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Title: Influence of Interfraction Interval on Local Tumor Control in Patients With Limited-Disease Small-Cell Lung Cancer Treated With Radiochemotherapy

Abstract

Purpose: To investigate the influence of interfraction interval (IFI) on local recurrence-free survival (LRFS) in patients with limited-disease small-cell lung cancer (LD SCLC) treated with accelerated hyperfractionated radiotherapy (Acc Hfx RT) and concurrent cisplatin and etoposide (PE). Methods and Materials: A total of 103 patients were treated with either 'early' (Cycle 1) or 'late' (Cycle 4) concurrent Acc Hfx RT/PE. Two daily fractions were nonrandomly given using an IFI of either 4.5-5.0 h ('shorter') (n = 52) or 5.5-6.0 h ('longer') (n = 51). Results: The median LRFS and 5-year LRFS rate for all 103 patients were 52 months and 48%, respectively. Besides gender, Karnofsky performance status, and treatment group, IFI also influenced LRFS, whereas age and weight loss did not. When a multivariate model was used, IFI was marginally insignificant (p = 0.0770) as a predictor of LRFS. In terms of individual treatment groups, IFI was not significant in 'early' Acc Hfx RT/PE but showed a strong trend in a 'late' Acc Hfx RT/PE regimen. Although a shorter IFI led to a higher incidence of high-grade ({>=}3) esophagitis, leukopenia, and infection, a correlation analysis of toxicities with all potential prognostic factors showed that a shorter IFI was not anmore » independent predictor of any acute high-grade toxicity. Conclusion: 'Shorter' IFI had a marginally insignificant influence on LRFS. A strong trend favoring it was observed in patients treated with 'late' concurrent Acc Hfx RT/PE. This may be of interest because it could contribute to further understanding of potential biologic parameters influencing treatment outcome.« less

Authors:
 [1];  [2]
  1. Department of Oncology, University Hospital, Kragujevac (Serbia). E-mail: b.jeremic@iaea.org
  2. Department of Oncology, University Hospital, Kragujevac (Serbia)
Publication Date:
OSTI Identifier:
20951661
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 68; Journal Issue: 2; Other Information: DOI: 10.1016/j.ijrobp.2006.12.008; PII: S0360-3016(06)03632-7; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CARCINOMAS; CHEMOTHERAPY; LEUKOPENIA; LUNGS; MULTIVARIATE ANALYSIS; PATIENTS; RADIOTHERAPY; TOXICITY

Citation Formats

Jeremic, Branislav, and Milicic, Biljana. Influence of Interfraction Interval on Local Tumor Control in Patients With Limited-Disease Small-Cell Lung Cancer Treated With Radiochemotherapy. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.12.008.
Jeremic, Branislav, & Milicic, Biljana. Influence of Interfraction Interval on Local Tumor Control in Patients With Limited-Disease Small-Cell Lung Cancer Treated With Radiochemotherapy. United States. doi:10.1016/j.ijrobp.2006.12.008.
Jeremic, Branislav, and Milicic, Biljana. Fri . "Influence of Interfraction Interval on Local Tumor Control in Patients With Limited-Disease Small-Cell Lung Cancer Treated With Radiochemotherapy". United States. doi:10.1016/j.ijrobp.2006.12.008.
@article{osti_20951661,
title = {Influence of Interfraction Interval on Local Tumor Control in Patients With Limited-Disease Small-Cell Lung Cancer Treated With Radiochemotherapy},
author = {Jeremic, Branislav and Milicic, Biljana},
abstractNote = {Purpose: To investigate the influence of interfraction interval (IFI) on local recurrence-free survival (LRFS) in patients with limited-disease small-cell lung cancer (LD SCLC) treated with accelerated hyperfractionated radiotherapy (Acc Hfx RT) and concurrent cisplatin and etoposide (PE). Methods and Materials: A total of 103 patients were treated with either 'early' (Cycle 1) or 'late' (Cycle 4) concurrent Acc Hfx RT/PE. Two daily fractions were nonrandomly given using an IFI of either 4.5-5.0 h ('shorter') (n = 52) or 5.5-6.0 h ('longer') (n = 51). Results: The median LRFS and 5-year LRFS rate for all 103 patients were 52 months and 48%, respectively. Besides gender, Karnofsky performance status, and treatment group, IFI also influenced LRFS, whereas age and weight loss did not. When a multivariate model was used, IFI was marginally insignificant (p = 0.0770) as a predictor of LRFS. In terms of individual treatment groups, IFI was not significant in 'early' Acc Hfx RT/PE but showed a strong trend in a 'late' Acc Hfx RT/PE regimen. Although a shorter IFI led to a higher incidence of high-grade ({>=}3) esophagitis, leukopenia, and infection, a correlation analysis of toxicities with all potential prognostic factors showed that a shorter IFI was not an independent predictor of any acute high-grade toxicity. Conclusion: 'Shorter' IFI had a marginally insignificant influence on LRFS. A strong trend favoring it was observed in patients treated with 'late' concurrent Acc Hfx RT/PE. This may be of interest because it could contribute to further understanding of potential biologic parameters influencing treatment outcome.},
doi = {10.1016/j.ijrobp.2006.12.008},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 68,
place = {United States},
year = {Fri Jun 01 00:00:00 EDT 2007},
month = {Fri Jun 01 00:00:00 EDT 2007}
}
  • Purpose: To determine whether high-dose radiation leads to improved outcomes in patients with non-small-cell lung cancer (NSCLC). Methods and Materials: This analysis included 106 patients with newly diagnosed or recurrent Stages I-III NSCLC, treated with 63-103 Gy in 2.1-Gy fractions, using three-dimensional conformal radiation therapy (3D-CRT) per a dose escalation trial. Targets included the primary tumor and any lymph nodes {>=}1 cm, without intentionally including negative nodal regions. Nineteen percent of patients (20/106) received neoadjuvant chemotherapy. Patient, tumor, and treatment factors were evaluated for association with outcomes. Estimated median follow-up was 8.5 years. Results: Median survival was 19 months, andmore » 5-year overall survival (OS) was 13%. Multivariate analysis revealed weight loss (p = 0.011) and radiation dose (p = 0.0006) were significant predictors for OS. The 5-year OS was 4%, 22%, and 28% for patients receiving 63-69, 74-84, and 92-103 Gy, respectively. Although presence of nodal disease was negatively associated with locoregional control under univariate analysis, radiation dose was the only significant predictor when multiple variables were included (p = 0.015). The 5-year control rate was 12%, 35%, and 49% for 63-69, 74-84, and 92-103 Gy, respectively. Conclusions: Higher dose radiation is associated with improved outcomes in patients with NSCLC treated in the range of 63-103 Gy.« less
  • Classic teaching states that treatment of limited-stage small cell lung cancer (L-SCLC) requires large treatment fields covering the entire mediastinum. However, a trend in modern thoracic radiotherapy is toward more conformal fields, employing positron emission tomography/computed tomography (PET/CT) scans to determine the gross tumor volume (GTV). This analysis evaluates the dosimetric results when using selective nodal irradiation (SNI) to treat a patient with L-SCLC, quantitatively comparing the results to standard Intergroup treatment fields. Sixteen consecutive patients with L-SCLC and central mediastinal disease who also underwent pretherapy PET/CT scans were studied in this analysis. For each patient, we created SNI treatmentmore » volumes, based on the PET/CT-based criteria for malignancy. We also created 2 ENI plans, the first without heterogeneity corrections, as per the Intergroup 0096 study (ENI{sub off}) and the second with heterogeneity corrections while maintaining constant the number of MUs delivered between these latter 2 plans (ENI{sub on}). Nodal stations were contoured using published guidelines, then placed into 4 'bins' (treated nodes, 1 echelon away, >1 echelon away within the mediastinum, contralateral hilar/supraclavicular). These were aggregated across the patients in the study. Dose to these nodal bins and to tumor/normal structures were compared among these plans using pairwise t-tests. The ENI{sub on} plans demonstrated a statistically significant degradation in dose coverage compared with the ENI{sub off} plans. ENI and SNI both created a dose gradient to the lymph nodes across the mediastinum. Overall, the gradient was larger for the SNI plans, although the maximum dose to the '1 echelon away' nodes was not statistically different. Coverage of the GTV and planning target volume (PTV) were improved with SNI, while simultaneously reducing esophageal and spinal cord dose though at the expense of modestly reduced dose to anatomically distant lymph nodes within the mediastinum. The ENI{sub on} plans demonstrate that intergroup-style treatments, as actually delivered, had statistically reduced coverage to the mediastinum and tumor volumes than was reported. Furthermore, SNI leads to improved tumor coverage and reduced esophageal/spinal cord dose, which suggests the possibility of dose escalation using SNI.« less
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  • Purpose: The current tumor, node, metastasis system needs refinement to improve its ability to predict survival of patients with non-small-cell lung cancer (NSCLC) treated with (chemo)radiation. In this study, we investigated the prognostic value of tumor volume and N status, assessed by using fluorodeoxyglucose-positron emission tomography (PET). Patients and Methods: Clinical data from 270 consecutive patients with inoperable NSCLC Stages I-IIIB treated radically with (chemo)radiation were collected retrospectively. Diagnostic imaging was performed using either integrated PET-computed tomography or computed tomography and PET separately. The Kaplan-Meier method, as well as Cox regression, was used to analyze data. Results: Univariate survival analysismore » showed that number of positive lymph node stations (PLNSs), as well as N stage on PET, was associated significantly with survival. The final multivariate Cox model consisted of number of PLNSs, gross tumor volume (i.e., volume of the primary tumor plus lymph nodes), sex, World Health Organization performance status, and equivalent radiation dose corrected for time; N stage was no longer significant. Conclusions: Number of PLNSs, assessed by means of fluorodeoxyglucose-PET, was a significant factor for survival of patients with inoperable NSCLC treated with (chemo)radiation. Risk stratification for this group of patients should be based on gross tumor volume, number of PLNSs, sex, World Health Organization performance status, and equivalent radiation dose corrected for time.« less
  • Purpose: In non-small cell lung cancer, gross tumor volume (GTV) influences survival more than other risk factors. This could also apply to small cell lung cancer. Methods and Materials: Analysis of our prospective database with stage I to III SCLC patients referred for concurrent chemo radiation therapy. Standard treatment was 45 Gy in 1.5-Gy fractions twice daily concurrently with carboplatin-etoposide, followed by prophylactic cranial irradiation (PCI) in case of non-progression. Only fluorodeoxyglucose (FDG)-positron emission tomography (PET)-positive or pathologically proven nodal sites were included in the target volume. Total GTV consisted of post chemotherapy tumor volume and pre chemotherapy nodal volume.more » Survival was calculated from diagnosis (Kaplan-Meier ). Results: A total of 119 patients were included between May 2004 and June 2009. Median total GTV was 93 ┬▒ 152 cc (7.5-895 cc). Isolated elective nodal failure occurred in 2 patients (1.7%). Median follow-up was 38 months, median overall survival 20 months (95% confidence interval = 17.8-22.1 months), and 2-year survival 38.4%. In multivariate analysis, only total GTV (P=.026) and performance status (P=.016) significantly influenced survival. Conclusions: In this series of stage I to III small cell lung cancer patients treated with FDG-PET-based selective nodal irradiation total GTV is an independent risk factor for survival.« less