Results of combined-modality therapy for limited-stage small cell lung carcinoma in the elderly.

BACKGROUND: A Phase III trial was conducted by the North Central Cancer Treatment Group to determine whether chemotherapy (etoposide and cisplatin) plus either twice-daily radiotherapy (BIDRT) or once-daily radiotherapy (QDRT) resulted in a better outcome for patients with limited-stage small cell lung carcinoma (LD-SCLC). No difference in survival was identified between the two arms. The current analysis examined the relation between age and outcome for patients treated during this trial. METHODS: The current study included 263 patients with LD-SCLC and an Eastern Cooperative Oncology Group performance status of < or = 2 who were randomized to receive QDRT or split-course BIDRT. The outcomes of the 209 (79%) younger patients (age < 70 years old) were compared with the 54 (21%) elderly patients (age > or = 70 years old). RESULTS: Elderly patients presented with significantly greater weight loss and poorer performance status. The 2-year and 5-year survival rates were 48% and 22% for younger patients compared with 33% and 17% for older patients (P = 0.14). One specific toxicity (i.e., Grade > or = 4 pneumonitis [according to National Cancer Institute Common Toxicity Criteria]) occurred in 0% of those patients age < 70 years compared with 6% of older patients (P = 0.008). Grade 5 toxicity occurred in 1 of 209 (0.5%) patients age < 70 years compared with 3 of 54 (5.6%) older patients (P = 0.03). CONCLUSIONS: Despite having more weight loss, poorer performance status, increased pulmonary toxicity, and more deaths due to treatment, survival was not found to be significantly worse in older individuals. Fit elderly patients with LD-SCLC can receive combined-modality therapy with the expectation of relatively favorable long-term survival. Future research should focus on ways to decrease toxicity especially in the elderly.

Long-term results of a phase III trial comparing once-daily radiotherapy with twice-daily radiotherapy in limited-stage small-cell lung cancer.

PURPOSE: This Phase III study was performed to determine whether twice-daily (b.i.d.) radiotherapy (RT) resulted in better survival than once-daily (q.d.) RT for patients with limited-stage small-cell lung cancer (LD-SCLC). METHODS AND MATERIALS: A total of 310 patients with LD-SCLC initially received three cycles of etoposide and cisplatin. Subsequently, the 261 patients without significant progression were randomized to two cycles of etoposide and cisplatin plus either q.d. RT (50.4 Gy in 28 fractions) or split-course b.i.d. RT (24 Gy in 16 fractions, a 2.5-week break, and 24 Gy in 16 fractions) to the chest. Patients then received a sixth cycle of etoposide and cisplatin followed by prophylactic cranial RT. RESULTS: Follow-up ranged from 4.6 to 11.9 years (median, 7.4 years). The median survival and 5-year survival rate from randomization was 20.6 months and 21% for patients who received q.d. RT compared with 20.6 months and 22% for those who received b.i.d. RT (p = 0.68), respectively. No statistically significant differences were found in the rates of progression (p = 0.68), intrathoracic failure (p = 0.45), in-field failure (p = 0.62), or distant failure (p = 0.82) between the two treatment arms. No statistically significant difference was found in the overall rate of Grade 3 or worse (p = 0.83) or Grade 4 or worse toxicity (p = 0.95). Grade 3 or worse esophagitis (p = 0.05) was more common in the b.i.d. arm. Grade 5 toxicity occurred in 4 (3%) of 130 patients who received b.i.d. RT compared with 0 (0%) of 131 who received q.d. RT (p = 0.04). CONCLUSION: Although this study did not demonstrate an advantage to split-course b.i.d. RT, the long-term survival was favorable, likely reflecting the positive influences of concurrent combined modality therapy and prophylactic cranial RT.

A new graphic for quality adjusted life years (Q-TWiST) survival analysis: the Q-TWiST plot.

One of the challenges of interpreting a Quality-adjusted time without symptoms of disease and toxicity (Q-TWiST) analysis is examining the sensitivity of conclusions that may be drawn to varying values of the utility coefficients for days with toxicity and days after disease progression. We present a graphic that parsimoniously displays the impact on median Q-TWiST survival across treatment groups of varying values of the utility coefficients. The goal of the graphic is to present a concise Q-TWiST analysis. We use Zhao and Tsiatis (Biometrika 1997; 84(2): 339-348) to adjust for the bias in Kaplan-Meier (K-M) estimates. The graphic contains bounds that approximate points for which statistical significance would be achieved by comparing the median Q-TWiST survival between treatment alternatives for each value of the utility coefficients. The plot may be generalized to compare Q-TWiST means, medians or percentiles across treatment groups. We demonstrate the application of the Q-TWiST plot through a re-analysis of a randomized phase III North Central Cancer Treatment Group (NCCTG) clinical trial of recombinant Interferon-2alpha in patients with malignant melanoma. We explore alternative options to customize the graphic representation for other data sets drawn from several NCCTG clinical trials.

A quality-adjusted reanalysis of a Phase III trial comparing once-daily thoracic radiation vs. twice-daily thoracic radiation in patients with limited-stage small-cell lung cancer(1).

PURPOSE: We undertook an analysis of quality-adjusted survival using the Q-TWiST (Quality Time Without Symptoms or Toxicity) methodology and developed a new graphic representation called a quality-adjusted life-years plot, which presents a complete and concise Q-TWiST analysis on a single plot. METHODS AND MATERIALS: The Q-TWiST plot incorporates the time without symptoms or toxicity and several combinations of utility coefficients for toxicity and relapse days into the same plot. In addition, the plot includes threshold lines, to judge whether a particular combination of utility coefficients reaches a significance level. RESULTS: The differential in toxicity incidence and severity between the two thoracic radiation treatment arms was inconsequential. Sensitivity analyses were run using Q-TWiST plots. For all combinations of the various toxicity definitions and utility coefficients, the median Q-TWiST was greater for the once-daily thoracic radiation treatment arm than for the twice-daily treatment arm, without achieved significance. CONCLUSION: This work refines the results previously reported for this Phase III clinical trial in patients with limited-stage small-cell cancer, and there was no significant difference in survival after adjusting for toxicity and progression. Furthermore, the new methods developed for this trial allow for a more detailed and parsimonious presentation of survival and toxicity data for all oncology clinical trials.