Plant root-associated microbes influence plant phenotype and tolerance to environmental stress, and thus have been hypothesized to play a role in plant local adaptation. Here we test this hypothesis with factorial experiments addressing the role of microbes in local adaptation of Hypericum perforatum (St. BMS202 John’s wort) to stressful limestone barrens (alvars) compared to neighboring old-fields. Alvar plants benefited more from microbes in early life history stages, while at later growth stages, alvar and old-field plants benefited equally from microbes but only in the old-field habitat. Patterns of local adaptation were changed by the presence of microbes. Alvar plants grown in association with alvar microbes outperformed old-field plants in the alvar habitat, whereas old-field plants showed patterns of maladaptation when grown with microbes. In this demonstration of microbe-mediated adaptation, we show that rhizosphere microbes can be important for plant fitness and patterns of local adaptation but that those effects are dependent on life-history stage and habitat. This article is protected by copyright. All rights reserved.BACKGROUND Circulating cell-free tumor DNA (ctDNA)-based mutation profiling, if sufficiently sensitive and comprehensive, can efficiently identify genomic targets in advanced lung adenocarcinoma. Therefore, the authors investigated the accuracy and clinical utility of a commercially available digital next-generation sequencing platform in a large series of patients with non-small-cell lung cancer (NSCLC). METHODS Plasma-based comprehensive genomic profiling results from 8388 consecutively tested patients with advanced NSCLC were analyzed. Driver and resistance mutations were examined with regard to their distribution, frequency, co-occurrence, and mutual exclusivity. RESULTS Somatic alterations were detected in 86% of samples. The median variant allele fraction was 0.43% (range, 0.03%-97.62%). Activating alterations in actionable oncogenes were identified in 48% of patients, including EGFR (26.4%), MET (6.1%), and BRAF (2.8%) alterations and fusions (ALK, RET, and ROS1) in 2.3%. Treatment-induced resistance mrican Cancer Society.BACKGROUND The role of arsenic trioxide (As2 O3 ) in the maintenance of first complete remission (CR1) in acute promyelocytic leukemia (APL) is unclear. METHODS A total of 129 consecutive adult patients with APL of all risk categories who achieved CR1 with conventional induction (all-trans retinoic acid [ATRA]/daunorubicin) and consolidation (daunorubicin/cytarabine [induction daunorubicin and consolidation omitted for age ≥70 years]) underwent maintenance comprising ATRA (45 mg/m2 /day), oral As2 O3 (10 mg/day), and ascorbic acid (1 g/day) (AAA) for 2 weeks every 2 months for 2 years. RESULTS Over a 17-year period from August 1, 2002, to July 31, 2019, 63 men and 66 women (median age, 46 years [range, 18-82 years]) received AAA maintenance, which was already completed in 117 patients. At a median follow-up of 100 months (range, 8-215 months), 17 patients (13%) developed first relapse (R1) (hematologic, n = 14; molecular, n = 3) after a median of 19 months (range, 7-96 months) from CR1. Two R1 patients had concomitant central nervous system (CNS) involvement. All patients achieved CR2 with oral As2 O3 -based salvage. Five patients had a subsequent relapse and died. Eight patients died of unrelated causes while still in CR1. The 5-year and 10-year rates of relapse-free survival (RFS) were 89% and 85%, respectively. The 5-year and 10-year rates of overall survival (OS) were 94% and 87%, respectively. Multivariate analysis showed that inferior RFS was associated with FLT3-ITD (P = .005) and CNS involvement on presentation (P = .004), and inferior OS was associated with therapy-related APL (P = .03), FLT3-ITD (P = .03), and relapse (P = .03). The safety profile was favorable, with no grade 3/4 organ toxicities. CONCLUSION CR1 maintenance with AAA is safe and results in favorable long-term survival in patients with APL. © 2020 American Cancer Society.BACKGROUND Adolescent and young adult (AYA) cancer survivors have high risks of late effects. Little is known about the late-effect information needs of AYAs early in treatment or their role in treatment decision making. This study evaluated the importance, quality, and implications of information about late effects in AYAs recently diagnosed with cancer. METHODS This study surveyed 201 AYAs with cancer who were 15 to 29 years old and were treated at the Dana-Farber Cancer Institute (Boston, Massachusetts). Patients were approached within 6 weeks of their diagnosis and were asked about their late-effect and infertility information needs, treatment decision making, and communication outcomes. RESULTS Forty-five percent of the participants were female; 88% were white. Most AYAs (87% [173 of 200]) considered information about the risks of late effects to be extremely or very important; 80% (159 of 200) valued information about infertility. Many were distressed by information about late effects (53% [105 of 200]) and infertility (45% [89 of 200]); those who considered late-effect information distressing were more likely to value this information (P  less then  .0001). Consideration of late effects (41% [82 of 201]) and infertility (36% [72 of 201]) greatly influenced many patients’ treatment decision making. Although 92% of the patients (184 of 199) reported receiving high-quality information about the diagnosis, 57% (113 of 199; P  less then  .0001) and 65% (130 of 199; P  less then  .0001) felt that they had received high-quality information about late effects and infertility, respectively. CONCLUSIONS Most AYAs with cancer value early information about the risks of late effects and infertility, yet many patients felt that they had not received high-quality information about these topics. The development of age-appropriate late-effect communication strategies that recognize high AYA distress may help to address the gap between desired information and perceived information quality. © 2020 American Cancer Society.BACKGROUND Patients with cetuximab-resistant, recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) have poor outcomes. This study hypothesized that dual blockade of mammalian target of rapamycin and epidermal growth factor receptor (EGFR) would overcome cetuximab resistance on the basis of the role of phosphoinositide 3-kinase signaling in preclinical models of EGFR resistance. METHODS In this multicenter, randomized clinical study, patients with recurrent/metastatic HNSCC with documented progression on cetuximab (in any line in the recurrent/metastatic setting) received 25 mg of temsirolimus weekly plus cetuximab at 400/250 mg/m2 weekly (TC) or single-agent temsirolimus (T). The primary outcome was progression-free survival (PFS) in the TC arm versus the T arm. Response rates, overall survival, and toxicity were secondary outcomes. RESULTS Eighty patients were randomized to therapy with TC or T alone. There was no difference for the primary outcome of median PFS (TC arm, 3.5 months; T arm, 3.5 months).