Kwan Ho Cho

Dosimetric comparison of four different external beam partial breast irradiation techniques: Three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, helical tomotherapy, and proton beam therapy

BACKGROUND AND PURPOSE As an alternative to whole breast irradiation in early breast cancer, a variety of accelerated partial breast irradiation (APBI) techniques have been investigated. The purpose of our study is to compare the dosimetry of four different external beam APBI (EB-APBI) plans: three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), helical tomotherapy (TOMO), and proton beam therapy (PBT). METHODS AND MATERIALS Thirty patients were included in the study, and plans for four techniques were developed for each patient. A total dose of 30Gy in 6Gy fractions once daily was prescribed in all treatment plans. RESULTS In the analysis of the non-PTV breast volume that was delivered 50% of the prescribed dose (PD), PBT (mean: 16.5%) was superior to TOMO (mean: 22.8%), IMRT (mean: 33.3%), and 3D-CRT (mean: 40.9%) (p<0.001). The average ipsilateral lung volume percentage receiving 20% of the PD was significantly lower in PBT (0.4%) and IMRT (2.3%) compared with 3D-CRT (6.0%) and TOMO (14.2%) (p<0.001). The average heart volume percentage receiving 20% and 10% of the PD in left-sided breast cancer (N=19) was significantly larger with TOMO (8.0%, 19.4%) compared to 3D-CRT (1.5%, 3.1%), IMRT (1.2%, 4.0%), and PBT (0%, 0%) (p<0.001). CONCLUSIONS All four EB-APBI techniques showed acceptable coverage of the PTV. However, effective non-PTV breast sparing was achieved at the cost of considerable dose exposure to the lung and heart in TOMO.

Prediction of Survival by [18F]Fluorodeoxyglucose Positron Emission Tomography in Patients With Locally Advanced Non–Small-Cell Lung Cancer Undergoing Definitive Chemoradiation Therapy: Results of the ACRIN 6668/RTOG 0235 Trial

PURPOSE In this prospective National Cancer Institute-funded American College of Radiology Imaging Network/Radiation Therapy Oncology Group cooperative group trial, we hypothesized that standardized uptake value (SUV) on post-treatment [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) correlates with survival in stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients received conventional concurrent platinum-based chemoradiotherapy without surgery; postradiotherapy consolidation chemotherapy was allowed. Post-treatment FDG-PET was performed at approximately 14 weeks after radiotherapy. SUVs were analyzed both as peak SUV (SUVpeak) and maximum SUV (SUVmax; both institutional and central review readings), with institutional SUVpeak as the primary end point. Relationships between the continuous and categorical (cutoff) SUVs and survival were analyzed using Cox proportional hazards multivariate models. RESULTS Of 250 enrolled patients (226 were evaluable for pretreatment SUV), 173 patients were evaluable for post-treatment SUV analyses. The 2-year survival rate for the entire population was 42.5%. Pretreatment SUVpeak and SUVmax (mean, 10.3 and 13.1, respectively) were not associated with survival. Mean post-treatment SUVpeak and SUVmax were 3.2 and 4.0, respectively. Post-treatment SUVpeak was associated with survival in a continuous variable model (hazard ratio, 1.087; 95% CI, 1.014 to 1.166; P = .020). When analyzed as a prespecified binary value (≤ v > 3.5), there was no association with survival. However, in exploratory analyses, significant results for survival were found using an SUVpeak cutoff of 5.0 (P = .041) or 7.0 (P < .001). All results were similar when SUVmax was used in univariate and multivariate models in place of SUVpeak. CONCLUSION Higher post-treatment tumor SUV (SUVpeak or SUVmax) is associated with worse survival in stage III NSCLC, although a clear cutoff value for routine clinical use as a prognostic factor is uncertain at this time.

A new homogeneity index based on statistical analysis of the dose–volume histogram

The goal of the present study was to develop a new dose–volume histogram (DVH)– based homogeneity index for effectively evaluating the dose homogeneity of intensity‐modulated radiotherapy plans. The new index, called the sigma‐index (“S‐index”) is defined as the standard deviation of the normalized differential DVH curve. In a study of 16 patients with brain tumors at our institution, the S‐index was found to vary from 0.80 to 3.15. Our results showed that the S‐index provides a more reliable and accurate measure of dose homogeneity than that given by conventional methods. A guideline for evaluating the dose homogeneity of treatment plans based on the S‐index and its relation to equivalent uniform dose is discussed. PACS numbers: 87.53.Xd, 87.53.Tf

Single-Dose Versus Fractionated Stereotactic Radiotherapy for Brain Metastases

PURPOSE To evaluate the efficacy of stereotactic radiotherapy in patients with brain metastases by comparing two different treatment regimens, single-dose radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT). METHODS AND MATERIALS Between November 2003 and December 2008, 98 patients with brain metastases were included. Fifty-eight patients were treated with SRS, and forty were treated with FSRT. Fractionated stereotactic radiotherapy was used for large lesions or lesions located near critical structures. The median doses were 20 Gy for the SRS group and 36 Gy in 6 fractions for the FSRT group. RESULTS With a median follow-up period of 7 months, the median survival was 7 months for all patients, with a median of 6 months for the SRS group and 8 months for the FSRT group (p = 0.89). Local progression-free survival (LPFS) rates at 6 months and 1 year were 81% and 71%, respectively, for the SRS group and 97% and 69%, respectively, for the FSRT group (p = 0.31). Despite the fact that FSRT was used for large lesions and lesions in adverse locations, LPFS was not inferior to SRS. Toxicity was more frequently observed in the SRS group than in the FSRT group (17% vs. 5%, p = 0.05). CONCLUSIONS Because patients treated with FSRT exhibited similar survival times and LPFS rates with a lower risk of toxicity in comparison to those treated with SRS, despite the fact that FSRT was used for large lesions and lesions in adverse locations, we find that FSRT can particularly be beneficial for patients with large lesions or lesions located near critical structures. Further investigation is warranted to determine the optimal dose/fractionation.

Primary chemotherapy for newly diagnosed nonsmall cell lung cancer patients with synchronous brain metastases compared with whole-brain radiotherapy administered first : result of a randomized pilot study.

This randomized pilot trial investigated whether primary chemotherapy was feasible in terms of efficacy, survival, toxicity profile, and quality of life compared with whole‐brain radiotherapy (WBRT) given first in chemotherapy‐naive patients nonsmall cell lung cancer (NSCLC) with synchronous brain metastasis when neurologic symptoms or signs are absent or controlled by supportive care.

Radiation-Induced Cancers From Modern Radiotherapy Techniques: Intensity-Modulated Radiotherapy Versus Proton Therapy

PURPOSE To assess and compare secondary cancer risk resulting from intensity-modulated radiotherapy (IMRT) and proton therapy in patients with prostate and head-and-neck cancer. METHODS AND MATERIALS Intensity-modulated radiotherapy and proton therapy in the scattering mode were planned for 5 prostate cancer patients and 5 head-and-neck cancer patients. The secondary doses during irradiation were measured using ion chamber and CR-39 detectors for IMRT and proton therapy, respectively. Organ-specific radiation-induced cancer risk was estimated by applying organ equivalent dose to dose distributions. RESULTS The average secondary doses of proton therapy for prostate cancer patients, measured 20-60 cm from the isocenter, ranged from 0.4 mSv/Gy to 0.1 mSv/Gy. The average secondary doses of IMRT for prostate patients, however, ranged between 3 mSv/Gy and 1 mSv/Gy, approximately one order of magnitude higher than for proton therapy. Although the average secondary doses of IMRT were higher than those of proton therapy for head-and-neck cancers, these differences were not significant. Organ equivalent dose calculations showed that, for prostate cancer patients, the risk of secondary cancers in out-of-field organs, such as the stomach, lungs, and thyroid, was at least 5 times higher for IMRT than for proton therapy, whereas the difference was lower for head-and-neck cancer patients. CONCLUSIONS Comparisons of organ-specific organ equivalent dose showed that the estimated secondary cancer risk using scattering mode in proton therapy is either significantly lower than the cases in IMRT treatment or, at least, does not exceed the risk induced by conventional IMRT treatment.

Treatment-Related Pneumonitis and Acute Esophagitis in Non–Small-Cell Lung Cancer Patients Treated With Chemotherapy and Helical Tomotherapy

PURPOSE To assess clinical outcomes and complications in patients with non-small-cell lung cancer (NSCLC) treated with helical tomotherapy (HT) with or without chemotherapy. METHODS AND MATERIALS Data from 37 NSCLC patients treated between January 2007 and August 2008 were analyzed retrospectively. Twenty-eight patients had Stage III disease. Concurrent and neoadjuvant chemotherapy was given to 24 and 14 patients, respectively. Radiotherapy was delivered to a total dose of 60-70.4 Gy at 2.0-2.4 Gy per fraction to the gross tumor volume and 50-64 Gy at 1.8-2.0 Gy per fraction to the planning target volume. RESULTS With a median follow-up of 18 months (range, 6-27 months), 2-year local control and overall survival rates were 63% and 56% for all 37 patients, respectively, and were 78% and 75% for the patients with Stage III disease who received concurrent chemoradiotherapy alone. Acute esophagitis and treatment-related pneumonitis (TRP) ≥Grade 3 occurred in 5 and 7 patients, respectively. Four patients died of treatment-related death (TRD) after HT. In univariate analysis, poor performance status, total lung V(5), contralateral lung (CL) V(5), and V(10) were associated with TRD. Only CL V(5) remained significant in the multivariate analysis (p = 0.029). CONCLUSIONS HT with chemotherapy has shown promising clinical outcomes, esophagitis, and TRPs. However, HT has produced a somewhat high rate of fatal pulmonary complications. Our data suggest that CL V(5) should be considered and kept as low as possible (<60%) in addition to the conventional dosimetric factors.

Hepatocellular Cancer Arises from Loss of Transforming Growth Factor Beta Signaling Adaptor Protein Embryonic Liver Fodrin Through Abnormal Angiogenesis

We have previously demonstrated that 40%‐70% of elf+/− mice spontaneously develop hepatocellular cancer (HCC) within 15 months, revealing the importance of the transforming growth factor‐beta (TGF‐β) signaling pathway in suppressing tumorigenesis in the liver. The current study was carried out to investigate mechanisms by which embryonic liver fodrin (ELF), a crucial Smad3/4 adaptor, suppresses liver tumor formation. Histological analysis of hyperplastic liver tissues from elf+/− mice revealed abundant newly formed vascular structures, suggesting aberrant angiogenesis with loss of ELF function. In addition, elf+/− mice displayed an expansion of endothelial progenitor cells. Ectopic ELF expression in fetal bovine heart endothelial (FBHE) cells resulted in cell cycle arrest and apoptosis. Further analysis of developing yolk sacs of elf−/− mice revealed a failure of normal vasculature and significantly decreased endothelial cell differentiation with embryonic lethality. Immunohistochemical analysis of hepatocellular cancer (HCC) from the elf+/− mice revealed an abnormal angiogenic profile, suggesting the role of ELF as an angiogenic regulator in suppressing HCC. Lastly, acute small interfering RNA (siRNA) inhibition of ELF raised retinoblastoma protein (pRb) levels nearly fourfold in HepG2 cells (a hepatocellular carcinoma cell line) as well as in cow pulmonary artery endothelial (CPAE) cells, respectively. Conclusion: Taken together these results, ELF, a TGF‐β adaptor and signaling molecule, functions as a critical adaptor protein in TGF‐β modulation of angiogenesis as well as cell cycle progression. Loss of ELF in the liver leads the cancer formation by deregulated hepatocyte proliferation and stimulation of angiogenesis in early cancers. Our studies propose that ELF is potentially a powerful target for mimetics enhancing the TGF‐β pathway tumor suppression of HCC. (HEPATOLOGY 2008.)

Intensity-modulated radiotherapy with a belly board for rectal cancer

Background and aimIntensity-modulated radiotherapy (IMRT) techniques can reduce the irradiated small bowel volume in rectal cancer patients, but combined use of IMRT and a belly board is yet to be reported on for rectal cancer patients. The aim of this study was to determine whether additional use of a belly board reduced the irradiated small bowel volume observed using IMRT alone in rectal cancer patients.Materials and methodsTwenty patients scheduled to receive preoperative radiotherapy for rectal cancer underwent two series of CT scans, with and without a belly board. IMRT planning was performed using 6-MV photon beams and seven equispaced fields. The bladder, small bowel, and planning target volume (PTV) were analyzed for doses between 10% and 100% of the prescribed dose at 10% intervals. Data were analyzed using Wilcoxon signed rank tests.ResultsThere were no significant differences between patients undergoing IMRT with a belly board and those without a belly board in terms of total small bowel volumes, bladder, and PTV (p=0.571, p=0.841, and p=0.870, respectively). Statistical analysis showed that the irradiated small bowel volume with a belly board was smaller than that without a belly board (p<0.05 at 20–100% dose levels), with the mean relative reduction in the irradiated small bowel volume being 37.8±32.8%.ConclusionIMRT with a belly board is more effective than IMRT alone in reducing the irradiated small bowel volume. These findings suggest that the use of a belly board with IMRT may reduce small bowel complications in preoperative radiotherapy.

Low Initial Human Papilloma Viral Load Implicates Worse Prognosis in Patients With Uterine Cervical Cancer Treated With Radiotherapy

PURPOSE To evaluate whether human papillomavirus (HPV) viral load measured in cervical smear and HPV type 18 are associated with radiotherapy outcomes in uterine cervical cancer. PATIENTS AND METHODS HPV DNA: was semiquantitatively measured in the cervical smears of 169 radiotherapy patients. HPV viral load was classified as low or high according to median HPV DNA titer and examined for its prognostic value. The multivariable Cox proportional hazards model was used to adjust for covariates. A relapse-predicting model was constructed to classify three risk groups for disease-free survival (DFS), which were used for internal validation. RESULTS Patients with lower HPV viral load showed worse DFS in univariate analysis. HPV type 18, younger patient age, stage group, nodal status, histologic grade, and histologic type were other prognostic factors for poor DFS. Among these factors, all except stage group were associated with HPV viral load. Multivariate analysis showed the strong influence of HPV viral load for poor DFS. The prognostic model developed using our outcome data performed well in predicting the risk of relapse. CONCLUSION Our data suggest that HPV viral load is a strong independent prognostic factor for DFS. HPV type 18 showed a significant relationship with poor radiotherapy outcome in univariate analysis, but not in multivariate analysis.