[Radiotherapy of carcinomas of the anal canal. Tenon Hospital experience]. / Traitement des cancers du canal anal par irradiation. Expérience de l'hôpital Tenon.

Since 1980, curative-intent radiation therapy of epidermoid carcinoma of the anal canal is the standard first line treatment. The combined concomitant chemotherapy and radiation therapy is presently established for locally advanced tumors more than 4 cm in length and/or with nodal involvement. We report the Tenon hospital experience since 1972 concerning the long term results after radiation therapy, the modifications of the radiation technique, and the evolution of treatment strategy.

[Locoregional recurrence of adenocarcinomas of the rectum treated with irradiation combined with or without excision surgery]. / Rechutes locorégionales d'adénocarcinomes du rectum traitées par irradiation associée ou non à une chirurgie d'exérèse.

PURPOSE: Retrospective study to analyze the results of external beam radiation treatment with or without surgery for loco-regional recurrence of adenocarcinoma of the rectum following previous surgery without pre- or post-operative radiotherapy. PATIENTS AND METHODS: Between March 1973 and November 1991, 211 patients with loco-regional recurrence of rectum cancer were treated with external beam radiation treatment. Radical surgery was the only initial treatment modality. Surgical resection of local recurrence was done in 36 patients and only 17 patients could undergo complete resection. Forty-seven patients underwent radiotherapy (RT) combined with surgery and 164 received external beam radiation treatment alone to a mean total dose of 46 Gy. RESULTS: Among the 151 patients whose recurrence was revealed by pain, 64 (42%) were considered to have a complete symptomatic response after loco-regional treatment with radiosurgery or RT alone. The mean duration of response was 12 months. The 3-year overall survival rate was 16%. Five prognostic factors decreased the overall survival rate in multivariate analysis: high age, sex (male), concomitant distant metastasis, no tumor resection, and low total radiation dose with external beam radiation treatment alone. The 3-year overall survival rate for patients with completely resected recurrences was 39%. CONCLUSION: External beam RT treatment can only be considered a palliative symptomatic treatment. New techniques of early detection of local recurrence and new combined modalities approaches (radiation sensitizers or intra-operative radiotherapy) with surgical resection in some favorable cases should be studied.

Local recurrences and distant metastases after breast-conserving surgery and radiation therapy for early breast cancer.

PURPOSE: To identify predicting factors for local failure and increased risk of distant metastases by statistical analysis of the data after breast-conserving treatment for early breast cancer. METHODS AND MATERIALS: Between January 1976 and December 1993, 528 patients with nonmetastatic T1 (tumors < or = 1 cm [n = 197], >1 cm [n = 220]) or T2 (tumors < or = 3 cm [n = 111]) carcinoma of the breast underwent wide excision (n = 435) or quadrantectomy (n = 93) with axillary dissection (negative nodal status [n-]: 396; 1-3 involved nodes: 100; >3 involved nodes: 32). Radiotherapy consisted of 45 Gy to the entire breast via tangential fields. Patients with positive axillary lymph nodes received 45 Gy to the axillary and supraclavicular area. Patients with positive axillary nodes and/or inner or central tumor locations received 50 Gy to the internal mammary lymph node area. A boost dose was delivered to the primary site by iridium 192 Implant in 298 patients (mean total dose: 15.2+/-0.07 Gy, range: 15-25 Gy) or by electrons in 225 patients (mean total dose: 14.8+/-0.09 Gy, range: 5-20 Gy). The mean age was 52.5+/-0.5 years (range: 26-86 years) and 267 patient were postmenopausal. Histologic types were as follows: 463 infiltrating ductal carcinomas, 39 infiltrating lobular carcinomas, and 26 other histotypes. Grade distribution according to the Scarff, Bloom, and Richardson (SBR) classification was as follows: 149 grade 1, 271 grade 2, 73 grade 3, and 35 nonclassified. The mean tumor size was 1.6+/-0.3 cm (range: 0.3-3 cm). The intraductal component of the primary tumor was extensive (EIC = IC > or = 25%) in 39 patients. Tumors were microscopically bifocal in 33 cases. Margins were assessed in the majority of cases by inking of the resection margins and were classified as positive in 13 cases, close (< or = 2 mm) in 21, negative (>2 mm tumor-free margin) in 417, and indeterminate in 77. Peritumoral vascular invasion was observed in 40 patients. Tamoxifen was administered for at least 2 years in 176 patients. At least six cycles of adjuvant systemic chemotherapy were administered in 116 patients. The mean follow-up period from the beginning of the treatment was 84.5+/-1.7 months. RESULTS: First events included 44 isolated local recurrences, 8 isolated axillary node recurrences, 44 isolated distant metastases, 1 local recurrence with synchronous axillary node recurrence, 7 local recurrences with synchronous metastases, and 2 local recurrences with synchronous axillary node recurrences and distant metastases. Of 39 pathologically evaluable local recurrences, 33 were classified as true local recurrences and 6 as ipsilateral new primary carcinomas. Seventy patients died (47 of breast carcinoma, 4 of other neoplastic diseases, 10 of other diseases and 9 of unknown causes). The 5- and 10-year rates were, respectively: specific survival 93% and 86%, disease-free survival 85% and 75%, distant metastasis 8.5% and 14%, and local recurrence 7% and 14%. Mean intervals from the beginning of treatment for local recurrence or distant metastases were, respectively, 60+/-6 months (median: 47 months, range: 6-217 months) and 49.5+/-5.4 months (median: 33 months, range: 6-217 months). After local recurrence, salvage mastectomy was performed in 46 patients (85%) and systemic hormonal therapy and/or chemotherapy was administered to 43 patients. The 5-year specific survival rate after treatment for local recurrence was 78+/-8.2%. Multivariate analysis (multivariate generalization of the proportional hazards model) showed that the probability of local control was decreased by the following four independent factors: young age (< or = 40 yr vs. >40 yr; relative risk [RR]: 3.15, 95% confidence interval [CI]: 1.7-5.8, p = 0.0002), premenopausal status (pre vs. post; RR: 2.9, 95% CI: 1.4-6, p = 0.0048), bifocality (uni- vs. bifocal; RR: 2.7, 95% CI: 2.6-2.8,p = 0.018), and extensive intraductal component (IC <25% vs. IC > or = 25%; RR: 2.6, 95% CI: 13-5.2, p = 0

Total-body irradiation before bone marrow transplantation for acute leukemia in first or second complete remission. Results and prognostic factors in 326 consecutive patients.

AIM: In order to assess the influence of total-body irradiation (TBI) on the outcome and incidence of complication after bone marrow transplantation (BMT), we retrospectively analyzed our patients treated for acute leukemia and conditioned with TBI prior to BMT. PATIENTS AND METHODS: Between 1980 and 1993, 326 patients referred to our department with acute non-lymphoblastic leukemia (ANLL, n = 182) and acute lymphoblastic leukemia (ALL, n = 144) in complete remission underwent TBI either in single dose (190 patients: 10 Gy administered to the midplane, and 8 Gy to the lungs [STBI]) or in 6 fractions (136 patients: 12 Gy on 3 consecutive days, and 9 Gy to the lungs [FTBI]) before BMT. The male-to-female ratio was 204/122 (1.67), and the median age was 30 years (mean: 30 +/- 11, range: 3 to 63). The patients were analyzed according to 3 instantaneous dose rate groups: 118 patients in the LOW group (< or = 0.048 Gy/min), 188 in the MEDIUM group (> 0.048 and < or = 0.09 Gy/min), and 20 in the HIGH group (> 0.09 cGy/min). Conditioning chemotherapy consisted of cyclophosphamide (CY) alone in 250 patients, CY and other drugs in 54, and 22 patients were conditioned using combinations without CY. Following TBI, allogeneic and autologous BMT were realized respectively in 118 and 208 patients. Median follow-up period was 68 months (mean: 67 +/- 29, range: 24 to 130 months). RESULTS: Five-year survival, LFS, RI and TRM rates were 42%, 40%, 47%, and 24%, respectively. Five-year LFS was 36% in the STBI and 45% in the FTBI group (p = 0.17). It was 36% in the LOW group, 42% in the MEDIUM group, and 30% in the HIGH group (p > 0.05). Five-year RI was 50% in STBI, 43% in FTBI, 55% in LOW, 41% in MEDIUM, and 44% in HIGH groups (STBI vs. FTBI, p = 0.48; LOW vs. MEDIUM, p = 0.03; MEDIUM vs. HIGH, p = 0.68). TRM was not influenced significantly by the different TBI techniques. When analyzing separately the influence of fractionation and the instantaneous dose rate either in ANLL or ALL patients, no difference in terms of survival and LFS was observed. Fractionation did not influence the 5-year RI both in ANLL and ALL patients. However, among the patients with ANLL, 5-year RI was significantly higher (58%) in the LOW group than the MEDIUM group (31%, p = 0.001), whereas instantaneous dose rate did not significantly influence the RI in ALL patients. The 5-year TRM rate was significantly higher in allogeneic BMT group both in ANLL (37%) and ALL (37%) patients than those treated by autologous BMT (ANLL: 15%, ALL: 18%; p = 0.002 and 0.02, respectively). The 5-year estimated interstitial pneumonitis (IP) and cataract incidence rates were 22% and 19%, respectively, in all patients. IP incidence seemed to be higher in the HIGH group (46%) than the MEDIUM (19%, p = 0.05) or LOW (25%, p = 0.15) groups. Furthermore, cataract incidence was significantly influenced by fractionation (STBI vs. FTBI, 29% vs. 9%; p = 0.003) and instantaneous dose rate (LOW vs. MEDIUM vs. HIGH, 0% vs. 27% vs. 33%; p < 0.0001). Multivariate analyses revealed that the best factors influencing the survival were 1st CR (p = 0.0007), age < or = 40 years (p = 0.003), and BMT after 1985 (p = 0.008). The RI was influenced independently only by the remission status (p = 0.0002). On the other hand, the TRM rate was lower in patients who did not experience graft-vs.-host disease (GvHD, p < 0.0001), and in those treated after 1985 (p = 0.0005). GvHD was the only independent factor involved in the development of IP (p = 0.01). When considering the cataract incidence, the only independent factor was the instantaneous dose rate (p = 0.0008). CONCLUSION: The outcome of BMT patients conditioned with TBI for acute leukemia was not significantly influenced by the TBI technique, and TRM seemed to be lower in patients treated after 1985. On the other hand, cataract incidence was significantly influenced by the instantaneous dose rate.

Primary chemotherapy and preoperative irradiation for patients with stage II larger than 3 cm or locally advanced non-inflammatory breast cancer.

BACKGROUND AND PURPOSE: To evaluate possibility of breast-conserving therapy and outcome for patients with locally advanced non-inflammatory breast cancer (LABC) and stage II >3 cm in diameter after primary chemotherapy (CT) followed by external preoperative irradiation (RT). MATERIALS AND METHODS: Between 1982 and 1990, 147 patients were treated by four courses of induction CT (doxorubicin, vincristine, cyclophosphamide, 5-fluorouracil) followed by preoperative RT (45 Gy to the breast and nodal areas) and a fifth course of CT. Three different loco-regional approaches were proposed depending on tumour characteristics and tumour response. After completion of local therapy, all patients received a sixth course of CT and a maintenance adjuvant CT regimen without anthracycline. RESULTS: Mastectomy and axillary dissection were performed in 52 patients, and conservative treatment in 95 patients (48 achieved complete remission and received additional radiation boost to initial tumour bed; 47 had a residual mass < or =3 cm in diameter and were treated by wide excision and axillary dissection followed by a boost to the excision site. Ten-year actuarial loco-regional failure rate was 20% after RT alone, 23% after wide excision and RT and 6% after mastectomy (P = 0.85). After multivariate analysis, possibility of breast-conserving therapy was related to initial tumour size. Ten-year overall survival rate was 66%; it was not influenced by local treatment (conservative vs. non-conservative local treatment, P = 0.89). However, local failure significantly decreased overall survival (P < 0.0001). After multivariate analysis, tumour response after induction CT and clinical stage had a significant impact on survival. CONCLUSIONS: The present data indicate that induction CT followed by preoperative RT may permit the selection of some patients with LABC or stage II >3 cm for conservative treatment. The impact of this treatment modality on long term survival remains to be established.

Total body irradiation prior to bone marrow transplantation: efficacy and safety of granisetron in the prophylaxis and control of radiation-induced emesis.

PURPOSE: Radiation-induced emesis is one of the most disturbing side effects of total body irradiation (TBI). To evaluate the efficacy and to determine the best schedule of granisetron (a selective 5-hydroxytryptamine3 serotonin receptor antagonist) administration in the prevention of radiation-induced nausea and vomiting, we conducted a trial involving patients receiving single-dose TBI before bone marrow transplantation (BMT). METHODS AND MATERIALS: Thirty-six patients with non-Hodgkin's lymphoma (n = 12), multiple myeloma (n = 8), acute lymphoblastic leukemia (n = 7), acute nonlymphoblastic leukemia (n = 6), and chronic myeloid leukemia (n = 3) referred to our department between March 1992 and February 1994 were enrolled in this study to assess the efficacy of granisetron during single-dose TBI before autologous BMT (n = 26), allogeneic BMT (n = 8), or syngeneic BMT (n = 2). The male-to-female ratio was 22:14 (1.57), and the mean age was 41 +/- 11 years (range 16-58). Before TBI, conditioning chemotherapy consisted of cyclophosphamide (CY) alone (60 mg/kg per day on 2 successive days) in 24 patients, CY combined with other drugs in 6, and combinations without CY in 6. All patients received single-dose TBI (10 Gy administered to the midplane at L4, and 8 Gy to the lungs). The mean instantaneous and average dose rates were 0.039 +/- 0.012 Gy/min (range 0.031-0.058), and 0.025-0.006 Gy/min (range 2.08-3.96), respectively. Granisetron was administered 30-45 min before TBI according to two different modalities: a total dose of 3 mg as a 5-min intravenous (i.v.) infusion (Treatment A, n = 15; 42%) or the same treatment plus 3 mg of granisetron as a 24-h continuous i.v. infusion (total dose: 6 mg, Treatment B, n = 21; 58%). Depending on the BMT teams, hyperdiuresis was continued (n = 19, 53%) or suspended (n = 17, 47%) during TBI. Nausea and vomiting were assessed during the TBI session and the following 12 h, and were scored as follows: S1 = no nausea or vomiting; S2 = moderate nausea; S3 = severe nausea and/or single episode of vomiting; and S4 = multiple episodes of vomiting. RESULTS: During TBI, 18 (50%) patients were scored as complete responders (S1), 1 (3%) as a major responder (S2), 9 (25%) as minor responders (S3), and 8 (22%) as nonresponders (S4). During the following 12 h, 28 (78%) patients were free of severe nausea and vomiting (S1 or S2), whereas 8 (22%) vomited (S3 or S4). In univariate analyses, the 12-h probability of emesis was significantly higher in patients undergoing hyperdiuresis (63% vs. 30%; p = 0.05), and in patients older than 45 years (65% for age > 45 vs. 33% for age < or = 45; p = 0.05). The probability of S3 or S4 emesis was 50% with Treatment A and 47% with Treatment B (p = 0.86). Sex, body weight, and type of conditioning chemotherapy did not influence the 12-h probability of emesis. Multivariate analysis revealed that hyperdiuresis (p = 0.02) and Treatment A (p = 0.04) were independently associated with radiation-induced emesis, whereas sex (p = 0.85), body weight (p = 0.13), age (p = 0.12), and type of conditioning chemotherapy (p = 0.92) were not. No early toxicity related to granisetron was observed. CONCLUSION: Granisetron is a well-tolerated and effective antiemetic agent that can be used as monotherapy during single-dose TBI. Good control of nausea and vomiting is obtained with this antiemetic drug, and its effect is increased when hyperdiuresis is suspended during TBI.

Remote instrument telemaintenance.

In the past decade, great technological progress has been made in telemaintenance of mainframe and mini computers. As hardware technology is now available at an acceptable cost, computer aided trouble-shooting can be adapted to laboratory instrumentation in order to significantly improve repair time, avoid instrument downtime by taking advantage of predictive methods, and provide general diagnostic assistance. Depending on the size of the instrument, the telemaintenance facility can be dedicated to a single instrument or alternatively a telemaintenance server can manage multiple distributed small instruments through a Local Area Network. As complex failures can occur, the local diagnosis capabilities may be exceeded and automatic dialing for connection to computerized Remote Maintenance Centers is needed. The main advantages of such a centre, as compared to local diagnosis systems, are the increased access to more information and experience of failures from instrument installations, and consequently the provision of training data updates for Artificial Neural Networks and Knowledge Based Systems in general. When an abnormal situation is detected or anticipated by a diagnosis module, an automatic alert is given to the user, local diagnosis is activated, and for simple solutions, instructions are given to the operator. In the last resort, a human expert can be alerted who, with remote control tools, can attend to the failures. For both local and remote trouble-shooting, the data provided by the instrument and connected workstation is of paramount importance for the efficiency and accuracy of the diagnosis. Equally, the importance of standardization of telemaintenance communication protocols is addressed.

Cataractogenesis after total body irradiation.

PURPOSE: To evaluate the prognostic factors and the ophthalmologic follow-up on cataract formation following total body irradiation (TBI) prior to bone marrow transplantation (BMT). METHODS AND MATERIALS: Between 1980 and 1992, 494 patients were referred to our department for TBI prior to BMT. The mean age was 32 +/- 11 (median: 32, range: 2-63) years and the male to female ratio was 1.6 (304:190). The majority of patients were treated for acute leukemia (lymphoblastic, n = 177, 36%; or nonlymphoblastic , n = 139, 28%); 80 (16%) for chronic myeloid leukemia, 60 (12%) for non-Hodgkin's lymphoma, 23 (5%) for multiple myeloma, and 15 (3%) for other malignancies. Two hundred and fifty-four (51%) patients were grafted in the first complete remission (CR), 118 (24%) in second CR. Allogenic BMT was performed in 210 (43%) patients, and autologous BMT in 284 (57%). Methotrexate combined to steroids (n = 47, 22%) or to cyclosporine (n = 163, 78%) was administered for graft-versus-host disease (GvHD) prophylaxis. In 188 patients (38%), heparin was used in the prevention of veno-occlusive disease (VOD) of the liver. Furthermore, steroid administration was registered in 223 (45%). The conditioning chemotherapy consisted of cyclophosphamide (Cy) alone in 332 (67%) patients. Total-body irradiation was administered either in single dose (STBI; 10 Gy in 1 day, n = 291) or in six fractions (FTBI; 12 Gy over 3 consecutive days, n = 203) before BMT. The mean instantaneous dose rate was 0.0574 +/- 0.0289 Gy/min (0.024-0.1783). It was < 0.048 Gy/min in 157 patients (LOW group), > or = 0.048 Gy/min and <0.09 Gy/min in 301 patients (MEDIUM group), and > or = 0.09 Gy/min in 36 patients (HIGH group). RESULTS: When considering all patients, 42 (8.5%) patients developed cataracts after 13 to 72 months (median: 42 months) with a 5-year estimated cataract incidence (ECI) of 23%. Thirty-three (11.3%) out of 291 patients in the STBI group, and 9 (4.4%) out of 203 patients in the FTBI group developed cataracts with 5-year estimated incidences of 34 and 11%, respectively (p = 0.0004). Seven (19.4%) out of 36 patients in the HIGH group, 33 (10.9%) out of 301 in the MEDIUM group, and 2 (1.2%) out of 157 in the LOW group developed cataracts with respective 5-year cataract incidences of 54%, 30%, and 3.5% (HIGH vs. MEDIUM, p = 0.07; MEDIUM vs. LOW, p = 0.0001; HIGH vs. LOW, p < 0.0001). On the other hand, patients who received heparin as prophylactic treatment against VOD of the liver had less cataracts than those who did not receive (5-year ECI of 16% vs. 28%, respectively; p = 0.01). There was no statistically significant difference in terms of 5-year ECI according to age, sex, administration of steroids, GvHD prophylaxis, type of BMT, or previous cranial radiotherapy in children. Multivariate analysis revealed that the instantaneous dose rate (p = 0.001), and the administration of heparin against VOD (p = 0.05) were the two independent factors influencing the cataract incidence, while age, fractionation, and use of steroids were not. Among the 42 patients who developed cataracts, 38 had bilateral extracapsular cataract extraction and intraocular lens implantation, and only 4 (10%) developed secondary cataracts in a median follow-up period of 39 months. CONCLUSION: Among the abovementioned TBI parameters, high instantaneous dose rate seems to be the main risk factor of cataract formation, and the administration of heparin appears to have a protective role in cataractogenesis. On the other hand, ionizing radiation seems to have a protective effect on posterior capsule opacification following extracapsular cataract extraction and intraocular lens implantation.

Possibility of conservative local treatment after combined chemotherapy and preoperative irradiation for locally advanced noninflammatory breast cancer.

PURPOSE: The aims of this prospective study were to evaluate the outcome and the possibility of breast conservation therapy for patients with locally advanced noninflammatory breast cancer after primary chemotherapy followed by external preoperative irradiation. METHODS AND MATERIALS: Between April 1982 and June 1990, 97 patients with locally advanced nonmetastatic and noninflammatory breast cancer were treated. The median follow-up was 93 months from the beginning of treatment. The induction treatment consisted of four courses of chemotherapy (doxorubicin, vincristine, cyclophosphamide, 5-fluorouracil) followed by preoperative irradiation (45 Gy to the breast and nodal areas). A fifth course of chemotherapy was given after irradiation therapy. Three different loco-regional approaches were proposed, depending on the tumoral response. In 37 patients (38%) with residual tumor larger than 3 cm in diameter or located behind the nipple or with bifocal tumors, mastectomy and axillary dissection were performed. Sixty other patients (62%) benefited from conservative treatment: 33 patients (34%) achieved complete remission and no surgery was done but additional radiation boost was given to the initial tumor bed; 27 patients (28%) who had a residual mass less than or equal to 3 cm in diameter were treated by wide excision and axillary dissection followed by a boost to the excision site. After completion of local therapy, all patients received a sixth course of chemotherapy. A maintenance adjuvant chemotherapy regimen without anthracycline was prescribed (12 monthly cycles). RESULTS: The 5-year actuarial loco-regional relapse rate was 16% after radiotherapy alone, 16% following wide excision and radiotherapy, and 5.4% following mastectomy. The 5-year loco-regional relapse rate was significantly higher after conservative local treatment (wide excision and radiotherapy, and radiotherapy alone) than after mastectomy (p= 0.04). After conservative local treatment, the 5-year breast conserving rate of patients with loco-regional disease-free status was 84%. For all patients included in this study, the 5-year breast-conserving rate of those who were loco-regional disease-free was 52%. In multivariate analysis, the possibility of breast conservative treatment was significantly related to the initial tumor size and age (more conservative treatment for tumor size < 6cm and age < 50 years). Five- and 10-year overall survival rates and disease-free survival rates were 80, 69, 73, and 61% respectively. Five- and 10-year overall survival rates were not influenced by the local treatment (conservative vs. nonconservative local treatment, p = 0.9). On the other hand, local failure significantly decreased the 5- and 10-year overall survival rates (p , 0.0001). In multivariate analysis, three factors had a significant impact on overall survival and disease-free survival: tumor response after induction chemotherapy, initial tumor size, and clinical stage. Arm lymphedema was noted in 12.5% (8 out of 64) of the patients treated with axillary dissection and in 3% (1 out of 33) without axillary dissection. Cosmetic results were satisfactory in 79% of patients after wide excision and radiotherapy and in 71% of patients treated by radiotherapy alone. CONCLUSIONS: Induction chemotherapy followed by preoperative irradiation may permit the selection of some patients with locally advanced breast cancer for conservative treatment. However, the impact of this treatment modality on long-term survival remains to be established.

[Radiation injury of the small intestine. Radiobiological, radiopathological aspects; risk factors and prevention]. / Grêle radique. Aspects radiobiologiques et radiopathologiques; facteurs de risque et prévention.

Small bowel radiolesions are a dose-limiting factor in radiotherapy of the abdomen ether administered alone or in combination with surgery and/or chemotherapy. Acute radiolesions on the small intestine are frequent and related to the rapid turnover of mucosal cells. The acute effects of radiation are rapidly regressive after completion of radiation therapy. The reported incidence of severe late chronic radiation injury of the small intestine varies between 0.5 and 15%. Most of chronic injuries occur between 12 and 24 months after radiation. Chronic radiation enteropathy is related to the low turnover of the intestinal wall tissues. It is characterized by progressive cell depletion, collagen fibrosis and obliterative vascular injury. The main factors predisposing to late small bowel complications are: the total radiation dose, the dose per fraction, the volume of small bowel irradiated, previous surgery, and chemotherapy combined to radiation therapy. The knowledge of the predisposing conditions of chronic small bowel injuries facilitates estimation of late small bowel potential morbidity and allows the proposal of personalised therapeutic adjustments to reduce this risk.

[The first century of radiotherapy in France]. / Le premier siècle de la radiothérapie en France.

The first X-ray treatment ever given to a patient was done by Victor Despeignes of Lyon, five months after Roentgen's discovery. The first brachytherapies with radium emanation (radon) were performed a few years after the discovery (March 1st, 1896) of natural radioactivity by Becquerel and that of radium by the Curies (December 28, 1898). Marie Curie organised the Radium Institute and personally calibrated more than five thousand sources of radium disseminated in various French cancer departments. Bergonie and Tribondeau discovered (1906) the basic laws of tissular radiosensitivity. Since the work of Regaud and Coutard, published in 1925, fractionation has become the widely accepted mode of external radiation therapy. Mallet discovered the Cerenkov effect in 1926 and the Joliot-Curies artificial radioactivity in 1934. After the golden age of 200 kV X-rays and radium applications, the megavoltage era with imported telecobaltherapy units and betatrons began in 1954. Then the first french linear accelerator was manufactured. Recently the national manufacturer of linear accelerators (CGR-MeV) became a branch of General Electric Medical Systems. The French Atomic Energy Commission produces radioactive cobalt, cesium and iridium sources. In France, one century after the discovery of X rays, 326 megavoltage units are operating in 185 cancer centers, 18 university hospital radiotherapy departments, 20 comprehensive cancer centers including the Curie and the Gustave Roussy Institutes, 51 general public hospitals and 96 private clinics for a population of 58 millions inhabitants.

Interstitial pneumonitis following autologous bone-marrow transplantation conditioned with cyclophosphamide and total-body irradiation.

PURPOSE: To assess the influence of different total-body irradiation (TBI) regimens on interstitial pneumonitis (IP), we retrospectively analyzed our clinical data concerning an homogeneous group of patients conditioned with cyclophosphamide (CY) alone and single-dose or fractionated TBI before autologous bone-marrow transplantation (ABMT). METHODS AND MATERIALS: One hundred eighty-six patients with acute nonlymphoblastic leukemia (n = 101), acute lymphoblastic leukemia (n = 62), chronic myeloid leukemia (n = 11), non-Hodgkin's lymphoma (n = 10), and multiple myeloma (n = 2) referred to our department between May 13, 1981 and September 16, 1992, underwent TBI before ABMT. The male-to-female ratio was 123:63 (1.95), and mean and median age was 33 +/- 12 (6-63 years) and 35 years, respectively. Cyclophosphamide alone (60 mg/kg/day on each of 2 successive days) was used as conditioning chemotherapy in all patients. Patients were irradiated according to two techniques: either with single-dose (STBI) (n = 124; 10 Gy administered to the midplane at the level of L4, and 8 Gy to the lungs) or with fractionated (FTBI) (n = 62; 12 Gy in 6 fractions over 3 consecutive days to the midplane at the level of L4, and 9 Gy to the lungs) TBI. The mean instantaneous dose rate was 0.057 +/- 0.0246 Gy/min (0.0264-0.1692 Gy/min). It was < or = 0.048 Gy/min in 48 patients (LOW group), > 0.048 and < or = 0.09 Gy/min in 129 patients (MEDIUM group), and > 0.09 Gy/min in 9 patients (HIGH group). The median follow-up period was 5 years (24-120 months). RESULTS: In January 1994, the 5-year overall (including all causes of death) and disease-free survival (DFS) rates were 50 and 48%, respectively. The 5-year DFS was 47.9% in the STBI group, and 47.8% in the FTBI group (p = 0.77). It was 44% in the HIGH group, 53% in the MEDIUM group, and 34% in the LOW group (LOW vs. MEDIUM, p = 0.009). The 5-year IP incidence was 17% in all patients, 16% in the STBI group and 18% in the FTBI group (p = 0.37), but it was significantly higher in patients receiving high instantaneous dose rate TBI (56% in the HIGH, 13% in the MEDIUM, 20% in the LOW groups; HIGH vs. MEDIUM, p = 0.002). However, sex (p = 0.37), age (18% for > 20 vs. 10% for < or = 20 years, p = 0.37), and body weight (> 60 kg vs. < or = 60 kg, p = 0.09) did not influence the IP incidence in univariate analyses. Multivariate analysis (Cox model) revealed that the instantaneous dose rate (p = 0.05), and the age (p = 0.04) were the two independent factors influencing the incidence of IP. CONCLUSION: This retrospective study including only the patients transplanted with ABMT conditioned with CY alone and STBI or FTBI concluded that instantaneous dose rate and age significantly influenced the incidence of IP, whereas sex, body weight, and fractionation did not.

Is veno-occlusive disease incidence influenced by the total-body irradiation technique?

BACKGROUND: In order to assess the influence of total-body irradiation technique on veno-occlusive disease (VOD) incidence, we retrospectively analyzed our leukemia patients treated with bone-marrow transplantation conditioned using total-body irradiation and high-dose chemotherapy. PATIENTS AND METHODS: Between 1980 and 1992, 305 patients with acute non-lymphoblastic leukemia (ANLL; n = 170) and acute lymphoblastic leukemia (ALL; n = 135) were treated with bone-marrow transplantation in their first complete remission (CR; n = 223) or in second CR (n = 82). All patients underwent total-body irradiation either in single dose (n = 176; 10 Gy to L4, 8 Gy to the lungs) or in 6 fractions (n = 129; 12 Gy in 3 consecutive days to L4, 9 Gy to the lungs) before bone-marrow transplantation. Patients were analyzed in 2 instantaneous dose rate groups: 104 (34%) patients received an instantaneous dose rate < or = 4.80 cGy/min (mean: 3.07 +/- 0.60 cGy/min), and 201 (66%) > 4.80 cGy/min (mean: 6.60 cGy/min +/- 0.30). Conditioning chemotherapy consisted of cyclophosphamide alone in 231 patients, cyclophosphamide and etoposide or melphalan in 53 patients, and 21 patients were conditioned with cytosine arabinoside and melphalan. Bone-marrow transplantation was autologous in 197 patients, and allogeneic in 108 patients. RESULTS: Thirty (10%) of the 305 patients experienced VOD. In univariate analyses, its incidence was not influenced by instantaneous dose rate (9.6% [10/104] in < or = 4.80 cGy/min group vs. 10% [20/201] in > 4.80 cGy/min group; p = 0.91), fractionation (11% [19/176] in single-dose total-body irradiation vs. 8.5% [11/129] in fractionated total-body irradiation, p = 0.64), age (9% [21/241] in < or = 40-year old-patients vs. 14% [9/64] in > 40-year-old patients, p = 0.29), sex (6% [7/113] in male patients vs. 12% [23/192] in female patients, p = 0.15), type of VOD prevention (16% [16/101] in patients using heparin vs. 10% [14/142] in those receiving dinoprostone and pentoxifylline combination, p = 0.23), type of bone-marrow transplantation (9% [10/108] in allogeneic bone-marrow transplantation group vs. 10% [20/197] in autologous bone-marrow transplantation group, p = 0.96), or type of acute leukemia (9.6% [13/135] in ALL vs. 10% [17/170] in ANLL, p = 0.93). However, VOD incidence was significantly lower in patients whose conditioning chemotherapy consisted of cyclophosphamide alone (6.5% [15/231] vs. 20% [15/74] by other drugs +/- cyclophosphamide, p < 0.0001), and in patients treated after 1985 (7% [16/226] vs. 18% [14/79] in those treated before 1985, p = 0.01). Multivariate logistic regression analysis revealed that the best independent factors influencing the occurrence of VOD were the male sex (p = 0.03), conditioning chemotherapy consisting of cyclophosphamide alone (p = 0.01), and bone-marrow transplantation after 1985 (p = 0.008). CONCLUSION: In our series of 305 acute leukemia patients treated with allogenic or autologous bone-marrow transplantation, total-body irradiation technique (fractionation or instantaneous dose rate) did not seem to influence the incidence of VOD.

Epidermoid carcinoma of the anal margin: 17 cases treated with curative-intent radiation therapy.

Between 1973 and 1991, 17 patients with epidermoid carcinoma of the anal margin without evidence of distant metastasis were treated with curative-intent radiation therapy (RT). There were nine T1-tumors, six T2-, one T3- and one T4-tumor; two patients presented with inguinal node involvement: one N1 and one N3. Nine patients underwent prior incomplete local excision (six with microscopic involvement of surgical margins and two with macroscopic residual disease). The radiation dose to the tumor was 60-70 Gy; the radiation dose to the inguinal lymph nodes was 40-45 Gy in N0, and 50-60 Gy for involved inguinal nodes. The 5- and 10-year cancer-specific survival rates were 86.2% and 77.5%, respectively. The same probabilities were 100% and 100% for T1-tumors, 60% and 40% for T2-tumors. Severe complications occurred in two patients, one anal radionecrosis requiring a colostomy and one permanent anal incontinence after local excision, which was non-related to irradiation. For the cured patients, the sphincter preservation rate after 5 years was 82% (9/11). In univariate analysis and in Cox multivariate analysis, the cancer-specific survival rate was influenced by one factor: the tumor size.

[Which equipment for proton therapy of the future?]. / Quel appareillage pour la protonthérapie de demain?

The success of proton therapy depends on its cost. Hospital based equipment in fabrication for the Massachusetts General Hospital in Boston costs in the excess of 17 millions dollars, the accelerator being only a fraction of the cost. We think that price can be significantly decreased. We review the different new ways of accelerating protons currently under study in France in order to build a smaller, less expensive but reliable treatment device.

Synchronous and metachronous head and neck carcinomas.

BACKGROUND: The incidence of head and neck cancer is increasing. To improve the survival of head and neck cancer patients, an effective program of screening and/or chemoprevention of second malignancies is essential. An analysis of the incidence, time to development, and risk factors of second malignant tumors in head and neck cancer patients can contribute to the design of effective screening and chemoprevention programs. METHODS: Eight hundred, fifty-one patients with initial squamous cell carcinoma of the larynx (n = 224), tonsils (n = 189), pyriform sinus (n = 165), oral cavity (n = 129), mobile tongue (n = 72), and base of tongue (n = 72) treated from 1978 to 1990 were analyzed for the presence of a second malignancy after initial therapy. Of these 851 patients, 544 (64%) were documented smokers and 35 (4%) were nonsmokers. No smoking information was available for 272 patients. Four hundred, fifty-four patients (53%) were consumers of alcohol and 64 patients (8%) were nondrinkers. Alcohol consumption information was not available for 333 patients. RESULTS: One hundred, sixty-two (19%) second head and neck carcinomas occurred in the original 851 patients. Sixty-six patients (41%) had synchronous tumors, and 96 patients (59%) had metachronous tumors. The probability of developing a second metachronous cancer 5-years after undergoing treatment for the initial head and neck cancer was 22%. Borderline statistical significance was observed in the 5-year second cancer incidence based on the site of the initial primary cancer (46% for the base of tongue, 34% for the pyriform sinus, 23% for the larynx, 18% for the oral cavity, 15% for the tonsils, and 10% for the mobile tongue). Tobacco smoking (3% for nonsmokers vs. 26% for < or = 20 pack-years vs. 42% for > 20 and < or = 40 packs/year vs. 30% for > 40 packs/year of smoking) and the consumption of alcohol (5% for non-drinkers vs. 32% for drinkers) were both statistically significant in predicting the likelihood of developing a second malignancy. Multivariate analysis revealed that the two independent variables that influenced the occurrence of a second metachronous cancer were the anatomic site of the original primary cancer and patient age. The survival rate after the second cancer was influenced significantly by the site of the second cancer (20% for a second head or neck cancer, 3% for a second esophageal cancer, and 2% for a second lung cancer). Continued smoking (20% for non-smokers vs. 5% for smokers) and continued alcohol consumption (27% for nondrinkers vs. 6% for drinkers) also adversely influenced the survival after the occurrence of a second cancer. CONCLUSIONS: This study confirms the high rate of second cancers in patients with initial head and neck malignancies. The development of a second malignancy is almost always fatal. Screening programs and chemoprevention trials should be directed toward cancer patients with initial head and neck cancers. Only the small subset of nonsmokers and nondrinkers should be excluded from such trials.