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1.  Randomized Trial of Hypofractionated External-Beam Radiotherapy for Prostate Cancer 
Journal of Clinical Oncology  2013;31(31):3860-3868.
To determine if escalated radiation dose using hypofractionation significantly reduces biochemical and/or clinical disease failure (BCDF) in men treated primarily for prostate cancer.
Patients and Methods
Between June 2002 and May 2006, men with favorable- to high-risk prostate cancer were randomly allocated to receive 76 Gy in 38 fractions at 2.0 Gy per fraction (conventional fractionation intensity-modulated radiation therapy [CIMRT]) versus 70.2 Gy in 26 fractions at 2.7 Gy per fraction (hypofractionated IMRT [HIMRT]); the latter was estimated to be equivalent to 84.4 Gy in 2.0 Gy fractions. High-risk patients received long-term androgen deprivation therapy (ADT), and some intermediate-risk patients received short-term ADT. The primary end point was the cumulative incidence of BCDF. Secondarily, toxicity was assessed.
There were 303 assessable patients with a median follow-up of 68.4 months. No significant differences were seen between the treatment arms in terms of the distribution of patients by clinicopathologic or treatment-related (ADT use and length) factors. The 5-year rates of BCDF were 21.4% (95% CI, 14.8% to 28.7%) for CIMRT and 23.3% (95% CI, 16.4% to 31.0%) for HIMRT (P = .745). There were no statistically significant differences in late toxicity between the arms; however, in subgroup analysis, patients with compromised urinary function before enrollment had significantly worse urinary function after HIMRT.
The hypofractionation regimen did not result in a significant reduction in BCDF; however, it is delivered in 2.5 fewer weeks. Men with compromised urinary function before treatment may not be ideal candidates for this approach.
PMCID: PMC3805927  PMID: 24101042
2.  Stereotactic Ablative Radiotherapy (SABR): Impact on the Immune System and Potential for Future Therapeutic Modulation 
Stereotactic ablative radiotherapy (SABR) has been demonstrated to provide excellent local control in several malignancies. Recent reports have suggested that this ablative dose may impact disease outside of the radiated area. Furthermore, these studies have implicated immune modulation as the primary mechanism of disease response outside the irradiated area. More specifically, T-cell stimulation and tumor necrosis factor-α modulation following high dose irradiation have been suggested as the responsible components of this phenomenon. In addition, the “abscopal effect” may play a role in disease response outside of the radiated area. We review the current literature regarding the effects of ablative radiation therapy, the potential for immune modulation from it, and the mechanisms of the distant effects it elicits.
PMCID: PMC4128167  PMID: 25126157
Ablative Radiotherapy; Immune Response; Therapeutic Modulation
3.  Chemoradiation for Definitive, Pre-operative, or Post-Operative Therapy of Locally Advanced Non-Small Cell Lung Cancer 
Cancer journal (Sudbury, Mass.)  2013;19(3):222-230.
Over the last few decades, the integration of chemotherapy and radiation has played a crucial role in the management of locally advanced NSCLC. Locally advanced NSCLC is a very heterogeneous disease. Because of this heterogeneity, advanced NSCLC can be managed in various different ways depending on the bulk of disease, the comorbidities of the patient and the expertise and resources of the treating physicians and facilities. This review describes the evolution of current treatment strategies and predicted future changes for the management of locally advanced NSCLC.
PMCID: PMC3703658  PMID: 23708069
Non-small cell lung cancer; locally advanced; stage III; chemoradiotherapy; combined modality; chemoradiation; chemotherapy; radiation
4.  Spatial-Temporal FDG-PET Features for Predicting Pathologic Response of Esophageal Cancer to Neoadjuvant Chemoradiotherapy 
To extract and study comprehensive spatial–temporal 18F-FDG PET features for the prediction of pathologic tumor response to neoadjuvant chemoradiotherapy (CRT) in esophageal cancer.
Methods and Materials
Twenty patients with esophageal cancer were treated with trimodality therapy (CRT plus surgery) and underwent FDG PET/CT scans both before (pre-CRT) and after (post-CRT) CRT. The two scans were rigidly registered. A tumor volume was semiautomatically delineated using a threshold of standardized uptake value (SUV) ≥ 2.5, followed by manual editing. Comprehensive features were extracted to characterize the SUV intensity distribution, spatial patterns (texture), tumor geometry, and associated changes resulting from CRT. The usefulness of each feature in predicting pathologic tumor response to CRT was evaluated using the area under the receiver operating characteristic curve (AUC).
The best traditional response measure was maximum SUV (SUVmax) decline (AUC 0.76). Two new intensity features (SUVmean decline and skewness) and three texture features (inertia, correlation, and cluster prominence) were found to be significant predictors with AUCs ≥ 0.76. According to these features, a tumor was more likely a responder when the mean SUV decline was larger, when there were relatively fewer voxels with higher SUVs pre-CRT, or when FDG uptake post-CRT was relatively homogeneous. All of the most accurate predictive features were extracted from the entire tumor rather than from the most active part of the tumor. For SUV intensity features and tumor size features, changes were more predictive than pre- or post-CRT assessments alone.
Spatial–temporal FDG PET features were found to be useful predictors of pathologic tumor response to neoadjuvant chemoradiotherapy in esophageal cancer. Key words: FDG PET/CT, Tumor response, Esophageal cancer, Quantitative image analysis
PMCID: PMC3606641  PMID: 23219566
FDG PET/CT; Tumor response; Esophageal cancer; Quantitative image analysis
5.  Impact of neck dissection on long-term feeding tube dependence in head and neck cancer patients treated with primary radiation or chemoradiation 
Head & neck  2010;32(3):341-347.
The impact of post-treatment neck dissection on prolonged feeding tube dependence in head and neck squamous cell cancer (HNSCC) patients treated with primary radiation or chemoradiation remains unknown.
Retrospective cohort study using propensity score adjustment to investigate the effect of neck dissection on prolonged feeding tube dependence.
A review of 67 patients with node positive HNSCC (T1-4N1-3), treated with primary radiation or chemoradiation, with no evidence of tumor recurrence and follow-up of at least 24 months was performed. Following adjustment for covariates, the relative risk of feeding tube dependence at 18 months was significantly increased in patients treated with post-treatment neck dissection (RR 4.74, 95% CI 2.07-10.89). At 24 months, the relative risk of feeding tube dependence in the patients having undergone neck dissection increased further (RR 7.66, 95% CI 2.07-10.89). Of patients with feeding tubes two years after completing treatment, 75% remained feeding tube dependent.
Neck dissection may contribute to chronic oropharyngeal dysphagia in HNSCC patients treated with primary radiation or chemoradiation.
PMCID: PMC3457780  PMID: 19693946
6.  The Use of a Conventional Low Neck Field (LNF) and Intensity-Modulated Radiation Therapy (IMRT): No Clinical Detriment of IMRT to an Anterior LNF during the Treatment of Head and Neck Cancer 
Appropriate treatment of the lower neck when using IMRT is controversial. Our study tried to determine differences in clinical outcomes using IMRT or a standard LNF to treat low neck.
Methods and Materials
This is a retrospective, single institution study. Ninety-one patients with squamous cell carcinoma of head and neck cancer were treated with curative intent. Based on physician preference, some patients were treated with LNF (PTV3) field using a single anterior photon field matched to the IMRT field. Field junctions were not feathered. The endpoints were time to failure and use of PEG tube (as a surrogate of laryngeal edema causing aspiration) and analysis done with chi-square and the log-rank tests.
Median follow up 21 months (range 2 – 89). The median age 60 years. Thirty seven (41%) were treated with LNF, 84% were stage III or IV. PEG tube was required in 30% as opposed to 33% without the use of LNF. N2 or 3 neck disease was treated more commonly without a LNF (38% vs. 24%, p = 0.009). Failures occurred in 12 patients (13%). Only one patient treated with LNF failed regionally, 4.5 cm above the match line. The 3-year disease-free survival rate was 87%, 79% with LNF and without LNF respectively (p = 0.2) and the 3-year LR failure rate was 4%, 21% respectively, (p = 0.04).
Using LNF to treat the low neck did not increase the risk of regional failure “in early T& early N diseases” or decrease PEG tube requirements.
PMCID: PMC3339153  PMID: 20385457
IMRT; Head and Neck cancer; Low neck field; RT toxicities; PEG tube
7.  Esophageal Motion During Radiotherapy: Quantification and Margin Implications 
To evaluate inter- and intra-fraction esophageal motion in the right-left (RL) and anterior-posterior (AP) directions using computed tomography (CT) in esophageal cancer patients.
Methods and Materials
Eight patients underwent CT simulation and CT-on-rails imaging before and after radiotherapy. Inter-fraction displacement was defined as differences between pre-treatment and simulation images. Intra-fraction displacement was defined as differences between pre- and post-treatment images. Images were fused using bone registries, adjusted to the carina. The mean, average of the absolute, and range of esophageal motion were calculated in RL and AP directions, above and below the carina.
Thirty-one CT image sets were obtained. The incidence of esophageal inter-fraction motion ≥5 was 24% and ≥10 mm was 3%; intra-fraction motion ≥ 5mm was 13% and ≥10 mm was 4%. The average RL motion was 1.8±5.1 mm, favoring leftward movement, and the average AP motion was 0.6±4.8 mm, favoring posterior movement. Average absolute motion was 4.2 mm or less in RL and AP directions. Motion was greatest in the RL direction above the carina. Coverage of 95% of esophageal mobility requires 12mm left, 8mm right, 10mm posterior, and 9mm anterior margins.
In all directions, the average of the absolute inter-fraction and intra-fraction displacement was 4.2 mm or less. These results support a 12 mm left, 8 mm right, 10 mm posterior, and 9 mm anterior margin for ITV and can guide margins for future IMRT trials to account for organ motion and set up error in 3-dimesional planning.
PMCID: PMC2933373  PMID: 20095993
Esophageal cancer; Radiotherapy; Treatment margin; Organ motion
To compare the toxicity and biochemical outcomes of intensity-modulated radiation therapy (IMRT) and 125I transperineal permanent prostate seed implant (125I) for patients with low-risk prostate cancer.
Methods and Materials
Between 1998 and 2004, a total of 374 low-risk patients (prostate-specific antigen < 10 ng/ml, T1c–T2b, Gleason score of 6 or less, and no neoadjuvant hormones) were treated at Fox Chase Cancer Center (216 IMRT and 158 125I patients). Median follow-up was 43 months for IMRT and 48 months for 125I. The IMRT prescription dose ranged from 74–78 Gy, and 125I prescription was 145 Gy. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was recorded by using a modified Radiation Therapy Oncology Group scale. Freedom from biochemical failure was defined by using the Phoenix definition (prostate-specific antigen nadir + 2.0 ng/ml).
Patients treated by using IMRT were more likely to be older and have a higher baseline American Urological Association symptom index score, history of previous transurethral resection of the prostate, and larger prostate volumes. On multivariate analysis, IMRT was an independent predictor of lower acute and late Grade 2 or higher GU toxicity and late Grade 2 or higher GI toxicity. Three-year actuarial estimates of late Grade 2 or higher toxicity were 2.4% for GI and 3.5% for GU by using IMRT compared with 7.7% for GI and 19.2% for GU for 125I, respectively. Four-year actuarial estimates of freedom from biochemical failure were 99.5% for IMRT and 93.5% for 125I (p = 0.09).
The IMRT and 125I produce similar outcomes, although IMRT appears to have less acute and late toxicity.
PMCID: PMC2763097  PMID: 18207665
Prostate cancer; Radiation therapy; IMRT; Brachytherapy; Toxicity
The α/β ratio for prostate cancer is postulated to be between 1 and 3, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. The dosimetry and acute toxicity are described in the first 100 men enrolled in a randomized trial.
Patients and Methods
The trial compares 76 Gy in 38 fractions (Arm I) to 70.2 Gy in 26 fractions (Arm II) using intensity modulated radiotherapy. The planning target volume (PTV) margins in Arms I and II were 5 mm and 3 mm posteriorly and 8 mm and 7 mm in all other dimensions. The PTV D95% was at least the prescription dose.
The mean PTV doses for Arms I and II were 81.1 and 73.8 Gy. There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity acutely. However, there was a slight but significant increase in Arm II GI toxicity during Weeks 2, 3, and 4. In multivariate analyses, only the combined rectal DVH parameter of V65 Gy/V50 Gy was significant for GI toxicity and the bladder volume for GU toxicity.
Hypofractionation at 2.7 Gy per fraction to 70.2 Gy was well tolerated acutely using the planning conditions described.
PMCID: PMC1892754  PMID: 16242256
IMRT; Dosimetry; Hypofractionation; Toxicity

Results 1-9 (9)