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Hypofractionated radiation therapy offers shorter treatment for poor-performance NSCLC
The use of accelerated hypofractionated radiation therapy produced equivalent OS and PFS outcomes as conventional radiation therapy in patients with non–small cell lung cancer who were not considered candidates for standard-of-care therapy, according to an interim analysis of a phase 3 trial presented at the ASTRO Annual Meeting.
However, accelerated hypofractionated radiation therapy resulted in fewer high-grade toxicities and reduced treatment time by half, results showed.
“The standard of care for a patient with stage III NSCLC is to receive concurrent chemotherapy and radiation,” Puneeth Iyengar, MD, PhD, assistant professor of radiation oncology at University of Texas Southwestern at Dallas, said during a press conference. “For patients with stage II disease, the standard of care is surgery. However, there is a distinct population within these two groups who cannot receive standard-of-care surgery or chemoradiation due to existing medical comorbidities.”
Iyengar and colleagues first conducted a phase 1 dose-escalation study, which showed a 3-week hypofractionated course of radiation therapy did not increase toxicities compared with conventional chemotherapy and radiation.
The current phase 3 study included data from 60 patients (median age, 68 years; stage II, n = 7; stage III, n = 53) who had poor performance–status disease and, thus, were not candidates for standard of care for their disease stage. Fifty-three percent of patients had squamous cell carcinoma, and 47% had adenocarcinoma.
Researchers randomly assigned patients to 60 Gy of radiation therapy, given in 30 to 33 treatments over the course of 6 weeks (arm A; n = 28) or in 15 treatments over the course of 3 weeks (arm B; n = 32).
OS served as the primary endpoint. Secondary endpoints included toxicity, PFS, quality of life and cost-effectiveness.
The researchers permitted patients to receive sequential chemotherapy before or after radiation therapy; however, due to their performance status, they could not receive concurrent chemotherapy.
The interim analysis included data from 48 patients, of whom 56% (n = 27) were alive at the most recent follow-up.
Patients evaluable for the interim analysis had a median OS of 14 months and a median PFS of 11.5 months. The researchers observed no statistical differences in survival between the treatment arms.
The researchers observed three deaths caused by hypoxia (arm A, n = 2; arm B, n = 1) which potentially could be linked to treatment.
Ten grade 3 toxicities occurred in arm A and six occurred in arm B. The researchers did not observe any grade 4 toxicities attributable to radiation.
“We would hope that the completion of this study would eventually change the paradigm of how we treat patients who cannot receive their standard of care,” Iyengar said. – by Cameron Kelsall
Reference:
Iyengar P, et al. Abstract 3110. Presented at: ASTRO Annual Meeting; Sept. 25-28, 2016; Boston.
Disclosure: Iyengar reports no relevant financial disclosures. One researcher reports honoraria from Varian and stock in Global Oncology. Another researcher reports honoraria from Varian and scientific advice to D3 Corporation.
Perspective
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This is a preliminary interim analysis, but its timing is important. This trial is a form of treatment intensification, because the patients are receiving a similar amount of Gy in a shorter period of time. Based on other data in the lung cancer literature, we need to make sure that survival outcomes, as well as the toxicity outcomes, are similar before the completion of the trial. This analysis does so quite effectively.
From a patient perspective, there are those who cannot receive standard-of-care treatment because of comorbidities, but there is another population that just does not want chemotherapy. For many of our patients, travel is an issue as well, so this might be to their advantage. I look forward to the completion of this trial.
Perspective
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Non–small cell lung cancer remains the number-one cause of cancer-related mortality in the United States. A majority of patients are diagnosed with advanced-stage disease. Many patients with lung cancer also have other health problems caused in part by risk factors common to lung cancer, such as aging and smoking. Patients with particularly failing health are considered to have poor performance status.
For patients with NSCLC that remains localized but not amenable to surgery, radiation is potentially curative and is the standard primary treatment. Patients with more advanced disease, including large invasive tumors and spread to regional lymph nodes, are at greater risk for treatment failure, development of metastatic disease and death of lung cancer. Therefore, these patients classified as having stages II and III disease receive a combination of radiation delivered over 6 weeks in daily treatments of 2 Gy along with chemotherapy. A significant portion of patients with NSCLC have poor performance status and cannot receive chemotherapy. These patients have a particularly poor prognosis due to increased rates of treatment failure.
For patients with stage II and III NSCLC with poor performance status, increasing the intensity of radiation may improve outcomes. One approach to intensify radiation is to deliver higher daily doses of radiation, termed hypofractionated radiation therapy. A representative hypofractionated regimen is 60 Gy delivered in 4 Gy daily treatments over 3 weeks. Hypofractionated radiation is proposed to improve disease control and survival compared with standard radiation delivery. A major obstacle in using hypofractionated radiation for lung cancer is the potential for more severe and even life-threatening side effects associated with intensified radiation. Advanced radiation targeting and delivery technologies promise to improve the safety of hypofractionated radiation therapy to allow its use.
Investigators at University of Texas Southwestern have recently published data demonstrating the safety of hypofractionated radiation therapy for stage II and III NSCLC among patients with poor performance status. They are now conducting a trial at many North American cancer institutions among patients with stage II and III NSCLC with poor performance status comparing survival following standard delivery of 60 Gy radiation over 6 weeks to hypofractionated radiation of 60 Gy in 3 weeks. Researchers have enrolled 60 patients on this trial, with half receiving each regimen.
Iyengar and colleagues reported the interim analysis of this study from 48 enrolled patients. Importantly, researchers have found that hypofractionated radiation therapy was well-tolerated and demonstrated side effects similar to conventional radiation. Survival outcomes are too early to report, but do not yet appear to be different between the regimens.
The investigators conclude that, once completed, this trial will establish hypofractionated radiation therapy as the standard of care for these patients with poor performance status. Although any potential survival benefit remains to be seen, hypofractionated radiation would halve the necessary treatment time and lower treatment costs. This in itself would be a significant improvement in value and accessibility of radiation therapy for these patients, and the final results of this trial will be eagerly anticipated.
