six percent of patients achieved complete response and 24% partial response. Median survival was 62 months, 5-year and 10-year overall survival was 59% and 41%, and disease-free survival was 56% and 30%, respectively. Grade III or IV toxicity was gastrointestinal in 38% of patients and hematologic in 30%. No toxic death or delayed complications were observed., Conclusion: Extended-field irradiation is feasible and efficient after failure of chemotherapy in follicular NHL.

Standard treatment of advanced ovarian cancer is a combination of surgery and chemotherapy. Additional therapies using the i.p. route are considered as a potential means of improving the locoregional control rate. This Phase II study evaluated the efficacy of i.p. radioimmunotherapy (RIT) in patients with minimal residual ovarian adenocarcinoma after primary treatment with surgery and chemotherapy. Between February 1995 and March 1996, six patients with residual macroscopic (<5 mm) or microscopic disease as demonstrated by laparotomy and multiple biopsies received i.p. RIT. All had initial stage III epithelial carcinoma and were treated with debulking surgery and one line (four patients) or two lines (two patients) of chemotherapy. RIT was performed with 60 mg of OC 125 F(ab')2 monoclonal antibody labeled with 4.44 GBq (120 mCi) of 131I injected 5-10 days after the surgical procedure. Systematic laparoscopy or laparotomy with multiple biopsies performed 3 months after RIT in five patients (clinical progression was seen in one patient) showed no change in three patients and progression in two patients. Toxicity was mainly hematological, with grade III neutropenia and thrombocytopenia in two patients. Human antimouse antibody production was demonstrated in all six patients. This study showed little therapeutic benefit from i.p. RIT in patients with residual ovarian carcinoma.

Purpose: To evaluate the therapeutic efficacy of moderate-dose total abdominopelvic irradiation (TAI) in a retrospective series of pretreated non-Hodgkin's lymphomas (NHL)., Methods and Materials: From 1977 to 1994, 45 patients received TAI after failure of chemotherapy (CT). According to the Working Formulation, 10 patients were diagnosed with class A (group I), 19 with class B, C, or D (follicular) (group II), and 16 with class E or more severe (group III) NHL. Irradiation consisted of two daily fractions of 0.80 Gy each for a total dose of 20 Gy., Results: Mean follow-up after TAI was 102 months (range 8-156). For the entire group, the complete response (CR) rate was 66%, the partial response (PR) rate 29%, 10-year overall survival (OS) 35%, 10-year disease-free survival (DFS) 29%, and median survival 32 months. When results between subgroups were compared, CR was 70% in group I, 84% in group II, and 44% in group III; and survival was statistically higher in group II than in groups I and III: 10-year OS 52% vs. 10% (p < 0.01) and 31% (p < 0.05), respectively, 10-year DFS 37% vs. 10% (p < 0.03) and 19% (p < 0.05), respectively. Grade III or IV complications were gastrointestinal in 27% of patients and hematologic in 25%., Conclusion: Large-field irradiation in moderate doses could provide an alternative to bone marrow transplantation in refractory NHL, especially in cases showing a follicular growth pattern.

Chromosome aberrations were evaluated in the lymphocytes of 30 patients who had undergone radiotherapy several years before for non-Hodgkin's lymphoma. Twelve had received 20 Gy over the entire abdomen (group I), 12 wholebody irradiation at 1.5 Gy (group II) and 6 wholebody irradiation at 15 Gy (group III). Unirradiated patients seen for cytogenetic analysis during the same period served as controls. Overall results for the irradiated population were 13/27 (48%) evaluable patients with chromosome aberrations and 50/710 (7%) abnormal cells for a total of 73 aberrations (unstable: 35, stable: 38). The frequency of aberrations was statistically higher in group I (12% of cells) than in groups II (3.5%, p < 0.0001) and III (2.5%, p < 0.0002). Differences in irradiation dose and volume may account for the variations between groups.

Purpose: To evaluate the feasibility and oncologic results of intraoperative radiation therapy (IORT) for recurrent uterine cervical carcinoma in a cohort of patients treated in seven French institutions., Methods and Materials: From 1985 to 1993, 70 patients with pelvic recurrences underwent IORT with/ without external radiation therapy (ERT) and chemotherapy (CT). Treatment modalities for recurrence were IORT alone (40 out of 70), IORT + ERT (30 out of 70), additional chemotherapy (20 out of 70). Gross complete resection (CR) was performed in 30 out of 70 cases, partial resection (PR) in 37 out of 70, and unspecified surgery in 3 out of 70. Sixty-five patients had electron beam IORT and 5, 100 KV photon IORT. Mean IORT cone size, electron beam energy, and dose (calculated at the 90% isodose line) were, respectively, 75 mm (40 to 90), 12 MeV (6 to 20), and 18 Gy (10 to 25) after CR and 80 mm (45 to 100), 15 MeV (7 to 24), and 19 Gy (10 to 30) after PR., Results: Mean follow-up after IORT was 15 months (2 to 69). One, 2- and 3-year overall survival rates were 47, 17, and 8%, respectively; median survival was 11 months and local control, 21%. Median survival and local control rates increased after CR (13 months, 27%) vs. PR (10 months, 17%) and when initial treatment consisted of surgery (S) alone (15 months, 25%) vs. radiation therapy (RT +/- S) (10 months, 16%). However, these differences were not statistically significant. No death-related toxicity was observed. Grade 2 or 3 toxicity was observed in 19 out of 70 patients (27%), including 9 not directly IORT-related complications (13%) (three digestive tract fistulas, one rectal stricture, three urinary fistulas, two infections) and 10 directly IORT-related complications (14%) (five neuropathies, four ureteral obstructions, and one rectal stricture)., Conclusion: This retrospective study demonstrates the feasibility of IORT. The usefulness of IORT still needs to be evaluated in primary treatment of advanced stages of cervical carcinoma.

Purpose: Prognosis of recurrent rectal cancer remains poor, mainly because of the difficulties of achieving a satisfactory local control. Intraoperative radiation therapy (IORT) allows for the delivery of a complementary single dose to the tumor residues or to the tumor bed and could be useful jn a multimodal treatment. In an attempt to evaluate this interest, a retrospective analysis of patients treated with IORT in six French hospitals has been performed., Methods and Materials: Data have been collected in 73 patients (41 men), with a mean age of 62 years, treated with IORT. Initial rectal tumors were large (mean diameter: 45 mm), partially or totally fixed to the contiguous structures in 39%, and with nodal involvement in 50% of the cases. Initial surgery had been a sphincter-sparing surgery in 67%; external radiation therapy had been delivered in 52%, and a chemotherapy had been given in 10% of the patients. Recurrences were isolated (without metastases) in 86%, and were posterior or posterolateral in 55% of the cases. Surgery allowed for a complete macroscopical resection in 57%, a partial resection with gross residual disease in 29%, and no resection in 14% of the recurrences. Intraoperative radiation therapy was delivered in a dose of 10 to 25 Gy (mean 18.5) through localizators of a mean diameter of 75 mm (60 to 110). External radiation therapy, either preoperative or postoperatively was given to 30 patients without prior radiation therapy. Ten patients received additional chemotherapy with 5-fluorouracil., Results: Four postoperative deaths occurred. Postoperative morbidity occurred in 16 patients and some complications were probably related to the IORT procedure. Four long-term complications were observed. Overall actuarial survival occurred in 72.4% of the patients at 1 year, in 44.6% at 2 years, and in 30.6% at 3 years. Twenty-one local failures have been observed. Actuarial local control occurred in 71.3% of the patients at 1 year, 47.7% at 2 years, and 31.3% at 3 years., Conclusion: Intraoperative radiation therapy is a complementary treatment for recurrences of rectal cancer. It provides encouraging results, particularly in some selected situations, when patients have not previously been treated with external radiation therapy. Further studies of multimodal treatments are necessary.

Radioimmunotherapy is based on the use of radioactive agents (iodine 131, yttrium 90...), murine-derived monoclonal antibodies and specific tumour-related membrane antigens. This new treatment modality was applied in 800 patients with different types of malignant tumours which had not responded to traditional therapy. Among the haematologic tumours, the most promising results were obtained in B phenotype non-Hodgkin lymphoma. More modest results were obtained for solid tumours although good results were observed after intraperitoneal administration in patients with cancer of the ovary. The main side effects are acute reversible anaphylactic shock, haematologic toxicity and development of anti-murine human antibodies. Several methods are currently under study to increase irradiation dose delivered at the tumoural site since less than 1% of the injected radioactive dose is absorbed by tumoural cells. Several clinical studies are to be conducted in France, particularly for malignant non-Hodgkin lymphoma and cancer of the ovary.

Patients with stage IV high/intermediate grade cutaneous non-epidermotropic lymphoma of skin as first localization of the disease have a poor prognosis. In this setting, autologous bone marrow transplantation (BMT) has rarely been evaluated. We report here on the treatment of four patients with such lymphomas with autologous BMT using 12 Gy total body irradiation (TBI) and CBV (cyclophosphamide, carmustine and etoposide). Using a plexiglass screen, TBI delivered an homogenized dose to the skin. With this conditioning regimen, all patients are still in complete remission 22, 44, 46 and 51, respectively, months after high-dose chemotherapy, TBI and autologous BMT.