Combined Endoscopy-Laparoscopy Surgery: When and How to Utilize This Tool.

Combined endoscopic and laparoscopic surgery (CELS) has been used to resect colon polyps since the 1990s. These colon-sparing techniques, however, have not yet been widely adopted. With the evolution of technology in both diagnosing and treating colon cancer, colorectal surgeons should strive for a diverse and complete armamentarium through which they can best serve their patients.

Barriers to Implementation of Advanced Endoscopic Procedures.

Advanced endoscopy has been shown to be useful in the diagnosis and treatment of both benign and low-grade malignant colorectal lesions. In fact, advanced endoscopic procedures are being adopted as standard approaches to these lesions in many places around the world; however, their implementation in the United States has not been as widespread. We ascribe the difficulty in implementation to two reasons: (1) lack of advanced endoscopic training and (2) failure in reimbursement models as they relate to endoscopy.

Integrated Proteogenomic Analysis Reveals Distinct Potentially Actionable Therapeutic Vulnerabilities in Triple-Negative Breast Cancer Subtypes.

Triple-negative breast cancer (TNBC) is characterized by an aggressive clinical presentation and a paucity of clinically actionable genomic alterations. Here, we utilized the Cancer Genome Atlas (TCGA) to explore the proteogenomic landscape of TNBC subtypes to see whether genomic alterations can be inferred from proteomic data. We found only 4% of the protein level changes are explained by mutations, while 21% of the protein and 35% of the transcriptomics changes were determined by copy number alterations (CNAs).

Effect of sponsor on enrollment criteria in non-small cell lung cancer clinical trials.

Background: Inclusion and exclusion criteria in clinical trials are used to mitigate the effects of confounding variables on study outcomes. In 2017 and 2021, ASCO and the Friends of Cancer Research published recommendations to loosen enrollment criteria in cancer clinical trials to improve generalizability. The purpose of this study is to determine if the source of funding influences the degree of transparency and selection of inclusion and exclusion criteria.

Circulating Tumor Cell Transcriptomics as Biopsy Surrogates in Metastatic Breast Cancer.

Background: Metastatic breast cancer (MBC) and the circulating tumor cells (CTCs) leading to macrometastases are inherently different than primary breast cancer. We evaluated whether whole transcriptome RNA-Seq of CTCs isolated via an epitope-independent approach may serve as a surrogate for biopsies of macrometastases.

Methods: We performed RNA-Seq on fresh metastatic tumor biopsies, CTCs, and peripheral blood (PB) from 19 newly diagnosed MBC patients.

Identification of putative actionable alterations in clinically relevant genes in breast cancer.

Background: Individualising treatment in breast cancer requires effective predictive biomarkers. While relatively few genomic aberrations are clinically relevant, there is a need for characterising patients across different subtypes to identify actionable alterations.

Methods: We identified genomic alterations in 49 potentially actionable genes for which drugs are available either clinically or via clinical trials.

Theory, methods, and operational results of the Young Women's Health History Study: a study of young-onset breast cancer incidence in Black and White women.

Purpose: The etiology of young-onset breast cancer (BC) is poorly understood, despite its greater likelihood of being hormone receptor-negative with a worse prognosis and persistent racial and socioeconomic inequities. We conducted a population-based case-control study of BC among young Black and White women and here discuss the theory that informed our study, exposures collected, study methods, and operational results.

Methods: Cases were non-Hispanic Black (NHB) and White (NHW) women age 20-49 years with invasive BC in metropolitan Detroit and Los Angeles County SEER registries 2010-2015.

Incidence of radiation induced sarcoma attributable to radiotherapy in adults: A retrospective cohort study in the SEER cancer registries across 17 primary tumor sites.

Background: Previous studies have noted the incidence of radiation-induced sarcomas (RIS) but have not investigated the relative risk (RR) of developing RIS based on primary tumor organ disease site. By examining data from the Surveillance, Epidemiology, and End Results (SEER) database, we hypothesized that breast cancer would have a higher incidence of RIS compared to seventeen other primary cancer sites.

Methods: This was a retrospective cohort study that examined patients from SEER registries between 1973 and 2013.

EP300 knockdown reduces cancer stem cell phenotype, tumor growth and metastasis in triple negative breast cancer.

Background: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype with basal features, lacking the expression of receptors targeted successfully in other breast cancer subtypes. Treatment response to adjuvant and neoadjuvant chemotherapy is often short-lived and metastatic spread occurs at higher rates than other subtypes within the first five years after diagnosis. TNBCs exhibit stem cell features and are enriched for cancer stem cell (CSC) populations.

A comparison of general, genitourinary, bowel, and sexual quality of life among long term survivors of prostate, bladder, colorectal, and lung cancer.

Objectives: Studies of local stage prostate cancer survivors suggest that treatments carry risk of persistent impotence, incontinence, and bowel dysfunction. To examine impacts of cancer type and side effects on health-related quality of life (HRQoL) in long-term cancer survivorship, we evaluated 5-year follow-up of patients with prostate cancer and compared results with a matched group of male long-term survivors of other local-stage cancers.

Materials And Methods: We examined genitourinary, bowel and sexual symptoms, and general quality of life.

A Pilot Study for the Feasibility of Exome-Sequencing in Circulating Tumor Cells Versus Single Metastatic Biopsies in Breast Cancer.

The comparison of the landscape of somatic alterations in circulating tumor cells (CTCs) versus metastases is challenging. Here, we comprehensively characterized the somatic landscape in bulk (amplified and non-amplified), spike-in breast cancer cells, CTCs, and metastases from breast cancer patients using whole-exome sequencing (WES). We determined the level of genomic concordance for somatic nucleotide variants (SNVs), copy number alterations (CNAs), and structural variants (SVs).

Untenable dosing: A common pitfall of modern DLT-targeting Phase I designs in oncology.

Background: There is increasing use of Phase I statistical designs to find a dose that causes rapidly emerging and particularly concerning severe or life-threatening toxicities (dose-limiting toxicities, DLTs) in a specified percent of patients most commonly 25%. While a convenient statistical framework, the foundation for selecting any specified target DLT rate, and its relevance to the recommended Phase II dose is generally lacking.

Method: We surveyed 78 medical oncologists, most (69%) with experience as a principal investigator on a Phase I study, to ascertain their opinions related to this approach to Phase I studies and the targets often chosen.

A Phase I Study of the Combination of Rituximab and Ipilimumab in Patients with Relapsed/Refractory B-Cell Lymphoma.

Purpose: Based on the potential for ipilimumab (I) to augment T-cell activation, we hypothesize that ipilimumab would augment the efficacy of rituximab (R) in patients with relapsed/refractory (R/R) CD20non-Hodgkin's lymphoma (NHL). This phase I study aimed to identify a recommended phase 2 dose, document toxicities, and preliminarily assess efficacy and potential predictive biomarkers.

Patients And Methods: Thirty-three patients with R/R CD20B-cell lymphoma received R at 375 mg/mweekly for 4 weeks and I at 3 mg/kg on day 1 and every 3 weeks for four doses.

Local Injection of Submicron Particle Docetaxel is Associated with Tumor Eradication, Reduced Systemic Toxicity and an Immunologic Response in Uro-Oncologic Xenografts.

Intratumoral (IT) administration of submicron particle docetaxel (NanoDoce, NanOlogy LLC, Fort Worth, TX, USA) and its efficacy against genitourinary-oncologic xenografts in rats and mice, xenograft-site docetaxel concentrations and immune-cell infiltration were studied. IT-NanoDoce, IV-docetaxel and IT-vehicle were administered to clear cell renal carcinoma (786-O: rats), transitional cell bladder carcinoma (UM-UC-3: mice) and prostate carcinoma (PC-3: mice). Treatments were given every 7 days with 1, 2, or 3 doses administered.

A Phase I Study to Assess the Safety and Pharmacokinetics of Single-agent Lorvotuzumab Mertansine (IMGN901) in Patients with Relapsed and/or Refractory CD-56-positive Multiple Myeloma.

Background: Despite therapeutic advancements that have significantly improved outcomes in multiple myeloma (MM), it remains an incurable disease. Patients with relapsed and/or refractory MM have an aggressive disease course, with inferior outcomes, necessitating the need for agents with novel therapeutic mechanisms. We present the results of a completed phase I trial of single-agent lorvotuzumab mertansine, a unique antibody-drug conjugate targeting CD56, which is frequently expressed in MM.

RNA-Seq of Circulating Tumor Cells in Stage II-III Breast Cancer.

Background: We characterized the whole transcriptome of circulating tumor cells (CTCs) in stage II-III breast cancer to evaluate correlations with primary tumor biology.

Methods: CTCs were isolated from peripheral blood (PB) via immunomagnetic enrichment followed by fluorescence-activated cell sorting (IE/FACS). CTCs, PB, and fresh tumors were profiled using RNA-seq.

Rationale for combination of therapeutic antibodies targeting tumor cells and immune checkpoint receptors: Harnessing innate and adaptive immunity through IgG1 isotype immune effector stimulation.

Immunoglobulin (Ig) G1 antibodies stimulate antibody-dependent cell-mediated cytotoxicity (ADCC). Cetuximab, an IgG1 isotype monoclonal antibody, is a standard-of-care treatment for locally advanced and recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) and metastatic colorectal cancer (CRC). Here we review evidence regarding the clinical relevance of cetuximab-mediated ADCC and other immune functions and provide a biological rationale concerning why this property positions cetuximab as an ideal partner for immune checkpoint inhibitors (ICIs) and other emerging immunotherapies.

Efficacy of the PARP Inhibitor Veliparib with Carboplatin or as a Single Agent in Patients with Germline - or -Associated Metastatic Breast Cancer: California Cancer Consortium Trial NCT01149083.

We aimed to establish the MTD of the poly (ADP-ribose) (PAR) polymerase inhibitor, veliparib, in combination with carboplatin in germline - and -associated metastatic breast cancer (MBC), to assess the efficacy of single-agent veliparib, and of the combination treatment after progression, and to correlate PAR levels with clinical outcome. Phase I patients received carboplatin (AUC of 5-6, every 21 days), with escalating doses (50-20 mg) of oral twice-daily (BID) veliparib. In a companion phase II trial, patients received single-agent veliparib (400 mg BID), and upon progression, received the combination at MTD.

A Study of Thymidylate Synthase Expression as a Biomarker for Resectable Colon Cancer: Alliance (Cancer and Leukemia Group B) 9581 and 89803.

Purpose: Tumor levels of thymidylate synthase (TS), a target of 5-fluorouracil (5-FU)-based chemotherapy for colorectal cancer, have been studied as a predictive or prognostic biomarker with mixed results.

Patients And Methods: Tumor TS levels were prospectively evaluated in two adjuvant therapy trials for patients with resected stage II or III colon cancer. TS expression was determined by standard immunohistochemistry and by automated quantitative analysis.

Meta-Analysis Evaluating the Impact of Site of Metastasis on Overall Survival in Men With Castration-Resistant Prostate Cancer.

Purpose: Reports have suggested that metastatic site is an important predictor of overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC), but these were based on a limited number of patients. We investigate the impact of site of metastases on OS of a substantial sample of men with mCRPC who received docetaxel chemotherapy in nine phase III trials.

Patients And Methods: Individual patient data from 8,820 men with mCRPC enrolled onto nine phase III trials were combined.

Impact of the AYA HOPE Comorbidity Index on Assessing Health Care Service Needs and Health Status among Adolescents and Young Adults with Cancer.

Background: Existing comorbidity indices were not developed for adolescent and young adults (AYA) 15 to 39 years of age. The aim of this study was to assess impact of comorbidities on health care service needs and health status among AYA cancer survivors using the newly developed AYA HOPE comorbidity index in comparison with the existing indices.

Methods: Data on comorbid conditions were obtained from medical records and service needs and health status were from a survey of AYA cancer survivors.