Cardiovascular Concerns, Cancer Treatment, and Biological and Chronological Aging in Cancer: JACC Family Series.

Cardiovascular disease (CVD) and cancer are leading causes of death globally, particularly among the rapidly growing population of older adults (OAs). CVD is a leading cause of mortality among cancer survivors, often accelerated by cancer treatments associated with short- or long-term cardiotoxicity. Moreover, there is a dynamic relationship among CVD, cancer, and aging, characterized by shared risk factors and biological hallmarks, that plays an important role in caring for OAs, optimizing treatment approaches, and developing preventive strategies. Assessment of geriatric domains (eg, functional status, comorbidities, cognition, polypharmacy, nutritional status, social support, psychological well-being) is critical to individualizing treatment of OAs with cancer. The authors discuss considerations in caring for an aging population with cancer, including methods for the assessment of OAs with CVD and/or cardiovascular risk factors planned for cancer therapy. Multidisciplinary care is critical in optimizing patient outcomes and maintaining quality of life in this growing vulnerable population.

Precision Medicine in the Era of Genetic Testing: Microsatellite Instability Evolved.

The recognized importance of microsatellite instability (MSI) in cancer has evolved considerably in the past 30 years. From its beginnings as a molecular predictor for Lynch syndrome, MSI first transitioned to a universal screening test in all colorectal and endometrial cancers, substantially increasing the identification of patients with Lynch syndrome among cancer patients. More recently, MSI has been shown to be a powerful biomarker of response to immune checkpoint blockade therapy across a diversity of tumor types, and in 2017 was granted Food and Drug Administration approval as the first tumor histology-agnostic biomarker for a cancer therapy. Focusing on colorectal cancer specifically, immune checkpoint blockade therapy has been shown to be highly effective in the treatment of both MSI-high (MSI-H) colon and rectal cancer, with data increasingly suggesting an early role for immune checkpoint blockade therapy in MSI-H colorectal tumors in the neoadjuvant setting, with the potential to avoid more toxic and morbid approaches using traditional chemotherapy, radiation therapy, and surgery. The success of MSI as an immune checkpoint blockade target has inspired ongoing vigorous research to identify new similar targets for immune checkpoint blockade therapy that may help to one day expand the reach of this revolutionary cancer therapy to a wider swath of patients and indications.

Evidence-Based Care of Older Adults With Metastatic Colorectal Cancer: Insights From Landmark Clinical Trials.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States with more than half of the patients diagnosed being older than 65 years, and an expected further increase in older adults (OA) diagnosed with this cancer in the coming years as the population ages. Prospective data guiding the management of older patients with metastatic CRC (mCRC) have been limited and treatment decisions for these patients are often guided by chronologic age, crude evaluation of performance status, and extrapolation from trials conducted in younger individuals. Recent evidence from randomized clinical trials specifically designed for OA supports treatment deintensification and dose modification to increase tolerability without compromising efficacy in older, frailer patients with mCRC. Additional studies support the incorporation of geriatric assessment (GA)-driven care to further improve the outcomes of OA with mCRC. Although the use of GA has not been validated in guiding specific treatment selection or modification for OA with mCRC, it provides a comprehensive and objective evaluation of a patient's functional status, comorbidities, risk of potential toxicities, effect on the quality of life, goals of care, and assists with personalizing therapy. With the increase in the number of OA we care for in our practices, it is time to stop extrapolating and define an evidence-based approach for this population that is based on data from prospective elderly specific clinical trials.

Guidance for Treating the Older Adults with Colorectal Cancer.

OPINION STATEMENT: The need for evidence-based data in the rapidly growing group of older patients is vast and more elderly-specific studies are desperately needed, for which there is clear demand from both patients and providers. Notably, many of the studies discussed in this review included unplanned subset analyses based on age and/or were not originally stratified by age; therefore, these data, particularly overall survival data, need to be interpreted with some caution as they may not be statistically valid based on the initial trial design and statistical plan. As we await data from ongoing elderly-specific trials, our recommendation for managing older patients with CRC should include geriatric screening tools (e.g., CSGA, VES-13, G8, CARG, CRASH) to help guide treatment adjustments for improved tolerability without sacrificing efficacy. For patients with a positive screen for significant geriatric concerns, a full geriatric assessment is recommended to guide treatment approach and supportive care. Prior data support the use of all approved medications for CRC in older adults who are fit; however, treatment breaks and dose attenuation with potential escalation are reasonable options for these patients. Ultimately, management decisions in the care of older adults with mCRC must be made through shared decision-making with the patient with consideration for the patient's functional status, comorbidities, goals of care, social support, as well as potential toxicities and possible effect on QoL.

The GIANT trial (ECOG-ACRIN EA2186) methods paper: A randomized phase II study of gemcitabine and nab-paclitaxel compared with 5-fluorouracil, leucovorin, and liposomal irinotecan in older patients with treatment-naïve metastatic pancreatic cancer - defining a new treatment option for older vulnerable patients.

INTRODUCTION: Pancreatic cancer is the fourth leading cause of cancer-related death in the US with an increasing incidence in older adults (OA) over age 70. There are currently no treatment guidelines for OA with metastatic pancreatic cancer (mPCA) and selecting a chemotherapy regimen for these patients is subjective, based largely on chronologic age and performance status (PS). Geriatric screening tools provide a more objective and accurate evaluation of a patient's overall health but have not yet been validated in patient selection for mPCA treatment. This study aims to elucidate the optimal chemotherapy treatment of vulnerable OA with mPCA and understand the geriatric factors that affect outcomes in this population. METHODS/DESIGN: The GIANT (ECOG-ACRIN EA2186) study is multicenter, randomized phase II trial enrolling patients over age 70 with newly diagnosed mPCA. This study utilizes a screening geriatric assessment (GA) which characterizes patients as fit, vulnerable, or frail. Patients with mild abnormalities in functional status and/or cognition, moderate comorbidities, or over age 80 are considered vulnerable. Enrolled patients are randomized to one of two dose-reduced treatment regimens (gemcitabine/nab-paclitaxel every other week, or dose-reduced 5-fluoruracil (5FU)/ liposomal irinotecan (nal-IRI) every other week). GA and quality of life (QoL) evaluations are completed prior to treatment initiation and at each disease evaluation. Overall survival (OS) is the primary endpoint, with secondary endpoints including progression free survival (PFS) and objective response rate (ORR). Enrolled patients will be stratified by age (70-74 vs ≥75) and ECOG PS (0-1 vs 2). Additional endpoints of interest for OA include evaluation of risk factors identified through GA, QoL evaluation, and toxicities of interest for older adults. Correlative studies include assessment of pro-inflammatory biomarkers of aging in the blood (IL-6, CRP) and imaging evaluation of sarcopenia as predictors of treatment tolerance. DISCUSSION: The GIANT study is the first randomized, prospective national trial evaluating vulnerable OA with mPCA aimed at developing a tailored treatment approach for this patient population. This trial has the potential to establish a new way of objectively selecting vulnerable OA with mPCA for modified treatment and to establish a new standard of care in this growing patient population. TRIAL REGISTRATION: This trial is registered with ClinicalTrial.gov Identifier NCT04233866.

Optimal Management of Patients with Advanced or Metastatic Cholangiocarcinoma: An Evidence-Based Review.

Cholangiocarcinomas are rare tumors originating at any point along the biliary tree. These tumors often pose significant challenges for diagnosis and treatment, and often carry a poor prognosis. However, in recent years, studies have identified significant molecular heterogeneity with up to 50% of tumors having detectable mutations, leading to the guideline recommendations for molecular testing as part of the diagnostic workup for these tumors. In addition, better classification of these tumors and understanding of their biology has led to new drugs being approved for treatment of this resistant tumor. This manuscript will provide a comprehensive review of the epidemiology, risk factors, diagnostic approach, molecular classification, and treatment options for patients with advanced cholangiocarcinomas.

Treatment modalities, adverse events, and survival outcomes in older patients with head and neck squamous cell carcinoma.

BACKGROUND: Chemoradiation with curative intent in older adults with locally advanced head and neck squamous cell carcinoma (HNSCC) has been a challenge, because of its potential toxicities. METHODS: We selected primary HNSCC cases from the SEER-Medicare linked database, assessed overall survival (OS) and adverse events and their associations with different treatments, across four age groups including the youngest (66-69 years) and the oldest (≥80 years). RESULTS: Better OS was associated with chemoradiation compared to radiation alone, not only in all patients (N = 5879) (hazard ratio [HR] = 0.82, p < 0.001), but also in the oldest group (N = 1380) (HR = 0.77, p = 0.006) in whom the adverse events rates were not higher than those in the youngest (N = 1562); more of the latter (26%-30%) than the former (14%-19%) received chemoradiation, regardless of their comorbidity indices. CONCLUSIONS: Our findings provide evidence that patients' characteristics, other than chronological age, should be equally considered in selecting the best therapy for older patients with HNSCC.