Pembrolizumab and chemotherapy in high-risk, early-stage, ER/HER2 breast cancer: a randomized phase 3 trial.

Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.

Respiratory effects of prone position in COVID-19 acute respiratory distress syndrome differ according to the recruitment-to-inflation ratio: a prospective observational study.

Background: Improvements in oxygenation and lung mechanics with prone position (PP) in patients with acute respiratory distress syndrome (ARDS) are inconstant. The objectives of the study were (i) to identify baseline variables, including the recruitment-to-inflation ratio (R/I), associated with a positive response to PP in terms of oxygenation (improvement of the ratio of arterial oxygen partial pressure over the inspired oxygen fraction (PaO/FiO) ≥ 20 mmHg) and lung mechanics; (ii) to evaluate whether the response to the previous PP session is associated with the response to the next session.

Methods: In this prospective, observational, single-center study in patients who underwent PP for ARDS due to COVID-19, respiratory variables were assessed just before PP and at the end of the session.

Testing preload responsiveness by the tidal volume challenge assessed by the photoplethysmographic perfusion index.

Background: To detect preload responsiveness in patients ventilated with a tidal volume (Vt) at 6 mL/kg of predicted body weight (PBW), the Vt-challenge consists in increasing Vt from 6 to 8 mL/kg PBW and measuring the increase in pulse pressure variation (PPV). However, this requires an arterial catheter. The perfusion index (PI), which reflects the amplitude of the photoplethysmographic signal, may reflect stroke volume and its respiratory variation (pleth variability index, PVI) may estimate PPV.

Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial.

The mechanisms of action of and resistance to trastuzumab deruxtecan (T-DXd), an anti-HER2-drug conjugate for breast cancer treatment, remain unclear. The phase 2 DAISY trial evaluated the efficacy of T-DXd in patients with HER2-overexpressing (n = 72, cohort 1), HER2-low (n = 74, cohort 2) and HER2 non-expressing (n = 40, cohort 3) metastatic breast cancer. In the full analysis set population (n = 177), the confirmed objective response rate (primary endpoint) was 70.

Relationship of Extravascular Lung Water and Pulmonary Vascular Permeability to Respiratory Mechanics in Patients with COVID-19-Induced ARDS.

During acute respiratory distress syndrome (ARDS), the increase in pulmonary vascular permeability and lung water induced by pulmonary inflammation may be related to altered lung compliance. A better understanding of the interactions between respiratory mechanics variables and lung water or capillary permeability would allow a more personalized monitoring and adaptation of therapies for patients with ARDS. Therefore, our main objective was to investigate the relationship between extravascular lung water (EVLW) and/or pulmonary vascular permeability index (PVPI) and respiratory mechanic variables in patients with COVID-19-induced ARDS.

Futibatinib for -Rearranged Intrahepatic Cholangiocarcinoma.

Background: Alterations in fibroblast growth factor receptor 2 () have emerged as promising drug targets for intrahepatic cholangiocarcinoma, a rare cancer with a poor prognosis. Futibatinib, a next-generation, covalently binding FGFR1-4 inhibitor, has been shown to have both antitumor activity in patients with -altered tumors and strong preclinical activity against acquired resistance mutations associated with ATP-competitive FGFR inhibitors.

Methods: In this multinational, open-label, single-group, phase 2 study, we enrolled patients with unresectable or metastatic fusion-positive or rearrangement-positive intrahepatic cholangiocarcinoma and disease progression after one or more previous lines of systemic therapy (excluding FGFR inhibitors).

Volumetric Enhancing Tumor Burden at CT to Predict Survival Outcomes in Patients with Neuroendocrine Liver Metastases after Intra-arterial Treatment.

Purpose To investigate whether liver enhancing tumor burden (LETB) assessed at contrast-enhanced CT indicates early response and helps predict survival outcomes in patients with multifocal neuroendocrine liver metastases (NELM) after intra-arterial treatment. Materials and Methods This retrospective study included patients with NELM who underwent intra-arterial treatment with transarterial embolization (TAE) or chemoembolization (TACE) between April 2006 and December 2018. Tumor response in treated NELM was evaluated by using the Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST).

Emerging and Evolving Concepts in Cancer Immunotherapy Imaging.

Criteria based on measurements of lesion diameter at CT have guided treatment with historical therapies due to the strong association between tumor size and survival. Clinical experience with immune checkpoint modulators shows that editing immune system function can be effective in various solid tumors. Equally, novel immune-related phenomena accompany this novel therapeutic paradigm.

Tissue Selection for PD-L1 Testing in Triple Negative Breast Cancer (TNBC).

Atezolizumab in combination with nab-paclitaxel has been introduced for the treatment of locally advanced or recurrent triple negative breast cancer (TNBC). Patient selection relies on the use of immunohistochemistry using a specific monoclonal PD-L1 antibody (clone SP142) in a tightly controlled companion diagnostic test (CDx) with a defined interpretative algorithm. Currently there are no standardized recommendations for selecting the optimal tissue to be tested and there is limited data to support decision making, raising the possibility that tissue selection may bias test results.

Loco-Regional Therapies in Oligometastatic Adrenocortical Carcinoma.

Objective: The recommended first-line treatment for low-tumor-burden ACC (stage IVa ACC) not amenable to radical resection is mitotane in association with loco-regional treatments (LRs). The aim of this study was to determine the patient population that would benefit the most from LR. Materials and methods: This retrospective monocentric expert center chart review study was performed from 2008 to 2021 and included stage IVa patients (≤2 tumoral organs) treated with LR (either radiotherapy, surgery, or interventional radiology).

Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer.

Background: Metastatic castration-resistant prostate cancer remains fatal despite recent advances. Prostate-specific membrane antigen (PSMA) is highly expressed in metastatic castration-resistant prostate cancer. Lutetium-177 (Lu)-PSMA-617 is a radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and the surrounding microenvironment.

Prophylactic Percutaneous Consolidation of Large Osteolytic Tumors of the Pelvic Ring Using Fixation by Internal Cemented Screws.

Purpose To evaluate the efficacy, durability, and safety of percutaneous fixation by internal cemented screw (FICS) for prophylactic consolidation of impending pathologic fractures of the pelvic ring. Materials and Methods In this single-institute retrospective study, patients with large, minimally symptomatic to asymptomatic osteolytic tumors of the pelvic ring that were treated with percutaneous cone-beam CT-guided FICS procedures were included (January 2014 to May 2019). Follow-up cross-section imaging and clinical reports were reviewed for procedural complications and assessment of the long-term consolidation efficacy on the basis of the development of pathologic fracture or need for additional surgical intervention.

Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2).

ARIEL2 (NCT01891344) is a single-arm, open-label phase 2 study of the PARP inhibitor (PARPi) rucaparib in relapsed high-grade ovarian carcinoma. In this post hoc exploratory biomarker analysis of pre- and post-platinum ARIEL2 samples, RAD51C and RAD51D mutations and high-level BRCA1 promoter methylation predict response to rucaparib, similar to BRCA1/BRCA2 mutations. BRCA1 methylation loss may be a major cross-resistance mechanism to platinum and PARPi.

Phenotypic discordance between primary and metastatic breast cancer in the large-scale real-life multicenter French ESME cohort.

Expression of hormone receptor (HR) for estrogens (ER) and progesterone (PR) and HER2 remains the cornerstone to define the therapeutic strategy for breast cancer patients. We aimed to compare phenotypic profiles between matched primary and metastatic breast cancer (MBC) in the ESME database, a National real-life multicenter cohort of MBC patients. Patients with results available on both primary tumour and metastatic disease within 6 months of MBC diagnosis and before any tumour progression were eligible for the main analysis.

Exploratory window-of-opportunity trial to investigate the tumor pharmacokinetics/pharmacodynamics of the IAP antagonist Debio 1143 in patients with head and neck cancer.

Inhibitor of apoptosis proteins (IAPs) regulate apoptosis and modulate NF-κB signaling thereby driving expression of genes involved in immune/inflammatory responses. The orally available IAP antagonist Debio 1143 has potential to enhance tumor response to chemoradiotherapy and/or immunotherapy. Patients with pre-operative squamous cell carcinomas of the head and neck (SCCHN) received: Debio 1143 monotherapy (200 mg/day [D]1-15 +/- 2); Debio 1143 (200 mg/day D1-15 +/- 2) plus cisplatin (40 mg/m D 1 and 8); cisplatin alone (40 mg/m D 1 and 8; EudraCT: 2014-004655-31).

Risk factors of de novo malignancies after liver transplantation: a French national study on 11004 adult patients.

Background: After liver transplantation (LT),de novo malignancies are one of the leading causes of late mortality. The aim of the present retrospective study was to identify the risk factors of de novo malignancies in a large cohort of LT recipients in France, using Fine and Gray competing risks regression analysis.

Methods: The study population consisted in 11004 adults transplanted between 2000 and 2013, who had no history of pre-transplant malignancy, except primary liver tumor.

Image-guided Percutaneous Fixation with Internal Cemented Screws of Impending Femoral Neck Pathologic Fractures in Patients with Metastatic Cancer: Safety, Efficacy, and Durability.

Background Prophylactic image-guided procedures performed by interventional radiologists for impending pathologic fractures are becoming more pertinent, as patients with metastatic cancer have extended overall survival because of advanced therapies. Purpose To evaluate the efficacy, safety, and palliative durability of collimated-beam CT-guided percutaneous fixation with internal cemented screws (FICS) for impending pathologic fractures of the femoral neck. Materials and Methods This single-institute retrospective study examined all patients with metastatic cancer treated between February 2010 and October 2019 with collimated-beam CT-guided percutaneous FICS procedures for preventive consolidation of impending femoral neck pathologic fractures.

Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide.

Background: Darolutamide is a structurally distinct androgen-receptor inhibitor that is approved for the treatment of nonmetastatic, castration-resistant prostate cancer. In the planned primary analysis of a phase 3 trial, the median metastasis-free survival was significantly longer with darolutamide (40.4 months) than with placebo (18.

Pimasertib Versus Dacarbazine in Patients With Unresectable -Mutated Cutaneous Melanoma: Phase II, Randomized, Controlled Trial with Crossover.

This study investigated the efficacy and safety of pimasertib (1/2 inhibitor) versus dacarbazine (DTIC) in patients with untreated -mutated melanoma. Phase II, multicenter, open-label trial. Patients with unresectable, stage IIIc/IVM1 -mutated cutaneous melanoma were randomized 2:1 to pimasertib (60 mg; oral twice-daily) or DTIC (1000 mg/m; intravenously) on Day 1 of each 21-day cycle.