OPIOID USE
Consensus-based guidance on opioid management in individuals with advanced cancer-related pain and opioid misuse or use disorder
While opioids are an important aspect of cancer pain management, there is a lack of consensus on how to treat pain in cancer patients who also have struggled with opioid use disorder or prescription opioid misuse. A recent qualitative study provides consensus-based guidance for clinicians and highlights key research and policy gaps (JAMA Oncol 2022; doi: 10.1001/jamaoncol.2022.2191). An online Delphi study platform was used to explore consensus among 120 palliative care and addiction experts about how they would approach treatment of a hypothetical 50-year-old patient with advanced cancer who has cancer-related pain and either a history of opioid use disorder or prescription opioid misuse. The participants were asked to rate and comment on various management strategies, such as prescribing methadone and buprenorphine. For a patient with untreated opioid misuse and opioid use disorder, the researchers reported that, regardless of prognosis, it was deemed appropriate to begin treatment with buprenorphine/naloxone. However, the participants noted that it was inappropriate to refer to a methadone clinic. Additionally, the data showed that initiating split-dose methadone was deemed appropriate for patients with shorter prognoses while the appropriateness for those with longer prognoses was uncertain. For a hypothetical cancer patient who did not have a history of opioid use disorder but was misusing opioids, experts recommended continuing their opioid regime but increasing monitoring through more visits or shorter prescriptions. "The use of buprenorphine/naloxone for opioid use disorder was deemed appropriate, but its use for opioid misuse was less clear," the study authors concluded. "Participants considered methadone an important tool for treating opioid use disorder and cancer-related pain, but policy and safety concerns exist."
AUTHOR COMMENTARY: "There is no standard of care for treating cancer pain and managing opioids in people who come into their cancer diagnosis with a history of substance use, or who are at increased risk for adverse events due to prescription opioid misuse behaviors, such as taking more opioids than prescribed," said first author Katie Fitzgerald Jones, MSN, a palliative and addiction nurse practitioner at the VA Boston Healthcare System, in a statement. "If we are going to prescribe opioids for pain, it is our moral obligation to also treat an important consequence of that opioid prescribing-opioid addiction-if and when it occurs in our patients."
MAMMOGRAPHY
Diagnostic mammography performance across racial and ethnic groups in a national network of community-based breast imaging facilities
Recent findings found that the accuracy of diagnostic mammograms differed across racial and ethnic groups, with variation in several measures of diagnostic performance (Cancer Epidemiol Biomarkers Prev 2022; doi: 10.1158/1055-9965.EPI-21-1379). In this cohort study, researchers used data from 267,868 diagnostic mammograms performed at 98 facilities in the Breast Cancer Surveillance Consortium between 2005 and 2017. Breast Imaging Reporting and Data System (BI-RADS) assessments were used to identify mammograms that were likely positive (malignant) and likely negative (benign). The racial distribution in the study was as follows: 70 percent non-Hispanic White, 13 percent non-Hispanic Black, 10 percent Asian/Pacific Islander, and 7 percent Hispanic. Among the study population, the researchers reported that the invasive cancer detection rate (the number of cancers detected following a mammogram, per 1,000 mammograms performed) was highest in non-Hispanic Whites (35.8), followed by Asian/Pacific Islander (31.6), non-Hispanic Black (29.5), and Hispanic (22.3). They also found that short interval follow-up recommendations were most common among non-Hispanic Black women (31.0%) compared with other groups. Asian/Pacific Islander women were the most likely to receive a false-positive report, according to the study authors. Non-Hispanic Black women were most likely to receive a false-negative report. The researchers also assessed the positive predictive value and found it was highest among non-Hispanic White women (27.8) followed by Asian/Pacific Islander (24.3), non-Hispanic Black (23.4), and Hispanic (19.4). The data also revealed differences in the tumors detected through the diagnostic mammograms. Overall, the study authors found that Asian/Pacific Islander women had the largest proportion of ductal carcinoma in situ, while Black women were more likely to be diagnosed with later-stage tumors and higher tumor grade. "Diagnostic mammography performance varied across racial/ethnic groups. Addressing characteristics related to imaging facility and access, rather than personal characteristics, may help reduce some of these disparities," the study authors concluded.
AUTHOR COMMENTARY: "Breast imaging is an important first step to being diagnosed and getting into the treatment pathway. It's reasonable to think that differences at the beginning of care would affect later outcomes," noted study author Sarah J. Nyante, PhD, Associate Professor of Radiology at the University of North Carolina School of Medicine, in a statement. "Examining differences in diagnostic digital mammography performance and tumor characteristic outcomes by race and ethnicity may help us understand why disparities in cancer detection and quality of care persist for some demographic groups."
MELANOMA
Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy
A new study found that androgen receptor signaling affects response to BRAF/MEK inhibitor therapy in both males and females with melanoma (Nature 2022; https://doi.org/10.1038/s41586-022-04833-8). These findings have important implications for therapy and provide a new target to address therapeutic resistance, according to the study authors. Their research also sheds light on one possible reason why men face a poorer prognosis than women when diagnosed with melanoma. The researchers studied a group of patients with melanoma who were treated with neoadjuvant BRAF/MEK-targeted therapy (NCT02231775) and found that women had significantly higher rates of major pathological response and improved recurrence-free survival when compared with their male counterparts. They validated their findings in several additional cohorts. "Studies in preclinical models demonstrated significantly impaired anti-tumor activity in male versus female mice after BRAF/MEK-targeted therapy (P=0.006), with significantly higher expression of the androgen receptor in tumors of male and female BRAF/MEK-treated mice versus the control (P=0.0006 and P=0.0025)," the study authors reported. The data showed that pharmacological inhibition of androgen receptor signaling improved responses to BRAF/MEK-targeted therapy in male and female mice. Induction of androgen receptor signaling-through testosterone administration-was correlated with a significantly impaired response to BRAF/MEK-targeted therapy in male and female patients, according to the researchers.
AUTHOR COMMENTARY: "By using translational studies in patient samples alongside preclinical models, we showed that treatment with BRAF/MEK inhibitors is associated with upregulation of the androgen receptor on tumor cells, thus promoting resistance to therapy. We found that blocking the androgen receptor actually improved treatment response in males and females, and that activating androgen receptor signaling with testosterone abrogated therapeutic response," noted co-corresponding author Joseph Marszalek, PhD, Head of Research at the University of Texas MD Anderson Cancer Center.