Literature selections curated by Lewis Flint, MD, FACS, and reviewed by the ACS Brief editorial board.
PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer Shows Promising Results
Cercek A, Lumish M, Sinopoli J, et al. PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. N Engl J Med. 2022;386(25):2363-2376. doi:10.1056/NEJMoa2201445
Sanoff HK. Improving Treatment Approaches for Rectal Cancer. N Engl J Med. 2022;386(25):2425-2426. doi:10.1056/NEJMe2204282
Andrea Cercek, MD, and colleagues noted that a subset of locally advanced metastatic rectal cancers is characterized by a deficiency in mismatch repair. They further noted that this type of cancer is responsive to immunotherapy with programmed death–one (PD-1) blocking agents. They hypothesized that patients with locally advanced rectal cancer, confirmed mismatch repair deficiency, and no evidence of metastatic disease who had PD-1 added to chemoradiation therapy might have improved tumor response.
They conducted a prospective study in which a single PD-1 agent was administered before routine chemoradiation therapy. Follow-up at 6 months after therapy was available for the 12 patients in the prospective cohort, and all 12 patients had a complete clinical response to the therapy. No sign of recurrence or progression was noted in a small proportion of the cohort followed with careful surveillance out to 24 months post-treatment. The authors emphasized that additional studies with longer follow-up are needed.
In the editorial that accompanied this article, author Hanna Sanoff, MD, MPH, noted that outcomes of standard rectal cancer treatment, including chemoradiation therapy and surgical resection, have improved progressively; 3-year disease-free survival is 77%. The addition of immunotherapy with PD-1 agents may provide a pathway that permits nonoperative management of rectal cancer. Despite the encouraging data reported by Dr. Cercek, the endpoint of the study (complete clinical response) does not represent evidence of complete control of the malignancy. Dr. Sanoff emphasized that in other studies of this therapeutic agent, long-term recurrence rates of cancer have approached 30%. Additional studies are necessary to confirm the reported findings and provide additional evidence to support a nonoperative approach to rectal cancer care.
Article Summarizes Monkeypox Health Concerns and Recent Developments in the US
Harris E. What to Know About Monkeypox. JAMA. 2022;327(23):2278-2279. doi:10.1001/jama.2022.9499
The increasing number of monkeypox cases reported in the US is concerning. Previously, cases were identified largely in patients who had traveled to countries where the disease is prevalent. Recent cases reported domestically have occurred in patients with no history of such travel. Transmission of monkeypox is thought to occur through direct physical contact with a person who has the disease and less frequently via respiratory droplet transmission.
Author Emily Harris noted that the case fatality rate for the West African virus, the most common source of US cases, is 4%, whereas the case fatality rate for the Central African virus approaches 11%. To date, the US has no reported deaths from monkeypox. Symptoms, including fever and enlarged lymph nodes, usually occur 1 to 2 weeks after exposure to the virus. A few days following the onset of these symptoms, the characteristic rash develops. The rash will progress through several stages, beginning with blistering and ending with scab development. Scabs will then fall off revealing normal tissue. Body regions affected by rash development include the head, legs, palms of hands, and soles of feet. In some of the cases reported in the US, the rash started in the genital areas.
Two vaccines are available and public health officials have recommended administering the vaccine as soon as possible after exposure. Healthcare professionals who encounter a patient with signs and symptoms of monkeypox should report these findings to local health departments.
