Abstract Background Despite a high response rate to front-line therapy, prognosis of epithelial ovarian carcinoma (EOC) remains poor. Approaches that combine Cytoreductive Surgery (CRS) and ...Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with this strategy. Patients and methods A retrospective cohort multicentric study from French centres was performed. All consecutive patients with advanced and recurrent EOC treated with CRS and HIPEC were included. Results The study included 566 patients from 13 centres who underwent 607 procedures between 1991 and 2010. There were 92 patients with advanced EOC (first-line treatment), and 474 patients with recurrent EOC. A complete cytoreductive surgery was performed in 74.9% of patients. Mortality and grades 3 to 4 morbidity rates were 0.8% and 31.3%, respectively. The median overall survivals were 35.4 months and 45.7 months for advanced and recurrent EOC, respectively. There was no significant difference in overall survival between patients with chemosensitive and with chemoresistant recurrence. Peritoneal Cancer Index (PCI) that evaluated disease extent was the strongest independent prognostic factor for overall and disease-free survival in all groups. Conclusion For advanced and recurrent EOC, curative therapeutic approach combining optimal CRS and HIPEC should be considered as it may achieve long-term survival in patients with a severe prognosis disease, even in patients with chemoresistant disease. PCI should be used for patient's selection.
Pelvic lymph node dissection has been the standard of care for patients with early cervical cancer. Sentinel node (SN) mapping is safe and feasible and may increase the detection of metastatic ...disease, but benefits of omitting pelvic lymph node dissection in terms of decreased morbidity have not been demonstrated.
In an open-label study, patients with early cervical carcinoma (FIGO 2009 stage IA2 to IIA1) were randomly assigned to SN resection alone (SN arm) or SN and pelvic lymph node dissection (SN + PLND arm). SN resection was followed by radical surgery of the tumour (radical hysterectomy or radical trachelectomy). The primary end-point was morbidity related to the lymph node dissection; 3-year recurrence-free survival was a secondary end-point.
A total of 206 patients were eligible and randomly assigned to the SN arm (105 patients) or SN + PLND arm (101 patients). Most patients had stage IB1 lesion (87.4%). No false-negative case was observed in SN + PLND arm. Lymphatic morbidity was significantly lower in the SN arm (31.4%) than in the SN + PLND arm (51.5%; p = 0.0046), as was the rate of postoperative neurological symptoms (7.8% vs. 20.6%, p = 0.01, respectively). However, there was no significant difference in the proportion of patients with significant lymphoedema between the two groups. During the 6-month postoperative period, the difference in morbidity decreased over time. The 3-year recurrence-free survival was not significantly different (92.0% in SN arm and 94.4% in SN + PLND arm).
SN resection alone is associated with early decreased lymphatic morbidity when compared with SN + PLND in early cervical cancer.
•Randomised study comparing sentinel node biopsy and pelvic lymph node dissection.•Sentinel node biopsy alone is associated with decreased minor lymphatic morbidity.•No increased risk of recurrence while omitting pelvic lymph node dissection.
Triple-negative breast cancers (TNBCs) are considered as associated with poor outcome, but prognosis of subcentimetric, node-negative disease remains controversial and evidence that adjuvant ...chemotherapy (CT) is effective in these small tumours remains limited.
Our objective was to investigate the impact of CT on survival in pT1abN0M0 TNBC. Patients were retrospectively identified from a cohort of 22,475 patients who underwent primary surgery in 15 French centres between 1987 and 2013. As rare pathological types may display very particular prognoses in these tumours, we retained only the invasive ductal carcinomas of no special type according to the last World Health Organisation (WHO) classification which is the most common TNBC histological type. End-points were disease-free survival (DFS) and metastasis-free survival (MFS). A propensity score for receiving CT was estimated using a logistic regression including age, tumour size, Scarff Bloom and Richardson (SBR) grade and lymphovascular invasion.
Of a total of 284 patients with pT1abN0M0 ductal TNBC, 144 (51%) received CT and 140 (49%) did not. Patients receiving CT had more adverse prognostic features, such as tumour size, high grade, young age, and lymphovascular invasion. CT was not associated with a significant benefit for DFS (Hazard ratio, HR = 0.77 0.40–1.46; p = 0.419, log-rank test) or MFS (HR = 1.00 0.46–2.19; p = 0.997), with 5-year DFS and MFS in the group with CT versus without of 90% 81–94% versus 84% 74–90%, and 90% 81–95% versus 90% 83%–95%, respectively. Results were consistent in all supportive analyses including multivariate Cox model and the use of the propensity score for adjustment and as a matching factor for case–control analyses.
This study did not identify a significant DFS or MFS advantage for CT in subcentimetric, node-negative ductal TNBC. Although current consensus guidelines recommend consideration of CT in all TNBC larger than 5 mm, clinicians should carefully discuss benefit/risk ratio with patients, given the unproven benefits.
•Consensus guidelines recommend consideration of treatment in patients with triple-negative breast cancer larger than 5 mm.•We did not identify significant advantage for adjuvant chemotherapy in pT1abN0M0 TNBC patients.•Clinicians should carefully discuss benefit/risk ratio with patients.
Diffuse malignant peritoneal mesothelioma (DMPM) is a severe disease with mainly locoregional evolution. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the ...reported treatment with the longest survival. The aim of this study was to evaluate the impact of perioperative systemic chemotherapy strategies on survival and postoperative outcomes in patients with DMPM treated with curative intent with CRS-HIPEC, using a multi-institutional database: the French RENAPE network.
From 1991 to 2014, 126 DMPM patients underwent CRS-HIPEC at 20 tertiary centres. The population was divided into four groups according to perioperative treatment: only neoadjuvant chemotherapy (NA), only adjuvant chemotherapy (ADJ), perioperative chemotherapy (PO) and no chemotherapy before or after CRS-HIPEC (NoC).
All groups (NA: n = 42; ADJ: n = 16; PO: n = 16; NoC: n = 48) were comparable regarding clinicopathological data and main DMPM prognostic factors. After a median follow-up of 61 months, the 5-year overall survival (OS) was 40%, 67%, 62% and 56% in NA, ADJ, PO and NoC groups, respectively (P = 0.049). Major complications occurred for 41%, 45%, 35% and 41% of patients from NA, ADJ, PO and NoC groups, respectively (P = 0.299). In multivariate analysis, NA was independently associated with worse OS (hazard ratio, 2.30; 95% confidence interval, 1.07-4.94; P = 0.033).
This retrospective study suggests that adjuvant chemotherapy may delay recurrence and improve survival and that NA may impact negatively the survival for patients with DMPM who underwent CRS-HIPEC with curative intent. Upfront CRS and HIPEC should be considered when achievable, waiting for stronger level of scientific evidence.
Abstract Background Two thirds of node-positive breast cancer patients have limited pN1 disease and could benefit from a less extensive axillary lymph node dissection (ALND). Methods 172 breast ...cancers patients requiring an ALND were prospectively enrolled in the Sentibras Protocol of Axillary Reverse Mapping (ARM). Radioisotope was injected in the ipsilateral hand the day before surgery. ALND was standard. Removed lymph nodes were classified into non radioactive nodes and radioactive nodes (ARM nodes). Among ARM nodes, nodes located in the upper outer part of the axilla, above the second intercostal brachial nerve and lateral to the lateral thoracic vein were identified as "zone D ARM nodes". The main objective was: feasibility of identification of the zone D ARM nodes. Secondary objectives were: metastatic involvement and lymphedema rate. Results 100% of patients had ARM nodes identified. The "zone D ARM nodes" were identified in 92 % of cases. The rate of metastatic nodes was 60% in the all cohort, 31% in ARM nodes and 9 % in zone D ARM nodes. Among those, metastatic rate was 6% in patients undergoing ALND for a positive sentinel node biopsy, 6% in case of primary ALND versus 14% after neo-adjuvant chemotherapy (p<0.05). After 34 months of median follow up, 27 % of interviewed patients had a lymphedema. Conclusion The ARM technique reliably identifies the "zone D ARM nodes". These nodes can also easily be identified using knowledge of axillary anatomy. In selected patients, a selective ALND sparing the zone D ARM nodes could be performed.
Abstract Purpose Predictive factors of non-sentinel lymph node (NSN) involvement at axillary lymph node dissection (ALND) have been studied in the case of sentinel node (SN) involvement, with ...validation of a nomogram. This nomogram is not accurate for SN micrometastasis. The purpose of our study was to determine a nomogram for predicting the likelihood of NSN involvement in breast cancer patients with a SN micrometastasis. Methods We collated 909 observations of SN micrometastases with additional ALND. Characteristics of the patients, tumours and SN were analysed. Results Involvement of SN was diagnosed 490 times (53.9%) with standard staining (HES) and 419 times solely on immunohistochemical analysis (IHC) (46.1%). NSN invasion was observed in 114 patients (12.5%), whereas 62.3% (71) had only one NSN involved and 37.7% (43) two or more NSN involved. In multivariate analysis, significant predictive factors were: tumour size (pT stage ≤10 mm or >11 and ≤20 or >20 mm odds ratio (OR) 2.1 and 3.43, micrometastases detected by HES or IHC OR 1.64, presence or absence of lymphovascular invasion (LVI) OR 1.76, tumour histological type mixed or not OR 2.64. The rate and probability of NSN involvement with the model are given for 24 groups, with a representation by a nomogram. Conclusion One group, corresponding to 10.1% of the patients, was associated with a risk of NSN involvement of less than 5%, and five groups, corresponding to 29.8% of the patients, were associated with a risk ≤10%. Omission of ALND could be proposed with minimal risk for a low probability of NSN involvement.
Abstract Background Omission of completion axillary lymph node dissection (ALND) is a standard practice in patients with breast cancer (BC) and negative sentinel nodes (SNs) but has shown ...insufficient evidence to be recommended in those with SN invasion. Methods A retrospective analysis of a cohort of patients with BC and micrometastases (Mic) or isolated tumour cells (ITCs) in SN. Factors associated with ALND were identified, and patients with ALND were matched to patients without ALND. Overall survival (OS) and recurrence-free survival (RFS) were estimated in the overall population, in Mic and in ITC cohorts. Findings Among 2009 patients analysed, 1390 and 619 had Mic and ITC in SN, respectively. Factors significantly associated with ALND were SN status, histological type, age, number of SN harvested and absence of adjuvant chemotherapy. After a median follow-up of 60.4 months, ALND omission was independently associated with reduced OS (hazard ratio HR 2.41, 90 confidence interval CI 1.36–4.27, p = 0.0102), but not with increased RFS (HR 1.21, 90 CI 0.74–2.0, p = 0.52) in the overall population. In matched patients, the increased risk of death in case of ALND omission was found only in the Mic cohort (HR 2.88, 90 CI 1.46–5.69), not in the ITC cohort. The risk of recurrence was also significantly increased in the subgroup of matched Mic patients (HR 1.56, 90 CI 0.90–2.73). Interpretation A separate analysis of Mic and ITC groups, matched for the determinants of ALND, suggested that patients with Mic had increased recurrence rates and shorter OS when ALND was not performed. Our results are consistent with those of previous studies for patients with ITC but not for those with Mic. Randomised controlled clinical trials are still warranted to show with a high level of evidence if ALND can be safely omitted in patients with micrometastatic disease in SN.
A subgroup of T1N0M0 breast cancer (BC) carries a high potential of relapse, and thus may require adjuvant systemic therapy (AST).
Retrospective analysis of all patients with T1 BC, who underwent ...surgery from January 1999 to December 2009 at 13 French sites. AST was not standardized.
Among 8100 women operated, 5423 had T1 tumors (708 T1a, 2208 T1b and 2508 T1c 11–15 mm). T1a differed significantly from T1b tumors with respect to several parameters (lower age, more frequent negative hormonal status and positive HER2 status, less frequent lymphovascular invasion), exhibiting a mix of favorable and poor prognosis factors. Overall survival was not different between T1a, b or c tumors but recurrence-free survival was significantly higher in T1b than in T1a tumors (P = 0.001). In multivariate analysis, tumor grade, hormone therapy and lymphovascular invasion were independent prognostic factors.
Relatively poor outcome of patients with T1a tumors might be explained by a high frequency of risk factors in this subgroup (frequent negative hormone receptors and HER2 overexpression) and by a less frequent administration of AST (endocrine treatment and chemotherapy). Tumor size might not be the main determinant of prognosis in T1 BC.
We determined the prognostic impact of lymphovascular invasion (LVI) in a large, national, multicenter, retrospective cohort of patients with early breast cancer (BC) according to numerous factors.
...We collected data on 17 322 early BC patients treated in 13 French cancer centers from 1991 to 2013. Survival functions were calculated using the Kaplan–Meier method and multivariate survival analyses were carried out using the Cox proportional hazards regression model adjusted for significant variables associated with LVI or not. Two propensity score-based matching approaches were used to balance differences in known prognostic variables associated with LVI status and to assess the impact of adjuvant chemotherapy (AC) in LVI-positive luminal A-like patients.
LVI was present in 24.3% (4205) of patients. LVI was significantly and independently associated with all clinical and pathological characteristics analyzed in the entire population and according to endocrine receptor (ER) status except for the time period in binary logistic regression. According to multivariate analyses including ER status, AC, grade, and tumor subtypes, the presence of LVI was significantly associated with a negative prognostic impact on overall (OS), disease-free (DFS), and metastasis-free survival (MFS) in all patients hazard ratio (HR) = 1.345, HR = 1.312, and HR = 1.415, respectively; P < 0.0001, which was also observed in the propensity score-based analysis in addition to the association of AC with a significant increase in both OS and DFS in LVI-positive luminal A-like patients. LVI did not have a significant impact in either patients with ER-positive grade 3 tumors or those with AC-treated luminal A-like tumors.
The presence of LVI has an independent negative prognostic impact on OS, DFS, and MFS in early BC patients, except in ER-positive grade 3 tumors and in those with luminal A-like tumors treated with AC. Therefore, LVI may indicate the existence of a subset of luminal A-like patients who may still benefit from adjuvant therapy.
•In a study of 17 322 early BC patients, LVI had a significant independent negative prognostic impact on survival.•LVI negatively impacted survival in almost every patient category and cancer subtype, with and without AC.•LVI did not have a negative survival impact in patients with ER+ grade 3 or with luminal A-like tumors with chemotherapy.•Results suggest a possible benefit of AC in LVI-positive luminal A-like patients.
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