Pathological response and safety of two neoadjuvant strategies with bevacizumab in MRI-defined locally advanced T3 resectable rectal cancer: a randomized, noncomparative phase II study.

BACKGROUND: In T3 rectal cancer (RC), preoperative chemoradiotherapy [5-fluorouracil (5-FU-RT)] reduces local recurrences, but does not affect overall survival. New therapeutic options are still necessary to improve clinical outcomes. PATIENTS AND METHODS: This randomized, noncomparative, open-label, multicenter, two arms, phase II study was conducted in MRI-defined locally advanced T3 resectable RC. In arm A, patients received 12-week bevacizumab plus 5-FU, leucovorin and oxaliplatin (Folfox-4) followed with bevacizumab-5-FU-RT before total mesorectal excision (TME). In arm B, patients received only bevacizumab-5-FU-RT before TME. Primary end point was pathological complete response (pCR) rate. RESULTS: Forty-six patients were randomized in arm A and 45 patients in arm B. In arm A, the rate of pCR was 23.8% [95% confidence interval (CI) 12.1% to 39.5%] statistically superior to the defined standard rate of 10%, P = 0.015. In arm B, the rate of pCR of 11.4% (95% CI 3.8% to 24.6%) was not different from 10%, P = 0.906. No death occurred during the study period, from the start until 8 weeks following surgery. Postoperative fistulas were reported for 16 patients (7 in arm A and 9 in arm B). CONCLUSION: Even if the addition of bevacizumab induced manageable toxicities including an increased risk of postoperative fistula and no treatment-related death, arm B did not achieve the expected pCR rate in the population of patients included. Induction bevacizumab-Folfox-4 followed by bevacizumab-5-FU-RT is promising. It is however necessary to continue investigations in the management of locally advanced RC. ClinicalTrials.gov Identifier: NCT 00865189.

Evaluation properties of the French version of the OUT-PATSAT35 satisfaction with care questionnaire according to classical and item response theory analyses.

PURPOSE: The present study investigates the properties of the French version of the OUT-PATSAT35 questionnaire, which evaluates the outpatients' satisfaction with care in oncology using classical analysis (CTT) and item response theory (IRT). METHODS: This cross-sectional multicenter study includes 692 patients who completed the questionnaire at the end of their ambulatory treatment. CTT analyses tested the main psychometric properties (convergent and divergent validity, and internal consistency). IRT analyses were conducted separately for each OUT-PATSAT35 domain (the doctors, the nurses or the radiation therapists and the services/organization) by models from the Rasch family. We examined the fit of the data to the model expectations and tested whether the model assumptions of unidimensionality, monotonicity and local independence were respected. RESULTS: A total of 605 (87.4%) respondents were analyzed with a mean age of 64 years (range 29-88). Internal consistency for all scales separately and for the three main domains was good (Cronbach's α 0.74-0.98). IRT analyses were performed with the partial credit model. No disordered thresholds of polytomous items were found. Each domain showed high reliability but fitted poorly to the Rasch models. Three items in particular, the item about "promptness" in the doctors' domain and the items about "accessibility" and "environment" in the services/organization domain, presented the highest default of fit. A correct fit of the Rasch model can be obtained by dropping these items. Most of the local dependence concerned items about "information provided" in each domain. A major deviation of unidimensionality was found in the nurses' domain. CONCLUSIONS: CTT showed good psychometric properties of the OUT-PATSAT35. However, the Rasch analysis revealed some misfitting and redundant items. Taking the above problems into consideration, it could be interesting to refine the questionnaire in a future study.

DCF (docetaxel, cisplatin and 5-fluorouracil) chemotherapy is a promising treatment for recurrent advanced squamous cell anal carcinoma.

BACKGROUND: Squamous cell carcinoma of the anal canal (SCCA) is a rare disease, mostly diagnosed at early stage. After concurrent chemoradiation (CRT) with mitomycin C and 5-fluorouracil (5FU), local or metastatic recurrences occur in >20% of the patients. After treatment failure, cisplatin (CDDP)-based chemotherapy is the standard option, but complete response (CR) is a rare event and the prognosis remains poor. PATIENTS AND METHODS: Eight consecutive patients with advanced recurrent SCCA after CRT were treated with DCF regimen (docetaxel 75 mg/m(2) day 1, CDDP 75 mg/m(2) day 1 and 5FU at 750 mg/m(2)/day for 5 days every 3 weeks). Tumour samples were analysed for human papillomavirus (HPV) genotyping, as well as p16 and p53 expression. RESULTS: After a median follow-up of 41 months, the overall survival rate at 12 months was 62.5% (95% CI 22.9-86.1 months). Four patients achieved a complete remission and remain relapse-free at the time of analysis with a progression-free survival of 19, 33, 43 and 88 months. Three of these patients underwent surgery for all involved metastatic sites. For all of them, pathological CR was confirmed. DCF regimen appeared feasible in these patients previously exposed to pelvic CRT, and no grade IV toxicity occurred. All patients in complete remission had HPV-16-positive SCCA, while HPV could only be detected among 50% of the non-responding patients. Of interest, immunohistochemical study revealed a p16(+)/p53(-) phenotype in these patients, while none of non-responders expressed p16. CONCLUSION: The high level of complete and long-lasting remission among SCCA patients treated with DCF regimen supports the assessment of this strategy in prospective cohorts.

Multicentre analysis of oncological and survival outcomes following anastomotic leakage after rectal cancer surgery.

BACKGROUND: The association between diverting stomas and symptomatic anastomotic leakage after rectal cancer surgery was studied, as well as the impact of leakage on local recurrence, distant metastasis, and disease-free, overall and cancer-specific survival. METHODS: Data from the Swedish Rectal Cancer Trial, Dutch TME trial, CAO/ARO/AIO-94 trial, EORTC 22921 trial and Polish Rectal Cancer Trial were pooled (n = 5187). All eligible patients without distant metastases at the time of low anterior resection were selected (n = 2726); overall survival was studied in patients aged 75 years or less (n = 2480). Multivariable models were used to study the association between diverting stomas and anastomotic leakage, and between leakage and recurrence or survival. RESULTS: Some 9.7 per cent of patients were diagnosed with a symptomatic anastomotic leak; diverting stomas were negatively associated with leakage (11.6 per cent without and 7.8 per cent with a stoma; P = 0.002). Anastomotic leakage was negatively associated with overall survival in the multivariable analysis (hazard ratio (HR) 1.29 (95 per cent confidence interval 1.02 to 1.63); P = 0.034), but not with cancer-specific survival (HR 1.12 (0.83 to 1.52); P = 0.466). CONCLUSION: Diverting stomas were associated with less symptomatic anastomotic leakage. Oncological outcome was not significantly influenced by leakage, but overall survival was reduced.

[Dosimetric impact of the 2D motion of a platform simulating breathing during a dynamic mode treatment]. / Impact dosimétrique du mouvement 2D d'une plateforme simulant la respiration lors d'un traitement en mode dynamique.

Breathing-adapted techniques in external radiotherapy lead to the improvement of the taken into account of the tumour motion during the patient treatment. Indeed, this motion involves dosimetric uncertainties, in particular during a dynamic treatment (intensity-modulated radiation therapy, dynamic wedge...). As tumoral movement is complex and is carried out in various directions of space, a dynamic platform moving in one or two plans was conceived. This article approaches the technical aspects of design and functioning of this prototype. A study of the dosimetric effects of the respiratory movement on one and two plans during a dynamic treatment without gating will be presented. Films were irradiated while varying the rates with wedged fields at various speeds. The penumbra of beams were compared with the static case and appeared twice broader in the majority of the cases. The results highlighted the contributions of the longitudinal and the axial components of the motion on the form of the dose distribution. These results were completed with gamma index measurements to determine an internal margin. Moreover, this platform proves to be a promising tool for breathing-adapted treatment, in particularly to test the synchronisation of RPM system in fluoroscopic mode in board imaging system.

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.

The diagnosis and management of rectal cancer: expert discussion and recommendations derived from the 9th World Congress on Gastrointestinal Cancer, Barcelona, 2007.

Knowledge of the biology and management of rectal cancer continues to improve. A multidisciplinary approach to a patient with rectal cancer by an experienced expert team is mandatory, to assure optimal diagnosis and staging, surgery, selection of the appropriate neo-adjuvant and adjuvant strategy and chemotherapeutic management. Moreover, optimal symptom management also requires a dedicated team of health care professionals. The introduction of total mesorectal excision has been associated with a decrease in the rate of local failure after surgery. High quality surgery and the achievement of pathological measures of quality are a prerequisite to adequate locoregional control. There are now randomized data in favour of chemoradiotherapy or short course radiotherapy in the preoperative setting. Preoperative chemoradiotherapy is more beneficial and has less toxicity for patients with resectable rectal cancer than postoperative chemoradiotherapy. Furthermore chemoradiotherapy leads also to downsizing of locally advanced rectal cancer. New strategies that decrease the likelihood of distant metastases after initial treatment need be developed with high priority. Those involved in the care for patients with rectal cancer should be encouraged to participate in well-designed clinical trials, to increase the evidence-based knowledge and to make further progress. Health care workers involved in the care of rectal cancer patients should be encouraged to adopt quality control processes leading to increased expertise.

[Radiochemotherapy for oesophageal cancer: a locoregional failure history]. / Chimioradiothérapie des cancers de l'oesophage: chronique d'un échec locorégional.

Esophageal cancer is characterized by various degrees of lymph node invasion and metastasis, both of which are associated with a poor prognosis. Exclusive concomitant radiochemotherapy (RCT) at a dose of 50 Gy delivered over 25 sessions, according to the RTOG 85-01 protocol, has led to improved five-year survival in 25% of patients, whereas no patients survive for five years using radiotherapy alone. Surgery, even when combined with preoperative RCT, also gives disappointing results for locally advanced tumors, which casts serious doubts on the usefulness of preoperative radiotherapy. By varying the fractionation schedule, the length of treatment or the radiotherapy volumes, it has become possible to obtain levels of locoregional relapse of around 35 to 45%. The increasing incidence of adenocarcinoma, which differs from epidermoid cancer with regard to the degree of lymph node invasion, has revived discussion on radiotherapy volumes. Given this difference between these two histological forms, we propose here a number of recommendations concerning radiotherapy volumes for patients presenting with cancer of the esophagus. Finally, analysis of the results for locoregional relapse according to the dose of radiation and the recommended radiotherapy volumes, has led us to investigate why increasing the dose of radiation has no impact in esophageal cancers.

Tumor lymphocyte immune response to preoperative radiotherapy in locally advanced rectal cancer: The LYMPHOREC study.

Introduction: Some studies have suggested that baseline tumor-infiltrating-lymphocytes (TILs), such as CD8+ and FoxP3+ T-cells, may be associated with a better prognosis in colorectal cancer. We sought to investigate modulation of the immune response by preoperative radiotherapy (preopRT) and its impact on survival in locally advanced rectal cancer (LARC). Materials & Methods: We analyzed data for 237 patients with LARC who received RT. Density of TILS (CD8+ and FoxP3+) in intraepithelial (iTILs) and stromal compartments (sTILs) were evaluated from surgery pathological specimens and biopsies performed at baseline. The primary endpoint was to assess the impact of infiltration of the tumor or tumor site after preopRT on progression-free survival (PFS) and overall survival (OS). Secondary endpoints were the impact of dose fractionation scheme on TILs. Results: In univariate analysis, several factors significantly correlated (p<0.05) with PFS and/or OS (T-stage, M-stage, the delay between RT and surgery). A high level of post-treatment FoxP3+ TIL density correlated significantly with a better PFS (p = 0.007). In multivariate analysis, a decrease in the CD8+/FoxP3+ iTILs ratio after preopRT correlated with better PFS and OS (p = 0.049 and p = 0.024, respectively). More particularly, patients with a delta CD8+/FoxP3+ <-3.8 had better PFS and OS. Interestingly, the dose fractionation scheme significantly influenced the CD8+/FoxP3+ ratio after treatment (p = 0.027) with a lower ratio with hypofractionated RT (≥2 Gy). Conclusion: Patients with LARC who had a significant decrease in the CD8+/FoxP3+ ratio after preopRT were more likely to live longer. This ratio needs to be validated prospectively to guide physicians in adjuvant treatment decision-making.

[Preoperative treatments of rectal cancers]. / Traitements préopératoires des cancers rectaux.

Surgery alone is no longer appropriate to the treatment of T3-T4 resecable rectal cancer. Preoperative chemoradiotherapy has recently been approved as the new standard treatment. This approach improves local control with local failure rate raranging now around 6-8%. However, it does not impact on overall survival. It becomes urgent to develop new concepts and a basic research in the understanding of the biological mechanisms that may explain the resistance of the micrometastatic process.

Equivalent uniform dose concept evaluated by theoretical dose volume histograms for thoracic irradiation.

BACKGROUND AND PURPOSE: The goal of our study was to quantify the limits of the EUD models for use in score functions in inverse planning software, and for clinical application. MATERIALS AND METHODS: We focused on oesophagus cancer irradiation. Our evaluation was based on theoretical dose volume histograms (DVH), and we analyzed them using volumetric and linear quadratic EUD models, average and maximum dose concepts, the linear quadratic model and the differential area between each DVH. RESULTS: We evaluated our models using theoretical and more complex DVHs for the above regions of interest. We studied three types of DVH for the target volume: the first followed the ICRU dose homogeneity recommendations; the second was built out of the first requirements and the same average dose was built in for all cases; the third was truncated by a small dose hole. We also built theoretical DVHs for the organs at risk, in order to evaluate the limits of, and the ways to use both EUD(1) and EUD/LQ models, comparing them to the traditional ways of scoring a treatment plan. For each volume of interest we built theoretical treatment plans with differences in the fractionation. CONCLUSION: We concluded that both volumetric and linear quadratic EUDs should be used. Volumetric EUD(1) takes into account neither hot-cold spot compensation nor the differences in fractionation, but it is more sensitive to the increase of the irradiated volume. With linear quadratic EUD/LQ, a volumetric analysis of fractionation variation effort can be performed.

Implementation of intensity-modulated radiotherapy for head and neck cancers in routine practice.

PURPOSE: To report on patterns of relapse following implementation of intensity-modulated radiotherapy and subsequent changes in practice in a tertiary care centre. PATIENTS AND METHODS: Between 2008 and 2011, 188 consecutive patients (mean age 59 years old) received intensity-modulated radiotherapies with curative intent for squamous cell carcinomas of the oral cavity (17.5%), oropharynx (43%), hypopharynx (21%), larynx (14%), sinonasal cavities (6%), nasopharynx (1.5%) at the university hospital of Besançon. There were stage I and II 9%, III 24.5%, IV 66.5%. One hundred and thirty-eight underwent exclusive intensity-modulated radiotherapy, 50 underwent postoperative intensity-modulated radiotherapy, 174 had concurrent chemotherapy, 57 had induction chemotherapy. Dynamic intensity-modulated radiotherapy with static fields was performed for all patients using sequential irradiation in 174 patients and simultaneous integrated boost irradiation in 14 patients. RESULTS: With a median follow-up was 27.5 months, there was 79% of locoregional failures occurred in the 95% isodose. Two-year overall survival, disease-free, local failure-free and locoregional failure-free survival rates were73%, 60%, 79% and 72%, respectively. Prognostic factors for disease-free survival were stage (IV vs. I-III) with a relative risk of 1.7 [1.1-2.8] (P=0.02) and T stage with 1.6 [1.04-2.5] (P=0.03). CONCLUSION: The current series showed similar patterns of failure as in other tertiary care centres. We did not identify intensity-modulated radiotherapy specific relapse risks.

Esophageal cancer: determination of internal target volume for conformal radiotherapy.

BACKGROUND AND PURPOSE: To evaluate esophageal tumor and OAR movement during the respiratory cycle in order to obtain optimal values for ITV and PRV. To correlate tumor motion with chest wall displacement - information of value in the free-breathing gating system. MATERIAL AND METHOD: Inclusion criteria were: histologically proven squamous-cell carcinoma (SCC) or adenocarcinoma at stage T3 - T4 NX or TX N1 M0 according to the UICC 1997 classification. Two spiral scans were performed with breath-hold respiration under spirometric control: one at end expiration (EBH) and the other at end inspiration (IBH). Displacements between exhalation and inhalation were calculated according to ICRU report 42 recommendations. For the correlation study, CT-scan acquisition was performed at the isocenter over a 20 - 40 s period. After Fourier Transform, frequency spectra for amplitude and phase of tumor and chest wall motions were performed for each patient. RESULTS: Cumulative distribution of CTV motion in absolute values showed that 95% of data ranged from 0 to 1 cm. Cumulative distribution of GTV motion in absolute values showed that 95% of data ranged from 0 to 0.8 cm. The correlation study demonstrated no specific relationship between respiratory and esophageal motions. CONCLUSION: The ITV margin for 3D conformal radiotherapy in esophageal cancer was 1 cm when 95% of motions were taken into account in this clinical study involving eight patients. Before using a free-breathing gating system, the correlation between external markers and target displacement during irradiation must be established for each patient.

[Radiotherapy for PSA failure after prostatectomy: which volumes?]. / Radiothérapie pelvienne pour récidive biochimique isolée après prostatectomie pour cancer de prostate: quels volumes?

After prostatectomy, radiotherapy is a potential curable treatment. From the surgery series, it is possible to identify all the localization at risk in case of biochemical relapse after prostatectomy. The target volume of irradiation has to be defined according to the pathological findings. The CTV is limited to the pelvic fascia laterally, to the anterior wall of the rectum behind. The inferior limit includes the anastomosis, and the superior is easier to define with the length of the prostatic gland. The inclusion of area of seminal vesicles and pelvic node areas should be discussed. The use of surgical clips on the anastomosis and image fusionning techniques including the preoperative imaging would help physicians to define the CTV's limits.

[What to do with a rising PSA after complete remission post-prostatectomy?]. / Conduite à tenir devant une ascension du PSA après rémission complète postprostatectomie?

Between twenty and to forty percent of patients will develop an isolated PSA failure after a radical prostatectomy. Pelvic irradiation is a therapeutic option with curative intention. It is the best therapeutic option for young people with good prognostic factors. Combined radiation with hormonal or chemotherapy should be evaluated in patients with poor prognostic factors. For patients with a short life expectancy, hormonotherapy or a watch and see policy are acceptable options.

[Second malignancies after radiotherapy for testicular seminoma: 2 cases]. / Seconds cancers après radiothérapie pour séminome testiculaire: à propos de deux cas.

Orchiectomy with adjuvant radiotherapy of retroperitoneal paraaortic and ipsilateral iliac nodes is the standard treatment for localized testicular seminoma (I, IIA, IIB). Post therapeutic follow-up allows to detect local relapse and radio-induced second cancer. Nevertheless, evaluation of risk of second malignancy still remains difficult. We report 2 cases of rectal cancer after radiotherapy for testicular seminoma.

[Concurrent administration of adjuvant chemotherapy and radiotherapy after breast-conservative surgery enhances late toxicities]. / La chimiothérapie concomitante de la radiothérapie augmente la toxicité tardive après chirurgie conservatrice du cancer du sein.

PURPOSE: In 1996, a multicenter randomized study comparing after breast-conservative surgery, sequential vs concurrent adjuvant chemotherapy (CT) with radiation therapy (RT) was initiated (ARCOSEIN study). Seven hundred sixteen patients were included in this trial. After a median follow-up of 6.7 (4.3-9) years, we decided to prospectively evaluate the late effects of these two strategies. PATIENTS AND METHODS: A total of 297 patients were asked to follow-up from the five larger including institutions. Seventy-two percent (214 patients) were eligible for late toxicity. After breast-conserving surgery with axillary dissection, patients were treated either with sequential treatment with CT first followed by RT (arm A) or CT administered concurrently with RT (arm B). In all patients, CT regimen combined mitoxantrone (12 mg/m(2)), 5-FU (500 mg/m(2)), and cyclophosphamide (500 mg/m(2)), 6 cycles (day 1-day 21). In arm B, patients received concurrently the first 3 cycles of CT with RT. In arm A, RT started 3 to 5 weeks after the 6th cycle of CT. Conventional RT was delivered to the whole breast using a 2 Gy-fraction protocol to a total dose of 50 Gy (+/-boost to the primary tumour bed). The assessment of toxicity was blinded to treatment and was graded by the radiation oncologist according to the LENT-SOMA scale. Skin pigmentation was also evaluated using a personal 5-points scoring system (excellent, good, moderate, poor, very poor). RESULTS: Among the 214 evaluated patients, 107 were treated in each arm. The two populations were homogeneous for patients', tumors' and treatment characteristics. Subcutaneous fibrosis (SF), telengectasia (T), skin pigmentation (SP), and breast atrophy (BA) were significantly increased in arm B. Twenty patients experienced grade superior or equal to 2 (SF) in arm B vs five in arm A (P=0.003). Twenty-five and seven patients showed grade superior or equal to 2 (T) in arm B and A, respectively (P=0.001). Forty-four and twenty patients showed grade superior or equal to 2 (BA) in arm B and A, respectively (P=0.0006). Thirty patients experienced grade superior or equal to 3 (SP) in arm B vs fifteen in arm A (P=0.02). No statistical difference was observed between the two arms concerning grade superior or equal to 2 pain, breast oedema, and lymphoedema. No deaths were caused by late toxicity. CONCLUSION: Following breast conserving surgery, the concurrent use of CT with RT is significantly associated with an increase incidence of grade 2 or greater late side effects.

Dosimetric consequences of breath-hold respiration in conformal radiotherapy of esophageal cancer.

The objective of this paper is to study the dosimetric impact of respiratory gated radiotherapy in locally advanced esophageal carcinomaand to define the optimal respiratory phase for this treatment. The study included 8 consecutive patients with squamous-cell carcinoma (SCC) or histologically proved adenocarcinoma, for both at least T3-T4 NX or TX N1 M0 stage. Informed consent was obtained before beginning the study. Three spiral scans were performed in breath-hold respiration: one acquisition in end expiration (EBH), one in end inspiration (IBH) and one in deep inspiration breathhold (DIBH); and one acquisition was performed in Free Breathing (FB). A 3 mm-margin was defined as Internal Target Volume (ITV) on FB CT-scan. No ITV was applied on EBH, IBH and DIBH CT-scan. Target volumes were analyzed and we performed dosimetric comparisons on DVH data of each CT-scan for PTV and Organs at Risk (OAR) (Conformity Index, V(dose), D(mean), Equivalent Uniform Dose). DIBH and IBH correlated with a 32% (p=0.77) and 20% (p=0.52) decrease in lung V(20) respectively as compared to FB (13.5%and 15.6% respectively versus 19.9%). DIBH and IBH correlated with a 25% (p=0.25) and 17% (p=0.39) decrease in cardiac V(40) respectively, as compared with FB (16.9% and 18.9% respectively versus 22.7%). For spinal cord irradiation, the minimum dose was obtained in IBH (36.5 Gy). Conformal radiotherapy with respiratory gating for esophageal cancer decreases the irradiated dose to OAR. We suggest that DIBH technique should be used when irradiation is performed using the spirometric system. In the Tidal Volume, the inspiration phase is the most favourable and should be chosen for irradiation with a free breathing gating system.

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.

[Rectal squamous cell carcinoma treatment: Retrospective experience in two French university hospitals, review and proposals]. / Prise en charge du carcinome épidermoïde du rectum : expérience de deux centres universitaires français, revue de la littérature et recommandations.

After publishing a retrospective series of 23 patients treated for a rectal squamous cell carcinoma with exclusive curative and conservative intent chemoradiation, we aim to propose a review of the literature about this rare tumour. We identified 11 retrospective studies, on 106 patients, treated between 2007 and 2016. Treatment of rectal squamous cell carcinoma should be similar to anal carcinoma, based on exclusive chemoradiation, displaying a 5-year overall survival rate over 80%, while it was 32% in surgical series. Baseline explorations should be similar as for anal carcinoma, with an interest in PET-CT at diagnosis and monitoring, after a delay over 6 weeks after chemoradiation. Intensity-modulated radiotherapy is legitimate, to a prophylactic dose between 36 and 45Gy, and over 54Gy to the tumour. Concomitant chemotherapy should combine an antimetabolite (5-fluorouracil or capecitabine) and mitomycin C, or cisplatin. This treatment seems well tolerated, associated with grade 2 or above toxicity below 30%. Follow-up should be established on anal squamous cell carcinoma schedule, with endoscopic ultrasonography and PET-CT. Rectal squamous cell carcinoma is a rare tumour; it management should be based on anal curative and conservative intent chemoradiation.