Prediction of 177Lu-DOTATATE PRRT Outcome Using Multimodality Imaging in Patients with Gastroenteropancreatic Neuroendocrine Tumors: Results from a Prospective Phase II LUMEN Study.

Our objective was to predict the outcome of peptide receptor radionuclide therapy (PRRT) using multimodality imaging and tumor dosimetry on gastroenteropancreatic neuroendocrine tumor (GEP-NET) lesions and patients. Methods: This prospective study included patients with progressive GEP-NETs. Treatment consisted of 4 cycles of 7.4 GBq of 177Lu-DOTATATE. Imaging parameters were measured on 68Ga-DOTATATE PET/CT (SUVmax/mean, somatostatin receptor [SSTR] tumor volume [TV], total lesion SSTR expression, and tumor-to-blood and tumor-to-spleen ratios), 18F-FDG PET/CT (SUVmax/mean, metabolically active TV, and total lesion glycolysis), and diffusion-weighted MRI (apparent diffusion coefficient) in a maximum of 5 target lesions per patient at approximately 10 wk after each injection. Tumor dosimetry was performed using SPECT/CT at 3 time points for every cycle. Baseline imaging parameters, their relative changes after PRRT cycle 1 (C1), and the tumor-absorbed dose at C1 were correlated with lesion morphologic outcome. The average values of the imaging parameters and the minimal, maximal, and mean C1 tumor-absorbed dose in each patient were tested for association with progression-free survival (PFS) and best objective response (RECIST 1.1). Results: In the 37 patients, the median PFS was 28 mo. Eleven of the 37 (30%) achieved a partial response (RECIST 1.1). After a median follow-up of 57 mo, the median time to lesion progression had not been reached in 84 morphologically evaluable lesions, with only 12 (14%) progressing (size increase ≥ 20% from baseline). Patients receiving a minimal C1 dose of 35 Gy in all target lesions exhibited a significantly longer PFS (48.1 vs. 26.2 mo; hazard ratio, 0.37; 95% CI, 0.17-0.82; P = 0.02). Volumetric 68Ga-DOTATATE PET parameters correlated with lesion and patient outcome: patients with an SSTR TV decrease of more than 10% after C1 had a longer PFS (51.3 vs. 22.8 mo; hazard ratio, 0.35; 95% CI, 0.16-0.75; P = 0.003). There was no statistical evidence of an association between other dosimetric or imaging parameters and the lesion or patient outcome. Conclusion: Minimal tumor-absorbed dose at C1 is predictive of outcome in patients with GEP-NETs treated with PRRT, providing a basis for personalized dosimetry-guided treatment strategies. An SSTR TV decrease after C1 could be used for early therapy response assessment as a predictor of PRRT outcome.

Progression-free survival assessment by local investigators versus blinded independent central review in randomized clinical trials in metastatic breast cancer: A systematic review and meta-analysis.

INTRODUCTION: In randomized clinical trials (RCTs), blinded independent central review (BICR) is used to minimize heterogeneity and bias associated with radiological response evaluation by local investigators. However, BICR adds costs and complexity to the trial management. We assessed the discrepancy index between progression-free survival (PFS) assessment by local investigators and by BICR in RCTs conducted in patients with metastatic breast cancer (MBC). METHODS: A systematic search of PubMed, Embase, Cochrane databases and conference proceedings (ASCO, SABCS, ESMO) was performed up to January 4, 2023 (PROSPERO: CRD42021229865). All RCTs published from 2000 to 2022, including MBC patients treated in first- or second-line, and reporting PFS assessed by local investigators and BICR were included. A discrepancy index between BICR-assessed and investigator-assessed HR was calculated for each trial and an overall combined DI was obtained using a fixed-effects model. The agreement between hazard ratios (HR) of PFS assessed by local investigators and BICR was measured using intraclass correlation coefficient (ICC). RESULTS: We analyzed 24 studies including 13,168 patients. Among them, 19 (79%) were in first-line, 18 (75%) were phase III trials and 23 (96%) had PFS as primary endpoint. The overall combined discrepancy index was 0.97 (95%CI 0.85-1.10; ICC 0.831, p < 0.001) suggesting no statistically significant difference in PFS assessment between local investigators and BICR. This result was consistent across all analyzed subgroups. CONCLUSIONS: The good concordance between local investigator and BICR assessments supports the reliability of local investigator-assessed PFS as primary endpoint for RCTs in MBC and questions the practical utility of implementing BICR in all RCTs.

Ki-67 index after neoadjuvant endocrine therapy as a prognostic biomarker in patients with ER-positive/HER2-negative early breast cancer: a systematic review and meta-analysis.

BACKGROUND: Neoadjuvant treatment discriminates responders, but pathologic complete response is uncommon in oestrogen receptor (ER)-positive/HER2-negative early breast cancer. We aimed to assess the prognostic value of Ki-67 index after neoadjuvant endocrine therapy (NET). METHODS: We conducted a systematic literature search of PubMed, Embase, CENTRAL, and conference proceedings up to 22nd August 2023 to identify studies reporting the association of Ki-67 index after NET with recurrence-free survival (RFS) and/or overall survival (OS) in women with ER-positive/HER2-negative early breast cancer. We combined RFS and OS hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Twelve studies including 7897 patients were analysed. Most studies were clinical trials (n = 7547) including only postmenopausal women (n = 3953) treated with aromatase inhibitor (n = 3359). Three studies evaluated Ki-67 in a preplanned core biopsy at 2-4 weeks of NET (n = 3348), while nine evaluated Ki-67 in the surgical specimen (n = 4549) after 2-24 weeks of NET. Median follow-up ranged between 37 and 95 months for RFS and 62-84 months for OS. High Ki-67 index after NET was significantly associated with worse RFS (HR 2.48, 95% CI 1.86-3.30) and OS (HR 2.66, 95% CI 1.65-4.28). A sensitivity analysis including three studies that measured Ki-67 in a preplanned core biopsy showed similar association with RFS (HR 2.41, 95% CI 1.77-3.30). CONCLUSIONS: High Ki-67 after NET is associated with worse survival outcomes, even after a short course of NET, emphasising the prognostic value of this biomarker in women with ER-positive/HER2-negative early breast cancer.

Immune response to anti-SARS-CoV-2 prime-vaccination in patients with cancer: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the immune response to anti-SARS-CoV-2 prime-vaccination in patients with cancer. METHODS: We performed a systematic literature search using PubMed, Embase, and Cochrane Library until 28/09/2021, and conference proceedings from ASCO and ESMO 2021 annual meetings. We screened for observational or interventional studies including subjects ≥ 16 years old with cancer diagnosis who were vaccinated against SARS-CoV-2. Prime-vaccination was defined as one dose of Ad26.COV2-S vaccine or two doses of BNT162b2, mRNA-1273, ChAdOx1-S or inactivated SARS-CoV-2 vaccine. The outcomes were humoral and adaptive immune responses (proportion of subjects with positive titers of antibody anti-SARS-CoV-2 spike protein and anti-SARS-CoV-2 cellular responses, respectively). RESULTS: We included 89 records reporting data from 30,183 subjects. The overall seropositive rate within the first month after complete anti-SARS-CoV-2 prime-vaccination was 80% [95% confidence interval (CI), 72-86%], 60% (95%CI, 53-67%) in patients with hematological malignancies (HM) versus 94% (95%CI, 88-97%) in patients with solid malignancies (SM). The diagnosis of HM was significantly associated with a lower seropositive rate on multivariate meta-regression (odds ratio 0.35, 95% CI 0.18-0.69, HM versus both, p = 0.002). The overall humoral response was 49% (95% CI, 42-56%) after incomplete prime-vaccination and 79% (95% CI, 70-86%) at 2 months after complete prime-vaccination. These responses were also lower in patients with HM at these time points. The overall cellular response rate at any time after vaccination was 61% (95% CI, 44-76%). CONCLUSION: This meta-analysis provides compelling evidence of humoral and adaptive immune responses against SARS-CoV-2 in patients with cancer, which last for at least 2 months following complete prime-vaccination.

Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer.

BACKGROUND: Empiric antifungal therapy is considered the standard of care for high-risk neutropenic patients with persistent fever. The impact of a preemptive, diagnostic-driven approach based on galactomannan screening and chest computed tomography scan on demand on survival and on the risk of invasive fungal disease (IFD) during the first weeks of high-risk neutropenia is unknown. METHODS: Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and allogeneic hematopoietic cell transplant recipients were randomly assigned to receive caspofungin empirically (arm A) or preemptively (arm B), while receiving fluconazole 400 mg daily prophylactically. The primary end point of this noninferiority study was overall survival (OS) 42 days after randomization. RESULTS: Of 556 patients recruited, 549 were eligible: 275 in arm A and 274 in arm B. Eighty percent of the patients had AML or MDS requiring high-dose chemotherapy, and 93% of them were in the first induction phase. At day 42, the OS was not inferior in arm B (96.7%; 95% confidence interval [CI], 93.8%-98.3%) when compared with arm A (93.1%; 95% CI, 89.3%-95.5%). The rates of IFDs at day 84 were not significantly different, 7.7% (95% CI, 4.5%-10.8%) in arm B vs 6.6% (95% CI, 3.6%-9.5%) in arm A. The rate of patients who received caspofungin was significantly lower in arm B (27%) than in arm A (63%; P < .001). CONCLUSIONS: The preemptive antifungal strategy was safe for high-risk neutropenic patients given fluconazole as prophylaxis, halving the number of patients receiving antifungals without excess mortality or IFDs. Clinical Trials Registration. NCT01288378; EudraCT 2010-020814-27.

Patient-reported outcomes in terms of swallowing and quality of life after prophylactic versus reactive percutaneous endoscopic gastrostomy tube placement in advanced oropharyngeal cancer patients treated with definitive chemo-radiotherapy: Swall PEG study.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is often used to provide nutritional support in locally advanced head and neck cancer patients undergoing multimodality treatment. However, there is little published data on the impact of prophylactic versus reactive PEG. PEG placement may affect swallowing-related physiology, function, and quality of life. The Swall PEG study is a randomized controlled phase III trial testing the impact of prophylactic versus reactive PEG on patient-reported outcomes in terms of swallowing and quality of life in oropharyngeal cancer patients. METHODS: Patients with locally advanced oropharyngeal cancer receiving chemo-radiotherapy will be randomized to either the prophylactic or reactive PEG tube group. Randomization will be stratified by human papillomavirus (HPV) status and unilateral versus bilateral positive neck lymph nodes. The primary objective of the study is the patient's reported outcome in terms of swallowing (MD Anderson Dysphagia Inventory (MDADI)) at 6 months. Secondary objectives include health-related quality of life, dosimetric parameters associated with patient-reported outcomes, chemo-radiation toxicities, PEG tube placement complications, the impact of nutritional status on survival and toxicity outcomes, loco-regional control, overall survival, the impact of HPV and tobacco smoking on survival outcomes and toxicities, and the cost-effectiveness of each treatment strategy. DISCUSSION: Findings from this study will enhance clinical evidence regarding nutritional management in oropharyngeal cancer patients treated by concurrent chemo-radiation. TRIAL REGISTRATION: ClinicalTrials.gov NCT04019548, study protocol version 2.0_08/08/2019. Registered on 15 July 2019.

PREDICT underestimates survival of patients with HER2-positive early-stage breast cancer.

The prognostic performance of PREDICT in patients with HER2-positive early breast cancer (EBC) treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies is unclear. Therefore, we investigated its prognostic performance using data extracted from ALTTO, a phase III trial evaluating adjuvant lapatinib ± trastuzumab vs. trastuzumab alone in patients with HER2-positive EBC. Our analysis included 2794 patients. After a median follow-up of 6.0 years (IQR, 5.8-6.7), 182 deaths were observed. Overall, PREDICT underestimated 5-year OS by 6.7% (95% CI, 5.8-7.6): observed 5-year OS was 94.7% vs. predicted 88.0%. The underestimation was consistent across all subgroups, including those according to the type of anti HER2-therapy. The highest absolute differences were observed for patients with hormone receptor negative-disease, nodal involvement, and large tumor size (13.0%, 15.8%, and 15.3%, respectively). AUC under the ROC curve was 73.7% (95% CI 69.7-77.8) in the overall population, ranging between 61.7% and 77.7% across the analyzed subgroups. In conclusion, our analysis showed that PREDICT highly underestimated OS in HER2-positive EBC. Hence, it should be used with caution to give prognostic estimation to HER2-positive EBC patients treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies.

ROSALINE: a phase II, neoadjuvant study targeting ROS1 in combination with endocrine therapy in invasive lobular carcinoma of the breast.

Invasive lobular carcinoma (ILC) is the most common histologic subtype of breast cancer after invasive ductal carcinoma (i.e., no special type [NST]). ILC differs from NST in clinical presentation, site-specific metastases and response to conventional therapies. Loss of E-cadherin protein expression, due to alterations in its encoding gene CDH1, is the most frequent oncogenic event in ILC. Synthetic lethality approaches have shown promising antitumor effects of ROS1 inhibitors in models of E-cadherin-defective breast cancer in in vivo studies and provide the rationale for testing their clinical activity in patients with ILC. Entrectinib is a tyrosine kinase inhibitor targeting TRK, ROS1 and ALK tyrosine kinases. Here, the authors present ROSALINE (NCT04551495), a phase II study testing neoadjuvant entrectinib and endocrine therapy in women with estrogen receptor-positive, HER2-negative early ILC.

Breast cancer is the most common cancer among women worldwide. Breast cancer is not a unique disease, but rather a heterogeneous disease, with different subtypes. Lobular breast cancer is the second most common histologic subtype of breast cancer after ductal breast cancer. Lobular breast cancer has some peculiar characteristics that make it a distinct entity in the context of breast cancer. Nevertheless, few clinical studies so far have focused specifically on this subtype. ROSALINE is a clinical study aimed to test entrectinib, a new drug that showed promising activity in preliminary research studies, in combination with endocrine therapy in women with lobular breast cancer before surgery. Trial Registration Number: NCT04551495 (ClinicalTrials.gov).

PARIS score for evaluation of probability of SARS-CoV-2 infection in cancer patients.

Control of transmissible diseases as COVID-19 needs a testing and an isolation strategy. The PARIS score developed by Torjdman et al. was aimed at improving patient selection for testing and quarantining but was derived from a general population. We performed a retrospective analysis of the validity of the PARIS score in a cancer patient population. We included 164 patients counting for 181 visits at the emergency department of the Jules Bordet Institute between March 10th and May 18th which had a SARS-CoV-2 RT-PCR test at admission. Twenty-six cases (14.3%) were tested positive with a higher proportion of positive tests among hematological patients compared to those with solid tumors (26% vs 11% p = 0.02). No clinical symptoms were associated with a positive SARS-CoV-2 PCR. No association between anticancer treatment and SARS-CoV-2 infection was found. The PARIS score failed to differentiate SARS-CoV-2-positive and SARS-CoV-2-negative groups (AUC 0.61 95% CI 0.48-0.73). The negative predictive value of a low probability PARIS score was 0.89 but this concerned only 11% of the patients. A high probability PARIS score concerned 49% patients but the positive predictive value was 0.18. CT scan had a sensitivity of 0.77, specificity 0.51, a positive predictive value of 0.24, and a negative predictive value of 0.92. The performance of the PARIS score is thus very poor in this cancer population. A low-risk score can be of some utility but this concerns a minority of patients.

Combined Metabolically Active Tumor Volume and Early Metabolic Response Improve Outcome Prediction in Metastatic Colorectal Cancer.

Stratification of metastatic colorectal cancer (mCRC) patients is mostly based on clinical and biologic characteristics. This study aimed to validate the prognostic value of 18F-FDG PET/CT-based biomarkers such as baseline whole-body metabolically active tumor volume (WB-MATV) and early metabolic response (mR) in mCRC. Methods: The development cohort included chemorefractory mCRC patients enrolled in 2 prospective Belgian multicenter trials evaluating last-line treatments (multikinase inhibitors). The validation cohort included mCRC patients from an Italian center treated with chemotherapy and bevacizumab as first-line. Baseline WB-MATV was defined as the sum of metabolically active volumes of all target lesions identified on the baseline 18F-FDG PET/CT. Early mR assessment was performed following usual response criteria (response threshold of 30% [PERCIST-30%], response threshold of 15% [PERCIST-15%], European Organization for Research and Treatment of Cancer) and the so-called CONSIST method, which defines response as a decrease of SULmax ≥ 15% for all target lesions. Baseline WB-MATV and early mR assessment were investigated along with usual clinical factors and correlated with overall survival (OS) and progression-free survival (PFS). Results: Clinical factors, baseline WB-MATV, and early mR were evaluable in 192 of 239 and 94 of 125 patients of the development and validation cohorts, respectively. Except for PERCIST-30%, all response methods were equivalent in terms of outcome prediction, and CONSIST was found to be the most accurate. Baseline WB-MATV and early mR using the CONSIST method were independent prognostic parameters after adjustment for clinical factors in the development and validation sets for both OS (hazard ratio [HR] WB-MATV: 1.87 [95% CI, 1.17-2.97], P = 0.005, and HR early mR: 1.79 [95% CI, 1.08-2.95], P = 0.02 for the validation set) and PFS (HR WB-MATV: 1.94 [95% CI, 1.27-2.97], P = 0.002, and HR early mR: 1.69 [95% CI, 1.04-2.73], P = 0.03 for the validation set). Conclusion: Baseline WB-MATV and early mR are strong independent prognostic biomarkers for OS and PFS in mCRC, regardless of treatment received. Therefore, combining these biomarkers improves risk stratification for OS and PFS in mCRC.

Initiation of a new anti-cancer medical treatment in ICU: a retrospective study.

PURPOSE: The purpose of our study is to evaluate the characteristics of patients whose medical anti-cancer treatment has been initiated at the ICU and to release prognostic factors for hospital mortality in these patients. MATERIAL AND METHODS: We analyzed retrospectively all the records of cancer patients admitted between 01/01/2007 and 31/12/2017 in our ICU and for whom a new anti-cancer medical treatment was initiated during their ICU stay. RESULTS: Our study includes 147 patients, 78 men (53%) and 69 women (47%), with a median age of 58 years. Eighty patients (54%) had a solid tumor and 67 (46%) a hematological malignancy. ICU mortality was 23% and hospital mortality 32%. The poor prognostic factors for hospital mortality were: higher SOFA, higher Charslon comorbidity index and the presence of a therapeutic limitation (introduced at the time of admission or within 24 hours of admission to the ICU). One-year survival for patients who survived hospital stay was 37% (17% for those with a solid tumor and 61% for the ones with a hematological malignancy). CONCLUSION: Initiation of an anti-cancer medical treatment is feasible and can lead to good 1 year survival rate, especially for those with a hematological tumor.

FDG positron emission tomography imaging and ctDNA detection as an early dynamic biomarker of everolimus efficacy in advanced luminal breast cancer.

Biomarkers to identify patients without benefit from adding everolimus to endocrine treatment in metastatic breast cancer (MBC) are needed. We report the results of the Pearl trial conducted in five Belgian centers assessing 18F-FDG-PET/CT non-response (n = 45) and ctDNA detection (n = 46) after 14 days of exemestane-everolimus (EXE-EVE) to identify MBC patients who will not benefit. The metabolic non-response rate was 66.6%. Median PFS in non-responding patients (using as cut-off 25% for SUVmax decrease) was 3.1 months compared to 6.0 months in those showing response (HR: 0.77, 95% CI: 0.40-1.50, p = 0.44). The difference was significant when using a "post-hoc" cut-off of 15% (PFS 2.2 months vs 6.4 months). ctDNA detection at D14 was associated with PFS: 2.1 months vs 5.0 months (HR-2.5, 95% CI: 1.3-5.0, p = 0.012). Detection of ctDNA and/or the absence of 18F-FDG-PET/CT response after 14 days of EXE-EVE identifies patients with a low probability of benefiting from treatment. Independent validation is needed.

Heparanase: a potential marker of worse prognosis in estrogen receptor-positive breast cancer.

Heparanase promotes tumor growth in breast tumors. We now evaluated heparanase protein and gene-expression status and investigated its impact on disease-free survival in order to gain better insight into the role of heparanase in ER-positive (ER+) breast cancer prognosis and to clarify its role in cell survival following chemotherapy. Using pooled analysis of gene-expression data, we found that heparanase was associated with a worse prognosis in estrogen receptor-positive (ER+) tumors (log-rank p < 10-10) and predictive to chemotherapy resistance (interaction p = 0.0001) but not hormonal therapy (Interaction p = 0.62). These results were confirmed by analysis of data from a phase III, prospective randomized trial which showed that heparanase protein expression is associated with increased risk of recurrence in ER+ breast tumors (log-rank p = 0.004). In vitro experiments showed that heparanase promoted tumor progression and increased cell viability via epithelial-mesenchymal transition, stemness, and anti-apoptosis pathways in luminal breast cancer. Taken together, our results demonstrated that heparanase is associated with worse outcomes and increased cell viability in ER+ BC.

Fortnightly or fractionated weekly docetaxel-cisplatin-5-FU as first-line treatment in advanced gastric and gastroesophageal junction adenocarcinoma: The randomized phase II DoGE study.

BACKGROUND: While docetaxel/cisplatin/5-fluorouracil (DCF) outperforms CF in first-line gastric adenocarcinoma, toxicity remains an issue. METHODS: This multicenter phase II trial randomized chemonaïve metastatic gastric adenocarcinoma patients to fractionated weekly DCF (D 40 mg/m2 , C 35 mg/m², F 1800 mg/m² over 24 h, on days 1 and 8 every 3 weeks, arm (1) or fortnightly DCF (D 50 mg/m2 , C 50 mg/m², F 2000 mg/m² over 48 h every 2 weeks, arm (2). Prophylactic granulocyte colony-stimulating factor (G-CSF) was not allowed. The primary endpoint was the rate of febrile neutropenia within the first six treatment weeks (early FN). RESULTS: A total of 106 eligible patients were recruited. The early and overall FN rates were 9.5% and 17% in arm 1, respectively, and 5.9% and 8% in arm 2, respectively. Grade ≥3 toxicities occurred in 81% of patients in arm 1 and 90% of patients in arm 2, the most common being neutropenia (33% vs. 61%), fatigue (27% vs. 25%), vomiting (21% vs. 12%), anorexia (19% vs. 18%), and diarrhea (17% vs. 10%). Median progression-free survival and overall survival were 5.1 (95% CI, 3.2-6.5) and 8.2 months (95% CI, 6.0-14.5), respectively, in arm 1 and 5.2 (95% CI, 3.0-6.9) and 11.9 months (95% CI, 7.4-15.9), respectively, in arm 2. CONCLUSIONS: Fractionated weekly and fortnightly DCF regimens are associated with a low risk of early FN, and a better hematological toxicity profile as compared to historical DCF without compromising efficacy. Both regimens offer greater convenience removing the need for systematic use of prophylactic G-CSF.

The INTER-ACT E-Health Supported Lifestyle Intervention Improves Postpartum Food Intake and Eating Behavior, but Not Physical Activity and Sedentary Behavior-A Randomized Controlled Trial.

Unhealthy postpartum lifestyle is related to long-term adverse psychological, metabolic and cardiovascular health outcomes as well as to complications in the next pregnancy. Especially women with preceding excessive gestational weight gain are at risk. This paper aims to evaluate the effect of the postpartum phase of the INTER-ACT randomized controlled trial (RCT) on food intake, eating behavior, physical activity and sedentary time at the end of the intervention (six months postpartum) and at six-months follow-up (12 months postpartum). The study population comprised women with excessive gestational weight gain in the preceding pregnancy. The lifestyle intervention combined a smartphone application with four face-to-face coaching sessions between six weeks and six months postpartum. After the intervention, restrained eating score was 1 point higher (95% CI 0.5, 1.5; p < 0.001), uncontrolled eating score was 1 point lower (95% CI -1.9, -0.2; p = 0.02) and energy intake was 69 kcal lower (95% CI -123, -15; p = 0.01) in the intervention group compared to the control group. The differences were no longer statistically significant at follow-up. No significant effects on emotional eating, physical activity and sedentary behavior were found. In conclusion, the postpartum phase of the INTER-ACT RCT was effective in improving nutrition-related outcomes, however, these improvements could not be sustained at follow-up. ClinicalTrials.gov identifier: NCT02989142.

Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants.

Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR-]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I-III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60-0.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94-2.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients' counseling on treatment, prevention, and surveillance strategies.

Gestational weight gain and postpartum weight retention after bariatric surgery: data from a prospective cohort study.

BACKGROUND: It is unknown whether international guidelines on gestational weight gain can be used in pregnancies after bariatric surgery. OBJECTIVES: To investigate gestational weight gain, intrauterine growth, and postpartum weight retention in postbariatric women. SETTING: 8 Belgian hospitals. METHODS: Prospective data from 127 postbariatric pregnancies from September 2014 through October 2018. Patients were grouped according to achievement of 2009 Institute of Medicine (IOM) guidelines. RESULTS: In 127 patients with a mean age of 30.2 years (standard deviation [SD], 4.7), the mean gestational weight gain was 12.5 kg (SD, 6.7). Of these patients, 24% (30 of 127) showed insufficient weight gain, 20% (26 of 127) showed adequate weight gain, and 56% (71 of 127) showed excessive weight gain. Of 127 patients, 27 (21%) had small-for-gestational-age infants. This peaked in the group with insufficient weight gain (47%; 95% confidence interval [CI], 29%-65%; P < .001). The prevalence of large-for-gestational-age infants was comparable between groups, although highest in the group with excessive weight gain (0% in those with insufficient weight gain, 4% in those with adequate weight gain, and 8% in those with excessive weight gain). Preterm births were recorded more in patients with insufficient weight gain (23%; 95% CI, 8%-38%; P = .048). The mean amounts of postpartum weight retained were 4.0 kg (SD, 7.4) at 6 weeks and 3.0 kg (SD, 9.1) at 6 months. Weight retention at 6 weeks (7.1 kg; 95% CI, 5.5-8.7; P < .001) and 6 months (8.3 kg; 95% CI, 4.5-12.2; P < .001) was highest in women gaining excessive weight. CONCLUSION: Achievement of IOM guidelines is low in postbariatric pregnancies. Insufficient weight gain increases the risk for small-for-gestational-age babies. Excessive weight gain increases weight retention after delivery and could precipitate weight regain. After bariatric surgery, women should be encouraged to achieve IOM recommendations.

Sepsis and Septic Shock Definitions in Patients With Cancer Admitted in ICU.

INTRODUCTION: In 2016, a new definition of sepsis and septic shock was adopted. Some studies based on the general population demonstrated that the Sequential Organ Failure Assessment (SOFA) score is more accurate than the systemic inflammatory response syndrome (SIRS) criteria to predict hospital mortality of infected patients requiring intensive care. PATIENTS AND METHOD: We have analyzed all the records of patients with cancer admitted for a suspected infection between January 1, 2013, and December 31, 2016, in our oncological intensive care unit (ICU). Sequential Organ Failure Assessment score and quick SOFA (qSOFA) score as well as SIRS criteria were calculated. We analyzed the accuracy of each score to predict hospital mortality in the setting of the new and old definitions of septic shock. RESULTS: Our study includes 241 patients with a solid tumor and 112 with a hematological malignancy. The hospital mortality rate is 37% (68% in patients with septic shock according to the new definition and 60% according to old definition) between 2013 and 2016. To predict hospital mortality, the SOFA score has an area under the receiver operating characteristic curve of 0.74 (95% confidence interval [CI], 0.68-0.79), the qSOFA of 0.65 (95% CI, 0.59-0.70), and the SIRS criteria of 0.58 (95% CI, 0.52-0.63). In multivariate analysis, a higher SOFA score or a higher qSOFA score indicates poor prognosis: odds ratio (OR) per 1-point increase by 1.28 (95% CI, 1.18-1.39) and 1.48 (95% CI, 1.04-2.11), respectively. Complete remission is a good prognostic factor for hospital mortality: OR 0.39 (95% CI, 0.22-0.67). CONCLUSION: The new definition of sepsis and septic shock is applicable in an ICU oncological population with the same reliability as in the general population. The SOFA score is more accurate than qSOFA and SIRS criteria to predict hospital mortality.