Faculty Bibliography

PURPOSE/OBJECTIVE:We report on a retrospective comparison of biochemical outcomes using an ultra-high dose of conventionally fractionated intensity-modulated radiation therapy (IMRT) vs. a lower dose of IMRT combined with high-dose-rate (HDR) brachytherapy to increase the biologically effective dose of IMRT. METHODS:Patients received IMRT of 86.4Gy (n=470) or HDR brachytherapy (21Gy in three fractions) followed by IMRT of 50.4Gy (n=160). Prostate-specific antigen (PSA) relapse was defined as PSA nadir+2. Median followup was 53 months for IMRT alone and 47 months for HDR. RESULTS:The 5-year actuarial PSA relapse-free survival (PRFS) for HDR plus IMRT vs. ultra-high-dose IMRT were 100% vs. 98%, 98% vs. 84%, and 93% vs. 71%, for National Comprehensive Cancer Network low- (p=0.71), intermediate- (p<0.001), and high-risk (p=0.23) groups, respectively. Treatment (p=0.0006), T stage (p<0.0001), Gleason score (p<0.0001), pretreatment PSA (p=0.0037), risk group (p<0.0001), and lack of androgen-deprivation therapy (p=0.0005) were significantly associated with improved PRFS on univariate analysis. HDR plus IMRT vs. ultra-high-dose IMRT (p=0.0012, hazard ratio [HR]=0.184); age (p=0.0222, HR=0.965); and risk group (p<0.0001, HR=2.683) were associated with improved PRFS on multivariate analysis. CONCLUSION/CONCLUSIONS:Dose escalation of IMRT by adding HDR brachytherapy provided improved PRFS in the treatment of prostate cancer compared with ultra-high-dose IMRT, independent of risk group on multivariate analysis, with the most significant benefit for intermediate-risk patients.

INTRODUCTION/BACKGROUND:Intensity modulated radiation therapy (IMRT) has been incorporated at several institutions for early stage laryngeal cancer (T1/T2N0M0), but its utility is controversial. METHODS:In three representative patients, multiple plans were generated: 1) Conventional 2D planning, with the posterior border placed at either the anterior aspect ("tight" plan) or the mid-vertebral body ("loose" plan), 2) 3D planning, utilizing both 1.0 and 0.5 cm margins for the planning target volume (PTV), and 3) IMRT planning, utilizing the same margins as the 3D plans. A dosimetric comparison was performed for the target volume, spinal cord, arytenoids, and carotid arteries. The prescription dose was 6300 cGy (225 cGy fractions), and the 3D and IMRT plans were normalized to this dose. RESULTS:For PTV margins of 1.0 cm and 0.5 cm, the D95 of the 2D tight/loose plans were 3781/5437 cGy and 5372/5869 cGy, respectively (IMRT/3D plans both 6300 cGy). With a PTV margin of 1.0 cm, the mean carotid artery dose was 2483/5671/5777/4049 cGy in the 2D tight, 2D loose, 3D, and IMRT plans, respectively. When the PTV was reduced to 0.5 cm, the the mean carotid artery dose was 2483/5671/6466/2577 cGy to the above four plans, respectively. The arytenoid doses were similar between the four plans, and spinal cord doses were well below tolerance. CONCLUSIONS:IMRT provides a more ideal dose distribution compared to 2D treatment and 3D planning in regards to mean carotid dose. We therefore recommend IMRT in select cases when the treating physician is confident with the GTV.

PURPOSE/OBJECTIVE:To report prostate-specific antigen (PSA) relapse-free survival and distant metastases-free survival (DMFS) outcomes for patients with clinically localized prostate cancer treated with high-dose conformal radiotherapy. METHODS AND MATERIALS/METHODS:Between 1988 and 2004, a total of 2,047 patients with clinically localized prostate cancer were treated with three-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Prescribed dose levels ranged from 66-86.4 Gy. Median follow-up was 6.6 years (range, 3-18 years). RESULTS:Although no differences were noted among low-risk patients for the various dose groups, significant improvements were observed with higher doses for patients with intermediate- and high-risk features. In patients with intermediate-risk features, multivariate analysis showed that radiation dose was an important predictor for improved PSA relapse-free survival (p < 0.0001) and improved DMFS (p = 0.04). In patients with high-risk features, multivariate analysis showed that the following variables predict for improved PSA relapse-free survival: dose (p < 0.0001); age (p = 0.0005), and neoadjuvant-concurrent androgen deprivation therapy (ADT; p = 0.01). In this risk group, only higher radiation dose was an important predictor for improved DMFS (p = 0.04). CONCLUSIONS:High radiation dose levels were associated with improved biochemical tumor control and decreased risk of distant metastases. For high-risk patients, despite the delivery of high radiation dose levels, the use of ADT conferred an additional benefit for improved tumor control outcomes. We observed a benefit for ADT in high-risk patients who received higher doses.

BACKGROUND:The purpose was to define the rate of local recurrence (LR) and identify prognostic factors for LR in patients with extremity soft-tissue sarcoma (STS) treated with limb-sparing surgery and a pathologically negative re-resection specimen without radiotherapy (RT). METHODS:A review of the prospective sarcoma database identified 200 patients with primary, nonmetastatic, extremity STS treated with limb-sparing surgery between June 1982 and December 2002 who had a pathologically confirmed negative re-resection. None of the patients had adjuvant RT. Univariate and multivariate analyses were performed to determine clinicopathologic factors associated with LR. RESULTS:With a median follow-up of 82 months the 5-year actuarial LR rate was 9%. Factors associated with higher LR rates on univariate and multivariate analysis were older age, stage III presentation, and histology. The 5-year LR rate was 5% for those<50 compared with 15% for those>or=50 (P=.001). For patients with stage III the LR rate was 26% versus 7% for those with stage I/II (P<.001). On multivariate analysis only age>or=50 (relative risk [RR] 3.3; P=.02) and stage III disease (RR 3.4; P=.01) remained significant predictors for LR. When the cohort of patients was divided into 3 groups based on the number of risk factors present, the 5-year LRs were as follows: no risk factors (stage I/II and<50 years old) 4%, 1 risk factor (stage III or>or=50) 12%, and 2 risk factors (stage III and>or=50) 31% (P<.01). CONCLUSIONS:Patients with a pathologically negative re-excision represent a heterogeneous group. Whereas the overall rate of local recurrence at 5 years was 9% for the entire cohort, patients with older age and/or stage III disease had a higher rate of LR. Therefore, treatment decisions especially with regard to adjuvant RT should be individualized and not be based solely on the finding of a negative re-resection.

PURPOSE/OBJECTIVE:To report toxicity and preliminary biochemical outcomes with high-dose intensity-modulated radiation therapy (IMRT) to a dose of 86.4 Gy for localized prostate cancer. METHODS AND MATERIALS/METHODS:Between August 1997 and March 2004, 478 patients were treated with 86.4 Gy using a 5- to 7-field IMRT technique. To adhere to normal tissue constraints, the mean D95 and V100 for the planning target volume were 83 Gy and 87%, respectively. Toxicity data were scored according to the Common Terminology Criteria for Adverse Events Version 3.0. Freedom from biochemical relapse was calculated. The median follow-up was 53 months. RESULTS:Thirty-seven patients (8%) experienced acute Grade 2 gastrointestinal (GI) toxicity. There was no acute Grade 3 or 4 GI toxicity. One hundred and five patients (22%) experienced acute Grade 2 genitourinary (GU) toxicity and three patients (0.6%) had Grade 3 GU toxicity. There was no acute Grade 4 GU toxicity. Sixteen patients (3%) developed late Grade 2 GI toxicity and two patients (<1%) developed late Grade 3 GI toxicity. Sixty patients (13%) had late Grade 2 GU toxicity and 12 (<3%) experienced late Grade 3 GU toxicity. The 5-year actuarial PSA relapse-free survival according to the nadir plus 2 ng/mL definition was 98%, 85% and 70% for the low, intermediate, and high risk NCCN prognostic groups. CONCLUSION/CONCLUSIONS:This report represents the largest data set of patients treated to ultra-high radiation dose levels of 86.4 Gy using IMRT for localized prostate cancer. Our findings indicate that this treatment is well tolerated and the early excellent biochemical control rates are encouraging.

Since its introduction into clinical use in the mid-1990s, intensity-modulated radiation therapy (IMRT) has emerged as the most effective and widely used form of external-beam radiotherapy for localized prostate cancer. Multiple studies have confirmed the importance of delivering sufficiently high doses to the prostate to achieve cure. The dosimetric superiority of IMRT over conventional techniques to produce conformal dose distributions that allow for organ sparing has been shown. A growing number of reports have confirmed that IMRT is the safest way to deliver high doses of external-beam irradiation to the prostate and the regional lymph nodes. Advances in imaging and onboard verification systems continue to advance the capabilities of IMRT and have potential implications with regards to further dose escalation and hypofractionated regimens. The clinical data in support of IMRT and the associated technical aspects of IMRT treatment planning and implementation are highlighted in this review.

BACKGROUND:Concurrent chemoradiation is becoming an increasingly popular treatment for patients with locally advanced head and neck cancer. The full extent of treatment related complications has not been completely documented in the literature. METHODS:We present the case of a patient treated with definitive intensity modulated radiation therapy and concurrent carboplatin and fluorouracil for a locally advanced oral cavity and base of tongue cancer. RESULTS:The patient suffered acute grade 4 dermatitis and mucositis during treatment. One month after completion of treatment, the patient was found to have permanent adherence of the tongue to the buccal mucosa as a result of severe scar tissue formation. CONCLUSIONS:As more patients undergo chemoradiation for the treatment of locally advanced head and neck cancer, the full extent of treatment related complications are being identified. To our knowledge, this is the first report of chemoradiation for head and neck cancer resulting in adherence of the tongue to the buccal mucosa.