Significant Clinical Activity of Olaparib in a Somatic BRCA1-Mutated Triple-Negative Breast Cancer With Brain Metastasis

Breast cancer is a biologically and clinically heterogeneous disease, and patients with similar clinical stage have markedly different outcomes. Triple-negative breast cancer (TNBC) is defined by the lack of expression of estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2).1,2 This subtype represents 15% to 20% of all breast cancers and is associated with the worst outcome of all subtypes, with greater tendency to distant recurrence in general and visceral metastasis in particular, including brain metastasis.3,4 To date, chemotherapy remains the standard of care for TNB

Natural language processing for automatic evaluation of free-text answers — a feasibility study based on the European Diploma in Radiology examination

Abstract Background Written medical examinations consist of multiple-choice questions and/or free-text answers. The latter require manual evaluation and rating, which is time-consuming and potentially error-prone. We tested whether natural language processing (NLP) can be used to automatically analyze free-text answers to support the review process. Methods The European Board of Radiology of the European Society of Radiology provided representative datasets comprising sample questions, answer keys, participant answers, and reviewer markings from European Diploma in Radiology examinations. Three free-text questions with the highest number of corresponding answers were selected: Questions 1 and 2 were “unstructured” and required a typical free-text answer whereas question 3 was “structured” and offered a selection of predefined wordings/phrases for participants to use in their free-text answer. The NLP engine was designed using word lists, rule-based synonyms, and decision tree learning based on the answer keys and its performance tested against the gold standard of reviewer markings. Results After implementing the NLP approach in Python, F1 scores were calculated as a measure of NLP performance: 0.26 (unstructured question 1, n = 96), 0.33 (unstructured question 2, n = 327), and 0.5 (more structured question, n = 111). The respective precision/recall values were 0.26/0.27, 0.4/0.32, and 0.62/0.55. Conclusion This study showed the successful design of an NLP-based approach for automatic evaluation of free-text answers in the EDiR examination. Thus, as a future field of application, NLP could work as a decision-support system for reviewers and support the design of examinations being adjusted to the requirements of an automated, NLP-based review process. Clinical relevance statement Natural language processing can be successfully used to automatically evaluate free-text answers, performing better with more structured question-answer formats. Furthermore, this study provides a baseline for further work applying, e.g., more elaborated NLP approaches/large language models. Key points • Free-text answers require manual evaluation, which is time-consuming and potentially error-prone. • We developed a simple NLP-based approach — requiring only minimal effort/modeling — to automatically analyze and mark free-text answers. • Our NLP engine has the potential to support the manual evaluation process. • NLP performance is better on a more structured question-answer format. Graphical Abstrac

Syndrome and outcome of antibody-negative limbic encephalitis

Background and purpose: The aim was to report the clinical characteristics of 12 patients with limbic encephalitis (LE) who were antibody‐negative after a comprehensive immunological study. Methods: The clinical records of 163 patients with LE were reviewed. Immunohistochemistry on rat brain, cultured neurons and cell‐based assays were used to identify neuronal autoantibodies. Patients were included if (i) there was adequate clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging information to classify the syndrome as LE, (ii) magnetic resonance images were accessible for central review and (iii) serum and CSF were available and were confirmed negative for neuronal antibodies. Results: Twelve (7%) of 163 LE patients [median age 62 years; range 40-79; 9 (75%) male] without neuronal autoantibodies were identified. The most frequent initial complaints were deficits in short‐term memory leading to hospital admission in a few weeks (median time 2 weeks; range 0.5-12). In four patients the short‐term memory dysfunction remained as an isolated symptom during the entire course of the disease. Seizures, drowsiness and psychiatric problems were unusual. Four patients had solid tumors (one lung, one esophagus, two metastatic cervical adenopathies of unknown primary tumor) and one chronic lymphocytic leukemia. CSF showed pleocytosis in seven (58%) with a median of 13 white blood cells/mm3 (range 9-25). Immunotherapy included corticosteroids, intravenous immunoglobulins and combinations of both drugs or with rituximab. Clinical improvement occurred in six (54%) of 11 assessable patients. Conclusions: Despite the discovery of new antibodies, 7% of LE patients remain seronegative. Antibody‐negative LE is more frequent in older males and usually develops with predominant or isolated short‐term memory loss. Despite the absence of antibodies, patients may have an underlying cancer and respond to immunotherapy

Pseudoprogression as an adverse event of glioblastoma therapy

We explored predictive factors of pseudoprogression (PsP) and its impact on prognosis in a retrospective series of uniformly treated glioblastoma patients. Patients were classified as having PsP, early progression (eP) or neither (nP). We examined potential associations with clinical, molecular, and basal imaging characteristics and compared overall survival (OS), progression-free survival (PFS), post-progression survival (PPS) as well as the relationship between PFS and PPS in the three groups. Of the 256 patients studied, 56 (21.9%) were classified as PsP, 70 (27.3%) as eP, and 130 (50.8%) as nP. Only MGMT methylation status was associated to PsP. MGMT methylated patients had a 3.5-fold greater possibility of having PsP than eP (OR: 3.48; 95% CI: 1.606-7.564; P=0.002). OS was longer for PsP than eP patients (18.9 vs. 12.3months; P=0.0001) but was similar for PsP and nP patients (P=0.91). OS was shorter-though not significantly sofor PsP than nP patients (OS: 19.5 vs. 27.9months; P=0.63) in methylated patients. PPS was similar for patients having PsP, eP or nP (PPS: 7.2 vs. 5.4 vs. 6.7; P=0.43). Neurological deterioration occurred in 64.3% of cases at the time they were classified as PsP and in 72.8% of cases of eP (P=0.14). PsP confounds the evaluation of disease and does not confer a survival advantage in glioblastoma