Pre-treatment prognostic factors in patients with Stage III non-small cell lung cancer treated with hyperfractionated radiation therapy with or without concurrent chemotherapy

doi:10.1016/0169-5002(95)00480-O

Lung Cancer

Volume 13, Issue 1, August 1995, Pages 21-30

https://doi.org/10.1016/0169-5002(95)00480-O Get rights and content

Abstract

We analyzed prognostic factors for non-small cell lung cancer (NSCLC) treated with hyperfractionated radiotherapy (HFX RT) with or without concurrent chemotherapy. Onehundred sixty-nine patients with histologically or cytologically proven, Stage III NSCLC, Karnofsky performance status (KPS) ≥ 50, and no previous therapy were treated in a randomized trial as follows: Group 1—HFX RT to a total dose of 64.8 Gy (61 patients); Group 2—the same HFX RT with chemotherapy consisting of 100 mg of carboplatin on days 1 and 2 and 100 mg of etoposide on days 1–3 of each week during the RT course (52 patients); and Group 3—the same HFX RT with chemotherapy consisting of 200 mg of carboplatin on days 1 and 2 and 100 mg of etoposide on days 1–5 of the first, third, and fifth weeks of the RT course (56 patients). The median survival time for all 169 patients was 13 months and the 5-year survival rate was 13.4%. The median time to relapse (local or distant) was 11 months and the 5-year relapse-free survival was 12.8%. Group 2 patients had a better prognosis than Group 1 patients (P = 0.0028) but there were no differences in prognosis between Groups 2 and 3 and between Groups 1 and 3. Of potential prognostic factors examined, female gender (P = 0.00012), age ≥ 60 (P = 0.00000), KPS ≥ 80 (P = 0.00000), Stage IIIA (P = 0.00000), and previous weight loss ≤ 5% (P = 0.00000) were associated with better prognosis. These findings were confirmed by multivariate analysis.

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SFNEP oncology nutrition guidelines: When and how to assess the nutritional status? How to diagnose undernutrition and severe undernutrition? Which situations are most at risk for undernutrition?
2012, Nutrition Clinique et Metabolisme
Population-based estimates of survival benefit associated with combined modality therapy in elderly patients with locally advanced non-small cell lung cancer
2011, Journal of Thoracic Oncology
Citation Excerpt :
In contrast, subset analyses of several trials have found benefits associated with CMT for the elderly. These include a study by Langer et al.26 that evaluated an elderly subset from a trial comparing CMT-SEQ with CMT-ONLY (RTOG 9410) and a study by Jeremic and Shibamoto27 comparing effects of hyperfractionated radiotherapy with or without chemotherapy. Socinski et al.28 examined results from five Cancer and Leukemia Cooperative Group B trials and concluded that age was not an independent predictive factor of outcome.
Combined modality therapy (CMT; radiation and chemotherapy) is indicated for fit, elderly patients with inoperable, locally advanced non-small cell lung cancer. We used population level data to examine effects of CMT on survival.
Medicare patients who are 66 years or older with locally advanced non-small cell lung cancer (stages IIIA and IIIB without pleural effusion) from 1997 to 2002 were identified in Surveillance Epidemiology and End Results-Medicare. Detailed insurance claims were used to characterize treatment modality (none, chemotherapy only, radiotherapy only [XRT-ONLY], or CMT). CMT was further categorized as sequential (CMT-SEQ), or concurrent chemoradiation alone (CMT-ONLY), with induction (CMT-IND), or with consolidation chemotherapy (CMT-CON). Nonparametric models estimated survival effects of treatment regimens, controlling for patient characteristics, including claims-based indicators of performance status. Propensity score analysis adjusted for treatment selection.
Of the 6325 patients, 66% received therapy, with 41% (N = 1745) receiving XRT-ONLY and 45% (N = 1909) receiving CMT (12.5% CMT-SEQ, 35.3% CMT-ONLY, 11.3% CMT-IND, and 20.3% with CMT-CON). CMT had a survival benefit relative to XRT-ONLY (hazard ratio: 0.782, 95% confidence interval: 0.750–0.816; additional 4.4 months median survival; adjusted 10.7% increase in 1-year survival). Relative to CMT-SEQ, concurrent CMT-ONLY was associated with an increased mortality risk, whereas CMT-IND regimens provided a survival benefit (hazard ratio: 0.731, 95% confidence interval: 0.600–0.891; additional 3.8 months; and adjusted 14.4% increase in 1-year survival).
Survival benefits associated with CMT in clinical trials can extend to the elderly in routine care settings. CMT-ONLY is associated with the greatest mortality risk, suggesting that more gradual strategies (CMT-IND) may be more appropriate for the elderly population.
Palliative thoracic radiotherapy in locally advanced non-small cell lung cancer: Can quality-of-life assessments help in selection of patients for short- or long-course radiotherapy?
2006, Journal of Thoracic Oncology
Citation Excerpt :
In our multivariate analyses, appetite loss emerged as the most significant independent indicator for survival in this cohort of patients, whereas Karnofsky PS and weight loss did not reach significance. This finding was surprising because the prognostic significance of PS on survival is well documented in localized stage III disease.29–31 On the other hand, HRQOL items have been evaluated to a much lesser extent as prognostic factors in NSCLC.
Patient-assessed health-related quality-of-life (HRQOL) scores, together with demographic and clinical factors in stage III non-small cell lung cancer (NSCLC) patients, are important prognostic factors for survival and may be helpful in determining thoracic radiotherapy (TRT) strategy.
In a previously published randomized trial, 301 patients were treated with different palliative radiotherapy schedules, comparing short-term hypofractionated TRT (arm A: 17 Gy/2 fractions [n = 105]) with more protracted TRT (arm B: 42 Gy/15 fractions [n = 104]); arm C: 50 Gy/25 fractions [n = 92]). Baseline HRQOL, demographic, and clinical data were available for all patients. All possible prognostic factors from univariate analysis were entered into the Cox multivariate regression model to identify variables of independent prognostic relevance.
Overall survival was similar, whereas long-term survival was restricted to higher-dose radiotherapy with 3-year survival rates of 1, 8, and 6% (p = 0.40) and 5-year survival rates of 0, 4, and 3% (p = 0.12) in arms A, B, and C, respectively. In univariate analysis, Karnofsky performance status, use of analgesics, and weight loss were highly significant non-HRQOL factors (p < 0.001), and physical function, appetite loss, cough, and pain were the most powerful HRQOL factors (p < 0.001). In multivariate analysis, appetite loss appeared as the most powerful independent prognostic indicator. In the group of patients treated with protracted fractionation (n = 196), the 2-, 3-, and 5-year survival rates in patients with no appetite loss (n = 95) were 22% (21/95), 12% (11/95), and 8% (8/95) compared with 3% (3/101), 1% (1/101), and 1% (1/101) in patients with appetite loss present at baseline (n = 101).
In addition to performance status and weight loss, patient-reported appetite loss should be assessed in stage III NSCLC patients before administrating TRT; such assessment is a valuable tool for selecting patients to normofractionated or lower-dose hypofractionated palliative TRT.
Post-chemotherapy gross tumor volume is predictive of survival in patients with stage III non-small cell lung cancer treated with combined modality therapy
2006, Lung Cancer
To evaluate the influence of clinical covariates, particularly pre-chemotherapy gross tumor volume (GTV), post-chemotherapy GTV, on overall survival in the treatment of stage III non-small cell lung cancer (NSCLC).
We retrospectively analyzed 102 patients who were enrolled on three consecutive clinical trials, which employed the treatment paradigm of two cycles of induction chemotherapy followed by thoracic radiation therapy. The pre-chemotherapy GTV, post-chemotherapy GTV, change in GTV, histology, disease stage, performance status, age, race, treatment with concurrent chemoradiotherapy versus radiotherapy alone were evaluated to determine their impact on overall survival. The log₁₀ of the GTV was used to normalize the data and thereby reduce the impact of exceptionally large values.
Both the log₁₀ of the post-chemotherapy GTV and Eastern Cooperative Oncology Group (ECOG) performance status covariates were highly prognostic for overall survival (p = 0.006 and p = 0.008, respectively). Disease stage (at diagnosis) was also significant (p = 0.048). The log₁₀ pre-chemotherapy GTV covariate was borderline significant (p = 0.067). The strongest prognostic model was the two-covariate model, which contained the log₁₀ post-chemotherapy GTV and ECOG performance status covariates, (model χ² of 18.67, with p = 0.001 for each covariate).
The log₁₀ post-chemotherapy GTV has significant prognostic survival value when the strategy of induction chemotherapy is employed in the treatment on stage III NSCLC. ECOG performance status and stage were also significant prognostic factors for survival.
Multivariate analysis of survival, local control, and time to distant metastases in patients with unresectable non-small-cell lung carcinoma treated with 3-dimensional conformal radiation therapy with or without concurrent chemotherapy
2005, Clinical Lung Cancer
BACKGROUND: Three-dimensional (3D) conformal radiation therapy (CRT) and chemotherapy have recently improved lung cancer management. PATIENTS AND METHODS: We reviewed outcomes in 68 patients with unresectable stage I-III non–small-cell lung cancer. Treatment consisted of 3D CRT alone or with concurrent chemotherapy (CCR). RESULTS: Concurrent chemotherapy improved survival, to a median of 17 months ± 4.9 months, compared with 8 months ± 4.1 months for the radiation therapy (RT) alone group (P = 0.0347). The 2- and 5-year survival rates were 40.3% ± 7.7% and 14.1% ± 6.4%, repectively, with CCR, compared with 19.6% ± 9.6% and 0, respectively, for RT alone. In a subgroup analysis for age > 65, patients who received CCR (n = 20) had significantly improved survival and local control (P = 0.005 and P = 0.0286, respectively). Acute esophageal toxicity Radiation Therapy Oncology Group grade ≤ 3 was significantly higher in the CCR group and correlated with the RT dose (19% in CCR vs. 0 in RT, P = 0.0234; P = 0.050). The overall incidences of esophageal and pulmonary toxicity grade ≤ 3 were 20.6% and 5.9%, respectively. CONCLUSION: Our study confirms that CCR is associated with improved survival over RT alone, with a tolerable increase in acute toxicity.
Combined modality trials of the cancer and leukemia group B in stage III non-small-cell lung cancer: Analysis of factors influencing survival and toxicology
2004, Annals of Oncology
Citation Excerpt :
The analysis of prognostic factors in NSCLC has been useful in defining subsets of patients with differing survival outcomes. Most of the prognostic information previously published in stage III NSCLC has predominantly analyzed patients treated with TRT alone [20-24], although recent reports include increasing numbers of patients treated with CMT [25-29]. Some of these analyses have yielded conflicting information [26, 27].
Background: Combined modality therapy (CMT) is the standard of care for patients with unresectable stage III non-small-cell lung cancer (NSCLC); however, insufficient data are available regarding prognostic factors in this disease setting.
Patients and methods: Six hundred and ninety-four patients included in five trials conducted by the Cancer and Leukemia Group B evaluating CMT in stage III NSCLC were included in this analysis. The primary objective was to identify factors that were predictors of survival and selected radiation-related toxicities using Cox regression models and logistic regression analysis.
Results: The Cox model shows that performance status (PS) 1 [hazard ratio (HR) 1.24; 95% confidence interval (CI) 1.06–1.45; P=0.009] and thoracic radiation therapy (TRT) only (HR 1.58; 95% CI 1.22–2.05; P=0.001) predicted for poorer survival, while baseline hemoglobin ≥12 g/dl predicted for improved survival (HR 0.67; 95% CI 0.55–0.81; P ≤0.0001). Multivariate logistic regression showed an increase of grade 3 + esophagitis among patients with PS 0 [odds ratio (OR) 1.7; 95% CI 1.1–2.7; P=0.029), >5% weight loss (OR 2.9; 95% CI 1.3–6.6; P=0.008) and patients receiving concurrent chemoradiation (OR 7.3; 95% CI 3.4–15.6; P=0.0001).
Conclusions: Baseline hemoglobin and PS, as well as the use of CMT, have the greatest effect on survival in unresectable stage III NSCLC. The use of concurrent chemoradiation increases the risk of esophagitis, which remains the primary radiation-related toxicity.

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Original articlePre-treatment prognostic factors in patients with Stage III non-small cell lung cancer treated with hyperfractionated radiation therapy with or without concurrent chemotherapy

Abstract

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

J Thorac Cardiovasc Surg

Int J Radiat Oncol Biol Phys

Ann Thorac Surg

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Ann Thorac Surg

A randomized phase III trial of hyperfractionated radiation therapy with total doses of 60.0 Gy to 79.2 Gy: possible survival benefit with ≥69.6 Gy in favorable patients with Radiation Therapy Oncology Group Stage III non-small cell lung carcinoma: report of Radiation Therapy Oncology Group 83-11

J Clin Oncol

Comparison of Radiation Therapy Oncology Group and American Joint Committee on Cancer Staging Systems among patients with non-small cell lung cancer receiving hyperfractionated radiation therapy. A report of the Radiation Therapy Oncology Group protocol 83-11

Cancer

Original article
Pre-treatment prognostic factors in patients with Stage III non-small cell lung cancer treated with hyperfractionated radiation therapy with or without concurrent chemotherapy