Survival of patients managed in France for duodenal neuroendocrine tumors (D-NET): a 20-year multicenter cohort study from the GTE group: a cohort study.

INTRODUCTION: Duodenal neuroendocrine tumours (D-NETs) have a low incidence; however, their diagnosis has been increasing. Features such as tumour location, size, type, histological grade, and stage were used to adapt the treatment to either endoscopic (ER) or surgical (SR) resections. There is no consensus regarding the definitive treatment. The authors' study aimed to describe the management of non-metastatic, well-differentiated D-NETs in France and its impact on patient survival. METHODS: A registry-based multicenter study using prospectively collected data between 2000 and 2019, including all patients managed for non-metastatic G1 and G2 D-NETs, was conducted in the GTE group. RESULTS: A total of 153 patients were included. Fifty-eight benefited from an ER, and 95 had an SR. No difference in recurrence-free survival (RFS) was observed regardless of treatment type. There was no significant difference between the two groups (ER vs. SR) in terms of location, size, grade, or lymphadenopathy, regardless of the type of incomplete resection performed or regarding the pre-therapeutic assessment of lymph node invasion in imaging. The surgery allowed for significantly more complete resection (patients with R1 resection in the SR group: 9 vs. 14 in the ER group, P <0.001). Among the 51 patients with positive lymph node dissection after SR, tumour size was less than or equal to 1 cm in 25 cases. Surgical complications were more numerous ( P =0.001). In the sub-group analysis of G1-G2 D-NETs between 11 and 19 mm, there was no significant difference in grade ( P =0.977) and location ( P =0.617) between the two groups (ER vs. SR). No significant difference was found in both morphological and functional imaging, focusing on the pre-therapeutic assessment of lymph node invasion ( P =0.387). CONCLUSION: Regardless of the resection type (ER or SR) of G1-G2 non-metastatic D-NETs, as well as the type of management of incomplete resection, which was greater in the ER group, long-term survival results were similar between ER and SR. Organ preservation seems to be the best choice owing to the slow evolution of these tumours.

[Thrombosis and cancer: Awareness of private practitioners and patients in Poitou-Charentes, a French region]. / Thrombose et cancer : sensibilisation des professionnels de santé libéraux et des patients en région Poitou-Charentes.

OBJECTIVE: The purpose of this study was to enhance awareness among healthcare professionals about the application of guidelines relating to the management of venous thromboembolism (VTE) in cancer patients. METHODS: This collective approach involved: the Regional Health Agency (ARS), the Unions of Representatives of Healthcare Professionals (URPS), the Observatory of Drugs, the Medical Devices and Therapeutic Innovation agency (OMEDIT), the regional Oncology Network and specialist physicians. Performance indicators were defined to evaluate the actions performed. RESULTS: Multidisciplinary information meetings were organized. A standardized patient's folder was proposed in all healthcare institutions dealing with cancer, as a link between healthcare professionals and patients. Information brochures were prepared for healthcare professionals and patients. Web-based surveys were taken among healthcare professionals to evaluate changes in their knowledge and practices before and after the first actions taken. CONCLUSION: This collective approach improved the awareness of health professionals about care practices for VTE in cancer patients.

Predictors of disease-free survival in colorectal cancer with microsatellite instability: An AGEO multicentre study.

BACKGROUND: A microsatellite instability (MSI) phenotype is found in about 12% of colorectal cancers (CRCs) and is associated with a low recurrence rate after curative surgery. Several studies have identified clinical and pathological factors predictive of recurrence in resected CRC, but not in the MSI subgroup. PATIENTS AND METHODS: This multicentre retrospective study included patients with stage I, II or III MSI CRCs. Disease-free survival (DFS) was calculated with the Kaplan-Meier method. Factors associated with DFS were identified in univariate and multivariate Cox analyses. RESULTS: We studied 521 patients with MSI CRC. Respectively 11%, 51% and 38% of patients were at stage I, II and III. Mean age was 68.7years and 36% of the patients received adjuvant chemotherapy. Median follow-up was 32.8months. The disease recurrence rates were 6% and 21% in stage II and III patients, respectively. The 3-year DFS rate was 77%. In univariate analysis, age, bowel obstruction, lymph node invasion, stage T4, vascular emboli, lymphatic invasion and perinervous invasion were associated with poorer DFS (P<0.05). Three relevant independent predictors of poor DFS were identified in multivariate analysis, namely bowel obstruction (HR=2.46; 95%CI 1.31-4.62, P=0.005), vascular emboli (HR=2.79; 95%CI 1.74-4.47, P<0.001) and stage T4 (HR=2.16; 95%CI 1.31-3.56, P=0.002). CONCLUSIONS: Bowel obstruction, vascular emboli and stage T4 are independently associated with MSI CRC recurrence, suggesting that screening for vascular emboli in routine clinical practice may assist with adjuvant chemotherapy decision-making.

[Adherence to guidelines for the treatment of venous thromboembolism in cancer patients: a retrospective analysis of 145 cases]. / Application des recommandations dans le traitement de la maladie thromboembolique veineuse chez les patients atteints de cancer: étude rétrospective sur 145 cas.

OBJECTIVES: To assess adherence to French guidelines for curative treatment of thromboembolism in cancer patients, and to identify factors limiting their implementation. PATIENTS AND METHODS: Retrospective analysis of the medical files of cancer patients diagnosed with deep vein thrombosis (DVT) and/or pulmonary embolism (PE) in one site between January 1st, 2010 and June 30th, 2011. Central venous catheter thrombosis and superficial vein thrombosis were excluded. RESULTS: The series included 145 patients, among whom 113 (78%) had solid tumors (at a metastatic stage in 68% of cases) and 33 (22%) had hematologic malignancies. Low molecular weight heparin (LMWH) was prescribed as long-term treatment (>10 days) for 83 patients (57.2%) and a vitamin K antagonist (VKA) for 33 patients (22.7%). Bleeding required treatment modifications or discontinuation in 11 (7.5%) and 10 (6.8%) patients respectively. After 6 months, LMWH, VKA and fondaparinux were prescribed for 28, 27 and six (19.3%, 18.6% et 4.1%) patients respectively. Mean duration of anticoagulation was 176.8 days. Treatment was not affected by a history of venous thromboembolism, the presence of pulmonary embolism or proximal deep vein thrombosis but it was significantly shorter in case of thrombosis limited to muscular veins (115.5 vs 182.3 days, P<0.05). Overall, guidelines were fully implemented in only 68 (46.9%) patients, with regards to the choice of pharmacological class and duration of treatment. CONCLUSION: Adherence to national guidelines is insufficient and actions must be taken to improve the management of venous thromboembolism in cancer patients.

Effect of low-frequency KRAS mutations on the response to anti-EGFR therapy in metastatic colorectal cancer.

BACKGROUND: Only patients with wild-type (WT) KRAS tumors benefit from anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (Mabs) in metastatic colorectal cancer (mCRC). Pyrosequencing is now widely used for the determination of KRAS mutation burden and a conservative cut-off point of 10% has been defined. Up until now, the impact of low-frequency KRAS mutations (<10%) on the response to anti-EGFR Mabs has yet to be evaluated. PATIENTS AND METHODS: Tumors from patients receiving anti-EGFR Mabs based on a WT genotype for KRAS, as determined using direct sequencing, have been retrospectively analyzed by pyrosequencing. Patients were categorized as WT (no KRAS mutation) or low-frequency mutation when KRAS mutation was <10% (KRAS low MT). RESULTS: A total of 168 patients treated by anti-EGFR Mabs for mCRC were analyzed. According to pyrosequencing, 138 tumors remained KRAS WT, while 30 tumors were KRAS low MT. In the KRAS low MT and KRAS WT groups, the response rates were 6.7% and 37.0%, respectively, while stabilization amounted to 23.3% versus 32.6% and progression to 70% versus 29% (P < 0.01). Progression-free survival (PFS) was 2.7 ± 0.5 months for KRAS low MT and was 6.0 ± 0.3 months for KRAS WT (P < 0.01). CONCLUSIONS: These results appear to validate consideration of low-frequency KRAS mutation tumors as positive, and justify a large-scale prospective study.

The status of CDKN2A alpha (p16INK4A) and beta (p14ARF) transcripts in thyroid tumour progression.

CDKN2A locus on chromosome 9p21 encodes two tumour suppressor proteins pl6INK4A, which is a regulator of the retinoblastoma (RB) protein, and p14ARF, which is involved in the ARF-Mdm2-p53 pathway. The aim of this study was to determine if CDKN2A gene products are implicated in differentiated thyroid carcinogenesis and progression. We used real-time quantitative RT-PCR and immunohistochemistry to assess both transcripts and proteins levels in 60 tumours specimens. Overexpression of p14ARF and pl6INK4A was observed in follicular adenomas, follicular carcinomas and papillary carcinomas, while downregulation was found in oncocytic adenomas compared to nontumoral paired thyroid tissues. These deregulations were statistically significant for pl6INK4a (P=0.006) in follicular adenomas and close to statistical significance for p14ARF in follicular adenomas (P=0.06) and in papillary carcinomas (P=0.05). In all histological types, except papillary carcinomas, we observed a statistically significant relationship between p14ARF and E2F1 (r=0.64 to 1, P<0.05). Our data are consistent with involvement of CDKN2A transcript upregulation in thyroid follicular tumorigenesis as an early event. However, these deregulations do not appear to be correlated to the clinical outcome and they could not be used as potential prognostic markers.

Expression of TAp73 and DeltaNp73 isoform transcripts in thyroid tumours.

AIM: This study was aimed to determine p73 status in thyroid tumours. METHODS: Differential expression of the TAp73, DeltaTAp73 transcripts was measured in a panel of 60 thyroid malignancies by quantitative RT-PCR. RESULTS: By comparison to normal thyroid tissue surrounding the tumours, we observed significant downregulation of TP73 transcripts in adenomas and in differentiated carcinomas. Correlations were found in normal tissue specimens between the expression of TAp73 and DeltaNp73 transcripts and that of p53, p14ARF p16INK4a, but these correlations were lost in carcinomas (PTC or FTC). CONCLUSIONS: We have found significant variations of TAp73, DeltaNp73, p53, p14ARF p16INK4a, expressions and correlations between the expressions of those different genes in thyroid cancer.