Asymptomatic Fat Research Articles

Thermally boosted interstitial high-dose-rate brachytherapy in high-risk early-stage breast cancer conserving therapy - large cohort long-term results.

Early-stage high-risk breast cancer (BC) is standardly treated with breast-conserving therapy (BCT), combined with systemic therapy and radiotherapy (RT) ± tumor bed boost, e.g., with interstitial high-dose-rate brachytherapy (HDR-BT). To improve local recurrence rate (LRR), BT radiosensitization (thermal boost, TB) with interstitial microwave hyperthermia (MWHT) may be an option. The paper aims to report a retrospective single-institutional study on 5- and 10-year local control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS), overall survival (OS), cosmetic outcome (CO), and late toxicity (fibrosis, fat necrosis) after thermally enhanced HDR-BT boost to the BC tumor bed. In 2006-2018, 557 early-stage (I-IIIA) high-risk BC patients were treated with BCT. If indicated, they were administered systemic therapy, then referred for 40.0-50.0 Gy whole breast irradiation (WBI) and 10 Gy interstitial HDR-BT boost (group A). Eligible patients had a single MWHT session preceding BT (group B). Based on present risk factors (RF), medium-risk (1-2 RF) and high-risk subgroups (≥ 3 RF) were formed. Patients were standardly checked, and control mammography (MMG) was performed yearly. Breast cosmesis (Harvard scale) and fibrosis were recorded. LC, DMFS, DFS, and OS were statistically analyzed. Out of 557 patients aged 57 years (26-84), 364 (63.4%) had interstitial HDR-BT boost (group A), and 193 (34.6%) were preheated with MWHT (group B). Patients in group B had a higher clinical stage and had more RFs. The median follow-up was 65.9. Estimated 5-year and 10-year LC resulted in 98.5% and 97.5%, respectively. There was no difference in LC, DMFS, DFS, and OS between groups A and B and between extracted high-risk subgroups A and B. Five- and ten-year OS probability was 95.4% and 88.0%, respectively, with no difference between groups A and B. Harvard criteria-based CO assessment revealed good/excellent cosmesis in 74.9-79.1%. Tumor bed hardening was present in 40.1-42.2%. Asymptomatic fat necrosis-related macrocalcifications were detected in 15.6%, more frequently in group B (p = 0.016). Thermally boosted or not, HDR-BT was locally highly effective as part of combined treatment. Five- and ten-year LC, DMFS, DFS, and OS were high and equally distributed between the groups, although TB was prescribed in more advanced one with more RFs. TB did not influence CO and fibrosis. TB added to late toxicity regarding asymptomatic fat necrosis detected on MMG.

Interstitial multicatheter HDR-brachytherapy as accelerated partial breast irradiation after second breast-conserving surgery for locally recurrent breast cancer.

ABSTRACTOur aim was to evaluate the efficacy and toxicity of interstitial multicatheter high dose rate brachytherapy (imHDR-BRT) as accelerated partial breast irradiation (APBI) after second breast-conserving surgery (BCS) in patients with ipsilateral breast tumor recurrence (IBTR). Between January 2010 and December 2019, 20 patients with IBTR who refused salvage mastectomy (sMT) were treated with second BCS and post-operative imHDR-BRT as APBI. All patients had undergone primary BCS followed by adjuvant external beam radiotherapy. Median imHDR-BRT dose was 32 Gy delivered in twice-daily fractions of 4 Gy. Five-year IBTR-free survival, distant metastasis-free survival (DMFS), overall survival (OS) as well as toxicity and cosmesis were evaluated in the present retrospective analysis. Median age at recurrence and median time from the first diagnosis to IBTR was 65.1 years and 12.2 years, respectively. After a median follow-up of 69.9 months, two patients developed a second local recurrence resulting in 5-year IBTR free-survival of 86.8%. Five-year DMFS and 5-year OS were 84.6% and 92.3%, respectively. Grade 1–2 fibrosis was noted in 60% of the patients with no grade 3 or higher toxicity. Two (10%) cases of asymptomatic fat necrosis were documented. Cosmetic outcome was classified as excellent in 6 (37.5%), good in 6 (37.5%), fair in 3 (18.75%) and poor in 1 (6.25%) patient, respectively. We conclude that imHDR-BRT as APBI re-irradiation is effective and safe for IBTR and should be considered in appropriately selected patients.

Accelerated partial breast irradiation with 3-dimensional conformal and image-guided intensity-modulated radiotherapy following breast conserving surgery – 7-Year results of a phase II trial

PurposeTo present the 7-year results of accelerated partial breast irradiation (APBI) using three-dimensional conformal (3D-CRT) and image-guided intensity-modulated radiotherapy (IG-IMRT) following breast-conserving surgery (BCS). Patients and methodsBetween 2006 and 2014, 104 patients were treated with APBI given by means of 3D-CRT using 3–5 non-coplanar, isocentric wedged fields, or IG-IMRT using kV-CBCT. The total dose of APBI was 36.9 Gy (9 × 4.1 Gy) using twice-a-day fractionation. Survival results, side effects and cosmetic results were assessed. ResultsAt a median follow-up of 90 months three (2.9%) local recurrences, one (0.9%) regional recurrence and two (1.9%) distant metastases were observed. The 7-year local (LRFS), recurrence free survival was 98.9%. The 7-year disease-free (DFS), metastases free (MFS) and overall survival (OS) was 94.8%, 97.9% and 94.8%, respectively. Late side effects included G1 skin toxicity in 15 (14.4%), G1, G2, and G3 fibrosis in 26 (25%), 3 (2.9%) and 1 (0.9%) patients respectively. Asymptomatic (G1) fat necrosis occurred in 10 (9.6%) patients. No ≥ G2 or higher late side effects occurred with IMRT. The rate of excellent/good and fair/poor cosmetic results was 93.2% and 6.8%, respectively. Conclusion7-year results of APBI with 3D-CRT and IG-IMRT are encouraging. Toxicity profile and local tumor control are comparable to other series using multicatheter interstitial brachytherapy. Therefore, these external beam APBI techniques are valid alternatives to whole breast irradiation and brachytherapy based APBI.

Adding Insult to Injury: Asymptomatic Fat Embolism Identified on Computed Tomography.

Fat embolism (FE) is a classically taught complication of long bone fractures, with the potential to cause high morbidity and mortality; however, it is rarely apparent on emergency department (ED) presentation or imaging. If recognized by the ED clinician, development of symptoms of FE may be avoided by early surgical fixation and potentially by corticosteroid administration.

Second breast conserving surgery and interstitial radiotherapy for the treatment of breast tumor local recurrences. Five-year results

To report the clinical outcomes of second breast-conserving therapy with perioperative interstitial radiotherapy for the treatment of ipsilateral breast tumor recurrences. Between 1999 and 2015, 33 patients, presenting with an ipsilateral breast tumor recurrence after previous breast conserving therapy, were salvaged by re-excision and perioperative high-dose-rate interstitial brachytherapy. A median of 8 (range: 4-24) catheters were implanted into the tumor bed intraoperatively. A total dose of 22 Gy in 5 fractions of 4.4 Gy was delivered to the tumor bed with a margin of 1-2 cm, on 3 consecutive days. The adjuvant systemic treatments consisted of hormonal therapy for 24 patients (73%) and chemotherapy for 6 patients (18%). The survival results were estimated by the Kaplan-Meier method. Late side effects and cosmetic results were also registered. The median follow-up time following the second breast conserving therapy was 61 months (range: 26-189 months). During the follow-up, 4 patients (12.1%) developed second local recurrence. The five-year actuarial rates of the second local, regional and distant recurrence were 6.3%, 6.1%, and 14.9%, respectively. The five-year probabilities of disease-free, cancer-specific and overall survival were 76.2%, 92.4%, and 89.2%, respectively. Four (12%), 19 (58%), 4 (12%) and 6 (18%) patients had excellent, good, fair and poor cosmetic results, respectively. Grade 2 and 3 fibrosis developed in 9 (27%) and 1 (3%) patients. Asymptomatic fat necrosis was detected in 7 (21%) women. Second breast conserving therapy with perioperative high-dose-rate interstitial brachytherapy is a safe and feasible option for the management of ipsilateral breast tumor recurrences. Interstitial brachytherapy may decrease the risk of second local relapse with acceptable cosmetic results and low rate of late side effects. Hence, in selected cases it can provide a feasible alternative to salvage mastectomy. Orv Hetil. 2018; 159(11): 430-438.

Seven fractions to deliver partial breast irradiation: the toxicity is Low

PurposeTo assess toxicity and clinical outcome, in breast cancer patients treated with external beam partial breast irradiation (PBI) consisting of 35 Gy in 7 daily fractions (5 Gy/fraction).Materials and MethodsPatients affected by early-stage breast cancer were enrolled in this phase II trial. Patients had to be 60 years old or over and treated with breast conservative surgery for early stage invasive carcinoma.ResultsSeventy-three patients were analyzed. Median follow-up was 40 months. The proposed schedule was well tolerated. No Grade 3 toxicity was documented. Late toxicity was assessable for all the treated patients. Two patients (2.7%) developed Grade 2 pain 6 months after PBI. Four patients (5%) developed asymptomatic fat necrosis. Grade 2 fibrosis was observed in 5 patients (6.7%). No correlation was found between early and late toxicity and the type of adjuvant systemic therapy (no therapy vs. hormonal therapy vs. chemotherapy). No statistical correlation between dosimetric parameters and toxicity was found. Patients who developed Grade 2 radiation fibrosis had not higher radiation volumes to the untreated normal breast than those without fibrosis. Cosmesis was judged good/excellent in the majority of the cases (93%). One patient relapsed locally, and one developed distant metastases, corresponding to a 5-year local control and distant metastases-free survival of 98% and 96.7%, respectively.Conclusions35 Gy in 7 daily fractions is an effective and well-tolerated regimen to deliver PBI.

A renal angiomyolipoma with extension to the renal vein and asymptomatic fat pulmonary embolus.

Renal angiomyolipoma (AML) is a rare benign tumor that can extend into the renal vein, inferior vena cava and the right atrium. AML is a mesenchymal tumor composed of smooth muscle, fat and vascular elements. In rare instances, the tumor may release a fatty tissue to the pulmonary vasculature, which can lead to cardiopulmonary collapse and death. Only four cases of fat pulmonary embolism secondary to AML have been reported in the literature but our case was the first to present as asymptomatic. Our patient had left renal AML extending to the renal vein that was associated with fat pulmonary embolus. The patient underwent uncomplicated radical nephrectomy and was discharged home on no anticoagulation. Follow-up chest computed tomography showed no extension of the pulmonary embolism. Whether embolectomy or anticoagulation is necessary in asymptomatic pulmonary embolism secondary to renal AML is unclear. Although controversial, some surgeons prefer to place an inferior vena cava filter prior to radical nephrectomy to prevent dislodgement of new intraoperative emboli, which can lead to catastrophic outcome.

Accelerated partial breast irradiation with external beam three-dimensional conformal radiotherapy

The aim of this study was to report the 5-year results of accelerated partial breast irradiation (APBI) using external beam three-dimensional conformal radiotherapy (3D-CRT). Between 2006 and 2011, 44 patients with low-risk, stage I-II breast cancer underwent breast-conserving surgery. Postoperative APBI was given by means of 3D-CRT using three to five non-coplanar fields. The total dose of APBI was 36.9 Gy (nine fractions of 4.1 Gy b.i.d.). The mean follow-up time was 58.2 months for surviving patients. Survival results, side effects, and cosmetic results were assessed. One (2.3%) local recurrence was observed, for a 5-year actuarial rate of 3.7%. Neither regional nor distant failure was observed. Two patients died of internal disease. The 5-year disease-free, cancer-specific, and overall survival rates were 96.3, 100, and 95.1%, respectively. Acute side effects included grade 1 (G1) erythema in 75%, G1 parenchymal induration in 46%, and G1 pain in 46% of patients. No G2 or higher acute side effect occurred. Late side effects included G1, G2, and G3 fibrosis in 44, 7, and 2% of patients, respectively, G1 skin pigmentation in 12%, and G1 pain in 2%. Asymptomatic fat necrosis occurred in 14%. Cosmetic results were rated excellent or good in 86% of cases by the patients themselves and 84% by the physicians. The 5-year local tumor control, toxicity profile, and cosmetic results of APBI delivered with external beam 3D-CRT are encouraging and comparable to other APBI series.

Second breast-conserving surgery and reirradiation with interstitial high-dose-rate brachytherapy for the management of intra-breast recurrences -- 5-year results

The purpose of our work was to evaluate the efficacy of second breast-conserving surgery (BCS) and reirradiation with interstitial high-dose-rate (HDR) brachytherapy (BT) for the management of local recurrences. Between 1999 and 2010, fifteen patients initially treated for breast carcinoma by BCS and radiation therapy who had isolated intra-breast recurrence underwent second BCS and perioperative HDR multicatheter BT. Breast cancer related events, late side effects, and cosmetic results were assessed. At a median follow-up of 62 months (range: 11-127) second local recurrence has not occurred, yielding a 100% mastectomy-free survival. Four patients (27%) developed subsequent distant metastasis and died of breast cancer. The 5-year actuarial rate of disease-free and overall survival was 69% and 85%, respectively. Cosmetic results were rated excellent, good, fair, poor, and unknown in 1 (7%), 10 (66%), 2 (13%), 1 (7%), and 1 (7%) patients, respectively. Grade 2 fibrosis and skin toxicity occurred in 1 (7%) and 1 (7%) patients. Asymptomatic fat necrosis was detected in 9 (60%) women. No patient developed grade 3-4 late side effects. Second BCS followed by partial breast reirradiation is a safe and effective option for the management of selected patients developing intra-breast recurrence after previous breast-conserving therapy. Perioperative HDR BT may decrease the risk of second local relapse with acceptable cosmetic results and low rate of late side effects.

Counterpoint: The device with the most dose modulation capacity

from the tissue by a balloon, modulation can be more finely tuned, with a trade-off that the V200 and V150 are higher than in the balloon devices. The SAVI is clearly neither a balloon device nor an interstitial implant, lacking some of the flexibility that makes interstitial the gold standard, but also not needing the requisite skill and experience demanded by the interstitial technique. Guidelines were developed empirically for the MammoSite (Hologic, Bedford, MA), and mandating balloon to skin distance of $5 mm was considered safe and have kept the toxicity acceptably low. However, although we know that the V150 and V200 guidelines established by MammoSite are safe, it does not mean that doses that exceed this in the absence of a balloon to displace the catheters from the normal tissue are unsafe. Nearly 2-year data on the SAVI catheter show acceptable toxicity with Grade 1 telangiectasias, hyperpigmentation, Grade 2 fibrosis, asymptomatic seromas, and asymptomatic fat necrosis rates of 1.9%, 9.8%, 1.9%, 2%, and 1.9%, respectively. Recurrence rate in this same population is acceptable at 1% as well (1).

Initial Clinical Experience With the Strut-Adjusted Volume Implant (SAVI) Breast Brachytherapy Device for Accelerated Partial-Breast Irradiation (APBI): First 100 Patients With More Than 1 Year of Follow-Up

The Strut-Adjusted Volume Implant (SAVI; Cianna Medical, Aliso Viejo, CA) is a multichannel single-entry brachytherapy device designed to allow dose modulation to minimize normal tissue dose while simultaneously maximizing target coverage. This is the first report on the initial 102 patients with nearly 2 years of median follow-up. One hundred two patients were treated at two institutions. Data were collected on eligibility and dosimetry and followed for toxicity and recurrence. The median follow-up is 21 months. Overall dosimetry is outstanding (median percent of target volume receiving 90% of the prescription dose was 95.9%, volume of target receiving 150% of the prescription dose was 27.8 mL, and volume of target receiving 200% of the prescription dose was 14.0 cm(3)). No devices were pulled prior to treatment completion. For patients with a skin bridge of less than 7 mm, the maximum median skin dose was 280 cGy (median percent of target volume receiving 90% of the prescription dose was 95.2%, volume of target receiving 150% of the prescription dose was 25.8 cm(3) and volume of target receiving 200% of the prescription dose was 12.7 mL). For patients with both chest wall and skin of less than 7 mm, the maximum median lung dose was 205 cGy with simultaneous skin dose of 272 cGy. The rate of telangiectasia was 1.9%. Grade 1 hyperpigmentation developed in 10 patients (9.8%) and Grade 2 fibrosis in 2 patients (1.9%). There were 2 symptomatic seromas and 2 cases of asymptomatic fat necrosis (1.9%). Of the patients, 27% were not eligible for MammoSite balloon brachytherapy (Hologic, Inc., Marlborough, MA) and 5% were not eligible for any balloon brachytherapy. The recurrence rate was 1%. The SAVI appears to safely allow an increase in eligibility for APBI over balloon brachytherapy or three-dimensional conformal radiation, highlighting the outstanding device flexibility to maximize the target dose and minimize the normal tissue dose. The device was well tolerated by patients.

A case of asymptomatic fat necrosis in the abdomen showing a tumor-like appearance in the ultrasonogram

症例：患者は69歳男性，健診後の精査目的のため来院．超音波検査にて右上腹部に無症状な腫瘤性病変を指摘．腫瘤径は47mm×35mm，内部は均一で右腎皮質に比して高エコーを呈した．後方エコーは不変から増強，境界は明瞭で辺縁に低エコー帯を認めた．内部の血流は認めなかった．術後の病理組織学的検査では，線維性被膜に覆われた脂肪壊死と診断された．考察：偽腫瘍性脂肪壊死は発見時の病期の違いから質的診断が困難と思われる．しかし，腸間膜内において内部に血流の認めない被膜形成を伴う腫瘤性病変を発見した場合は，この種の脂肪壊死も念頭に置くべきであろう．また，癒着の度合いや範囲により術式が変化する可能性もあるため，腫瘤の可動性をリアルタイムに観察出来る超音波検査の利点を活用し，癒着の有無や範囲を検索することが重要であると思われた．

Initial clinical experience with the Strut-Adjusted Volume Implant brachytherapy applicator for accelerated partial breast irradiation

Purpose Accelerated partial breast irradiation is becoming increasingly popular. The Cianna single-entry high-dose-rate applicator, Strut-Adjusted Volume Implant (SAVI, Cianna Medical, Aliso Viejo, CA), contains peripheral struts allowing greater planning flexibility for small-breasted women, technically easier insertion, and normal tissue exposure minimization. This study evaluates early clinical experience. Methods and Materials Thirty patients treated with the SAVI with a median followup of 12 months were evaluated. The median age was 59.5. Tumor size averaged 0.9 cm. Fifteen cancers were ductal carcinoma in situ (50%), 1 was invasive lobular (3.3%), 4 were tubular (6.7%), and the rest infiltrating ductal (40%). Most of them were estrogen receptor (ER) positive (90%). Nine women (30%) were premenopausal. Results Dosimetry was outstanding with median V90, V150, and V200 of 96.2%, 24.8, and 12.8 cc. There were no symptomatic seromas, and one report of asymptomatic fat necrosis seen on mammogram at 1 year. In patients who had skin spacing of less than 1 cm, the median skin dose was 245 cGy/fraction. The median rib and lung dose per fraction for those patients with either structure less than 1 cm was 340 and 255 cGy (75% of prescribed dose), respectively. There have been no local recurrences to date. Conclusions Early clinical experience with the SAVI demonstrates the ease of placement of a single-entry brachytherapy device combined with the increased dose modulation of interstitial brachytherapy. Dose to normal structures has remained exceedingly low. Almost half of evaluated patients were not candidates for other single-entry brachytherapy devices because of skin spacing or breast size, demonstrating an expansion of candidates for single-entry partial breast brachytherapy.

5126 Ipsilateral breast tumour relapse: local recurrence versus new primary and the effect of whole breast radiotherapy on the rate of new primaries

To examine the incidence and clinical relevance of fat necrosis after accelerated partial-breast irradiation (PBI) using interstitial high-dose-rate brachytherapy (HDR-BT) in comparison with partial-breast electron irradiation (ELE) and whole-breast irradiation (WBI).Between 1998 and 2004, 258 early-stage breast cancer patients were randomized to receive 50 Gy WBI (n = 130) or PBI (n = 128). The latter consisted of either 7 × 5.2 Gy HDR-BT (n = 88) or 50 Gy ELE (n = 40). The incidence of fat necrosis, its impact on cosmetic outcome, accompanying radiologic features, and clinical symptoms were evaluated.The 4-year actuarial rate of fat necrosis was 31.1% for all patients, and 31.9%, 36.5%, and 17.7% after WBI, HDR-BT and ELE, respectively (pWBI/HDR-BT = 0.26; pWBI/ELE = 0.11; pELE/HDR-BT = 0.025). The respective rate of asymptomatic fat necrosis was 20.2%, 25.3%, and 10% of patients. The incidence of symptomatic fat necrosis was not significantly different after WBI (8.5%), HDR-BT (11.4%), and ELE (7.5%). Symptomatic fat necrosis was significantly associated with a worse cosmetic outcome, whereas asymptomatic fat necrosis was not. Fat necrosis was detectable with mammography and/or ultrasound in each case. Additional imaging examinations were required in 21% of cases and aspiration cytology in 42%.Asymptomatic fat necrosis is a common adverse event of breast-conserving therapy, having no significant clinical relevance in the majority of the cases. The incidence of both symptomatic and asymptomatic fat necrosis is similar after conventional WBI and accelerated partial-breast HDR-BT.

Five-year results: the initial clinical trial of Mammosite balloon brachytherapy for partial breast irradiation in early-stage breast cancer

Objective Patients with early-stage invasive ductal breast cancer were prospectively evaluated using MammoSite RTS balloon brachytherapy (RTS Cytyc Corp, Marlborough, MA) as the sole modality for delivering accelerated partial breast irradiation to the lumpectomy bed with breast-conserving surgery. This report presents the 5-year results of the treated patients. Methods From May 2000 to October 2001, 70 patients were enrolled in this prospective study. Forty-three patients completed accelerated partial breast irradiation with MammoSite brachytherapy following lumpectomy and axillary staging. Thirty-six patients have been followed for a median of 5.5 years (mean 65.2 months). Criteria for entry into the study were unifocal invasive ductal carcinoma, tumor size ≤2 cm, age ≥45 years, absence of extensive intraductal component, cavity size ≥3 cm in 1 dimension, node-negative, and final margins negative per National Surgical Adjuvant Breast and Bowel Project definition. A minimum balloon-to-skin surface distance of 5 mm was required. A dose of 34 Gy was delivered in 10 fractions over 5 days prescribed to 1 cm from the applicator surface using iridium-192 high-dose-rate brachytherapy. Data on infection, seromas, cosmetic outcome, and toxicities were collected at 3 and 6 months and at yearly intervals. Local recurrences, both true recurrences in the lumpectomy bed and failures outside the initially treated target volume (elsewhere failures), were recorded. Contralateral breast failure rates were noted. Results The catheter was not implanted in 16 of the 70 enrolled patients due to cavity size not amenable to balloon placement (n = 10), ineligible by criteria (n = 4), and skin spacing (n = 2). Fifty-four patients were implanted and 43 were successfully treated with MammoSite balloon brachytherapy. Reasons for catheter explantation in 11 patients were poor cavity conformance in 7, inadequate skin spacing in 2, positive node in 1 and age less than 45 years in 1. Of the 43 patients who completed treatment, the infection rate was 9.3%. Seroma formation occurred in 32.6% of patients, of which 12% were symptomatic requiring aspiration. Asymptomatic fat necrosis was identified in 4 of the 43 patients, noted from time of catheter removal at 11, 14, 42, and 63 months. Good–excellent cosmetic outcomes were achieved in 83.3% of the 36 patients with more than 5 years of follow-up. Cosmetic outcomes were improved, with increased skin spacing having statistical significance at skin spacing ≥7 mm. The only serious adverse events were 2 infections: mastitis and abscess. Seven of the 43 treated patients have been discontinued from follow-up. None had a local recurrence recorded at last visit. Reasons for exit from the study were death from metastatic disease (n = 3), lost to follow-up (n = 2), and placed in hospice for other medical conditions (n = 2). No local recurrences (either at the tumor bed or elsewhere in the breast) or regional recurrences have occurred in the 36 patients who have been followed for a median of 5.5 years. No contralateral cancers have developed. Conclusions MammoSite balloon brachytherapy as a sole modality for delivering radiation to the tumor bed has been successful in achieving excellent local control in this initial clinical study of patients with early-stage invasive ductal breast cancer. This has been achieved with minimal toxicities and good–excellent cosmetic outcomes in 83.3%. Accelerated partial breast irradiation using the MammoSite balloon in a carefully selected group of patients has demonstrated 5-year local recurrence results comparable to those achieved with conventional whole breast radiation therapy and interstitial catheter brachytherapy as reported at 5-year data points in studies of these treatment modalities. Poor cavity conformance and inadequate skin distance were the main factors limiting use of the MammoSite device. Extended follow-up will be required to determine the long-term efficacy of this treatment modality.

Fat Necrosis After Partial-Breast Irradiation With Brachytherapy or Electron Irradiation Versus Standard Whole-Breast Radiotherapy—4-Year Results of a Randomized Trial

To examine the incidence and clinical relevance of fat necrosis after accelerated partial-breast irradiation (PBI) using interstitial high-dose-rate brachytherapy (HDR-BT) in comparison with partial-breast electron irradiation (ELE) and whole-breast irradiation (WBI). Between 1998 and 2004, 258 early-stage breast cancer patients were randomized to receive 50 Gy WBI (n = 130) or PBI (n = 128). The latter consisted of either 7 x 5.2 Gy HDR-BT (n = 88) or 50 Gy ELE (n = 40). The incidence of fat necrosis, its impact on cosmetic outcome, accompanying radiologic features, and clinical symptoms were evaluated. The 4-year actuarial rate of fat necrosis was 31.1% for all patients, and 31.9%, 36.5%, and 17.7% after WBI, HDR-BT and ELE, respectively (p(WBI/HDR-BT) = 0.26; p(WBI/ELE) = 0.11; p(ELE/HDR-BT) = 0.025). The respective rate of asymptomatic fat necrosis was 20.2%, 25.3%, and 10% of patients. The incidence of symptomatic fat necrosis was not significantly different after WBI (8.5%), HDR-BT (11.4%), and ELE (7.5%). Symptomatic fat necrosis was significantly associated with a worse cosmetic outcome, whereas asymptomatic fat necrosis was not. Fat necrosis was detectable with mammography and/or ultrasound in each case. Additional imaging examinations were required in 21% of cases and aspiration cytology in 42%. Asymptomatic fat necrosis is a common adverse event of breast-conserving therapy, having no significant clinical relevance in the majority of the cases. The incidence of both symptomatic and asymptomatic fat necrosis is similar after conventional WBI and accelerated partial-breast HDR-BT.

Long-term toxicity of an intraoperative radiotherapy boost using low energy X-rays during breast-conserving surgery

Intraoperative radiotherapy (IORT) as a boost for breast cancer delivers a high single dose of radiation to a late-reacting tissue; therefore late toxicity is of particular interest, and long-term follow-up is warranted. To date there are only limited data available on breast cancer patients treated with IORT using low energy X-rays. We analyzed toxicity and cosmesis after IORT as a boost with a minimum follow-up of 18 months. A total of 73 patients treated with IORT (20 Gy/50 kV X-rays; INTRABEAM [Carl Zeiss Surgical, Oberkochen, Germany]) to the tumor bed during breast-conserving surgery as a boost followed by whole-breast radiotherapy (WBRT, 46 Gy) underwent a prospective, predefined follow-up (median, 25 months; range 18-44 months), including clinical examination and breast ultrasound at 6-months and mammographies at 1-year intervals. Toxicities were documented using the common toxicity criteria (CTC)/European Organization for Research and Treatment of Cancer and the LENT-SOMA score. Cosmesis was evaluated with a score from 1 to 4. The IORT in combination with WBRT was well tolerated, with no Grade 3 or 4 skin toxicities and no telangiectasias. Fibrosis of the entire breast was observed in 5% of the patients. A circumscribed fibrosis around the tumor bed was palpable in up to 27% with a peak around 18 months after therapy and a decline thereafter. The observed toxicitiy rates were not influenced by age, tumor stage, or systemic therapy. The cosmetic outcome was good to excellent in>or=90% of cases. After IORT of the breast using low-energy X-rays, no unexpected toxicity rates were observed during long-term-follow-up.

Fat Necrosis after Conserving Surgery and Interstitial Brachytherapy and/or External-Beam Irradiation in Women with Breast Cancer

To investigate the incidence of fat necrosis, breast tissue fibrosis and breast pain after conserving surgery and accelerated partial-breast irradiation (APBI, group A), whole-breast external-beam irradiation (EBRT, group B), or EBRT combined with an interstitial boost (EBIB, group C) in women with breast cancer. 85 patients who received breast-conserving therapy from 02/2000 to 03/2002 were analyzed. 30 patients received EBRT, 33 patients APBI, and 22 patients EBIB. Median follow-up was 35.5, 35.0, and 37.5 months, respectively. Fat necrosis was detected and rated by mammograms, fibrosis and pain were clinically rated with the LENT-SOMA scores. The incidence of fat necrosis was 15.3% for all patients; and 15.2%, 20.0%, and 9.0% for groups A, B, and C, respectively. The 3-year fat necrosis-free survival probability was 83%, 76%, and 95% (difference not significant). The mean time to first diagnosis of fat necrosis was 25.6, 26.2, and 26.0 months. No patient needed surgical intervention because of fat necrosis-related pain. Fibrosis was present in 27.3%, 63.3%, and 77.3% (p < 0.001), breast pain in 9.0%, 33.4%, and 18.1% (p < 0.05). Asymptomatic fat necrosis is a common finding after both percutaneous and interstitial irradiation after breast-conserving surgery. This analysis did not support the hypothesis that APBI with multicatheter implants leads to higher rates of fat necrosis, fibrosis, or pain.

High-dose-rate brachytherapy alone versus whole breast radiotherapy with or without tumor bed boost after breast-conserving surgery: Seven-year results of a comparative study

To report the 7-year results of a prospective study of accelerated partial breast irradiation (APBI) using interstitial high-dose-rate brachytherapy and compare the treatment results with those achieved by standard, whole breast radiotherapy (WBRT), with or without a tumor bed boost (TBB). Between 1996 and 1998, 45 prospectively selected patients with T1N0-N1mi (single nodal micrometastasis), nonlobular breast cancer without the presence of an extensive intraductal component and with negative surgical margins were treated with APBI using interstitial high-dose-rate implants. A total dose of 30.3 Gy (n = 8) and 36.4 Gy (n = 37) in seven fractions within 4 days was delivered to the tumor bed plus a 1-2-cm margin. During the same period, 80 patients, who met the eligibility criteria for APBI but who were treated with 50 Gy WBRT with (n = 36) or without (n = 44) a 10-16-Gy TBB, were selected as controls. The median follow-up for the APBI and control groups was 81 and 83 months, respectively. Local control, relapse-free survival, cancer-specific survival, late side effects, and cosmetic results were assessed. The crude rate of total ipsilateral breast failure was 6.7% (3 of 45), 11.4% (5 of 44), and 8.3% (3 of 36) for patients treated with APBI, WBRT, and WBRT + TBB, respectively. The differences in the 5- and 7-year actuarial rates of ipsilateral breast recurrence were not statistically significant among patients treated with APBI (4.4% and 9.0%), WBRT (4.7% and 14.8%), and WBRT + TBB (5.7% and 9.5%). No statistically significant difference in either the 7-year probability of relapse-free survival (79.8%, 73.5%, and 77.7% for APBI, WBRT, and WBRT + TBB, respectively) or cancer-specific survival (93.3%, 92.9%, and 93.9% for APBI, WBRT, and WBRT + TBB, respectively) was found. The 7-year actuarial elsewhere breast failure rate was 9.0% in the APBI group and 8.3% in the control group (p = 0.80). The rate of excellent/good cosmetic results was 84.4% in the APBI group and 68.3% in the control group (p = 0.04). The corresponding rates of asymptomatic fat necrosis were 20.0% and 20.6%. Symptomatic fat necrosis occurred in 1 patient (2.2%) treated with APBI. The incidence of Grade 2 or worse late radiation side effects was similar for both groups (26.7% vs. 28.6%). Accelerated partial breast irradiation using interstitial high-dose-rate implants, with proper patient selection and quality assurance, yields similar 7-year results to those achieved with standard breast-conserving therapy. APBI does not increase the risk of elsewhere breast failures.