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Purpose In 1998 a translational research was initiated in Lyon aiming at identifying a prognostic “biomolecular signature” in rectal cancer. This paper presents the clinical outcome of the patients included in this study. Patients and methods A total of 94 patients were included between 1998 and 2001. A staging with rectoscopy and biopsies was performed before treatment. In case of surgery, the operative specimen was analysed to evaluate the pathological response. There were two types of treatment: neoadjuvant radiotherapy (with or without concurrent chemotherapy) followed by surgery (76 cases) and radiotherapy alone with ‘contactherapy’ often associated with external beam radiotherapy (18 patients). Results The patients had a mean age of 63 years. Stage was T1: 4, T2: 24, T3: 65 and T4: 1. The overall survival of the 94 patients was 62% at 8 years with a rate of distant metastases of 29%. Rate of local recurrence at 8 years was 6% in the neoadjuvant group and 16% in the radiotherapy group with an overall 8 years survival in both groups respectively: 64% and 53%. There was a trend towards more metastases in cT3, tumour diameter above 4 cm, circumferential extension. There was a significant increase in the risk of metastases for ypT3, ypN1-2 and Dworak score 1-2-3. In multivariate analysis ypT3 was significantly associated with a high rate of metastases (55%; P = 0.0003). Conclusion The rate of distant metastases is a major prognostic factor. These clinical results will serve as the base line to identify a “biomolecular signature” which could complement the TN(M) classification.

A differential responsiveness of patients to ionizing radiation is observed after preoperative radiotherapy for rectal adenocarcinoma that might be related, in part, to an apoptosis defect. To establish if proteins of the apoptotic cascades [pro-apoptotic: active caspase 3, 8, and 9 and DIABLO (direct inhibitor of apoptosis-binding protein with low pI); anti-apoptotic: XIAP (X-linked inhibitor of apoptosis)] are involved, we analyzed their profile in radioresistant (SW480) and radiosensitive (SW48) human colorectal cell lines. We demonstrated that, after irradiation, the SW48 cells increased the expression of the pro-apoptotic proteins, whereas the SW480 cells increased the expression of the anti-apoptotic protein XIAP. Moreover, XIAP knockdown in SW480 cells enhanced the basal and radiation-induced apoptotic index; the propensity of the SW480 cells to undergo apoptosis after radiation was higher compared with SW48 cells. In a translational study of 38 patients with rectal carcinoma, we analyzed the apoptotic profile for tumor and noncancerous tissue for each biopsy specimen using IHC. According to their response to preoperative radiotherapy, patients were classified into two groups: responsive and nonresponsive. Although no difference in expression of caspase 3, 8, or 9 was observed in the tumor/normal tissue ratio between responsive and nonresponsive patients, the ratio decreased for DIABLO and increased for XIAP. In conclusion, inhibition of XIAP rescues cellular radiosensitivity and both DIABLO and XIAP might be potential predictive markers of radiation responsiveness in rectal adenocarcinoma.

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.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.The 10-year cumulated rate of permanent colostomy (CRPC) was 63% in the EBRT group vs. 29% in the EBRT+CXRT group (p0.001). 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 CR50% (11 patients vs. 2 patients) (p0.001). 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 CR50% (p = 0.014).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.

Infiltrating MBC represents less than 1% of all male cancers. Our study details clinico-pathological features, treatments and prognostic factors in a large French cohort.Four hundred and eighty-nine patients were collected from 1990 to 2005. Median age was 66 years (34% over 70 years) and median follow-up 58 months.According to TN classification, we found T(1): 39%, T(2): 41%, T(3)T(4): 9%, T(x): 11% and N(1)N(2): 27%. Lumpectomy (L) and mastectomy (M) were performed in 8.6% and 91.4% of the cases. Axillary dissection (AD), sentinel node biopsy or both were performed in 90%, 2% and 5% of the cases, respectively. Ninety-five percent of tumours were ductal carcinomas; 47% were pT(1), 20% pT(2) and 33% pT(3)-T(4). Axillary nodal involvement was present in 52.8% cases. ER and PgR were positive in 92% and 89% cases. Radiotherapy (RT) was performed in 85% of the patients. Hormonal treatment (HT) was delivered in 72% of the cases. Tamoxifen and aromatase inhibitors were used in 85% and 12% of the cases; 34% of the patients received chemotherapy (CT). Local recurrence (LR), nodal recurrences (NR) and metastases occurred in 2%, 5% and 22% of the cases; 2% and 10% developed contralateral BC and second cancer. The 5- and 10-year overall survival (OS) rates were 81% and 59%; disease-specific survivals (DSS) were 89% and 72%. Death causes were BC 56%, second cancer 8%, complications 3%, intercurrent disease 15% and unknown 18%. In a univariate analysis, metastatic risk factors were T stage (T1: 19%, T(2): 26%, T(3)T(4): 40%; p=0.013), pN status (pN(0): 12% pN(1-3): 26% pN(3): 44%; p0.0001) and presence of locoregional recurrence (62% versus 18% p0.0001). In a multivariate analysis, axillary nodal involvement and high SBR remain prognostic factors.Earlier diagnosis and wide use of adjuvant treatments (RT/HT/CT) widely decreased LR and increased survival rates in MBC, reaching female ones. Prognostic factors were also very similar to female ones.

International audience; The aim of this study was to evaluate antitumor effects of cyclooxygenase-2 inhibitors in breast carcinoma and their ability to act synergistically with aromatase inhibitors (AIs). Postmenopausal metastatic breast cancer patients without previous adjuvant AI treatment received exemestane 25 mg/days plus either celecoxib 400 mg twice daily or placebo. The primary endpoint was progression-free survival (PFS). This trial was prematurely terminated ( = 157 of 342 planned) after cardiovascular toxicity was reported in other celecoxib trials. Although no PFS difference was observed between the two arms (9.8 months for both, = 0.72), a trend favoring celecoxib was observed in 60 tamoxifen-resistant patients (9.6 vs. 5.1 months; = 0.14) and in 126 patients treated ≥3 months before study termination (12.2 vs. 9.8 months; = 0.09). No severe adverse events were reported. Cyclooxygenase-2 inhibitors seemingly contribute to reverse endocrine resistance in breast cancer patients, although further study is necessary to allow development of a new therapeutic strategy.

Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. In this review, we present updated results of the literature and we detail the French multicentric randomized trial evaluating the impact of a 16 Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days. This protocol will start inclusions in October 2008.

Attempts to increase survival in stage III ovarian cancer patients with minimal residual disease at second-look laparotomy have included consolidation radiotherapy. We present long-term survival of 106 consecutive patients treated between 1983 and 1993 in 4 French institutions for stage III ovarian adenocarcinoma with first-look debulking, cisplatin-based chemotherapy, second-look surgery with a residual disease1 cm and consolidation radiotherapy.Median age was 52 years. Residual disease after first look surgery was1 cm for 40.5% of patients. Median number of chemotherapy cycles was 6 (range 4-12). Residual disease1 cm at second-look laparotomy was observed in 79% of the patients, with 33% of patients in complete histologic remission. Residual disease1 cm was obtained in all patients after tumor excision during second-look surgery. Radiation was performed using a linear accelerator with a whole abdomen dose of 22.5 Gy, an additional 22 Gy pelvic boost for 71 patients, and an additional 12 Gy lombo-aortic boost for 33 patients.Median follow-up was 14 years. Radiation was stopped for acute toxicity in 11 patients. Long-term toxicities included radiation enteritis in 21 patients with 9 patients requiring surgery for bowel obstruction. Four deaths were related to enteritis complications. Overall survival at 5 and 10 years was respectively 53% and 36%.This sequential treatment with final consolidation abdominopelvic radiotherapy is an effective treatment for a selected group of stage III ovarian cancer patients with a high intestinal toxicity incidence.

The purpose here was to identify whether ionizing radiation and oxaliplatin triggered testicular germ cells apoptosis through different executionary pathways.Adult male mice are treated with oxaliplatin (0.5 mg/kg, Ox) 4 h before being locally irradiated (0.5 Gy, IR, considered as time 0 h).The number of apoptotic germ cells was significantly higher for IR (p0.008), Ox (p0.0001) and Ox + IR (p0.0001) groups compared to the untreated mice group. Similarly, the different treatments induced an increase of p53 expression. Downstream p53, IR and Ox used different pathways. Indeed, IR increased effector caspase-3 expression in terms of mRNA (p0.002), pro-enzyme p0.0001) and active (3.7-fold, p0.003) protein levels but not the inhibitors of apoptosis proteins (IAP) including cIAP1, cIAP2 and XIAP. In contrast, while oxaliplatin treatment had no apparent effect on caspase-3 expression, it significantly decreased the cIAP1 (p0.005), cIAP2 (p0.008) and XIAP (p0.02) proteins levels. Finally, the combination of both treatments decreased IAP expression but did not modify caspase-3 levels while it increased the AIF (apoptosis-inducing factor) protein levels (5.5-fold, p0.003). No modification of AIF levels was observed with OX or IR alone.Together, these results indicate that the platinum analogue oxaliplatin and the ionizing radiations trigger apoptosis in the testicular germ cells, probably through different pathways.

Purpose Investigate whether the use of non coplanar fields and intensity modulated radiation therapy (IMRT) reduces the dose to the heart, in irradiation of middle and lower lung tumors. Materials and methods Four plans are compared on 10 CT scans: (1) a reference plan, corresponding to coplanar plan of 3D conformal radiotherapy (3DCRT); (2) a 3DCRTnoncopl plan, differing from reference plan by the change of one field in non coplanar fields; (3) an IMRTcopl plan optimized on the same coplanar plan as reference plan; and (4) an IMRTnoncopl plan optimized on the same non coplanar beams as 3DCRTnoncopl plan. The equivalent uniform dose (EUD) for PTV was 74 Gy in 37 fractions. Results In all plans, the 95% isodose surface covers at least 99% of the PTV with very similar conformity index values. A significant reduction in EUD, V30, V40 and V50 is observed for heart when either non coplanar fields or IMRT is used. IMRT also reduces the lung NTCP, V5, V13, V20 and V30 values and esophagus NTCP. Conclusion Both the use of non coplanar fields and IMRT dramatically reduces the dose received by the heart. The largest benefit is seen when the two techniques are combined.

X-ray repair cross-complementing 1 (XRCC1) is required for single-strand break repair in human cells and several polymorphisms in this gene have been implicated in cancer risk and clinical prognostic factors. We examined the frequency of the 5'-untranslated region (5'-UTR) variant -77T-->C (rs 3213235) in 247 French breast cancer (BC) patients, 66 of whom were adverse radiotherapy responders, and 380 controls and determined the haplotypes based on this and the previously genotyped variants Arg194Trp, Arg280His and Arg399Gln. The -77T-->C variant alone showed no significant association with BC risk or therapeutic radiation sensitivity. The H5 haplotype (variant allele codon 280, wild-type allele other positions) was associated with increased BC risk [odds ratio (OR), 1.90; 95% confidence interval (CI), 1.12-3.23] and the H3 haplotype (wild-type allele all four positions) was inversely associated with therapeutic radiation sensitivity compared with the reference group (H1 haplotype, -77C, wild-type allele codons 194, 280, 399) (OR, 0.39; 95% CI, 0.16-0.92). However given that the global tests for association were not significant these results should be interpreted carefully. Lymphoblastoid cell lines heterozygous for the H1/H3 haplotypes had a significantly higher cell survival (P=0.04) after exposure to ionising radiation (IR) than those with the H1/H1 haplotypes, in agreement with the association study. However no haplotype-specific differences in XRCC1 expression or cell cycle progression were noted in the 24 h following IR exposure. These results suggest that the -77T-->C genotype or another variant in linkage disequilibrium influences the cellular response to DNA damage, although the underlying molecular mechanisms remain to be established.

To report our patient experience with squamous cell carcinoma of the anal margin and to evaluate the prognostic factors influencing outcome. Between 1980 and 2001, 26 patients with anal margin squamous cell carcinoma were treated in Lyon-Sud: 7 T1, 14 T2, 4 T3, and 1 T4 with 20 N0, 3 N1, and 3 N2. The anal canal was invaded in five patients. Treatment consisted of definitive external irradiation in 14 patients and adjuvant irradiation (after a local excision) in 12 patients. External irradiation was combined with chemotherapy in seven patients, brachytherapy in four patients, and both brachytherapy and chemotherapy in one patient. The local control rate was initially 61.4%, and it was 80.8% after salvage treatment. The 5-year overall and specific survival rates were 71 and 88.3%, respectively. Three factors correlated with specific survival: cell differentiation (P=0.038) and T (P=0.001) and N category (P=0.0005). A salvage abdominoperineal resection was successfully employed in five of seven local recurrences. Four grade 3 and two grade 4 toxicities were observed. Sphincter preservation was possible in 66% of alive patients. Our results confirm the dominating place of definitive irradiation and radiochemotherapy in the treatment of anal margin squamous cell carcinoma. The indications for abdominoperineal resection must be limited to local relapse. The prognosis of squamous cell carcinoma is correlated to T and N staging and cell differentiation.

The aim of the study was to evaluate and compare incidence and risk factors of left ventricular dysfunction (LVD) in early breast cancer patients receiving (E+) or not (E-) epirubicin-based adjuvant chemotherapy.Among eight FASG trials, 3577 assessable patients were analyzed retrospectively: 2553 received epirubicin, 662 received hormonotherapy alone and 362 had no systemic treatment. Chemotherapy was FEC regimen in 86% of cases (fluorouracil, epirubicin, cyclophosphamide). Epirubicin cumulative dose was300 mg/m2 in 1040 patients, 300-600 in 1155,or = 600 in 279, followed by radiotherapy in 96% of cases.Twenty delayed LVD occurred: two in E- patients and 18 in E+ patients. In E+ patients, 14 patients normalized their cardiac function or did not require further investigations, one patient was stabilized with specific treatment, two patients worsened their functions and one died of congestive heart failure. The 7-year risk of LVD was 1.36% (95% CI 0.85-1.87) in E+ patients and 0.21% (95%CI: 0.00-0.52) in E- patients (P = 0.004). Two significant risk factors were identified: ageor = 65 years and body mass index27 kg/m2.After a long-term follow-up, epirubicin-related LVD risk was acceptable (1.36%) with one toxic death (0.04%). In 78% of cases, LVD were transient or well controlled.

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: 80% but 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. ≤80%. The group with a T3-T4 lesion and tumor regression ≤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 ≤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.

The prevalence of BRCA1/2 germ-line mutations was assessed in a prospective population-based series of early-onset breast cancer (BC) patients in France, and the usefulness of a clinical assessment of hereditary BC risk, based on multiple criteria including pedigree structure, was evaluated. Through the Rhone region BC registry, 232 women diagnosed with BC before 46 years of age were included. They were tested for BRCA1/2 mutations an average of 10 months after diagnosis. All the women were classified according to their family history of cancer: high risk of hereditary breast cancer (HBC), low risk of HBC, isolated BC, and unknown HBC risk. Deleterious mutations were observed in 21 women (9.1%): 15 (6.5%) BRCA1 and 6 (2.6%) BRCA2. Mutations were more prevalent in women who developed BC before age 41 than in women who developed BC between ages 41 and 45 (12.8% versus 5.2%, respectively, P = 0.04). A high prevalence of BRCA1/2 mutations was found among women in the high-risk category with particular family features (i.e., small family size, predominantly male pedigree, specific cancers; 23.5%) and among women with isolated BC before age 41 and with five or fewer close adult female relatives (16.6%). According to the 10% probability level recommended by the American Society of Clinical Oncology guidelines for genetic testing of cancer, BRCA1/2 mutation screening should be considered for all women diagnosed before age 41, except for those with isolated BC in a large pedigree including multiple unaffected female relatives. The clinical assessment of HBC risk that we have developed should help in the decision to perform genetic testing.

To investigate the clinical history, management, and pattern of recurrence of very early-stage anal canal cancer in a French retrospective survey.The study group consisted of 69 patients with Stage Tis and T1 anal canal carcinomaor =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).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 doses60 Gy and 37% for those who received doses ofor =60 Gy (p = 0.04).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).

This retrospective 12-year study evaluated the prognostic value of initial and postoperative staging of rectal tumors.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.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 (p0.001) and cN stage (p0.006) 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 (p0.014) but not for uN (p0.47) stage. In contrast, pT and pN stages were strong prognostic factors (p0.001 and p0.001, respectively).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.

Over the past 20 years there have been many advances in the management of rectal cancer. The medico-surgical school in Lyon, France, has a long tradition in managing this malignancy. The progression of ideas and practices requires a better knowledge of the patterns of tumor spread and local recurrence. Technical advances have greatly helped to facilitate sphincter preservation. Advances in radiotherapy have led to its routine use in the preoperative period. This approach has now emerged as the best therapeutic sequence. Our experience concerns 46 patients with low rectal carcinoma treated with this strategy. There were no post-operative deaths and no leakage. One patient (2%) had a pelvic abscess. Median follow-up was 50 months (1-151). At five years, the local recurrence rate was 8.5% and the actuarial survival rate was 72%, with a local control rate of 91%. Functional outcome, evaluated with a scoring system, was good in 60% of cases at one year and 78% at 5 years. Quality of life, evaluated with the American Society of Colon and Rectal Surgeons scale (A.S.C.R.S.), was 107 +/- 21 (range 33-140). The absence of defunctioning stoma (initial or late), good sexual and urinary well-being, and psychologic assessment are essential factors, requiring rigorous evaluation before the operation and specialized management after the operation. The proposed strategy based on this safe procedure and "French-type" neoadjuvant radiotherapy, permits sphincter preservation in patients with T2 and T3 tumors located near the dentate line, with good late oncological outcome. It is often amenable to the laparoscopic approach.

The aim of the survey Parcours de Femmes 2001 was to evaluate at a national level, the overall management of patients with breast or gynecological cancers and to determine their needs. Eligible patients had either received at least 3 months of treatment or had completed treatment less than 1 year before the study. from February to November 2001, 2 839 questionnaires were distributed ; 1 870 were returned (66% response rate); 87% of patients had breast cancer and 76% de novo cancer (primary management). Overall, 92% of women received information/explanations with an acceptable quality. Information of patients clearly improved during last years but insufficiencies persist for two points : adverse events of treatments and disease progression, especially for recurrent patients. Fatigue (78%), anxiety (66%) and chemotherapy adverse events were the most frequent problems and were well managed by caregivers, except for fatigue due to diagnostic and treatment difficulties. Problems relating to daily life (48% of patients reported difficulty in doing housework), material and social life were poorly identified and remained largely unmanaged. Information given to female cancer patients must be improved particularly in relapsed patients. Psychosocial management requires a more holistic approach through new channels together with the coordination of existing structures.

The identification of an interaction between BRCA1 and acetyl-CoA carboxylase alpha (ACCalpha), a key enzyme in lipid synthesis, led us to investigate the role of ACCalpha in breast cancer development, where it might contribute to the energy-sensing mechanisms of malignant transformation. In order to investigate if certain ACCalpha alleles may be high-risk breast cancer susceptibility alleles, 37 extended breast and breast/ovarian cancer families negative for BRCA1 and BRCA2 mutations were exhaustively screened for sequence variations in the entire coding sequence, intron-exon junctions, 5'UTR, 3'UTR (untranslated regions) and the promoter regions of the ACCalpha gene. Two possibly disease-associated ACCalpha variants were each identified in a single family and were not present in 137 controls. Multiple polymorphisms were detected in breast cancer families, including 12 single nucleotide polymorphisms where the frequency of the rare allele estimated in controls was >0.10. The observed lack of variation in the ACCalpha coding region along with the presence of extended areas of linkage disequilibrium and low haplotype diversity indicates an overall high preservation of this gene. The prevalence of the ACCalpha haplotypes composed of common polymorphisms was determined in 453 breast cancer cases and 469 female controls. One haplotype was found to be associated with a substantial and highly significant increase in breast cancer risk (odds ratio = 3.10, 95% confidence interval 1.87-5.14, P < 0.0001), whereas three other haplotypes were found to have a protective effect. Our results indicate that mutations in the ACCalpha gene are unlikely to be a major cause of high-risk breast cancer susceptibility; however, certain common ACCalpha alleles may influence breast cancer risk. This study provides the first insight into the involvement of the ACCalpha gene in breast cancer predisposition and calls for further, large-scale studies that will be needed to understand the role of ACCalpha in tumour susceptibility and development.

It is well known that the conservative reference treatment of infiltrative carcinoma of the breast, after en bloc complete excision, should be completed by irradiation of the whole breast delivering 50 Gy in 25 fractions. The discussion related to the validity and the procedures of delivery of the boost of the tumor bed has to be adjusted with our knowledge of specific prognostic factors of local recurrence. Through the two phase III randomized trials published in the literature, the young age of the patient, palpable tumor and negative receptor to progesterone may be recognized as statistically linked to a higher risk of local recurrence. Tumor size and palpable tumor remain unquestionable factors of bad prognosis. The true level of significativeness of age remains controversial as well as peri-tumoral characteristics such as ductal carcinoma in situ. Treatment technique should be rigorous either in terms of prescription of external radiation therapy or for the boost. They have a major impact on the cosmetic result and the fibrosis rate. Improvement of the results is expected through careful analysis of genic and molecularly prognostic factors of the tumor in order to select patients amenable to this type of technique.

Aims: To report outcomes of adults with retroperitoneal sarcoma (RS) treated by surgery, external beam radiotherapy (EBRT) and intraoperative electron beam radiotherapy (IORT). Methods: From July 1988 to February 2001; 24 patients with primary and recurrent RS were diagnosed and treated. The median dose and energy of IORT delivered was 15Gy/9meV. EBRT dose varies between 45–50Gy. Results: There were five primary and 19 recurrent tumours. One primary and five recurrent tumours underwent R0 resection. There were 12 liposarcomas and 19 grade I tumours; 13 patients developed local recurrence and three developed distant metastases. Twenty-two patients received IORT associated with EBRT: 11 developed recurrences. Six patients developed Neurotoxicity (4 grade II and 2 grade III). Disease free survival and overall survival at 5 years was 28 and 56% respectively. Conclusions: EBRT with IORT treatment is a promising technique for local control. Lower recurrence rates are associated with radical (R0) surgical procedures.

Resume Le traitement conservateur des carcinomes du canal anal et des petits cancers du bas rectum est une alternative valide a la chirurgie radicale grâce a des strategies associant radiotherapie externe et/ou endocavitaire de contact, chimiotherapie concomitante et curietherapie interstitielle par iridium 192. Faisabilite, tolerance et resultats de la technique sont maintenant eprouves. Le taux de controle local de la maladie et les fonctions anales sont satisfaisants. Le traitement necessite un grand soin dans la selection des patients et dans leur suivi.

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.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.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 aged80 years, it was 78% with 10 patients alive and well ator =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 patients80 years old.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.

To the Editor, In most institutions, standard treatment of T2-T3 rectal adenocarcinoma is radical surgery using total mesorectal excision (TME) with or without neo-adjuvant treatment [radiotherapy ...

BACKGROUND The authors performed a specific analysis of the clinical significance of inguinal lymph nodes metastases in patients with anal canal carcinoma (ACC). METHODS A retrospective analysis was conducted of 270 patients who were treated in Lyon between 1980 and 1996 with radiotherapy with curative intent for ACC: No elective irradiation of clinically normal inguinal areas was performed. Patients with metastatic inguinal lymph nodes were treated with inguinal dissection and postoperative irradiation with a dose of 50 grays over 5 weeks. Concomitant chemoradiation, usually with a regimen of fluorouracil and cisplatinum, was given to 159 patients. RESULTS The median follow-up for the whole series was 72 months. Synchronous inguinal metastases were observed in 10% of patients (n = 27; the rate was 16% for patients with T3–T4 lesions), and the 5-year overall survival rate was 54.4%. Metachronous inguinal metastases were seen in 19 patients (7.8%), and the 5-year overall survival rate of these patients was 41.4%. An original finding was that, when the primary tumor clearly was located on a single lateral side of the anal canal, the inguinal lymphatic metastases was always homolateral to it (36 of 36 synchronous plus metachronous tumors). CONCLUSIONS The data from this series of patients and a review of the literature are in favor of a selective approach in the management of inguinal lymph node involvement for patients with ACC, depending on the disease stage and the location of the primary tumors. Cancer 2001;92:77–84. © 2001 American Cancer Society.

Resume La Societe francaise de radiotherapie oncologie (SFRO) et le Syndicat national des radiotherapeutes oncologues (SNRO) ont elabore et edite un livret d'information sur la radiotherapie au debut de 1999. L'etude presente a pour objectif d'evaluer la pertinence de ce livret, sur la forme et le fond, apres presque un an d'utilisation. Huit centres francais ont participe a cette recherche qui a concerne 1 62 personnes malades, en debut de traitement en radiotherapie. Les conclusions de cette etude demontrent la volonte affirmee des patients d'etre clairement informes sur leur maladie, sur leur traitement, ainsi que sur les effets secondaires du traitement. Il est important de souligner que 97 % d'entre eux estiment qu'un livret d'information est une reelle necessite et que celui presente par la SFRO repond a la majorite de leurs questions. Acquerir des connaissances techniques et pratiques sur ce qui leur arrive a permis a 62 % d'entre eux de se sentir rassures, et pour 55 % d'etre mieux prepares au traitement a venir. Le chiffre le plus revelateur: ils sont 87 % a demander un discours-verite et que le cancer soit appele par son nom et non remplace par des termes plus evasifs. Cependant, les patients souhaitent (dans 72 % des cas) plus d'informations encore sur leur cancer, les choix de traitement, leur qualite de vie, dans une tentative de s'approprier psychiquement leur ≪ guerison ≫ par rapport a une maladie dont ils n'ont pas pu controler l'emergence et dont le developpement leur a echappe. Les patients ne veulent plus etre passifs, ne plus subir mais reclament le droit de devenir les ≪ partenaires ≫ de leurs medecins, de leurs soins, de leur guerison.

Background: Radical prostatectomy and external beam radiation therapy (EBRT) are the mainstays of treatment of prostate cancer with curative intent. The possible development of radiation proctitis and rectal bleeding are major concerns when using EBRT. Recently, conformal radiotherapy has been introduced in an attempt to improve the results of EBRT. This paper presents an overview of the Lyon experience using standard EBRT with doses of 68 Gy, and reports the preliminary results of a study of conformal radiotherapy with dose escalation. Methods: From 1981 to 1995, EBRT was used to treat 231 patients with localized adenocarcinomas of the prostate. The dose of EBRT was 68 Gy/34 fractions/7 weeks using a four-field box technique with 18-MeV photons. A feasibility study of conformal radiotherapy was commenced in 1996. To date, 145 patients have been treated with doses escalating from 68 to 80 Gy. Results: In the EBRT group of 231 patients, the 5-year overall survival was 80.3%. Anorectal function was scored as excellent in 90% of patients. Rectal bleeding was seen in 14.3% of patients and required local treatment in only seven. In the group treated with conformal radiotherapy, the preliminary results indicate good early tolerance. Conclusion: The curative treatment of patients with prostate cancer using EBRT gives good long-term survival with low rectal toxicity. Conformal radiotherapy appears to be an interesting approach to improve local control and perhaps survival.

Resume Objectif. Etude retrospective d'une serie de 96 patients atteints d'un sarcome des parties molles traite de facon homogene entre 1980 et 1992 par une chirurgie conservatrice et une irradiation postoperatoire. Patients et methodes. L'âge median des 96 patients etait de 58 ans. Le siege du sarcome etait: membre superieur (20 patients), membre inferieur (46 patients), tronc (30 patients). La tumeur mesurait 5 cm ou moins (T1) dans 35 cas. Aucun malade n'avait de metastases. Les types histologiques les plus frequents etaient l'histiocytome fibreux malin (28 cas) et le liposarcome (28 cas). La chirurgie etait macroscopiquement complete dans 89 cas. La radiotherapie, realisee par cobalt ou par photons X de 18 MV, a delivre une dose de 50 Gy avec un complement de dose de 10 Gy. Il n'y a pas eu de chimiotherapie adjuvante. Resultats. La duree de surveillance moyenne etait de 68 mois. Une rechute locale a ete observee dans 19 cas, dont six ont ete rattrapes par chirurgie. Une amputation de membre a ete necessaire quatre fois. Les taux de survie globale a cinq et dix ans etaient de 70 et 64 %. Il n'y a pas eu de complication secondaire a la radiotherapie necessitant une chirurgie. La fonction du membre a ete bien conservee dans la totalite des cas. Conclusion. Ces resultats conformes a ceux de la litterature justifient une attitude conservatrice dans ces sarcomes des tissus mous.

Purpose : To evaluate the long-term results of the treatment of anal canal carcinoma (ACC) with a combined concomitant radiochemotherapy (CCRT) treatment using fluorouracil (5 FU) and cisplatinum (CDDP) with a high dose of radiation therapy. Patients and methods : Between 1982 and 1993 a series of 95 patients were treated. Staging showed a majority of advanced squamous ACC, i.e. 6 T1, 47 T2, 28 T3, 14 T4, 53 N0, 32 N1, 6 N2 and 4 N3. Irradiation was done with high dose external beam radiation therapy (EBRT) followed by a boost with 192 Iridium implant. During EBRT all patients received one course of 5 FU continuous infusion (1 g/m 2 /day, days 1–4) and CDDP (25 mg/m 2 /day, bolus days 1–4). Results : The median follow-up time was 64 months. At 5 and 8 years the overall survival was 84 and 77%, the cancer specific survival was 90 and 86% and the colostomy-free survival was 71 and 67%, respectively. The stage and the response of the tumor after EBRT were of prognostic significance. Patients with pararectal lymph nodes had an overall 5-year survival of 76% (versus 88% for non-N1). Among 78 patients who preserved their anus, the anal sphincter function was excellent or good in 72 (92%). Conclusion : According to these results and recent randomized trials, CCRT appears as the standard treatment of ACC. Radical surgery should be reserved for local recurrence or persisting disease after irradiation. High dose irradiation in a small volume with concomitant 5 FU-CDDP appears to give a high rate of long-term local control and survival. Careful evaluation of pararectal nodes is essential for a good staging of the disease.

Endocavitary radiation therapy (Endo RT) is performed mainly with a contact x-ray tube. Interstitial brachy-therapy is a supplementary method to boost the tumor bed. Only strictly selected patients can be treated for cure by Endo RT. More than 1,000 patients have been treated in Europe and North America, since 1950. In T1 N0 adenocarcinoma, the primary local control rate is close to 90%. The overall 5-year survival is between 60% and 90% depending on patient selection. Careful follow-up is necessary because the majority of local failures can be salvaged, usually by radical surgery. The main advantages of Endo RT are a fully ambulatory and simple treatment that can be applied even in frail or elderly inoperable patients, a low risk of complications, and an inexpensive treatment. Results show it is possible to perform curative treatment in patients with more advanced rectal carcinoma. With the combination of external-beam radiation therapy and Endo RT in stage T2–3 N0-1 tumors, the primary local control rate is around 70%, and the incidence of severe radiation toxicity is less than 5%. Overall 5-year survival is between 50% and 70%. Endo RT can also be used as an adjuvant treatment after local excision, in the treatment of villous adenomas, and for palliation of advanced inoperable tumors.

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.

Background and purpose : To evaluate the impact of intraoperative radiotherapy (IORT) combined with postoperative external beam irradiation in patients with pancreatic cancer treated with curative surgical resection. Materials and methods : From January 1986 to April 1995 25 patients (11 male and 14 female, median age 61 years) underwent a curative resection with IORT for pancreatic adenocarcinoma. The tumour was located in the head of the pancreatic gland in 22 patients, in the body in two patients and in the tail in one patient. The pathological stage was pT1 in nine patients, pT2 in nine patients, pT3 in seven patients, pN0 in 14 patients and pN1 in 11 patients. All the patients were pM0. A pancreaticoduodenectomy was performed in 22 patients, a distal pancreatectomy was performed in two patients and a total pancreatectomy was performed in one patient. The resection was considered to be complete in 20 patients. One patient had microscopic residual disease and gross residual disease was present in four patients. IORT using electrons with a median energy of 12 MeV was performed in all the patients with doses ranging from 12 to 25 Gy. Postoperative EBRT was delivered to 20 patients (median dose 44 Gy). Concurrent chemotherapy with 5-fluorouracil was given to seven patients. Results : The overall survival was 56% at 1 year, 20% at 2 years and 10% at 5 years. Nine local failures were observed. Twelve patients developed metastases without local recurrence. Twenty patients died from tumour progression and two patients died from early postoperative complications. Three patients are still alive; two patients in complete response at 17 and 94 months and one patient with hepatic metastases at 13 months. Conclusion : IORT after complete resection combined with postoperative external beam irradiation is feasible and well tolerated in patients with pancreatic adenocarcinoma.

Standard treatment for limited stage adenocarcinoma of the breast includes lumpectomy (or a quadrantectomy), axillary node dissection, regional radiation therapy and, if the prognostic factors are unfavourable, chemotherapy and/or hormone therapy. This is supported by the results of American and European randomised trials. There have been many attempts at improving the modalities of conservative surgery and postoperative radiation therapy in order to maximize local control and minimize late sequellae. It is also likely that induction chemotherapy and external beam radiotherapy applied in selected cases increase the proportion of patients who can be offered conservative surgery.

Resume La radiotherapie du sein est toujours en evolution. Bien que le reperage des volumes cibles, glande mammaire et aires ganglionnaires, soit le plus souvent realise cliniquement, par palpation et reperage osseux, la scanographie a permis de mieux definir les volumes en profondeur et de realiser des dosimetries tridimensionnelles. L'analyse des resultats preliminaires sur 50 centres d'une enquete lancee aupres des 194 centres de radiotherapie de France montre que l'acquisition des donnees anatomiques se fait le plus souvent avec un simulateur–scanneur ou un scanneur (92 % des centres). La mise en place des faisceaux est realisee soit directement au simulateur (20 centres), soit sur le systeme de planification (16 centres). On se sert d'une station de simulation virtuelle dans 8 des 50 centres. De plus, dans environ 20 % (11) des services de radiotherapie les volumes cibles sont delinees et les faisceaux adaptes a ces volumes.

Radiosurgery (RS) was initiated in Lyon in October 1989. The technique was adapted from that described by Lutz and Saunders in Boston (BRW stereotactic frame). Irradiation is delivered with 18-MV photons produced by a LINAC. From December 1989 to December 1992, 41 patients with arteriovenous malformations were treated by RS; the median age was 33 years. The largest lesion diameter was 11.2-38.5 mm. Fifteen to 20 Gy were delivered on the 70% isodose line. Angiography was performed at 2 years post-treatment in 32 patients demonstrating an overall complete thrombosis rate of 81.3%. This incidence was significantly correlated with the Spetzler and Martin grade before RS (P = 0.0055). Two patients (4.9%) experienced haemorrhage after radiosurgical treatment and one died from an intracerebral-intraventricular haemorrhage. Four patients (9.7%) experienced permanent radiation-induced neurological complications.

To evaluate the efficacy of irradiation of internal mammary nodes (IMN) on 10-year overall survival in breast cancer patients after mastectomy.This multicenter phase 3 study enrolled patients with positive axillary nodes (pN+) or central/medial tumors with or without pN+. Other inclusion criteria were age75 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.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.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.

Learning Objectives After completing this course, the reader will be able to: Evaluate the therapeutic impact of hysterectomy after chemoradiation therapy in locally advanced cervical cancer.Evaluate the rate of histologic residual disease in patients with complete clinical and radiologic response after chemoradiation therapy. This article is available for continuing medical education credit at CME.TheOncologist.com Background. Concomitant chemoradiation (CRT) (including brachytherapy) is considered the standard management for stage IB2 or II cervical cancer in many countries. Nevertheless, some of them discuss completion surgery (hysterectomy [HT]) after CRT. The aim of this study was to investigate the therapeutic impact of such surgery. Methods. A randomized trial was opened in France in 2003 to evaluate the interest in HT after CRT. Inclusion criteria were: (a) stage IB2 or II cervical cancer without extrapelvic disease on conventional imaging; (b) pelvic external radiation therapy (45 Gy with or without parametrial or nodal boost) with concomitant cisplatin chemotherapy (40 mg/m2 per week) followed by uterovaginal brachytherapy (15 Gy to the intermediate risk clinical target volume); and (c) complete clinical and radiological response 6–8 weeks after brachytherapy. Patients were randomized between HT (arm A) and no HT (arm B). Unfortunately this trial was closed because of poor accrual: 61 patients were enrolled (in 2003–2006) and are reported on here. Results. Thirty one and 30 patients were enrolled, respectively, in arm A and arm B. Twelve patients recurred (five of them died): respectively, eight and four in arm A and arm B. The 3-year event-free survival rates were 72% (standard error [SE], 9%) and 89% (SE, 6%) (not significant [NS]) in arm A and arm B, respectively. The 3-year overall survival rates were 86% (SE, 6%) and 97% (SE, 3%) (NS) in arm A and arm B, respectively. Conclusions. Results of the current trial seem to suggest that completion HT had no therapeutic impact in patients with clinical and radiological complete response after CRT (but this conclusion is limited by the lack of power).

Nineteen patients (14 women, 5 men) received external radiation therapy (ERT) between 1980 and 1988 for gall-bladder carcinoma. Eleven patients had complete resection (cholecystectomy in eight cases), six incomplete gross resection and two only percutaneous transhepatic biliary drainage (PTBD). The modalities of ERT were variable and doses ranged from 30 Gy/10 fractions to 50 Gy/25 fractions. Among 11 patients with complete resection (9/11 with T1 or T2 stages), overall survival was 55% at 48 months and 36% at 60 months, median survival was 48 months and at the time of this report 3/11 patients were alive with no evidence of disease, 54, 65, 76 months after surgery, and eight dead of cancer 8-114 months. Local control was achieved in 66 patients with T1 or T2 stages. All eight patients who had palliative surgery or PTBD died of cancer after 4-20 months with median survival of 6 months. Three complications were noted: one gastric ulcer in the course of ERT (surgical treatment), one duodenal ulcer which occurred 6 months after completion of ERT (medical treatment) and one regressive radiation hepatitis. From this experience it appears that ERT in gall-bladder carcinoma is well tolerated, can obtain local control and prolonged survival after complete resection and good palliation in non-resectable tumors.

In order to evaluate the effect on prolonging survival of alternating chemotherapy and radiotherapy schedules in patients with limited disease small cell lung cancer, 89 patients were included in a multi-institutional pilot study between January 1986 and May 1989. Treatment consisted of induction chemotherapy using the combination of doxorubicin, etoposide and ifosfamide (AVI) for four consecutive courses, followed by two cycles of the VI chemotherapy alternating with three hyperfractionated radiotherapy courses and then followed by two additional courses of AVI. Objective response to the four cycles of AVI combination was observed in 65 patients (75%). Thirteen out of 30 patients (44%) who were in partial response (PR) after induction chemotherapy were converted into complete response (CR) after the three alternating courses of chemotherapy and radiotherapy. The principal side effect related to combined modality treatment was acute radiation pneumonitis (21.5% cases) reversible except one which resulted in toxic death, and a second with chronic lung fibrosis with permanent WHO Grade 2 dyspnea (14%). Local relapse was observed in 47% of the patients who were considered in CR at the end of the treatment program and cerebral metastases were the first site of detectable relapse in 25% cases. The 3-year actuarial disease-free survival of the 89 patients is 5%, and the median actuarial survival is 14 months. This study shows that the promising survival rates seen in our previously published interim analysis were not maintained. Reasons for this might include the choice of a non cisplatinum containing induction chemotherapy, the late introduction of thoracic irradiation and/or to the use of non-restrictive criteria for selecting patients.

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.

Between April 1982 and June 1989, 65 patients (15 T1, 13 T2, 32 T3, 5 T4) with squamous cell carcinoma of the oesophagus were treated with a curative intent with multimodality combined treatment. A first course of 5-fluorouracil and cisplatin was given during work up, especially if NdYAG laser therapy was used. Irradiation was started 3–4 weeks after induction and two courses of concomitant chemotherapy were given during the radio therapy (aiming at 64 Gy over 7 weeks). Actuarial survival was 79.6% at 1, 36.7% at 3 and 26.7% at 5 years. 5 year survival rates were 56.3% for T1, 29.8% for T2 and 12.9% for T3. All T4 cases died within 16 months. Complete initial disease response was achieved in 76%. Tolerance was good. Thus patients with squamous cell carcinoma of the oesophagus can have long survival and may be cured with combined modality therapy. This treatment may be an alternative to radical surgery when there is a high risk of operative mortality.

International audience; BACKGROUND AND PURPOSE: The aim of this study was to prospectively assess the quality of life (QOL) of patients treated by concomitant chemo radiation for locally advanced anal canal carcinoma. MATERIALS AND METHODS: We report on a subgroup of 119 patients enrolled in a 306-patient therapeutic intensification prospective trial (ACCORD 03). This trial evaluated the impact on colostomy-free survival of induction chemotherapy and/or high dose radiotherapy (factorial design 2 *2 treatment arms). QOL was assessed both before and 2 months after treatment using the EORTC QLQ-C30 questionnaire as well as a questionnaire relating to anal sphincter conservative treatment (AS-CT). RESULTS: Compared to pre-treatment scores, patients reported significant improvement in their emotional function (+8.4 points p=0.002), global health status (+5.9 points p=0.0007), as well as a decrease in insomnia (-13.8 points p

From January 1986 through December 1988, 227 patients were included in a multi-institutional pilot study for small cell lung cancer (SCLC). Out of the 211 patients who fully completed the staging procedures, 77 (35%) appeared to have SCLC limited to the thorax. All patients received combination therapy consisting of AVI (Adriamycin, VP-16 and Ifosfamide), except during radiotherapy when the Adriamycin was omitted, plus twice daily fractionated 18 MV radiotherapy. Treatment protocol consisted of 4 initial courses of AVI, followed by 3 courses of radiotherapy alternating with modified chemotherapy (VP-16 and Ifosfamide), completed by 2 courses of initial chemotherapy (AVI). Radiotherapy consisted of 1.5 Gy/fraction, 2 fractions/day, 5 days/week in the first course, and 1.8 Gy/fraction, 2 fractions/day, 5 days/week, in the second and third courses, for a total tumor dose of 51 Gy, felt to be equivalent to 60 Gy at normal fractionation. CT treatment planning was employed to design a treatment consisting of multiport radiotherapy, using AP-PA and laterals or obliques beams. During the first course, the homolateral hemithorax received 9 Gy total dose on days 1, 3, 5. During the third course, 360° arctherapy was generally used to boost the reduced tumor volume to a 51 Gy. Besides chest X ray and CT scan, staging and restaging procedures included fiberoptic bronchoscopy. Response rate after irradiation is 61%, with 46% complete responders and 51% local control. The median survival is 14 months, and disease-free survival 42% at 1 year. Complications consisted of cardiac toxicity in 2 patients, 1 death of acute pulmonary toxicity, and 4 instances of moderate chronic radiation pneumonitis. Thus, high doses of radiation can be delivered combined with chemotherapy using this protocol, with an acceptable toxicity and encouraging results in response rate and local control. A longer follow-up is needed to evaluate the impact of these results on survival.

Aims To determine the feasibility of radiotherapy-associated capecitabine, irinotecan and oxaliplatin administration at five dose levels for the treatment of locally advanced rectal cancer, with or without metastasis. Patients and methods This was a bicentric phase I trial, including patients with locally advanced rectal cancer, with or without metastasis. Chemotherapy comprised capecitabine (1100, 1300 or 1500mg/m 2 /day, every day), irinotecan (30, 40 or 50mg/m 2 , once per week for 6 weeks) with the addition of oxaliplatin (40mg/m 2 at level 4 or 50mg/m 2 at level 5, once per week for 6 weeks). Radiotherapy at 46Gy plus a boost of 4Gy was administered concomitantly. Results Twelve patients received four levels of dose. As a supplement to radiotherapy, the combination of capecitabine and irinotecan at the respective doses of 1500mg/m 2 /day and 50mg/m 2 /week was feasible and well tolerated. The addition of oxaliplatin to this combination provoked toxicity (grade 3/4 vomiting, diarrhoea) for two-thirds of the patients. Conclusion A treatment associating radiotherapy (46Gy+4Gy) with concomitant chemotherapy comprising capecitabine (1500mg/m 2 /day, every day) and irinotecan (50mg/m 2 /week, for 5 weeks) was feasible and well tolerated. The addition of oxaliplatin to these doses was prohibitory to the continuation of treatment due to unacceptable toxicity.

This paper is an overview of the French experience with contact X-ray radiation for rectal cancer. The analysis was mainly carried out on 50 years of experience in Lyon or since 1980 in the Centre Hospitalier Universitaire Lyon Sud. The results obtained in Dijon and Nancy are also reported. In early rectal cancer, contact X-ray radiation can play an important role in three different situations: (1) small T1 less than 2 cm: adjuvant contact X-ray radiotherapy after local excision; (2) T2 N0 or large T1: first-line contact X-ray radiotherapy combined with external beam radiotherapy (±chemotherapy) followed by surgery (anterior resection or local excision); (3) early T3 N0 in frail patients: the same approach as for T2 N0 with, in case of clinical complete response, local excision or follow-up.

Aims and background Adenocarcinoma of the body and tail of the pancreas is a rare malignancy with a poor prognosis. Few long-term survivors have been reported in the literature. The role of adjuvant treatment after curative resection has not yet been assessed. This retrospective study aims to describe the patterns of failure and the survival of 10 patients treated with resection and adjuvant radiotherapy. Materials and methods from 1982 to June 1994, 10 patients with adenocarcinoma of the body and tail of the pancreas received adjuvant radiotherapy in our department. There were 4 females and 6 males, with a median age of 63 years (range, 45–77). The pT distribution was 2 pT1, 4 pT2, 4 pT3 and for pN it was 7 pN0 and 3 pN1. Four patients had stage I, 3 stage II and 3 stage III disease. All the patients underwent a resection: distal pancreatectomy in 7, partial resection of the body in 1, and total pancreatectomy in 2. Gross residual disease was present in 2 cases. Three patients received intraoperative radiotherapy up to a dose of 12–15 Gy. Postoperative radiotherapy was given in 9 patients with a dose ranging from 40 to 50 Gy (median, 45). One patient who received intraoperative radiotherapy had no postoperative radiotherapy. In 4 patients, chemotherapy with 5-fluorouracil was given during the first week of irradiation. Results Six patients experienced a local-regional relapse and 3 developed metastases. The median survival was 21 months. The 5-year overall survival was 15%. Eight patients died of progressive disease. One patient who presented with stage I disease was alive and free of disease at 24 months from diagnosis and, interestingly, one with stage III disease was alive at 111 months. No severe treatment-related complications were observed. Conclusions As in carcinoma of the head of the pancreas, adjuvant radiotherapy should be considered as an adjuvant treatment of resected adenocarcinoma of the body and tail of the pancreas. Further evaluation is necessary to assess the role of intraoperative radiotherapy.

Background: The purpose was to compare disease-free survival (DFS) between epirubicin-based chemoendocrine therapy and tamoxifen alone in one to three node-positive (N1–3), estrogen-receptor-positive (ER+), postmenopausal early breast cancer (EBC) patients. Patients and methods: We analyzed, retrospectively, 457 patients randomized in FASG 02 and 07 trials who received: tamoxifen alone (30 mg/day, 3 years); or FEC50 (fluorouracil 500 mg/m2, epirubicin 50 mg/m2, cyclophosphamide 500 mg/m2, six cycles every 21 days) plus tamoxifen started concurrently. Radiotherapy was delivered after the third cycle in FASG 02 trial, and after the sixth in FASG 07 trial. Results: The 9-year DFS rates were 72% with tamoxifen and 84% with FEC50-tamoxifen (P = 0.008). The multivariate analysis showed that pathological tumor size >2 cm was an independent prognostic factor (P = 0.002), and treatment effects remained significantly in favor of chemoendocrine therapy (P = 0.0008). The 9-year overall survival rates were 78% and 86%, respectively (P = 0.11). In the multivariate model, there was a trend in favor of chemoendocrine therapy (P = 0.07). Conclusion: The addition of FEC50 adjuvant chemotherapy to tamoxifen significantly improves long-term DFS in N1–3, ER+ and postmenopausal women. Chemoendocrine therapy seems to be more effective than tamoxifen in terms of long-term survival.

Breast radiotherapy is still in progress. The target volumes - whole breast and lymph nodes - are usually located by clinical palpation and the use of bony landmarks. However computed tomography has allowed a better definition of the deep edge of the volumes and the calculation of 3D dose distributions. A survey of 194 centers has started in June 2005 in France. The questionnaire that was sent included questions about general techniques in breast radiotherapy. Preliminary results on 50 centers showed that patient anatomical data were in the vast majority acquired by a simulator-CT or a CT (for 92%). In the 50 departments, beam placement is done either directly at the simulator (20 centers), or on the TPS (16 centers). Virtual simulation software is used in 8 centers. In about 20% (11) radiotherapy departments, 3D target volumes are contoured and the beams adapted to their shapes.

It has been shown that a delay in radiotherapy (RT) initiation resulted in a higher local relapse (LR) rate. The present analysis investigated retrospectively if the RT-adjuvant therapy sequence modified local-disease-free survival (L-DFS) after breast-conserving surgery (BCS) in node-positive (N +) breast cancer patients. Among seven French Adjuvant Study Group trials, 1,831 patients were assessable: 475 received RT directly after BCS, 567 after the 3rd chemotherapy (CT) cycle, and 789 after the 6th CT cycle. In the 1,356 patients receiving CT, it consisted of FEC regimens (fluorouracil, epirubicin, cyclophosphamide) in 83.5% of patients. After a 102-month median follow-up, 214 patients (11.7%) developed LR. The 9-year L-DFS rates were 92.0%, 81.5%, and 87.4%, respectively (p0.0001). In the multivariate analysis, the timing of RT was not associated with a higher rate of LR, whereas tumor size and hormonotherapy were prognostic factors. In our population, there was no increase in the risk of LR when RT was delayed to deliver adjuvant CT. Prognostic factors were tumor size, and hormonotherapy. The number of CT courses could modify this risk.

The multidisciplinary dimension which imposes the follow up of patients suffering from breast cancer raises difficulties of communication between community and hospital practitioners. The aim of this study was to assess information needs and expectations when the general practitioners and private gynecologists on one hand, and the hospital practitioners on the other hand, exchange medical information in the follow up of patients suffering from breast cancer. This descriptive study included a sample of 225 general practitioners and 216 gynecologists in private practice, and 233 hospital practitioners in the Rhone-Alps French region. Response rate was respectively 68 % (153), 64 % (139) and 42 % (99). This study showed different perceptions on the frequency of shared documents (reports, letters) or phone calls according to the speciality. In spite of a strongly felt partnership, an expectation of change was found with notably the wish of a stronger implication in the follow up and the wish to receive numerous information concerning the patients. The community practitioners expected to be more aware of the stage of the cancer, the prognosis and the level of information given to the patients. The hospital specialists expected to be informed about psychological problems or comorbidity. Pending the generalization of an electronic shared medical records, the experiment of a patient-held records may help to fulfil these expectations.