E. Day Werts

Breast conservation surgery and interstitial brachytherapy in the management of locally recurrent carcinoma of the breast: the Allegheny General Hospital experience.

PURPOSE To evaluate lumpectomy followed by interstitial brachytherapy as an acceptable salvage therapy for women who have developed localized recurrence of breast cancer after conservation surgery and postoperative external radiotherapy. METHODS AND MATERIALS Between 1/1998 and 10/2006, 21 patients with T0 or T1 in-breast recurrence of carcinoma were offered interstitial low-dose rate brachytherapy after tumor re-excision as an alternative to salvage mastectomy. All patients had failed lumpectomy followed by standard postoperative external beam radiotherapy (range, 5000-6040cGy) as treatment for the initial breast carcinoma. Seven recurred as ductal carcinoma in situ, 2 as infiltrating lobular carcinoma, and 12 as recurrent invasive carcinoma. The recurrent tumors were excised with final margins of resection free of residual disease per National Surgical Adjuvant Breast and Bowel Project definition. Tumor bed implantation was then carried out with an interstitial technique using (192)Ir with the target volume consisting of the tumor bed plus a minimum 1.0-cm clinical margin. The required minimum dose delivered to the target volume was 4500-5000cGy (range, 4500-5530). RESULTS Twenty of 21 patients were free of local disease with a median observation time of 40 months (range, 3-69). The single patient who developed a second local recurrence was treated successfully with simple mastectomy. Two patients succumbed to systemic disease at 17 and 24 months after salvage implant therapy. One patient developed a contralateral breast cancer. Cosmetic results defined by the National Surgical Adjuvant Breast and Bowel Project cosmesis scale were acceptable. One patient developed a localized seroma requiring multiple needle aspirations before complete resolution. Two patients developed localized skin breakdown in the tumor bed. One healed after 6 months of conservative treatment. The other healed 9 months later with Grade II cosmesis. This patient also developed a concurrent postoperative wound infection. CONCLUSIONS Repeat lumpectomy followed by brachytherapy is feasible and may be an acceptable alternative to salvage mastectomy in patients who locally fail conservation breast therapy; however, longer followup and greater patient numbers may be needed to better define the role of salvage brachytherapy.

Tolerance of the aorta using intraoperative iodine-125 interstitial brachytherapy in cancer of the lung

PURPOSE A retrospective review to assess the efficacy and morbidity of surgical resection and (125)I interstitial lung brachytherapy placed in approximation to the aorta. METHODS AND MATERIALS The records and postoperative films of 278 patients who had undergone intrathoracic (125)I brachytherapy at our institution were reviewed. All patients had undergone a gross total resection of a non-small-cell lung cancer using segmental resection, wedge resection, or sublobar resection. Frozen section margins of resection were required to be negative before the intraoperative delivery of the implant. Of those reviewed, 29 patients were implanted with (125)I impregnated Vicryl mesh that contacted greater than 50% with the aorta. Implants consisted of (125)I seeds sewn into a nomographically guided geometric array. Only implants where 50% or greater of the implant volume directly approximated the aorta were selected for inclusion into this study. The mean aortic volume receiving the entire prescribed dose was 17.2cc (mean surface area=34.4cm(2)) and the mean prescribed dose was 114Gy (range, 85-120) over the permanent life of the implant calculated by isodose curve distribution at a depth of 0.5cm from the plane of the implant. Five patients have received postoperative mediastinal dose supplementation with external beam irradiation to further address occult mediastinal nodal disease not revealed during the intraoperative frozen section analysis. RESULTS All patients tolerated the surgery and brachytherapy well with no perioperative mortality. With a median followup of 45.3 months (range, 1-117), 1 of the 29 patients suffered a fatal hemorrhage from suspected great vessel rupture. A review of this case demonstrated that the interstitial therapy had been supplemented with 4500cGy of external irradiation, which overlapped a small portion of the implant volume overlying the aorta. No other patients suffered even minor events referable to the implant and have continued to do well without symptomatic evidence of chronic sequelae as of the publication of this article or the time of their death. Local control has been achieved in all patients still living and had been achieved in all patients who died from subsequent progression of metastatic disease or other cause. CONCLUSIONS Interstitial (125)I intrathoracic brachytherapy is a safe and effective method when used with sublobar resection in high-risk stage I non-small-cell lung cancer patients and may be used even in situations that require placement of the sources in close approximation to the aorta. The tolerance of the aorta seems to be greater than previously thought, and may well exceed 12,000cGy over the permanent life of the interstitial implant. Interstitial (125)I brachytherapy can safely be used to deliver significant radiation dose in direct contact with the aorta but supplemental, overlapping external beam irradiation should be avoided.

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.

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.

Dosimetric comparison of partial and whole breast external beam irradiation in the treatment of early stage breast cancer.

A dosimetric comparison was performed on external-beam three-dimensional conformal partial breast irradiation (PBI) and whole breast irradiation (WBI) plans for patients enrolled in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 protocol at our institution. Twenty-four consecutive patients were treated with either PBI (12 patients) or WBI (12 patients). In the PBI arm, the lumpectomy cavity was treated to a total dose of 38.5 Gy at 3.85 Gy per fraction twice daily using a four-field noncoplanar beam setup. A minimum 6 h interval was required between fractions. In the WBI arm, the whole breast including the entirety of the lumpectomy cavity was treated to a total dose of 50.4 Gy at 1.8 Gy per fraction daily using opposed tangential beams. The lumpectomy cavity volume, planning target volume for evaluation (PTV_EVAL), and critical structure volumes were contoured for both the PBI and WBI patients. Dosimetric parameters, dose volume histograms (DVHs), and generalized equivalent uniform dose (gEUD) for target and critical structures were compared. Dosimetric results show the PBI plans, compared to the WBI plans, have smaller hot spots in the PTV_EVAL (maximum dose: 104.2% versus 110.9%) and reduced dose to the ipsilateral breast (V50: 48.6% versus 92.1% and V100: 10.2% versus 50.5%), contralateral breast (V3: 0.16% versus 2.04%), ipsilateral lung (V30: 5.8% versus 12.7%), and thyroid (maximum dose: 0.5% versus 2.0%) with p values < or = 0.01. However, similar dose coverage of the PTV_EVAL (98% for PBI and 99% for WBI, on average) was observed and the dose difference for other critical structures was clinically insignificant in both arms. The gEUD data analysis showed the reduction of dose to the ipsilateral breast and lung, contralateral breast and thyroid. In addition, preliminary dermatologic adverse event assessment data suggested reduced skin toxicity for patients treated with the PBI technique.

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.

Audiometric Outcomes for Acoustic Neuroma Patients After Single Versus Multiple Fraction Stereotactic Irradiation

Objective: To compare tumor control and changes in audiometric parameters of acoustic neuroma patients treated with either linac-based stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) at Allegheny General Hospital. Study Design: Twenty-three patients with acoustic neuroma were treated between February 2003 and April 2009 with either SRS (n = 13) or SRT (n = 10). The median age for all patients was 69 years and the median size of lesions was 1.2 cm (range 0.5-2.2 cm). The prescribed dose was a single dose of 1250 cGy for all SRS patients compared to 2500 cGy in 5 daily fractions for SRT patients. All patients had pre- and post-procedure audiometry including hearing acuity assessed using pure tone average (PTA), speech discrimination score (SDS), and speech reception threshold (SR). The results of treatment type and tumor variables resulting in hearing degradation were evaluated and compared. Results: At a median follow-up of 13 months (range 3-36 months), only 1 of 13 patients treated with SRS and 2 of 10 patients treated with SRT develped progression of disease. However; all patients developed deterioration in PTA, SDS, or SR on the treated side. There were no statistically significant audiometric differences between patients treated with SRT or SRS and tumor response was similar regardless of irradiation technique. Conclusion: Both SRS and SRT provide excellent local control rates for the treatment of acoustic neuroma. While SRS demonstrated a trend toward worsening of SDS and the treatment of lesions >1.2 cm demonstrated a trend toward worsening of PTA, neither reached statistical significance. Our data suggest that single dose irradiation using the SRS technique should be considered primarily for patient convenience. All patients treated with radiotherapy for acoustic neuromas should undergo formal hearing testing before and after treatment.

Evaluation of the interfractional biological effective dose (BED) variation in MammoSite high dose rate brachytherapy

The objective of this work is to evaluate the interfractional biological effective dose (BED) variation in MammoSite high dose rate (HDR) brachytherapy. Dose distributions of 19 patients who received 34 Gy in 10 fractions were evaluated. A method was employed to account for nonuniform dose distribution in the BED calculation. Furthermore, a range of α/β values was utilized for specific clinical end points: fibrosis, telangiectasia, erythema, desquamation and breast carcinoma. Two scenarios were simulated to calculate the BED value using: i) the same dose distribution of fraction 1 over fractions 2–10 (constant case, CC), and ii) the actual delivered dose distribution for each fraction 1–10 (interfraction dose variation case, IVC). Although the average BED difference (IVC – CC) was <0.7 Gy for all clinical endpoints, the range of difference for fibrosis and telangiectasia reached −11% to +3% and −9% to +9% for one of the patients, respectively. By disregarding high inhomogeneity in HDR brachytherapy, the conventional BED calculation tends to overestimate the BED for fibrosis by 16% on average, while it underestimates the BED for erythema (7.6%) and desquamation (10.2%). In conclusion, the BED calculation accounting for the nonuniform dose distribution provides a more clinically relevant description of the clinical delivered dose. Though the average BED difference was clinically insignificant, the maximum difference of BED for late effects can differ by a single fractional dose (10%) for a specific patient due to the interfraction dose variation in MammoSite treatment. PACS number: 87.53.Jw

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.

Local failure and acute radiodermatological toxicity in patients undergoing radiation therapy with and without postmastectomy chest wall bolus: Is bolus ever necessary?

PURPOSE Postmastectomy chest wall radiation therapy has historically used bolus to increase dose at the skin surface. Despite the theoretical benefits of bolus, the clinical implications of locoregional tumor control, cosmesis, and the incidence of radiodermatitis are less well characterized. We hypothesized that treatment in the presence or absence of bolus results in equivalent chest wall recurrence rates, but its presence results in more severe acute dermatologic toxicity. METHODS AND MATERIALS Locally advanced breast cancer patients undergoing chest wall radiation therapy were retrospectively reviewed from 2005 to 2015 (n = 106; 53 with bolus, 53 without). Outcomes including local failure, acute skin toxicity, and treatment interruptions were recorded. Median age was 59 years (range, 28-91) and median follow-up was 34 months. Histology was invasive ductal carcinoma (73%), invasive lobular carcinoma (20%), inflammatory (6%), and neuroendocrine (1%). Fifty-nine percent were T3/T4 primary tumors and 29.2% had clinical/pathologic skin involvement. Node-positive patients accounted for 80.2%. Chemotherapy was administered in 84.0%. All patients had 3-dimensional conformal radiation therapy and received a median dose of 61Gy (range, 50-63 Gy). RESULTS Local failure was 6.6% (n = 7) overall, with 4 failures in the bolus group and 3 in the no bolus group. No pathological factors were associated with local failure. Acute grade 2 and 3 skin toxicities (37 vs 22) and treatment interruptions (20 vs 3) were more common in the bolus group (P < .05). Mean treatment interruption (14.5 vs 5 days) was longer for patients receiving bolus. Patients undergoing treatment interruption were more likely to fail locally than patients not requiring a treatment interruption (17.4% vs 3.6%, P = .0322). CONCLUSIONS Bolus omission in adjuvant chest wall radiation therapy may be a reasonable approach to avoid acute skin toxicity and treatment interruptions while preserving local control; however, further study will be needed to reach a definitive conclusion.