Curious Explorer: a Provable Exploration Strategy in Policy Learning.

A coverage assumption is critical with policy gradient methods, because while the objective function is insensitive to updates in unlikely states, the agent may need improvements in those states to reach a nearly optimal payoff. However, this assumption can be unfeasible in certain environments, for instance in online learning, or when restarts are possible only from a fixed initial state. In these cases, classical policy gradient algorithms like REINFORCE can have poor convergence properties and sample efficiency.

The Clinical Features and Outcomes of Pseudocirrhosis in Breast Cancer.

Pseudocirrhosis is a diffuse nodularity of the liver that radiologically mimics cirrhosis but is a distinct pathological process. It is seen almost exclusively in patients with liver metastases and may represent a response to systemic treatment. Data on the risk factors for pseudocirrhosis and outcomes are limited.

The emerging predictive and prognostic role of HER2 in HER2-negative early breast cancer: a retrospective study.

Purpose: Many patients with early breast cancer (eBC) undergoing neoadjuvant chemotherapy do not achieve pathological complete response (pCR), which is a prognostic factor. We examined the role of HER2-low expression in predicting pCR and prognosis in HER2-negative eBC.

Methods: We evaluated patients with stage I-III HER2-negative BC, treated between 2013 and 2023 at The Royal Marsden NHS Foundation Trust, London.

A Novel Variant in Causing Muscle Weakness and Concomitant Hypercontractile Phenotype.

A novel variant of unknown significance c.8A > G (p.Glu3Gly) in was detected in two unrelated families.

Imaging in metastatic breast cancer, CT, PET/CT, MRI, WB-DWI, CCA: review and new perspectives.

Background: Breast cancer is the most frequent cancer in women and remains the second leading cause of death in Western countries. It represents a heterogeneous group of diseases with diverse tumoral behaviour, treatment responsiveness and prognosis. While major progress in diagnosis and treatment has resulted in a decline in breast cancer-related mortality, some patients will relapse and prognosis in this cohort of patients remains poor.

Integrin α7 Mutations Are Associated With Adult-Onset Cardiac Dysfunction in Humans and Mice.

Background Integrin α7β1 is a major laminin receptor in skeletal and cardiac muscle. In skeletal muscle, integrin α7β1 plays an important role during muscle development and has been described as an important modifier of skeletal muscle diseases. The integrin α7β1 is also highly expressed in the heart, but its precise role in cardiac function is unknown.

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer.

Background: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS).

Neratinib in advanced HER2-positive breast cancer: experience from the royal Marsden hospital.

Purpose: To describe the tolerability and efficacy of neratinib as a monotherapy and in combination with capecitabine in advanced HER2-positive breast cancer in a real-world setting.

Methods: Patients who received neratinib for advanced HER2-positive at the Royal Marsden Hospital NHS Trust between August 2016 and May 2020 were identified from electronic patient records and baseline characteristics, previous treatment and response to treatment were recorded. The primary endpoint of the study was progression-free survival (PFS).

Vinorelbine After Prior Treatment With Eribulin for Advanced Breast Cancer: A Single-Centre Experience Suggesting Cross-Resistance.

Introduction: The tubulin inhibitor, eribulin, improves survival for previously treated advanced breast cancer (ABC) compared to chemotherapy of physician's choice, including vinorelbine, an older anti-tubulin. Vinorelbine is commonly still used after eribulin, but potentially risks cross-resistance and its efficacy in this setting is unproven.

Materials And Methods: A retrospective analysis of all patients who received vinorelbine after prior eribulin (VAE) 2011-2015 and a parallel cohort of consecutive patients who received vinorelbine without prior eribulin (VWE) for previously treated ABC between 2005 and 2011.

Real-World Data on Access to Standards of Care for People With Spinal Muscular Atrophy in the UK.

Spinal Muscular Atrophy (SMA) is characterized by muscle atrophy and weakness and has an incidence of 1:11. 000 live births which projects an estimated population in the UK of 650-1,300 affected patients. Standards of Care (SoC) were updated in 2017 and they have been widely adopted as a reference for implementation of care in SMA across the globe.

Clinical outcomes in patients with triple negative or HER2 positive lobular breast cancer: a single institution experience.

Purpose: Invasive lobular carcinomas (ILC) are characterised by loss of the cell adhesion molecule E-cadherin. Approximately 15% of ILC are ER negative at the time of breast cancer diagnosis, or at relapse due to loss of ER expression. Less than 5% of classical ILC but up to 35% of pleomorphic ILC are HER2 positive (HER2+).

Impact of the Sessile Serrated Polyp Pathway on Predicted Colorectal Cancer Outcomes.

Background And Aims: Approximately 20%-30% of colorectal cancers (CRCs) arise from the serrated polyp pathway. CRC screening options have differential sensitivity to detect sessile serrated polyps (SSPs). We used the Colorectal Cancer and Adenoma Incidence and Mortality Microsimulation Model (CRC-AIM) to assess how the detection of SSPs impacts predicted life years gained (LYG), CRC incidence, and CRC mortality with multitarget stool DNA (mt-sDNA) or fecal immunochemical test (FIT) screening.

Impact of timing of adjuvant chemothapy for early breast cancer: the Royal Marsden Hospital experience.

Background: The optimal time to deliver adjuvant chemotherapy has not been defined.

Methods: A retrospective study of consecutive patients receiving adjuvant anthracycline and/or taxane 1993-2010. Primary endpoint included 5-year disease-free survival (DFS) in patients commencing chemotherapy <31 versus ≥31 days after surgery.

Longitudinal observational study investigating outcome measures for clinical trials in inclusion body myositis.

Objective: To describe decline in muscle strength and physical function in patients with sporadic inclusion body myositis (IBM).

Methods: Manual muscle testing (MMT), quantitative muscle testing (QMT) and disability scoring using the IBM Functional Rating Scale (IBMFRS) were undertaken for 181 patients for up to 7.3 years.

Cutaneous toxicities occurring during palbociclib (CDK4/6 inhibitor) and endocrine therapy in patients with advanced breast cancer: a single-centre experience.

Purpose: Treatment with Palbociclib, a cyclin-dependent kinase 4/6 inhibitor, has demonstrated significantly improved progression-free survival in patients with hormone receptor-positive, HER2-negative, advanced breast cancer, when used in combination with letrozole or fulvestrant endocrine therapies. However, limited information exists on its cutaneous adverse effects (AE). Hence, we conducted a retrospective cohort study to investigate the prevalence and management of cutaneous AE during palbociclib and endocrine therapy.

Recent trends in colorectal cancer screening methods based on Medicare claims data.

Objective: Despite the availability of multiple screening modalities for early detection of colorectal cancer (CRC), participation rates remain well below guideline recommendation goals in the United States. This study analyzed and compared recent national trends in utilization of CRC screening modalities using Medicare claims data.

Method: Medicare claims data for CRC screening during 2014-2018 were aggregated and analyzed by CPT code frequency.

Estimating the impact of differential adherence on the comparative effectiveness of stool-based colorectal cancer screening using the CRC-AIM microsimulation model.

Background: Real-world adherence to colorectal cancer (CRC) screening strategies is imperfect. The CRC-AIM microsimulation model was used to estimate the impact of imperfect adherence on the relative benefits and burdens of guideline-endorsed, stool-based screening strategies.

Methods: Predicted outcomes of multi-target stool DNA (mt-sDNA), fecal immunochemical tests (FIT), and high-sensitivity guaiac-based fecal occult blood tests (HSgFOBT) were simulated for 40-year-olds free of diagnosed CRC.

Impact of screening and follow-up colonoscopy adenoma sensitivity on colorectal cancer screening outcomes in the CRC-AIM microsimulation model.

Background: Real-world data for patients with positive colorectal cancer (CRC) screening stool-tests demonstrate that adenoma detection rates are lower when endoscopists are blinded to the stool-test results. This suggests adenoma sensitivity may be lower for screening colonoscopy than for follow-up to a known positive stool-based test. Previous CRC microsimulation models assume identical sensitivities between screening and follow-up colonoscopies after positive stool-tests.

Differential Diagnoses of Inclusion Body Myositis.

Inclusion body myositis is a slowly progressive myopathy, characteristically affecting quadriceps and long finger flexors. Atypical presentations do occur, however, and there is overlap with other myopathies, including inflammatory and hereditary etiologies. This article discusses atypical cases and differential diagnoses and considers the role of imaging and histopathology in differentiating inclusion body myositis.

Safety and efficacy of T-DM1 in patients with advanced HER2-positive breast cancer The Royal Marsden experience.

Background: Ado-trastuzumab emtansine (T-DM1) is standard of care for patients with advanced HER2+ breast cancer who relapse within 6 months of adjuvant trastuzumab or progress on first-line anti-HER2 therapy. We evaluated its safety and efficacy in our real-world population.

Methods: We identified patients on T-DM1 from 01/01/2014 to 12/03/2018 from our electronic records.

The impact of Oncotype DX breast cancer assay results on clinical practice: a UK experience.

Background: Genomic tests are increasingly being used by clinicians when considering adjuvant chemotherapy for patients with oestrogen receptor-positive (ER+), human epidermal growth factor 2-negative (HER2-) breast cancer. The Oncotype DX breast recurrence score assay was the first test available in the UK National Health Service. This study looked at how UK clinicians were interpreting Recurrence Scores (RS) in everyday practice.

Inactivating Mutations Are Enriched in Advanced Breast Cancer and Contribute to Endocrine Therapy Resistance.

Purpose: Advanced breast cancer (ABC) has not been subjected to the same degree of molecular scrutiny as early primary cancer. Breast cancer evolves with time and under the selective pressure of treatment, with the potential to acquire mutations with resistance to treatment and disease progression. To identify potentially targetable mutations in advanced breast cancer, we performed prospective molecular characterization of a cohort of patients with ABC.