mTOR-inhibitor treatment of metastatic renal cell carcinoma: contribution of Choi and modified Choi criteria assessed in 2D or 3D to evaluate tumor response.

PURPOSE: To determine whether 2D or 3D Choi and modified Choi (mChoi) criteria could assess the efficacy of everolimus against metastatic renal cell carcinoma (mRCC). METHODS: RECIST-1.1, Choi, and mChoi criteria were applied retrospectively to analyse baseline and 2-month contrast-enhanced computed tomography (CECT) images in 48 patients with mRCC enrolled in the everolimus arm of the French randomized double-blind multicentre phase III trial comparing everolimus versus placebo (RECORD-1). The primary endpoint was centrally reviewed progression-free survival (PFS) calculated from the initial RECORD-1 analysis. Mean attenuation was determined for 2D target lesion regions of interest drawn on CECT sections whose largest diameters had been measured, and for the 3D whole target lesion. RESULTS: The median PFS was 5.5 months. The median PFS for everolimus responders defined using 3D mChoi criteria was significantly longer than for non-responders (7.6 versus 5.4 months, respectively), corresponding to a hazard ratio for progression of 0.45 (95 % CI: 0.22-0.92), with respective 1-year survival rates of 31 % and 9 %. No other 2D or 3D imaging criteria at 2 months identified patients who would benefit from everolimus. CONCLUSIONS: At 2 months, only 3D mChoi criteria were able to identify mRCC patients with a PFS benefit from everolimus. KEY POINTS: Choi criteria could not identify everolimus-treated patients with significantly prolonged PFS. mCHOI enabled identification of everolimus-treated mRCC patients with a PFS benefit. 3D attenuation measurement criteria appeared to perform better than single-slice measurement.

Effects of preset sequential administrations of sunitinib and everolimus on tumour differentiation in Caki-1 renal cell carcinoma.

BACKGROUND: Sunitinib (VEGFR/PDGFR inhibitor) and everolimus (mTOR inhibitor) are both approved for advanced renal cell carcinoma (RCC) as first-line and second-line therapy, respectively. In the clinics, sunitinib treatment is limited by the emergence of acquired resistance, leading to a switch to second-line treatment at progression, often based on everolimus. No data have been yet generated on programmed alternating sequential strategies combining alternative use of sunitinib and everolimus before progression. Such strategy is expected to delay the emergence of acquired resistance and improve tumour control. The aim of our study was to assess the changes in tumours induced by three different sequences administration of sunitinib and everolimus. METHODS: In human Caki-1 RCC xenograft model, sunitinib was alternated with everolimus every week, every 2 weeks, or every 3 weeks. Effects on necrosis, hypoxia, angiogenesis, and EMT status were assessed by immunohisochemistry and immunofluorescence. RESULTS: Sunitinib and everolimus programmed sequential regimens before progression yielded longer median time to tumour progression than sunitinib and everolimus monotherapies. In each group of treatment, tumour growth control was associated with inhibition of mTOR pathway and changes from a mesenchymal towards an epithelial phenotype, with a decrease in vimentin and an increase in E-cadherin expression. The sequential combinations of these two agents in a RCC mouse clinical trial induced antiangiogenic effects, leading to tumour necrosis. CONCLUSIONS: In summary, our study showed that alternate sequence of sunitinib and everolimus mitigated the development of mesenchymal phenotype compared with sunitinib as single agent.

Early PSA decrease is an independent predictive factor of clinical failure and specific survival in patients with localized prostate cancer treated by radiotherapy with or without androgen deprivation therapy.

BACKGROUND: The aim was to identify predictors of outcome in patients with localized prostate cancer treated with external beam radiotherapy (EBRT), with or without androgen deprivation therapy (ADT). MATERIALS AND METHODS: A total of 448 patients with prostate cancer received EBRT alone (n = 361, group 1) or ADT followed by EBRT (n = 87, group 2). In group 2, ADT was initiated 3 months before EBRT. After baseline prostate-specific antigen (PSA) determination (PSA(preRT)), PSA was assessed during the 6th week of the EBRT course (PSA(6wRT)) in group 1. In group 2, PSA was measured again 3 months after the start of ADT, before EBRT (PSA(ADT-preRT)). RESULTS: In group 1, median PSA(6wRT)/PSA(preRT) was 0.72 and median prostate-specific antigen velocity (PSAV) was -1.5 ng/ml/month. In the multivariate analysis, prognostic groups and PSA(6wRT)/PSA(preRT) (or PSAV) independently predicted biochemical failure (BF), clinical failure (CF), and prostate cancer-specific survival. In group 2, the median PSA(ADT-preRT) was 1.3 ng/ml. In the high-risk group, an undetectable PSA(ADT-preRT) (< or =0.2 ng/ml) predicted BF (P < 0.01) and CF (P = 0.007). CONCLUSION: A PSA decline 6 weeks after the start of EBRT when used as monotherapy and 3 months after the start of ADT in patients treated with combined ADT and EBRT is predictive of progression and specific survival.

Risk factors for brain relapse in patients with metastatic breast cancer.

BACKGROUND: The occurrence of brain metastases is an emerging problem in patients with metastatic breast cancer. In the present study, we looked at risk factors for brain metastasis among patients with metastatic breast cancer. PATIENTS AND METHODS: The risk factors for brain metastasis were first determined in a series of 215 patients with metastatic breast cancer. Risk factors identified in the multivariate analysis were re-evaluated in a confirmatory series of 199 patients with metastatic breast cancer. All the patients had been included in prospective randomized trials that evaluated chemotherapy or endocrine therapy in an adjuvant setting. RESULTS: In the first series, the presence of lung metastases (hazard ratio = 4.3, 95% CI: 1.9-9.3, P=0.0003) and negative hormone receptor status (hazard ratio = 4.2, 95% CI: 1.7-11, P=0.002) were the only predictive factors associated with the occurrence of brain metastases in the multivariate analysis. The second series confirmed that the presence of lung metastases and negative hormone receptor status were associated with the occurrence of brain metastases. CONCLUSION: The presence of lung metastases as the first site of relapse and a negative hormone receptor status are predictive for the occurrence of brain metastases in patients with metastatic breast cancer. A prophylactic treatment should be evaluated in these subsets of patients.

[Gougerot-Sjögren syndrome disclosed by MALT lymphoma of the salivary glands. Report of 3 cases]. / Syndrome de Gougerot-Sjögren révélé par un lymphome MALT des glandes salivaires. A propos de trois cas.

Sjögren's syndrome is characterized by an increased risk of developing non-Hodgkin's lymphoma. The lymphoma is most frequently extra-nodal, preferentially affecting the salivary gland: low-grade MALT lymphoma. Conversely, underlying Sjögren's syndrome has been recently identified by some authors in patients with non-Hodgkin's lymphoma. In the present report, we present three cases of Sjögren's syndrome disclosed by low-grade salivary gland MALT lymphoma. The patients were all women aged 33, 38 and 52 years. Extension work-up revealed nodal and bone marrow involvement in one case and no evidence of disseminated disease in the two others. Using the European criteria, all of our patients had certain Sjögren's syndrome. Labial salivary gland biopsy and immunopathological studies in newly diagnosed low-grade MALT lymphoma would be helpful in identifying the real frequency of this association.

Rupture of an abdominal aortic aneurysm after endovascular graft placement and aneurysm size reduction.

Reduction in aneurysm size during the months after an endovascular graft placement generally is considered one of the criteria of success. We report the case of a patient with an abdominal aortic aneurysm rupture occurring 9 months after a bifurcated endovascular graft placement despite a greater than 45% reduction in size noted on contrast-enhanced computed tomography scan performed at 7 months. Biomaterial modifications of the stent and of the Dacron explanted stent-graft are analyzed.