Evidence of circulating autoantibodies in cancer patient sera has created opportunities for exploiting them as biomarkers. We report the identification and the clinical validation of an autoantibody ...panel in newly diagnosed patients with early‐stage breast cancer. Proteomic approach and serological screening of a discovery set of sera (n = 80) were performed to identify tumor‐associated antigens (TAAs). Autoantibody levels were then measured in an independent validation set (n = 182) against a panel of five TAAs by enzyme‐linked immunosorbent assay. Sixty‐seven antigens that elicited a specific humoral response in breast cancer were identified and five antigens (GAL3, PAK2, PHB2, RACK1 and RUVBL1) were selected for validation. GAL3 and RACK1 showed significantly increased reactivity in early‐stage breast cancer. When combined, the five markers significantly discriminated early‐stage cancer from healthy individuals (AUC = 0.81; 95% CI 0.74–0.86). Interestingly, this value was high in both node‐negative early‐stage primary breast cancer (AUC = 0.81; 95% CI 0.72–0.88) and ductal carcinoma in situ (AUC = 0.85; 95% CI 0.76–0.95) populations. This autoantibody panel could be useful as a diagnostic tool in a screening strategy of early‐stage invasive breast cancer and preinvasive breast cancer. It could be particularly appropriate in complement to mammography for women with high breast density.
What's new?
This study shows the clinical relevance of a combination of five antigens as a blood‐screening test for early breast cancer detection. The antigens were identified using a proteomic approach and validated in an independent cohort of 182 samples by ELISA. Since the effectiveness of mammographic screening declines in cohorts of patients with dense breast tissue and small lesions, testing for the status of this biomarker panel may help improve the detection of early‐stage cancer in women.
Pelvic exenteration and its reconstructive techniques have been associated with high postoperative morbidity and a negative impact on patient quality of life. The aim of our study was to compare ...postoperative complications and quality of life in patients undergoing continent compared with non-continent urinary diversion after pelvic exenteration for gynecologic malignancies.
We designed a multicenter study of patients from 10 centers who underwent an anterior or total pelvic exenteration with urinary reconstruction for histologically confirmed persistent or recurrent gynecologic malignancy after previous treatment with radiotherapy. From January 2005 to September 2008, we included patients retrospectively, and from September 2008 to May 2009, patients were included prospectively which allowed collection of quality of life data. Demographic, surgical, and follow-up data were analyzed. Postoperative complications were classified according to the Clavien-Dindo classification. Quality of life was assessed using the European Organization for Research and Treatment of Cancer (EORTC)-QLQ-C30 (V.3.0) and EORTC-QLQ-OV28 quality of life questionnaires. We compared patients who underwent a continent urinary diversion with those who underwent a non-continent reconstruction.
We included 148 patients, 92 retrospectively and 56 prospectively. Among them, 77.4% had recurrent disease and 22.6% persistent disease after the primary treatment. In 70 patients, a urinary continent diversion was performed, and 78 patients underwent a non-continent diversion. Median age of the continent and incontinent groups was 53.5 (range 33-78) years and 57 (26-79) years, respectively. There were no significant differences between the continent and non-continent groups in median length of hospitalization (28.5 vs 26 days, P=0.19), postoperative grade III-IV complications (42.9% vs 42.3%, P=0.95), complications needing surgical (27.9% vs 34.6%, P=0.39) or radiological (14.7% vs 12.8%, P=0.74) intervention, and complication type (digestive (23.2% vs 16.7%, P=0.32) and urinary (15.9% vs 16.7%, P=0.91)). There were no significant differences between the groups in global health, global quality of life, and body image perception scores 1 year after surgery.
Continent and incontinent urinary reconstructions are equivalent in terms of postoperative complications and quality of life scores.
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.
Right colectomy is the standard surgical treatment for tumors in the right colon and surgical complications are reduced with minimally-invasive laparoscopy compared with open surgery, with potential ...further benefits achieved with robotic assistance. The anastomotic technique used can also have an impact on patient outcomes. However, there are no large, prospective studies that have compared all techniques.
MIRCAST is the Minimally-Invasive Right Colectomy Anastomosis Study that will compare laparoscopy with robot-assisted surgery, using either intracorporeal or extracorporeal anastomosis, in a large prospective, observational, multicenter, parallel, four-cohort study in patients with a benign or malignant, non-metastatic tumor of the right colon. Over 2 years of follow-up, the study will prospectively evaluate peri- and postoperative complications, postoperative recovery, hospital stay, and mid-term results including survival, local recurrence, metastases rate, and conversion rate. The primary composite endpoint will be the efficacy of the surgical method regarding surgical wound infections and postoperative complications (Clavien-Dindo grade III-IV complications at 30 days post-surgery). Secondary endpoints include long-term oncologic results, conversion rate, operative time, length of stay, and quality of life.
This will be the first large, international study to prospectively evaluate the use of minimally-invasive laparoscopy or robot-assisted surgery during right hemicolectomy and to control for the impact of the anastomotic technique. The research will contribute to current knowledge regarding the medical care of patients with malignant or benign tumors of the right colon, and enable physicians to determine which technique may be the most appropriate for their patients.
This study was registered on Clinicaltrials.gov (clinicaltrials.gov identifier: NCT03650517 ) on August 28th 2018 (study protocol version CI18/02 revision A, 21 February 2018).
To determine the rate of nonsentinel lymph node (NSN) involvement at axillary lymph node dissection (ALND) and predictive factors of this involvement following detection of micrometastasis in ...sentinel nodes (SN).
We analyzed 700 observations of SN micrometastases with additional ALND with the characteristics of the patients, tumors, and SN.
Involvement of SN was diagnosed 388 times by serial sections (55.4%) with standard hemoxylin and eosin staining (HES) and 312 times solely on immunohistochemical analysis (IHC; 44.6%). The accurate size of the micrometastases was indicated in 488 cases: 301 larger than 0.2 mm (61.7%) and 187 < or = 0.2 mm (38.3%). Ninety-four patients (13.4%) presented an NSN involvement with only one NSN involved in 62 cases (66%). Predictive factors of NSN involvement were in univariate analysis (pT stage P < .000, menopausal status P = .048, T stage P = .006, grade P = .013, lymphovascular invasion LVI; P = .013, histologic tumor type P = .017, and method of micrometastasis detection, by HES or IHC P = .015) and in multivariate analysis (pT stage < or = or > 20 mm odds ratio, 2.54, micrometastases detected by HES or IHC odds ratio,1.734, presence or absence of LVI odds ratio, 1.706). Micrometastasis size < or = or greater than 0.2 mm was not predictive.
This study confirms the value of serial sections and the vital role played by IHC in screening for small micrometastases. Omission of additional ALND may be envisaged with minimal risk for pT1a and pT1b tumors, and pT1a-b-c tumors corresponding to tubular, colloidal, or medullar cancers.
is a candidate oncogene with a wide variety of deleterious functions in breast cancer. Here, we aimed at investigating in a pilot prospective study the association between
mRNA expression levels and ...the clinical response to neoadjuvant endocrine therapy (ET) in postmenopausal ER-positive (ER+) breast cancer patients. Core surgical biopsy samples before treatment initiation and post-treatment were obtained from 68 patients, and Ki-67 values measured by immunohistochemistry (IHC) were used to identify responders (
= 59) and non-responders (
= 9) after 4 months of ET. We report for the first time that high
mRNA expression level measured by RT-qPCR in the initial tumor samples (pre-treatment) is associated with poor response to neoadjuvant ET. Indeed, the clinical positive response rate in patients with low
expression levels was significantly higher than that in those with high
expression levels (
= 0.027). Additionally, a retrospective analysis evaluating
expression levels in primary breast tumor of ER+/HER2-/LN0 breast cancer patients treated with adjuvant ET enabled the identification of poorer responders prone to earlier relapse (
= 0.013), while
did not retain any prognostic value in the ER+/HER2-/LN0 breast cancer patients who did not receive any treatment. Altogether, these data suggest that
expression might be predictive of clinical response to ET.
Postoperative upper gastrointestinal fistula (PUGIF) is a devastating complication, leading to high mortality (reaching up to 80%), increased length of hospital stay, reduced health-related quality ...of life and increased health costs. Nutritional support is a key component of therapy in such cases, which is related to the high prevalence of malnutrition. In the prophylactic setting, enteral nutrition (EN) is associated with a shorter hospital stay, a lower incidence of severe infectious complications, lower severity of complications and decreased cost compared to total parenteral nutrition (TPN) following major upper gastrointestinal (GI) surgery. There is little evidence available for the curative setting after fistula occurrence. We hypothesize that EN increases the 30-day fistula closure rate in PUGIF, allowing better health-related quality of life without increasing the morbidity or mortality.
The NUTRILEAK trial is a multicenter, randomized, parallel-group, open-label phase III trial to assess the efficacy of EN (the experimental group) compared with TPN (the control group) in patients with PUGIF. The primary objective of the study is to compare EN versus TPN in the treatment of PUGIF (after esophagogastric resection including bariatric surgery, duodenojejunal resection or pancreatic resection with digestive tract violation) in terms of the 30-day fistula closure rate. Secondary objectives are to evaluate the 6-month postrandomization fistula closure rate, time of first fistula closure (in days), the medical- and surgical treatment-related complication rate at 6 months after randomization, the fistula-related complication rate at 6 months after randomization, the type and severity of early (30 days after randomization) and late fistula-related complications (over 30 days after randomization), 30-day and 6-month postrandomization mortality rate, nutritional status at day 30, day 60, day 90 and day 180 postrandomization, the mean length of hospital stay, the patient's health-related quality of life (by self-assessment questionnaire), oral feeding time and direct costs of treatment. A total of 321 patients will be enrolled.
The two nutritional supports are already used in daily practice, but most surgeons are reluctant to use the enteral route in case of PUGIF. This study will be the first randomized trial testing the role of EN versus TPN in PUGIF.
ClinicalTrials.gov: NCT03742752. Registered on 14 November 2018.
The management of pT1a‐bN0M0 breast cancer remains an area of controversy. Data from 714 patients classified as having pT1a‐bN0M0 breast cancer and treated, from 1999 to 2004 in the ...Languedoc‐Roussillon France, were analyzed. The human epidermal growth factor receptor 2 (HER2) status analyses were centralized. The objective of this study was to describe the prognosis of pT1a‐bN0M0 breast cancer according to HER2 distribution and hormonal status. The median follow‐up was 6.4 years. Ten‐year overall survival was 94%. HER2 overexpression was observed in 6.1% of the patients. The 10‐year prognosis of patients with HER2‐positive tumors was worse than that of those with HER2‐negative (disease‐free survival 73% vs. 89%, P < 0.0001). Tumor size (T1a/T1b) was not a relevant prognostic factor. The co‐expression of HER2 with hormonal receptors (HR) was associated with high recurrence at 10 years. In both univariate and multivariate analyses, the most relevant prognostic factor for this population was HER2 amplification. In multivariate analysis, patients with HER2‐positive tumors had higher risk of mortality (HR, 3.89; 95% CI, 1.58–9.56). In pT1a‐bN0M0 breast cancers, HER2 amplification or overexpression is a risk factor for recurrence. In HER2‐positive breast cancers, HR expression is associated with a poor prognosis despite the hormone therapy. For this population, a personalized management may be required.
The management of pT1a‐bN0M0 breast cancer remains an area of controversy. Ten‐year results from 714 small breast carcinoma (SBC) showed 6.1% human epidermal growth factor receptor 2 (HER2) overexpression, a 10‐year overall survival of 94%, worse for HER2+ tumors (hormonal receptor HR:3.89). Hormonal therapy for HR+ HER2+ SBC is not sufficient, a personalized management may be required.
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