Inauspicious Beginnings: Cancer and Financial Hardship among Children, Adolescents, and Young Adults in the United States.

With the release of the American Association of Cancer Research Cancer Progress Report 2024, we address two aspects of cancer and its treatment in younger age groups addressed in the progress report: first, the chronicity of financial hardship and second, inequities that burden the totality of society and hinder progress of scientific advances in cancer control and treatment. Financial hardship for younger age groups diagnosed with cancer causes lasting financial damage to both the patients and their families. Advancements in new technologies and treatments that improve survival may not be as effective if they are unaffordable or will cause lasting financial distress.

PGC-1α drives small cell neuroendocrine cancer progression toward an ASCL1-expressing subtype with increased mitochondrial capacity.

Adenocarcinomas from multiple tissues can converge to treatment-resistant small cell neuroendocrine (SCN) cancers composed of ASCL1, POU2F3, NEUROD1, and YAP1 subtypes. We investigated how mitochondrial metabolism influences SCN cancer (SCNC) progression. Extensive bioinformatics analyses encompassing thousands of patient tumors and human cancer cell lines uncovered enhanced expression of proliferator-activatedreceptor gamma coactivator 1-alpha (PGC-1α), a potent regulator of mitochondrial oxidative phosphorylation (OXPHOS), across several SCNCs.

Simplified methods for variance estimation in microbiome abundance count data analysis.

The complex nature of microbiome data has made the differential abundance analysis challenging. Microbiome abundance counts are often skewed to the right and heteroscedastic (also known as overdispersion), potentially leading to incorrect inferences if not properly addressed. In this paper, we propose a simple yet effective framework to tackle the challenges by integrating Poisson (log-linear) regression with standard error estimation through the Bootstrap method and Sandwich robust estimation.

A First-in-Human Study of Cinrebafusp Alfa, a HER2/4-1BB Bispecific Molecule, in Patients with HER2-Positive Advanced Solid Malignancies.

Purpose: 4-1BB (CD137) is a costimulatory immune receptor expressed on activated T cells, activated B cells, NK cells, and tumor-infiltrating lymphocytes, making it a promising target for cancer immunotherapy. Cinrebafusp alfa, a monoclonal antibody-like bispecific protein targeting HER2 and 4-1BB, aims to localize 4-1BB activation to HER2-positive tumors. This study evaluated the safety, tolerability, and preliminary efficacy of cinrebafusp alfa in patients with previously treated HER2-positive malignancies.

Centralized Quality Assurance of Stereotactic Body Radiation Therapy for the Veterans Affairs Cooperative Studies Program Study Number 2005: A Phase 3 Randomized Trial of Lung Cancer Surgery or Stereotactic Radiotherapy for Operable Early-Stage Non-Small Cell Lung Cancer (VALOR).

Purpose: The phase 3 Veterans Affairs Lung Cancer Surgery Or Stereotactic Radiotherapy study implemented centralized quality assurance (QA) to mitigate risks of protocol deviations. This report summarizes the quality and compliance of the first 100 participants treated with stereotactic body radiation therapy (SBRT) in this study.

Methods And Materials: A centralized QA program was developed to credential and monitor study sites to ensure standard-of-care lung SBRT treatments are delivered to participants.

Randomized Phase III Study of Amcenestrant Plus Palbociclib Versus Letrozole Plus Palbociclib in Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Primary Results From AMEERA-5.

Purpose: AMEERA-5 investigated amcenestrant (oral selective estrogen receptor [ER] degrader) plus palbociclib versus letrozole plus palbociclib as first-line treatment for ER-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced/metastatic breast cancer (aBC).

Materials And Methods: In AMEERA-5 (ClinicalTrials.gov identifier: NCT04478266), a double-blind, double-dummy, international phase III trial, adult pre-/post-menopausal women and men without previous systemic therapy for ER+/HER2- aBC were randomly assigned 1:1 to amcenestrant 200 mg once daily + standard palbociclib dosage (125 mg once daily, 21 days on/7 days off) or letrozole 2.

Real-World Multicenter Study of PD-1 Blockade in HIV-Associated Classical Hodgkin Lymphoma Across the United States.

Background: Despite a higher risk of classical Hodgkin lymphoma (cHL) in people with HIV and the demonstrated safety and efficacy of PD-1 blockade in cHL, there are limited data on the use of these agents in HIV-associated cHL (HIV-cHL).

Patients/methods: We retrospectively identified patients with HIV-cHL from the "Cancer Therapy using Checkpoint inhibitors in People with HIV-International (CATCH-IT)" database who received nivolumab or pembrolizumab, alone or in combination with other agents, and reviewed records for demographics, disease characteristics, immune-mediated adverse events (imAEs), and treatment outcomes. Changes in CD4 T-cell counts with treatment were measured via Wilcoxon signed-rank tests.

Cancer diagnosis and treatment in working-age adults: Implications for employment, health insurance coverage, and financial hardship in the United States.

The rising costs of cancer care and subsequent medical financial hardship for cancer survivors and families are well documented in the United States. Less attention has been paid to employment disruptions and loss of household income after a cancer diagnosis and during treatment, potentially resulting in lasting financial hardship, particularly for working-age adults not yet age-eligible for Medicare coverage and their families. In this article, the authors use a composite patient case to illustrate the adverse consequences of cancer diagnosis and treatment for employment, health insurance coverage, household income, and other aspects of financial hardship.

Lung Cancer Survival Trends in the Veterans Health Administration.

Introduction: Lung cancer survival is improving in the United States. We investigated whether there was a similar trend within the Veterans Health Administration (VHA), the largest integrated healthcare system in the United States.

Materials And Methods: Data from the Veterans Affairs Central Cancer Registry were analyzed for temporal survival trends using Kaplan-Meier estimates and linear regression.

Disparity in initiation of checkpoint inhibitors among commercially insured and Medicare Advantage patients with metastatic melanoma.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced melanoma, but racial disparities in melanoma outcomes continue. These inequities are not fully explained by individual factors. To investigate the associations of neighborhood factors with the use of ICIs in metastatic melanoma.

Dynamic Risk Prediction of Treatment Discontinuation Using Patient-Reported Outcomes Data in the Phase III NSABP B-35 Trial.

Unlabelled: Predicting an individual's risk of treatment discontinuation is critical for the implementation of precision chemoprevention. We developed partly conditional survival models to predict discontinuation of tamoxifen or anastrozole using patient-reported outcome (PRO) data from postmenopausal women with ductal carcinoma in situ enrolled in the NSABP B-35 clinical trial. In a secondary analysis of the NSABP B-35 clinical trial PRO data, we proposed two models for treatment discontinuation within each treatment arm (anastrozole or tamoxifen treated patients) using partly conditional Cox-type models with time-dependent covariates.

Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma.

Background: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown.

Methods: In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population.

Simulation study comparing analytical methods for single-item longitudinal patient-reported outcomes data.

Purpose: Efficient analytical methods are necessary to make reproducible inferences on single-item longitudinal ordinal patient-reported outcome (PRO) data. A thorough simulation study was performed to compare the performance of the semiparametric probabilistic index models (PIM) with a longitudinal analysis using parametric cumulative logit mixed models (CLMM).

Methods: In the setting of a control and intervention arm, we compared the power of the PIM and CLMM to detect differences in PRO adverse event (AE) between these groups using several existing and novel summary scores of PROs.

AMEERA-5: a randomized, double-blind phase 3 study of amcenestrant plus palbociclib letrozole plus palbociclib for previously untreated ER+/HER2- advanced breast cancer.

Background: For estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), the current standard first-line treatment includes an aromatase inhibitor in combination with a cyclin-dependent kinase 4/6 inhibitor. When resistance occurs, often related to the occurrence of mutations, selective estrogen receptor modulators or degraders (SERDs) may be used, alone or in combination regimens. Amcenestrant (SAR439859), an optimized oral SERD, has shown clinical antitumor activity in combination with palbociclib in patients with ER+/HER2- ABC and, as monotherapy, in patients with and without mutations.