Aspirin & Lung Cancer/ Actinic Keratosis / Arterial Thrombosis & Cancer

Educational Objectives

After hearing and assimilating this program, the listener will be better able to:

1. Increase his/her basic knowledge of important advances in medicine
2. Identify a broad range of clinical research reported in the medical literature
3. Synthesize research findings through one-on-one interviews with authors, editorialists, or experts in the field
4. Integrate new treatments reviewed in the summaries into current practice
5. Challenge oneself with thoughtful, clinically relevant questions.

Summary

Summary Narrators

Carole Wyand

Tom Linden, MD
Professor of Medical Journalism
University of North Carolina, Chapel Hill

NEW EVIDENCE OF LOWER RISK FOR LUNG CANCER WITH LOW-DOSE ASPIRIN

The inhibition of cyclooxygenase by aspirin is a plausible explanation for how aspirin could lower the risk for lung cancer. Some randomized trials have shown a benefit for long-term, low-dose aspirin use, but epidemiological and cohort studies, especially in women, have shown no benefit. In a study in JAMA Network Open (https://doi.org/10.1001/jamanetworkopen.2019.0185), researchers in the Republic of Korea used a national database to identify nearly 13,000,000 patients for whom information on aspirin use and lung cancer diagnoses was available. Low-dose aspirin use was defined as doses of up to 100 mg/day, at least 2 days/week.

During an average follow-up of 5 years, more than 60,000 cases of lung cancer were diagnosed. Analyses were adjusted for demographic variables and clinical risk factors. Compared with no aspirin use, long-term, low-dose aspirin use was associated with a significantly lower risk for lung cancer; risk reductions were 4% after aspirin use for 5 years to 6 years; 6% after aspirin use for 7 years to 8 years, and 11% after aspirin use for 9 years. In subgroup analyses, there were similar benefits for patients 65 or older. Relative risk reductions for patients younger than 65 were small and not statistically significant.

Although the results of this observational study could reflect confounding, the correlation between the longer use of low-dose aspirin and a lower risk for lung cancer strengthens the findings. But the magnitude of benefit is small and needs to be factored into a more comprehensive assessment.

TREATING ACTINIC KERATOSIS: A RANDOMIZED TRIAL

Often, patients with actinic keratoses, which can progress to cutaneous squamous cell carcinoma, are treated with any of several so-called “field-directed” therapies when they have areas with multiple lesions. In a randomized trial in the March 7, 2019 New England Journal of Medicine (https://doi.org/10.1056/NEJMoa1811850), researchers compared four field-directed alternatives in 600 patients. The therapies were:

• 5% fluorouracil cream (which disrupts DNA synthesis)

• 5% imiquimod cream (which stimulates local immune response)

• Photodynamic therapy (which induces cell necrosis when a photosensitizing drug is applied and the skin is exposed to light)

• Ingenol mebutate gel (which injures mitochondria and plasma membranes)

All of the patients had at least five actinic keratoses on their heads, within an area of 25 cm2 to 100 cm2. The patients could be retreated if their initial response was inadequate. The primary endpoint was at least a 75% reduction in the number of lesions at a year; a dermatologist who was unaware of treatment assignment evaluated this outcome. The proportion of patients who achieved the primary endpoint was significantly higher with fluorouracil (75%) than with imiquimod (54%), photodynamic therapy (38%), or ingenol mebutate (29%).

Each of these field-directed treatments for patients with multiple, closely spaced actinic keratoses has some advantages and disadvantages that might influence patients’ preferences. But 5% fluorouracil was clearly the most effective agent in this trial, and its adverse effects profile was similar to those of the other agents. For patients with a few isolated actinic keratoses, liquid nitrogen cryotherapy is a good option.

ARTERIAL THROMBOSIS AND OCCULT CANCER

The association between venous thromboembolism and cancer is well established, but the association between arterial thromboembolism (namely, myocardial infarction, ischemic stroke, systemic artery thromboembolism, and mesenteric ischemia) and subsequent malignancy is unclear.

In a retrospective, case-control study in the February 21, 2019 issue of Blood (https://doi.org/10.1182/blood-2018-06-860874), researchers sought to determine the risk for arterial thromboembolic events during the year before a diagnosis of cancer using the Surveillance, Epidemiology, and End Results (SEER) registry and Medicare claims data on roughly 400,000 pairs of patients with cancer and age- and comorbidity-matched controls without cancer; the patients’ average age was 76.

Results were as follows:

• The risk for arterial thromboembolic events progressively increased in the patients with cancer relative to the controls beginning 5 months before the diagnosis of cancer; the risk peaked at a month before diagnosis (0.62% vs. 0.11%; P<0.001).

• The most common cancers associated with past arterial thromboembolic events were lung (29%), colorectal (24%), prostate (11%), breast (10%), non-Hodgkin lymphoma (6%), pancreatic (5%), gastric (4%), and uterine (3%); odds ratios correlated directly with cancer stage.

This study strengthens the association between arterial thrombosis and occult malignancy. The researchers acknowledge important limitations, including the lack of information on smoking prevalence. Plus, these results can’t be generalized to younger patients. Even so, these findings remind clinicians that the hypercoagulability of cancer includes arterial thrombosis, and, as with venous thromboembolism, a new diagnosis of myocardial infarction or ischemic stroke should prompt age-appropriate malignancy screening (www.bloodjournal.org/content/133/8/769).

Readings

Disclosures

For this program, Dr. Alok Khorana reported receiving personal fees and/or nonfinancial support from Janssen, Bayer, Sanofi, Parexel, Halozyme, Pfizer, Seattle Genetics, Pharmacyclics, Pharmacyte, AngioDynamics, Leo Pharma, TriSalus, and Medscape; and research grants to his institution from Merck, Array, Bristol-Myers Squibb, and Leap Pharma.

Acknowledgements

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

JW300801

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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