[en] Purpose/Objective: The purpose of this investigation is to quantify dose inhomogeneity of intact breast irradiation in off-axis planes, and determine how dose inhomogeneity varies according to patient breast size and anatomical region of the breast. Methods and Materials: Eleven patients treated with intact breast radiation underwent a treatment-planning computer tomography (CT) scan with 1-cm slices through the entire breast. The area of breast tissue was defined on each CT slice. Treatment planning with lung correction factors was performed using a two-dimensional treatment-planning system that calculates off-axis dose distributions on a slice-by-slice basis. Each plan utilized tangential beams with matched non divergent posterior borders and with collimator rotation to match the chest wall slope. Dose inhomogeneity within the central plane was minimized during treatment planning by the use of a wedge on the lateral tangent field and by the differential weighting of fields. Dose was normalized at the breast and pectoralis major interface at mid separation in the central plane. Off-axis dose inhomogeneity was not considered in the optimization of the treatment plan. Dose distributions were plotted for each 1-cm slice, and the area of each isodose curve within the breast on each CT slice was calculated. The results of each slice were summed to give an approximation of dose-volume relationships. Results: For the entire population, an average of 10% of the breast volume (range 1-40%) received 110% or greater of the prescribed dose. Increasing dose inhomogeneity was positively correlated with increasing breast sizes (r 0.72, p = 0.01--Spearmen rank test). Analysis of dose as a function of location within the breast, revealed that the greatest dose inhomogeneity occurred in the lower anatomical quadrants of the breast (p 0.003--Kruskal-Wallis test). For the group, the mean breast volume that received a 110% or greater dose was: 30% at 6 cm below central axis, 14% at 4 cm below central axis, 6% at central axis, 5% at 4 cm above central axis, and 7% at 6 cm above central axis. Conclusion: Our study demonstrates that a significant volume of breast tissue receives 110% or greater of the prescribed dose. This inhomogeneity is greatest in women with larger breast sizes, providing a possible explanation for the poorer cosmetic result seen in this subset of patients compared to women with small breast sizes. In addition, our results show the greatest dose inhomogeneity in the lower quadrants of the breast. Off-axis dose inhomogeneity should be considered in the planning of tumor bed boosts in women with lower quadrant tumors

[en] PURPOSE/OBJECTIVE: The number of patients with early stage prostate cancer electing to receive transperineal interstitial permanent prostate brachytherapy (TIPPB) is rapidly escalating. However, quality assessment of this treatment modality remains relatively unaddressed. Particularly lacking is the ability to define implant quality. This study was undertaken to dosimetrically characterize a series of TIPPB cases from a single institution in order to assist in the establishment of benchmarks for post-operative quality assessment. METHODS/MATERIALS: Between November 1994 and February 1997, 135 patients with adenocarcinoma of the prostate underwent TIPPB; 110 as primary therapy and 25 as a boost following external beam. 73 patients received an I-125 implant with a median activity of 0.435 mCi/seed to a prescribed minimum peripheral dose (mPD) of 144 Gy (TG-43 defined), and 62 patients received a Pd-103 implant with a median activity of 1.4 mCi/seed prescribed to 115 Gy mPD (90 mPD for boosts). The number of seeds ranged from 28 to 142 (median 81) per case, and were implanted using a Mick applicator (25), rapid-strand (16), or loose seeds in preloaded needles (94) as the technique developed. Pre-treatment plans were generated using an in-house brachytherapy planning system based on ultrasound (US). Prostate US volumes ranged from 8.2 to 61.5 cc (median 28.8 cc). Post-implant dosimetry was based upon CT scans with 3 mm abutting slices, 15 cm FOV, performed 1 to 64 days post-operatively (mean 11.5 days). CT volumes were determined by the same physician, and ranged from 13.5 cc to 80.5 cc (median 35.6 cc). Gland coverage was evaluated by performing dose volume histogram (DVH) analysis, recording the percentage of the prostate gland encompassed by 80% and 100% of the reference dose (RD). Dose uniformity was quantified using the dose homogeneity index (DHI), defined as the volume of the prostate receiving more than 1.5 times the RD divided by the prostate volume. Dose surface histograms were also performed in a subset of patients to quantitate the area of the urethra (n=35) and rectum (n=77) receiving greater than 150% and 100% RD, respectively. RESULTS: The median percentage of the prostate volume encompassed by the 80% and 100% RD were 91.4% ± 8.8 (range 62.3%-100%) and 81.5% ± 12.7 (range 50.4%-100%), respectively. The median DHI achieved was 0.556 ± 0.091 (range 0.290-0.719). The mean urethral surface area receiving ≥ 150% RD was 1.64 cm². The mean rectal surface area receiving ≥ 100% RD was 3.86 cm². Univariate and covariate analyses of implant parameters which were examined for correlation to the DVH-based quantities included: case sequence number, number of days post-implant to CT scan, isotope, prescribed dose, number of seeds, activity/seed, implant technique, pre-implant ultrasound volume, and post-implant CT volume. The best combination of parameters in a multivariate analysis for predicting dose coverage of the prostate was a three-covariate model which included number of seeds (p ≤ 0.001), CT volume (p ≤ 0.0003), and case sequence number (p ≤ 0.0012). Prostate dose coverage significantly improved with experience. The mean prostate volume covered by the 80% RD was 85.0% for the first 27 cases compared to 90.3% for subsequent cases (p=0.005). CONCLUSIONS: This report constitutes the first detailed description of a dose-volume analysis of a large series of TIPPB patients. In our single institution experience, implant quality as measured by dose coverage of the prostate, is improved with a greater number of seeds, smaller target volume, and experience with the modality, irrespective of other factors. Dose coverage and resultant dose uniformity appear to be inversely related. An initial distinct learning curve was demonstrated reflecting experience with selection, pre-planning, and operative technique. These data show that 80% RD delivered to at least 90% of the prostate volume is reasonably achieved with TIPPB. Such a dose-volume relationship might be considered in future trials. Similar analyses from other institutions with correlation to outcome is required to validate these initial benchmarks

[en] Purpose: Hyperfractionated, accelerated radiotherapy (HART) has been advocated for patients with local-regionally recurrent breast cancer because it is believed to enhance treatment effects in rapidly proliferating or chemoresistant tumors. This report examines the value of HART in patients with local-regionally recurrent breast cancer treated with multimodality therapy. Methods and Materials: The study included 148 patients with local-regionally recurrent breast cancer after mastectomy, who were treated with definitive local irradiation and systemic therapy consisting of either tamoxifen, cytotoxic chemotherapy, or both, along with excision of the recurrent tumor when possible. Patients with distant metastases were excluded, except for two patients with ipsilateral supraclavicular nodal metastases. Patients received comprehensive irradiation to the chest wall and regional lymphatics to a median dose of 45 Gy, with a boost to 60 Gy to areas of recurrence. Sixty-eight patients (46%) were treated once daily at 2 Gy/fraction (fx), and 80 (54%) were treated twice daily at 1.5 Gy/fx. Forty-eight patients (32%), who had palpable gross disease that was unresponsive to systemic therapy and/or unresectable, were irradiated. The median follow-up time of surviving patients was 78 months. Results: Overall actuarial local-regional control (LRC) rates at 5 and 10 years were 68% and 55%, respectively. Five- and ten-year actuarial overall survival (OS) and disease-free survival (DFS) rates were 50% and 35%, 39% and 29%, respectively. Univariate analysis revealed that LRC was adversely affected by 1. advanced initial American Joint Committee on Cancer (AJCC) stage (p0.001), 2. clinically evident residual disease at time of treatment (p < 0.0001), 3. more than three positive nodes at initial mastectomy (p = 0.014), 4. short interval from mastectomy to recurrence (< 24 months, p = 0.0007), 5. nuclear grade (III vs. I or II, p = 0.045), and 6. number of recurrent nodules (1 vs. > 1, p = 0.02). Patient age at time of recurrence (< 40 vs. ≥ 40 years), recurrence location on the chest wall, estrogen receptor status, progesterone receptor status or menopausal status did not adversely affect LRC. On multivariate analysis, only clinically evident residual disease at the time of treatment and short interval from mastectomy to recurrence remained significant. When once-a-day irradiation was compared to the twice-a-day schedule, no significant differences were seen in LRC (67% vs. 68%), OS (47% vs. 52%), or DFS (42% vs. 36%) for the entire group of patients at 5 years. Pairwise comparison of the two fractionation schedules in each of the adverse outcome subgroups identified above showed no clinically significant differences in LRC at 5 years. For the 48 patients who began radiotherapy with measurable gross local recurrence, the complete response rate to radiotherapy was 73%, with no difference seen between the two fractionation schedules. The incidence of acute and chronic radiation-related complications was similar in both treatment groups. Conclusions: Hyperfractionated accelerated radiotherapy, although well tolerated by patients with local-regionally recurrent breast cancer, did not result in superior local-regional control rates when compared to daily fractionated regimens. Alternative strategies, such as dose escalation or chemoradiation, may be required to improve control

[en] Purpose: To evaluate the correlations and relative contributions of components of a radiation oncology-specific patient satisfaction survey to their overall satisfaction scores. Methods and Materials: From September 2006 through August 2012, we prospectively collected data from 8069 patients receiving radiation treatments with a 26-question survey. Each question was rated on a 10-point Likert scale. We analyzed the correlation between scores for each question and the overall satisfaction question. We also dichotomized the scores to reflect satisfaction versus dissatisfaction and used logistic regression to assess the relationship between items in 4 domains (the patient–provider relationship, access and environmental issues, wait times, and educational information) and overall satisfaction. Results: Scores on all questions correlated with overall patient satisfaction scores (P<.0001). Satisfaction with patient–provider relationships had the greatest influence on overall satisfaction (R²=0.4219), followed by wait times (R²=0.4000), access/environment (R²=0.3837), and patient education (R²=0.3700). The specific variables with the greatest effect on patient satisfaction were the care provided by radiation therapists (odds ratio 1.91) and pain management (odds ratio 1.29). Conclusions: We found that patients' judgment of provider relationships in an outpatient radiation oncology setting were the greatest contributors to their overall satisfaction ratings. Other measures typically associated with patient satisfaction (phone access, scheduling, and ease of the check-in process) correlated less strongly with overall satisfaction. These findings may be useful for other practices preparing to assess patient ratings of quality of care

[en] Purpose: The objective of this study was to evaluate the influence of pathologic factors other than tumor size and number of involved axillary nodes on the risk of locoregional recurrence (LRR) following mastectomy. Patients and Methods: We reviewed the medical records of 1031 patients treated with mastectomy and doxorubicin-based chemotherapy without radiation on 5 prospective clinical trials. Median follow-up was 116 months (range, 6-262 months). Results: Patients with gross multicentric disease were at increased risk of LRR (37% at 10 years). However, patients with multifocal disease and those with microscopic multicentric disease did not experience higher rates of LRR than those with single lesions (17% at 10 years). Patients with lymph-vascular space invasion (LVSI) or involvement of the skin or nipple also experienced high rates of LRR (25%, 32%, and 50%, respectively). The presence of close (<5 mm) or positive margins was associated with an increased risk of LRR (45%). The increased risk of LRR observed for patients with pectoral fascial invasion (33%) was not reduced when negative deep margins were obtained. On multivariate analysis, the presence of 4 or more involved axillary nodes, tumor size of greater than 5 cm, close or positive surgical margins, and gross multicentric disease were found to be independent predictors of LRR (all, p<0.01). In a separate analysis including only patients with 1-3 involved axillary nodes, microscopic invasion of the skin or nipple, pectoral fascial invasion, and the presence of close or positive margins were significant predictors of LRR. Conclusion: In addition to the extent of primary and nodal disease, other factors that predict for high rates of LRR include the presence of LVSI, involvement of the skin, nipple or pectoral fascia, close or positive margins, or gross multicentric disease. These factors predict for high LRR rates regardless of the number of involved axillary nodes

[en] Purpose: Postmastectomy irradiation (PMI) is a technically complex treatment requiring consideration of the primary tumor location, possible risk of internal mammary node involvement, varying chest wall thicknesses secondary to surgical defects or body habitus, and risk of damaging normal underlying structures. In this report, we describe the application of a customized three-dimensional (3D) electron bolus technique for delivering PMI. Methods and Materials: A customized electron bolus was designed using a 3D planning system. Computed tomography (CT) images of each patient were obtained in treatment position and the volume to be treated was identified. The distal surface of the wax bolus matched the skin surface, and the proximal surface was designed to conform to the 90% isodose surface to the distal surface of the planning target volume (PTV). Dose was calculated with a pencil-beam algorithm correcting for patient heterogeneity. The bolus was then fabricated from modeling wax using a computer-controlled milling device. To aid in quality assurance, CT images with the bolus in place were generated and the dose distribution was computed using these images. Results: This technique optimized the dose distribution while minimizing irradiation of normal tissues. The use of a single anterior field eliminated field junction sites. Two patients who benefited from this option are described: one with altered chest wall geometry (congenital pectus excavatum), and one with recurrent disease in the medial chest wall and internal mammary chain (IMC) area. Conclusion: The use of custom 3D electron bolus for PMI is an effective method for optimizing dose delivery. The radiation dose distribution is highly conformal, dose heterogeneity is reduced compared to standard techniques in certain suboptimal settings, and excellent immediate outcome is obtained

[en] Purpose: To help establish standards of care for transperineal interstitial permanent prostate brachytherapy (TIPPB) by obtaining data regarding current clinical practice among the most experienced TIPPB brachytherapists in the United States. Methods and Materials: The 70 brachytherapists who performed the greatest number of TIPPB cases in 1995 in the U.S. were surveyed. Each received a comprehensive four page questionnaire that included sections on training and experience, patient and isotope selection criteria, manpower, technique, and follow-up. Thirty-five (50%) surveys were ultimately returned after three mailings and follow-up phone calls. The cumulative experience of the 35 respondents represented approximately 45% of the total TIPPB volume in the U.S. for 1995. Respondents included 29 from the private sector and six from academic programs. Results: The median physician experience with TIPPB was reported as 4.9 years. Each performed an average of 73 TIPPB procedures in 1995 (range 40-300). This represented an increase in volume for most (74%) of the respondents. Sixty-three percent of the respondents attended a formal training course, 54% had TIPPB-specific residency training, and 31% had been proctored (16 had received two or more types of training experience). The most commonly reported selection criteria for implant alone was on Gleason score ≤7, PSA <15, ≤ Stage T2a, and gland size ≤60 cc, although no clear consensus was found. Fifty-four percent considered a history of TURP to be a relative contraindication, while 34% considered TURP to have no impact on patient selection. Eighty-six percent of respondents combine brachytherapy with external beam radiation in an average of 32% of their patients. Boosts were given with both ¹²⁵I prescribed to 120 Gy (75%) or ¹⁰³Pd to 90 Gy (50%). Sixty percent reported using a Mick applicator, 46% prefer using preloaded needles, and (11%) use both techniques. Real-time imaging was usually performed with ultrasound (94%); most included fluoroscopy (60%). Definitions of PSA control varied widely. Conclusions: TIPPB clinical practice in the U.S. demonstrates similarities in technique, but differences in patient selection and definitions of biochemical control. It is, therefore, incumbent on those beginning TIPPB programs to carefully review the specific practice details of those institutions with a broad experience

[en] Purpose: Postmastectomy irradiation improves overall survival for breast cancer patients at high risk for locoregional recurrence (LRR). The objective of this study was to use recursive partitioning analysis (RPA) to define patient subgroups at high risk for LRR following mastectomy. Patients and Methods: A cohort of 1031 patients treated on prospective trials with mastectomy and doxorubicin-based chemotherapy without irradiation was analyzed. The variables considered in the RPA were tumor size, number of involved nodes, number of nodes examined, and percentage of nodes involved (nodes involved/nodes examined). The endpoint was LRR ± distant metastasis. Only patients with complete data were analyzed (n=913). Median follow-up was 8 years (range, 0.7-22 years). Results: Involvement of 20% or more of the lymph nodes examined was the most significant variable predicting LRR. Three risk categories were defined. Patients with 20% or more involved nodes and tumors of 3.5 cm or more were at greatest risk for LRR (41% at 8 years). An intermediate-risk group included patients with 20% or more involved nodes and tumors of less than 3.5 cm as well as those with less than 20% involved nodes and tumor size of 5 cm or greater (18% at 8 years). Patients with less than 20% involved nodes and tumor size of less than 5 cm were at lowest risk for LRR (10% at 8 years). Conclusion: Tumor size and extent of nodal involvement play interrelated roles in predicting LRR following mastectomy and systemic therapy. Patients with 20% or greater involved nodes and those with less than 20% nodes and tumors of 5.0 cm or greater are at significant risk of LRR and should be considered for postoperative irradiation

[en] Purpose: To analyze the long-term outcome of breast conservation therapy in patients with ductal carcinoma in situ (DCIS) in a single institution and to analyze the prognostic importance, if any, of young patient age. Methods and Materials: The hospital records of 150 patients with DCIS treated with surgical excision and radiotherapy at our institution between 1980 and 1997 were retrospectively reviewed. For most of the patients, intraoperative specimen radiographs or postoperative mammograms were available for use in assessing that an adequate surgical resection had been performed. The median patient age was 53 years (range 32-81), with 13% of patients ≤40 years old. Results: At a median follow-up of 63 months, 12 patients had local disease recurrence. The actuarial rate of local recurrence-free survival at 5 and 10 years was 96% and 88%, respectively. Local recurrence correlated with nuclear grade (p=0.002) but was not associated with patient age at diagnosis (<40 years vs. ≥40 years, p=0.39). In all cases of local recurrence, patients underwent surgery with or without chemotherapy, and disease control was achieved. Conclusion: The results of this study demonstrate high rates of long-term overall survival, disease-specific survival, and local control in patients with DCIS of the breast treated conservatively with segmental mastectomy and radiotherapy. On the basis of the excellent long-term local control and 100% disease-specific survival rates, we found that patient age does not affect the outcome if the margins are clear. Continued studies in young patients treated with breast conservative therapy for DCIS are needed

[en] Purpose: To determine local-regional failure rates in breast cancer patients treated with surgery and high-dose chemotherapy with stem cell transplant and to relate local-regional failure to the use and timing of radiation treatment. Methods and Materials: We retrospectively reviewed the records of 165 breast cancer patients treated on institutional protocols with surgery and high-dose chemotherapy with stem cell transplant. All patients had either Stage III disease, 10 or more positive axillary lymph nodes, or 4 or more positive axillary lymph nodes following neoadjuvant chemotherapy. Twelve patients had inflammatory breast cancer. Thirteen patients treated with breast preservation and 5 patients who died from toxicity within 30 days of transplant were excluded from the analyses of local-regional recurrences. In the remaining 147 patients, 108 were treated with adjuvant radiation and 39 were not. The disease stage distribution for these two groups was comparable. The median follow-up for surviving patients was 35 months. Results: The 3- and 5-year actuarial disease-free survival (DFS) for the entire group was 60% and 51%, respectively. The 5-year rates of freedom from isolated local-regional recurrence were 95% in the patients treated with adjuvant radiation and 86% in the patients who did not receive radiation (p 0.014, log rank comparison). The 5-year rates of any local-regional recurrence as a first event (isolated recurrences plus those with simultaneous local-regional and distant recurrences) were 92% versus 82%, respectively for patients whose treatment did and did not include radiation (p = 0.038). We could not demonstrate a correlation of the timing of radiation with the risk of local-regional recurrence. Conclusions: These data indicate that high-dose chemotherapy does not negate the importance of radiation in optimizing local-regional control in patients with high-risk breast cancer. Given the results of recent randomized trials studying postmastectomy radiation, which show that improving local-regional control improves overall survival (OS), we believe that all breast cancer patients with high-risk primary breast cancer who are treated with high-dose chemotherapy with stem cell transplant should receive radiation as a component of their treatment