A genome-wide atlas of human cell morphology.

A key challenge of the modern genomics era is developing empirical data-driven representations of gene function. Here we present the first unbiased morphology-based genome-wide perturbation atlas in human cells, containing three genome-wide genotype-phenotype maps comprising CRISPR-Cas9-based knockouts of >20,000 genes in >30 million cells. Our optical pooled cell profiling platform (PERISCOPE) combines a destainable high-dimensional phenotyping panel (based on Cell Painting) with optical sequencing of molecular barcodes and a scalable open-source analysis pipeline to facilitate massively parallel screening of pooled perturbation libraries.

Brief Report: Not Created Equal: Survival Differences by Mutation Subtype in NSCLC Treated With Immunotherapy.

Introduction: The predictive and prognostic implications of different mutation (m) subtypes in metastatic NSCLC have not been clearly defined. We used a nationwide observational database to investigate whether m subtypes differ in their association with survival in metastatic NSCLC treated with immune checkpoint inhibitor (ICI)-based therapy, across programmed death-ligand 1 (PD-L1) levels.

Methods: Patients with advanced nonsquamous NSCLC who initiated first-line ICI-based therapy from 2016 to 2021 and had known PD-L1 expression and comprehensive genomic profiling including , , , and were included.

Radiotherapy with cetuximab or durvalumab for locoregionally advanced head and neck cancer in patients with a contraindication to cisplatin (NRG-HN004): an open-label, multicentre, parallel-group, randomised, phase 2/3 trial.

Background: Management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) when cisplatin is contraindicated is controversial. We aimed to assess whether radiotherapy with concurrent and adjuvant durvalumab would improve outcomes compared with radiotherapy with cetuximab.

Methods: NRG-HN004 was designed as an open-label, multicentre, parallel-group, randomised, phase 2/3 trial with safety lead-in conducted at 89 academic and community medical centres in North America.

Phase Ib Study of the Immunocytokine Simlukafusp Alfa (FAP-IL2v) in Combination with Cetuximab in Patients with Head and Neck Squamous Cell Carcinoma.

Purpose: This phase Ib trial evaluated fibroblast activation protein-α-targeted IL2 variant (FAP-IL2v), a novel immunocytokine engineered to minimize CD25-mediated toxicities, in combination with cetuximab, in patients with recurrent, unresectable, or metastatic head and neck squamous cell carcinoma (HNSCC).

Patients And Methods: Patients received FAP-IL2v either on a continuous weekly (QW) schedule or QW for 4 weeks and then every 2 weeks (Q2W). Cetuximab was dosed at QW or Q2W schedules.

Telehealth vs In-Person Early Palliative Care for Patients With Advanced Lung Cancer: A Multisite Randomized Clinical Trial.

Importance: Numerous studies show that early palliative care improves quality of life and other key outcomes in patients with advanced cancer and their caregivers, although most lack access to this evidence-based model of care.

Objective: To evaluate whether delivering early palliative care via secure video vs in-person visits has an equivalent effect on quality of life in patients with advanced non-small cell lung cancer (NSCLC).

Design, Setting, And Participants: Randomized, multisite, comparative effectiveness trial from June 14, 2018, to May 4, 2023, at 22 US cancer centers among 1250 patients within 12 weeks of diagnosis of advanced NSCLC and 548 caregivers.

Real-world treatment sequencing and effectiveness of second- and third-generation ALK tyrosine kinase inhibitors for ALK-positive advanced non-small cell lung cancer.

Introduction: With multiple targeted therapies approved for anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC), it is increasingly important to understand outcomes with various sequences of next-generation ALK tyrosine kinase inhibitors (TKIs). We describe contemporary sequencing patterns and treatment effectiveness of first-line (1L) and second-line (2L) treatments in patients who received second-generation ALK TKIs in the 1L treatment of ALK-positive NSCLC in the United States.

Methods: A cohort of adults with ALK-positive advanced NSCLC who initiated treatment with 1L alectinib or brigatinib between June 2017 and April 2021 in the Flatiron Health electronic health record-derived de-identified database were followed through April 2023.

T-cell Responses to Individualized Neoantigen Therapy mRNA-4157 (V940) Alone or in Combination with Pembrolizumab in the Phase 1 KEYNOTE-603 Study.

mRNA-4157 (V940) is an individualized neoantigen therapy targeting up to 34 patient-specific tumor neoantigens to induce T-cell responses and potentiate antitumor activity. We report mechanistic insights into the immunogenicity of mRNA-4157 via characterization of T-cell responses to neoantigens from the first-in-human, phase 1, KEYNOTE-603 study (NCT03313778) in patients with resected non-small cell lung cancer (Part A: 1-mg mRNA-4157, n = 4) or resected cutaneous melanoma (Part D: 1-mg mRNA-4157 + 200-mg pembrolizumab, n = 12). Safety, tolerability, and immunogenicity were assessed.

X-ray Imaging Versus Anatomical Dissection for Identification of the Fabella.

Introduction: Reported prevalence rates of the fabella sesamoid bone vary widely, particularly between studies based on either X-ray imaging or anatomical dissection approaches. The purpose of this study was to directly compare these two methodologies in their detection of fabellae and investigate whether variability in the density of fabellae could explain any discrepancies.

Methods: Fifty cadaveric knee segments were examined for the presence of a fabella by both X-ray imaging and anatomical dissection.

Heat-Related Illnesses.

There is a growing incidence of heat-related illnesses due to rising global temperatures. Heat-related illnesses range from mild to severe, with heat stroke being the most critical. The wet bulb global temperature index considers humidity and solar intensity; its use is recommended to estimate heat stress on an individual and mitigate risk.

Proportion and predictors of FVC decline in patients with interstitial lung disease.

Rationale: The proportion of patients who develop progressive pulmonary fibrosis (PPF), along with risk factors for progression remain poorly understood.

Objectives: To examine factors associated with an increased risk of developing PPF among patients at a referral center.

Methods: We identified patients with a diagnosis of interstitial lung disease (ILD) seen within the Cleveland Clinic Health System.

Durvalumab in combination with chemoradiotherapy in patients with head and neck squamous cell carcinoma: Results from the Phase 1 CLOVER study.

Background: The Phase 1 CLOVER study (NCT03509012) assessed durvalumab in combination with concurrent chemoradiotherapy (cCRT) in patients with advanced solid tumors; we report results from the head and neck squamous cell carcinoma (HNSCC) cohort.

Methods: Patients with histologically/cytologically confirmed locally advanced HNSCC, eligible for definitive cCRT and not considered for primary surgery, received durvalumab plus cisplatin and concurrent external beam radiation. Objectives were to assess safety/tolerability and preliminary efficacy.

Durvalumab in combination with chemoradiotherapy for patients with unresectable stage III non-small-cell lung cancer: Results from the phase 1 CLOVER study.

Introduction: For patients with unresectable, stage III non-small-cell lung cancer (NSCLC), current standard of care is concurrent chemoradiotherapy (cCRT) followed by consolidation durvalumab. However, earlier initiation of durvalumab simultaneously with cCRT may increase antitumor activity relative to initiation after cCRT. The phase 1 CLOVER study (NCT03509012) evaluated durvalumab combined with cCRT in patients with advanced solid tumors; we report findings from the NSCLC cohort.

Outcomes in patients treated with frontline immune checkpoint inhibition (ICI) for advanced NSCLC with KRAS mutations and STK11/KEAP1 comutations across PD-L1 levels.

Introduction: In patients with advanced NSCLC (aNSCLC), the impact of KRAS mutations (m) and comutations with STK11 and KEAP1 on outcomes across different PD-L1 levels remains incompletely understood. We aimed to investigate the frequency of KRAS mutations and comutations across PD-L1 levels, and the association between these mutations and survival, stratified by PD-L1 expression.

Methods: We conducted a nationwide cohort study of patients diagnosed with aNSCLC between 2016 and 2021 treated with frontline (chemo)immunotherapy, who underwent molecular genotyping including KRAS, STK11, and KEAP1.

The impact of an oncology urgent care center on health-care utilization.

Introduction: Studies suggest that many emergency department (ED) visits and hospitalizations for patients with cancer may be preventable. The Centers for Medicare & Medicaid Services has implemented changes to the hospital outpatient reporting program that targets acute care in-treatment patients for preventable conditions. Oncology urgent care centers aim to streamline patient care.

Hematology and Oncology Fellow Education About Sexual and Reproductive Health: A Survey of Program Directors in the United States.

Purpose: Clinical oncology guidelines recommend addressing sexual and reproductive health (SRH) concerns in routine cancer care. However, limited training often hinders clinicians' ability to do so effectively. The objective of this study was to understand the state of current fellowship education on SRH (ie, sexual health, safe sex practices, and fertility) through conducting a national survey of US hematology/oncology fellowship program directors (PDs).