Two new studies discover advances in radiation therapy are extending or enhancing the lives of individuals with anal cancer, even those whose cancer has progressed to stage IV. Both studies appeared in the International Journal of Radiation Oncology * Biology * Physics (Red Journal), the official scientific journal of the American Society for Radiation Oncology (ASTRO).
One trial, of patients with stage III anal cancer whose disease has spread to the para-aortic lymph nodes, discovered that a combination of extended-field radiation therapy and chemotherapy could significantly enhance overall survival and control the cancer without adding severe side effects. A second research study discovered that, in patients with locally advanced anal cancer, the application of intensity modulated radiation therapy (IMRT) rather than standard radiation therapy enhanced the tolerance to radiation therapy and minimized the requirement for ostomy (surgical creation of an alternative pathway for waste removal from the body).
Anal cancer is relatively uncommon, with an estimated 8,000 new cases identified annually in the United States. The majority of anal canal cancers are squamous cell carcinomas (SCC) that are not yet metastasized to other sites in the body. About 20 percent of anal SCC patients are diagnosed annually with distant metastatic disease, or stage IV disease.
Aggressive combination therapy extends survival for certain patients with stage IV anal cancer
Stage IV anal cancer patients have generally not been thought to be candidates for curative treatment after their cancer had spread to other areas of their bodies. A new study indicates that, if that cancer has only spread to the para-aortic lymph nodes, aggressive treatment in the form of extended-field radiation therapy may be able to enhance their long-term survival.
“‘Stage IV’ cancer is not one size fits all,” explained lead author Emma B. Holliday, MD, an assistant professor in the department of radiation oncology at the University of Texas MD Anderson Cancer Center in Houston. “There are emerging data in a number of cancer types where aggressive treatment of metastatic disease can improve survival.
“While the involvement of the para-aortic nodes is metastatic disease in squamous cell carcinoma of the anal canal, we have long suspected that these patients do not share the poor prognosis that is associated with a stage IV diagnosis in other malignancies,” she stated. “The findings of this study were that aggressive combination therapy with definitive extended-field chemoradiation can result in good outcomes.”
It is not unusual for SCC to metastasize to the pelvic and inguinal nodes prior to extending on to the para-aortic (PA) nodes. Holliday reported that her findings were consistent with what has been observed in other studies of SCC of the cervix patients who had been staged as IV based on metastasis to the para-aortic nodes.
In this case-control retrospective analysis, Holliday and colleagues reviewed long-term results for 30 patients treated with curative-intent, extended-field chemoradiation — combined chemotherapy and radiation therapy — from September 2002 to February 2016 at the University of Texas MD Anderson Cancer Center in Houston and the Mayo Clinic in Rochester, Minnesota.
During the course of the study, external beam radiation therapy methods changed. Thus, some patients were treated with 3D conformal methods in the initial period of the study and a few were treated with intensity modulated proton therapy in the subsequent periods. The majority of patients were treated with IMRT, however. For chemotherapy regimens, patients were treated with either six weekly cycles of cisplatin with 5-fluoruracil/capecitabine (5-FU), two cycles of mitomycin-C with 5-FU or daily capecitabine.
At 3.1 years of follow-up, 18 of 30 patients were alive and 17 had no evidence of anal cancer. The rate of overall survival was 67 percent (95% CI 49-89), and the rate of disease-free survival was 42 percent (95% CI 25-69). Cancer recurred in 15 patients (50 percent), mostly as distant metastases.
No patients succumbed to side effects of the aggressive combination therapy. The therapies were well tolerated, although patients who receive chemoradiation therapy for anal cancer inevitably develop severe (grade 3-4) hematologic side effects, such as loss of white and red blood cells, heightened risk of infection and loss of blood platelets; gastrointestinal side effects, such as nausea, vomiting, diarrhea and loss of appetite; and/or skin reactions. Six (20 percent) of these patients developed severe hematologic complications, nine (30 percent) developed severe gastrointestinal side effects and eight (27 percent) developed severe skin reactions.
I think we do know that patients with metastases in the para-aortic nodes can be curable because the para-aortic nodes are the next echelon after what we would consider regional nodes in the pelvis,” Holliday said. “Most importantly, if we can deliver a curative dose of radiation to all the sites of disease, we have the potential to improve survival in these patients.”.
IMRT increases ability to complete cycles of treatment, decreases need for breaks and additional surgery
Another recent study in the Red Journal examined how advancements in radiation therapy technology have translated into fewer side effects and treatment interruptions in patients with locally advanced anal cancer. This retrospective analysis of a large clinical database found that a technologically advanced type of radiation, IMRT, had the potential to reduce toxicities for anal canal cancer patients receiving radiation.
“By comparing radiation side effects in veterans with anal cancer who were treated with IMRT to older radiation therapy, based on data from the national Veterans Affairs health system, we found significant benefits of IMRT, including lowering the rate of treatment breaks and improving rates of chemotherapy completion,” said lead author Alex K. Bryant, MD, a resident physician at the University of California, San Diego, School of Medicine department of radiation medicine and applied sciences.
IMRT is an advanced type of radiation therapy that sends photon or proton radiation beams into the geometry of the tumors to be irradiated, in order to decrease exposure to the surrounding healthy tumor tissues.
Bryant and his team identified 779 patients in a national Veterans Affairs database who had been diagnosed with locally advanced anal SCC between 2000 and 2015. The patients had been treated with conventional radiation therapy (n=403) or IMRT (n=376), both with concurrent chemotherapy. The adoption of IMRT increased substantially during the study period; no patients received IMRT prior to 2004, compared to 89 percent of patients treated from 2012 to 2015.
The researchers found that patients treated with IMRT were 42 percent less likely to require a break from radiation treatment of more than five days. IMRT patients also had a 40 percent lower risk of needing ostomy surgery related to cancer progressing or recurring.
IMRT patients were also more likely to get and finish two cycles of standard chemotherapy. Together, 19 percent (n=63) of IMRT patients were unable to finish two cycles of chemotherapy, compared to 43 percent (n=153) receiving conventional radiotherapy. The association between IMRT and completing standard chemotherapy remained significant after patient and tumor factor adjustment.
We were surprised that IMRT permitted more patients to receive the entire course of chemotherapy,” Bryant said. “Earlier studies have established that the combination of chemotherapy and radiation therapy is extremely significant in curing anal cancer, and we were hopeful that IMRT permitted more patients to receive this potentially life-saving treatment.”.
Authors have discovered no difference in short-term severe hematologic or gastrointestinal toxicity or long-term survival results in the two study arms of radiotherapy. Less severe toxicities were not evaluated in the trial.
“Although we could not ascertain why we perceived an advantage to finishing therapy, one hypothesis is that IMRT reduced toxicities we could not measure, such as dermatologic toxicity and lower grades of gastrointestinal and hematologic toxicity, and that allowed more patients to finish chemotherapy,” Bryant said. “It would require more study to know whether there is a relationship between a reduction in those toxicities and chemotherapy completion. If that’s true, that would be a great secondary effect of IMRT and of considerable interest to patient outcomes.”
Source: AMERICAN SOCIETY FOR RADIATION ONCOLOGY
