An Assortment of Journal Abstracts to Enhance Oncology Care

OPIOID USE Opioid-free discharge after pancreatic resection through a learning health system paradigm A recent study demonstrated how a new approach successfully reduced inpatient opioid use by 50 percent following pancreatic cancer surgery and lowered the median opioid prescription volumes at discharge to zero. This could help lessen the risk of long-term opioid dependence in patients, according to the research team (JAMA Surg 2023; doi:10.1001/jamasurg.2023.4154). This cohort study included 832 patients with a median age of 65 years who underwent pancreatic resection between October 2016 and April 2022. Participants included in the trial underwent 541 pancreatoduodenectomies, 285 distal pancreatectomies, and six other pancreatectomies. Of the enrolled patients, 611 were White, 90 were Hispanic, 58 were Asian, 56 were Black, and 17 identified as other ethnicities. The research team explored how incremental modifications to post-surgery procedures impacted the amount of opioids used by inpatients as well as at the point of discharge. Data showed that the total inpatient oral morphine equivalents (OME) decreased from a median of 290 mg to 129 mg. Additionally, the researchers reported that OME at discharge decreased from a median of 150 mg to 0 mg. Over 75 percent of patients were discharged with an OME of 50 mg or less. “These findings suggest that this learning health system model may be generalizable to other hospitals and other major abdominal surgeries to reduce inpatient opioid use and increase the number of patients discharged opioid-free,” the study authors noted. AUTHOR COMMENTARY: “Our enhanced recovery program, which includes generalizable protocols to reduce reliance on opioid medications, is the first to demonstrate continuous decreases in opioid use and distribution after pancreatic surgery,” said senior author Ching-Wei Tzeng, MD, Associate Professor of Surgical Oncology at the University of Texas MD Anderson Cancer Center. “By making purposeful, successive improvements to existing processes, we showed that we can reduce the amount of opioids patients need after a major surgery while ensuring they recover well without any extra costs.” SKIN CANCER Assessing skin cancer risk factors, sun safety behaviors, and melanoma concern in Atlantic Canada: A comprehensive survey study Given the rising incidence of cutaneous melanoma worldwide, a new study examined why people living in Atlantic regions are more at risk for developing melanoma than other Canadians (Cancers 2023; https://doi.org/10.3390/cancers15153753). Researchers conducted a cross-sectional survey in Atlantic provinces between July 2020 and August 2022. Survey results between geographic and demographic groups were compared via two-sided Z-tests for equality of proportions and logistic regression models. The analysis included 7,861 participants with a mean age of 61 years. The data showed that higher-income individuals had an increased risk of melanoma. Contributing factors include more lifetime sun burns, tanning bed use, and being tanned, according to the study authors. The research also showed that individuals earning less than $50,000 were more likely to work outdoors and, in turn, were at a higher risk of developing skin cancer as well. Policies protecting outdoor workers could help reduce melanoma risk, the researchers recommended. When comparing men and women, the investigators found women had less sun exposure and practiced more sun protection than their male counterparts. However, women tended to wear fewer long-sleeve shirts and frequented tanning beds more often. Study results also revealed individuals living in high-risk communities—Prince Edward Island and Nova Scotia—had more sunburns and sun exposure compared with people in regions like Newfoundland and Labrador. These findings suggest, according to the study authors, that “future efforts aimed at reducing the cutaneous melanoma burden in Atlantic Canada should be tailored for target geographic and/or demographic groups.” AUTHOR COMMENTARY: “A higher socioeconomic status is known to be associated with more vacations in sunny climates and recreational tanning, which likely ultimately drives melanoma incidence in this population,” noted Ivan Litvinov, MD, PhD, Associate Professor in the Department of Medicine and Chair of the Dermatology Division at McGill University. HEAD & NECK CANCER Identification of multidrug chemoresistant genes in head and neck squamous cell carcinoma cells Researchers have uncovered two new genes associated with chemotherapy resistance in patients with head and neck cancer (Mol Cancer 2023; doi.org/10.1186/s12943-023-01846-3). The study authors used data mining to identify genes that may be linked to tumor response. Twenty-eight genes on 12 strains of chemoresistant cancer cell lines were tested. Through this analysis, 10 multi-drug chemoresistance genes—TOP2A, DNMT1, INHBA, CXCL8, NEK2, FOXO6, VIM, FOXM1B, NR3C1, and BIRC5—were identified. Of these, the researchers reported that four genes—TOP2A, DNMT1, INHBA, and NEK2—were upregulated among a cohort of patients with head and neck squamous cell carcinoma (n=221). The data showed that silencing NEK2 negated chemoresistance in all drug-resistant cell strains. Additionally, the study authors found that INHBA and TOP2A conferred chemoresistance in the majority of the drug-resistant cell strains. On the other hand, DNMT1 had heterogeneous results, according to the investigators. Drug library screens were also conducted and two compounds—Sirodesmin A and Carfilzomib—targeting INHBA and NEK2 and re-sensitized cisplatin-resistant cells were identified. This study provides the first evidence that the genes NEK2 and INHBA cause chemoresistance in head and neck squamous cell carcinoma and silencing of either gene could combat chemoresistance to multiple therapies. “The two existing compounds could be repurposed to counteract cisplatin chemoresistance in HNSCC. This finding may lead to novel personalized biomarker-linked therapeutics that can prevent and/or abrogate chemoresistance in HNSCC and other tumor types with elevated NEK2 and INHBA expression,” the study authors stated, while noting further investigation is needed to understand their signaling mechanisms in tumor chemoresistance. AUTHOR COMMENTARY: “These results are a promising step towards cancer patients in the future receiving personalized treatment based on their genes and tumor type that give them a better survival rate and treatment outcome,” noted senior study author Muy-Teck Teh, PhD, senior lecturer in Head and Neck Cancer at Queen Mary University of London. “Unfortunately, there are lots of people out there who do not respond to chemotherapy or radiation. But our study has shown that, in head and neck cancers at least, it is these two particular genes that could be behind this, which can then be targeted to fight against chemoresistance.”

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