Treatment decisions in estrogen receptor-positive early breast cancer patients with intermediate oncotype DX recurrence score results

This retrospective study evaluated the impact of intermediate Recurrence Score(®) results on adjuvant treatment decisions in estrogen receptor-positive (ER+) early invasive breast cancer, comparing treatment recommendations pre-testing with actual treatments received post-testing. Of the 111 patients included in the analysis, 78 (70.3%) had hormonal therapy (HT) and 33 (29.7%) had chemohormonal therapy (CHT) recommendations pre-testing. The Recurrence Score was significantly higher in those with a pre-testing CHT recommendation compared with those with a pre-testing HT recommendation (median of 24 vs. 22; P = 0.047; Mann–Whitney–Wilcoxon [MWW] test). Post-testing, treatment of 24 patients (21.6%) was different from their pre-testing recommendation. The difference between CHT recommendation rate pre-testing and the rate of CHT received post-testing was nonsignificant for the entire cohort and for patients’ subgroups (by age, tumor size, and grade) (P >0.17; McNemar’s test). Following classification of the cohort into two Recurrence Score subcategories (low-intermediate, [18-25]; high-intermediate, [26-30]), changes in treatment decisions (pre-testing recommendations vs. actual treatments received post testing) were reported for 16.5% of low-intermediate and 34.4% of high-intermediate patients. Post-testing, the rate of CHT decreased (by 58%) in the low-intermediate subcategory and increased (by 64%) in the high-intermediate subcategory (P <0.01, both subcategories). In logistic regression analyses, the Recurrence Score subcategory was the only significant predictor of changes in treatment decisions (pre-testing recommendations vs. actual treatments received post testing; P <0.01). The only significant difference between the two subsets of patients with such a change (HT to CHT, 11 patients; CHT to HT, 13 patients) was the Recurrence Score (median of 28 vs. 20, respectively; P = 0.0014; MWW test). These findings demonstrate that intermediate Recurrence Score results provide clinically relevant information and impact treatment decisions in ER + early breast cancer

Oxaliplatin-Induced Pulmonary Toxicity in Gastrointestinal Malignancies: Two Case Reports and Review of the Literature

Oxaliplatin is a common chemotherapy drug, used mainly for colon and gastric cancer. Most common side effects are peripheral sensory neuropathy, hematological toxicity, and allergic reactions. A less common side effect is pulmonary toxicity, characterized mainly by interstitial pneumonitis. The incidence of this side effect is unknown, but the toxicity can be fatal. Twenty-six cases of pulmonary toxicity have been described in the literature, seven in the setting of adjuvant treatment. We describe two fatal cases of pulmonary injury related to oxaliplatin and a review of the literature.</jats:p

Validation of a cloud-based tele-stroke system reliability in determining national institutes of health stroke scale scores for acute ischemic stroke screening in the emergency department

Remote diagnosis; Tele-strokeDiagnóstico remoto; Tele-ictusDiagnòstic remot; Tele-ictusBackground and purpose: The National Institutes of Health Stroke Scale (NIHSS) is the most recommended tool for objectively quantifying the impairment caused by a suspected stroke. Nevertheless, it is mainly used by trained neurologists in the emergency department (ED). To bring forward the NIHSS to the pre-hospital setting, a smartphone-based Telestroke system was developed. It captures the full NIHSS by video, transmits it off-line, and enables assessment by a distant stroke physician. We aimed to compare the reliability of an NIHSS score determined by a neurologist from afar, using the platform with a standard NIHSS assessment performed in the emergency departments. Methods: A multi-center prospective study was conducted in two centers (Vall d'Hebron, Barcelona, and Rambam, Israel). Patients admitted to the ED with suspected stroke had a neurological exam based on the NIHSS, while being recorded by the system. A skilled neurologist rated the NIHSS according to the videos offline. The results were compared with the NIHSS score given by a neurologist at the bedside. Results: A total of 95 patients with suspected stroke were included. The overall intraclass correlation coefficient was 0.936 (0.99 in VdH and 0.84 in Rambam), indicating excellent and good reliability, respectively. Conclusion: Remote stroke assessment based on the NIHSS, using videos segments collected by a dedicated platform, installed on a standard smartphone, is a reliable measurement as compared with the bedside evaluation.The authors declare that this study received funding from CVAID Company. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication

Biomarker-Directed Targeted Therapy Plus Durvalumab in Advanced Non-Small-Cell Lung Cancer: A Phase 2 Umbrella Trial

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance—which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment—and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure of anti-PD-(L)1-containing immunotherapy and platinum-doublet therapy. A total of 268 patients received durvalumab (anti-PD-L1 monoclonal antibody)–ceralasertib (ATR kinase inhibitor), durvalumab–olaparib (PARP inhibitor), durvalumab–danvatirsen (STAT3 antisense oligonucleotide) or durvalumab–oleclumab (anti-CD73 monoclonal antibody). Greatest clinical benefit was observed with durvalumab–ceralasertib; objective response rate (primary outcome) was 13.9% (11/79) versus 2.6% (5/189) with other regimens, pooled, median progression-free survival (secondary outcome) was 5.8 (80% confidence interval 4.6–7.4) versus 2.7 (1.8–2.8) months, and median overall survival (secondary outcome) was 17.4 (14.1–20.3) versus 9.4 (7.5–10.6) months. Benefit with durvalumab–ceralasertib was consistent across known immunotherapy-refractory subgroups. In ATM-altered patients hypothesized to harbor vulnerability to ATR inhibition, objective response rate was 26.1% (6/23) and median progression-free survival/median overall survival were 8.4/22.8 months. Durvalumab–ceralasertib safety/tolerability profile was manageable. Biomarker analyses suggested that anti-PD-L1/ATR inhibition induced immune changes that reinvigorated antitumor immunity. Durvalumab–ceralasertib is under further investigation in immunotherapy-refractory NSCLC

Biological Insights From Plasma Proteomics of Non-small Cell Lung Cancer Patients Treated With Immunotherapy

INTRODUCTION: Immune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes in blood plasma to gain a better understanding of treatment response and resistance. METHODS: Pre-treatment (T0) and on-treatment (T1) plasma samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma was profiled using aptamer-based technology to quantify approximately 7000 plasma proteins per sample. Proteins displaying significant fold changes (T1:T0) were analyzed further to identify associations with clinical outcomes using clinical benefit and overall survival as endpoints. Bioinformatic analyses of upregulated proteins were performed to determine potential cell origins and enriched biological processes. RESULTS: The levels of 142 proteins were significantly increased in the plasma of NSCLC patients following ICI-based treatments. Soluble PD-1 exhibited the highest increase, with a positive correlation to tumor PD-L1 status, and, in the ICI monotherapy dataset, an association with improved overall survival. Bioinformatic analysis of the ICI monotherapy dataset revealed a set of 30 upregulated proteins that formed a single, highly interconnected network, including CD8A connected to ten other proteins, suggestive of T cell activation during ICI treatment. Notably, the T cell-related network was detected regardless of clinical benefit. Lastly, circulating proteins of alveolar origin were identified as potential biomarkers of limited clinical benefit, possibly due to a link with cellular stress and lung damage. CONCLUSIONS: Our study provides insights into the biological processes activated during ICI-based therapy, highlighting the potential of plasma proteomics to identify mechanisms of therapy resistance and biomarkers for outcome