DOE OSTI2011
Lung cancer remains one of the most prevalent and deadliest malignancies worldwide. For 2008, the International Agency for the Research of Cancer (IARC) estimated 1.6 million new cancer cases of lung cancer (1.095 million in men and 0.514 million in women), with an associated 1.38 million deaths (0.95 million in men and 0.43 million in women). In the United States, lung cancer remained the number one cancer killer for both sexes in 2009, with 219,440 new cases diagnosed overall and an estimated 159,390 deaths. Recent biological and technological advances in lung cancer management notwithstanding, disease recurrence is still the dominant cause of death after initial treatment of lung cancer. This is irrespective of histology (NSCLC vs. small cell cancer), stage (early vs. locally advanced vs. metastatic), or initial treatment (surgery, RT, chemotherapy [CHT] or combinations thereof). Time to recurrence of lung cancer is not predictable, with some failures appearing early and others manifesting years later. Patterns of failure are also not easily anticipated as local (e.g., lung parenchyma, bronchial stump, or chest wall), regional (e.g., mediastinal lymph nodes), or distant (e.g., brain, liver, or bone) recurrences can appear alone or in combination. Whatever the presentation, recurrent lung cancer has historically been judged almost universally fatal as only rarely did efforts at treatment lead to control, let alone cure. More importantly, recurrence is often associated with significant distress requiring substantial supportive treatment. Recurrence leads ultimately to a significant decrease in patient quality of life, making further interventions even more limited. Because of the bleak outcome associated with recurrence, palliative retreatment has nonetheless often been attempted precisely as a means of preventing this decline in quality of life and/or reversing symptoms. However, complicating these attempts at retreatment has been the forms of initial therapy used to manage the lung cancer, the site of recurrence, and the performance of the patient at relapse. All of these have been relevant to the issue of whether the modality used initially for primary treatment could be both safe and effective in the setting of retreatment. That said, some reports in the surgical literature have suggested, for example, that re-resection in the case of local relapses in selected patients who had previous surgery for stage I lung cancer is feasible and effective and could predict for survival compared to providing the patients with supportive care alone. A particular challenge has been the question of the role and safety of thoracic reirradiation for local recurrences in those patients where RT was used as part of their initial management strategy. Thus, it has been generally assumed that once definitive EBRT has been administered further RT cannot be given because it would likely exceed normal tissue tolerances (6), or, if done, thoracic reirradiation could only be a palliative measure, as the expectation was that patients would not survive to experience potential late effects. A 2007 retrospective study by Estall et al. (4) is instructive in regard to rates of chest reirradiation. Of 527 lung cancer patients treated between 1993 and 1996, the authors reported that 279 (53%) patients were treated at least once with RT, with initial treatment being palliative for 79% of patients, definitive for 14% of patients, and adjuvant for 7% of patients. Of these 279 initial cases, 73 (27%) patients subsequently received a second course of RT, 19 (7%) patients had a third RT course, and 6 (2%) patients received a fourth course. Contemporary technological advances in the diagnosis and staging of lung cancer as well as in the delivery of EBRT, along with the increasing primary role of RT in lung cancer care, now raise the question as to the appropriateness of a palliative-only model for dealing with locally recurrent lung cancer. However, in order to appropriately characterize the historic practice relevant to thoracic reirradiation of recurrent lung cancer, we carried out a comprehensive search of the English-language literature to identify and review relevant studies of the use of EBRT in the treatment of locally recurrent cancer. We limited our scope to treatment of NSCLC and excluded other RT modalities such as brachytherapy and stereotactic body radiotherapy (SBRT). The goal of this systematic review was to better inform current practice in order to ultimately generate appropriate future research endeavors in this setting.
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