Background
Robotic total mesorectal excision (R-TME), a novel way for minimally invasive treatment of rectal cancer, was shown in previous studies to be safe and effective. However, comparison with ...laparoscopic total mesorectal excision (L-TME) has drawn contradictory disputes, especially concerning operative high-risk patients. The aim of this study was to compare R-TME and L-TME on the rectal technical approach.
Methods
Between October 2009 and March 2013, a total of 120 consecutive rectal carcinomas, operated for sphincter-saving procedure, were enrolled. The patient population included the last 60 laparoscopic procedures and the first 60 robotic surgeries (six hybrid approaches, then 54 full robotic surgeries). There were no exclusions.
Results
Patients’ baseline characteristics were similar in both the R-TME and L-TME groups. Outcomes were equivalent for blood loss (200 vs. 100 mL), postoperative hospital stay (12 vs. 11 days), conversion rate (3.2 vs. 4.8 %), lymph nodes yield (15 vs. 19), no positive distal margin (0 %), positive radial margin (6.4 vs. 9.3 %), diverting ileostomy (73 vs. 58 %) and severe morbidity (28 vs. 20 %). Significant differences were found for median operative time (274 vs. 228 min;
p
= 0.003) and proctectomy performed via transanal approach (1.7 vs. 16.7 %;
p
= 0.004). The R-TME operative time curve stabilized to 245 min after the first 25 procedures.
Conclusions
For rectal cancer, R-TME may be as feasible and safe as L-TME in terms of technique. In our practice and for difficult cases, R-TME allows complete rectal dissection by an abdominal approach, while L-TME requires a transanal approach.
About 15% of Triple-Negative-Breast-Cancer (TNBC) present silencing of the
promoter methylation and are assumed to be Homologous Recombination Deficient (HRD).
-methylated (
-Me) TNBC could, thus, be ...eligible to treatment based on PARP-inhibitors or Platinum salts. However, their actual HRD status is discussed, as these tumors are suspected to develop resistance after chemotherapy exposure.
We interrogated the sensitivity to olaparib
. carboplatin of 8 TNBC Patient-Derived Xenografts (PDX) models. Four PDX corresponded to
, of which 3 were previously exposed to NeoAdjuvant-Chemotherapy (NACT). The remaining PDX models corresponded to two
-mutated (
) and two BRCA1-wild type PDX that were respectively included as positive and negative controls. The HRD status of our PDX models was assessed using both genomic signatures and the functional BRCA1 and RAD51 nuclear foci formation assay. To assess HR restoration associated with olaparib resistance, we studied pairs of
deficient cell lines and their resistant subclones.
The 3
-
PDX that had been exposed to NACT responded poorly to olaparib, likewise
PDX. Contrastingly, 3 treatment-naïve BRCA1-deficient PDX (1
-Me and 2
-mutated) responded to olaparib. Noticeably, the three olaparib-responsive PDX scored negative for BRCA1- and RAD51-foci, whereas all non-responsive PDX models, including the 3 NACT-exposed
PDX, scored positive for RAD51-foci. This suggested HRD in olaparib responsive PDX, while non-responsive models were HR proficient. These results were consistent with observations in cell lines showing a significant increase of RAD51-foci in olaparib-resistant subclones compared with sensitive parental cells, suggesting HR restoration in these models.
Our results thus support the notion that the actual HRD status of
TNBC, especially if previously exposed to chemotherapy, may be questioned and should be verified using the BRCA1- and RAD51-foci assay.
While the utility of circulating cell‐free DNA (cfDNA) in cancer screening and early detection have recently been investigated by testing genetic and epigenetic alterations, here, an original ...approach by examining cfDNA quantitative and structural features is developed. First, the potential of cfDNA quantitative and structural parameters is independently demonstrated in cell culture, murine, and human plasma models. Subsequently, these variables are evaluated in a large retrospective cohort of 289 healthy individuals and 983 patients with various cancer types; after age resampling, this evaluation is done independently and the variables are combined using a machine learning approach. Implementation of a decision tree prediction model for the detection and classification of healthy and cancer patients shows unprecedented performance for 0, I, and II colorectal cancer stages (specificity, 0.89 and sensitivity, 0.72). Consequently, the methodological proof of concept of using both quantitative and structural biomarkers, and classification with a machine learning method are highlighted, as an efficient strategy for cancer screening. It is foreseen that the classification rate may even be improved by the addition of such biomarkers to fragmentomics, methylation, or the detection of genetic alterations. The optimization of such a multianalyte strategy with this machine learning method is therefore warranted.
Certain circulating DNA structural characteristics enable the distinction between plasma from healthy and cancer individuals. Using this observation, a machine learning decision tree prediction model is implemented for noninvasive early detection. The high sensitivity and specificity of the test on more than 1000 individuals supports the belief in the need for machine learning assistance when combining quantitative and/or multiple biomarkers.
The value of MR radiomic features at a microscopic scale has not been explored in ovarian cancer. The objective of this study was to probe the associations of MR microscopy (MRM) images and ...MRM-derived radiomic maps with histopathology in high-grade serous ovarian cancer (HGSOC). Nine peritoneal implants from 9 patients with HGSOC were imaged
with MRM using a 9.4-T MR scanner. All MRM images and computed pixel-wise radiomics maps were correlated with the slice-matched stroma and tumor proportion maps derived from whole histopathologic slide images (WHSI) of corresponding peritoneal implants. Automated MRM-derived segmentation maps of tumor and stroma were constructed using holdout test data and validated against the histopathologic gold standard. Excellent correlation between MRM images and WHSI was observed (Dice index = 0.77). Entropy, correlation, difference entropy, and sum entropy radiomic features were positively associated with high stromal proportion (r = 0.97,0.88, 0.81, and 0.96 respectively,
< 0.05). MR signal intensity, energy, homogeneity, auto correlation, difference variance, and sum average were negatively associated with low stromal proportion (r = -0.91, -0.93, -0.94, -0.9, -0.89, -0.89, respectively,
< 0.05). Using the automated model, MRM predicted stromal proportion with an accuracy ranging from 61.4% to 71.9%. In this hypothesis-generating study, we showed that it is feasible to resolve histologic structures in HGSOC using
MRM at 9.4 T and radiomics.
Chemotherapy is increasingly used in colorectal liver metastases (CRLMs) even when they are initially resectable. The aim of our study was to address the still pending question of whether ...perioperative chemotherapy is really beneficial in patients developing solitary metastases at a distance from surgery of the primary.
We analyzed a multicentric cohort of 1471 patients resected for solitary, metachronous, primarily resectable CRLMs without extrahepatic disease in the LiverMetSurvey International Registry over a 15-year period. Patients who received at least 3 cycles of oxaliplatin- or irinotecan-based chemotherapy before liver surgery (group CS, n = 169) were compared with those who were resected upfront (group S, n = 1302).
Patients of group CS were more frequently females (49% vs 36%, P = 0.001) and had larger metastases (≥5 cm, 33% vs 23%, P = 0.007); no difference was observed with regard to age, site of the primary tumour, time delay to occurrence of metastases, and carcinoembryonic antigen (CEA) levels at the time of diagnosis in the 2 groups. The rate of postoperative complications was significantly higher in group CS (37.2% vs 24% in group S, P = 0.006). At univariate analysis, preoperative chemotherapy did not impact the overall survival (OS) (60% at 5 years in both groups); however, postoperative chemotherapy was associated with better OS (65% vs 55% at 5 years, P < 0.01). At multivariate analysis, age 70 years or older (P = 0.05), lymph node positivity in the primary tumor (P = 0.02), a primary-to-metastases time delay of less than 12 months (P = 0.04), raised CEA levels of more than 5 ng/mL at diagnosis (P < 0.01), a tumor diameter of 5 cm or more (P < 0.01), noncurative liver resection (P < 0.01), and the absence of postoperative chemotherapy (P < 0.01) were independent prognostic factors of survival. The disease-free survival (DFS) was negatively influenced by CEA level of more than 5 ng/mL (P < 0.01), size of the metastases 5 cm or more (P = 0.05), and the absence of postoperative chemotherapy (P < 0.01). When patients with metastases of less than 5 cm in size were compared to those with metastases of size 5 cm or more, preoperative chemotherapy did not influence the OS or DFS in either group. Postoperative chemotherapy, on the other hand, improved OS and DFS in patients with metastases of size 5 cm or more but not in patients with metastases of less than 5 cm in size.
Although preoperative chemotherapy does not seem to benefit the outcome of patients with solitary, metachronous CRLM, postoperative chemotherapy is associated with better OS and DFS, mainly when the tumor diameter exceeds 5 cm.
Triple negative breast cancers (TNBC) are a more aggressive subset of breast cancer. A better understanding of its biology could allow the rational development of targeted therapies.
We extensively ...analyzed the EGFR/PI3K/PTEN axis in a large, homogeneous population of TNBC to help defining the putative role of anti-EGFR and -PI3K targeted therapies in this setting. EGFR gene amplification, EGFR protein expression, PIK3CA and PTEN gene alterations (two members of EGFR downstream pathways) and their clinicopathological and prognostic implications were analyzed in 204 TNBC samples from European patients.
EGFR amplification was detected in 18 of the 204 TNBC specimens (8.9 %) and was significantly associated with higher EGFR protein levels. Fourteen PIK3CA mutations were identified in exon 9 (6.7 %), and 17 in exon 20 (8.3 %). PIK3CA mutations, especially in exon 9, were significantly associated with grade I-II tumors. PTEN deletions were detected in 43 samples (21.50 %) and were significantly associated with grade III tumors (p < 0.001). Univariate analysis showed a significant association between relapse-free survival (RFS), T and N stage and exon 9 PIK3CA mutations. Overall survival was significantly associated with T stage, N stage and adjuvant chemotherapy, which was administered to 70.3 % of patients. In multivariate analyses, T stage, N stage, presence of exon 9 PIK3CA mutations and high EGFR protein level were independent poor prognostic factors for RFS, while adjuvant chemotherapy was associated with a better outcome.
High EGFR protein expression and exon 9 PIK3CA activating mutations are independent prognostic factors in TNBC. The efficacy of anti-PI3K targeted therapies needs to be evaluated in this setting.
Background
Invasive lobular carcinomas (ILCs) represent approximately 10% of all breast cancers. Despite this high frequency, benefit of adjuvant chemotherapy (CT) is still unclear.
Methods
Our ...objective was to investigate the impact of CT on survival in ILC. Patients were retrospectively identified from a cohort of 23,319 patients who underwent primary surgery in 15 French centers between 1990 and 2014. Only ILC, hormone-positive, human epidermal growth factor 2 (HER2)-negative patients who received adjuvant endocrine therapy (ET) were included. End-points were disease-free survival (DFS) and overall survival (OS). A propensity score for receiving CT, aiming to compensate for baseline characteristics, was used.
Results
Of a total of 2318 patients with ILC, 1485 patients (64%) received ET alone and 823 (36%) received ET + CT. We observed a beneficial effect of addition of CT to ET on DFS and OS in multivariate Cox model (HR = 0.61, 95% confidence interval, CI 0.41–0.90;
p
= 0.01 and 0.52, 95% CI 0.31–0.87;
p
= 0.01, respectively). This effect was even more pronounced when propensity score matching was used. Regarding subgroup analysis, low-risk patients without CT did not have significant differences in DFS or OS compared to low-risk patients with CT.
Conclusion
ILC patients could derive significant DFS and OS benefits from CT, especially for high-risk patients.
γδ T-cells contribute to the immune response against many tumor types through their direct cytolytic functions and their capacity to recruit and regulate the biological functions of other immune ...cells. As potent effectors of the anti-tumor immune response, they are considered an attractive therapeutic target for immunotherapies, but their presence and abundance in the tumor microenvironment are not routinely assessed in patients with cancer. Here, we validated an antibody for immunohistochemistry analysis that specifically detects all γδ T-cell subpopulations in healthy tissues and in the microenvironment of different cancer types. Tissue microarray analysis of breast, colon, ovarian, and pancreatic tumors showed that γδ T-cell density varies among cancer types. Moreover, the abundance of γδ tumor-infiltrating lymphocytes was variably associated with the outcome depending on the cancer type, suggesting that γδ T-cell recruitment is influenced by the context. These findings also suggest that γδ T-cell detection and analysis might represent a new and interesting diagnostic or prognostic marker.
Objective: High-grade serous ovarian cancers (HGSOC) are heterogeneous, often diagnosed at an advanced stage, and associated with poor overall survival (OS, 39% at five years). There are few data ...about the prognostic factors of late relapses in HGSOC patients who survived ≥five years, long-term survivors (LTS). The aim of our study is to assess the probability of survival according to the already survived time from diagnosis. Methods: Data from HGSOC patients treated between 1995 and 2016 were retrospectively collected to estimate the conditional probability of survival (CPS), probability of surviving Y years after diagnosis when the patient had already survived X years, and to determine the LTS prognostic factors. The primary endpoint was OS. Results: 404 patients were included; 120 of them were LTS. Patients were aged 61 years (range: 20–89), WHO performance status 0–1 in 86.9% and 2 in 13.1%, and Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) staging III and IV in 82.7% and 17.3% patients. Breast cancer (BRCA) status was available in 116 patients (33% mutated), including 58 LTS (36% mutated). No macroscopic residual disease was observed in 58.4% patients. First-line platinum-based chemotherapy plus paclitaxel was administered in 80.4% of patients (median: six cycles (range: 1–14)). After a 9 point 3-year follow-up, median OS was four years (95% CI: 3.6–4.5). The CPS at five years after surviving one year was 42.8% (95% CI: 35.3–48.3); it increased to 81.7% (95% CI: 75.5–87.8) after four survived years. Progression-free interval>18 months was the only LTS prognostic factor in the multivariable analysis (hazard ratio (HR) = 0.23; 95% CI: 0.13–0.40; p < 0.001). Conclusion: The CPS provided relevant and encouraging clinical information on the life expectancy of HGSOC patients who already survived a period of time after diagnosis. LTS prognostic factors are useful for clinicians and patients.
•Time to treatment (TTR) did not worse disease-free survival and overall survival.•An impact of time to treatment on local recurrence rate could not be excluded.•Robot-associated laparoscopy did not ...lengthen the treatment delay.•Treatment delay seems highly dependent of health-care organization.
Time to adjuvant treatment could have an impact on cancer prognosis. It is possible that robotic surgery lengthens the healing time of vaginal cuff after minimally invasive hysterectomy. The objective of this study was to state the impact of time to RT (TTR) on prognosis in endometrial carcinoma (EC) patients and to assess variables associated with TTR.
We conducted a multicentric retrospective study in two cancer centers. We included EC patients, between January 1996 and January 2016. We searched variables associated with TTR and impact of TTR on end-points: local recurrence-free survival, metastatic-free survival, event-free survival and overall survival.
329 patients were included and 279 were analyzed for TTR impact. Robotic surgery was associated with shorter TTR (8 weeks, 8.9 w for laparotomy, 9.2 w for laparoscopy). Pelvic lymphadenectomy, para-aortic lymphadenectomy, discussion in multidisciplinary meeting and treatment center was independently associated with TTR. No impact of TTR was shown on metastatic-free survival, event-free survival and overall survival but there was a trend of a decreased local recurrence rate in case of prolonged TTR (HRcontinuous variable = 1.08; CI95 %: 0.97–1.2).
Our study did not show any impact of treatment delay on survival end-points although prolonged TTR could moderate the benefit of radiotherapy on local control rate. Surgical route was not associated with TTR, particularly robot-associated laparoscopy did not lengthen treatment delay. TTR seems dependent of health-care organization and could represent a quality criterion of EC care for institutions.
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