THERANOSTICS

Semiconducting Polymers Enhance Cerenkov Radiation Energy Transfer for Multimodal Cancer Theranostics

Researchers have successfully developed a novel cancer treatment approach that utilizes Cerenkov radiation energy to target and destroy cancer cells more effectively (J Nucl Med 2021; https://jnm.snmjournals.org/content/62/supplement_1/71). The approach uses light from decaying radiopharmaceuticals, known as Cerenkov luminescence, as an energy source to activate semiconducting polymer nanoparticles that kill cancer cells. Over the past several decades, many studies have been conducted on photodynamic therapy, which uses an external light source to activate nanomaterials for cancer therapy. This therapy, however, is limited by the ability of external light to penetrate tissues. As Cerenkov luminescence is spontaneously produced from certain radiopharmaceuticals as they decay in the body, it has recently been proposed as an internal energy source for cancer therapy. While Cerenkov luminescence is advantageous because it is a light source produced inside of the body, the light source is generally very weak. The light source can be amplified with semiconducting polymers, which greatly increases its potential to target and destroy cancer cells. The researchers aimed to determine how to best utilize radiopharmaceuticals and nanoparticles to create the ideal cancer theranostics nanosystem. Researchers found that semiconducting polymer nanoparticles optimized with photosensitizers dramatically intensified Cerenkov luminescence to kill cancer cells. Positron emission tomography and optical imaging studies also clearly visualized tumor uptake of these optimized semiconducting polymer nanoparticles. This approach was found to have excellent potential as a cancer theranostics nanosystem without any tissue penetration limits.

OVARIAN CANCER

Computational Modeling of Ovarian Cancer Dynamics Suggests Optimal Strategies for Therapy and Screening

Certain patients with an aggressive form of ovarian cancer have a better chance of a cure through surgical removal of their tumor before chemotherapy instead of the reverse, a new study shows (PNAS 2021; https://doi.org/10.1073/pnas.2026663118). The study used a mathematical tool to examine how doctors should coordinate available treatments for high-grade serous ovarian cancer (HGSC). The new analysis argues that patients who can undergo complete debulking surgery first, with chemotherapy added after (termed primary debulking surgery or PDS), should have a superior outcome to the other main treatment option: giving patients a few cycles of chemotherapy to shrink the tumor before surgery (neoadjuvant chemotherapy or NACT). The researchers used clinical data from roughly 300 patients in previous studies of patients' responses to PDS or NACT, taken from the Princess Margaret Cancer Center in Toronto and the Canadian Cancer Trials Group. The researchers found that in patients who are well enough for surgery, debulking provides better results because it has the best chance of removing cancer cells resistant to chemotherapy. For patients who are too ill for debulking surgery, the study suggests that a shorter period of initial chemotherapy, rather than the currently recommended interval, might provide a greater benefit. The current analyses suggest several questions that future randomized clinical trials should examine, say the study authors. These include how much the influence of the time gap between surgery and subsequent chemotherapy may affect treatment outcome, whether there is a link between the number of initial chemotherapy cycles and outcomes, and whether complete secondary surgery on relapsed tumor improves prognosis.

FINANCIAL TOXICITY

Evaluating Meaningful Levels of Financial Toxicity in Gynecologic Cancers

In a new study designed to provide a more comprehensive picture of how a diverse cohort of gynecologic cancer patients are affected by financial distress-also called financial toxicity in acknowledgment of the health hazards it can pose-researcher-physicians at Beth Israel Deaconess Medical Center (BIDMC) and the University of Alabama at Birmingham (UAB) analyzed previously collected survey data of gynecologic oncology patients from their respective institutions (Int J Gynecol Cancer 2021;31:801-806). Using the Comprehensive Score for Financial Toxicity (COST) to measure the economic burden experienced by patients with cancer, researchers analyzed previously collected survey data from 308 patients with gynecologic cancer-240 patients surveyed at BIDMC and 121 surveyed at UAB. The team adapted a proposed grading scale to define three groups: no/mild, moderate, and severe financial toxicity. They evaluated the frequency of financial toxicity among each group and found that nearly half of patients with gynecologic cancer reported experiencing moderate to severe financial toxicity. Further analysis of survey data revealed that younger patients were at greater risk of experiencing financial toxicity for a variety of reasons. Younger patients are not eligible for Medicare, and diagnosis and treatment may impact their ability to work. They have also had fewer earning years to accumulate a financial safety net. Patients reporting severe financial toxicity accounted for 15 percent of those surveyed. Researchers found this group more likely to report changing spending habits and borrowing money due to the costs of cancer care. Most alarmingly, those reporting severe financial hardship were nearly five times more likely to attempt to cope with the high cost of care through medication non-compliance.

BREAST CANCER GENETICS

Comparison of the Prevalence of Pathogenic Variants in Cancer Susceptibility Genes in Black Women and Non-Hispanic White Women With Breast Cancer in the United States

The prevalence of genetic mutations associated with breast cancer in Black and White women is the same, according to a new study of nearly 30,000 patients led by researchers in the Basser Center for BRCA at the Abramson Cancer Center (JAMA Oncol 2021; doi:10.1001/jamaoncol.2021.1492). About 5 percent of both Black and White women have a genetic mutation that increases their risk of breast cancer. Black women are more likely to be diagnosed with breast cancer before age 50 or with estrogen receptor (ER)-negative and triple-negative breast cancer than non-Hispanic White women. It has remained unclear whether these disparities are related to racial differences in germline genetic pathogenic variants (PVs) in known breast cancer genes and if race should inform strategies for genetic testing. The latest multi-institutional effort-which follows a 2020 study that investigated relative breast cancer risk in Black women but with no direct comparison to White women-analyzed data from seven population-based studies in the CARRIERS consortium. The researchers measured the prevalence of PVs in 12 genes known to confer breast cancer risk. The CARRIERS consortium is a group of 17 large epidemiology studies in the U.S. focused on women in the general population who develop breast cancer. Among 3,946 Black and 25,287 non-Hispanic White women, there was no statistically significant difference in PVs by race: 5.65 percent of Black women versus 5.06 percent of non-Hispanic White women had PVs in the 12 genes. The researchers also found that younger age and ER-negative breast cancer were risk factors in the most impactful genes, including BRCA1, BRCA2, and PALB2, for both White and Black women. Compared to White women, Black women are much less likely to undergo genetic counseling and testing, largely due to differences in physician recommendations or access to care.