Five or more circulating tumor cells (CTCs) per 7.5 mL of blood predicts for poorer progression-free survival (PFS) in patients with metastatic breast cancer (MBC). We conducted a prospective study ...to demonstrate that CTC results correlate strongly with radiographic disease progression at the time of and in advance of imaging.
Serial CTC levels were obtained in patients starting a new treatment regimen for progressive, radiographically measurable MBC. Peripheral blood was collected for CTC enumeration at baseline and at 3- to 4-week intervals. Clinical outcomes were based on radiographic studies performed in 9- to 12-week intervals.
Sixty-eight patients were evaluable for the CTC-imaging correlations, and 74 patients were evaluable for the PFS analysis. Median follow-up was 13.3 months. A statistically significant correlation was demonstrated between CTC levels and radiographic disease progression in patients receiving chemotherapy or endocrine therapy. This correlation applied to CTC results obtained at the time of imaging (odds ratio OR, 6.3), 3 to 5 weeks before imaging (OR, 3.1), and 7 to 9 weeks before imaging (OR, 4.9). Results from analyses stratified by type of therapy remained statistically significant. Shorter PFS was observed for patients with five or more CTCs at 3 to 5 weeks and at 7 to 9 weeks after the start of treatment.
We provide, to our knowledge, the first evidence of a strong correlation between CTC results and radiographic disease progression in patients receiving chemotherapy or endocrine therapy for MBC. These findings support the role of CTC enumeration as an adjunct to standard methods of monitoring disease status in MBC.
Abstract
Background: 1L pembro + platinum-based chemo has shown clinical activity in metastatic NSCLC regardless of tissue tumor mutational burden (tTMB) status. bTMB assessed using circulating tumor ...DNA in plasma may be a surrogate for tTMB. The single-arm, phase 2 KEYNOTE-782 study (NCT03664024) evaluated the correlation of bTMB with efficacy of 1L pembro + chemo in nonsquamous NSCLC.
Methods: Eligible patients (pts) had histologically or cytologically confirmed stage IV nonsquamous NSCLC with measurable disease per RECIST v1.1 and were not eligible for EGFR-, BRAF-, ROS1-, or ALK-directed therapy. Pts were not previously treated for advanced or metastatic disease, had an ECOG PS of 0 or 1, and had an evaluable biopsy sample for biomarker analysis. All pts received intravenous pembro 200 mg Q3W + platinum chemo doublet Q3W (pemetrexed 500 mg/m2 + 4 cycles of carboplatin AUC 5 mg/mL/min or cisplatin 75 mg/m2). The primary objective was to evaluate the association of baseline bTMB with ORR per RECIST v1.1 by investigator assessment. Secondary objectives were to determine safety and the association of baseline bTMB with PFS per RECIST v1.1 by investigator assessment and OS. A study-specific next-generation sequencing-based assay using a 1.9 Mb/654-gene cancer panel, which includes specific lung cancer-associated gene targets, was used to measure bTMB (continuous scale) in cell-free DNA extracted from baseline plasma samples. Paired white blood cell DNA sequencing was also performed to eliminate potential clonal hematopoiesis-derived somatic mutations. Database cutoff: November 5, 2021.
Results: 117 pts were enrolled; median age was 64.0 years (range, 37-85), and the majority were male (60.7%), had an ECOG PS of 1 (69.2%), and no brain metastases at baseline (92.3%). Median time from first dose to data cutoff was 19.3 months (range, 1.0-35.5). ORR was 40.2% (95% CI, 31.2-49.6; 6 CRs, 41 PRs), median PFS was 7.2 months (95% CI, 5.6-9.8), and median OS was 18.1 months (95% CI, 13.5-25.6). Treatment-related adverse events (TRAEs) occurred in 113 pts (96.6%) and grade 3-5 TRAEs occurred in 56 (47.9%). Eight pts (6.8%) died due to a TRAE (febrile neutropenia and pneumonitis n = 2 each, and septic shock, pulmonary sepsis, general physical health deterioration, and neutropenia n = 1 each). bTMB data were available for 101 pts. The area under the receiver operating curve for bTMB as a continuous variable to discriminate response was 0.47 (95% CI, 0.36-0.59). The posterior probabilities for a positive association of bTMB with PFS and OS were 16.8% and 7.8%, respectively.
Conclusions: Baseline bTMB showed no evidence of an association with ORR, PFS, or OS in pts with nonsquamous NSCLC treated with 1L pembro + chemo. These findings indicate no clinical utility of bTMB in this patient population and treatment setting. No new safety signals were observed.
Citation Format: Jair Bar, Emilio Esteban, Delvys Rodríguez-Abreu, Santiago Ponce Aix, Zsuzsanna Szalai, Enriqueta Felip, Maya Gottfried, Mariano Provencio Pulla, Andrew Robinson, Andrea Fülöp, Suman B. Rao, D. Ross Camidge, Giovanna Speranza, Steven M. Townson, Julie Kobie, Mark Ayers, Elisha J. Dettman, Robert McDaniel, Byoungsok Jung, David Burkhardt, Ruth Mauntz, Tibor Csőszi. Response to first-line (1L) pembrolizumab (pembro) + chemotherapy (chemo) in non-small cell lung cancer (NSCLC) by blood tumor mutational burden (bTMB): the phase 2 KEYNOTE-782 trial abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT216.
INTRODUCTION: Medication errors (MEs) can prolong hospital stay and are a cause of morbidity and mortality. Studies evaluating MEs and its determinants in Indian neonatal intensive care units (NICUs) ...are limited. Therefore, this study was done to assess the prevalence, characteristics, determinants, and outcomes of MEs in an Indian NICU setting.
METHODOLOGY: A prospective observational study was conducted over a 1-year period (January-December 2016) among neonates receiving medications in NICU. Systematic random sampling was done, and data were collected using a semi-structured questionnaire after obtaining informed consent from the mother. An ME self-reporting system was also established. Data were analyzed using Chi-squared test and Student's t-test. Binary logistic regression was used to analyze the determinants of MEs.
RESULTS: Among 269 babies included in the study, 57% (n = 154) were male babies with mean (standard deviation SD) birth weight of 2.59 kg (0.701). About 79% (n = 213/269) of the neonates were appropriate for gestational age. The mean (SD) duration of stay in NICU was 7.58 (5.07) days, and 67% of the babies had polypharmacy (use of ≥5 medications). The prevalence of MEs was 22% (95% confidence interval CI: 16.96%, 26.84%, n = 108) of all babies, of which only 2% (n = 2) were life threatening. Seventy-seven percent (n = 83) of these errors occurred during administration/preparation and 18% (n = 19) while prescribing. The significant determinants of MEs (adjusted odds ratio 95% CI) include polypharmacy (4.126 1.917-8.880), duration of stay >7 days (1.335 1.198-1.488), and babies referred from outside (2.592 1.217-5.521).
CONCLUSIONS: MEs were common in NICU setting. The occurrence of life-threatening MEs was minimal. Longer duration of hospital stay, polypharmacy, and babies born outside were significantly associated with occurrence of MEs.
Aim
Kangaroo mother care (KMC) has immense short‐term benefits, but data on long‐term outcomes are scarce. Hence, this study aimed to compare the neurodevelopmental outcomes at 12 months of corrected ...age (CA) in infants <2000 g receiving early and prolonged KMC to a control group.
Methods
This was a cohort study that was conducted from January 2017 to November 2018. All neonates<2000 g were eligible for the study. Neonates that received early initiation (<72 h of life) and prolonged KMC comprised the intervention group and were compared to neonates without the intervention. Bayley Scales of Infant and Toddler Development, Third edition (BSID‐III) was done at 12 months of CA, and this was analysed using t‐test and multi‐linear regression analysis.
Results
There were 75 neonates in the intervention and 69 in the control group. Baseline characteristics were comparable. We found higher composite scores for cognition (110.38 ± 9.89 vs. 105.44 ± 8.77, p value = 0.023), language (107.51 ± 10.72 vs. 101.05 ± 12.06, p value = 0.014) and adaptive behaviour (87.97 ± 9.97 vs. 80 ± 9.1, p value<0.001) in the early and prolonged KMC group in comparison to the control group.
Conclusion
Infants with early and prolonged KMC have better neurodevelopmental outcomes in terms of cognition, language and adaptive behaviour at 12 months of CA.
Zinc malnutrition is a major issue in developing countries where polished rice is a staple food. With the existing significant genetic variability for high zinc in polished rice, the development of ...biofortified rice varieties was targeted in India with support from HarvestPlus, Department of Biotechnology, and Indian Council of Agricultural Research of Government of India. Indian Institute of Rice Research (IIRR) facilitates rice varietal release through All India Coordinated Rice Improvement Project (AICRIP) and also supports rice biofortification program in India. Various germplasm sets of several national institutions were characterized at IIRR for their zinc content in brown rice using energy-dispersive X-ray fluorescence spectroscopy indicating the range of zinc to be 7.3 to 52.7 mg/kg. Evaluation of different mapping populations involving wild germplasm, landraces, and varieties for their zinc content showed the feasibility of favorable recombination of high zinc content and yield. Ninety-nine genotypes from germplasm and 344 lines from mapping populations showed zinc content of ≥28 mg/kg in polished rice meeting the target zinc content set by HarvestPlus. Through AICRIP biofortification trial constituted since 2013, 170 test entries were nominated by various national institutions until 2017, and four biofortified rice varieties were released. Only the test entry with target zinc content, yield, and quality parameters is promoted to the next year; thus, each test entry is evaluated for 3 years across 17 to 27 locations for their performance. Multilocation studies of two mapping populations and AICRIP biofortification trials indicated the zinc content to be highly influenced by environment. The bioavailability of a released biofortified rice variety,
., DRR Dhan 45 was found to twice that of control IR64. The technology efficacy of the four released varieties developed through conventional breeding ranged from 48 to 75% with zinc intake of 38 to be 47% and 46 to 57% of the RDA for male and female, respectively. The observations from the characterization of germplasm and mapping populations for zinc content and development of national evaluation system for the release of biofortified rice varieties have been discussed in the context of the five criteria set by biofortification program.
To evaluate the effect of cord milking on short term morbidity and hematologic parameters at 6 weeks in preterm neonates requiring resuscitation.
This trial randomized preterm infants requiring ...resuscitation to milking group and no milking group. Multiple pregnancy, Rh negative mothers, hydrops, cord abnormalities were excluded. The primary outcome was hemoglobin and serum ferritin at 6 weeks of life. Secondary outcomes were common preterm morbidities and mortality.
60 neonates were included in the study. Infants in the milking group had higher hemoglobin (10.07 g/dl vs 8.9 g/dl; p 0.003) and higher serum ferritin level (244.8 ng/ml vs 148.5 ng/ml; p 0.04) compared to no milking group.
In preterm neonates requiring resuscitation, umbilical cord milking results in higher hemoglobin and ferritin at 6 weeks of life. It can be a used as a placental transfusion strategy in preterm neonates requiring resuscitation with no significant adverse effects.
Clinical trial registration: Clinical trials registry -India CTRI/2015/01/005436, www.ctri.nic.in.
Series of 4H-chromen-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives 7a–7zb, 8a–8d and 9a–9d were synthesized and screened for their in vitro anti-mycobacterial activity against Mycobacterium ...tuberculosis H₃₇Rv (MTB) and cytotoxicity against three human cancer cell lines including A549, SK-N-SH and HeLa. The results indicate that six compounds are more potent and 7za is most effective anti-mycobacterial derivative compared to the standard drugs Ethambutol and Ciprofloxacin. However, 12 compounds exhibited cytotoxicity against human neuroblastoma cell line; amongst them the compound 7v is most effective compared to the standard drug Doxorubicin. This is the first report assigning in vitro anti-mycobacterial, anticancer and structure–activity relationship for this new class of 4H-chromen-1,2,3,4-tetrahydropyrimidine-5-carboxylates.
In this randomized, controlled trial conducted in hospitals with limited resources and involving infants who weighed between 1.0 and 1.799 kg at birth, mortality was lower among those assigned to ...immediate “kangaroo mother care” (skin-to-skin contact) than among those assigned to conventional care until stabilization and to kangaroo mother care thereafter.
Polished rice is widely consumed staple food across the globe, however, it contains limited nutrients especially iron (Fe) and zinc (Zn). To identify promising genotypes for grain Zn, a total of 40 ...genotypes consisting 20 rice landraces, and 20 released high yielding rice varieties were evaluated in three environments (wet seasons 2014, 2015 and 2016) for nine traits including days to 50% flowering (DFF), plant height (PH), panicle length (PL), total number of tillers (TNT), single plant yield (SPY), Fe and Zn in brown (IBR, ZBR) and polished rice (IPR, ZPR). Additive Main Effect and Multiplicative Interaction (AMMI), Genotype and Genotype × Environment Interaction (GGE) analyses identified genotypes G22 (Edavankudi Pokkali), G17 (Taraori Basmati), G27 (Chittimuthyalu) and G26 (Kalanamak) stable for ZPR and G8 (Savitri) stable for SPY across three environments. Significant negative correlation between yield and grain Zn was reaffirmed. Regression analysis indicated the contribution of traits toward ZPR and SPY and also desirable level of grain Zn in brown rice. A total of 39,137 polymorphic single nucleotide polymorphisms (SNPs) were obtained through double digest restriction site associated DNA (dd-RAD) sequencing of 40 genotypes. Association analyses with nine phenotypic traits revealed 188 stable SNPs with six traits across three environments. ZPR was associated with SNPs located in three putative candidate genes (LOC_Os03g47980, LOC_Os07g47950 and LOC_Os07g48050) on chromosomes 3 and 7. The genomic region of chromosome 7 co localized with reported genomic regions (rMQTL
7
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1
) and OsNAS3 candidate gene. SPY was found to be associated with 12 stable SNPs located in 11 putative candidate genes on chromosome 1, 6, and 12. Characterization of rice landraces and varieties in terms of stability for their grain Zn and yield identified promising donors and recipients along with genomic regions in the present study to be deployed rice Zn biofortification breeding program.
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