Adjuvant Chemotherapy in Rectal Cancer after Chemoradiotherapy.

The aim of this overview was to investigate whether adjuvant chemotherapy has a favourable effect on the outcome of patients with rectal cancer who had preoperative (chemo)radiotherapy. A review of randomised clinical trials that allocated patients between fluorouracil-based and observation or between fluorouracil-based and oxaliplatin-based adjuvant chemotherapy after preoperative (chemo)radiotherapy was carried out, including their corresponding meta-analyses. None of the five randomised trials has shown a significant benefit of fluorouracil-based adjuvant chemotherapy for overall survival or disease-free survival. Also, the three corresponding meta-analyses failed to show a benefit of adjuvant treatment. Of three randomised trials - two phase III and one phase II with a 3-year disease-free survival end point - two showed a small benefit of adding oxaliplatin to fluorouracil, one failed. The corresponding meta-analyses showed that the pooled difference was not significant. In conclusion, the use of postoperative 5-fluorouracil-based chemotherapy with or without oxaliplatin in patients with rectal cancer after preoperative (chemo)radiotherapy is not scientifically proven.

[Preoperative chemoradiotherapy for rectal cancer: experience from one centre]. / Chimioradiothérapie préopératoire du cancer du rectum : expérience d'un centre.

PURPOSE: In recent decades, the management of rectal cancer has been significantly improved by optimizing the surgical treatment with the total mesorectal excision and the development of neoadjuvant radiotherapy with or without chemotherapy. In this study, we investigated the impact of changes in practice over a period of 15 years in an expert centre. PATIENTS AND METHODS: A monocentric study was conducted retrospectively on cT3-resectable T4 patients who received chemoradiotherapy for a locally advanced rectal adenocarcinoma between 1993 and 2008. We studied sphincter preservation, pathological complete response (ypT0), survival, and toxicities by different concomitant chemotherapy and treatment period. RESULTS: Among the 179 patients who had a chemoradiotherapy, 56.4% were received concomitant 5-fluoro-uracil-leucovorin, 28.5% with concomitant capecitabine, and 15.1% with concomitant oxaliplatin and capecitabine. The average dose of radiotherapy was 45 Gy (25×1.8 Gy). Five-year disease-free survival was 74.3% and overall survival 68.8%. The rate of local recurrence and distant metastases were 6.1 and 23.6%. In multivariate analysis, concomitant chemotherapy oxaliplatin and capecitabine improved the pathological complete response rate (ypT0; capecitabine: 6%, 5-fluoro-uracil-leucovorin: 10.3%, capecitabine-oxaliplatin: 22.2%), but not significantly (P=0.12) and with more toxicities, and treatment interruptions. Sphincter preservation rate was not improved significantly during the study period (1993-2004 vs. 2005-2008), but disease-free survival improved from 72.2% up to 87.5% (P=0.03). CONCLUSION: Our results are consistent with those published in the literature. Concomitant chemotherapy with 5-fluoro-uracil or capecitabine remains the standard scheme. Upfront chemotherapy, before chemoradiotherapy, should be investigated with regard to the predominance of metastasis.

[Radiation therapy in thyroid cancer]. / Place de la radiothérapie externe dans les cancers de la thyroïde.

Anaplastic thyroid cancers represent 1-2% of all thyroid tumours and are of very poor prognosis even with multimodality treatment including external beam radiation therapy. Conversely, differentiated thyroid carcinomas (at least 80% of thyroid cancers) hamper good prognosis with surgery with or without radioiodine and there is hardly any room for external beam radiation therapy. Insular and medullar carcinomas have intermediary prognosis and are rarely irradiated. We aimed to update recommendations for external beam irradiation in these different clinical situations and put in light the benefits of new irradiations techniques. A search of the French and English literature was performed using the following keywords: thyroid carcinoma, anaplastic, chemoradiation, radiation therapy, surgery, histology and prognostic. Non-mutilating surgery (often limited to debulking) followed by systematic external beam radiation therapy is the standard of care in anaplastic thyroid cancers (hyperfractionated-accelerated radiation therapy with low-dose weekly doxorubicin with or without cisplatin if possible). Given anaplastic thyroid cancers' median survival of 10 months or less, neoadjuvant and adjuvant chemotherapy may also be discussed. Ten-year survival rates for patients with papillary, follicular and Hürthle-cell carcinomas are 93%, 85%, and 76%, respectively. Massive primary incompletely resected iodine-negative disease indicates external beam radiation therapy. Older age (45 or 60-year-old), poor-prognosis histological variants (including tall cell cancers) and insular cancers are increasingly reported as criteria for external beam radiation therapy. Massive extracapsular incompletely resected nodal medullary disease suggests external beam radiation therapy. Radiation therapy morbidity has been an important limitation. However, intensity modulated radiation therapy (IMRT) offers clear dosimetric advantages on tumour coverage and organ sparing, reducing late toxicities to less than 5%. The role of radiation therapy is evolving for anaplastic thyroid cancers using multimodal strategies and new chemotherapy molecules, and for differentiated cancers using minor criteria, such as histological variants, with IMRT becoming a standard of care.

[Multidisciplinary management of rectal cancer]. / État des lieux du traitement multidisciplinaire du cancer du rectum.

In the last 10 years, a number of important European randomized published studies investigated the optimal management of rectal cancer. In order to define an evidence-based approach of the clinical practice based, an international consensus conference was organized in Italy under the endorsement of European Society of Medical Oncology (ESMO), European Society of Surgical Oncology (ESSO) and European Society of Therapeutic Radiation Oncology (ESTRO). The aim of this article is to present highlights of multidisciplinary rectal cancer management and to compare the conclusions of the international conference on 'Multidisciplinary Rectal Cancer Treatment: looking for an European Consensus' (EURECA-CC2) with the new National Comprehensive Cancer Network (NCCN) guidelines.

[Preoperative radiochemotherapy for rectal cancer: forecasting the next steps through ongoing and forthcoming studies]. / Chimioradiothérapie préopératoire des cancers du rectum : ce que laissent présager les études en cours et à venir.

Protracted preoperative radiochemotherapy with a 5-FU-based scheme, or a short course of preoperative radiotherapy without chemotherapy, are the standard neoadjuvant treatments for resectable stage II-III rectal cancer. Local failure rates are low and reproducible, between 6 and 15% when followed with a "Total Mesorectal Excision". Nevertheless, the therapeutic strategy needs to be improved: distant metastatic recurrence rates remain stable around 30 to 35%, while both sphincter and sexual sequels are still significant. The aim of the present paper was to analyse the ongoing trials listed on the following search engines: the Institut National du Cancer in France, the National Cancer Institute and the National Institute of Health in the United States, and the major cooperative groups. Keywords for the search were: "rectal cancer", "preoperative radiotherapy", "phase II-III", "preoperative chemotherapy", "adjuvant chemotherapy" and "surgery". Twenty-three trials were selected and classified in different groups, each of them addressing a question of strategy: (1) place of adjuvant chemotherapy; (2) optimization of preoperative radiotherapy; (3) evaluation of new radiosensitization protocols and/or neoadjuvant chemotherapy; (4) optimization of techniques and timing of surgery; (5) place of radiotherapy for non resectable or metastatic tumors.

Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study.

BACKGROUND: The role of chemoradiation with systemic chemotherapy compared with chemotherapy alone in locally advanced pancreatic cancer (LAPC) is uncertain. PATIENTS AND METHODS: One hundred and nineteen patients with LAPC, World Health Organization performance status of zero to two were randomly assigned to either the induction CHRT group (60 Gy, 2 Gy/fraction; concomitant 5-fluorouracil infusion, 300 mg/m(2)/day, days 1-5 for 6 weeks; cisplatin, 20 mg/m(2)/day, days 1-5 during weeks 1 and 5) or the induction gemcitabine group (GEM: 1000 mg/m(2) weekly for 7 weeks). Maintenance gemcitabine (1000 mg/m(2) weekly, 3/4 weeks) was given in both arms until disease progression or toxicity. RESULTS: Overall survival was shorter in the CHRT than in GEM arm [median survival 8.6 (99% confidence interval 7.1-11.4) and 13 months (8.7-18.1), P = 0.03]. One-year survival was, respectively, 32% and 53%. These results were confirmed in a per-protocol analysis for patients who received 75% or more of the planned dose of radiotherapy. More overall grades 3-4 toxic effects were recorded in the CHRT arm, both during induction (36 versus 22%) and maintenance (32 versus 18%). CONCLUSION: This intensive induction schedule of CHRT was more toxic and less effective than gemcitabine alone.

Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study.

PURPOSE: This multicenter study compared the therapeutic ratio of a monthly schedule of low-dose leucovorin (LV) and fluorouracil (5-FU) bolus with a bimonthly schedule of high-dose LV and 5-FU bolus plus continuous infusion in patients with advanced colorectal cancer. PATIENTS AND METHODS: Of the 448 patients randomly assigned to treatment, 433 were assessable. Treatment A was a monthly regimen of intravenous (IV) LV 20 mg/m2 plus bolus 5-FU 425 mg/m2 for 5 days every 4 weeks. Treatment B was a bimonthly regimen of IV LV 200 mg/m2 as a 2-hour infusion followed by bolus 5-FU 400 mg/m2 and 22-hour infusion 5-FU 600 mg/m2 for 2 consecutive days every 2 weeks. Therapy was continued until disease progression. Second-line chemotherapy, which included 5-FU continuous infusion, was allowed in both arms. RESULTS: The response rates in 348 patients with measurable lesions were 14.4% (monthly regimen) and 32.6% (bimonthly regimen) (P = .0004). The median progression-free survival times were 22 weeks (monthly regimen) and 27.6 weeks (bimonthly regimen) (P = .0012). The median survival times were 56.8 weeks (monthly regimen) and 62 weeks (bimonthly regimen) (P = .067). Grade 3-4 toxicities occurred in 23.9% of patients in the monthly arm compared with 11.1% of those in the bimonthly arm (P = .0004). Patients in arm A more frequently experienced severe granulocytopenia (7.3% v 1.9%), diarrhea (7.3% v 2.9%), and mucositis (7.3% v 1.9%) than patients in arm B. CONCLUSION: The bimonthly regimen was more effective and less toxic than the monthly regimen and definitely increased the therapeutic ratio. However, there was no evidence of increased survival.

Determination of the optimal dose of 5-fluorouracil when combined with low dose D,L-leucovorin and irradiation in rectal cancer: results of three consecutive phase II studies. EORTC Radiotherapy Group.

In three consecutive phase II trials, 5-fluorouracil (5FU)-low dose leucovorin (20 mg/m2/day) was delivered in two 5-day courses during the first (d1 to d5) and the last (d29 to d33) week of a limited pelvic irradiation (45 Gy, 5 weeks, 25 fractions) in patients with locally extended rectal cancer. The three trials differed only by the 5FU dose in the chemotherapy (CT) schemes. In trial 1 (first CT course 5FU dose 425 mg/m2/day, second CT course 370 mg/m2/day), 16 patients were included. 5 patients suffered a grade 3+ toxicity and the compliance was 63%. In trial 2 (first and second CT course 5FU dose 370 mg/m2/day), 53 patients were included. 5 patients suffered a grade 3+ toxicity. The compliance was 94%. In the trial 3 (first and second CT course 5FU dose 350 mg/m2/day), 16 patients were included. 1 patient suffered a grade 3 toxicity and the compliance was 100%. The overall response rate (complete and partial responses) of local disease and distant metastasis were 87 and 7%, respectively. 43 patients were operated on after a mean delay of 8 weeks. Among the 41 macroscopic complete resections, 6 (14.6%) were sterilised and 12 (29.3%) were classified Asler-Coller A/B1. Regression curve analysis using either grade 3+ toxicity or incomplete treatment as an end point against the 5FU dose indicates that a 350 mg/m2/day 5FU dose is advisable for a phase III adjuvant multicentre trial.

[Leiomyosarcoma of the esophagus. Apropos of a case with a review of the literature]. / Léiomyosarcome de l'oesophage. A propos d'un cas avec revue de la littérature.

The authors report a new case of leiomyosarcoma of the oesophagus, and a review of the literature since 1960 (during this period almost every case has been resected). Four macroscopic aspects are observed: polypoid, mediastinal, intra-mural and infiltrating. The accurate diagnosis is difficult and was established before the operation only in half cases. It is based on barium swallow examination and esophagoscopy, that reveal different appearances depending on the anatomical type, and on the biopsy. The interpretation of the biopsy may be difficult because of the superficial nature of the sampling, frequently taking only mucosa or necrotic tissue. It is necessary to remove the necrotic tissue to discover the tumoral tissue, or to perform a wide diathermic snare biopsy. The diagnosis of malignancy is mainly based on the mitosis count, and interpretation of the peroperative pathologic examination is difficult. The surgeon may have to decide on an esophageal resection, according to the gross appearance. Esophagectomy is the most logical treatment; adjuvant radiation therapy could have some efficiency.