Jessica Wobb

Use of intensity modulated radiation therapy to reduce acute and chronic toxicities of breast cancer patients treated with traditional and accelerated whole breast irradiation

PURPOSE The purpose of this analysis was to examine the impact of applying intensity modulated radiation therapy (IMRT) on toxicity with traditional and accelerated whole breast irradiation (AWBI). METHODS AND MATERIALS A total of 335 patients with stage 0-IIB breast cancer were treated with either a conventional wedge technique (S-WBI, n = 87), IMRT (I-WBI, n = 93), or AWBI with IMRT (I-AWBI, n = 155). S-WBI and I-WBI patients received a median dose of 45 Gy to the breast with a median 16-Gy tumor bed boost for a cumulative median dose of 61 Gy. I-AWBI patients received a median dose of 42.56 Gy via an accelerated IMRT plan, without a boost. Acute and chronic toxicities were assessed using Common Toxicity Criteria v.3.0. RESULTS Median follow-up was 11.0, 9.1, and 1.1 years for S-WBI, I-WBI, and I-AWBI patients, respectively. When comparing patients of all breast sizes, I-WBI showed decreased incidences of grade 2+ acute radiation dermatitis and induration compared with I-AWBI (1% vs 23%, P < .001/0% vs 5%; P = .05 ) and S-WBI (1% vs 12%, P = .007/0% vs 6%; P = .02). I-WBI also had lower rates of chronic edema compared with S-WBI patients (3% vs 13%, P = .03). In larger breasted patients, I-WBI was associated with reduced acute toxicities compared with S-WBI with regard to grade 2 + dermatitis and edema (0% vs 19%, P = .02/7% vs 24%, P = .06). No differences were seen between I-WBI and I-AWBI with IMRT techniques with the exception of increased acute radiation dermatitis in I-AWBI patients (0% vs 38%, P < .001). CONCLUSIONS This analysis confirms previous data which have demonstrated that RT with IMRT is associated with reduced toxicities compared with conventional techniques. In larger breasted women, with the exception of acute skin reactions, I-AWBI showed comparable rates of toxicities compared with I-WBI. These data support the use of IMRT to expand the role of AWBI and the currently accruing Radiation Therapy Oncology Group 1005 trial.

Cost-effectiveness of 3-dimensional conformal radiotherapy and applicator-based brachytherapy in the delivery of accelerated partial breast irradiation.

Purpose:To compare reimbursement and cost efficacy between accelerated partial breast irradiation (APBI) techniques. Materials/Methods:Four hundred fifty-three patients were treated with APBI using either 3-dimensional conformal radiotherapy (3D-CRT, n=207) or balloon-based brachytherapy (BB) [single-lumen (SL, n=161) and multilumen (ML, n=85)] between March 2000 and October 2011. To evaluate cost-effectiveness, reimbursement by treatment technique was calculated based on 2011 Medicare schedules. Facility costs were generated by technique based on ICD-9 codes. Incremental cost effectiveness ratios (ICER), which compares cost with clinical outcomes, were calculated according to the difference in reimbursement to the criteria being evaluated. Results:With a median follow-up of 3.6 years, the 5-year rate of local recurrence was 1.9% for all patients (3D-CRT, 0%; BB, 4.1%; P=0.23). When pooled, BB patients had a significant improvement in excellent/good cosmesis (91.6% vs. 80.0%; P=0.03). Rates of combined grade 2 or higher dermatitis, hyper/hypopigmentation, pain, or fibrosis per technique were 62%, 28%, and 34% for 3D-CRT, SL, and ML patients, respectively (P=0.26). The ICER per percent improved cosmesis for SL/ML was

The Effects of Pulsed Radiation Therapy on Tumor Oxygenation in 2 Murine Models of Head and Neck Squamous Cell Carcinoma

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Nomogram for Predicting the Risk of Locoregional Recurrence in Patients Treated With Accelerated Partial-Breast Irradiation

850 based on reimbursement and

Brachytherapy-based Accelerated Partial Breast Irradiation Provides Equivalent 10-Year Outcomes to Whole Breast Irradiation: A Matched-Pair Analysis.

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Impact of the Number of Cautionary and/or Unsuitable Risk Factors on Outcomes After Accelerated Partial Breast Irradiation

643 based on cost compared with 3D-CRT. Conclusions:On the basis of ICER, brachytherapy for APBI is a cost-effective option with regard to cosmesis and toxicity. This economic analysis suggests the increased cost of applicator-based brachytherapy may be justified in appropriately selected patients.

Gene Expression Characterization of HPV Positive Head and Neck Cancer to Predict Response to Chemoradiation

PURPOSE To evaluate the efficacy of low-dose pulsed radiation therapy (PRT) in 2 head and neck squamous cell carcinoma (HNSCC) xenografts and to investigate the mechanism of action of PRT compared with standard radiation therapy (SRT). METHODS AND MATERIALS Subcutaneous radiosensitive UT-SCC-14 and radioresistant UT-SCC-15 xenografts were established in athymic NIH III HO female mice. Tumors were irradiated with 2 Gy/day by continuous standard delivery (SRT: 2 Gy) or discontinuous low-dose pulsed delivery (PRT: 0.2 Gy × 10 with 3-min pulse interval) to total doses of 20 Gy (UT14) or 40 Gy (UT15) using a clinical 5-day on/2-day off schedule. Treatment response was assessed by changes in tumor volume, (18)F-fluorodeoxyglucose (FDG) (tumor metabolism), and (18)F-fluoromisonidazole (FMISO) (hypoxia) positron emission tomography (PET) imaging before, at midpoint, and after treatment. Tumor hypoxia using pimonidazole staining and vascular density (CD34 staining) were assessed by quantitative histopathology. RESULTS UT15 and UT14 tumors responded similarly in terms of growth delay to either SRT or PRT. When compared with UT14 tumors, UT15 tumors demonstrated significantly lower uptake of FDG at all time points after irradiation. UT14 tumors demonstrated higher levels of tumor hypoxia after SRT when compared with PRT as measured by (18)F-FMISO PET. By contrast, no differences were seen in (18)F-FMISO PET imaging between SRT and PRT for UT15 tumors. Histologic analysis of pimonidazole staining mimicked the (18)F-FMISO PET imaging data, showing an increase in hypoxia in SRT-treated UT14 tumors but not PRT-treated tumors. CONCLUSIONS Differences in (18)F-FMISO uptake for UT14 tumors after radiation therapy between PRT and SRT were measurable despite the similar tumor growth delay responses. In UT15 tumors, both SRT and PRT were equally effective at reducing tumor hypoxia to a significant level as measured by (18)F-FMISO and pimonidazole.

Seven-Year Outcomes Following Accelerated Partial Breast Irradiation Stratified by ASTRO Consensus Groupings.

PURPOSE To develop a nomogram taking into account clinicopathologic features to predict locoregional recurrence (LRR) in patients treated with accelerated partial-breast irradiation (APBI) for early-stage breast cancer. METHODS AND MATERIALS A total of 2000 breasts (1990 women) were treated with APBI at William Beaumont Hospital (n=551) or on the American Society of Breast Surgeons MammoSite Registry Trial (n=1449). Techniques included multiplanar interstitial catheters (n=98), balloon-based brachytherapy (n=1689), and 3-dimensional conformal radiation therapy (n=213). Clinicopathologic variables were gathered prospectively. A nomogram was formulated utilizing the Cox proportional hazards regression model to predict for LRR. This was validated by generating a bias-corrected index and cross-validated with a concordance index. RESULTS Median follow-up was 5.5 years (range, 0.9-18.3 years). Of the 2000 cases, 435 were excluded because of missing data. Univariate analysis found that age <50 years, pre-/perimenopausal status, close/positive margins, estrogen receptor negativity, and high grade were associated with a higher frequency of LRR. These 5 independent covariates were used to create adjusted estimates, weighting each on a scale of 0-100. The total score is identified on a points scale to obtain the probability of an LRR over the study period. The model demonstrated good concordance for predicting LRR, with a concordance index of 0.641. CONCLUSIONS The formulation of a practical, easy-to-use nomogram for calculating the risk of LRR in patients undergoing APBI will help guide the appropriate selection of patients for off-protocol utilization of APBI.

Mutational landscape of radiation-associated angiosarcoma of the breast

Introduction:Although whole breast irradiation (WBI) represents the standard radiotherapy technique in breast conserving therapy, accelerated partial breast irradiation (APBI) has emerged as an option to reduce treatment duration with comparable clinical outcomes. The purpose of this analysis is to present long-term clinical outcomes between WBI and APBI. Methods:A total of 3009 patients were treated with breast conserving therapy at a single institution between 1980 and 2012. Among them, 2528 patients received WBI and 481 received APBI (interstitial or balloon based). A matched-pair analysis was performed with patients matched by age (±3 years), stage (T-stage vs. T1 vs. T2), and estrogen receptor status (+/−). All patients had a minimum of 12 months follow-up. A total of 274 matches (ratio 1:1) were made. Results:No differences between groups were noted with respect to clinicopathologic features; WBI patients demonstrated a trend for slightly larger tumors (1.3 vs. 1.1 cm, P=0.06). At 10 years, no differences were noted with respect to rates of ipsilateral breast tumor recurrence (4% vs. 4%, P=0.11), regional recurrence (1% vs. 1%, P=0.20), contralateral breast failure (9% vs. 3%, P=0.06), or distant metastases (3% vs. 6%, P=0.47) for WBI and APBI, respectively. In addition, 10-year disease-free survival (93% vs. 91%, P=0.10) and overall survival (83% vs. 75%, P=0.34) were similar. Long-term cosmesis was good to excellent in 94% of WBI patients versus 95% of APBI patients (P=0.78). Conclusions:At 10 years, no differences in recurrence or survival were found between patients undergoing WBI or brachytherapy-based APBI.

Outcomes of patients with triple-negative breast cancer treated with radiation therapy.

PURPOSE To examine clinical outcomes of accelerated partial-breast irradiation (APBI) stratified by the number of American Society for Radiation Oncology consensus statement cautionary/unsuitable risk factors (RFs) present. METHODS AND MATERIALS A total of 692 patients were treated with APBI at a single institution between April 1993 and January 2012 using interstitial (n=195), balloon (n=292), and 3-dimensional conformal radiation therapy (n=205) techniques. Clinical outcomes were evaluated by risk group and number of RFs. RESULTS Median follow-up was 5.2 years (range, 0-18.3 years). Most patients were classified as suitable (n=240, 34%) or cautionary (n=343, 50%) risk, whereas 16% (n=109) were unsuitable. In patients with increasing total RFs (1 RF, 2 RF, 3+ RF), higher rates of grade 3 histology (10% vs 18% vs 32%, P<.001), estrogen receptor negativity (0 vs 12% vs 29%, P<.001), close/positive margins (0 vs 6% vs 17%, P<.001), and use of adjuvant chemotherapy (3% vs 12% vs 33%, P<.001) were noted. When pooling cautionary and unsuitable patients, increased ipsilateral breast tumor recurrence/regional recurrence was most notable for patients with 3 or more combined RFs versus 2 or fewer combined RFs (P<.001). CONCLUSIONS Patients with 3 or more cautionary or unsuitable RFs may be at risk for higher local, regional, and distant recurrence after breast-conserving therapy using APBI. Patients with 2 or fewer total RFs have 98% locoregional control at 5 years. Inclusion of total number of RFs in future risk stratification schemes for APBI may be warranted.