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Biomedical subjects

Frank A Vicini

Publications and source records attributed to Frank A Vicini.

At least 19 recordsLinked to original sources
PubMed2006

The impact of lobular carcinoma in situ in association with invasive breast cancer on the rate of local recurrence in patients with early-stage breast cancer treated with breast-conserving therapy.

PURPOSE: The significance of lobular carcinoma in situ (LCIS) associated with invasive breast cancer in patients undergoing breast-conserving therapy (BCT) remains controversial. We examined the impact of the presence and extent of LCIS associated with invasive breast cancer on clinical outcome in BCT patients. METHODS AND MATERIALS: From 1980 to 1996, 607 cases of invasive breast cancer were treated with BCT. All slides were reviewed by a single pathologist. Positive margin was defined as presence of invasive carcinoma/ductal carcinoma in situ at the inked margin. Multiple clinical, pathologic, and treatment-related variables were analyzed for their association with ipsilateral breast tumor recurrence (IBTR) and true recurrence/marginal miss (TR/MM). Median follow-up was 8.7 years. RESULTS: Fifty-six patients (9%) had LCIS in association with invasive cancer. On univariate analysis, positive final margin, positive/no reexcision, smaller maximum specimen dimension, and the presence of LCIS predicted for IBTR. The 10-year IBTR rate was 14% for cases with LCIS vs. 7% without LCIS (p=0.04). On multivariate analysis, positive margin (p<0.01), positive/no reexcision (p=0.04), and presence of LCIS (p=0.02) remained independently associated with IBTR; positive margin (p<0.01) and LCIS (p=0.04) were also associated with TR/MM failure. When examining only cases with negative final margins, the presence of LCIS remained associated with higher IBTR and TR/MM rates (p<0.01). CONCLUSION: The presence of LCIS was independently associated with higher rate of IBTR and TR/MM after BCT for invasive breast cancer. LCIS may have significant premalignant potential and progress to an invasive IBTR at the site of index lesion. The adequacy of excision of LCIS associated with invasive carcinoma should be considered in patients undergoing BCT.

Adult↗
PubMed2006

Unification of a common biochemical failure definition for prostate cancer treated with brachytherapy or external beam radiotherapy with or without androgen deprivation.

PURPOSE: Minimal data are available regarding selection of an optimal biochemical failure (BF) definition for patients treated with brachytherapy, external beam radiotherapy (EBRT), and combinations of these treatments with or without androgen deprivation (AD). We retrospectively analyzed our institution's experience treating localized prostate cancer in an attempt to determine a BF definition that could be applied for these various treatment modalities. METHODS AND MATERIALS: A total of 2376 patients with clinical stage T1-T3 N0 M0 prostate cancer were treated with conventional dose (median, 66.6 Gy) EBRT (n = 1201), high-dose (median, 75.6 Gy) adaptive radiation therapy (n = 465), EBRT + high-dose-rate brachytherapy boost (n = 416), or brachytherapy alone (n = 294) between 1987 and 2003. A total of 496 patients (21%) received neoadjuvant AD with radiation therapy. There were 21924 posttreatment prostate-specific antigen (PSA) measurements. Multiple BF definitions were tested for their sensitivity, specificity, positive predictive value (+PV), and negative PV (-PV) in predicting subsequent clinical failure (CF) (any local failure or distant metastasis), overall survival (OS), and cause-specific survival (CSS). Median follow-up was 4.5 years. The date of BF was the date BF criteria were met (e.g., date of third rise). RESULTS: A total of 290 patients (12%) experienced CF at a median interval of 3.6 years (range, 0.2-15.2 years). The 5- and 10-year CF rates were 12% and 26%, respectively. Three consecutive rises yielded a 46% sensitivity and 84% specificity for predicting CF. The 10-year CF for those 475 patients who experienced three rises (BF) was 37% vs. 17% for those patients who did not meet these criteria (biochemically controlled [BC]). For all patients, the following definitions were superior to three rises for predicting CF for both +PV, and -PV: n + 1 (> or =1 ng/mL above nadir), n + 2, n + 3, threshold 2 (any PSA > or =2.0 ng/mL at or after nadir), threshold 3, threshold 4, and threshold 5. For the subset of patients treated with EBRT alone, the n + k definitions and threshold k definitions maintained superior predictive capacity. However, the threshold k definitions seemed to maintain a slightly greater separation in 10-year CF rates (43% for BF vs. 13% for BC = 30% difference for threshold 3). Surprisingly, all definitions generally had better predictive capacity for those patients who received brachytherapy or neoadjuvant AD vs. EBRT alone. The endpoints appeared similar for n + 1 vs. threshold 3 and n + 2 vs. threshold 4 in EBRT alone patients, but for brachytherapy or neoadjuvant AD patients, there were similarities for n + 2 vs. threshold 3 and n + 3 vs. threshold 4. This may be a reflection of the lower nadir levels in patients receiving AD (median <0.1 ng/mL vs. 0.2 ng/mL for brachytherapy vs. 0.8 ng/mL for EBRT alone, p < 0.01). When examining CF correlation for the various classes of BF definitions, the threshold k definitions clearly demonstrated the greatest area under the receiver operating characteristic curve, followed by the n + k definitions. For OS, the threshold k definitions again demonstrated the greatest area under the curve, followed by definitions based on specific nadir cutoffs (nadir > or =k ng/mL). CONCLUSIONS: Biochemical failure definitions applying a PSA threshold at or after the nadir (e.g., threshold 3) demonstrated the highest association with CF, OS, and CSS for all assessed treatment modalities. Definitions incorporating a PSA increase above the nadir value (e.g., nadir + 2 ng/mL) were also superior for all modalities. In general, BF definitions have greater predictive capacity for clinical outcome with brachytherapy or neoadjuvant AD than EBRT alone, possibly because of less "noise" from production of background PSA.

Adult↗
PubMed2006

Clinicopathologic analysis of extracapsular extension in prostate cancer: should the clinical target volume be expanded posterolaterally to account for microscopic extension?

PURPOSE: We performed a complete pathologic analysis examining extracapsular extension (ECE) and microscopic spread of malignant cells beyond the prostate capsule to determine whether and when clinical target volume (CTV) expansion should be performed. METHODS AND MATERIALS: A detailed pathologic analysis was performed for 371 prostatectomy specimens. All slides from each case were reviewed by a single pathologist (N.S.G.). The ECE status and ECE distance, defined as the maximal linear radial distance of malignant cells beyond the capsule, were recorded. RESULTS: A total of 121 patients (33%) were found to have ECE (68 unilateral, 53 bilateral). Median ECE distance=2.4 mm [range: 0.05-7.0 mm]. The 90th-percentile distance = 5.0 mm. Of the 121 cases with ECE, 55% had ECE distance>or=2 mm, 19%>or=4 mm, and 6%>or=6 mm. ECE occurred primarily posterolaterally along the neurovascular bundle in all cases. Pretreatment prostrate-specific antigen (PSA), biopsy Gleason, pathologic Gleason, clinical stage, bilateral involvement, positive margins, percentage of gland involved, and maximal tumor dimension were associated with presence of ECE. Both PSA and Gleason score were associated with ECE distance. In all 371 patients, for those with either pretreatment PSA>or=10 or biopsy Gleason score>or=7, 21% had ECE>or=2 mm and 5%>or=4 mm beyond the capsule. For patients with both of these risk factors, 49% had ECE>or=2 mm and 21%>or=4 mm. CONCLUSIONS: For prostate cancer with ECE, the median linear distance of ECE was 2.4 mm and occurred primarily posterolaterally. Although only 5% of patients demonstrate ECE>4 to 5 mm beyond the capsule, this risk may exceed 20% in patients with PSA>or=10 ng/ml and biopsy Gleason score>or=7. As imaging techniques improve for prostate capsule delineation and as radiotherapy delivery techniques increase in accuracy, a posterolateral CTV expansion should be considered for patients at high risk.

Aged↗
PubMed2006

Initial outcomes for patients treated on the American Society of Breast Surgeons MammoSite clinical trial for ductal carcinoma-in-situ of the breast.

BACKGROUND: The MammoSite device was designed as a breast brachytherapy applicator and is currently used to deliver accelerated partial breast irradiation (APBI). We hypothesized that APBI delivered with the MammoSite device would be well tolerated and be associated with a good cosmetic outcome in patients with ductal carcinoma-in-situ (DCIS). METHODS: From 2002 to 2004, 191 patients with DCIS were enrolled in a registry trial to assess the MammoSite applicator. Fifteen patients were excluded from analysis because of device- or patient-related factors; 7 patients were excluded after receiving a radiotherapy boost, thus leaving 169 patients available for study. Follow-up information was available for 158 patients. The average length of follow-up was 7.35 months. Forty-three patients had at least 1 year of follow-up. RESULTS: Skin spacing for the MammoSite applicator was as follows: < 5 mm, 3 patients (1.78%); 5 to 7 mm, 18 patients (10.65%); and > or = 7 mm, 148 patients (87.57%). Patients with a device-to-skin distance of > or = 7 mm had the best cosmetic result. Patients with a device-to-skin distance of > or = 7 mm also had a lower incidence of radiation dermatitis. Data on 43 patients who were followed up for at least 1 year confirmed these findings. Additional adverse events were primarily related to skin changes, with breast infections occurring in five patients (3.16%). No patient in the study has experienced a recurrence. CONCLUSIONS: APBI delivered via MammoSite is well tolerated in patients with DCIS, and the lowest toxicity was obtained in patients with the greatest device-to-skin distance. Long-term follow-up data regarding patient satisfaction, cosmesis, and efficacy are needed and will be determined from a recently opened large randomized study.

Adult↗
PubMed2006

Long-term cosmetic results and toxicity after accelerated partial-breast irradiation: a method of radiation delivery by interstitial brachytherapy for the treatment of early-stage breast carcinoma.

BACKGROUND: The objective of this study was to assess the cosmesis and toxicities in patients with early-stage breast carcinoma who received treatment with accelerated partial breast irradiation (APBI) using interstitial brachytherapy. METHODS: From April 1993 to December 2001, 199 patients with Stage I-II breast carcinoma received breast-conserving therapy with APBI to the tumor bed alone through a low-dose-rate (LDR) or high-dose-rate (HDR) implant. A template guide was used. The LDR dose was 50 Gray (Gy) over 96 hours; the outpatient HDR implant delivered 32 Gy in 8-Gy or 34 Gy in 10-Gy twice-daily fractions. Cosmesis (Harvard criteria) and toxicities (Radiation Therapy Oncology Group guidelines) were assessed at < or = 6 months, 2 years, and 5 years. RESULTS: The median follow up was 6.4 years. Breast pain, edema, erythema, and hyperpigmentation all diminished over time. Breast fibrosis and hypopigmentation increased until the 2-year mark and then stabilized. Fat necrosis and telangiectasia increased over time, with a fat necrosis rate of 11% at 5 years. Nearly all telangiectasias (34% at 5 yrs) were Grade 1 (< 2 mm). The remaining toxicities were Grade 1 at all follow-up intervals. Infections (11%) occurred predominantly within the first month after treatment. Good-to-excellent cosmetic outcomes were noted in 95-99% of patients over time; cosmetic results stabilized at 2 years with excellent results increased out to 5 years. CONCLUSIONS: APBI with interstitial brachytherapy resulted in mild chronic toxicities, the majority of which diminished or reached a plateau over time. Long-term cosmesis was good to excellent in 95-99% of patients and stabilized at 2 years.

Adult↗
PubMed2005

First analysis of patient demographics, technical reproducibility, cosmesis, and early toxicity: results of the American Society of Breast Surgeons MammoSite breast brachytherapy trial.

BACKGROUND: Eighty-seven institutions participated in a Registry Trial that was designed to collect data on the clinical use of the MammoSite breast brachytherapy catheter for delivering breast irradiation. Patient demographics, technical reproducibility, cosmesis, and early toxicity were evaluated. METHODS: From May 4, 2002 through July 30, 2004, 1419 patients with Stage 0, I, or II breast carcinoma who were undergoing breast-conserving therapy were enrolled on the trial. The device was placed in 1403 of these patients. The 1237 patients (87% of enrolled patients) who received accelerated partial breast irradiation (APBI) (34 grays prescribed to 1.0 cm in 10 fractions; 95% of patients who received APBI) constituted the study population; 86% of those patients (1068) had Stages I-II breast carcinoma (median tumor size, 10 mm), and 14% of those patients (169) had Stage 0 breast carcinoma. Ninety-one percent of the patients with invasive carcinoma (977 of 1068 patients) had negative lymph node status, and 99% of all patients had negative margins. The median patient age was 65 years. Systemic chemotherapy alone was administered to 79 patients with invasive carcinoma (7%), hormone therapy was administered to 501 patients (45%), and both were administered to 39 patients (4%). The median follow-up was 5 months. RESULTS: Five hundred fifty-four catheters (45%) were placed with an open cavity at the time of lumpectomy, and 683 catheters (55%) were placed with a closed cavity after lumpectomy. Skin spacing ranged from 2 mm to 75 mm (median, 10 mm). In 89% of patients, there was a minimum balloon-to-skin distance of 7 mm (2% of patients had distances < 5 mm). In terms of cosmetic assessment, 95% of patients (1030 of 1084 patients) who had a cosmetic assessment had a good/excellent result (last follow-up visit). Cosmetic results at 12 months were good/excellent in 92% of 248 evaluable patients. The median skin spacing (> or = 7 mm vs. < 7 mm) was associated significantly with a good/excellent cosmetic result (96.1% vs. 86.8%; P = 0.0001) overall and at 6 months (P = 0.006). Increasing skin spacing was associated with a good/excellent cosmetic result as a continuous variable (P < 0.0001). In total, 92 of 1140 evaluable patients (8.1%) developed an infection in the breast, which was device-related in 5.3% of patients (60 of 1140 patients). Good/excellent cosmetic results were noted in 86% of these patients (last follow-up visit). Fifteen of 442 evaluable patients (3.4%) developed a radiation recall reaction. Good/excellent cosmetic results were noted in 93% of these patients at their last follow-up visit. One local recurrence (0.1%) was reported (new primary carcinoma). CONCLUSIONS: Clinical evaluation of the ability of the MammoSite breast brachytherapy catheter to deliver APBI demonstrated acceptable technical reproducibility between multiple institutions and use in appropriate groups of patients. Cosmetic results at 12 months (92% good/excellent) were comparable to those reported with whole-breast RT. Early toxicity rates (infections, radiation recall) appeared to be acceptable.

Adult↗
PubMed2005

Dose-volume analysis of predictors for chronic rectal toxicity after treatment of prostate cancer with adaptive image-guided radiotherapy.

PURPOSE: We analyzed our experience treating localized prostate cancer with image-guided off-line correction with adaptive high-dose radiotherapy (ART) in our Phase II dose escalation study to identify factors predictive of chronic rectal toxicity. MATERIALS AND METHODS: From 1999-2002, 331 patients with clinical stage T1-T3N0M0 prostate cancer were prospectively treated in our Phase II 3D conformal dose escalation ART study to a median dose of 75.6 Gy (range, 63.0-79.2 Gy), minimum dose to confidence limited-planning target volume (cl-PTV) in 1.8 Gy fractions (median isocenter dose = 79.7 Gy). Seventy-four patients (22%) also received neoadjuvant/adjuvant androgen deprivation therapy. A patient-specific cl-PTV was constructed using 5 computed tomography scans and 4 sets of electronic portal images by applying an adaptive process to assure target accuracy and minimize PTV margin. For each case, the rectum (rectal solid) was contoured from the sacroiliac joints or rectosigmoid junction (whichever was higher) to the anal verge or ischial tuberosities (whichever was lower), with a median volume of 81.2 cc. The rectal wall was defined using the rectal solid with an individualized 3-mm wall thickness (median volume = 29.8 cc). Rectal wall dose-volume histogram was used to determine the prescribed dose. Toxicity was quantified using the National Cancer Institute Common Toxicity Criteria 2.0. Multiple dose-volume endpoints were evaluated for their association with chronic rectal toxicity. RESULTS: Median follow-up was 1.6 years. Thirty-four patients (crude rate = 10.3%) experienced Grade 2 chronic rectal toxicity at a median interval of 1.1 years. Nine patients (crude rate = 2.7%) experienced Grade > or =3 chronic rectal toxicity (1 was Grade 4) at a median interval of 1.2 years. The 3-year rates of Grade > or =2 and Grade > or =3 chronic rectal toxicity were 20% and 4%, respectively. Acute toxicity predicted for chronic: Acute Grade 2-3 rectal toxicity (p < 0.001) including any acute rectal Grade 2-3 tenesmus (p = 0.02) and pain (p = 0.008) were significant predictors of chronic Grade > or =2 rectal toxicity. Any acute rectal toxicity (p = 0.001), any acute tenesmus (p = 0.03), and any acute diarrhea (p < 0.001) were also found to be predictive for chronic toxicity, as continuous variables. Dose-volume histogram predicted for chronic toxicity: Rectal wall absolute and relative V50, V60, V66.6, V70, and V72 and rectal solid relative V60-V72 were significantly associated with chronic Grade > or =2 rectal toxicity both as categorical and continuous variables (t test, linear regression) and when divided into subgroups (chi-square table). The chronic rectal toxicity Grade > or =2 risk was 9%, 18%, and 25% for the rectal wall relative V70 <15%, 25%-40%, and >40% respectively. The volume of rectum or rectal wall radiated to > or =50 Gy was a strong predictor for chronic rectal toxicity. Nonpredictive factors: Rectal solid/wall absolute or relative volumes irradiated to < or =40 Gy, dose level, and use of androgen deprivation were not found predictive. CONCLUSIONS: In our ART dose escalation study, rectal wall or rectum relative > or =V50 are closely predictive for chronic rectal toxicity. If rectal dose-volume histogram constraints are used to select the dose level, the risk of chronic rectal toxicity will reflect the risk of toxicity of the selected constraint rather than the dose selected as found in our study using an adaptive process. To select the prescribed dose, different dose-volume histogram constraints may be used including the rectal wall V70. Patients experiencing acute rectal toxicity are more likely to experience chronic toxicity.

Acute Disease↗
PubMed2005

Assessing the benefit of radiation therapy after breast-conserving surgery for ductal carcinoma-in-situ.

PURPOSE: To assess women's preferences regarding the trade-off between the risks and benefits of treatment with radiation therapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma-in-situ (DCIS). PATIENTS AND METHODS: Utilities were obtained from 120 patients and 210 nonpatients for eight relevant health states using standard gambles. RESULTS: Differences in utilities obtained from patient and nonpatient participants between health states were relatively similar. Reduction in the likelihood of local recurrence associated with RT did not result in higher utilities. Utilities for noninvasive recurrence were only lower after initial treatment with RT. Patient and nonpatient participants had the lowest utilities for invasive local recurrence, regardless of initial treatment or manner of salvage therapy. When comparing patient and nonpatient utilities directly, patients had higher utility for being without recurrence after initial RT and lower utility for invasive recurrence salvaged by mastectomy after initial BCS alone. None of the clinical or sociodemographic factors examined explained more than 5% of the variability in the patients' or nonpatients' utilities or their differences. CONCLUSION: The principal benefit associated with adding RT to BCS for DCIS seems to be its ability to reduce invasive recurrences.

Adult↗
PubMed2005

Factors associated with local recurrence and cause-specific survival in patients with ductal carcinoma in situ of the breast treated with breast-conserving therapy or mastectomy.

PURPOSE: We reviewed our institution's experience treating patients with ductal carcinoma in situ (DCIS) of the breast to determine risk factors for ipsilateral breast tumor recurrence (IBTR) and cause-specific survival (CSS) after breast-conserving therapy (BCT) or mastectomy. MATERIALS AND METHODS: Between 1981 and 1999, 410 cases of DCIS (405 patients) were treated at our institution; 367 were managed with breast-conserving surgery (54 with lumpectomy alone and 313 with adjuvant radiation therapy (RT) [median dose, 45 Gy]). Of these 313 patients, 298 received also a supplemental boost of RT to the lumpectomy cavity (median dose, 16 Gy). Forty-three patients underwent mastectomy; 2 (5%) received adjuvant RT to the chest wall. A true recurrence/marginal miss (TR/MM) IBTR was defined as failure within or adjacent to the tumor bed in patients undergoing BCT. Median follow-up for all patients was 7 years (mean: 6.1 years). RESULTS: Thirty patients (8.2%) experienced an IBTR after BCT (25 [8%] after RT, 5 [9.3%] after no RT), and 2 patients (4.7%) developed a chest wall recurrence after mastectomy. Of the 32 local failures, 20 (63%) were invasive (18/30 [60%] after BCT and 2/2 [100%] after mastectomy), and 37% were DCIS alone. Twenty-four (80%) of the IBTRs were classified as TR/MM. The 10-year freedom from local failure, CSS, and overall survival after BCT or mastectomy were 89% vs. 90% (p = 0.4), 98% vs. 100% (p = 0.7), and 89% vs. 100% (p = 0.3), respectively. Factors associated with IBTR on Cox multivariate analysis were younger age (p = 0.02, hazard ratio [HR] 1.06 per year), electron boost energy < or = 9 MeV (p = 0.03, HR 1.41), final margins < or = 2 mm (p = 0.007; HR, 3.65), and no breast radiation (p = 0.002, HR 5.56). On Cox univariate analysis for BCT patients, IBTR, TR/MM failures, and predominant nuclear Grade 3 were associated with an increased risk of distant metastases and a reduced CSS. CONCLUSIONS: After treatment for DCIS, 10-year rates of local control, CSS, and overall survival were similar after mastectomy and BCT. Young age (<45 years), close/positive margins (< or = 2 mm), no breast radiation, and lower electron boost energies (< or = 9 MeV) were associated with IBTR. Local failure and predominant nuclear Grade 3 were found to have a small (4%-12%) but statistically significantly negative impact on the rates of distant metastasis and CSS. These results suggest that optimizing local therapy (surgery and radiation) is crucial to improve local control and CSS in patients treated with DCIS.

Adult↗
PubMed2005

A cost comparison analysis of partial versus whole-breast irradiation after breast-conserving surgery for early-stage breast cancer.

PURPOSE: To assess, if and for whom, there are cost savings associated with alternate breast radiotherapy (RT) techniques when compared with the conventional external beam-based whole-breast RT with a boost (WBRT-B). METHODS AND MATERIALS: Treatment planning and delivery utilization data were modeled for eight different breast RT techniques: (1) WBRT-B: 60 Gy in 30 fractions; (2) WBRT: 50 Gy in 25 fractions; (3) WBRT-accelerated (AC): 42.5 Gy in 16 fractions; (4) WBRT-intensity-modulated RT (IMRT): 60 Gy in 30 fractions; (5) accelerated partial breast irradiation (APBI)-IC, MammoSite: 34 Gy in 10 twice-daily fractions; (6) APBI-IT, HDR interstitial: 34 Gy in 10 twice-daily fractions; (7) APBI three-dimensional conformal RT (3D-CRT): 38.5 Gy in 10 twice-daily fractions; or (8) APBI-IMRT: 38.5 Gy in 10 twice-daily fractions. Costs incurred by payer (i.e., direct medical costs; 2003 Medicare Fee Schedule) and patient (i.e., direct nonmedical costs; time and travel) were estimated. Total societal costs were then calculated for each treatment approach. RESULTS: Not all efforts to reduce overall treatment time result in total cost savings. The least expensive partial breast-based RT approaches were the external beam techniques (APBI-3D-CRT, APBI-IMRT). Any reduced cost to patients for the HDR brachytherapy-based APBI regimens were overshadowed by substantial increases in cost to payers, resulting in higher total societal costs; the cost of HDR treatment delivery was primarily responsible for the increased direct medical cost. For the whole breast-based RT approaches, treating without a boost (WBRT) or with WBRT-AC reduced total costs. Overall, WBRT-AC was the least costly of all the regimens, in terms of costs to society; APBI approaches, in general, were favored over whole-breast techniques when only considering costs to patients. CONCLUSIONS: Based on societal cost considerations, WBRT-AC appears to be the preferred approach. If one were to pursue a partial-breast RT regimen to minimize patient costs, it would be more advantageous from a societal perspective to pursue external beam-based approaches such as APBI-3D-CRT or APBI-IMRT in lieu of the brachytherapy-based regimens.

Breast Neoplasms↗
PubMed2005

Prostate gland motion assessed with cine-magnetic resonance imaging (cine-MRI).

PURPOSE: To quantify prostate motion during a radiation therapy treatment using cine-magnetic resonance imaging (cine-MRI) for time frames comparable to that expected in an image-guided radiation therapy treatment session (20-30 min). MATERIALS AND METHODS: Six patients undergoing radiation therapy for prostate cancer were imaged on 3 days, over the course of therapy (Weeks 1, 3, and 5). Four hundred images were acquired during the 1-h MRI session in 3 sagittal planes through the prostate at 6-s intervals. Eleven anatomic points of interest (POIs) have been used to characterize prostate/bony pelvis/abdominal wall displacement. Motion traces and standard deviation for each of the 11 POIs have been determined. The probability of displacement over time has also been calculated. RESULTS: Patients were divided into 2 groups according to rectal filling status: full vs. empty rectum. The displacement of POIs (standard deviation) ranged from 0.98 to 1.72 mm for the full-rectum group and from 0.68 to 1.04 mm for the empty-rectum group. The low standard deviations in position (2 mm or less) would suggest that these excursions have a low frequency of occurrence. The most sensitive prostate POI to rectal wall motion was the mid-posterior with a standard deviation of 1.72 mm in the full-rectum group vs. 0.79 mm in the empty-rectum group (p = 0.0001). This POI has a 10% probability of moving more than 3 mm in a time frame of approximately 1 min if the rectum is full vs. approximately 20 min if the rectum is empty. CONCLUSION: Motion of the prostate and seminal vesicles during a time frame similar to a standard treatment session is reduced compared to that reported in interfraction studies. The most significant predictor for intrafraction prostate motion is the status of rectal filling. A prostate displacement of <3 mm (90%) can be expected for the 20 min after the moment of initial imaging for patients with an empty rectum. This is not the case for patients presenting with full rectum. The determination of appropriate intrafraction margins in radiation therapy to accommodate the time-dependent uncertainty in positional targeting is a topic of ongoing investigations for the on-line image guidance model.

Humans↗
PubMed2005

Long-term outcome after breast-conservation treatment with radiation for mammographically detected ductal carcinoma in situ of the breast.

BACKGROUND: Ductal carcinoma in situ (DCIS) is detected most commonly on routine screening mammography in the asymptomatic patient, and has a long natural history. The objective of the current study was to determine the long-term outcome after breast-conservation surgery followed by definitive breast irradiation for women with mammographically detected DCIS of the breast. METHODS: In total, 1003 women with unilateral, mammographically detected DCIS of the breast underwent breast-conserving surgery followed by definitive breast irradiation. These women were treated in 10 institutions in North America and Europe. The median follow-up was 8.5 years (mean, 9.0 years; range, 0.2-24.6 years). RESULTS: The 15-year overall survival rate was 89%, and the 15-year cause-specific survival rate was 98%. The 15-year rate of freedom from distant metastases was 97%. In total, there were 100 local failures (10%) in the treated breast. The 15-year rate of any local failure was 19%, and the 15-year rate of local only first failure was 16%. Patient age > or = 50 years at the time of treatment and negative final pathology margins from the primary tumor excision both were associated independently with a lower risk of local failure in univariate analysis (P = 0.00062 and P = 0.024, respectively) and in multivariate analysis (P = 0.00057 and P = 0.0026, respectively). For favorable subgroups of patients age > or = 50 years or with negative resection margins, the 10-year risk of local failure was < or = 8%. CONCLUSIONS: The current results support the use of breast-conserving surgery followed by definitive breast irradiation for the treatment of patients with mammographically detected DCIS of the breast. Patient age > or = 50 years at the time of treatment and negative resection margins both were associated independently with a decreased risk of local failure.

Adult↗
PubMed2005

MRI-based volumetric assessment of cardiac anatomy and dose reduction via active breathing control during irradiation for left-sided breast cancer.

PURPOSE: Heart dose-volume analysis using computed tomography (CT) is limited because of motion artifact and poor delineation between myocardium and ventricular space. We used dedicated cardiac magnetic resonance imaging (MRI) to quantify exclusion of left ventricular (LV) myocardium via active breathing control (ABC) during left breast irradiation and to determine the correlation between irradiated whole heart and LV volumes. METHODS AND MATERIALS: Fifteen patients who completed adjuvant irradiation for early-stage left breast cancer participated. Treatment consisted of 45 Gy to the entire breast using ABC followed by a 16-Gy electron boost to the lumpectomy cavity. Patients underwent planning CT scans in free breathing (FB) and moderate deep inspiration breath hold (mDIBH). Electrocardiogram-gated cardiac MRI was performed in the treatment position using alpha-cradle immobilization. MRI scans were acquired in late diastole (LD), mid-diastole (MD), and systole (S) for both FB and mDIBH. After image fusion with the patients' radiation therapy planning CT scan, MRI LV volumes were defined for the three examined phases of the cardiac cycle, and comparative dose-volume analysis was performed. RESULTS: Cardiac volume definition was found to differ significantly because of combinations of respiratory and intrinsic heart motion. The fraction of LV myocardium receiving 50% (22.5 Gy) of the prescribed whole breast dose (V(22.5)) was reduced by 85.3%, 91.8%, and 94.6% via ABC for LD, MD, and S, respectively. Linear regression revealed strong correlation between MRI-defined whole heart and LV V(22.5) reduction via ABC, suggesting that LV myocardium accounts for up to approximately 50% of the excluded heart volume through this technique. Significant but weaker correlations were noted between CT-defined whole heart and LV V(22.5) reductions with marked variability in the measurements of patients with larger amounts of heart in the treatment field. CONCLUSIONS: Cardiac MRI demonstrated a significant reduction in LV myocardium irradiated with the use of ABC. The correlation between reduction in V(22.5) values for LV wall and CT-defined whole heart suggests that CT is adequate for determining which patients are likely to benefit from ABC treatment, but inaccuracies inherent to standard CT dictate that more detailed imaging studies such as MRI are required for accurate cardiotoxicity assessment.

Breast Neoplasms↗
PubMed2005

Improved biochemical outcome with adjuvant radiotherapy after radical prostatectomy for prostate cancer with poor pathologic features.

PURPOSE: The indications for adjuvant external beam radiotherapy (EBRT) after radical prostatectomy (RP) are poorly defined. We performed a retrospective comparison of our institution's experience treating prostate cancer with RP vs. RP followed by adjuvant EBRT. METHODS AND MATERIALS: Between 1987 and 1998, 617 patients with clinical Stage T1-T2N0M0 prostate cancer underwent RP. Patients who underwent preoperative androgen deprivation and those with positive lymph nodes were excluded. Of the 617 patients, 34 (5.5%) with an undetectable postoperative prostate-specific antigen (PSA) level underwent adjuvant prostatic fossa RT at a median of 0.25 year (range, 0.1-0.6) postoperatively because of poor pathologic features. The median total dose was 59.4 Gy (range, 50.4-66.6 Gy) in 1.8-2.0-Gy fractions. These 34 RP+RT patients were compared with the remaining 583 RP patients. Biochemical failure was defined as any postoperative PSA level > or =0.1 ng/mL and any postoperative PSA level > or =0.3 ng/mL (at least 30 days after surgery). Administration of androgen deprivation was also scored as biochemical failure when applying either definition. The median clinical follow-up was 8.2 years (range, 0.1-11.2 years) for RP and 8.4 years (range, 0.3-13.8 years) for RP+RT. RESULTS: Radical prostatectomy + radiation therapy patients had a greater pathologic Gleason score (mean, 7.3 vs. 6.5; p < 0.01) and pathologic T stage (median, T3a vs. T2c; p < 0.01). Age (median, 65.7 years) and pretreatment PSA level (median, 7.9 ng/mL) were similar between the treatment groups. Extracapsular extension was present in 72% of RP+RT patients vs. 27% of RP patients (p < 0.01). The RP+RT patients were more likely to have seminal vesicle invasion (29% vs. 9%, p < 0.01) and positive margins (73% vs. 36%, p < 0.01). Despite these poor pathologic features, the 5-year biochemical control (BC) rate (PSA <0.1 ng/mL) was 57% for RP+RT and 47% for RP (p = 0.28). For patients with extracapsular extension, the 5-year BC rate was 52% for RP+RT vs. 30% for RP (p < 0.01). The 5-year BC rate for patients with seminal vesicle invasion was 60% for RP+RT vs. 18% for RP (p < 0.01). For those with positive margins, the 5-year BC rate was 64% for RP+RT vs. 27% for RP (p < 0.01). The use of adjuvant RT remained statistically significant on multivariate analysis when applying either biochemical failure definition. Adjuvant RT also remained statistically significant when including the postoperative PSA level (>30 days after surgery) in the multivariate analyses. In addition, 99 (17%) of the 583 RP patients required salvage prostatic fossa RT (median dose, 59.4 Gy) at a median interval of 1.3 years after surgery (range, 0.1-8.4) for a palpable recurrence (n = 10) or a detectable/rising postoperative PSA level (n = 89). The median PSA level before salvage RT was 0.8 ng/mL (mean, 3.2 ng/mL). The 5-year and 8-year BC rate, using the PSA <0.1 ng/mL definition, from the date of salvage RT was 41% and 35%, respectively. The 5-year and 8-year BC rate, using the PSA <0.3 ng/mL definition, was 46% and 36%, respectively. The 8-year local recurrence rate after salvage RT was 4%. CONCLUSION: Adjuvant RT demonstrated improved efficacy against prostate cancer. For patients with poor pathologic features (extracapsular extension, seminal vesicle invasion, positive margins), adjuvant RT improved the biochemical outcome independent of other prognostic factors.

Aged↗
PubMed2005

Accelerated partial breast irradiation: a dosimetric comparison of three different techniques.

PURPOSE: We report the first single-institutional dosimetric comparison of patients treated with three forms of accelerated partial breast irradiation: interstitial HDR brachytherapy, the MammoSite balloon apparatus, and 3D conformal external beam quadrant irradiation (3D-CRT). METHODS: A retrospective dosimetric comparison of interstitial HDR brachytherapy, MammoSite balloon brachytherapy, and 3D-CRT was performed. Thirty patients including 10 from each treatment technique were included for a dosimetric comparison of the dose received by the ipsilateral breast, PTV, heart, and ipsilateral lung. Interstitial patients were treated with 4 Gy in 8 fractions to 32 Gy, and the MammoSite patients were treated with 3.4 Gy in 10 fractions to 34 Gy. 3D-CRT patients were treated with 3.85 Gy in 10 fractions to 38.5 Gy using multiple isocentric beams. The CT images from simulation or implant evaluation were transferred into our 3D treatment planning software. The lumpectomy cavities were outlined for every patient, except the MammoSite patients, where the cavity was defined by the balloon edge. The PTV was constructed as a uniform expansion of 1.5 cm for all interstitial HDR patients, 1.0 cm for the MammoSite patients, and a 1.0 cm expansion in addition to the CTV expansion of 1.0 cm (n=2), and 1.5 cm (n=8) for the 3D-CRT patients. The CTV expansion for 3D-CRT and the PTV expansion for the brachytherapy patients were limited to the chest wall and skin. Normal structures including both ipsilateral lung and breast and heart for left-sided lesions were outlined. The lumpectomy cavity was subtracted from the PTV and normal breast tissue for evaluation. To evaluate dose to the ipsilateral breast and lung, PTV, and heart, a dose-volume histogram (DVH) analysis was performed. All histograms were normalized to the volume of the structure (i.e., expressed as percent volume). RESULTS: The average percentage of the breast receiving 100% and 50% of the prescribed dose (PD) was higher in the 3D-CRT group (24% and 48%, respectively) compared with the MammoSite (5% and 18%, respectively) and interstitial patients (10% and 26%, respectively). Improved coverage of the PTV was noted in the 3D-CRT plans compared with the MammoSite and interstitial HDR plans. With the interstitial HDR technique, 58% of the PTV received 100% of the PD compared with 76% with MammoSite and 100% with 3D-CRT techniques. The percentage of the PTV receiving 90% of the PD was 68%, 91%, and 100% for the interstitial HDR, MammoSite, and 3D-CRT patients, respectively. The ipsilateral lung V20 was slightly higher for 3D-CRT at 5% compared with 0% for both brachytherapy techniques. CONCLUSION: In those treated with 3D-CRT, coverage of the PTV was better with 3D-CRT but varied with the definition used. At the coverage at 90% of the PD, no difference was observed between 3D-CRT and MammoSite (which were both better than interstitial). 3D-CRT resulted in better coverage of the PTV compared with MammoSite or interstitial brachytherapy techniques. Better PTV coverage with 3D-CRT came at the cost of a higher integral dose to the remaining normal breast. Dosimetrically, the best partial breast irradiation technique appears to depend on the clinical situation. Of the brachytherapy techniques, MammoSite appears to be superior in PTV coverage. When comparing MammoSite vs. 3D-CRT PTV coverage at 90% of the PD, the difference was not significantly different.

Brachytherapy↗
PubMed2005

Salvage treatment for local or local-regional recurrence after initial breast conservation treatment with radiation for ductal carcinoma in situ.

The present study evaluated the outcome of salvage treatment for women with local or local-regional recurrence after initial breast conservation treatment with radiation for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast. The study cohort consisted of 90 women with local only first failure (n=85) or local-regional only first failure (n=5). The histology at the time of recurrence was invasive carcinoma for 53 patients (59%), non-invasive carcinoma for 34 patients (38%), angiosarcoma for one patient (1%), and unknown for two patients (2%). The median follow-up after salvage treatment was 5.5 years (mean=5.8 years; range=0.2-14.2 years). The 10-year rates of overall survival, cause-specific survival, and freedom from distant metastases after salvage treatment were 83%, 95%, and 91%, respectively. Adverse prognostic factors for the development of subsequent distant metastases after salvage treatment were invasive histology of the local recurrence and pathologically positive axillary lymph nodes. These results demonstrate that local and local-regional recurrences can be salvaged with high rates of survival and freedom from distant metastases. Close follow-up after initial breast conservation treatment with radiation is warranted for the early detection of potentially salvageable local and local-regional recurrences.

Adult↗
PubMed2005

Breast brachytherapy: North American experience.

Accelerated partial breast irradiation (APBI) has been investigated for over a decade as a potential alternative adjuvant treatment approach after lumpectomy for women with early-stage breast cancer. The rationale for APBI is based on pathologic data regarding the spread of cancer within the breast and study of the patterns of in-breast recurrence after breast-conserving therapy performed with or without whole-breast irradiation. This report reviews the North American experience using interstitial brachytherapy for APBI. Studies achieving low failure rates have universally been distinguished from those with high failure rates by requiring documented microscopically negative surgical margins, using a target definition consisting of the lumpectomy cavity plus a 1- to 2-cm margin, and having a rigorous quality assurance program to assure target coverage. We conclude that APBI brachytherapy programs that include all of these components have great potential to overcome many of the barriers that have prevented women from pursuing standard breast-conserving therapy.

Brachytherapy↗