Elderly patients with stage III lung cancer who are not candidates for chemoradiotherapy may benefit from radiation therapy (RT) alone.
Platinum-based chemotherapy together with RT is the standard treatment for patients diagnosed with locally advanced, stage III non-small cell lung cancer (NSCLC). Chemoradiotherapy may not be suitable for patients older than age 65 who are less fit and have comorbidities, so they are sometimes offered RT alone.
This article, whose principal author was Keith Sigel from the Icahn School of Medicine at Mount Sinai, New York City, reviewed national data from the Surveillance, Epidemiology and End Results (SEER) registry linked to Medicare claims. The authors identified 10,376 patients aged older than 65 years with primary stage III NSCLC who were diagnosed between 1992 and 2007 and had not been treated with chemotherapy. Of these patients, 6,468 (62%) had received RT without chemotherapy. Multiple logistic regression parameters were established as to tumor size and location, stage and histology. Results were published in Lung Cancer (2013;82:266-270, PMID: 24011407).
Complexity of RT was determined by Current Procedural Terminology (CPT) codes, and categorized as simple (simulation and planning of a single treatment with either single portal or parallel opposed portals), intermediate (involving three or more portals or two separate treatment areas) or complex (tangential portals, three or more treatment areas, rotation or arc therapy, complex or custom blocks and/or three-dimensional reconstructed imaging).
The authors found increased overall survival (OS) in the RT versus no-treatment group. Median OS was 9.0 months (95% confidence interval [CI], 8.7-9.3) for patients treated with RT compared with 7.0 months (95% CI, 6.6-7.4) for untreated patients. In all stage III patients, RT showed an improvement in both OS (hazard ratio [HR], 0.87; 95% CI, 0.83-0.91) and lung cancer–specific survival (HR, 0.90; 95% CI, 0.85-0.93), using propensity score–adjusted models. The survival benefit was found to be greatest among those who received high-complexity RT. In these patients, OS was significantly improved (HR, 0.83; 95% CI, 0.76-0.90), as was lung cancer–specific survival (HR, 0.87; 95% CI, 0.79-0.95). However, toxicity and adverse events (AEs), including pneumonitis and esophagitis, were significantly greater in the RT group than in the untreated group. The authors concluded that the risks and benefits of lone RT should be considered and discussed with eligible NSCLC patients in this age group.
Karen L. Reckamp, MD, MS|
Co-Director, Lung Cancer and Thoracic Oncology Program
Associate Professor, Medical Oncology & Therapeutics Research
City of Hope
Recent statistics indicate the probabilities for developing lung cancer for people aged 70 or older are one in 15 for men and one in 20 for women in the United States,1 and the median age at diagnosis is 71 years.2 Furthermore, the incidence and mortality of lung cancer among this age group is expected to continue to rise as the population ages.3 Despite these statistics, older adults are underrepresented in clinical trials,4,5 and the basis for treatment options remains largely from studies performed in younger individuals and subset analyses.
The article by Keith Sigel and his colleagues in Lung Cancer provides a comprehensive evaluation of the use of RT alone in patients over the age of 65 for unresectable stage III NSCLC. They limited the analysis to patients who were not considered candidates for resection, those who did not receive any form of chemotherapy and those unlikely to receive RT. They found an improved survival for those who received RT compared with those who did not (nine vs. seven months, P<0.001). As might be expected, those who received RT had lower comorbidity scores, suggesting decisions to proceed with treatment were based on underlying medical problems. In assessing toxicity, Sigel et al used hospitalization for pneumonitis and esophagitis to identify significant AEs and found higher rates among those who received RT, although overall rates were low (2.2% pneumonitis; 1.1% esophagitis). The analysis confirms the utility of treatment for older adults with lung cancer in a large cohort that represents the general population, and it provides the foundation for further investigation.
Radiation alone has been accepted as definitive therapy for patients with early-stage NSCLC who are not considered surgical candidates,6 but for those with locally advanced disease sufficient evidence establishes that either concurrent or sequential chemoradiation is superior therapy to RT alone for patients younger than age 65.7-9 We also have learned that older individuals benefit from combination therapy despite an increase in toxicities from treatment.10-12 Current planning strategies and the use of newer modalities, such as stereotactic body radiation therapy (SBRT), were not a part of this retrospective study, although increased RT complexity was associated with improved outcomes. In early-stage lung cancer, SBRT is used as an alternative to surgery and is well tolerated by older adults, and its use has led to an increase in treatment in this population.13,14
The study by Sigel and his colleagues only begins to address the level of toxicity that patients experience from RT and does not address potential quality-of-life issues associated with treatments and AEs. Many patients experience side effects from RT, and most receive outpatient treatment for these sequelae. In an aging population, goals of care and quality-of-life discussions are essential to determining appropriate therapy, especially when survival is limited. The complexity associated with treating older adults with NSCLC necessitates our study of cohorts that represent the general population, and database analysis, such as that presented by Sigel et al, often stimulates further studies. In this era of precision medicine, targeting the growing population of older adults to develop optimal multidisciplinary therapeutic options for patients will require specific trials within this group.
- Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11-30, PMID: 23335087.
- Altekruse S, Kosary C, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2007, National Cancer Institute. Bethesda, MD. http://seer.cancer.gov/csr/1975_2007/. Accessed February 7, 2014.
- Blanchard EM, Arnaoutakis K, Hesketh PJ. Lung cancer in octogenarians. J Thorac Oncol. 2010;5:909-916, PMID: 20521358.
- Lewis JH, Kilgore ML, Goldman DP, et al. Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol. 2003;21:1383-1389, PMID: 12663731.
- Hutchins LF, Unger JM, Crowley JJ, et al. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med. 1999;341:2061-2067, PMID: 10615079.
- Gauden SJ, Tripcony L. The curative treatment by radiation therapy alone of Stage I non-small cell lung cancer in a geriatric population. Lung Cancer. 2001;32:71-79, PMID: 11282431.
- Auperin A, Le Pechoux C, Pignon JP, et al. Concomitant radio-chemotherapy based on platin compounds in patients with locally advanced non-small cell lung cancer (NSCLC): a meta-analysis of individual data from 1764 patients. Ann Oncol. 2006;17:473-483, PMID: 16500915.
- Dillman RO, Seagren SL, Propert KJ, et al. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med. 1990;323:940-945, PMID: 2169587.
- Schaake-Koning C, van den Bogaert W, Dalesio O, et al. Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer. N Engl J Med. 1992;326:524-530, PMID: 1310160.
- Langer CJ, Hsu C, Curran WJ, et al. Elderly patients with locally advanced non-small cell lung cancer benefit from combined modality therapy: secondary analysis of Radiation Therapy Oncology Group (RTOG) 94-10 [abstract 1193]. Proc Am Soc Clin Oncol. 2002;21.
- Quoix E, Zalcman G, Oster JP, et al. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011;378:1079-1088, PMID: 21831418.
- Topkan E, Parlak C, Topuk S, et al. Outcomes of aggressive concurrent radiochemotherapy in highly selected septuagenarians with stage IIIB non-small cell lung carcinoma: retrospective analysis of 89 patients. Lung Cancer. 2013;81:226-230, PMID: 23726526.
- Sandhu AP, Lau SK, Rahn D, et al. Stereotactic body radiation therapy in octogenarians with stage I lung cancer. Clin Lung Cancer. 2013 Oct 21 [Epub ahead of print], PMID: 24157245.
- Palma D, Visser O, Lagerwaard FJ, et al. Impact of introducing stereotactic lung radiotherapy for elderly patients with stage I non-small-cell lung cancer: a population-based time-trend analysis. J Clin Oncol. 2010;28:5153-5159, PMID: 21041709.