Role of cancer survivor health and health service use in spouses' use of mental health-related care.

BACKGROUND: Spouses of cancer survivors are at an increased risk of poor mental health outcomes but are known to underuse supportive services. The objective of the current study was to determine how the health and health care use of cancer survivors were associated with depression and anxiety-related health care use in their spouses. METHODS: The current observational study used data from the Medical Expenditure Panel Survey to identify married individuals with a cancer-related medical event or disability ("cancer survivors"), and linked health and health care use data across spousal dyads. Spouses reporting a prescription for an antidepressant or antianxiety medication or any psychotherapy were flagged as having used mental health care. Correlates of use were assessed, with a focus on the health and health care use of the cancer survivor. RESULTS: Greater than 25% of the spouses of cancer survivors used mental health care over the approximately 2.5 years of follow-up. Controlling for their own predisposing, enabling, and need characteristics, spouses were found to be less likely to use mental health care if the cancer survivor reported more health conditions or elevated depressed mood compared with dyads in which the survivor reported low distress and depression. Spouses were nearly 3 times more likely to use mental health care if the cancer survivor themselves had used mental health care (odds ratio, 2.98; 95% confidence interval, 2.17-4.09). CONCLUSIONS: The findings of the current study enhance understanding of how health outcomes are intertwined in families with cancer, and reinforce the importance of a family-centered approach to cancer care that facilitates psychosocial care. LAY SUMMARY: The health and well-being of cancer survivors and their spouses are intertwined. The results of the current study demonstrated that this interrelationship extends to mental health care related to depression and anxiety. Spouses of cancer survivors were found to be less likely to receive mental health care when the survivor had more health care needs. Spouses were nearly 3 times more likely to receive care if the survivor also was receiving mental health care. Caregiving spouses may face more challenges finding the time, money, or energy to engage in their own self-care. However, providing supportive care to one partner may help the other partner access care as well.

Primary care for cancer survivors: a review of national institutes of health-funded grants 2017-2022.

PURPOSE: To describe the characteristics of National Institutes of Health (NIH) grants on primary care cancer research in cancer survivorship funded over the past 5 years. METHODS: Research project grants (RPG) funded during Fiscal Year (FY) 2017 to 2022 focused on cancer survivorship were identified using a text mining algorithm of words from the NIH Research, Condition, and Disease Categorization (RCDC) thesaurus with survivorship-relevant terms. Grants were then reviewed and double-coded to identify those that were carried out in a primary care setting, targeted primary care providers, or had primary care providers in the study team. RESULTS: A total of 24 grants were identified; 23 were funded by the National Cancer Institute and one was funded by the National Institute on Minority Health and Health Disparities. The majority were funded under the R01 mechanism (70.8%) and led by established investigators. Most were interventional design (91.7%), including both survivors and providers (79.2%), and focused care coordination or healthcare utilization (91.7%). CONCLUSIONS: Grants focused on primary care cancer survivorship are uncommon in the NIH portfolio. IMPLICATIONS FOR SURVIVORS: For the over 18 million cancer survivors in the USA, being cared for in a primary care setting is common. Yet, NIH-funded research on primary care cancer survivorship is sparse.

Advancing health equity in cancer survivorship research: National institutes of health 2017-2022 portfolio review.

BACKGROUND: Communities and researchers have called for a paradigm shift from describing health disparities to a health equity research agenda that addresses structural drivers. Therefore, we examined whether the cancer survivorship research portfolio has made this shift. METHODS: We identified grants focused on populations experiencing health disparities from the National Institutes of Health (NIH) Cancer Survivorship Research Portfolio (N = 724), Fiscal Years 2017-2022. Grant characteristics were abstracted, drivers of health disparities were mapped onto the levels and domains of influence, and opportunities for future research were identified. RESULTS: A total of 147 survivorship grants focused on health disparities were identified, of which 73.5% of grants focused on survivors from racial and ethnic minoritized groups, 25.9% living in rural areas, 24.5% socioeconomically disadvantaged, and 2.7% sexual and gender minority groups. Study designs were 51.0% observational. 82.3% of grants measured or intervened on at least one individual-level of influence, compared to higher levels of influence (32.7% interpersonal, 41.5% institutional/community, and 12.2% societal). Behavioral and healthcare system domains of influence were commonly represented, especially at the individual level (47.6% and 36.1%, respectively). Less frequently represented was the physical/built environment (12.2%). CONCLUSIONS: NIH-funded cancer survivorship research on health disparities is still focused on individual-level of influence. However, the proportion of grants examining structural and social drivers as well as the mechanisms that drive disparities in healthcare and health outcomes among cancer survivors have increased over time. Gaps in funded research on specific populations, cancer types, and focus areas of survivorship science were identified and warrant priority.

Survivorship science at the National Institutes of Health 2017-2021.

PURPOSE: To describe the characteristics of National Institutes of Health (NIH) cancer survivorship grants funded over the past 5 years and identify gap areas for future efforts and initiatives. METHODS: Research project grants (RPG) funded during Fiscal Year (FY) 2017 to 2021 focused on cancer survivorship were identified using a text mining algorithm of words from the NIH Research, Condition, and Disease Categorization (RCDC) thesaurus with survivorship-relevant terms. The title, abstract, specific aims, and public health relevance section of each grant were reviewed for eligibility. Grants meeting the eligibility criteria were double coded to extract study characteristics (e.g., grant mechanism, study design, study population). RESULTS: A total of 586 grants were funded by 14 NIH Institutes from FY2017 to FY2021, and the number of newly funded grants increased each FY, from 68 in 2017 to 105 in 2021. Approximately 60% of all grants included an intervention study, and interventions most often focused on psychosocial or supportive care (32.0%). The most common primary focus of the grants was late- and long-term effects of cancer treatment (46.6%), and least often financial hardship. CONCLUSIONS: The results of this portfolio analysis indicate overall growth in the number and breadth of grants over the last five years, although notable gaps persist. IMPLICATIONS FOR CANCER SURVIVORS: This review of current NIH grants suggests a need for expanded research to understand and address survivor needs to ensure that the over 18 million cancer survivors in the United States have optimal quality of life and health outcomes.

Dual PI3K/mTOR Inhibition in Colorectal Cancers with APC and PIK3CA Mutations.

Therapeutic targeting of the PI3K pathway is an active area of research in multiple cancer types, including breast and endometrial cancers. This pathway is commonly altered in cancer and plays an integral role in numerous vital cellular functions. Mutations in the PIK3CA gene, resulting in a constitutively active form of PI3K, often occur in colorectal cancer, though the population of patients who would benefit from targeting this pathway has yet to be identified. In human colorectal cancers, PIK3CA mutations most commonly occur concomitantly with loss of adenomatous polyposis coli (APC). Here, treatment strategies are investigated that target the PI3K pathway in colon cancers with mutations in APC and PIK3CA Colorectal cancer spheroids with Apc and Pik3ca mutations were generated and characterized confirming that these cultures represent the tumors from which they were derived. Pan and alpha isomer-specific PI3K inhibitors did not induce a significant treatment response, whereas the dual PI3K/mTOR inhibitors BEZ235 and LY3023414 induced a dramatic treatment response through decreased cellular proliferation and increased differentiation. The significant treatment responses were confirmed in mice with Apc and Pik3ca-mutant colon cancers as measured using endoscopy with a reduction in median lumen occlusion of 53% with BEZ235 and a 24% reduction with LY3023414 compared with an increase of 53% in controls (P < 0.001 and P = 0.03, respectively). This response was also confirmed with 18F-FDG microPET/CT imaging.Implications: Spheroid models and transgenic mice suggest that dual PI3K/mTOR inhibition is a potential treatment strategy for APC and PIK3CA-mutant colorectal cancers. Thus, further clinical studies of dual PI3K/mTOR inhibitors are warranted in colorectal cancers with these mutations. Mol Cancer Res; 15(3); 1-11. ©2016 AACR.

Colon Tumors with the Simultaneous Induction of Driver Mutations in APC, KRAS, and PIK3CA Still Progress through the Adenoma-to-carcinoma Sequence.

Human colorectal cancers often possess multiple mutations, including three to six driver mutations per tumor. The timing of when these mutations occur during tumor development and progression continues to be debated. More advanced lesions carry a greater number of driver mutations, indicating that colon tumors might progress from adenomas to carcinomas through the stepwise accumulation of mutations following tumor initiation. However, mutations that have been implicated in tumor progression have been identified in normal-appearing epithelial cells of the colon, leaving the possibility that these mutations might be present before the initiation of tumorigenesis. We utilized mouse models of colon cancer to investigate whether tumorigenesis still occurs through the adenoma-to-carcinoma sequence when multiple mutations are present at the time of tumor initiation. To create a model in which tumors could concomitantly possess mutations in Apc, Kras, and Pik3ca, we developed a novel minimally invasive technique to administer an adenovirus expressing Cre recombinase to a focal region of the colon. Here, we demonstrate that the presence of these additional driver mutations at the time of tumor initiation results in increased tumor multiplicity and an increased rate of progression to invasive adenocarcinomas. These cancers can even metastasize to retroperitoneal lymph nodes or the liver. However, despite having as many as three concomitant driver mutations at the time of initiation, these tumors still proceed through the adenoma-to-carcinoma sequence.

Phospholipid ether analogs for the detection of colorectal tumors.

The treatment of localized colorectal cancer (CRC) depends on resection of the primary tumor with adequate margins and sufficient lymph node sampling. A novel imaging agent that accumulates in CRCs and the associated lymph nodes is needed. Cellectar Biosciences has developed a phospholipid ether analog platform that is both diagnostic and therapeutic. CLR1502 is a near-infrared fluorescent molecule, whereas 124/131I-CLR1404 is under clinical investigation as a PET tracer/therapeutic agent imaged by SPECT. We investigated the use of CLR1502 for the detection of intestinal cancers in a murine model and 131I-CLR1404 in a patient with metastatic CRC. Mice that develop multiple intestinal tumors ranging from adenomas to locally advanced adenocarcinomas were utilized. After 96 hours post CLR1502 injection, the intestinal tumors were analyzed using a Spectrum IVIS (Perkin Elmer) and a Fluobeam (Fluoptics). The intensity of the fluorescent signal was correlated with the histological characteristics for each tumor. Colon adenocarcinomas demonstrated increased accumulation of CLR1502 compared to non-invasive lesions (total radiant efficiency: 1.76×10(10) vs 3.27×10(9) respectively, p = 0.006). Metastatic mesenteric tumors and uninvolved lymph nodes were detected with CLR1502. In addition, SPECT imaging with 131I-CLR1404 was performed as part of a clinical trial in patients with advanced solid tumors. 131I-CLR1404 was shown to accumulate in metastatic tumors in a patient with colorectal adenocarcinoma. Together, these compounds might enhance our ability to properly resect CRCs through better localization of the primary tumor and improved lymph node identification as well as detect distant disease.