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Purpose The aim of this study is to correlate locoregional relapse with radiation therapy volumes in patients with rectal cancer treated with neoadjuvant chemoradiation in the ACCORD 12/0405-PRODIGE 02 trial. Patients and methods We identified patients who had a locoregional relapse included in ACCORD 12's database. We studied their clinical, radiological, and dosimetric data to analyze the dose received by the area of relapse. Results 39 patients (6.5%) presented 54 locoregional relapses. Most of the relapses were in-field (n = 21, 39%) or marginal (n = 13, 24%) with only six out-of-field (11%), 14 could not be evaluated. Most of them happened in the anastomosis, the perirectal space, and the usual lymphatic drainage areas (presacral and posterior lateral lymph nodes). Only patients treated for a lower rectum adenocarcinoma had a relapse outside of the treated volume. 2 patients with T4 tumors extending into anterior pelvic organs had relapses in anterior lateral and external iliac lymph nodes. Conclusions Lowering the upper limit of the treatment field for low rectal tumors increased the risk of out of the field recurrence. For very low tumors, including the inguinal lymph nodes in the treated volume should be considered. Recording locoregional involvement, treated volumes, and relapse areas in future prospective trials would be of paramount interest to refine delineation guidelines.

If androgen deprivation, chemical with LH-RH analogs or surgical with bilateral orchiectomy, still remains the stone edge of treatment of prostate cancer, in the metastatic setting, this hormonosensitivity, most of the time long, finally move on in hormonal-failure. If rare changes in the therapeutic strategy have been achieved in this setting since 2004 and the arrival of docetaxel, it is the global perception of the disease that has been modified and the definition of one specific entity: the castrate-resistant prostate cancer. This new definition and the changes of design and end-points of clinical trials testing new agents with strong recruitment during the past years have conducted to a real revolution in the management of castrate-refractory prostate cancer. The place of secondary hormonal manipulations, such as withdrawal of the anti-androgen, oestrogen or ketoconazole, still exists for a selected group of patients. In case of aggressive disease and symptoms, chemotherapy should be selected, docetaxel, in a three weeks schedule, and may be combined with Estracyt. It is time to consider the revolution of the post-chemotherapy setting with the arrival of two new drugs ; a cytotoxic one, the cabazitaxel and hormonal for the second one, the abiraterone acetate. The place of the immunotherapy with the sipuleucel-T may be more difficult to precise, especially in Europe, even if it has been finally indicated in the United States in the metastatic setting. Concerning bone metastasis, zoledronic acid was during a long time the only bone-targeted agent, effective in reducing the incidence of skeletal related events, and was recently exceeded by the denosumab, an anti-RANK ligand. Finally, let us hope that other changes will be achieved in the near future, with the cabazitaxel-docetaxel confrontation in the first-line setting, and the introduction of the abiraterone acetate before chemotherapy with docetaxel, already tested in ongoing trials.

Resume Rationnel Les manifestations renales associees aux cancers sont frequentes et diverses mais assez peu decrites. Materiel et methodes Une analyse de la litterature en anglais ou francais issue de Medline a ete realisee avec les mots-cles suivants : « cancer », « rein », « syndrome paraneoplasique », « glomerulopathie » et « insuffisance renale ». Resultats Les atteintes renales liees aux neoplasies sont soit specifiques, liees a une atteinte renale directe par la pathologie cancereuse, soit liees a un syndrome paraneoplasique secondaire a la pathologie neoplasique associee. Elles comprennent des glomerulopathies paraneoplasiques (dont la glomerulonephrite extramembraneuse est la plus frequente), des troubles hydroelectrolytiques (une hypercalcemie, un syndrome de secretion inappropriee d’hormone antidiuretique [SIADH]…), un envahissement du parenchyme renal, une compression vasculaire ou des voies excretrices, une fibrose retroperitoneale, une microangiopathie thrombotique et un syndrome de lyse tumorale. Le traitement de la maladie causale ne garantit pas toujours une restitution ad integrum . Conclusion La gravite et la frequence des atteintes renales necessitent un bilan initial et un suivi orientes.

If androgen deprivation, chemical with LH-RH analogs or surgical with bilateral orchiectomy, still remains the stone edge of treatment of prostate cancer, in the metastatic setting, this hormonosensitivity, most of the time long, finally move on in hormonal-failure. If rare changes in the therapeutic strategy have been achieved in this setting since 2004 and the arrival of docetaxel, it is the global perception of the disease that has been modified and the definition of one specific entity: the castrate-resistant prostate cancer. This new definition and the changes of design and end-points of clinical trials testing new agents with strong recruitment during the past years have conducted to a real revolution in the management of castrate-refractory prostate cancer. The place of secondary hormonal manipulations, such as withdrawal of the anti-androgen, oestrogen or ketoconazole, still exists for a selected group of patients. In case of aggressive disease and symptoms, chemotherapy should be selected, docetaxel, in a three weeks schedule, and may be combined with Estracyt. It is time to consider the revolution of the post-chemotherapy setting with the arrival of two new drugs ; a cytotoxic one, the cabazitaxel and hormonal for the second one, the abiraterone acetate. The place of the immunotherapy with the sipuleucel-T may be more difficult to precise, especially in Europe, even if it has been finally indicated in the United States in the metastatic setting. Concerning bone metastasis, zoledronic acid was during a long time the only bone-targeted agent, effective in reducing the incidence of skeletal related events, and was recently exceeded by the denosumab, an anti-RANK ligand. Finally, let us hope that other changes will be achieved in the near future, with the cabazitaxel-docetaxel confrontation in the first-line setting, and the introduction of the abiraterone acetate before chemotherapy with docetaxel, already tested in ongoing trials.

Treatment of metastatic renal cell carcinoma has radically changed during the last decade with the approval of new drugs, antiangiogenic agents and mammalian targets of rapamycin (m-TOR) inhibitors. The outcome of metastatic clear-cell carcinoma has been significantly improved, while other entities such as metastatic papillary renal cell carcinoma are still associated with a poor prognosis. To date, there is no standard guideline for metastatic non clear cell carcinoma. We report the case of a 68-year-old patient with a pulmonary metastatic evolution of a papillary kidney cancer who has had more than 3 years disease progression-free survival and is under ongoing treatment with m-TOR inhibitors.

Renal alterations in the context of neoplastic disease are relatively frequent manifestations but are overall poorly reported.A search in the English and French literature was performed using the following key words: "cancer", "renal", "paraneoplastic syndrome", "glomerulopathy" and "kidney failure".The various renal manifestations can be divided into specific and paraneoplastic. They include paraneoplastic glomerulopathies (membranous glomerulonephristis being the most frequent), direct involvement of the renal parenchyma, hydroelectrolytic abnormalities (hypercalcemia, inappropriate antidiuretic hormone secretion…), retroperitoneal fibrosis, micro-angiothrombotic disease and tumor lysis syndrome. Anticancer and symptomatic treatments do not guaranty complete recovery in all cases.The frequency and the severity of some renal manifestations associated with malignant hemopathies and carcinomas indicates a need for initial renal-oriented work-up and follow-up.

Dear Editor,mTOR inhibitors have been approved for treatment of metastatic renal cell carcinoma (MRCC) in first line (temsirolimus), or in second, or further line (everolimus), treatment after prog...

375 Background: The question regarding the benefit of a TKI rechallenge versus switch to an mTOR inhibitor (mTORi) in mRCC pts who responded to a previous line of TKI remains unanswered and is a common dilemma in clinical practice. We report results of a retrospective study to address this question. Methods: This study retrospectively investigated Duration of Treatment (DT), best radiological response (OR) and predictive factors in pts treated with either TKI-TKI or TKI-mTORi sequences for clear-cell mRCC. Eligibility criteria: 1 TKI in 1st line (L1) followed by another TKI or mTORi as 2nd line (L2). Prior immunotherapy was allowed but not intermediate lines with other drugs. Pts characteristics and Heng’s prognostic factors were collected at each line initiation. Response (resp) was classified with regard to DT and OR using 2 different definitions: def1 = Non Responders (NR): < 4months (m) + PD; Short-Term responders (STR): [4–6]m + SD/PR, Long-term Responders (LTR): >6m + SD/PR, and def2 = NR: < 4m + PD, STR: [4–12]m + SD/PR, LTR: >12m + SD/PR. Results: 127 pts from 7 European centers were retrospectively analyzed. Based on def1, resp to L1 was: LTR=93, STR=20, NR=14; among LTR pts, 54 received a L2=TKI and 39 a L2=mTORi. Based on def2, resp to L1 was: LTR=59, STR=53, NR=15; among LTR pts, 35 received a L2=TKI and 24 a L2=mTORi. Whether def1 or def2, resp (L1 and L2) was never related to Heng’s score. Among LTR pts at L1, 26 out of 54 were LTR after L2=TKI vs 18 out of 39 after L2=mTORi (p=0.85, Z-test) for def1 and 9 out of 35 were LTR after L2=TKI vs 6 out of 24 after L2=mTORi (p=0.95) for def2 (see table). For both def1 and def2, median DT was 7.2m and 6.9m for L2=TKI and L2=mTORi, respectively (p=0.86 and p=0.95, Log-Rank). Conclusions: Results suggest that long-term responders on 1st line TKI could benefit both from TKI and mTORi as 2nd line and there is no evidence to favor one sequence over the other. [Table: see text]