Preoperative Breast Magnetic Resonance Imaging in Women With Local Ductal Carcinoma in Situ to Optimize Surgical Outcomes: Results From the Randomized Phase III Trial IRCIS.

PURPOSE: We evaluated the addition of breast magnetic resonance imaging (MRI) to standard radiologic evaluation on the re-intervention rate in women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery. PATIENTS AND METHODS: Women with biopsy-proven DCIS corresponding to a unifocal microcalcification cluster or a mass less than 30 mm were randomly assigned to undergo MRI or standard evaluation. The primary end point was the re-intervention rate for positive or close margins (< 2 mm) in the 6 months after randomization ( ClinicalTrials.gov identifier: NCT01112254). RESULTS: A total of 360 patients from 10 hospitals in France were included in the study. Of the 352 analyzable patients, 178 were randomly assigned to the MRI arm, and 174 were assigned to the control arm. In the intent-to-treat analysis, 82 of 345 patients with the assessable end point were reoperated for positive or close margins within 6 months, resulting in a re-intervention rate of 20% (35 of 173) in the MRI arm and 27% (47 of 172) in the control arm. The absolute difference of 7% (95% CI, -2% to 16%) corresponded to a relative reduction of 26% (stratified odds ratio, 0.68; 95% CI, 0.41 to 1.1; P = .13). When considering only the per-protocol population with an assessable end point, the difference was 9% (stratified odds ratio, 0.59; 95% CI, 0.35 to 1.0; P = .05). Total mastectomy rates were 18% (31 of 176) in the MRI arm and 17% (30 of 173) in the control arm (stratified P = .93). For 100 lesions seen on MRI, nonmass-like enhancement was more predominant (82%) than mass enhancement (20%). Nevertheless, no specific morphologic and kinetic parameters for DCIS were identified. CONCLUSION: The study did not show sufficient surgical improvement with the use of preoperative MRI to be clinically relevant in DCIS staging. However, this could be reconsidered with the improvement of new MRI sequences and new modalities in magnetic resonance techniques.

[Clinical practice for morbidly obese endometrial cancer patients: A french multicentric study]. / Réalité de la prise en charge du cancer de l'endomètre chez les patientes en obésité morbide : étude française bicentrique.

INTRODUCTION: Morbid obesity may lead to difficulties for management of endometrial cancer. The aim of this study was the assessment of management of endometrial cancer for morbidly obese women and the implementation of recommendations. METHODS: this is retrospective study including women with BMI =40kg/m2 treated for endometrial cancer between November 2010 and April 2017 in the university hospital in Nantes and the Cancer Center René Gauducheau in Nantes. Patients' demographics, pre-operative intra operative, post-operative data and survival were analyzed. RESULTS: Twenty patients met the inclusion criteria with a median age of 65.5 (28-86) and a median BMI of 47kg/m2 (40-60). Type I histologic was identified in 90% and of a stage I FIGO I in 75% of the cases. All the patients have benefited from a biopsy of endometrium before surgery. 70% of the patients have benefited from a MRI before surgery (14/20). The surgery was realized by laparotomy in 40%, by mini invasive surgery in 50% and by vaginal procedure in 10% of. Mini invasive surgery was converted in laparotomy in 40% (4/10). A discrepancy of the ESMO's recommandation was observed in 40% of the cases (8/20). Two patients did not benefit from the adjuvant radiotherapy recommended because of delay of healing. DISCUSSION: Although good prognosis, the endometrial cancer of morbidly obese women seem to be under treat. These patients do not seem benefited an optimal pre-operative assessment. The surgery is mainly realized by laparotomy with a not complete surgical stadification for one more than a third of the patients.

Clinical and Survival Impact of FDG PET in Patients with Suspicion of Recurrent Ovarian Cancer: A 6-Year Follow-Up.

BACKGROUND: The aim of this retrospective study was to evaluate the contribution of fluorine-18-fluoro-deoxyglucose (FDG) positron emission tomography (PET) to the clinical management and survival outcome of patients (pts) suspected of recurrent ovarian carcinoma, with the hypothesis that early diagnosis of recurrent ovarian cancer may improve overall survival (OS). METHODS: Fifty-three FDG PET/CT scans were retrospectively analyzed for 42 pts. CT and PET/CT findings were confirmed by imaging and clinical follow-up, and/or pathology, which were considered as the gold standard diagnosis. The treatment plan based on CT staging was compared with that based on PET/CT findings. Medical records were reviewed for pts characteristics, progression-free survival (PFS), and OS. PFS and OS were analyzed using the Cox proportional hazards regression model. RESULTS: The final diagnosis of recurrence was established pathologically (n = 16), or by a median clinical follow-up of 6.5 years (range 0.5-7.5) after the PET/CT (n = 37). PET/CT provided a higher detection sensitivity (92.2%, 47/51) than CT (60.8%, 31/51) (p < 0.001). Globally, PET/CT modified the treatment plan in 56.6% (30/53) and in 65.2% (15/23) when the CT was negative prior to PET/CT. In 30 cases, those benefited from a modified treatment plan, these changes led to the intensification of a previous treatment procedure in 83.3% (25/30), and to a reduction in the previous treatment procedure in 16.6% of cases (5/30). The Cox regression multivariate analysis showed that the number of lesions visualized by CT and presence of lung lesions detected by PET/CT were significantly associated with PFS (p = 0.002 and p = 0.035, respectively). CONCLUSION: On account of its impact on treatment planning, and especially in predicting patient outcome, FDG PET is a valuable diagnostic tool for cases of suspected ovarian cancer recurrence.

Cost-Effectiveness of Conventional vs Robotic-Assisted Laparoscopy in Gynecologic Oncologic Indications.

OBJECTIVE: Robotic surgical techniques are known to be expensive, but they can decrease the cost of hospitalization and improve patients' outcomes. The aim of this study was to compare the costs and clinical outcomes of conventional laparoscopy vs robotic-assisted laparoscopy in the gynecologic oncologic indications. METHODS: Between 2007 and 2010, 312 patients referred for gynecologic oncologic indications (endometrial and cervical cancer), including 226 who underwent conventional laparoscopy and 80 who underwent robot-assisted laparoscopy, were included in this prospective multicenter study. The direct costs, operating theater costs, and hospital costs were calculated for both surgical strategies using the microcosting method. RESULTS: Based on an average number of 165 surgical cases performed per year with the robot, the total extra cost of using the robot was €1456 per intervention. The robot-specific costs amounted to €2213 per intervention, and the cost of the robot-specific surgical supplies was €957 per intervention. The cost of the surgical supplies specifically required by conventional laparoscopy amounted to €1432, which is significantly higher than that of the robotic supplies (P < 0.001). Hospital costs were lower in the case of the robotic strategy (€2380 vs €2841, P < 0.001) because these patients spent less time in intensive care (0.38 vs 0.85 days). Operating theater costs were higher in the case of the robotic strategy (€1490 vs €1311, P = 0.0004) because the procedure takes longer to perform (4.98 hours vs 4.38 hours). CONCLUSIONS: The main driver of additional costs is the fixed cost of the robot, which is not compensated by the lower hospital room costs. The robot would be more cost-effective if robotic interventions were performed on a larger number of patients per year or if the purchase price of the robot was reduced. A shorter learning curve would also no doubt decrease the operating theater costs, resulting in financial benefits to society.

Survival benefit of hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer: a multi-institutional case control study.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) and complete surgical removal of the tumor, in relapsing patients may provide a clinical benefit. There is no consensus considering the place of HIPEC for patients who had first ovarian cancer relapse. To assess for possible efficacy of HIPEC on overall survival (OS) rates in this situation, we performed a multi-institutional study. METHODS: The current study was a retrospective case control multi-institutional study comparing a group of patients treated with HIPEC to a group of patients treated without HIPEC. Inclusion criteria were first relapse of a serous ovarian carcinoma and >6 months after the end of initial treatment. Exclusion criteria were another pathological subtype of ovarian cancer, a relapse at <6 months after initial treatment, and a second relapse or more. We aimed to assess OS, morbidity, and mortality rates and prognostic factors. RESULTS: From June 1997-July 2011, 42 patients were included, 23 in the HIPEC group and 19 in the control group. Each patient from the two groups had a complete secondary surgery at the time of the first relapse. At 4 years OS was 75.6 % in the HIPEC group and 19.4 % in the control group (p = 0.013). In a multivariate analysis, HIPEC and interval-free before the end of initial treatment were both independent prognostic factors. CONCLUSION: When compared to the control group, complete secondary surgery and HIPEC appear to afford a better OS rate than complete secondary surgery alone, in case of first ovarian cancer relapse. Further randomized trials are warranted to confirm these results.

Margin width should not still enforce a systematic surgical re-excision in the conservative treatment of early breast infiltrative ductal carcinoma.

BACKGROUND: In cases where breast conservative surgery was performed for infiltrative ductal carcinoma (IDC), margin status is an independent prognostic factor for local ipsilateral relapse (LIR). There is no validated definition of a clear margin. We investigated factors associated with residual disease on re-excision specimen and the impact of margin status on the risk of LIR. METHODS: From January 1992 to December 2002, 454 patients were retrospectively included. Patients had undergone conservative surgery and radiotherapy for IDC. Two groups were defined: group 1, involved or close margin (<3 mm) and a re-excision; and group 2, involved or close margin without re-excision. The risk factors for residual disease in the re-excision specimen were analyzed in group 1, and the rate of 5-year LIR was analyzed in both groups. RESULTS: Among patients who experienced a surgical re-excision for involved or close margin, 21% (55 of 206) had residual tumor. The multivariate analysis showed that only a margin involved with intraductal carcinoma remained predictive for residual disease. According to the multivariate analysis, only hormone therapy (p < 10(-6)), diffuse involved margins (p = 0.003), and margins involved with intraductal component (p < 10(-6)) were predictive of LIR. Re-excision for a margin involved with intraductal carcinoma significantly improved local relapse-free survival (p < 0.001). CONCLUSIONS: In cases of IDC, re-excision for a close margin or a focally involved margin had no impact on local relapse-free survival. The decision to perform a surgical re-excision for an involved margin should not be systematic but should take multiple risk factors into consideration, such as patient age or margin diffuse involvement.

A quantitative deficiency in peripheral blood Vγ9Vδ2 cells is a negative prognostic biomarker in ovarian cancer patients.

Vγ9Vδ2 cells are cytotoxic T cells that are able to recognize epithelial ovarian carcinoma (EOC) cells. Therefore, Vγ9Vδ2 cell-based adoptive transfer is an attractive therapy for EOC. However, the inefficient ex vivo expansion after specific stimulation of Vγ9Vδ2 cells from some patients and the relationships between Vγ9Vδ2 cells and clinical course of EOC are issues that remain to be clarified. Herein, peripheral blood mononuclear cells (PBMCs) from 60 EOC patients were stimulated with bromohydrin pyrophosphate (BrHPP) or zoledronate, which are specific agonists of Vγ9Vδ2 cells. The compounds differed in their efficacies to induce ex vivo Vγ9Vδ2 PBMC expansion, but 16/60 samples remained inefficiently expanded with both stimuli. Interestingly, the Vγ9Vδ2 cells in these low-responding PBMCs displayed before expansion (ex vivo PBMCs) an altered production of the pro-inflammatory cytokines IFN-γ and TNF-α, a decreased naive fraction and a reduced frequency. No evidence of an involvement of CD4(+)CD25(+)Foxp3(+) regulatory cells was observed. Importantly, our data also demonstrate that a Vγ9Vδ2 cell frequency of 0.35% or less in EOC PBMCs could be used to predict low responses to both BrHPP and zoledronate. Moreover, our data highlight that such a deficiency is not correlated with advanced EOC stages but is associated with more refractory states to platinum-based chemotherapy and is an independent predictor of shorter disease-free survival after treatment. These results are the first to suggest a potential contribution of Vγ9Vδ2 cells to the anti-tumor effects of chemotherapeutic agents and they strengthen interest in strategies that might increase Vγ9Vδ2 cells in cancer patients.

Paraoxonase 1 (PON1) as a marker of short term death in breast cancer recurrence.

OBJECTIVE: To relate paraoxonase (PON1) activity to survival time and short term death in breast cancer recurrence. DESIGN AND METHODS: PON1 activity was measured by its rate of hydrolysis of two different substrates, paraoxon (PON) and phenylacetate (ARE) in 50 patients with recurrence of breast cancer. Results were compared between patients surviving more than one year after the analysis (22) and those who died within one year (28). RESULTS: In a logistic regression analysis, ARE was negatively associated with early death (OR=0.10 [0.02-0.58], p=0.0109). PON did not reach significance (OR=0.43 [0.17-1.11], p=0.0826). In a multiple logistic regression analysis model, ARE was independently associated with early death (OR=0.12 [0.02-0.98], p=0.0476), besides interval time between diagnosis and recurrence (OR=0.54 [0.27-1.07], p=0.0781) and undernutrition (OR=3.95 [0.81-19.19], p=0.0883). CONCLUSION: Paraoxonase is a potential marker of survival in patients with breast cancer recurrence.

[The role of interval surgery in the treatment's strategy of advanced ovarian cancer]. / Place de la chirurgie d'intervalle dans le traitement du cancer avancé de l'ovaire.

The extent of cytoreductive surgery and the amount of residual disease are among the most important factors impacting the survival of women with advanced ovarian cancer. Chronology of treatment is still debating. In the French standard treatment, primary surgery remains the cornerstone and interval surgery is an option. Neoadjuvant chemotherapy followed by surgery may reduce morbidity and mortality. Nevertheless the impact of this strategy on survival is still controversial.

Oxaliplatin-based hyperthermic intraperitoneal chemotherapy in primary or recurrent epithelial ovarian cancer: A pilot study of 31 patients.

BACKGROUND: The feasibility and safety of oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) associated with cytoreductive surgery (CRS) was assessed in patients with peritoneal carcinomatosis resulting from primary advanced or relapsing epithelial ovarian cancer (EOC). METHODS: Thirty-one patients received neoadjuvant platin-based chemotherapy followed by oxaliplatin-based HIPEC associated with CRS as consolidation of primary therapy (n = 19) or for relapsing disease (n = 12). Grade 3/4 complications were recorded according to National Cancer Institute definitions. RESULTS: Median peritoneal carcinomatosis index (PCI) was 2.7 after neoadjuvant chemotherapy. Mean duration of surgery was 352 min (range 105-614) and median hospital stay was 11 days (range 6-87). Grade 3 toxicity was observed in nine patients: five required repeat surgery, two an invasive procedure, four rehospitalization, and three a return to the ICU. No grade 4 toxicity occurred, excepted one hypokalemia. Median progression-free survival (PFS) for primary advanced EOC was 13.2 months and 1-year PFS was 59.3%. Median PFS for relapsing patients was 14.3 months and 1-year PFS was 54.4%. CONCLUSION: CRS with oxaliplatin-based HIPEC is feasible and relatively safe in recurrent and primary EOC. HIPEC after neoadjuvant chemotherapy reduces the PCI and decreases the number of surgical procedures and morbidity. Further evaluations of this procedure are required to assess the survival benefits.