News | Radiation Therapy | October 23, 2015

Involved Field Irradiation Therapy Reduces Toxicity for Locally Advanced Esophageal Cancer

Chinese trial finds more targeted radiotherapy reduces side effects for patients without negatively impacting recurrence or survival rates

October 23, 2015 — For patients with locally advanced esophageal cancer that has spread to the lymph nodes, radiation therapy (RT) targeting only the involved lymph nodes regions results in less toxicity without statistically significant differences in loco-regional lymph nodal recurrence, distant failure and overall survival rates, according to new research. Study findings were presented at the American Society for Radiation Oncology’s (ASTRO’s) 57th annual meeting.

The American Cancer Society estimates that while esophageal cancer makes up approximately one percent of all cancers diagnosed in the United States, it is far more prevalent in China, where esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in China. Many patients with ESCC are not diagnosed until the cancer is in an advanced stage.

Chemoradiation (the combination of chemotherapy and radiation therapy) is a standard treatment for locally advanced esophageal cancer. Elective nodal irradiation (ENI)—RT to the tumor and lymph nodes, including uninvolved lymph nodes in the region around the cancerous tumor—is a common form of RT used to treat ESCC. The use of ENI has been controversial due to increased level of irradiation and possible toxicity. This study evaluated the feasibility of reducing the nodal irradiation volume of RT by comparing ENI to involved-field irradiation (IFI)—RT that involves only the regions where the lymph nodes are located.

The prospective, randomized controlled clinical trial included 110 patients with esophageal cancer enrolled from nine cancer centers across China between April 2012 and November 2014. The patients had inoperable, newly diagnosed stage II – stage III thoracic ESCC.

Patients were treated with concurrent chemoradiotherapy and all of the patients received docetaxel (75 mg/m2 on day one) and CDDP (25 mg/m2 on days one-three) every 21 days for two to four cycles. The patients received image-guided radiation therapy (IGRT) in once-daily fractions of 1.8-2Gy to a total dose of 60-66 Gy to the gross tumor volume (GTV) and 50-54 Gy to the clinical target volume (CTV). The patients were randomly divided into two groups; 56 patients received elective nodal irradiation (the ENI group); and 54 patients received involved-field irradiation (the IFI group).

The primary endpoints of the study were toxicities (side effects) and loco-regional lymph nodal recurrence (indicating the cancer had returned to the area and nearby lymph nodes). The secondary end points were distant failure and overall survival (OS).

At a median follow-up of 20 months, data showed that IFI resulted in significantly decreased radiation pneumonitis (inflammation of the lungs) and radiation esophagitis (inflammation of the lining of the esophagus). Grade = 2 radiation pneumonitis in the ENI group was 26.8 percent, compared to 12.9 percent in the IFI group (p = 0.011); and the rate of radiation esophagitis was 37.5 percent in the ENI group compared to 20.4 percent in the IFI group (p = 0.001).

No significant differences in the loco-regional lymph nodal recurrence rate were observed between the two groups. The ENI group experienced a 17.9 percent loco-regional lymph nodal recurrence, compared to the IFI group, which experienced a 20.4 percent loco-regional lymph nodal recurrence (p = 0.819).

Evaluation of distant failure rates (measurement of whether the cancer appeared in other areas other than the original tumor site), indicated a positive result with no difference between the two groups. The ENI group had a 12.5 percent distant failure rate and the IFI group had a 13 percent distant failure rates (p = 0.465).

The two groups achieved similar one-year and two-year OS rates.  The one-year OS rate was 89.2 percent for the ENI group and 88.3 percent for the IFI group (p = 0.431); and the two-year OS rates was 64.2 percent for the ENI group, compared to 55.6 percent for the IFI group (p = 0.857).

“Elective nodal irradiation is the most commonly used type of RT for treating esophageal cancer, but its side effects and toxicity have been criticized,” said Tao Li, M.D., Ph.D., lead author of the study and vice chairman of the department of radiation oncology at Sichuan Cancer Hospital and Institute. “Researchers have suggested decreasing the nodal irradiation volume with the use of IFI, yet prior to this study its potential advantages had only been measured in smaller trials. We anticipated that IFI could significantly decrease toxicity such as radiation pneumonitis and radiation esophagitis, but were initially uncertain if IFI might increase the loco-regional lymph nodal recurrence rates, distant failure and overall survival. The mid-term results of our trial show that IFI is an acceptable and toxicity-minimizing method of treatment for thoracic ESCC. This is a significant discovery for future esophageal cancer radiotherapy care.”

For more information: www.astro.org

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