Biomedical subjects

Su-Min Zhou

Publications and source records attributed to Su-Min Zhou.

13 recordsLinked to original sources

PubMed2006

Impact of patient-specific factors, irradiated left ventricular volume, and treatment set-up errors on the development of myocardial perfusion defects after radiation therapy for left-sided breast cancer.

PURPOSE: The aim of this study was to assess the impact of patient-specific factors, left ventricle (LV) volume, and treatment set-up errors on the rate of perfusion defects 6 to 60 months post-radiation therapy (RT) in patients receiving tangential RT for left-sided breast cancer. METHODS AND MATERIALS: Between 1998 and 2005, a total of 153 patients were enrolled onto an institutional review board-approved prospective study and had pre- and serial post-RT (6-60 months) cardiac perfusion scans to assess for perfusion defects. Of the patients, 108 had normal pre-RT perfusion scans and available follow-up data. The impact of patient-specific factors on the rate of perfusion defects was assessed at various time points using univariate and multivariate analysis. The impact of set-up errors on the rate of perfusion defects was also analyzed using a one-tailed Fisher's Exact test. RESULTS: Consistent with our prior results, the volume of LV in the RT field was the most significant predictor of perfusion defects on both univariate (p = 0.0005 to 0.0058) and multivariate analysis (p = 0.0026 to 0.0029). Body mass index (BMI) was the only significant patient-specific factor on both univariate (p = 0.0005 to 0.022) and multivariate analysis (p = 0.0091 to 0.05). In patients with very small volumes of LV in the planned RT fields, the rate of perfusion defects was significantly higher when the fields set-up "too deep" (83% vs. 30%, p = 0.059). The frequency of deep set-up errors was significantly higher among patients with BMI > or =25 kg/m2 compared with patients of normal weight (47% vs. 28%, p = 0.068). CONCLUSIONS: BMI > or =25 kg/m2 may be a significant risk factor for cardiac toxicity after RT for left-sided breast cancer, possibly because of more frequent deep set-up errors resulting in the inclusion of additional heart in the RT fields. Further study is necessary to better understand the impact of patient-specific factors and set-up errors on the development of RT-induced perfusion defects.

Adult↗

PubMed2006

Does transforming growth factor-beta1 predict for radiation-induced pneumonitis in patients treated for lung cancer?

The purpose of the study was to reassess the utility of transforming growth factor-beta-1 (TGF-beta1) together with dosimetric and tumor parameters as a predictor for radiation pneumonitis (RP). Of the 121 patients studied, 32 (26.4%) developed grade > or =1 RP, and 27 (22.3%) developed grade > or =2 RP. For the endpoint of grade > or =1 RP, those with V30>30% and an end-RT/baseline TGF-beta1 ratio> or =1 had a significantly higher incidence of RP than did those with V30>30% and an end-RT/baseline TGF-beta1 ratio<1. For most other patient groups, there were no clear associations between TGF-beta1 values and rates of RP. These findings suggest that TGF-beta1 is generally not predictive for RP except for the group of patients with a high V30.

Adult↗

PubMed2006

Radiation-induced narrowing of the tracheobronchial tree: an in-depth analysis.

PURPOSE: Symptomatic narrowing of the tracheobronchial tree is not a common clinical problem after conventional-dose external beam radiation therapy but has been described when higher doses are utilized. This in-depth study quantifies changes in the caliber of the trachea and mainstem bronchi after high-dose external beam radiation therapy (EBRT). METHODS AND MATERIALS: As part of an IRB-approved prospective clinical trial to assess for radiation-induced lung injury, patients with thoracic malignancies had pre- and serial post-RT CT scans in the radiation oncology department. This report focuses on 18 enrolled patients who received high-dose (> or = 73.6 Gy) EBRT for NSCLC. The caliber of the trachea, right mainstem bronchus, and left mainstem bronchus were measured utilizing three-dimensional coordinates in axial and coronal planes such that multiple measurements were made of each structure. The decrease in airway caliber was tested for significance using a one-sided Wilcoxon matched-pairs signed-ranks test. The correlation between airway caliber changes, dose, and follow-up interval was tested using the Spearman rank correlation coefficient and the effect of chemotherapy on airway narrowing was evaluated with a one-sided exact Wilcoxon rank sum test. RESULTS: There was no significant narrowing of the trachea for all dose and time points. There were significant decreases in the caliber of both mainstem bronchi on axial measurements (p = 0.07 and 0.005 for right and left mainstem bronchi, respectively). Decrease in airway caliber ranged from 6 to 57% and appeared to be dose dependent (p = 0.08), progressed with increasing time post-RT (p = 0.04), and was worse in patients who also received chemotherapy (p = 0.04). CONCLUSION: High-dose EBRT (> or = 73.6 Gy) appears to cause narrowing of the mainstem bronchi as early as 3 months post radiation therapy. Additional study is needed to assess the impact of such narrowing on RT-induced pulmonary symptoms.

Aged↗

PubMed2006

Physics and imaging for targeting of oligometastases.

Oligometastases refer to metastases that are limited in number and location and are amenable to regional treatment. The majority of these metastases appear in the brain, lung, liver, and bone. Although the focus of interest in the past within radiation oncology has been on the treatment of intracranial metastases, there has been growing interest in extracranial sites such as the liver and lung. This is largely because of the rapid development of targeting techniques for oligometastases such as intensity-modulated and image-guided radiation therapy, which has made it possible to deliver single or a few fractions of high-dose radiation treatments, highly conformal to the target. The clinical decision to use radiation to treat oligometastases is based on both radiobiological and physics considerations. The radiobiological considerations involve improvement of treatment schema for time, dose, and volume. Areas of interests are hypofractionation, tumor and normal tissue tolerance, and hypoxia. The physics considerations for oligometastases treatment are focused mainly on ensuring treatment accuracy and precision. This article discusses the physics and imaging aspects involved in each step of the radiation treatment process for oligometastases, including target definition, treatment simulation, treatment planning, pretreatment target localization, radiation delivery, treatment verification, and treatment evaluation.

Dose Fractionation, Radiation↗

PubMed2005

The incidence and functional consequences of RT-associated cardiac perfusion defects.

PURPOSE: Radiation therapy (RT) for left-sided breast cancer has been associated with cardiac dysfunction. We herein assess the temporal nature and volume dependence of RT-induced left ventricular perfusion defects and whether these perfusion defects are related to changes in cardiac wall motion or alterations in ejection fraction. METHODS: From 1998 to 2001, 114 patients were enrolled onto an IRB-approved prospective clinical study to assess changes in regional and global cardiac function after RT for left-sided breast cancer. Patients were imaged 30 to 60 minutes after injection of technetium 99m sestamibi or tetrofosmin. Post-RT perfusion scans were compared with the pre-RT studies to assess for RT-induced perfusion defects as well as functional changes in wall motion and ejection fraction. Two-tailed Fisher's exact test and the Cochran-Armitage test for linear trends were used for statistical analysis. RESULTS: The incidence of new perfusion defects 6, 12, 18, and 24 months after RT was 27%, 29%, 38%, and 42%, respectively. New defects occurred in approximately 10% to 20% and 50% to 60% of patients with less than 5%, and greater than 5%, of their left ventricle included within the RT fields, respectively (p = 0.33 to 0.00008). The rates of wall motion abnormalities in patients with and without perfusion defects were 12% to 40% versus 0% to 9%, respectively; p values were 0.007 to 0.16, depending on the post-RT interval. CONCLUSIONS: Radiation therapy causes volume-dependent perfusion defects in approximately 40% of patients within 2 years of RT. These perfusion defects are associated with corresponding wall-motion abnormalities. Additional study is necessary to better define the long-term functional consequences of RT-induced perfusion defects.

Adult↗

PubMed2005

Preliminary report of the 6-minute walk test as a predictor of radiation-induced pulmonary toxicity.

PURPOSE: To assess the 6-minute walk test (6MWT) as a predictor of radiation therapy-induced lung injury (RTLI). METHODS AND MATERIALS: The 6MWT is a simple, economical, and reproducible test that measures both how far a person can walk in 6 min and any associated changes in vital signs. As part of a prospective trial to study RTLI, a pre-RT 6MWT was performed in 41 patients. The predictive capacities of pre-RT 6MWT, forced expiratory volume in 1 s (FEV1), and single-breath diffusing capacity for carbon monoxide (DLCO) for the development of RTLI were assessed with receiver operating curve (ROC) techniques. To evaluate the 6MWT, alone or with mean lung dose (MLD) of radiation, as a predictor of RTLI, the rates of RTLI in patient subgroups defined by 6MWT results were compared by using Fisher's exact test. RESULTS: Thirty-one patients with > or =3 months' follow-up were evaluable. The median baseline 6MWT result was 1400 ft. Of 31 patients, 7 developed Grade > or =2 RTLI. Of 15 patients with an MLD >18 Gy (the median), 5 developed RTLI, compared with 2 of 16 with MLD < or =18 Gy (p = 0.22). Among those with an MLD < or =18 Gy, the RTLI rates were 0 of 8 and 2 of 8 for 6MWT results > or =1400 ft or <1400 ft, respectively, p = 0.46. The ROC area under the curve for individual metrics was as follows: FEV1 0.66, MLD 0.70, DLCO 0.61, and 6MWT 0.47. Combining FEV1 with 6MWT increased the ROC to 0.71, suggesting that the ratio might be a better predictor than the individual values. Patients with a high 6MWT/FEV1 ratio had a lower rate of RTLI than those with a relatively low ratio. CONCLUSIONS: The 6MWT might provide prognostic information beyond pulmonary function tests and dosimetric parameters in predicting RTLI. Additional work is needed to better assess the utility of these functional metrics.

Adult↗

PubMed2005

Challenges in defining radiation pneumonitis in patients with lung cancer.

PURPOSE: To assess the difficulty of assigning a definitive clinical diagnosis of radiation (RT)-induced lung injury in patients irradiated for lung cancer. METHODS: Between 1991 and 2003, 318 patients were enrolled in a prospective study to evaluate RT-induced lung injury. Only patients with lung cancer who had a longer than 6-month follow-up (251 patients) were considered in the current analysis. Of these, 47 of 251 patients had Grade >/=2 (treated with steroids) increasing shortness of breath after RT, thought possibly consistent with pneumonitis/fibrosis. The treating physician, and one to three additional reviewing physicians, evaluated the patients or their medical records, or both. The presence or absence of confounding clinical factors that made the diagnosis of RT-induced uncertain lung injury were recorded. RESULTS: Thirty-one of 47 patients (66%) with shortness of breath had "classic" pneumonitis, i.e., they responded to steroids and had a definitive diagnosis of pneumonitis. In 13 of 47 patients (28%), the diagnosis of RT-induced toxicity was confounded by possible infection; exacerbation of preexisting lung disease (chronic obstructive pulmonary disease); tumor regrowth/progression; and cardiac disease in 6, 8, 5, and 1 patients, respectively (some of the patients had multiple confounding factors and were counted more than once). An additional 3 patients (6%) had progressive shortness of breath and an overall clinical course more consistent with fibrosis. All 3 had evidence of bronchial stenosis by bronchoscopy. CONCLUSIONS: Scoring of radiation pneumonitis was challenging in 28% of patients treated for lung cancer owing to confounding medical conditions. Recognition of this uncertainty is needed and may limit our ability to understand RT-induced lung injury.

Adult↗

PubMed2005

Bronchial stenosis: an underreported complication of high-dose external beam radiotherapy for lung cancer?

PURPOSE: To assess the incidence of clinically significant bronchial stenosis in patients treated with high doses (i.e., >70 Gy) of twice-daily external beam radiation therapy (RT). METHODS AND MATERIALS: The outcomes of 103 patients with unresectable non-small-cell lung cancer, treated twice daily to doses ranging from 7080 to 8640 cGy between 1992 and 2001, were analyzed. Most were treated on prospective clinical trials. For the dose-effect comparison, the patients were divided on the basis of the total dose: 67 received 74 Gy (range, 70.8-74.5 Gy; median, 73.6 Gy), 20 received 80 Gy, and 16 received 86 Gy (range, 85.2-86.4 Gy; median, 86.4 Gy). Sixty-six patients received sequential chemotherapy before RT. RT-induced bronchial stenosis was defined as symptomatic airway narrowing diagnosed by bronchoscopy or computed tomography scan without evidence of recurrent tumor in that region. RESULTS: Eight patients developed RT-induced, clinically significant, bronchial stenosis 2-48 months (median, 6 months) after RT. The 1-year and 4-year actuarial rate of stenosis was 7% and 38%, respectively. The median overall survival was 2.5 years (5 of 8 were alive at the writing of this report). A suggestion was also found of a dose-response effect with external beam radiotherapy-induced stenosis, with a rate of 4% and 25% at a dose of approximately 74 Gy and 86 Gy, respectively. CONCLUSION: Radiation therapy-induced bronchial stenosis is a significant clinical complication of dose escalation for lung cancer. This complication has been previously mentioned in the literature, but ours is the largest report to date, and the findings suggest that the risk rises with increasing dose. It is likely that this process would manifest in more patients if their disease were controlled well enough for more prolonged survival.

Bronchi↗

PubMed2004

Using FDG-PET activity as a surrogate for tumor cell density and its effect on equivalent uniform dose calculation.

The concept of equivalent uniform dose (EUD) has been suggested as a means to quantitatively consider heterogeneous dose distributions within targets. Tumor cell density/function is typically assumed to be uniform. We herein propose to use 18F-labeled 2-deoxyglucose (FDG) positron emission tomography (PET) tumor imaging activity as a surrogate marker for tumor cell density to allow the EUD concept to include intratumor heterogeneities and to study its effect on EUD calculation. Thirty-one patients with lung cancer who had computerized tomography (CT)-based 3D planning and PET imaging were studied. Treatment beams were designed based on the information from both the CT and PET scans. Doses were calculated in 3D based on CT images to reflect tissue heterogeneity. The EUD was calculated in two different ways: first, assuming a uniform tumor cell density within the tumor target; second, using FDG-PET activity (counts/cm3) as a surrogate for tumor cell density at different parts of tumor to calculate the functional-imaging-weighted EUD (therefore will be labeled fEUD for convenience). The EUD calculation can be easily incorporated into the treatment planning process. For 28/31 patients, their fEUD and EUD differed by less than 6%. Twenty-one of these twenty-eight patients had tumor volumes < 200 cm3. In the three patients with larger tumor volume, the fEUD and EUD differed by 8%-14%. Incorporating information from PET imaging to represent tumor cell density in the EUD calculation is straightforward. This approach provides the opportunity to include heterogeneity in tumor function/metabolism into the EUD calculation. The difference between fEUD and EUD, i.e., whether including or not including the possible tumor cell density heterogeneity within tumor can be significant with large tumor volumes. Further research is needed to assess the usefulness of the fEUD concept in radiation treatment.

Algorithms↗

PubMed2004

Relationship between the generalized equivalent uniform dose formulation and the Poisson statistics-based tumor control probability model.

The generalized equivalent uniform dose (GEUD) model uses a power-law formalism, where the outcome is related to the dose via a power law. We herein investigate the mathematical compatibility between this GEUD model and the Poisson statistics based tumor control probability (TCP) model. The GEUD and TCP formulations are combined and subjected to a compatibility constraint equation. This compatibility constraint equates tumor control probability from the original heterogeneous target dose distribution to that from the homogeneous dose from the GEUD formalism. It is shown that this constraint equation possesses a unique, analytical closed-form solution which relates radiation dose to the tumor cell survival fraction. It is further demonstrated that, when there is no positive threshold or finite critical dose in the tumor response to radiation, this relationship is not bounded within the realistic cell survival limits of 0%-100%. Thus, the GEUD and TCP formalisms are, in general, mathematically inconsistent. However, when a threshold dose or finite critical dose exists in the tumor response to radiation, there is a unique mathematical solution for the tumor cell survival fraction that allows the GEUD and TCP formalisms to coexist, provided that all portions of the tumor are confined within certain specific dose ranges.

Algorithms↗

PubMed2003

Long-term changes in pulmonary function tests after definitive radiotherapy for lung cancer.

PURPOSE: To evaluate the long-term changes in pulmonary function tests (PFTs) in patients surviving at least 2 years after definitive radiotherapy (RT) for unresectable lung cancer. METHODS AND MATERIALS: Between 1992 and 2000, 277 patients were enrolled in a prospective clinical study to relate RT-induced changes in lung function with dosimetric and functional metrics. Of these, 128 received definitive RT for lung cancer, and 13 of these had follow-up PFTs for approximately >/=2 years without evidence of recurrent or progressive cancer. PFTs were obtained before RT and approximately every 6 months after RT. The results were evaluated on the basis of each study's "percentage of predicted" of normal values (i.e., adjusted for age, gender, height), and a patient's sequential examinations were compared with their initial study and a percentage of the baseline value was calculated. Follow-up PFTs were available for a median of 38 months (range 23-95). The median patient age was 65 years (range 40-74), 6 patients were men, and 10 were white. Most had Stage T2-T4 and N2-N3. The median RT dose was 71.4 Gy (range 60-73), 6 had twice-daily RT. Four patients received chemotherapy, one concurrent and three neoadjuvant. None of the patients continued to smoke after their treatment. The median pre-RT PFT results were (percentage of predicted) forced expiratory volume in 1 s, 67% (range 24-121); forced vital capacity, 72% (range 45-116); and diffusing capacity of lung for carbon monoxide, 70% (range 41-129). RESULTS: At 6 months, all PFT values had declined, with some stabilization by 1 year. However, after 1 year, a gradual reduction occurred in all three parameters. Ten patients (77%) developed RT-induced respiratory symptoms (2 cough only, 8 dyspnea) at 2-21 months (median 5) after treatment. Two patients required inhalers, another required long-term steroids and oxygen. Of the 8 patients with dyspnea, 7 had an increase in symptoms beyond 2 years. No patient died of RT-induced pulmonary insufficiency. CONCLUSION: RT caused a decline in PFTs that was apparent at 6 months and continued well beyond 1 year. The continued decline in PFTs is suggestive of progressive/evolving RT-induced lung injury. "Late" pulmonary symptoms have also occurred in these patients. Because of the high mortality rate of unresectable lung cancer, few patients can be evaluated for long-term analysis. Additional studies and pooling of data from multiple institutions may help to clarify better the long-term impact of RT on pulmonary function in this subset of patients.

Adult↗

PubMed2002

Receiver operating characteristic curves to assess predictors of radiation-induced symptomatic lung injury.

PURPOSE: To assess the utility of dosimetric/functional metrics as predictors of symptomatic radiation pneumonitis using receiver operating characteristic curves. METHODS: Between 1991 and 1999, 277 patients were enrolled on a prospective clinical study to relate radiation therapy (RT) induced changes in lung function with dosimetric and functional metrics. Pre-RT whole and regional functional assessments included pulmonary function tests and single photon emission computed tomography lung perfusion scans. Patients had three-dimensional planning scans and dose calculations (reflecting tissue density heterogeneity) to provide a dose-volume histogram of the lung and associated dosimetric parameters (MLD = mean lung dose, V30 = % of lung receiving >or=30 Gy). Fusion of single photon emission computed tomography and computed tomography scans provides perfusion-weighted dose-function histograms and associated dosimetric parameters (mean perfusion-weighted lung dose). The incidence of clinically relevant radiation pneumonitis requiring steroids was related to the dosimetric and functional metrics. The predictive abilities of models (sensitivity and specificity) were calculated and compared based on the area beneath receiver operating characteristic (ROC) curves (Wilcoxon rank-sum and chi-square). RESULTS: Twenty-seven of 162 evaluable patients with >or=6 months' follow-up developed pneumonitis requiring steroids. Single metrics were typically not good predictors for pneumonitis ( area under ROC curve = 0.5-0.68). The two-dimensional models (e.g., MLD and pre-RT diffusion capacity for carbon monoxide) generally provided greater ROC areas (0.61-0.72). Overall, the models that considered a measure of pre-RT lung function (i.e., pulmonary function tests), the MLD, and mean perfusion-weighted lung dose were best correlated with outcome (ROC area: 0.7) (p < 0.05 compared to unidimensional models). However, because the area under the ROC curve for these models was <<1, they too seemed not to be ideal. CONCLUSION: Predicting symptomatic radiation pneumonitis remains difficult. Multiparameter models that consider pre-RT pulmonary function and the three-dimensional dose distribution seem to be best able to predict outcome. Additional studies are needed to better understand the dosimetric/functional determinants of radiation pneumonitis.

Adolescent↗

PubMed2002

Influence of tumor volume on survival in patients irradiated for non-small-cell lung cancer.

PURPOSE: To investigate the importance of CT-defined total tumor volume (TTV) on overall survival (OS) in patients with unresectable or medically inoperable non-small-cell lung carcinoma (NSCLC). METHODS AND MATERIALS: Between 1991 and 1998, 150 evaluable patients with Stage I-IIIB NSCLC were treated with three-dimensionally planned conformal radiotherapy and curative intent at Duke University Medical Center. On the treatment-planning CT, the primary tumor and nodal volumes were identified and subsequently combined to form the TTV. The TTV was compared with the stage and outcome with respect to OS, local progression-free survival, and distant failure-free survival using the Kruskall-Wallis analysis of variance and Kaplan-Meier actuarial method. To account for the potentially confounding effects of therapeutic and patient-specific covariates on survival, the Cox proportional hazard regression model was used. RESULTS: The TTVs in patients with Stage I disease (median 19 cm3) were smaller than in patients with Stage II (median 80 cm3) or Stage III (median 97 cm3; p <0.001) disease. The Stage II TTVs were not significantly different from those of Stage III (post-hoc test according to Bonferroni). Prolonged OS was independently associated with a small TTV (<80 vs. >80 cm3 [median]; p = 0.01), young age (<60 vs. > or =60 years; p = 0.03), high Karnofsky performance status (< o r =70 vs. >70; p = 0.04), and female gender (p = 0.04). Both stage (p = 0.7) and T stage (p = 0.06) were of less importance for OS than was the TTV, according to multivariate modeling. Increased local progression-free survival (p = 0.001) and distant failure-free survival (p = 0.03) were independently associated with a small TTV (i.e., <80 cm3). The results were unchanged if the TTV was analyzed as a continuous variable. CONCLUSION: A strong independent association between a small CT-defined TTV and prolonged survival in patients with NSCLC selected for curative/definitive RT was found. Future therapeutic studies in NSCLC should consider stratifying/adjusting for differences in TTV to avoid confounding effects on survival from variations in the TTV at baseline.

Adult↗