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Purpose: The Lyon R90-01 randomized trial investigated whether the interval between preoperative radiation therapy and surgery influenced rectal cancer outcome. Long-term results are reported here after a median follow-up of 17 years., Methods and Materials: Between February 1991 and December 1995, 210 patients from 29 French centers were randomly assigned (ratio of 1:1) to groups that waited either 2 weeks (short interval [SI]) or 6 to 8 weeks (long interval [LI]) between neoadjuvant radiation therapy and surgery. The primary endpoint was sphincter-preserving surgery., Results: LI group showed a better pathologic response (complete response or few residual cells) after radiation therapy than the SI group (26% vs 10.3%, P=.015). A better pathologic response was associated in multivariate analysis with significant improvement of overall survival (pT: P=.0293 and pN: P=.0048) but it was irrespective of the interval duration. The median follow-up was 17.2 years. The 5-, 10-, 15-, and 17-year overall survival rates were, respectively, 66.8%, 48.7%, 40.0%, and 34.0% for the SI group and, respectively, 67.1%, 53.5%, 41.9%, and 34.0% for the LI group. There were no significant differences between groups in terms of survival (P=.7656) or local recurrence rates (SI: 14.4% vs LI: 12.1%, respectively; P=.6202). Of 24 local disease recurrences, 20 (83%) occurred during the first 2 postoperative years, and all but one (96%) occurred during the first 5 postoperative years. The rate of second new malignancies was 9.4% (19 patients)., Conclusions: The radiation-induced sterilization rate of the preoperative cancer specimen was a marker of good prognosis. The interval duration (the treatment being the same) although it is modifying the sterilization rate has no impact on survival. Radiation therapy did not postpone local recurrence, because the rate of local relapse after 5 years was low. Radiation-induced cancers after radiation therapy were unusual and should not influence treatment decisions in adults., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the efficacy of irradiation of internal mammary nodes (IMN) on 10-year overall survival in breast cancer patients after mastectomy., Methods and Patients: This multicenter phase 3 study enrolled patients with positive axillary nodes (pN+) or central/medial tumors with or without pN+. Other inclusion criteria were age <75 and a Karnofsky index ≥70. All patients received postoperative irradiation of the chest wall and supraclavicular nodes and were randomly assigned to receive IMN irradiation or not. Randomization was stratified by tumor location (medial/central or lateral), axillary lymph node status, and adjuvant therapy (chemotherapy vs no chemotherapy). The prescribed dose of irradiation to the target volumes was 50 Gy or equivalent. The first 5 intercostal spaces were included in the IMN target volume, and two-thirds of the dose (31.5 Gy) was given by electrons. The primary outcome was overall survival at 10 years. Disease-free survival and toxicity were secondary outcomes., Results: T total of 1334 patients were analyzed after a median follow-up of 11.3 years among the survivors. No benefit of IMN irradiation on the overall survival could be demonstrated: the 10-year overall survival was 59.3% in the IMN-nonirradiated group versus 62.6% in the IMN-irradiated group (P=.8). According to stratification factors, we defined 6 subgroups (medial/central or lateral tumor, pN0 [only for medial/central] or pN+, and chemotherapy or not). In all these subgroups, IMN irradiation did not significantly improve overall survival., Conclusions: In patients treated with 2-dimensional techniques, we failed to demonstrate a survival benefit for IMN irradiation. This study cannot rule out a moderate benefit, especially with more modern, conformal techniques applied to a higher risk population., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To investigate, in rectal cancer, the benefit of a neoadjuvant radiation dose escalation with endocavitary contact radiotherapy (CXRT) in addition to external beam radiotherapy (EBRT). This article provides an update of the Lyon R96-02 Phase III trial., Methods and Materials: A total of 88 patients with T2 to T3 carcinoma of the lower rectum were randomly assigned to neoadjuvant EBRT 39 Gy in 13 fractions (43 patients) vs. the same EBRT with CXRT boost, 85 Gy in three fractions (45 patients). Median follow-up was 132 months., Results: The 10-year cumulated rate of permanent colostomy (CRPC) was 63% in the EBRT group vs. 29% in the EBRT+CXRT group (p < 0.001). The 10-year rate of local recurrence was 15% vs. 10% (p = 0.69); 10-year disease-free survival was 54% vs. 53% (p = 0.99); and 10-year overall survival was 56% vs. 55% (p = 0.85). Data of clinical response (CR) were available for 78 patients (36 in the EBRT group and 42 in the EBRT+CXRT group): 12 patients were in complete CR (1 patient vs. 11 patients), 53 patients had a CR ≥ 50% (24 patients vs. 29 patients), and 13 patients had a CR <50% (11 patients vs. 2 patients) (p < 0.001). Of the 65 patients with CR ≥ 50%, 9 had an organ preservation procedure (meaning no rectal resection) taking advantage of major CR. The 10-year CRPC was 17% for patients with complete CR, 42% for patients with CR ≥ 50%, and 77% for patients with CR <50% (p = 0.014)., Conclusion: In cancer of the lower rectum, CXRT increases the complete CR, turning in a significantly higher rate of long-term permanent sphincter and organ preservation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the benefit of prophylactic inguinal irradiation (PII) in anal canal squamous cell carcinoma (ASCC)., Methods and Materials: This retrospective study analyzed the outcome of 208 patients presenting with ASCC treated between 2000 and 2004 in four cancer centers of the south of France., Results: The population study included 35 T1, 86 T2, 59 T3, 20 T4, and 8 T stage unknown patients. Twenty-seven patients presented with macroscopic inguinal node involvement. Of the 181 patients with uninvolved nodes at presentation, 75 received a PII to a total dose of 45-50 Gy (PII group) and 106 did not receive PII (no PII group). Compared with the no PII group, patients in the PII group were younger (60% vs. 41% of patients age <68 years, p = 0.01) and had larger tumor (T3-4 = 46% vs. 27% p = 0.01). The other characteristics were well balanced between the two groups. Median follow-up was 61 months. Fourteen patients in the no PII group vs. 1 patient in the PII group developed inguinal recurrence. The 5-year cumulative rate of inguinal recurrence (CRIR) was 2% and 16% in PII and no PII group respectively (p = 0.006). In the no PII group, the 5-year CRIR was 12% and 30% for T1-T2 and T3-T4 respectively (p = 0.02). Overall survival, disease-specific survival, and disease-free survival were similar between the two groups. In the PII group, no Grade >2 toxicity of the lower extremity was observed., Conclusion: PII with a dose of 45 Gy is safe and highly efficient to prevent inguinal recurrence and should be recommended for all T3-4 tumors. For early-stage tumors, PII should also be discussed, because the 5-year inguinal recurrence risk remains substantial when omitting PII (about 10%)., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To retrospectively assess the clinical outcome in anal cancer patients treated with split-course radiation therapy and boosted through external-beam radiation therapy (EBRT) or brachytherapy (BCT)., Methods and Materials: From January 2000 to December 2004, a selected group (162 patients) with invasive nonmetastatic anal squamous cell carcinoma was studied. Tumor staging reported was T1 = 31 patients (19%), T2 = 77 patients (48%), T3 = 42 patients (26%), and T4= 12 patients (7%). Lymph node status was N0-1 (86%) and N2-3 (14%). Patients underwent a first course of EBRT: mean dose 45.1 Gy (range, 39.5-50) followed by a boost: mean dose 17.9 Gy (range, 8-25) using EBRT (76 patients, 47%) or BCT (86 patients, 53%). All characteristics of patients and tumors were well balanced between the BCT and EBRT groups., Results: The mean overall treatment time (OTT) was 82 days (range, 45-143) and 67 days (range, 37-128) for the EBRT and BCT groups, respectively (p < 0.001). The median follow-up was 62 months (range, 2-108). The 5-year cumulative rate of local recurrence (CRLR) was 21%. In the univariate analysis, the prognostic factors for CRLR were as follows: T stage (T1-2 = 15% vs. T3-4 = 36%, p = 0.03), boost technique (BCT = 12% vs. EBRT = 33%, p = 0.002) and OTT (OTT <80 days = 14%, OTT ≥80 days = 34%, p = 0.005). In the multivariate analysis, BCT boost was the unique prognostic factor (hazard ratio = 0.62 (0.41-0.92). In the subgroup of patients with OTT <80 days, the 5-year CRLR was significantly increased with the BCT boost (BC = 9% vs. EBRT = 28%, p = 0.03). In the case of OTT ≥80 days, the 5-year CRLR was not affected by the boost technique (BCT = 29% vs. EBRT = 38%, p = 0.21)., Conclusion: In anal cancer, when OTT is <80 days, BCT boost is superior to EBRT boost for CRLR. These results suggest investigating the benefit of BCT boost in prospective trials., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: The mathematical relationship between the dose to the parotid glands and salivary gland production needs to be elucidated. This study, which included data from patients included in a French prospective study assessing the benefit of intensity-modulated radiotherapy (RT), sought to elaborate a convenient and original model of salivary recovery., Methods and Materials: Between January 2001 and December 2004, 44 patients were included (35 with oropharyngeal and 9 with nasopharyngeal cancer). Of the 44 patients, 24 were treated with intensity-modulated RT, 17 with three-dimensional conformal RT, and 2 with two-dimensional RT. Stimulated salivary production was collected for 40 Gy., Conclusion: The results of this study show that the recommendation of a dose constraint for intensity-modulated RT planning should be established at the volume of the contralateral parotid gland receiving >40 Gy rather than the mean dose. For complete salivary production recovery after 24 months, the volume of the contralateral parotid gland receiving >40 Gy should be <33%. Our results permitted us to establish two convenient tools to predict the saliva production recovery function according to the dose received by the contralateral parotid gland.

Purpose: To evaluate whether the tumor response after an initial course of irradiation predicts for colostomy-free survival and overall survival in patients with anal canal cancer., Methods and Materials: Between 1980 and 1998, 252 patients were treated by pelvic external-beam radiotherapy (EBRT) followed by a brachytherapy boost in 218 or EBRT in 34. EBRT was combined with chemotherapy in 168 patients. An evaluation of tumor regression, before the boost, was available for 221 patients. They were divided into four groups according to the tumor response: <70%, 70-80%, >80% but <100%, and 100%., Results: The median follow-up time was 58 months. The overall survival rate was 72.6% +/- 3.1% and 57.3% +/- 4.2% at 5 and 10 years, respectively. The disease-free survival rate was 60.0% +/- 3.3% and 49.4% +/- 3.9% at 5 and 10 years, respectively. The colostomy-free survival rate was 61% at 5 years and 47% at 10 years. Two groups could be differentiated according to the percentage of tumor regression before the boost: >80% vs. < or = 80%. The group with a T3-T4 lesion and tumor regression < or = 80% had the poorest overall (52.8% +/- 12.3%), disease-free (19.9% +/- 9.9%), and colostomy-free survival (24.8% +/- 11.2%) rates., Conclusion: The amount of tumor regression before EBRT or brachytherapy boost is a strong prognostic factor of disease control without colostomy. When regression is < or = 80% in patients with an initial T3-T4 lesion, the use of conservative RT should be carefully evaluated because of the very poor disease-free and colostomy-free survival.

Purpose: To investigate the clinical history, management, and pattern of recurrence of very early-stage anal canal cancer in a French retrospective survey., Methods: The study group consisted of 69 patients with Stage Tis and T1 anal canal carcinoma < or =1 cm treated between 1990 and 2000 (12 were in situ, 57 invasive, 66 Stage N0, and 3 Stage N1). The median patient age was 67 years (range, 27-83 years). Of the 69 patients, 66 received radiotherapy (RT) and 3 with in situ disease were treated by local excision alone without RT. Twenty-six patients underwent local excision before RT (12 with negative and 14 with positive surgical margins). Of the 66 patients who underwent RT, 8 underwent brachytherapy alone (median dose, 55 Gy), 38 underwent external beam RT (median dose, 45 Gy) plus a brachytherapy boost (median boost dose, 20 Gy), and 20 underwent external beam RT alone (median dose, 55 Gy)., Results: Of the 69 patients, 68 had initial local control. Of the 66 patients treated by RT, 6 developed local recurrence at a median interval of 50 months (range, 13-78 months). Four patients developed local failure outside the initial tumor bed. Of the 3 patients with Tis treated by excision alone, 1 developed local recurrence. No relation was found among prior excision, dose, and local failure. The 5-year overall survival, colostomy-free survival, and disease-free survival rate was 94%, 85%, and 89%, respectively. The rate of late complications (Grade 1-3) was 28% and was 14% for those who received doses <60 Gy and 37% for those who received doses of > or =60 Gy (p = 0.04)., Conclusion: Most recurrences occurred after a long disease-free interval after treatment and often outside the initial tumor site. These small anal cancers could be treated by RT using a small volume and moderate dose (40-50 Gy for subclinical lesions and 50-60 Gy for T1).

Purpose: This retrospective 12-year study evaluated the prognostic value of initial and postoperative staging of rectal tumors., Methods and Materials: Between 1985 and 1996, 297 patients were treated with preoperative radiotherapy (39 Gy in 13 fractions) and surgery for Stage T2-T4N0-N1M0 rectal adenocarcinoma. Pretreatment staging included a clinical examination and endorectal ultrasonography (EUS) since 1988. Clinical staging was performed by digital rectal examination and rigid proctoscopy. EUS was performed in 236 patients. Postoperative staging was performed by examination of the pathologic specimen., Results: The median follow-up was 49 months. The overall 5-year survival rate was 67%, with a local failure rate of 9%. The rate of sphincter preservation was 65%. The clinical examination findings were strong prognostic factor for both cT stage (p < 0.001) and cN stage (p < 0.006) but had poor specificity for cN stage (only 25 lymph nodes detected). In both univariate and multivariate analyses, EUS had a statistically significant prognostic value for uT (p < 0.014) but not for uN (p < 0.47) stage. In contrast, pT and pN stages were strong prognostic factors (p < 0.001 and p < 0.001, respectively)., Conclusion: Pretreatment staging, including clinical examination and EUS, seemed accurate enough to present a high prognostic value for the T stage. EUS was insufficient to stage lymph node involvement. Owing to its lack of specificity, uN stage was not a reliable prognostic factor. An improvement in N staging is necessary and essential. Despite downstaging, postoperative staging remained a very strong prognostic factor for both T and N stages.

Purpose: To analyze the long-term result of patients presenting with T2-T3 rectal adenocarcinoma treated with curative intent by radiotherapy (RT) alone, using a combination of contact RT, external beam RT, and brachytherapy with an iridium implant. Patients were considered unsuitable for surgery because of the presence of severe comorbidity or because they did not consent to surgery and the possibility of a permanent stoma., Methods and Materials: Between 1986 and 1998, 63 patients (56 staged with endorectal ultrasonography) were entered into a pilot study. Patients had to have T2-T3, N0-N1, M0 adenocarcinoma of the middle or lower rectum involving less than two-thirds of the circumference. RT began with contact X-rays (80 Gy in 3 fractions for 21 days), followed by external beam RT (39 Gy in 13 fractions for 17 days) with a concomitant boost (4 Gy in 4 fractions). After a 4-6-week interval, an iridium implant delivered a completion dose of 20 Gy to the tumor. No chemotherapy was given., Results: The median age of the patients was 72 years. Of the 63 patients, 41 had T2 and 22 had T3 tumors. The mean distance of the tumor from the anal verge was 3.6 cm. All patients completed treatment according to the protocol, except for 7 for whom brachytherapy was not performed. With a median follow-up time of 54 months, the primary local tumor control rate was 63%; after salvage surgery, the ultimate pelvic control was 73% (46 of 63). The 5-year overall survival rate was 64.4%, and for 42 patients aged <80 years, it was 78% with 10 patients alive and well at > or =10 years. No severe Grade 3-4 toxicity was seen. Acute proctitis was seen in most patients but did not require treatment interruption. Late rectal bleeding occurred in 24 patients. Only 1 required blood transfusion. Good anorectal function was maintained in 92% of living patients. The T stage was a strong prognostic factor, with a 5-year overall survival rate of 84% and 53% for T2 and T3 lesions, respectively, in patients <80 years old., Conclusion: This is the first report of long-term local control and survival for ultrasound-staged T2-T3 rectal adenocarcinoma treated by RT alone, showing that high-dose irradiation to a small volume can provide a high therapeutic ratio for such tumors.

Purpose: By using as an experimental model the male mouse gonad, which contains both radiosensitive (germ) and radioresistant (somatic) cells, we have studied the growth factor (and/or receptor) expression of transforming growth factor-beta receptor (TGFbeta RI), stem cell factor (SCF), c-kit, Fas-L, Fas, tumor necrosis factor receptor (TNF R55), and leukemia inhibiting factor receptor (LIF-R) after local irradiation., Methods and Materials: Adult male mice were locally irradiated on the testes. Induction of apoptosis in the different testicular cell types following X-ray radiation was identified by the TdT-mediated dUTP Nick End Labeling (TUNEL) approach. Growth factor expression was evidenced by semiquantitative RT-PCR and Western blot analyses., Results: Apoptosis, identified through the TUNEL approach, occurred in radiosensitive testicular (premeotic) germ cells with the following kinetics: the number of apoptotic cells increased after 24 h (p < 0.001) and was maximal 48 h after a 2-Gy ionizing radiation (p < 0.001). Apoptotic cells were no longer observed 72 h after a 2-Gy irradiation. The number of apoptotic cells increased with the dose of irradiation (1-4 Gy). In the seminiferous tubules, the growth factor expression in premeiotic radiosensitive germ cells was modulated by irradiation. Indeed Fas, c-kit, and LIF-R expression, which occurs in (radiosensitive) germ cells, decreased 24 h after a 2-Gy irradiation, and the maximal decrease was observed with a 4-Gy irradiation. The decrease in Stra8 expression occurred earlier, at 4 h after a 2-Gy irradiation. In addition, a significant (p < 0.03) decrease in Stra8 mRNA levels was observed at the lowest dose used (0.5 Gy, 48 h). Moreover, concerning a growth factor receptor, such as TGFbeta RI, which is expressed both in radiosensitive and radioresistant cells, we observed a differential expression depending on the cell radiosensitivity after irradiation. Indeed, TGFbeta RI expression was increased after irradiation in interstitial radioresistant testicular cells in a dose- and time-dependent manner, while it decreased in seminiferous radiosensitive (germ cells) testicular cells. Such a differential expression between radioresistant and radiosensitive cells in TGFbeta RI levels was observed in terms of both mRNA and protein. In contrast, the growth factors specifically expressed in the somatic radioresistant (Sertoli) cells in the seminiferous tubules (SCF, Fas-L, TNF R55) were not affected by ionizing radiation (up to 4 Gy, 72 h)., Conclusion: Growth factor expression decreased in the radiosensitive testicular cells after irradiation. Such a decrease occurred before the detection of apoptosis using the TUNEL approach. TGFbeta RI mRNA levels decreased in the radiosensitive cells, whereas it increased in the radioresistant cells, suggesting that TGFbeta RI may represent a biomarker of the intrinsic radiosensitivity of cells.

Purpose: To describe the results of a series of 63 Western patients presenting with gastric adenocarcinoma and treated with surgery and intraoperative radiation therapy (IORT) over a 8-year period and to discuss the role of IORT when combined with limited lymph node dissection., Methods and Materials: From 1986 to 1993, 63 patients with gastric adenocarcinoma have been operated in the department of radiation oncology of the Hospices Civils de Lyon. The stage was: I in 17, II in 11, IIIA in 9, IIIB in 20, and IV in 6. The lymph node dissection was considered to be limited in 56 patients and extended in 7. The IORT dose ranged from 12 to 23 Gy (median: 15). Thirty patients also underwent a postoperative external beam irradiation with a standard dose of 44-46 Gy., Results: The postoperative mortality rate was 4.8%. The 5-year overall survival in the entire series was 47% and was 82, 55, 78, 20, and 0% in Stages I, II, IIIA, IIIB, and IV, respectively. Loco-regional relapse occurred in 15 of 63 patients and metastases in 15 of 63., Conclusion: In Western patients treated by gastrectomy for adenocarcinoma of the stomach, IORT combined with limited lymph node dissection may provide overall survival similar to that observed after gastrectomy with extended lymph node dissection but with less postoperative mortality.

Purpose: Radiotherapy is the standard treatment of anal canal carcinoma. We retrospectively analyzed our experience with 108 patients. Special attention was given in evaluating 51 patients who received concomitant chemotherapy with 5-FU-CDDP., Methods and Materials: From January 1980 to December 1989, 108 patients with anal canal carcinoma were treated with exclusive radiotherapy at the Centre Hospitalier Lyon Sud. There were 11 men and 97 women, mean age was 65 years (30-86). Histologic types were 94 epidermoid carcinomas, 13 basaloid carcinomas, and one adenocarcinoma. The TNM classification (UICC 87) was: 16 T1 (14.8%), 53 T2 (49%), 33 T3 (39.5%), six T4 (5.5%), 77 N0 (71.3%), 20 N1 (18.5%), nine N2 (8.3%) and two N3 (1.8%). Papillon's radiotherapy technique with a Cobalt direct perineal field was used in 82 patients. Ninety-six patients were treated with an interstitial 192Ir implant with a mean delay of 55 days after the end of the radiotherapy. In 59 patients at least one course of either 5-FU-mitomycin (8) or 5-FU-CDDP was added with at least one course concomitantly to the radiotherapy in 53 patients., Results: A complete response in 104/108 patients (96%) was obtained 2 months after the brachytherapy. A locoregional relapse (local and/or pelvic failure) was seen in 18 patients (16.6%) and inguinal node relapse in nine (8.3%). Eight patients with locoregional recurrence and five with inguinal relapse were salvaged. A systemic failure occurred in six (5.5%) patients. Twenty-nine patients died, 16 of progressive disease. One patient died of treatment related toxicity. The overall 5-year survival was 64% +/- 6 and specific survival 72% +/- 8. None of the patient parameters was found to be statistically significant but there was a trend toward longer 5-year survival in T1-T2 patients and in those with well or moderately differentiated tumors. Noteworthy are the same survival rates for N0 and N1-N3 patients (65 vs. 62%). The objective response and the locoregional failure rates were similar in the patients treated with or without chemotherapy. The difference did not reach statistical significance though it was important for the following parameters: overall survival rates for T1-T2 with and without chemotherapy (94 vs. 61%) and for N1-3 patients (73% vs. 27%). The main prognostic factors in this series were differentiation (5-year overall survival with chemotherapy 95% vs. 27% without chemotherapy p = 0.02) and the response at 3 months after treatment initiation, before brachytherapy implant (5-year overall survival for complete responders and "very good responders" 71% vs. 34% in partial responders p = 0.002). The complications rate was acceptable (Grade III 9%, Grade II 14%). Anal preservation was possible in 85% of the patients (92/108). Nine abdominoperineal resection were performed for recurrence and seven for severe necrosis. The T3-T4 group abdomino perineal resection was 23% while it was 9.2% of the T1-T2 group., Conclusion: We confirm that exclusive radiotherapy is the treatment of choice for epidermoid carcinomas of the anal canal. The role of chemotherapy is still unclear.

Twenty-four patients with T1 or T2 (17 T1 N0, 7 T2 N0 not exceeding 3 cm) epidermoid carcinomas from the middle third of the mobile tongue benefit from brachytherapy with "cavaliers-legos" consisting of guide-gutters that are inserted in a rigid support (legos) and covered with a lead plate. Several advantages can be advocated with this technique: easy implantation even with local anaesthetic, no risk of bleeding, good parallelism between Iridium wires, protection of the mandible with the lead plate. Local control was achieved in 22/24 patients (92%). Four patients (16%) developed soft tissue necrosis but only one required surgical intervention and no mandibular necrosis was seen.

Interstitial irradiation is a technique currently used in the treatment of bladder cancer. We report the data on 205 patients (177 men and 28 women) treated in eight French centers. The patients had received the following treatment: a short course of pre-operative pelvic irradiation, followed by surgery consisting of partial cystectomy or tumor resection, and implantation of plastic tubes filled with inactive lead wires, which were replaced by iridium 192 wires. The tumor characteristics were: transitional cell carcinoma, 88.8%; mean size of the tumor, 29 mm; pathological stages: pTis, 1; pT1, 98; pT2, 66; pT3a, 26; pT3b, 9; pT4, 1; unknown, 4 respectively; surgical lymph node status: N+, 3; N-, 118; no node dissection, 84. The mean follow-up was 51 months. Intravesical failures were seen in 35 patients (17.0%), 25 (71.4%) of them without metastases or regional recurrences. Twenty-one patients (10.2%) presented distant metastases, 2/3 of them suffered no bladder relapse. The 5-year survival, calculated according to the Kaplan-Meier method (all causes of death taken together) was 77.4% for the T1, 62.9% for the T2, and 46.8% for the T3. Fifty-three patients had immediate side-effects and three died from surgical complications. Twenty-nine patients had delayed bladder side-effects (haematuria, fistula, chronic cystitis). Six patients presented an ureteral stenosis. Of the disease-free survivors, 96.1% retained the bladder function. Three factors were significantly predictive of delayed side-effects: partial cystectomy, pre-operative radiotherapy total dose, and linear activity of the wires (p < 0.01). Comparing our results to different authors' series interstitial irradiation is likely to provide a high local and general control of the disease and good quality of life in patients with selected tumors.

Conservative treatment has become a valid alternative to radical surgery in most cases of cancer of the anal canal and in selected cases of cancer of the low rectum. In this strategy interstitial curietherapy has an appreciable role to play. The results of a series of 369 patients followed more than 3 years indicate that implantation of Iridium-192 is effective not as sole treatment but as a booster dose 2 months after a course of external beam or intracavitary irradiation. The dose delivered did not exceed 20 to 30 Gy and the implantations were always performed in one plane using either a plastic template or a steel fork. Three groups of cases must be considered: (a) among 221 patients with epidermoid carcinoma of the anal canal, the rate of death related to treatment failures was 20% and among the patients cured more than 90% retained normal sphincter function. (b) In 90 patients with T1-T2 invasive adenocarcinoma of the rectum, Iridium-192 was carried out after four applications of contact X ray therapy. The rate of control was 84%. (c) In 62 elderly, poor risk patients with T2-T3 tumor of the low rectum initially suitable for an abdomino-perineal resection, a tentative extension of the field of conservation was made using a split-course protocol combining a short course of external beam irradiation at a dose of 30-35 Gy in 10 fractions over 12 days and an Iridium-192 implant. The rate of death due to treatment failures was 14.5% and among the patients controlled 97% had a normal anal function. These results show that implantations of Iridium-192 may contribute to the control of anal and rectal cancers and may spare many patients a permanent colostomy, but the treatment requires great care in patient selection, treatment protocol, technical details, and follow-up. This treatment policy must be conceived as a team work of radiation oncologists and surgeons.