Comparison of Radiation With or Without Concurrent Trastuzumab for HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy: A Phase III Clinical Trial.

PURPOSE: Preclinical studies report that trastuzumab (T) can boost radiotherapy (RT) effectiveness. The primary aim of the B-43 trial was to assess the efficacy of RT alone vs concurrent RT plus T in preventing recurrence of ipsilateral breast cancer (IBTR) in women with ductal carcinoma in situ (DCIS). PATIENTS AND METHODS: Eligibility: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, DCIS resected by lumpectomy, known estrogen receptor (ER) and/or progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status by centralized testing. Whole-breast RT was given concurrently with T. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events occurred or all accrued patients were on study ≥ 5 years. RESULTS: There were 2,014 participants who were randomly assigned. Median follow-up time as of December 31, 2019, was 79.2 months. At primary definitive analysis, 114 IBTR events occurred: RT arm, 63 and RT plus T arm, 51 (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.17; P value = .26). There were 34 who were invasive: RT arm, 18 and RT plus T arm, 20 (HR, 1.11; 95% CI, 0.59 to 2.10; P value = .71). Seventy-six were DCIS: RT arm, 45 and RT plus T arm, 31 (HR, 0.68; 95% CI, 0.43 to 1.08; P value = .11). Annual IBTR event rates were: RT arm, 0.99%/y and RT plus T arm, 0.79%/y. The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all patients having been on study for ≥ 5 years. CONCLUSION: Addition of T to RT did not achieve the objective of 36% reduction in IBTR rate but did achieve a modest but statistically nonsignificant reduction of 19%. Nonetheless, this trial had negative results. Further exploration of RT plus T is needed in HER2-positive DCIS before its routine delivery in patients with DCIS resected by lumpectomy.

Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial.

BACKGROUND: Whole-breast irradiation after breast-conserving surgery for patients with early-stage breast cancer decreases ipsilateral breast-tumour recurrence (IBTR), yielding comparable results to mastectomy. It is unknown whether accelerated partial breast irradiation (APBI) to only the tumour-bearing quadrant, which shortens treatment duration, is equally effective. In our trial, we investigated whether APBI provides equivalent local tumour control after lumpectomy compared with whole-breast irradiation. METHODS: We did this randomised, phase 3, equivalence trial (NSABP B-39/RTOG 0413) in 154 clinical centres in the USA, Canada, Ireland, and Israel. Adult women (>18 years) with early-stage (0, I, or II; no evidence of distant metastases, but up to three axillary nodes could be positive) breast cancer (tumour size ≤3 cm; including all histologies and multifocal breast cancers), who had had lumpectomy with negative (ie, no detectable cancer cells) surgical margins, were randomly assigned (1:1) using a biased-coin-based minimisation algorithm to receive either whole-breast irradiation (whole-breast irradiation group) or APBI (APBI group). Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with or without a supplemental boost to the tumour bed, and APBI was delivered as 34 Gy of brachytherapy or 38·5 Gy of external bream radiation therapy in 10 fractions, over 5 treatment days within an 8-day period. Randomisation was stratified by disease stage, menopausal status, hormone-receptor status, and intention to receive chemotherapy. Patients, investigators, and statisticians could not be masked to treatment allocation. The primary outcome of invasive and non-invasive IBTR as a first recurrence was analysed in the intention-to-treat population, excluding those patients who were lost to follow-up, with an equivalency test on the basis of a 50% margin increase in the hazard ratio (90% CI for the observed HR between 0·667 and 1·5 for equivalence) and a Cox proportional hazard model. Survival was assessed by intention to treat, and sensitivity analyses were done in the per-protocol population. This trial is registered with ClinicalTrials.gov, NCT00103181. FINDINGS: Between March 21, 2005, and April 16, 2013, 4216 women were enrolled. 2109 were assigned to the whole-breast irradiation group and 2107 were assigned to the APBI group. 70 patients from the whole-breast irradiation group and 14 from the APBI group withdrew consent or were lost to follow-up at this stage, so 2039 and 2093 patients respectively were available for survival analysis. Further, three and four patients respectively were lost to clinical follow-up (ie, survival status was assessed by phone but no physical examination was done), leaving 2036 patients in the whole-breast irradiation group and 2089 in the APBI group evaluable for the primary outcome. At a median follow-up of 10·2 years (IQR 7·5-11·5), 90 (4%) of 2089 women eligible for the primary outcome in the APBI group and 71 (3%) of 2036 women in the whole-breast irradiation group had an IBTR (HR 1·22, 90% CI 0·94-1·58). The 10-year cumulative incidence of IBTR was 4·6% (95% CI 3·7-5·7) in the APBI group versus 3·9% (3·1-5·0) in the whole-breast irradiation group. 44 (2%) of 2039 patients in the whole-breast irradiation group and 49 (2%) of 2093 patients in the APBI group died from recurring breast cancer. There were no treatment-related deaths. Second cancers and treatment-related toxicities were similar between the two groups. 2020 patients in the whole-breast irradiation group and 2089 in APBI group had available data on adverse events. The highest toxicity grade reported was: grade 1 in 845 (40%), grade 2 in 921 (44%), and grade 3 in 201 (10%) patients in the APBI group, compared with grade 1 in 626 (31%), grade 2 in 1193 (59%), and grade 3 in 143 (7%) in the whole-breast irradiation group. INTERPRETATION: APBI did not meet the criteria for equivalence to whole-breast irradiation in controlling IBTR for breast-conserving therapy. Our trial had broad eligibility criteria, leading to a large, heterogeneous pool of patients and sufficient power to detect treatment equivalence, but was not designed to test equivalence in patient subgroups or outcomes from different APBI techniques. For patients with early-stage breast cancer, our findings support whole-breast irradiation following lumpectomy; however, with an absolute difference of less than 1% in the 10-year cumulative incidence of IBTR, APBI might be an acceptable alternative for some women. FUNDING: National Cancer Institute, US Department of Health and Human Services.

Tumor localization accuracy for high-precision radiotherapy during active breath-hold.

BACKGROUND: Conventionally fractionated and stereotactic body radiation therapy (SBRT) for thoracoabdominal tumors may utilize breath-hold techniques. However, there are concerns that differential amounts of inspired airflow may result in unplanned tumor dislocation and underdosing. Thus, we investigated tumor localization accuracy associated with lung volume variations during breath-hold treatment via an automated-gating interface. METHODS: Twelve patients received breath-hold treatment with the active breathing coordinator (ABC) through an automated-gating interface. All breath-hold volumes were recorded at CT simulation, setup imaging, and during treatment, and analyzed as a function of airflow rate into the ABC. The variation of breath-hold volumes was calculated for each fraction over entire course. Intrafraction target motion related to the breathing variation was investigated based on daily imaging acquired before the breath-hold treatment. Correlation between target location and breath-hold variation was statistically analyzed. RESULTS: The air volume held by the ABC increased as the airflow rate increased on inhalation and decreased on exhalation. The mean range of airflow rate was 0.77 L/s and 0.29 L/s in the conventionally fractionated and SBRT patients, respectively. The maximum air volume difference with respect to the reference volume at the CT simulation was 1.0 L for conventional fractionation and 0.16 L for SBRT. The target dislocation caused by 0.25 L of air volume difference was 6 mm for SBRT. Three patients showed significant correlation between the target location and breath-hold variations. CONCLUSIONS: This investigation shows that because variations in the breath-hold volume may cause target dislocation, patient-specific breath-hold setting is required to improve tumor localization accuracy.

Stereotactic body radiotherapy (SBRT) with or without surgery for primary and metastatic liver tumors.

OBJECTIVES: We report single center experience on the outcome and toxicity of SBRT alone or in combination with surgery for inoperable primary and metastatic liver tumors between 2007 and 2014. PATIENTS AND METHODS: Patients with 1-4 hepatic lesions and tumor diameter ≤9 cm received SBRT at 46.8Gy ± 3.7 in 4-6 fractions. The primary end point was local control with at least 6 months of radiographic followup, and secondary end points were toxicity and survival. RESULTS: Eighty-seven assessable patients (114 lesions) completed liver SBRT for hepatoma (39) or isolated metastases (48) with a median followup of 20.3 months (range 1.9-64.1). Fourteen patients underwent liver transplant with SBRT as a bridging treatment or for tumor downsizing. Eight patients completed hepatic resections in combination with planned SBRT for unresectable tumors. Two-year local control was 96% for hepatoma and 93.8% for metastases; it was 100% for lesions ≤4 cm. Two-year overall survival was 82.3% (hepatoma) and 64.3% (metastases). No incidence of grade >2 treatment toxicity was observed. CONCLUSION: In this retrospective analysis we demonstrate that liver SBRT alone or in combination with surgery is safe and effective for the treatment of isolated inoperable hepatic malignancies and provides excellent local control rates.

Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04.

PURPOSE: The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy (RT) for patients with rectal cancer is unknown. National Surgical Adjuvant Breast and Bowel Project trial R-04 compared four chemotherapy regimens administered concomitantly with RT. PATIENTS AND METHODS: Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in 25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous intravenous infusional fluorouracil (CVI FU; 225 mg/m(2), 5 days per week), with or without intravenous oxaliplatin (50 mg/m(2) once per week for 5 weeks) or oral capecitabine (825 mg/m(2) twice per day, 5 days per week), with or without oxaliplatin (50 mg/m(2) once per week for 5 weeks). Before random assignment, the surgeon indicated whether the patient was eligible for sphincter-sparing surgery based on clinical staging. The surgical end points were complete pathologic response (pCR), sphincter-sparing surgery, and surgical downstaging (conversion to sphincter-sparing surgery). RESULTS: From September 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, sphincter-sparing surgery, or surgical downstaging were identified between the CVI FU and capecitabine regimens or between the two regimens with or without oxaliplatin. Patients treated with oxaliplatin experienced significantly more grade 3 or 4 diarrhea (P < .001). CONCLUSION: Administering capecitabine with preoperative RT achieved similar rates of pCR, sphincter-sparing surgery, and surgical downstaging compared with CVI FU. Adding oxaliplatin did not improve surgical outcomes but added significant toxicity. The definitive analysis of local tumor control, disease-free survival, and overall survival will be performed when the protocol-specified number of events has occurred.

Merkel cell tumor of the skin treated with localized radiotherapy: are widely negative margins required?

Merkel's cell carcinoma is a rare cutaneous tumor that can affect a wide variety of sites throughout the body. Commonly, it affects the skin alone and the management of limited disease can be confusing since the natural history of the disease involves distant metastasis. Traditional management has required wide local excision with negative margins of resection. We describe a case treated with local therapy alone and review the literature to suggest that complete microscopic excision may not be required if adjuvant radiotherapy is used.

Mature follow-up for high-risk stage I non-small-cell lung carcinoma treated with sublobar resection and intraoperative iodine-125 brachytherapy.

PURPOSE: To update the Allegheny General Hospital experience of high-risk Stage I non-small-cell lung cancer patients treated with sublobar resection and intraoperative (125)I Vicryl mesh brachytherapy. METHODS AND MATERIALS: Between January 5, 1996 and February 19, 2008, 145 patients with Stage I non-small-cell lung cancer who were not lobectomy candidates because of cardiopulmonary compromise underwent sublobar resection and placement of (125)I seeds along the resection line. The (125)I seeds embedded in Vicryl suture were attached with surgical clips to a sheet of Vicryl mesh, inserted over the target area, and prescribed to a 0.5-cm planar margin. RESULTS: The mean target area, total activity, number of seeds implanted, and prescribed total dose was 33.3 cm(2) (range, 18.0-100.8), 20.2 mCi (range, 11.1-29.7), 46 (range, 30-100), and 117 Gy (range, 80-180), respectively. The median length of the surgical stay was 6 days (range, 1-111), with a perioperative mortality rate of 3.4%. At a median follow-up of 38.3 months (range, 1-133), 6 patients had developed local recurrence (4.1%), 9 had developed regional failure (6.2%), and 25 had distant failure (17.2%). On multivariate analysis, no patient- or tumor-specific factors or surgical or dosimetric factors were predictive of local recurrence. The overall median survival was 30.5 months with a 3- and 5-year overall survival rate of 65% and 35%, respectively. CONCLUSION: (125)I brachytherapy for high-risk, Stage I non-small-cell lung cancer after sublobar resection is well tolerated and associated with a low local failure rate.

Influence of concurrent anastrozole on acute and late side effects of whole breast radiotherapy.

OBJECTIVES: To retrospectively compare radiation toxicity in patients treated with concurrent anastrozole and whole breast irradiation versus women treated sequentially with whole breast irradiation followed by hormonal suppression. METHODS: The records of 249 consecutive estrogen or progesterone receptor positive breast cancer patients treated with breast-conserving surgery and postoperative whole breast irradiation were reviewed. Of total, 57 patients (the concurrent anastrozole group) received concurrent anastrozole prior to and during radiotherapy. In 126 patients (the sequential group), adjuvant hormone suppression therapy (anastrozole, other aromatase inhibitors, or tamoxifen) was administered after the completion of breast irradiation. In 66, women either concurrent tamoxifen was given with radiation or the sequence of hormonal therapy was not known. These women were excluded from the analysis. RESULTS: The frequency of acute grade 2 radiation dermatitis (24.6% in the concurrent anastrozole group vs. 20.6% in the sequential group; P = 0.55), grade 3 radiation dermatitis (8.8% vs. 7.1%; P = 0.77) and treatment interruptions due to skin reactions (14.0% vs. 11.2%; P = 0.69) did not differ between groups. The rates of clinically detectable breast fibrosis were not different (24.2% vs. 24.7%; P = 0.97). With a median follow-up of 28 months and 30.8 months, respectively, 1 local failure occurred in the concurrent anastrozole group and 5 in the sequential group. CONCLUSIONS: Anastrozole, administered concurrently with whole breast irradiation, did not increase acute or late morbidity when compared with sequential administration of radiation and hormonal suppression therapy.

Comparison of conservative management techniques in the re-treatment of ipsilateral breast tumor recurrence.

PURPOSE: To compare brachytherapy and three-dimensional (3-D) conformal external beam radiotherapy for breast cancer presenting in the previously irradiated breast. METHODS AND MATERIALS: Thirty-six patients with TIS-T2 breast carcinomas received brachytherapy or 3-D conformal radiotherapy (3-D CRT) after lumpectomy in a previously irradiated breast as an alternative to salvage mastectomy. Brachytherapy consisted of low-dose-rate (LDR) interstitial technique in 21 patients, whereas 11 patients were treated using high-dose-rate (HDR) balloon technique. Four patients received 3-D CRT. Cosmesis was graded according to the Harvard criteria and the Allegheny General Modification of the Harvard criteria. Acute sequelae were graded according to the Common Terminology Criteria for Adverse Events (version 3.0). RESULTS: Thirty-five of 36 patients remained free of local failure, with a mean followup of 37 months. Five patients treated with LDR developed Grade II and two developed Grade III acute side effects. No patient treated with balloon brachytherapy or 3-D CRT developed a Grade II or higher acute effect. Cosmetically, 12 LDR interstitial patients were scored as Grade I, six as Grade II, and three as Grade III. Nine of the HDR patients were scored as Grade I, one as Grade II, and one as Grade III. Two 3-D CRT patients were scored as Grade II and two as Grade III. The Allegheny Modification of the Harvard criteria more accurately reflected the cosmetic effects of re-treatment. CONCLUSION: Brachytherapy is feasible for patients who desire breast preservation in a previously irradiated breast. All techniques demonstrated similar local control rates. Acute side effects were less, and cosmesis was superior in HDR balloon brachytherapy.

Mammary fat necrosis following radiotherapy in the conservative management of localized breast cancer: does it matter?

PURPOSE: Fat necrosis is a well-described and relatively common complication arising from post-lumpectomy irradiation of the breast, most commonly breast brachytherapy. We wish to assess the clinical significance of fat necrosis resulting from post-lumpectomy breast irradiation. METHODS: We reviewed the literature to determine the overall incidence and significance of fat necrosis to determine whether or not fat necrosis poses a significant clinical problem. RESULTS: Fat necrosis occurs in up to one-quarter of patients following post-lumpectomy breast irradiation. Only rarely is invasive intervention required however, it does significantly degrade the quality of all modalities of breast imaging. CONCLUSIONS: Fat necrosis is a common complication of radiotherapy which rarely requires therapeutic intervention. However, post-therapeutic clinical imaging such as mammography, ultrasound and magnetic resonance imaging are affected which may result in additional diagnostic procedures up to and including biopsy.

Reduction in radiation-induced morbidity by use of an intercurrent boost in the management of early-stage breast cancer.

PURPOSE: Electron or photon boost immediately following whole-breast irradiation performed after conservation surgery for early-stage breast cancer is the accepted standard of care. This regimen frequently results in Grade III dermatitis, causing discomfort or treatment interruption. Herein, we compare patients treated with whole-breast irradiation followed by boost compared with a cohort with a planned intercurrent radiation boost. METHODS AND MATERIALS: The records of 650 consecutive breast cancer patients treated at Allegheny General Hospital (AGH) between 2000 and 2008 were reviewed. Selected for this study were 327 patients with T1 or T2 tumors treated with external beam radiotherapy postlumpectomy. One hundred and sixty-nine patients were treated by whole-breast radiotherapy (WBRT) followed by boost at completion. One hundred fifty-eight were treated with a planned intercurrent boost (delivered following 3,600 cGy WBRT). The mean whole breast radiation dose in the conventionally treated group was 5,032 cGy (range, 4500-5400 cGy), and the mean whole breast dose was 5,097 cGy (range, 4860-5040 cGy) in the group treated with a planned intercurrent boost. RESULTS: The occurrence of Grade III dermatitis was significantly reduced in the WBRT/intercurrent boost group compared with the WBRT/boost group (0.6% vs. 8.9%), as was the incidence of treatment interruption (1.9% vs. 14.2%). With a median follow-up of 32 months and 27 months, respectively, no significant difference in local control was identified. CONCLUSIONS: Patients treated with intercurrent boost developed less Grade III dermatitis and unplanned treatment interruptions with similar local control.

The allegheny general modification of the Harvard Breast Cosmesis Scale for the retreated breast.

The use of brachytherapy--and to a lesser extent, external-beam radiotherapy--in the management of locally recurrent breast cancer following ipsilateral breast tumor recurrence (IBTR) followed by repeat breast-conservation surgery and irradiation is currently an area of intense study. The current cosmetic scoring system is inadequate to score the outcome resulting from retreatment because it does not account for the cosmetic effect of the initial treatment. We propose a modification of the scale for patients who undergo retreatment--the Allegheny General Modification of the Harvard/NSABP/RTOG scoring scale.

A region growing method for tumor volume segmentation on PET images for rectal and anal cancer patients.

The application of automated segmentation methods for tumor delineation on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) images presents an opportunity to reduce the interobserver variability in radiotherapy (RT) treatment planning. In this work, three segmentation methods were evaluated and compared for rectal and anal cancer patients: (i) Percentage of the maximum standardized uptake value (SUV% max), (ii) fixed SUV cutoff of 2.5 (SUV2.5), and (iii) mathematical technique based on a confidence connected region growing (CCRG) method. A phantom study was performed to determine the SUV% max threshold value and found to be 43%, SUV43% max. The CCRG method is an iterative scheme that relies on the use of statistics from a specified region in the tumor. The scheme is initialized by a subregion of pixels surrounding the maximum intensity pixel. The mean and standard deviation of this region are measured and the pixels connected to the region are included or not based on the criterion that they are greater than a value derived from the mean and standard deviation. The mean and standard deviation of this new region are then measured and the process repeats. FDG-PET-CT imaging studies for 18 patients who received RT were used to evaluate the segmentation methods. A PET avid (PETavid) region was manually segmented for each patient and the volume was then used to compare the calculated volumes along with the absolute mean difference and range for all methods. For the SUV43% max method, the volumes were always smaller than the PETavid volume by a mean of 56% and a range of 21%-79%. The volumes from the SUV2.5 method were either smaller or larger than the PETavid volume by a mean of 37% and a range of 2%-130%. The CCRG approach provided the best results with a mean difference of 9% and a range of 1%-27%. Results show that the CCRG technique can be used in the segmentation of tumor volumes on FDG-PET images, thus providing treatment planners with a clinically viable starting point for tumor delineation and minimizing the interobserver variability in radiotherapy planning.

Investigation of simple IMRT delivery techniques for non-small cell lung cancer patients with respiratory motion using 4DCT.

Techniques for generating simplified IMRT treatment plans for treating non-small cell lung cancer (NSCLC) patients with respiratory motion were investigated. To estimate and account for respiratory motion, 4-dimensional computed tomography (4DCT) datasets from 5 patients were used to design 5-field 6-MV ungated step-and-shoot intensity modulated radiotherapy (IMRT) plans delivering a dose of 66 Gy to the planning target volume (PTV). For each patient, 2 plans were generated using the mean intensity and the maximum intensity of 10 CT datasets from different breathing phases. The plans also utilized different margins around the clinical target volume/internal target volume (CTV/ITV) to account for tumor motion. To reduce the treatment time and ensure accurate dose delivery to moving targets, the number of intensity levels was minimized while maintaining dose coverage to PTV and minimizing dose to organs at risk (OARs). Dose-volume histograms (DVHs), dosimetric metrics, and outcome probabilities were evaluated for all plans. Plans using the averaged CT image dataset were inferior, requiring larger margins around the PTV, with a maximum of 1.5 cm, to ensure coverage of the tumor, and therefore increased the dose to OARs located in proximity of the tumor. The plans based on superimposed CT image datasets achieved full coverage of the tumor, while allowing tight margins around the PTV and minimizing the dose to OARs. A small number of intensity-levels (3 to 5), resulting in IMRT plans with a total of 13 to 30 segments, were sufficient for homogeneous PTV coverage, without affecting the sparing of OARs. In conclusion, a technique involving treatment planning with the superimposed CT scans of all respiratory phases, and the application of IMRT with only a small number of segments was feasible despite significant tumor motion; however, greater patient numbers are needed to support the statistical significance of the results presented in this work.

Long-term cosmesis after lumpectomy and brachytherapy in the management of carcinoma of the previously irradiated breast.

OBJECTIVE: To evaluate the cosmetic outcome of brachytherapy after lumpectomy in the management of carcinoma of the previously irradiated breast. MATERIALS AND METHODS: Between January 1998 and April 2008, 26 patients with TIS or T1 breast carcinoma were offered interstitial or intracavitary brachytherapy after lumpectomy in a previously irradiated breast as an alternative to salvage mastectomy. Twenty-five of 26 patients had prior lumpectomy followed by standard postoperative external beam radiotherapy for early stage carcinoma of the breast [dose range 5000-6040 cGy]. One patient developed breast cancer after full mantle irradiation [4500 cGy to the mediastinum and axillae] for Hodgkin Lymphoma 27 years earlier. All tumors were excised with final margins of resection free of disease per National Surgical Adjuvant Breast and Bowel Project definition. After lumpectomy, tumor bed implantation was carried out utilizing a low dose rate interstitial technique in 22 patients, whereas 3 patients were treated with high dose rate brachytherapy using the MammoSite brachytherapy catheter and 1 patient was treated with high dose rate brachytherapy using the Contura catheter. The low dose rate treatment consisted of 4500 to 5000 cGy at 35 to 50 cGy per hour to the tumor bed plus a 1.0 cm margin, whereas the high dose rate treatment consisted of 3400 cGy in twice daily fractions of 340 cGy currently used in National Surgical Adjuvant Breast and Bowel Project B-39. Cosmesis was graded according to the B-39 cosmesis scale for de novo treatments: grade I as excellent, grade II as good, Grade III as fair, and Grade IV as poor. RESULTS: Eighteen patients were scored as grade I, 6 as grade II, and 2 as grade III. No patient received a Grade IV score. All 4 balloon brachytherapy patients were scored as Grade I. Twenty-five of 26 patients remained free of local failure with a median follow-up of 38 months (range 6-75 months). The only patient to develop a second local recurrence was graded as grade I before salvage mastectomy. Two patients developed wound dehiscence after immediate postlumpectomy implantation. Two have succumbed to metastatic breast carcinoma at 17 and 24 months after salvage implant therapy. An additional patient has succumbed to chronic obstructive pulmonary disease. All patients, regardless of cosmesis grade were satisfied with their decision for repeat conservation therapy. Factors affecting cosmesis were distance from the implant to the skin, the type of device used, and the amount of residual breast tissue after repeat lumpectomy. CONCLUSIONS: The cosmetic effect of brachytherapy after lumpectomy in the management of recurrent carcinoma of the previously irradiated breast is acceptable in highly selected patients. Intracavitary technique may provide superior cosmetic results for patients retreated with brachytherapy for salvage.

The use of the MammoSite balloon applicator in re-irradiation of the breast.

PURPOSE: To examine the feasibility of using the MammoSite brachytherapy applicator in the retreatment of the previously irradiated breast. METHODS AND MATERIALS: Between March 2004 and March 2007, three patients previously treated with external beam radiotherapy were retreated using the MammoSite brachytherapy device. Two patients were treated for an ipsilateral breast tumor recurrence after breast conservation surgery and postoperative irradiation, whereas the third patient developed an in-field breast cancer likely associated with Hodgkin's disease mantle irradiation 27 years before. The recurrent histology of two was ductal carcinoma in situ ([DCIS] one originally presenting as infiltrating ductal carcinoma [IDC] and the other as DCIS), whereas the Hodgkin's disease patient presented with IDC. All patients received a twice-daily tumor dose of 3400 cGy at 340 cGy/fraction. The mean maximum skin dose was 53.4% (range, 49.5-60.3%) of the prescribed dose. RESULTS: With a mean followup of 32 months, no patient developed a local recurrence. Cosmesis in all three cases as graded by the National Surgical Adjuvant Breast and Bowel Project, cosmesis criteria was excellent (Grade I) in all cases. Dosimetric calculations demonstrated that the device allows for appropriate local irradiation while sparing the previously irradiated skin of the involved breast as defined by the protocol standard. CONCLUSIONS: Use of the MammoSite device in the treatment of the previously irradiated breast is feasible and may provide adequate local control as well as acceptable cosmesis in carefully selected patients.

Paraganglioma: a potentially challenging tumor.

Paragangliomas are usually low-grade neoplasms with a benign natural history. While the treatment of paraganglioma has historically been controversial, surgery and radiotherapy have become standardized as therapies of choice for primary therapy. More recently, stereotactic radiosurgery has been used effectively against this rare tumor. The development of metastatic disease in patients with paraganglioma is an unusual and challenging event. This case report and review describes the specific features of this disease and the multiple therapeutic options.

Investigation of interfraction variations of MammoSite balloon applicator in high-dose-rate brachytherapy of partial breast irradiation.

PURPOSE: To measure the interfraction changes of the MammoSite applicator and evaluate their dosimetric effect on target coverage and sparing of organs at risk. METHODS AND MATERIALS: A retrospective evaluation of the data from 19 patients who received 10 fractions (34 Gy) of high-dose-rate partial breast irradiation was performed. A computed tomography-based treatment plan was generated for Fraction 1, and a computed tomography scan was acquired just before the delivery of each fraction to ensure a consistent shape of the balloon. The eccentricity, asymmetry, and planning target volume (PTV) for plan evaluation purposes (PTV_EVAL), as well as trapped air gaps, were measured for all patients. Furthermore, 169 computed tomography-based treatment plans were retrospectively generated for Fractions 2-10. Interfraction dosimetric variations were evaluated using the %PTV_EVAL coverage, target dose homogeneity index, target dose conformal index, and maximum doses to the organs at risks. RESULTS: The average variation of eccentricity and asymmetry from Fraction 1 values of 3.5% and 1.1 mm was -0.4% +/- 1.6% and -0.1 +/- 0.6 mm. The average trapped air gap volume was dramatically reduced from before treatment (3.7 cm(3)) to Fraction 1 (0.8 cm(3)). The PTV_EVAL volume change was insignificant. The average variation for the %PTV_EVAL, target dose homogeneity, and target dose conformal index from Fraction 1 values of 94.7%, 0.64, and 0.85 was 0.15% +/- 2.4%, -0.35 +/- 2.4%, and -0.34 +/- 4.9%, respectively. The average Fraction 1 maximum skin and ipsilateral lung dose of 3.2 Gy and 2.0 Gy varied by 0.08 +/- 0.47 and -0.16 +/- 0.29 Gy, respectively. CONCLUSION: The interfraction variations were patient specific and fraction dependent. Although the average interfraction dose variations for the target and organs at risk were not clinically significant, the maximum variations could be clinically significant.