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Eosinophilic fasciitis (EF) and generalized morphea (GM) are rare and difficult-to-treat sclerosing skin diseases which may occur in association with hematologic disorders. We present a 66-year-old man with EF and associated Waldenström macroglobulinemia who received combination therapy with rituximab (375mg/m2 every other week, gradually extended to every eight weeks), prednisolone (1.25-30mg/d), and methotrexate (7.5-15mg/w). Three months after rituximab initiation, his skin condition improved steadily accompanied by a significant improvement in joint mobility with only mild and transitory flares (observation period: 59 months under treatment with rituximab). To date, there are five case reports on rituximab treatment of EF/GM with an association to hypergammaglobulinemia in three of those cases. Therapy effected significant improvement in four patients. Our case adds to the hitherto limited evidence that rituximab may be a promising therapeutic strategy for EF/GM in association with hypergammaglobulinemia.

BackgroundEntrectinib is a potent inhibitor of tropomyosin receptor kinase (TRK) A, B, and C, which has been shown to have anti-tumour activity against NTRK gene fusion-positive solid tumours, including CNS activity due to its ability to penetrate the blood-brain barrier. We present an integrated efficacy and safety analysis of patients with metastatic or locally advanced solid tumours harbouring oncogenic NTRK1, NTRK2, and NTRK3 gene fusions treated in three ongoing, early-phase trials.MethodsAn integrated database comprised the pivotal datasets of three, ongoing phase 1 or 2 clinical trials (ALKA-372-001, STARTRK-1, and STARTRK-2), which enrolled patients aged 18 years or older with metastatic or locally advanced NTRK fusion-positive solid tumours who received entrectinib orally at a dose of at least 600 mg once per day in a capsule. All patients had an Eastern Cooperative Oncology Group performance status of 0-2 and could have received previous anti-cancer therapy (except previous TRK inhibitors). The primary endpoints, the proportion of patients with an objective response and median duration of response, were evaluated by blinded independent central review in the efficacy-evaluable population (ie, patients with NTRK fusion-positive solid tumours who were TRK inhibitor-naive and had received at least one dose of entrectinib). Overall safety evaluable population included patients from STARTRK-1, STARTRK-2, ALKA-372-001, and STARTRK-NG (NCT02650401; treating young adult and paediatric patients [aged ≤21 years]), who received at least one dose of entrectinib, regardless of tumour type or gene rearrangement. NTRK fusion-positive safety evaluable population comprised all patients who have received at least one dose of entrectinib regardless of dose or follow-up. These ongoing studies are registered with ClinicalTrials.gov, NCT02097810 (STARTRK-1) and NCT02568267 (STARTRK-2), and EudraCT, 2012-000148-88 (ALKA-372-001).FindingsPatients were enrolled in ALKA-372-001 from Oct 26, 2012, to March 27, 2018; in STARTRK-1 from Aug 7, 2014, to May 10, 2018; and in STARTRK-2 from Nov 19, 2015 (enrolment is ongoing). At the data cutoff date for this analysis (May 31, 2018) the efficacy-evaluable population comprised 54 adults with advanced or metastatic NTRK fusion-positive solid tumours comprising ten different tumour types and 19 different histologies. Median follow-up was 12.9 months (IQR 8·77-18·76). 31 (57%; 95% CI 43·2-70·8) of 54 patients had an objective response, of which four (7%) were complete responses and 27 (50%) partial reponses. Median duration of response was 10 months (95% CI 7·1 to not estimable). The most common grade 3 or 4 treatment-related adverse events in both safety populations were increased weight (seven [10%] of 68 patients in the NTRK fusion-positive safety population and in 18 [5%] of 355 patients in the overall safety-evaluable population) and anaemia (8 [12%] and 16 [5%]). The most common serious treatment-related adverse events were nervous system disorders (three [4%] of 68 patients and ten [3%] of 355 patients). No treatment-related deaths occurred.InterpretationEntrectinib induced durable and clinically meaningful responses in patients with NTRK fusion-positive solid tumours, and was well tolerated with a manageable safety profile. These results show that entrectinib is a safe and active treatment option for patients with NTRK fusion-positive solid tumours. These data highlight the need to routinely test for NTRK fusions to broaden the therapeutic options available for patients with NTRK fusion-positive solid tumours.FundingIgnyta/F Hoffmann-La Roche.

This document summarizes the key findings and insights from the 2023 European Society for Medical Oncology (ESMO) annual meeting, with a focus on thoracic oncology. It covers various topics such as immunotherapy-based therapy in nonmetastatic settings, radiotherapy in non-small cell lung cancer (NSCLC), and bispecific T-cell engagers in small cell lung cancer (SCLC). The report includes data from clinical trials and studies, highlighting the effectiveness and safety of different treatment approaches. It also mentions the approval of certain therapies by regulatory bodies and emphasizes the need for further research in specific patient subgroups. Authored by a team of experts, this report provides valuable insights and perspectives for library patrons conducting research in this field. [Extracted from the article]

This paper presents a comprehensive workflow for integrating revolving events into the transitive sequential pattern mining (tSPM+) algorithm and Machine Learning for Health Outcomes (MLHO) framework, emphasizing best practices and pitfalls in its application. We emphasize feature engineering and visualization techniques, demonstrating their efficacy in capturing temporal relationships. Applied to an EGFR lung cancer cohort, our approach showcases reliable temporal insights even in a small dataset. This work highlights the importance of temporal nuances in healthcare data analysis, paving the way for improved disease understanding and patient care. [ABSTRACT FROM AUTHOR]

Simple Summary: Identification of the optimal treatment strategy is challenging in elderly with non-small cell lung cancer (NSCLC). Outcomes (1) in elderly vs. younger patients and (2) with low-dose cisplatin vs. cisplatin/vinorelbine were studied. Elderly included more males, had a lower Karnofsky index, more comorbidities, and lower stages. Low-dose cisplatin patients had higher age, more comorbidities, and lower stages. We observed reduced dermatitis and dysphagia and increased anemia and thrombocytopenia in elderly, without increased ≥grade 3 toxicities. Low-dose cisplatin was less toxic than cisplatin/vinorelbine. Survival was lower in elderly vs. younger and comparable between both chemotherapy protocols. In elderly, gender, Karnofsky index, stage, and multimodal treatment (including additional surgery/systemic therapy) were prognostic factors. In elderly, we found acceptable toxicities with radiotherapy but the need for the improvement of outcomes. Multimodal strategies showed a favorable prognosis and can reasonably be considered. Low-dose cisplatin should be discussed on an individual basis due to favorable toxicity and outcomes. Identification of the optimal treatment strategy is challenging in elderly with localized non-small cell lung cancer (NSCLC). Concurrent chemotherapy with low-dose cisplatin represents an option for elderly. Outcomes (1) in elderly (≥70 years, n = 158) vs. younger patients (n = 188) and (2), independently of age, in definitive radiochemotherapy, with low-dose cisplatin (n = 125) vs. cisplatin/vinorelbine (n = 76) were studied. Elderly included more males, had a lower Karnofsky index, more comorbidities, and lower stages. Low-dose cisplatin patients (vs. cisplatin/vinorelbine) had higher age, more comorbidities, and lower stages. We observed reduced dermatitis and dysphagia and increased anemia and thrombocytopenia in elderly vs. younger patients, without increased ≥grade 3 toxicities. Low-dose cisplatin was less toxic than cisplatin/vinorelbine. Survival outcomes were lower in elderly vs. younger and comparable between low-dose cisplatin and cisplatin/vinorelbine. In elderly, gender, Karnofsky index, stage, and multimodal treatment (including additional surgery/systemic therapy) were identified as prognostic factors. In conclusion, we found evidence for an acceptable toxicity profile and the need for improvement of outcomes in elderly with localized NSCLC. Multimodal strategies (including additional surgery/systemic treatment) showed favorable outcomes and should be reasonably considered in elderly who are deemed fit enough. Low-dose cisplatin should be discussed on an individual basis due to favorable toxicity and outcomes. [ABSTRACT FROM AUTHOR]

Aims: Maintaining quality of life (QoL) in patients with cancer has gathered significant interest, but little is known about its major determinants. We sought to identify determinants of QoL in patients undergoing cancer treatment as well as in treatment‐naïve patients about to commence such therapy. Methods and results: QoL was assessed in 283 patients with cancer using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 questionnaire. All patients underwent a battery of tests including physical examination, resting electrocardiogram, hand grip strength, and biochemistry assessment. Using multivariable logistic regression, we found that age [odds ratio (OR) 0.954, 95% confidence interval (CI) 0.916–0.994], resting heart rate (OR 1.036, 95% CI 1.004–1.068), hand grip strength (OR 0.932, 95% CI 0.878–0.990), and the presence of cachexia (OR 4.334, 95% CI 1.767–10.631) and dyspnoea (OR 3.725, 95% CI 1.540–9.010; all P < 0.05) remained independently predictive of reduced QoL. Conclusions: Therefore, it may be reasonable to address circumstances that are affecting muscle mass, body weight, and heart rate to maintaining QoL; however, prospective studies to test these endpoints are required. [ABSTRACT FROM AUTHOR]