Machine Learning Predicts Oxaliplatin Benefit in Early Colon Cancer.

Purpose: A combination of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is the standard for adjuvant therapy of resected early-stage colon cancer (CC). Oxaliplatin leads to lasting and disabling neurotoxicity. Reserving the regimen for patients who benefit from oxaliplatin would maximize efficacy and minimize unnecessary adverse side effects.

Patient-Reported Financial Burden of Treatment for Colon or Rectal Cancer.

Importance: The longitudinal experience of patients is critical to the development of interventions to identify and reduce financial hardship.

Objective: To evaluate financial hardship over 12 months in patients with newly diagnosed colorectal cancer (CRC) undergoing curative-intent therapy.

Design, Setting, And Participants: This prospective, longitudinal cohort study was conducted between May 2018 and July 2020, with time points over 12 months.

Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial.

Background: HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T.

Validation of Immunotherapy Response Score as Predictive of Pan-solid Tumor Anti-PD-1/PD-L1 Benefit.

Unlabelled: Immunotherapy response score (IRS) integrates tumor mutation burden (TMB) and quantitative expression biomarkers to predict anti-PD-1/PD-L1 [PD-(L)1] monotherapy benefit. Here, we evaluated IRS in additional cohorts. Patients from an observational trial (NCT03061305) treated with anti-PD-(L)1 monotherapy were included and assigned to IRS-High (-H) versus -Low (-L) groups.

Sex- and Co-Mutation-Dependent Prognosis in Patients with SMARCA4-Mutated Malignancies.

Background: Whether sex and co-mutations impact prognosis of patients with SMARCA4-mutated (mutSMARCA4) malignancies is not clear.

Methods: This cohort included patients from Northern California Kaiser Permanente with next-generation sequencing (NGS) performed from August 2020 to October 2022. We used Cox regression modeling to examine the association between sex and overall survival (OS), adjusting for demographics, performance status, Charlson comorbidity index, receipt of treatment, tumor mutation burden (TMB), and , , , , and co-mutations.

Gain-of-Function and Non-Gain-of-Function Mutations Are Associated With Differential Prognosis in Advanced Pancreatic Ductal Adenocarcinoma.

Purpose: To examine the impact of gain-of-function (GOF) and non-GOF mutations on prognosis of advanced pancreatic ductal adenocarcinoma (PDAC) among patients with , , and comutations.

Methods: This cohort included patients with locally advanced, recurrent, and de novo metastatic PDAC with next-generation sequencing performed from November 2017 to May 2022. We defined R175H, R248W, R248Q, R249S, R273H, R273L, and R282W as GOF and all other p53 mutations (mutp53) as non-GOF.

Long-term outcomes of dual vs single HER2-directed neoadjuvant therapy in NSABP B-41.

Background: The primary aim of this randomized neoadjuvant trial in operable, HER2-positive breast cancer, was to determine the efficacy on pathologic complete response (pCR) of substituting lapatinib (L) for trastuzumab (T) or adding L to T, in combination with weekly paclitaxel (WP) following AC. Results on pCR were previously reported. Here, we report data on planned secondary endpoints, recurrence-free interval (RFI) post-surgery, and overall survival (OS).

Development and validation of an integrative pan-solid tumor predictor of PD-1/PD-L1 blockade benefit.

Background: Anti-PD-1 and PD-L1 (collectively PD-[L]1) therapies are approved for many advanced solid tumors. Biomarkers beyond PD-L1 immunohistochemistry, microsatellite instability, and tumor mutation burden (TMB) may improve benefit prediction.

Methods: Using treatment data and genomic and transcriptomic tumor tissue profiling from an observational trial (NCT03061305), we developed Immunotherapy Response Score (IRS), a pan-tumor predictive model of PD-(L)1 benefit.

E3 Ubiquitin Ligase NEDD4 Affects Estrogen Receptor α Expression and the Prognosis of Patients with Hormone Receptor-Positive Breast Cancer.

Neural precursor cell-expressed developmentally downregulated 4-1 (NEDD4) is an E3 ligase that leads to the degradation of proteins, including estrogen receptor α. We evaluated whether the expression level of NEDD4 affected the outcome of breast cancer patients. We performed a retrospective cohort study enrolling 143 patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer.

Improving outcomes in malignant pleural mesothelioma in an integrated health care system.

Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor that should be managed by an experienced surgical and multidisciplinary group. Our objective was to determine the impact of proficient surgeons and MPM bi-disciplinary review on outcomes of patients with MPM.

Methods: Through this cohort study, electronic medical records of 368 adult patients with MPM from 1/1/2009 to 12/31/2020 were reviewed and compared before and after MPM surgeries were regionalized to specialized surgeons and bi-disciplinary review of MPM patient treatment options.

Comparison of Survival by Multimodal Treatment Regimen Among Malignant Pleural Mesothelioma Patients in an Integrated Health System.

Background: Optimal therapy for malignant pleural mesothelioma (MPM) remains unclear. We compared overall survival in patients with MPM after various multimodal treatment regimens including combinations of immunotherapy, chemotherapy, and surgery.

Patients And Methods: We examined MPM patients treated within our integrated health system from January 1, 2009 to December 31, 2020.

Improving Time to Molecular Testing Results in Patients With Newly Diagnosed, Metastatic Non-Small-Cell Lung Cancer.

Purpose: Next-generation sequencing (NGS) is a crucial component of evaluation of patients with newly diagnosed metastatic non-small-cell lung cancer (NSCLC) to determine appropriate first-line treatment. This quality improvement project aimed to reduce time to NGS results in patients with metastatic NSCLC.

Methods: We reviewed electronic medical records of patients with newly diagnosed, untreated metastatic NSCLC from December 2018 to August 2021 and determined the number of days from pathologic diagnosis to NGS results.

Phase II Study of Copanlisib in Patients With Tumors With Mutations: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1F.

Purpose: Activating mutations in are observed across multiple tumor types. The NCI-MATCH (EAY131) is a tumor-agnostic platform trial that enrolls patients to targeted therapies on the basis of matching genomic alterations. Arm Z1F evaluated copanlisib, an α and δ isoform-specific phosphoinositide 3-kinase (PI3K) inhibitor, in patients with mutations (with or without loss).

S1417CD: A Prospective Multicenter Cooperative Group-Led Study of Financial Hardship in Metastatic Colorectal Cancer Patients.

Background: Financial toxicity is a growing problem in oncology, but no prior studies have prospectively measured the financial impact of cancer treatment in a diverse national cohort of newly diagnosed cancer patients. S1417CD was the first cooperative group-led multicenter prospective cohort study to evaluate financial hardship in metastatic colorectal cancer (mCRC) patients.

Methods: Patients aged 18 years or older within 120 days of mCRC diagnosis completed quarterly questionnaires for 12 months.

Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03).

Purpose: Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor approved for advanced breast cancer. In the adjuvant setting, the potential value of adding palbociclib to endocrine therapy for hormone receptor-positive breast cancer has not been confirmed.

Patients And Methods: In the prospective, randomized, phase III PALLAS trial, patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer were randomly assigned to receive 2 years of palbociclib (125 mg orally once daily, days 1-21 of a 28-day cycle) with adjuvant endocrine therapy or adjuvant endocrine therapy alone (for at least 5 years).

Gain-of-Function and Non-Gain-of-Function Mutations Are Differentially Associated With Sidedness-Dependent Prognosis in Metastatic Colorectal Cancer.

Purpose: To examine the association of gain-of-function (GOF) and non-gain-of-function (non-GOF) mutations with prognosis of metastatic right-sided (RCC) versus left-sided colorectal cancer (LCC).

Methods: This cohort study included patients with metastatic colorectal cancer (CRC) who had next-generation sequencing performed from November 2017 to January 2021. We defined R175H, R248W, R248Q, R249S, R273H, R273L, and R282W as GOF and all other mutp53 as non-GOF.

Randomized Phase II Study of PARP Inhibitor ABT-888 (Veliparib) with Modified FOLFIRI versus FOLFIRI as Second-line Treatment of Metastatic Pancreatic Cancer: SWOG S1513.

Purpose: PARP inhibitors synergize with topoisomerase inhibitors, and veliparib plus modified (m) FOLFIRI (no 5-FU bolus) had preliminary activity in metastatic pancreatic cancers. This study evaluated the safety and efficacy of second-line treatment with veliparib and mFOLFIRI versus FOLFIRI (control) for metastatic pancreatic cancer.

Patients And Methods: This randomized phase II clinical trial led by the SWOG Cancer Research Network enrolled patients between September 1, 2016 and December 13, 2017.

Real-World Performance of a Comprehensive Genomic Profiling Test Optimized for Small Tumor Samples.

Purpose: Tissue-based comprehensive genomic profiling (CGP) is increasingly used for treatment selection in patients with advanced cancer; however, tissue availability may limit widespread implementation. Here, we established real-world CGP tissue availability and assessed CGP performance on consecutively received samples.

Materials And Methods: We conducted a post hoc, nonprespecified analysis of 32,048 consecutive tumor tissue samples received for StrataNGS, a multiplex polymerase chain reaction (PCR)-based comprehensive genomic profiling (PCR-CGP) test, as part of an ongoing observational trial (NCT03061305).

[From the Standpoint of a Core Center Hospital for Cancer Genome Medicine-Establishment of a Provision System for Wide-Area Precision Oncology].

In Japan, 2 comprehensive genome profiling(CGP)tests for cancer was covered by national health insurance in June 2019, and cancer genome medicine was introduced at a total of 225 hospitals designated by the Ministry of Health, Labor and Welfare as"core center hospitals for cancer genome medicine(12 hospitals)"," core hospitals for cancer genome medicine (33 hospitals)", and"collaborative hospitals for cancer genome medicine(180 hospitals)". On the other hand, the interpretation of the results of the cancer CGP test must be discussed by an expert panel conducted at the core center hospitals for cancer genome medicine or the core hospitals for cancer genome medicine, and the results must be explained to patients in order to be covered by insurance. In other words, these hospitals are required to review not only their own cases but also those of collaborating hospitals.

Adjuvant Olaparib for Patients with - or -Mutated Breast Cancer.

Background: Poly(adenosine diphosphate-ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with or germline mutation-associated early breast cancer.

Methods: We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with or germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy.

[Precision Medicine Provided by National Health Insurance].

From June 2019, 2 different comprehensive genomic profiling(CGP)test panels were covered by National Health Insurance System in Japan. However, the indication of CGP was solid cancer patients refractory to standard chemotherapy or those without standard of care, while other countries indicate CGP to chemotherapy naIve advanced cancer patients. To be covered by National Health Insurance System, certified core hospital for genomic medicine should hold expert panel with affiliated hospitals.

Nivolumab Is Effective in Mismatch Repair-Deficient Noncolorectal Cancers: Results From Arm Z1D-A Subprotocol of the NCI-MATCH (EAY131) Study.

Purpose: The National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial, the largest national precision oncology study to date (> 1,100 sites) of patients with relapsed or refractory malignancies, assigned patients to targeted therapy in parallel phase II studies based on tumor molecular alterations. The anti-programmed death receptor 1 inhibitor nivolumab previously showed activity in mismatch repair (MMR)-deficient colon cancer. We hypothesized that nivolumab would have activity in patients with MMR-deficient, noncolorectal tumors.