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Title: Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?

Abstract

Purpose: To determine whether severity of lymphopenia is dependent on radiation dose and fractional volume of spleen irradiated unintentionally during definitive chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC). Methods: 177 patients with LAPC received induction chemotherapy (mainly gemcitabine-based regimens) followed by CRT (median 50.4 Gy with concurrent capecitabine) from January 2006 to December 2012. Absolute lymphocyte count (ALC) was recorded at baseline, before CRT, and 2 to 10 weeks after CRT. Splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and percentage of splenic volume receiving at least 5- (V5), 10- (V10), 15- (V15), and 20-Gy (V20) dose. Overall survival (OS) was analyzed with use of the Cox model, and development of post-CRT severe lymphopenia (ALC <0.5 K/UL) was assessed by multivariate logistic regression with use of baseline and treatment factors. Results: The median post-CRT ALC (0.68 K/UL; range, 0.13-2.72) was significantly lower than both baseline ALC (1.42 K/UL; range, 0.34-3.97; P<.0001) and pre-CRT ALC (1.32 K/UL, range 0.36-4.82; P<.0001). Post-CRT ALC <0.5 K/UL was associated with inferior OS on univariate analysis (median, 11.1 vs 15.3 months; P=.01) and multivariate analysis (hazard ratio = 1.66, P=.01). MSD (9.8 vs 6 Gy, P=.03), median V10 (32.6 vs 16%, P=.04), V15 (23.2 vs 9.5%, P=.03), and V20more » (15.4 vs 4.6%, P=.02) were significantly higher in patients with severe lymphopenia than in those without. On multivariate analysis, postinduction lymphopenia (P<.001; odds ratio [OR] = 5.25) and MSD (P=.002; OR= 3.42) were independent predictors for the development of severe post-CRT lymphopenia. Conclusion: Severe post-CRT lymphopenia is an independent predictor of poor OS in LAPC patients receiving CRT. Higher splenic doses increase the risk for the development of severe post-CRT lymphopenia. When clinically indicated, assessment of splenic DVHs before the acceptance of treatment plans may minimize the risk of severe post-CRT lymphopenia.« less

Authors:
;  [1];  [2]; ; ; ;  [1];  [3];  [3];  [4];  [3]; ;  [5]; ; ;  [6];  [1];  [2];  [1];  [1]
  1. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
  2. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
  3. Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
  4. (United States)
  5. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
  6. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
Publication Date:
OSTI Identifier:
22645770
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 97; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The 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; CHEMOTHERAPY; GY RANGE 01-10; GY RANGE 10-100; LYMPHOPENIA; MULTIVARIATE ANALYSIS; NEOPLASMS; PANCREAS; PATIENTS; RADIATION DOSES; RADIOTHERAPY

Citation Formats

Chadha, Awalpreet S., Liu, Guan, Chen, Hsiang-Chun, Das, Prajnan, Minsky, Bruce D., Mahmood, Usama, Delclos, Marc E., Suh, Yelin, Sawakuchi, Gabriel O., Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas, Beddar, Sam, Katz, Matthew H., Fleming, Jason B., Javle, Milind M., Varadhachary, Gauri R., Wolff, Robert A., Crane, Christopher H., Wang, Xuemei, Thames, Howard, and Krishnan, Sunil, E-mail: skrishnan@mdanderson.org. Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?. United States: N. p., 2017. Web. doi:10.1016/J.IJROBP.2016.10.046.
Chadha, Awalpreet S., Liu, Guan, Chen, Hsiang-Chun, Das, Prajnan, Minsky, Bruce D., Mahmood, Usama, Delclos, Marc E., Suh, Yelin, Sawakuchi, Gabriel O., Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas, Beddar, Sam, Katz, Matthew H., Fleming, Jason B., Javle, Milind M., Varadhachary, Gauri R., Wolff, Robert A., Crane, Christopher H., Wang, Xuemei, Thames, Howard, & Krishnan, Sunil, E-mail: skrishnan@mdanderson.org. Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?. United States. doi:10.1016/J.IJROBP.2016.10.046.
Chadha, Awalpreet S., Liu, Guan, Chen, Hsiang-Chun, Das, Prajnan, Minsky, Bruce D., Mahmood, Usama, Delclos, Marc E., Suh, Yelin, Sawakuchi, Gabriel O., Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas, Beddar, Sam, Katz, Matthew H., Fleming, Jason B., Javle, Milind M., Varadhachary, Gauri R., Wolff, Robert A., Crane, Christopher H., Wang, Xuemei, Thames, Howard, and Krishnan, Sunil, E-mail: skrishnan@mdanderson.org. Wed . "Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?". United States. doi:10.1016/J.IJROBP.2016.10.046.
@article{osti_22645770,
title = {Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?},
author = {Chadha, Awalpreet S. and Liu, Guan and Chen, Hsiang-Chun and Das, Prajnan and Minsky, Bruce D. and Mahmood, Usama and Delclos, Marc E. and Suh, Yelin and Sawakuchi, Gabriel O. and Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas and Beddar, Sam and Katz, Matthew H. and Fleming, Jason B. and Javle, Milind M. and Varadhachary, Gauri R. and Wolff, Robert A. and Crane, Christopher H. and Wang, Xuemei and Thames, Howard and Krishnan, Sunil, E-mail: skrishnan@mdanderson.org},
abstractNote = {Purpose: To determine whether severity of lymphopenia is dependent on radiation dose and fractional volume of spleen irradiated unintentionally during definitive chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC). Methods: 177 patients with LAPC received induction chemotherapy (mainly gemcitabine-based regimens) followed by CRT (median 50.4 Gy with concurrent capecitabine) from January 2006 to December 2012. Absolute lymphocyte count (ALC) was recorded at baseline, before CRT, and 2 to 10 weeks after CRT. Splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and percentage of splenic volume receiving at least 5- (V5), 10- (V10), 15- (V15), and 20-Gy (V20) dose. Overall survival (OS) was analyzed with use of the Cox model, and development of post-CRT severe lymphopenia (ALC <0.5 K/UL) was assessed by multivariate logistic regression with use of baseline and treatment factors. Results: The median post-CRT ALC (0.68 K/UL; range, 0.13-2.72) was significantly lower than both baseline ALC (1.42 K/UL; range, 0.34-3.97; P<.0001) and pre-CRT ALC (1.32 K/UL, range 0.36-4.82; P<.0001). Post-CRT ALC <0.5 K/UL was associated with inferior OS on univariate analysis (median, 11.1 vs 15.3 months; P=.01) and multivariate analysis (hazard ratio = 1.66, P=.01). MSD (9.8 vs 6 Gy, P=.03), median V10 (32.6 vs 16%, P=.04), V15 (23.2 vs 9.5%, P=.03), and V20 (15.4 vs 4.6%, P=.02) were significantly higher in patients with severe lymphopenia than in those without. On multivariate analysis, postinduction lymphopenia (P<.001; odds ratio [OR] = 5.25) and MSD (P=.002; OR= 3.42) were independent predictors for the development of severe post-CRT lymphopenia. Conclusion: Severe post-CRT lymphopenia is an independent predictor of poor OS in LAPC patients receiving CRT. Higher splenic doses increase the risk for the development of severe post-CRT lymphopenia. When clinically indicated, assessment of splenic DVHs before the acceptance of treatment plans may minimize the risk of severe post-CRT lymphopenia.},
doi = {10.1016/J.IJROBP.2016.10.046},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 97,
place = {United States},
year = {Wed Feb 01 00:00:00 EST 2017},
month = {Wed Feb 01 00:00:00 EST 2017}
}
  • Central review of radiation therapy (RT) delivery within multicenter clinical trials was initiated in the early 1970s in the United States. Early quality assurance publications often focused on metrics related to process, logistics, and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. A MEDLINE search was performed to identify multicenter studies that described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicenter studies (1980-2012) were identified, plus one Patterns of Care Study. Diseasemore » sites were hematologic, head and neck, lung, breast, and pancreas. Between 0 and 97% of treatment plans received an overall grade of acceptable. In 7 trials, failure rates were significantly higher after inadequate versus adequate RT. Five of 9 and 2 of 5 trials reported significantly worse overall and progression-free survival after poor-quality RT, respectively. One reported a significant correlation, and 2 reported nonsignificant trends toward increased toxicity with noncompliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question.« less
  • Purpose: To assess the magnitude and predictors of patient-reported fatigue among breast cancer patients receiving radiation therapy (RT). Methods and Materials: Patients receiving breast RT completed a survey querying fatigue at each weekly on-treatment visit. Patient-reported fatigue severity and interference was assessed on an ordinal scale of 0 to 4, using a validated scoring system. Baseline anxiety and depression scores were also obtained. The kinetics of mean fatigue scores per week and the maximum fatigue scores over the course of the entire treatment were assessed, and clinical predictors were identified by univariate and multivariate regression. Results: The average fatigue severitymore » and interference scores were 0.6 and 0.46. The average fatigue scores increased to an equivalent extent from week to week, with expected increases of 0.99 in fatigue severity and 0.85 in interference over 7 weeks. Patients treated with hypofractionated RT (HF-RT) versus conventionally fractionated RT (CF-RT) had significantly fewer maximum fatigue severity or interference scores that were >2 (ie, severe or very severe; 29% vs 10% for severity, and 26% vs 8% for interference, P<.01). Age ≤45 years, presence of psychiatric/pain-related comorbidities, and baseline sadness and anxiety severity were predictive of average and maximum fatigue scores (P<.05), but variables related to treatment intensity (eg, mastectomy vs lumpectomy, chemotherapy use, radiation target volumes) and other host factors (working, children, marital status, proximity to RT facility) were not. Conclusion: Patient-reported fatigue modestly increases over RT courses, with less maximum fatigue reported with HF-RT. Younger age and baseline sadness, anxiety, and psychiatric/pain-related comorbidities are powerful predictors of fatigue, whereas other factors, such as treatment intensity, are not. Future studies will investigate interventions for patients at high risk for fatigue.« less
  • Purpose: Although previous studies have demonstrated the prognostic value of positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer has yet to be well established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiation therapy (SBRT). Materials and Methods: Thirty-two patients with LAPC in a prospective clinical trial received up to 3 doses of gemcitabine, followed by 33 Gy in 5 fractions of 6.6 Gy, using SBRT. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesionmore » glycolysis (TLG), and maximum and peak standardized uptake values (SUV{sub max} and SUV{sub peak}) on pre-SBRT PET scans were calculated using custom-designed software. Disease was measured at a threshold based on the liver SUV, using the equation Liver{sub mean} + [2 × Liver{sub sd}]. Median values of PET parameters were used as cutoffs when assessing their prognostic potential through Cox regression analyses. Results: Of the 32 patients, the majority were male (n=19, 59%), 65 years or older (n=21, 66%), and had tumors located in the pancreatic head (n=27, 84%). Twenty-seven patients (84%) received induction gemcitabine prior to SBRT. Median overall survival for the entire cohort was 18.8 months (95% confidence interval [CI], 15.7-22.0). An MTV of 26.8 cm{sup 3} or greater (hazard ratio [HR] 4.46, 95% CI 1.64-5.88, P<.003) and TLG of 70.9 or greater (HR 3.08, 95% CI 1.18-8.02, P<.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19-22.21, P=.029) and TLG (HR 3.34, 95% CI 1.07-10.48, P=.038) remained independently associated with overall survival in separate multivariate analyses. Conclusions: Pre-SBRT MTV and TLG are potential predictive factors for overall survival in patients with LAPC and may assist in tailoring therapy.« less
  • Purpose: The criteria for administration of adjuvant radiation therapy (RT) in oral cavity squamous cell carcinoma (OSCC) remain controversial, and it is unclear whether patients with pT1-3N0 disease benefit from adjuvant radiation in the presence of free margins and perineural invasion. The goal of this report was to determine whether this group would benefit from adjuvant radiation therapy in terms of 5-year local control rate and overall survival rate. Methods and Materials: We retrospectively reviewed our case records from January 1996 to May 2005. In all, 460 pT1-3N0 OSCC patients had tumor-free margins, of whom 68 had perineural invasion. Postoperativemore » adjuvant RT was performed in patients with pT4 tumors, positive lymph nodes, or close margins ({<=}4 mm). In addition, selected OSCC patients with large pT3 tumors or perineural invasion received postoperative adjuvant RT. Local control and overall survival rates were plotted by Kaplan-Meier analysis. Results: There were no significant differences in 5-year local control (p 0.1936) and overall survival (p = 0.5580) rates between patients with perineural invasion compared with those without. Among patients with perineural invasion, the addition of adjuvant radiotherapy did not significantly alter the 5-year local control rate (p = 0.3170) or the overall survival rate (p = 0.0935). Conclusion: Altogether, these data seem to indicate that radical surgical resection alone should be considered a sufficient treatment for OSCC patients with pT1-3N0 disease, even in the presence of perineural invasion.« less
  • Purpose: We investigated predictors of fractional anisotropy (FA) change in the corticospinal white matter tract (CST) following radiation therapy (RT). Methods: Diffusion tensor imaging (DTI) is a non-invasive modality which models water diffusion properties. FA quantifies the extent of directional bias—a decrease indicates disrupted white matter integrity. Fifteen patients with high-grade glioma underwent DTI scans before, and ten months after RT to 59.4–60 Gy. The CST was segmented using an automated atlas-based algorithm on all DTI images. Treatment planning CT and DTI images were aligned using non-linear registration allowing for baseline FA, follow-up FA, and absorbed dose to be determinedmore » in each voxel. Relative FA change was dichotomized into a binary outcome using 25% decrease as cutoff. Three metrics were assessed as predictors: voxel dose, distance from the voxel to the center of the CST (Rc), and the number of neighboring voxels (Nadj from 0 to 26) with ≥25% decrease in FA. Logistic regression and the area under the receiver-operating characteristics curve (AUC) analysis were performed for each patient. Results: Median age of the cohort was 59 years (range: 40–85). The average number of voxels in the CST amongst all patients was 1181 (±172, SD). In logistic regression, the probability of FA change was highly associated with Nadj in all 15 patients with corresponding AUCs between 0.81 and 0.97. With all three metrics included in the logistic regression models, Nadj was highly significant (p<0.001) in all patients, voxel dose significant (p<0.05) in 3/15 patients, and Rc significant in 12/15 patients (p<0.05). Conclusion: The number of neighboring voxels with change in FA was the dominant predictor of FA change at any given voxel. This suggests that the microenvironment of surrounding white matter disruption after radiation therapy may drive local effects along a white matter tract. Pettersson and Cervino are funded by a Varian Medical Systems grant.« less