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Resume Objectif de l’etude Evaluer retrospectivement la tolerance, la faisabilite et l’efficacite d’une chimioradiotherapie concomitante apres chimiotherapie d’induction par docetaxel, cisplatine et 5-fluoro-uracile pour les cancers de la tete et du cou localement evolues. Patients et methodes Les donnees de patients de trois centres de radiotherapie du sud-est de la France, atteints de cancers de la tete et du cou localement evolues et pris en charge entre decembre 2007 et juillet 2013 par chimioradiotherapie concomitante, apres chimiotherapie d’induction par docetaxel, cisplatine et 5-fluoro-uracile, ont ete analysees. Les effets indesirables ont ete evalues selon la Common Terminology Criteria for Adverse Events v3.0. Les survies globales et sans maladie ont ete calculees selon la methode de Kaplan-Meier. Resultats Cent soixante-huit patients, majoritairement atteints d’une tumeur de stade T4 (46 %) et N2 (54 %) de l’oropharynx (38 %) ont recu apres chimiotherapie d’induction par docetaxel, cisplatine et 5-fluoro-uracile, une chimioradiotherapie concomitante a base de platine ou cetuximab de 66 a 70 Gy. Les effets indesirables de grade 3-4 etaient moins frequents dans le groupe de patients ayant recu du cisplatine (avec ou sans 5-fluoro-uracile) a la dose de 100 mg/m2 tous les 21 jours par rapport au cetuximab (radiomucite : 32,5 % contre 61 %, p = 0,018 ; radioepitheliite : 13 % contre 61 %, p 1 ; p = 0,006 ; survie sans maladie : 66 % si N Conclusion L’association de chimiotherapie d’induction par docetaxel, cisplatine et 5-fluoro-uracile et de chimioradiotherapie concomitante a donne des resultats satisfaisants au prix d’une toxicite acceptable. Les modalites de la chimiopotentialisation ainsi que sa superiorite par rapport a une chimioradiotherapie concomitante exclusive restent encore a etre precisees.

The advent of sentinel lymph node technique has led to a shift in lymph node staging, due to the emergence of new entities, namely micrometastases and isolated tumour cells. In addition, the therapeutic role of axillary lymph node dissection is more and more questioned and radiotherapy has been shown to be equivalent to complementary axillary lymph node dissection in patients without clinical node involvement. This article looks at the literature in favour of performing axillary irradiation in patients with pN1mi stage breast cancer who have undergone a mastectomy without a complementary axillary lymph node dissection, and in favour of abstention of any further treatment of the axilla in patients with pN0(i+) or pN1mi tumours who have undergone breast conserving surgery and a sentinel lymph node procedure followed by systemic treatment. The impact of regional lymph nodes irradiation in case of axillary involvement 2mm or less is also discussed.

Objectives: Mastectomy (Mt) is considered standard treatment for isolated local recurrence (LR) of breast carcinoma. The aim of our study was to evaluate a second conservative treatment (defined as lumpectomy followed by interstitial brachytherapy (LpIB)) and to determine if it compares favorably with the current standard treatment. Materials and methods: Between January 1981 and December 2009, 348 patients were treated to the Paoli Calmettes Institute (IPC) for an isolated LR: 232 (66,7 %) underwent Mt, 62 (17,8 %) received a second radio-surgical conservative treatment (LpIB) and 54 (15,5 %) a 2nd single surgical treatment (Lp). We classified each population according to the well known prognosis factors. Then, populations Mt and LpIB were matched taking into account these criteria to compare the overall survival (OS), metastasis free survival (MFS) and 2nd local recurrence free survival according to the treatment delivered. Results: On 348 reviewed patients, with a median follow-up of 73,3 months, 65 patients died (42/232 Mt, 8/62 TecCur, 15/54 Tec) and 100 presented metastasis (64/232 Mt, 15/62 TecCur, 21/54 Tec). There was no difference in MFS for the 2 groups, LpIB and Mt (80 % at 5 years) and the OS was non significantly better in the group LpIB compared to the group Mt (90 % and 82 % at 5 years respectively, p=0,28), whereas in the LpIB group 17% and 30% presented a relapse at 5 years and 10 years respectively. They subsequently underwent a salvage mastectomy. Worse results were obtained with lumpectomy alone (OS = 72 % and MFS = 68 % at 5 years) compared with 2 other option treatments. Conclusion: A second conservative treatment for breast cancer recurrence, i.e. lumpectomy and interstitial brachytherapy, is possible for selected patients, without any negative impact on overall survival, nor metastasis free survival. Keywords: Local recurrence, interstitial brachytherapy, lumpectomy, conservative treatment, mastectomy, overall survival, metastasis free survival, breast carcinoma. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-12-05.

Resume Objectif de l’etude L’objectif de cette etude retrospective etait, dans un premier temps, de rechercher une correlation entre la reponse tumorale et la survie, puis d’identifier les facteurs predictifs potentiels pour la reponse tumorale apres la chimioradiotherapie dans les cancers rectaux localement evolues. Patients et methodes Entre 1998 et 2008, 168 patients atteints d’un adenocarcinome rectal ont ete inclus dans l’etude. Le traitement consistait en une radiotherapie de 45 Gy et une chimiotherapie concomitante a base de 5-fluoro-uracile. Une correlation entre les probabilites de survie globale et de survie sans recidive, d’une part, la reponse tumorale, d’autre part, a ete recherchee. Des facteurs potentiellement predictifs pour la reponse tumorale a la chimioradiotherapie ont ete etudies. Resultats La duree mediane de suivi etait de 34 mois. Les probabilites de survie sans recidive et de survie globale a cinq ans etaient respectivement de 44,4 % et 74,5 % dans la population generale, 83,4 % et 83,4 % en cas de reponse complete, 38,6 % et 71,9 % en cas de downstaging, 29,1 % et 58,9 % en cas de non-reponse. Une concentration d’antigene carcinoembryonnaire de moins de 5 ng/mL etait associe significativement avec un downstaging tumoral et significativement et independamment avec une reponse tumorale complete (p = 0,019). Conclusion La reponse tumorale etait un facteur predictif pour la survie des patients atteints d’un adenocarcinome rectal localement evolue. Une concentration pre-therapeutique d’antigene carcinoembryonnaire de moins de 5 ng/mL etait un facteur predictif significatif pour le downstaging ainsi qu’un facteur predictif significatif et independant pour une reponse tumorale complete.

Rationale: Issues have been reported with aromatase inhibitors (AI) compliance in adjuvant breast cancer. The present study was performed in order to better assess patient (pt) compliance, and to test whether educational material (EM) can improve compliance rate. Methods: This 2-year observational study (NCT00681122) was conducted on 2,758 patients in 18 countries, and completed in March 2009. Pts were allocated to Standard Therapy AI (anastrozole or letrozole), Group A, or to Standard Therapy + EM (Group B) following a 1:1 randomisation. EM consisted of a range of information on breast cancer-related topics. Primary endpoint was compliance rate for AI: patient is defined as being compliant if she took more than 80% of her tablets during the last year. Secondary endpoints were: persistence rate at 1 and 2 years (patient is classified as a persistent user of adjuvant AI medication when the data supports the persistent intake of adjuvant AI medication during the one-year period), and reasons for and time to AI discontinuation. Specialised questionnaires were used to evaluate pt compliance and behaviour (EORTC-INPATSAT-32, OPTIMA-X, GHQ-12, FACT-ES, compliance questionnaire and EM feedback in Group B).Results: 711 pts were randomised in France, 348 in Groupe A and 363 in Groupe B. Pt characteristics were well balanced across randomised arms. Mean age was 65 years, mean BMI was 26, 20% of pts had received hormone replacement therapy, and 68% had associated co-morbidities, including musculoskeletal disorders in 12%. Preliminary analysis showed that compliance rate at 1 year was only 74%, with no difference between the 2 groups (73% in Group A vs. 74% in Group B). Persistence rates were also similar (77% vs.78%). AI discontinuations were mainly attributed to AI related side effects. Prognostic factor analysis showed no baseline characteristics associated with compliance behaviours.Conclusion: At 1 year, Cariatide preliminary analysis showed that compliance rate of adjuvant AI in France does not exceed 74%, and is not improved by EM. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-11-06.

Retrospectively evaluate the safety, feasibility and efficacy of concomitant chemoradiotherapy after induction chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil for locally advanced head and neck cancers.Patients' data from three radiotherapy centres in South of France, with locally advanced head and neck cancers, and treated between December 2007 and July 2013 by concomitant chemoradiotherapy, after induction chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil, were analysed. Adverse effects were graduated according to CTCAE v3.0 criteria. Overall survival and disease-free survival were calculated according to Kaplan-Meier method.One hundred and sixty-eight patients, mostly oropharynx (38%) T4 (46%) N2 (54%) tumors, received, after induction chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil, a concomitant chemoradiotherapy with platin or cetuximab, which delivered 66 to 70Gy. Grade 3-4 adverse effects were less frequent in the group of patients who received cisplatin (with or withour 5-fluoro-uracil) at 100mg/m(2) each 21 days compared to cetuximab (radiomucositis: 32.5% vs 61%, P=0.018; radioepithelitis: 13% vs 61 %, P0.0001). Chemopotentiation was incomplete for 21% of patients without impacting survival. Two years overall survival and disease-free survival were respectively of 81% and 64%. Lymph nodes status and WHO status significantly influenced these survivals (overall survival 84% if N3 vs 56% if N3, P=0.017 and 85 % if WHO status ≤ 1 vs 50% if WHO status1, P=0.006; disease-free survival 66% if N3 vs 47% if N3, P=0.046).The association of induction chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil and concomitant chemoradiotherapy shows satisfying results with an acceptable toxicity. The terms of the chemopotentiation and its superiority to a single concomitant chemoradiotherapy treatment still remain to be clarified.

The advent of sentinel lymph node technique has led to a shift in lymph node staging, due to the emergence of new entities, namely micrometastases and isolated tumour cells. In addition, the therapeutic role of axillary lymph node dissection is more and more questioned and radiotherapy has been shown to be equivalent to complementary axillary lymph node dissection in patients without clinical node involvement. This article looks at the literature in favour of performing axillary irradiation in patients with pN1mi stage breast cancer who have undergone a mastectomy without a complementary axillary lymph node dissection, and in favour of abstention of any further treatment of the axilla in patients with pN0(i+) or pN1mi tumours who have undergone breast conserving surgery and a sentinel lymph node procedure followed by systemic treatment. The impact of regional lymph nodes irradiation in case of axillary involvement 2mm or less is also discussed.

Prognostic factors for disease-free survival in patients treated before 2005 September: multivariate analysis. (DOCX 15Â kb)

Rectal cancer is increasingly prevalent in elderly patients. Their clinical history and outcome after treatment are poorly described. This retrospective study was undertaken to provide more data and to compare therapeutic strategies to the standard of care for younger patients.Patients concerned were aged 80 years or older, with a rectal cancer diagnosed between 2006 and 2008 and treated in Provence-Alpes-Côte-d'Azur (PACA), irrespective of stage and treatment of the disease. Overall survival and relapse-free-survival were correlated with patients' characteristics and treatment. The adopted therapeutic strategy was then compared to the standard-of-care for younger patients.With a median follow-up of 36 months, among the 160 patients included, the 3-year overall survival and relapse-free survival were 59.2% and 76.6%, respectively for the 117 patients who received a treatment with curative intent. In the multivariate analysis, node status and surgery independently influenced overall survival, while relapse-free survival was influenced by age, N status, and gender. For T0-T2 tumours, patients were treated similarly to younger patients with an overall survival of 83.6% and a relapse-free survival of 95.2%. For T3-T4 tumours, the 3-year relapse-free survival was 65%, even with a less aggressive strategy.Surgical resection after evaluation using the Comprehensive Geriatric Assessment (CGA) test should be the standard treatment for localized rectal cancer (T0-T2) in elderly patients, as it is in younger patients. For locally advanced lesions (T3-T4), results obtained after a conservative approach suggest that a non-surgical strategy can be used in elderly patients.

PURPOSE: To evaluate the best strategy for treatment of sarcoma that occurs after radiation therapy. MATERIALS AND METHODS: Records were retrospectively reviewed for 80 patients with a confirmed histologic diagnosis of sarcoma that occurred after radiation therapy performed during 1975–1995. The patients were treated for breast cancer (n = 33, 42%), non-Hodgkin lymphoma (n = 9, 11%), cervical cancer (n = 9, 11%), benign lesions (n = 4, 5%), or other tumors (n = 25, 31%). Sarcoma occurred after a mean latency of 12 years (range, 3-64 years), with most (70%) developing in the soft tissue. Treatment included surgery (28 patients), surgery and chemotherapy (18 patients), chemotherapy only (15 patients), and radiation therapy (14 patients). RESULTS: By the end of the study, 51 patients were dead, including 46 due to sarcoma. Median survival was 23 months. Overall survival rates at 2 and 5 years, respectively, were 69% and 39% for patients treated with surgery, 10% and 0% for those treated with chemotherapy, an...

Summary Background: Shared decision-making is increasingly advocated as an ideal model. However, very few studies have tested the feasibility of giving patients the opportunity to participate in the choice of treatment. Patients and methods: Women, with non-metastatic breast cancer, eligible for non-intensified adjuvant chemotherapy attending our hospital were proposed two administrations of chemotherapy and radiotherapy: a sequential and a concomitant one. Two patient-questionnaires were used to elicit motivations for their choice and their degree of comfort with the process of decision-making and one questionnaire to test physicians'ability to predict patients'choice. Results: Participation rate in the study was 75.3% (n = 64). Majority (64%) of patients chose the concomitant treatment. Multivariate analysis revealed that patients with a lower level of education, who discussed the choice with social circle, and who most feared side-effects were more likely to choose the sequential treatment. Physicians were able to predict patients' choice in 66% of cases. 89% of patients declared that they were ifully satisfiedi with having participated in the choice of treatment and 79% supported shared decision-making. Conclusions: Results are in favour of promoting active participation of cancer-patients in medical decision-making. The adequate degree of such participation remains however to be elicited and tested for therapeutic choices implying more difficult trade-offs between quantity and quality of life.

Resume Objectif de l'etude. Les cancers du col uterin de stade limite sont tres souvent traites en France par une association radio-chirurgicale incluant apres curietherapie uterovaginale, une hysterectomie radicale identique a celle pratiquee en cas de chirurgie premiere. L'analyse prospective presentee concerne les resultats d'une association de curietherapie et d'hysterectomie vaginale non elargie chez des patientes qui avaient les facteurs pronostiques les plus favorables. Patientes et methodes. Apres lymphadenectomie percœlioscopique n'ayant pas objective d'envahissement ganglionnaire sur un nombre median de 12 ganglions lymphatiques preleves, 22 patientes dont la mediane de la dimension tumorale maximale etait de 1 cm (trois de stade Ia2 avec emboles et 19 de stade Ib1) ont beneficie d'une hysterectomie simple par voie basse 6 semaines apres une curietherapie uterovaginale. Resultats. Deux complications peroperatoires ont ete observees, une hemorragie veineuse de 100 mL lors de la lymphadenectomie avec hemostase par cœlioscopie et une plaie vesicale lors de l'hysterectomie suturee par voie basse. Une seule complication tardive a ete observee, une complication vesicale de grade G2 (b). Avec un suivi median de 29 mois (extremes: 20–48 mois), aucune recidive n'a ete deploree. Conclusion. Sous reserve d'une confirmation avec un effectif plus important, il semble qu'une hysterectomie vaginale non elargie apres curietherapie uterovaginale soit suffisante pour traiter ces formes les plus favorables des cancers du col uterin. © 1998, Elsevier, Paris.

Background and purpose : Symptoms of acute radiation enteritis (ARE), dominated by diarrhea, occur in more than 70% of patients receiving pelvic irradiation. Eicosanoids and free radicals release have been implicated in the pathogenesis. Mesalazine (5-ASA) is a potent inhibitor of their synthesis in the mucosa and could therefore be of some interest in preventing ARE. Patients and methods : The study was performed in six radiotherapy units in France who agreed on standardized irradiation procedures. One hundred and fifty-three patients planned for external beam radiotherapy to the pelvis ≥45 Gy for prostate ( n = 97) or uterus ( n = 54) cancer were randomized on a double blind basis to receive prophylactic 5-ASA (4 g/day Pentasa ® ) or placebo. Patients with concomitant chemotherapy were excluded. Prostate and uterus cancers were chosen since these centropelvic tumors require a similar radiotherapy protocol during the first step of treatment and involve a comparable volume of small intestine. The symptoms of ARE and their severity were assessed every week during irradiation, and 1 and 3 months after its end. All patients followed a low fiber and low lactose diet. End points were diarrhea, use of antidiarrheal agents, abdominal pain, and body weight. Effficacy was evaluated using intention to treat. Results : (means ± SD) Groups did not differ for age (mean 64 ± 9 years), sex, tumor site, or irradiation procedure. During irradiation, diarrhea occurred in 69% and 66% of the 5-ASA and placebo groups, respectively ( χ 2 , P = 0.22). Curves of survival without diarrhea did not differ between groups (logrank P = 0.09). Severity of diarrhea did not differ between groups except at d15 where it was significantly more severe in the 5-ASA group (ANOVA P = 0.006). Duration of diarrhea did not differ (22 ± 15 days in both groups, P = 0.88). Abdominal pain was less frequently reported in the 5-ASA group at d28 (34% vs. 51%, P = 0.048). Use of antidiarrheal agents and body weight did not differ between groups. Conclusion : Mesalazine 4 g/day did not decrease the symptoms of ARE.

Resume But de l'etude Les myelofibroses (MF) et les leucemies myeloides chroniques (LMC) sont des maladies au cours desquelles apparait frequemment une splenomegalie, temoin d'une importante metaplasie splenique. Des irradiations spleniques sont pratiquees en pareil cas depuis fort longtemps, mais les donnees exploitables demeurent peu nombreuses et les modalites optimales de ces traitements restent a definir. Les resultats de l'irradiation splenique dans les hemopathies myeloides ont fait l'objet d'une analyse retrospective. Patients et methodes Il s'agissait de 24 patients dont 15 atteints de MF et neuf de LMC. Les doses totales d'irradiation medianes delivrees etaient respectivement de 9,8 et 7,7 Gy. Resultats La toxicite hematologique a ete moderee (hormis la toxicite plaquettaire survenue chez des patients en phase aigue de leur maladie). Aucune autre toxicite n'a ete observee. Nous avons mis en evidence certains facteurs predictifs de reponse a l'irradiation. Ainsi, dans les MF, il apparait necessaire, si possible, de delivrer une dose totale d'irradiation d'environ 14 Gy et d'initier l'irradiation avant d'etre confronte a des besoins transfusionnels trop importants. Dans les LMC, il est preferable d'exclure les splenomegalies tres volumineuses des indications d'irradiation ; il faut probablement tenter de delivrer des doses suffisantes d'au moins 10 Gy, mais notre travail ne nous permet pas de conclure. Conclusion Des etudes prospectives de phase Il restent a mettre en place afin d'etudier l'interet d'une radio-chimiotherapie et d'apprehender les mecanismes biologiques de radiosensibilite dans les MF.

The aim of this work was to measure the safety and efficacy of single i.v. doses of dolasetron mesilate for the control of emesis caused by single high-dose (at least 6 Gy) radiotherapy to the upper abdomen. The double-blind, placebo-controlled, multicenter study stratified patients on the basis of being naive or nonnaive to radiotherapy. Patients with or without a history of previous chemotherapy were enrolled. Patients were randomized to receive placebo or 0.3, 0.6, or 1.2 mg/kg dolasetron mesilate 30 min before radiotherapy, then monitored for 24 h. Antiemetic efficacy was assessed from the time to the first emetic episode or rescue, from whether there was a complete response (0 emetic episodes /no rescue medication) or a complete-plus-major response (0-2 emetic episodes/no rescue medication), from the severity of nausea (rated by patients and the investigator), and from the investigator's assessment of efficacy. Fifty patients completed the study (owing to changing medical practice, enrollment objectives were not met; consequently, no significant linear dose trend was expected). Pooled dolasetron was superior to the placebo in its effect on the time to first emesis or rescue in radiotherapy-nonnaive patients (P = 0.015). Dolasetron was statistically superior to the placebo in the overall population on the basis of a complete plus major response: 54%, 100%, 93%, and 83% for the placebo and 0.3-, 0.6-, and 1.2-mg/kg doses respectively (P = 0.002). The low response in the highest dose group may be due to an imbalance in the number of chemotherapy-nonnaive patients in that group. Dolasetron was superior to the placebo on the basis of nausea assessed by the investigator (P = 0.024) and administration of rescue medication (P = 0.006). Complete response at the 0.3-mg/ kg dose was superior to results with the placebo (P = 0.050). Treatment-related adverse events were rare, mild to moderate in intensity, and evenly distributed across the four groups. Overall, dolasetron mesilate was effective and well-tolerated in the control of single, high-dose radiotherapy-induced emesis.

Purpose : Thymoma is a rare disease. The treatment of patients with invasive thymoma remains controversial. The prognosis of such patients is poor, even with the use of postoperative radiation therapy and chemotherapy. We retrospectively reviewed the outcome and prognostic factors in a series of 90 patients presenting with an invasive thymoma treated by partial resection or biopsy and radiation therapy. Methods and Materials : From 1979-1990, 163 patients with the diagnosis of lymphoepithelial thymoma were treated in 10 French cancer centers. Patients were staged using the postoperative GETT classification derived from that of Masaoka. Ninety patients who presented with an invasive thymoma, 58 Stage III (21 IIIA : partial resection and 37 IIIB : biopsy) and 32 Stage IVA (intrathoracic thymoma spread), are the subject of this report. Treatment combined surgery and radiation therapy (± chemotherapy), with curative intent. Surgery consisted of partial resection in 31 patients (21 Stage III), and biopsy in 55 patients (37 Stage III). The median radiation dose to the tumor was 50 Gy (30-70 Gy). Supraclavicular radiation was performed in 59 patients (median dose 40 Gy). Chemotherapy, combined with radiation in 59 patients, consisted of multidrug regimens, mainly platinum based. Results : The median follow-up is 105 months (20-165 months). The 5- and 10-year overall survival rates are 51 and 39%, respectively. There is a great impact of the extent of surgery on survival : the 5- and 10-year survival rates were 64% and 43%, respectively, after partial resection, compared to 39% and 31% after biopsy (p 50 Gy) than doses used in this study, for incompletely resected patients. The role of chemotherapy needs to be further assessed.

Purpose: To evaluate the importance of fractionating total body hradiation (TBI) in patients receiving an aiiogenic bone marrow transplant (BMT) for an acute myeiobiastic leukemia @ML) in first complete remission (CRl). Methods and Materials: Between 1983 and 1990, 171 consecutive patients received either single dose TBI (STBX) (n = 65) or fractionated TBI (FTBI) (n = 106) after being conditioned with cyciophosphamide and before receiving a non-T-depleted Human Leucocyte Antigen (HLA)-identical marrow. Both groups were comparable except for date of BMT and diagnosis-to-EMT interval (D-BMT). Results: After 63 months median follow-up, transplant-related mortality (TRM), probability of relapse, and 5-year disease-free survival (DFS) were 0.38 and 0.27 @ = 0.04), 0.29 and 0.26 (p = 0.22), 0.43 and 0.56 @ = 0.06), respectively, for STBI and FTBI. The supposed inguence of the schedule of TBI disappeared in the multivariate analysis: TRM was enhanced by severe acute graft vs. host disease (p = 0.0002), early years of transplant (before January 1,1987) (p = O&003), and longer D-BMT intervals (p = 0.038). Relapse was linked to early years of transpi~t (p < O.~l), md the absence of chronic GVHD (p = O&07), Longer DFSs were observed for later years of tr~pI~t (after January 1,1987 and later) Ip = O.OOl), miider acute GVHD @ = O.OOS), and shorter D-BMT intervais @ = 0.045). Important improvement of the rest& were made during the 7-year observation period: TRM, probalitity of relapse, and DFS were, respectively, 0.36, 0.28, and 0.46 for patients transplanted before January 1, 1987 vs. 0.21, 0.15, and 0.67 after that date. Conclusion: Our data strongly suggest that aliogenic BMT is the best postremission treatment for AML in CRl, and the results are better when BMT shortly follows the achievement of remission. The schedule of TBI was of little importance compared with the improvements made in the management of patients undergoing BMT during the 198Os, and, therefore, reports concerning data prior to 1985 should be interpreted cautiously. Total body irradiation, Acute myeloblastic leukemia, Bone marrow transplant.

Thymomas is a rare disease. Staging systems and surgical adjuvant treatments remain controversial. We retrospectively reviewed the outcome and the prognostic factors in a series of 149 patients with non metastatic thymomas treated in ten French cancer centers between 1979 and 1990. Patients were staged according to the "GETT" classification derived from that of Masaoka. There were 13 stage I patients, 46 stage II, 58 stage III and 32 stage IV. Surgery consisted of complete resection in 63 patients, partial resection in 31 patients and biopsy alone in 55 patients. All patients received postoperative radiation therapy and 74 were given postoperative chemotherapy. Median follow-up was 7.7 years. Local control was obtained in 117 patients (78.5%) and was influenced by the extent of surgery (p 60 Gy) must be evaluated. Despite the benefit of the chemotherapy in this retrospective and multicentric study, the role of this treatment remains to be assessed.

Between 1979 and 1990, 149 patients with non-metastatic thymomas were treated in ten French cancer centers. Patients were staged according to the 'GETT' classification, derived from that of Masaoka. There were 13 stage I patients, 46 stage II, 58 stage III and 32 stage IVA. Gross total resections were performed in 63 cases, subtotal resections in 31 cases and in 55 cases a biopsy alone was performed. All patients received radiotherapy and 74 were given post-operative chemotherapy. Median follow-up was 7.7 years. Local control was achieved in 117 cases (78.5%) and was influenced by the stage of the disease (p < 0.01) and the extent of surgery (p < 0.01). Twenty-six patients developed metastatis after a median period of 9 months. Five- and ten-year disease-free survival rates were 59.5% (51-67%) and 49.5% (39-60%), respectively, and were influenced by the stage of the disease (p < 0.01), the extent of surgery (p < 0.001) and a mediastinal compression on presentation (p = 5 x 10(-6)). Four factors could predict a worse overall survival in the multivariate analysis: mediastinal compression on presentation (p < 0.001), absence of chemotherapy (p < 0.001), biopsy alone (p = 0.003), and young age (p = 0.013). A worse DFS was predicted by mediastinal compression on presentation (p < 0.001), absence of chemotherapy (p < 0.001), young age (p = 0.006), and stages III-IVA (p = 0.04). Future therapeutic strategies are discussed and the literature is reviewed.

La mastectomie totale est le traitement de reference en cas de recidive locale (RL) isolee d’un carcinome mammaire. Notre etude a pour objectif de comparer l’efficacite d’une alternative therapeutique a nouveau conservatrice, associant une nouvelle tumorectomie a de la curietherapie interstitielle (TecCur).

Le but de cette etude etait d’identifier l’impact sur la survie d’un diagnostic precoce de la maladie metastatique par le biais du dosage du CA15-3 dans la surveillance des patientes traitees pour cancer du sein non metastatique.

Adenoid cystic carcinoma represents 1% of head and neck cancers. Adenoid cystic carcinomas are slow growing tumours with high potential for local recurrence. Treatment usually associates radiotherapy and surgery, but the role of radiotherapy remains unclear. We report a retrospective multicentric study of the management and prognostic factors of 169 adenoid cystic carcinomas of head and neck.Between 1982 and 2010, 169 patients with adenoid cystic carcinoma of the head and neck were referred to the Cercle des oncologues radiothérapeutes du Sud departments of radiotherapy either for primary untreated tumour (n=135) or for a recurrence of previously treated tumour (n=34). The site of adenoid cystic carcinoma was: parotid gland (n=48, 28.4%), minor salivary gland (n=35, 20.7%), submandibular gland (n=22, 13%), sinus cavities (n=22, 13%), other (n=42, 24.9%). Tumour stages were: T1 (12.4%); T2 (14.2%); T3 (12.4%); T4 (41.4%) and Tx (19.5%). Lymph node involvement was 13% and distant metastasis 8.9%. For adenoid cystic carcinomas of the parotid gland, major nerve involvement was evaluated. Preferential site of metastasis was the lung (87.5%). Treatments were: surgery alone (n=27), surgery and adjuvant radiotherapy (n=89), surgery and adjuvant chemoradiotherapy (n=12), exclusive chemoradiotherapy (n=13), exclusive radiotherapy (n=14), other associations (n=5) and no treatment (n=7). Radiotherapy was delivered through photons (n=119), neutrons (n=6), both (n=4). Two patients had a brachytherapy boost. Median prescribed doses to T and N were respectively 65 Gy and 50 Gy for the 119 photons treated patients.Mean follow-up was 58 months (range 1-250 months). As of December 1, 2010, 83 patients were alive with no evolutive disease (49%), 35 alive and had recurred, 18 had uncontrolled evolutive disease, 28 had died of adenoid cystic carcinoma and 5 of intercurrent disease. Overall survival and disease free survival were respectively 72% and 72% at 5 years, 53% and 32% at 10 years; 5 and 10-year freedom from local recurrence were 81% and 52% respectively. Nerve involvement was found in 17/48 parotid gland adenoid cystic carcinomas. The Cox model including all patients, showed that surgery (P0.001), surgical margins (P=0.015), nerve involvement (P=0.0079), length of radiotherapy (P=0.018), and tumour location (P=0.041) were associated with disease free survival.In this large series of adenoid cystic carcinoma of head and neck with a majority of T3-T4 tumours, 10-year survivals were achieved for 50% of patients. Radiotherapy did not impact survival.

This study retrospectively describes the outcome of a series of 38 patients (pts) with T4 anal carcinoma exclusively treated by radio and chemotherapy.From 1992 to 2007, 38 pts with UST4-N0-2-M0 anal carcinoma were treated with exclusive radiotherapy and chemotherapy. All patients received external beam radiotherapy (EBRT) (median dose 45 Gy) with a concomitant chemotherapy (5-fluorouracil-cisplatin). Eleven patients received neo-adjuvant chemotherapy (5-fluorouracil-cisplatin). After 2-8 weeks, a 15-20 Gy boost was delivered either with EBRT (20 pts) or interstitial (192)Ir brachytherapy (18 pts). Mean follow-up was 66 months.After chemoradiation therapy (CRT), 13 pts (34%) had a complete response, 23 pts (60%) a response50% (2 pts were not evaluated). The 5-year-disease-free survival was 79.2 ± 6.5%, and the 5-year overall survival was 83.9 ± 6%. Eight patients developed tumor progression (mean delay 8.8 months), six of them requiring a salvage surgery with definitive colostomy for local relapse. Late severe complication requiring colostomy was observed in 2 pts. The 5-year-colostomy-free survival was 78 ± 6.9%. Patients who received primary chemotherapy had a statistically significant better 5-year colostomy-free survival (100% vs. 38 ± 16.4%, P = 0.0006).T4 anal carcinoma can be treated with a curative intent using a sphincter-sparing approach of CRT, and neo-adjuvant chemotherapy should be considered prior to radiotherapy.

International audience; The objective is to prospectively determine the factors responsible for reconstruction failure and capsular contracture in mastectomized breast cancer patients who underwent immediate two-stage breast reconstruction with a tissue expander and implant, followed by radiotherapy. This is a multicenter, prospective, non-randomized study. Between February 1998 and September 2006, we prospectively examined 141 consecutive patients, each of which received an implant after mastectomy, followed by chest wall radiotherapy at 46-50 Gy in 23-25 fractions. Radiotherapy was delivered during immediate post-mastectomy reconstruction. Patients were evaluated by both a radiation oncologist and a surgeon 24-36 months after treatment. The median follow-up duration was 37 months. According to Baker's classification, capsular contracture was grade 0, 1, or 2 in 67.5% of cases; it was grade 3 or 4 in 32.5% of cases. In total, 32 breast reconstruction failures required surgery. In univariate analysis, the following factors were associated with Baker grade 3 and 4 capsular contraction: adjuvant hormone therapy ( = 0.02), the surgeon ( = 0.04), and smoking ( = 0.05). Only one factor was significant in multivariate analysis: the surgeon ( = 0.009). Three factors were associated with immediate post-mastectomy breast reconstruction failure in multiple logistic regression analysis: T3 or T4 tumors ( = 0.0005), smoking ( = 0.001), and pN+ axillary status ( = 0.004). Patients with none, 1, 2, or all 3 factors have a probability of failure equal to 7, 15.7, 48.3, and 100%, respectively ( = 3.6 × 10). The model accurately predicts 80% of failures. Mastectomy, immediate reconstruction (expander followed by implant), and radiotherapy should be considered when conservative surgery is contraindicated. Three factors may be used to select patients likely to benefit from this technique with a low failure rate.

Neoadjuvant chemoradiation followed by surgery is the standard of care for locally advanced rectal cancer. The aim of this study was to correlate tumour response to survival and to identify predictive factors for tumour response after chemoradiation.From 1998 to 2008, 168 patients with histologically-proven locally advanced adenocarcinoma treated by preoperative chemoradiation before total mesorectal excision were retrospectively studied. They received a radiation dose of 45 Gy with a concomitant 5-fluoro-uracil-based chemotherapy. Analysis of tumour response was based on the lowering of T stage between pre-treatment endorectal ultrasound and pathologic specimens. Overall and progression-free survival was correlated with tumour response. Tumour response was analysed with predictive factors.The median follow-up was 34 months. Five-year disease-free survival and overall survival were respectively of 44.4% and 74.5% in the whole population, 83.4% and 83.4% in patients with pathological complete response, 38.6% and 71.9% in patients with tumour downstaging, 29.1% and 58.9% in patients with absence of response. A pre-treatment concentration of carcinoembryonnic antigen below 5 ng/mL was significantly associated with tumour downstaging and significantly independently associated with pathologic complete tumour response (P = 0.019).Downstaging and complete response after chemoradiation improved progression-free survival and overall survival of locally advanced rectal adenocarcinoma. In multivariate analysis, a pre-treatment concentration of carcinoembryonnic antigen below 5 ng/mL was associated with complete tumour response, hence with tumour downstaging.

Twenty-seven patients with evaluable metastatic cancer were treated with recombinant interleukin-2 (rIL-2) and escalating doses of interferon gamma (IFN-gamma). rIL-2 was infused over a 15 min period at a constant dose (8 x 10(6) IU/m2/8 h x 5 days first cycle, and 8 x 10(6) IU/m2/12 h x 5 days second and third cycles, with 9 days rest between each cycle). IFN-gamma was started 4 days before each cycle of rIL-2 and was given every other day at a dosage of 1 x 10(6) U/m2 x 3/cycle (four patients), 5 x 10(6) U/m2 x 3/cycle (four patients), 5 x 10(6) U/m2 x 5/cycle (four patients) and 10 x 10(6) U/m2 x 5/cycle (15 patients). Common side effects were fluid retention and hepatic toxicity (27 and 15% grade greater than or equal to 2); one ischemic chest pains and one acute respiratory distress occurred. Toxicities were not greater than those described with high dose rIL-2 alone and were similar in each dose level of IFN-gamma. No patient died from the procedure. Four patients responded, one complete response and three partial responses; all were treated with 25 or 50 x 10(6) U/m2/cycle of IFN-gamma (melanoma, two patients; renal cell carcinoma, one patient; lymphoma, one patient). Further phase II studies at these dosages are justified to precisely define the antitumoral efficacy of this association.

Surgery is the treatment of choice for localized uterine sarcomas. We conducted a retrospective study to define prognostic factors.We studied 111 cases of patients treated by adjuvant radiotherapy for uterine sarcoma in seven French centers. The median decline was 31 months. We conducted a univariate analysis to identify factors correlated with local recurrence. The statistically significant factors were studied in multivariate analysis by Cox model.The median dose of external beam radiotherapy was 45 Gy. Forty-three percent of patients had vaginal vault brachytherapy and 21 % chemotherapy. Only 6.3 % of patients had complications of acute grade III and 8.1 % of long-term sequelae of radiotherapy. The survival rate at 5 years was 74.6 %. They noted 12.6 % of isolated locoregional recurrences, against 29.7 % for distant recurrences, 80 % were pulmonary. Factors correlated with the risk of locoregional relapse were menopausal status (P = 0.045) and surgical margins suspicious or not healthy (P = 0.0095). The chemotherapy did not improve overall survival or disease free survival but the numbers were low.The postoperative radiotherapy provides good local control in this disease. Brachytherapy is sometimes done, but it does not improve local control. Chemotherapy is not a standard localized stage but the rate of metastatic recurrence calls for the development of strategies involving systemic treatment with radiotherapy.

To determine prospectively the factors associated with reconstruction failure (i.e. requiring expander removal) and capsular contracture in patients undergoing mastectomy and immediate two-stage breast reconstruction with a tissue expander and implant, and radiotherapy for breast cancer. This is a multi-institutional prospective nonrandomized trial.Between 2/1998 and 9/2006, we prospectively evaluated 141 consecutive patients who received 141 implants after mastectomy and underwent chest wall radiotherapy (46 to 50 Gy in 23 to 25 fractions). Patients were evaluated after 24 to 36 months by two senior physicians (radiation oncologist and surgeon).Medical follow-up was 37 months. Baker 1 and 2 capsular contracture was observed in 67.5% of patients, Baker 3 and 4 in 32.5%. There were 32 reconstruction failures. In a univariate analysis, the following factors were associated with Baker 3 and 4 capsular contracture: surgeon, use of hormonotherapy and smoking, of which only one remained in the multivariate analysis: surgeon. In a univariate analysis, the following factors were associated with reconstruction failure: tumor size T3 or T4, smoking, pN+ axilla. Three factors remained associated with reconstruction failure in a multiple logistic regression: large tumors T3/T4, smoking and pN+ axilla.Mastectomy, radiotherapy and immediate breast reconstruction with a tissue expander and implant should be considered when breast conserving surgery has been denied. Adequate patients can be easily selected by using three factors of favourable outcome.

It has been previously shown in vitro and in vivo that the human immunodeficiency virus type 1 can be dramatically enhanced by certain heterologous viral, chemical, and physical (ultraviolet irradiation) agents. A common denominator shared by these agents is their ability to cause stress responses in cells. To analyze if a similar effect could occur by X irradiations, we tested the in vitro effect of X rays on HIV LTR-directed gene expression. The results demonstrate that the HIV-1 LTR is activated by X irradiation in a dose- and time-dependent manner, in all cell types tested, including epitheloid, fibroblast, and lymphoid cell lines. This study raises the possibility that exposure of AIDS patients to ionizing radiation (e.g., during treatment of epidemic Kaposi's sarcoma) could play a role in the activation of HIV-1 in vivo.

Objectif Evaluation de la toxicite selon la classification CTCAEv.3 ( Common Terminology Criteria for Adverse Events version 3 ) en fin de radiotherapie et a 3 mois dans le cadre du protocole Artpelvis. Patients et methodes Les criteres d’inclusion etaient : cancers pelviens relevant d’une radiotherapie avec une chimiotherapie (canal anal, col uterin) ou une hormonotherapie de 3 ans (prostate). Les doses delivrees etaient : col uterin : 45 Gy en 25 fractions dans les ganglions non envahis, 59,4 Gy en 33 fractions dans les ganglions atteints et la tumeur, avec ou sans complement de radiotherapie externe ou de curietherapie ; canal anal : 45 Gy en 25 fractions dans les ganglions non envahis, 62 Gy en 35 fractions dans les ganglions atteints et la tumeur, avec ou sans complement de radiotherapie externe ou de curietherapie ; prostate : dans le bras 80 Gy de l’essai 18 du Groupe d’etudes des tumeurs urogenitales (Getug 18) : 46 Gy en 23 fractions dans les ganglions et les vesicules seminales et 80 Gy en 40 fractions dans la prostate ou si boost integre 54,4 Gy en 34 fractions (1,6 Gy par fraction) dans les ganglions et les vesicules seminales et 74,8 Gy en 34 fractions (2,2 Gy par fraction) dans la prostate. Resultats Entre avril 2011 et avril 2013, 118 patients ont ete inclus et les dossiers de 112, 58 hommes et 54 femmes, d’âge moyen 62 ans (29–83), etaient evaluables dans huit centres. Ils etaient atteints de 29 cancers du canal anal, 31 du col uterin et 52 de la prostate. Le suivi median etait de 15 mois. A la fin de la radiotherapie externe, une toxicite grade 3 a ete notee chez 35 % des patients (39/112), cutanee pour 16, gastro-intestinale pour cinq, genito-urinaire pour cinq, autre (douleurs, hematologique) pour 13, et a 3 mois chez 8 % (10/112), cutanee pour quatre, genito-urinaire pour trois, autre pour trois. Aucune toxicite de grade 4 n’etait rapportee. La toxicite cutanee etait notee principalement dans le canal anal (15/16 puis 4/4), ainsi que la toxicite gastro-intestinale (4/5 puis 2/3) et la toxicite genito-urinaire dans la prostate (4/5) Conclusion les resultats preliminaires de cette etude prospective confirment la bonne tolerance de la radiotherapie conformationnelle avec modulation d’intensite, independamment de la technique, dans les cancers pelviens avec seulement 8 % de cas de toxicite de grade 3 a 3 mois et aucun de grade 4. Un suivi prolonge est necessaire pour confirmer ces resultats a moyen et long termes.

The aim of this retrospective study was to evaluate the survival data and rates and patterns of complications and recurrences for patients who had early uterine cervix carcinoma and underwent brachytherapy and subsequent surgery.Between January 1990 and December 1997, 192 women with cervical carcinoma (Stages IA2 with vascular invasion [n = 28], IB1 [n = 144], and IIA [n = 20]) underwent brachytherapy, delivering 60 Gy and then hysterectomy with external iliac lymphadenectomy. Piver class I, II, and III hysterectomies were performed on 136, 38, and 18 patients, respectively. Adjuvant chemoradiotherapy was delivered to patients with positive lymph nodes.The median follow-up time was 61 months. After brachytherapy, a pathologically complete response (CR) was observed in 137 (71.3%) of 192 women. The distribution of CRs according to tumor stage was as follows: Stage IA2, 24 (85.7%) of 28; Stage IB1, 105 (72.9%) of 144; and Stage IIA, 8 (40%) of 20. Patients with Stage IB1 cancer had 13 lymph node metastases (9%), as did 6 with Stage IIA disease (30%). Pelvic recurrences occurred in 9 (4.6%) of the 192 patients; in 3, local relapses were associated with relapses at distant sites. Ten patients had systemic relapses (5.2%). Recurrences at distant sites were more frequent (p0.02) in partial responders, and other recurrences were more frequent in patients with lymph node metastases (p0.04). The overall 5-year disease-free survival rate was 91.2% (96.2% for Stage IA2, 91% for Stage IB1, and 84.4% for Stage IIA cancers). The class of hysterectomy did not influence the outcome. Late complications occurred in 28 patients (Grade 1, 24 [12.5%]; Grade 2, 4 [2%]; and Grade 3, 1 [0.5%] of 192 patients).Combined treatments resulted in high local control and low morbidity rates in patients with early-stage cervical carcinoma. Limited surgery seemed to be adequate after intracavitary therapy.

For a long time, combined external irradiation and brachytherapy has been considered as the standard treatment in patients with advanced cervical cancers. Recently, five clinical randomized trials assessing the role of cis-platin-based chemotherapy delivered concomitantly to radiotherapy have been conducted in the United States. Another clinical randomized trial assessing the role of epirubicin was conducted by the Queen Mary Hospital in Hong Kong. With more than 2,000 enrolled patients, these studies showed converging results with an overall and disease-free survival improvement in the arms combining cis-platin and epirubicin-based chemotherapy and irradiation. These combinations led to a significant decrease in loco-regional evolution or recurrence rates, or even in pulmonary metastases rates. The relative risk of recurrences was decreased by 50%. The relative risk of death was decreased by 40%. The differences, however, were less significant in patients with advanced stages III or IVA. Hematological and digestive acute toxicity was significantly higher in the radiochemotherapy groups, but long-term complications were comparable. The results of these randomized trials have led to a modification in the standard of treatment in these poor prognosis cervix cancers. Five of the randomized trials evidenced the superiority of cis-platin-based chemotherapy, but the optimal chemotherapeutic regimens remain to be defined.

To evaluate the best strategy for treatment of sarcoma that occurs after radiation therapy.Records were retrospectively reviewed for 80 patients with a confirmed histologic diagnosis of sarcoma that occurred after radiation therapy performed during 1975-1995. The patients were treated for breast cancer (n = 33, 42%), non-Hodgkin lymphoma (n = 9, 11%), cervical cancer (n = 9, 11%), benign lesions (n = 4, 5%), or other tumors (n = 25, 31%). Sarcoma occurred after a mean latency of 12 years (range, 3-64 years), with most (70%) developing in the soft tissue. Treatment included surgery (28 patients), surgery and chemotherapy (18 patients), chemotherapy only (15 patients), and radiation therapy (14 patients).By the end of the study, 51 patients were dead, including 46 due to sarcoma. Median survival was 23 months. Overall survival rates at 2 and 5 years, respectively, were 69% and 39% for patients treated with surgery, 10% and 0% for those treated with chemotherapy, and 52% and 35% for those treated with surgery and chemotherapy (P =.001). The 2- and 5-year rates for survival without recurrence were 54% and 32%, respectively.The results confirm the beneficial effect of surgery. Further study is needed to explore the roles of combined treatments.

Low-stage uterine cervix carcinoma can be treated by either surgery, radiation therapy or combined treatments with high cure rates ranging from 90 to 95% for stage IB1 tumors. However, the standard treatment, combining external beam plus intracavitary radiation, fails to control the progression of the disease in 35 to 90% of patients with locally advanced cervical cancer. No substantial improvements have been made in the treatment of these tumors in the past two decades. The addition of concurrent 5-FU in a phase III study failed to improve the results in the overall patient population, but the five-year DFS was significantly better in a subset of patients (tumor5 cm and IB/IIA or medial parametrial IIB disease). Concurrent chemoradiation and adjuvant chemotherapy with epirubicin showed, in a phase III study, a significantly longer DFS in patients treated with chemotherapy despite the same long-term local tumor control. After many phase II studies, five phase III studies have recently demonstrated a 40 to 60% reduction in the relative risk of recurrence with cisplatin-containing chemoradiation. Across these studies, the risk of death was reduced by 30 to 50%. The benefit was less clear in patients with stages III-IV tumors than in patients with lower stages associated with poor prognostic factors. Haematologic and gastrointestinal toxicity of chemoradiation was greater than that of radiotherapy alone. However, late side effects were similar in the different treatment groups. These results must be confirmed with a longer follow-up. The importance of concurrent chemotherapy during the brachytherapy procedure should be analyzed. It has yet to be determined which chemotherapy regimen achieves the most favorable therapeutic ratio.

The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the National Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres (CRLCC) and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery.To update, according to the methodology of SOR, the Standards, Options and Recommendations for the management of patients with cancer of the cervix, and in particular, the place of concomitant radiochemotherapy.Data have been identified by a literature search using Medline (to April 1999) and the personal reference lists of experts. Once the guidelines were defined, the document was submitted for review to independent national and international reviewers and to the medical committees of the CRCC.The principle recommendations concerning the place of radiochemotherapy in the treatment of cancer of the cervix are 1/ the available data shows a significant increase in local control (level of evidence A) and of overall survival (level of evidence B1) following concomitant radiochemotherapy as compared to radiotherapy alone or the combination of radiotherapy-hydroxyurea. For stages IB, IIA, proximal IIB with bad prognostic factors (tumour size greater than 4 cm and/or invasion of pelvic nodes and/or microscopic invasion of the parametrium) and without lumbo-aortic nodal invasion, concomitant radiochemotherapy can be considered as standard treatment. This benefit is less clear for stages distal IIB, III and IVA without para-aortic nodal invasion (level of evidence C) and must be confirmed (expert agreement). 2/ the toxicity of radiochemotherapy is essentially haematologic and gastrointestinal (level of evidence B1) and is greater than that of radiotherapy alone (level of evidence B1). 3/ these results have been obtained by the combination of chemotherapy based oncisplatin alone, or in combination with 5-FU. Although of equal benefit, the toxicity of the cisplatin/5-FU/ hydroxyurea combination was greater than that of cisplatin alone in a trial comparing the two protocols. A significantly longer survival have also been obtained by the combination of chemoradiation and adjuvant chemotherapy with epirubicin (level of evidence C). These results must be confirmed. 4/ the exact means of delivering the chemotherapy has not been clearly established. In fact, in these trials, some protocols use cisplatin weekly at a dose of 40 mg/m2 and others every three or four weeks at doses ranging from 50 to 75 mg/m2. Subsequent randomised studies are likely to establish optimal schema for the delivery of chemotherapy when combined with external radiotherapy and brachytherapy.

Purpose of this study was to assess prognostic value of endoscopic ultrasound in patients with inoperable squamous cell carcinoma of oesophagus treated by radio-chemotherapy.Between January 1993 and March 1996, 89 patients (77 males and 12 females, mean age 60.3 years) with squamous cell carcinoma of the oesophagus were treated exclusively by radio-chemotherapy consisting of 3 courses of chemotherapy using 5FU-Cis-platyl and 3 courses of radiation therapy (3 x 15 Gy). Endoscopy and endoscopic ultrasound (Pentax FG 32 UA) were performed before beginning treatment and two weeks after last cycle of radio-chemotherapy. Classical criteria for endoscopic ultrasound lymph node metastases were used after irradiation; response was considered as complete only if endoscopic ultrasound indicated that integrity of oesophageal wall was fully restored.Complete endoscopic ultrasound assessment was achieved in 73 cases (84.9%). Tumours were classified as T1N1 in 1 case, T2N1 in 7, T3N0 in 4, T3N1 in 24, T4N0 in 1 and T4N1 in 49. For patients with a non-invasive tumour (usT1 or T2), malignancy of lymph nodes was proved by endoscopic ultrasound guided biopsy. Eighty-two patients presented one or more suspicious lymph nodes. Metastatic lymph nodes were located in posterior mediastinum in 43 cases, at distant sites in 27 (laterotracheal in 16 and coeliac in 11) and in 16 lymph nodes were located simultaneously in mediastinum and at distant sites. Median overall survival in these 89 patients was 16 months. There was no significant difference in median survival between patients in stage T3 and T4. Conversely, there was a significant difference between patients with more or less than 4 metastatic lymph nodes (9 vs 36 months, respectively, p = 0.005). Site of lymph node metastasis was also a prognostic factor with better survival in patients presenting mediastinal nodes than those presenting coeliac nodes (30 vs 9 months, respectively, p0.0001). Median survival was also significantly better in patients considered as having achieved a complete response by both gastroduodenal fibrescopy and endoscopic ultrasound than in those considered to have a complete response by gastroduodenal fibrescopy but not by endoscopic ultrasound (49 vs 10 months). Conversely, there was no difference in survival in function of treatment response assessment by thoracic chemotherapy-scan.Endoscopic ultrasound findings regarding number and site of suspicious lymph nodes and degree of treatment response are significant prognostic factors in patients with squamous cell carcinoma of oesophagus treated exclusively by radio-chemotherapy.

The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the National Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres (CRLCC) and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery.To update, according to the methodology of SOR, the Standards, Options and Recommendations for the management of patients with cancer of the cervix, and in particular, the place of concomitant radiochemotherapy.Data have been identified by a literature search using Medline (to April 1999) and the personal reference lists of experts. Once the guidelines were defined, the document was submitted for review to independent national and international reviewers and to the medical committees of the CRLCC.The principle recommendations concerning the place of radiochemotherapy in the treatment of cancer of the cervix are: 1) the available data shows a significant increase in local control (level of evidence A) and of overall survival (level of evidence B1) following concomitant radiochemotherapy as compared to radiotherapy alone or the combination of radiotherapy-hydroxyurea. For stages IB, IIA, proximal IIB with bad prognostic factors (tumour size greater than 4 cm and/or invasion of pelvic nodes and/or microscopic invasion of the parametrium) and without lumbo-aortic nodal invasion, concomitant radiochemotherapy can be considered as standard treatment. This benefit is less clear for stages distal IIB, III et IVA without para-aortic nodal invasion (level of evidence C) and must be confirmed (expert agreement); 2) the toxicity of radiochemotherapy is essentially haematologic and gastrointestinal (level of evidence B1) and is greater than that of radiotherapy alone (level of evidence B1); 3) these results have been obtained by the combination of chemotherapy based on cisplatin alone, or in combination with 5FU. Although of equal benefit, the toxicity of the cisplatin/5FU/hydroxyurea combination was greater than that of cisplatin alone in a trial comparing the two protocols. A significantly longer survival have also been obtained by the combination of chemoradiation and adjuvant chemotherapy with epirubicin (level of evidence C). These results must be confirmed; 4) the exact means of delivering the chemotherapy has not been clearly established. In fact, in these trials, some protocols use cisplatin weekly at a dose of 40 mg/m2 and others every three or four weeks at doses ranging from 50 to 75 mg/m2. Subsequent randomised studies are likely to establish optimal schema for the delivery of chemotherapy when combined with external radiotherapy and brachytherapy.

Tumoral angiogenesis has been described as associated with poor prognosis in breast cancer, particularly for node negative breast cancer. The purpose of this study was to evaluate the influence of angiogenesis in node‐positive breast cancer and particularly its potential impact on adjuvant chemotherapy. Patients and methods: One hundred and thirty‐five node‐positive breast cancer patients who received anthracycline or derivative based adjuvant chemotherapy were selected from the data base of the Institut Paoli Calmettes. Angiogenesis was evaluated using CD31 antibody. Other prognosis variables studied were: hormonal status, tumor size, hormonal receptors, Elston and Ellis grade, and number of involved lymph nodes. Results: In multivariate analysis, a high level of angiogenesis was independently associated with a diminution of survival (p=0.007), and of metastasis‐free survival (p=0.003). Other variables associated with poor survival were progesterone receptor status p=0.003) and Elston' grade p=0.003), and with metastasis‐free survival, progesterone receptor status (p=0.018). Conclusion: Tumoral angiogenesis appears to be an independent prognostic factor for node‐positive breast cancer, when treated with adjuvant chemotherapy. Adjuvant strategies for patients with a high level of angiogenesis should be discussed.

The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery.To develop clinical practice guidelines according to the definitions of Standards, Options and Recommendations for the clinical care of malignant thymoma in adult.Data have been identified by literature search using Medline (december 1998) and the expert groups personal reference lists. Once the guidelines were defined, the document was submitted for review to national and international independent reviewers, and to the medical committees of the 20 French Cancer Centres.The main recommendations for malignant thymoma management are that: 1) the clinical diagnosis is based on appropriate clinical and radiological findings; 2) the final diagnosis is pathological and made from a biopsy, except in cases of well-encapsulated tumors which are completely resected. The biopsy, via anterior mediastinostomy, should be performed by the surgeon who will subsequently perform the definitive surgery; 3) surgical resection must be complete including thymus and perithymic fat and performed by an experienced surgeon; 4) the therapeutic strategy for malignant thymoma is based on the three current staging systems and involves surgery with radiotherapy given if the capsule is invaded or penetrated. Radiotherapy should be given in experienced centres. Inclusion of patients in prospective clinical trials is recommended in order to determine the usefulness of neoadjuvant chemotherapy and multimodality approaches; 5) treatment of metastatic malignant thymoma is based on chemotherapy. Secondary surgery may be performed with the aim of achieving complete resection. Inclusion in clinical trials is recommended; 6) at the present time, there are no clear data on which to base guidelines for timing and duration of follow-up studies in this condition. Because of late recurrence, follow-up should be long.

This study was designed to investigate the personal experience of patients with nonmetastatic breast carcinoma who were treated with the concurrent administration of radiotherapy and chemotherapy in terms of side effects and quality of life (QL).One hundred nine patients with nonmetastatic breast carcinoma, recruited between May 1995 and February 1997, were included in a protocol combining chemotherapy with mitoxantrone and cyclophosphamide, administered intravenously in 4 cycles of 21 days, and concomitant radiotherapy. Side effects of treatment and its impact on patients' daily lives were measured using ad hoc questionnaires; QL was measured by the European Organization for Research and Treatment of Cancer QLQ-C30 QL questionnaire, and pain was measured by a visual analogue scale (VAS).All patients agreed to participate. The mean number of chemotherapy and radiotherapy symptoms per cycle were: 7.2+/-2.5 and 2.4+/-1.8, respectively. Chemotherapy symptoms generally were more frequent and distressing than those of radiotherapy. The average pain score reported on the VAS by patients during treatment was 3.0+/-2.0. Multidimensional QL assessment showed that treatment mainly affects physical functioning and global QL. Multivariate analysis showed that the main determinants of QL at the end of treatment were fatigue, pain, and loss of appetite experienced during treatment. Moreover, 62.8% of patients required specific help for transportation to the hospital and/or home upkeep.The concurrent administration of chemotherapy and radiotherapy deteriorates patients' QL but in a proportion similar to sequential administration while presenting the advantage of a shorter duration of treatment. However, increased fatigue, pain, and loss of appetite as well as difficulties in patients' daily lives have to be taken into account in therapeutic decision-making analysis.

To determine the risk factors for local and distant failure in node-negative breast cancer treated with breast-conservative surgery and radiotherapy and to determine the relationship between these two events.We retrospectively selected 908 patients who received conservative surgery and radiotherapy but no chemotherapy between 1980 and 1995, for a node-negative breast cancer. Patients were divided in two groups according to the status of the margins of resection. All pathology specimens were reviewed.In case of negative margins, the risk factors for local recurrences picked up by the Cox model were histologic multifocality (P = 0.0076), peritumoral vessel invasion (P = 0.021) and ageor = 40 years (P = 0.024), and in case of involved margins, negative oestrogen receptors (P = 0.0012), histologic multifocality (P = 0.0028), and absence of hormonal therapy (P = 0.017). The 10-year local recurrence rate was 18% in case of negative margins and 29% in case of involved margins, although in the latter case patients received high-dose adjuvant radiotherapy. Accordingly, the 10-year distant failure rates were 16% and 27%, respectively. Many arguments suggest that local and distant failures are closely related.Patients with histologic multifocality or positive margins are at high risk of local failure and then of distant failure, and require a more aggressive initial treatment.

In patients with early cervix carcinoma, both radiotherapy and surgery or combined modalities provide effective therapies. In the two last modalities, recommended surgery is radical hysterectomy. The purpose of this prospective study was to assess the value of a limited vaginal hysterectomy after brachytherapy in patients without any unfavorable prognostic factor.Twenty-two patients (stage Ia2 with vascular invasion: three patients, stage Ib 1:19 patients) with 1 cm median maximal tumor size and with previous negative laparoscopic lymphadenectomy (median number of lymph nodes: 12) underwent a limited vaginal hysterectomy 6 weeks after utero-vaginal brachytherapy.Two mild intra-operative complications were noted. Venous hemorrhage (100 mL) occurred in one patient during lymphadenectomy and another patient presented bladder injury during hysterectomy. These two complications were successfully controlled with no need for laparotomy. Only one late complication was observed: bladder grade G2 (b). With a 29 months follow-up (20-48 months), no recurrence was reported.These results appear promising in patients with very early cervix carcinoma but remain to be confirmed on a larger scale.