Sharmistha Ghosh

BACKGROUND: Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, has robust efficacy in patients with ALK-positive non-small-cell lung cancer (NSCLC) that is refractory to crizotinib. The efficacy of brigatinib, as compared with crizotinib, in patients with advanced ALK-positive NSCLC who have not previously received an ALK inhibitor is unclear. METHODS: In an open-label, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced ALK-positive NSCLC who had not previously received ALK inhibitors to receive brigatinib at a dose of 180 mg once daily (with a 7-day lead-in period at 90 mg) or crizotinib at a dose of 250 mg twice daily. The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included the objective response rate and intracranial response. The first interim analysis was planned when approximately 50% of 198 expected events of disease progression or death had occurred. RESULTS: A total of 275 patients underwent randomization; 137 were assigned to brigatinib and 138 to crizotinib. At the first interim analysis (99 events), the median follow-up was 11.0 months in the brigatinib group and 9.3 months in the crizotinib group. The rate of progression-free survival was higher with brigatinib than with crizotinib (estimated 12-month progression-free survival, 67% [95% confidence interval {CI}, 56 to 75] vs. 43% [95% CI, 32 to 53]; hazard ratio for disease progression or death, 0.49 [95% CI, 0.33 to 0.74]; P<0.001 by the log-rank test). The confirmed objective response rate was 71% (95% CI, 62 to 78) with brigatinib and 60% (95% CI, 51 to 68) with crizotinib; the confirmed rate of intracranial response among patients with measurable lesions was 78% (95% CI, 52 to 94) and 29% (95% CI, 11 to 52), respectively. No new safety concerns were noted. CONCLUSIONS: Among patients with ALK-positive NSCLC who had not previously received an ALK inhibitor, progression-free survival was significantly longer among patients who received brigatinib than among those who received crizotinib. (Funded by Ariad Pharmaceuticals; ALTA-1L ClinicalTrials.gov number, NCT02737501 .).

Crucial transitions in cancer-including tumor initiation, local expansion, metastasis, and therapeutic resistance-involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecedented resolution. The Human Tumor Atlas Network (HTAN), part of the National Cancer Institute (NCI) Cancer Moonshot Initiative, will establish a clinical, experimental, computational, and organizational framework to generate informative and accessible three-dimensional atlases of cancer transitions for a diverse set of tumor types. This effort complements both ongoing efforts to map healthy organs and previous large-scale cancer genomics approaches focused on bulk sequencing at a single point in time. Generating single-cell, multiparametric, longitudinal atlases and integrating them with clinical outcomes should help identify novel predictive biomarkers and features as well as therapeutically relevant cell types, cell states, and cellular interactions across transitions. The resulting tumor atlases should have a profound impact on our understanding of cancer biology and have the potential to improve cancer detection, prevention, and therapeutic discovery for better precision-medicine treatments of cancer patients and those at risk for cancer.

OBJECTIVES: The aim of this study was to determine the association between women's decision-making power and utilisation of maternal healthcare services (MHS) among Bangladeshi women. SETTINGS: This is a nationally representative survey that encompassed Dhaka, Rajshahi, Rangpur, Chittagong, Khulna, Barisal and Sylhet in Bangladesh. Sample households were selected by a two-stage stratification technique. First, 207 clusters in urban areas and 393 in rural areas were selected for 600 enumeration areas with proportional probability. In the second stage, on average 30 households were selected systematically from the enumeration areas. Finally, 17 989 households were selected for the survey of which 96% were interviewed successfully. PARTICIPANTS: Cross-sectional data on 4309 non-pregnant women were collected from Bangladesh demographic and health survey 2014. Decision-making status on respondent's own healthcare, large household purchases, having a say on child's healthcare and visiting to family or relatives were included in the analysis. RESULTS: Prevalence of at least four antenatal attendance, facility delivery and postnatal check-up were respectively 32.6% (95% CI 31.2 to 34), 40.6% (95% CI 39.13 to 42.07) and 66.3% (95% CI 64.89 to 67.71). Compared with women who could make decisions alone, women in the urban areas who had to decide on their healthcare with husband/partner had 20% (95% CI 0.794 to 1.799) higher odds of attending at least four antenatal visits and those in rural areas had 35% (95% CI 0.464 to 0.897) lower odds of attending at least four antenatal visits. Women in urban and rural areas had respectively 43% (95% CI 0.941 to 2.169) and 28% (95% CI 0.928 to 1.751) higher odds of receiving postnatal check-up when their health decisions were made jointly with their husband/partner. CONCLUSION: Neither making decisions alone, nor deciding jointly with husband/partner was always positively associated with the utilisation of all three types of MHS. This study concludes that better spousal cooperation on household and health issues could lead to higher utilisation of MHS services.