Prophylactic cranial irradiation after chemotherapy significantly reduces the risk of brain metastasis and doubles one-year survival in small-cell lung cancer (SCLC), according to the results of the multicenter phase III randomized EORTC trial 08993-22993, published in the New England Journal of Medicine August 16.
Small cell lung cancer (SCLC) is an aggressive tumor that constitutes nearly 15% of all newly diagnosed lung cancers. The majority of patients with SCLC present with extensive disease (ED) at diagnosis, meaning that the cancer has spread to other areas of the body. Without treatment, consisting of chemotherapy, the median survival is two to four months. Despite treatment, in most patients, disease progression will lead to dead within one year. Cancer spreading to the brain is an important cause of death and has a profound negative effect on psychological and physical functioning.
Studies conducted primarily in the 1980 had shown that for patients with limited SCLC and complete response to chemotherapy, prophylactic brain irradiation reduced the risk of brain metastasis and improved survival.
In the EORTC 08993-22993 study, Ben Slotman, MD, PhD, Professor of Radiation Oncology at the VU University medical center in Amsterdam, and his European colleagues from the EORTC Radiation Oncology and Lung Cancer Groups extended the use of prophylactic cranial irradiation (PCI) to patients with extensive SCLC. 286 patients were randomized to either receive prophylactic irradiation or to being observed, following four to six cycles of chemotherapy that induced a response of their SCLC.
One year after being randomized in the trial, only 14.4 % of the patients that received PCI suffered from symptomatic spread of their cancer to the brain, compared with 40.4 % of the patients who did not receive PCI. Moreover, 27.1% of the patients receiving PCI were alive after one year, compared with 13.3% of the patients who were not prophylactically irradiated.
"Prophylactic cranial irradiation significantly reduces the risk of symptomatic brain metastases and significantly prolongs survival" according to Prof Slotman. "As this treatment is well tolerated and does not adversely influence quality of life, prophylactic cranial irradiation should now routinely be offered to all SCLC patients with extensive disease whose cancer responds to chemotherapy."
For Roy S Herbst, MD, PhD, Professor of Medicine in the Department of Thoracic/Head and Neck Medical Oncology, University of Texas/Section Chief of Thoracic Medical oncology at the MD Anderson Cancer center in Houston, Texas, the results of this study represented the most important clinical finding for the treatment of patients with lung cancer presented at ASCO 2007 in June this year. "I expect prophylactic cranial irradiation will be taken up quickly in the US, as well" he commented in an interview during ASCO 2007.
"Furthermore, this trial was impressive because it showed that a standard modality, such as radiation therapy, still has the potential to improve survival. In this era of targeted therapies, we cannot forget that standard modalities can still improve disease outcomes." he adds.
Moreover, the trial results give weight to the further research hypothesis that thoracic radiotherapy - using the nowadays advanced radiotherapy techniques - might be beneficial to this pretreated patient group as well - a hypothesis Prof Ben Slotman and colleagues are preparing to test in clinical randomized trial to run in The Netherlands, the UK and possibly more European countries.
"The challenge in the future remains how to integrate the current modalities with the newer targeted modalities. This EORTC trial shows once again that in clinical cancer research, pursuing a multidisciplinary research agenda can be crucial for improving patient survival." explains Françoise Meunier, MD, PhD, Director General of the EORTC.
Reference: Slotman, B.; Faivre-Finn, C. (2007). Prophylactic Cranial Irradiation in Extensive Small-Cell Lung Cancer. NEJM 357: 664-672.
Materials provided by European Organisation for Research and Treatment of Cancer. Note: Content may be edited for style and length.
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