Second breast cancer: recurrence score results, clinicopathologic characteristics, adjuvant treatments, and outcomes-exploratory analysis of the Clalit registry.

Data on using the 21-gene Recurrence Score (RS) testing on second breast cancer (BC; second primary or local recurrence) are lacking. This cohort study examined patients with first and second BC, who underwent 21-gene testing both times. It included a 'study-cohort' (60 N0/N1mi/N1 ER + HER2‒ BC patients with ≥2 RS results >1 year apart) and a 'general 21-gene-tested BC-cohort' (2044 previously described N0/N1mi/N1 patients). The median time between the first and second BC was 5.2 (IQR, 3.1-7.1) years; the second BC was ipsilateral in 68%. Patient/tumor characteristics of the first- and second-BC in the 'study-cohort' were similar, except for the RS which was higher in the second BC (median [IQR]: 23 [17-30] vs 17 [14-22], p < 0.001). Overall, 56 patients had follow-up data, of whom 5 experienced distant recurrence (2 RS 11-25 patients and 3 RS 26-100 patients). Studies exploring the prognostic utility of the RS in this setting are warranted.

Clinical outcomes in estrogen receptor-positive early-stage breast cancer patients with Recurrence Score 26-30: observational real-world cohort study.

Data on adjuvant chemotherapy (CT) benefit in ER + HER2‒ early-stage breast cancer (EBC) patients with Recurrence Score (RS) 26-30 are limited. This real-world study evaluated the relationships between the RS, adjuvant treatments, and outcomes in 534 RS 26-30 patients tested through Clalit Health Services (N0: n = 394, 49% CT-treated; N1mi/N1: n = 140, 62% CT-treated). The CT-treated and untreated groups were imbalanced (more high-risk clinicopathologic characteristics in CT-treated patients). With median follow-up of 8 years, Kaplan-Meier estimates for overall survival (OS), distant recurrence-free survival (DRFS), and BC-specific mortality (BCSM) were not significantly different between CT-treated and untreated N0 patients. Seven-year rates (95% CI) in CT-treated vs untreated: OS, 97.9% (94.4-99.2%) vs 97.9% (94.6-99.2%); DRFS, 91.5% (86.6-94.7%) vs 91.2% (86.0-94.6%); BCSM, 0.5% (0.1-3.7%) vs 1.6% (0.5-4.7%). For N1mi/N1 patients, OS/DRFS did not differ significantly between treatment groups; whereas BCSM did (1.3% [0.2-8.6%] vs 6.2% [2.0-17.7%] for CT-treated and untreated patients, respectively, p = 0.024).

Biopsy of breast cancer metastases: patient characteristics and survival.

BACKGROUND: Discordance in hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) status between primary tumors and metastatic sites for breast cancer is well established. However, it is uncertain which patient-related factors lead to biopsy when metastases are suspected and whether having a biopsy impacts survival. METHODS: The medical charts of metastatic breast cancer (MBC) patients diagnosed January 2000-August 2014 were retrospectively reviewed. A biopsy was defined as a procedure where tissue was obtained and assessed for both HR and HER2. Both bivariate and multivariate analyses were performed to assess patient characteristics related to biopsy and whether having a biopsy was associated with improved survival. RESULTS: Of 409 patients suspected of having MBC, 165 (40%) had a biopsy, and 34% of these had discordant HR or HER2 status when compared to the initial diagnosis. In multivariate analysis, having a biopsy was associated with: recurrence in years 2010-2014, disease-free interval of > =3 years, stage 0-IIA at presentation, suspected locoregional recurrence, being HR+/HER2-, or missing HR/HER2 at diagnosis. A similar multivariate analysis revealed that having a biopsy was associated with improved survival (HR = 0.67, p = 0.002). The association of biopsy and improved survival was noted in specific subgroups: patients with missing HR and HER2 data at initial diagnosis (p = 0.001), those without metastases in liver, lung or brain (p = 0.001), and being younger than 70 years old at recurrence (p < 0.001). CONCLUSIONS: Specific clinical factors were associated with biopsy at the time of suspected recurrence. Having a biopsy was associated with reduced mortality.

Prospective comparison of whole-body bone SPECT and sodium 18F-fluoride PET in the detection of bone metastases from breast cancer.

OBJECTIVE: The superiority of sodium F-fluoride PET (F-PET)/computed tomography (CT) over planar and single field-of-view single-photon emission computed tomography (SPECT) bone scintigraphy with Tc-methylene diphosphonate in bone metastases detection has been established. The present study prospectively compares whole-body Tc-methylene diphosphonate SPECT (WB-SPECT) and F-PET performance indices for the detection of bone metastases in breast cancer. METHODS: A total of 41 pairs of studies in female breast cancer patients (average age 58 years, range 30-75) were included. Half-time WB-SPECT and F-PET/CT were performed at a 4-day average interval (range 0-36 days), with subsequent fusion of CT to WB-SPECT. Two readers independently interpreted the studies, with differences resolved by consensus. Composite gold standard included the CT component of the F-PET/CT study with follow-up CT, MRI, F-fluoro-deoxyglucose-PET/CT, and bone scans. RESULTS: On patient-based analysis, metastases were diagnosed in 21 patients, with 19 patients detected by WB-SPECT and 21 with F-PET, the latter being the only modality to detect a single metastasis in two patients. The sensitivity of WB-SPECT and F-PET was 90 and 100% (P=NS), and the specificity were 95 and 85%, respectively (P=NS). On lesion-based analysis, 284 total sites of increased uptake were found. WB-SPECT detected 171/284 (60%) and F-PET 268/284 (94%) lesions, with good interobserver agreement for WB-SPECT (κ=0.679) and excellent agreement for F-PET (κ=0.798). The final analysis classified 204 lesions as benign and 80 as metastases. WB-SPECT identified 121 benign and 50 malignant sites compared with 192 and 76, respectively, for F-PET. WB-SPECT and F-PET had a sensitivity of 63 vs. 95%, P-value of less than 0.001, and a specificity of 97 vs. 96% (P=NS), respectively, on lesion-based analysis. CONCLUSION: F-PET had higher sensitivity for the diagnosis of bone metastases from breast cancer compared with WB-SPECT, showing a statistically significant 32% increase on lesion-based analysis.

Physicians' Considerations for Repeat Biopsy in Patients With Recurrent Metastatic Breast Cancer.

BACKGROUND: A strong recommendation has been made to perform repeat biopsy for recurrent metastatic breast cancer (RMBC), to reconfirm the histologic features, and to assess for possible changes in hormone receptors (HRs) or human epidermal growth factor receptor 2 (HER2) status. The present study was undertaken to assess the documented and nondocumented factors affecting physicians' decisions to perform a repeat biopsy in patients with RMBC. PATIENTS AND METHODS: We reviewed the medical records of 410 patients with RMBC for whom recurrence had developed between January 2000 and August 2014. The demographic data and characteristics regarding early and metastatic disease were recorded. The written follow-up records were examined, seeking considerations for or against repeat biopsy. Multivariate analysis was performed using logistic regression to determine the nondocumented reasons for repeat biopsy. RESULTS: A new biopsy was performed in 295 of 410 patients (72%). However, only 88 of the 295 patients (30%) had a documented reason for rebiopsy. The reason for not performing repeat biopsy was documented for only 1 of the 115 patients. The main documented consideration for rebiopsy was to obtain a new receptor status (recorded in 47 of 88 patients; 53%). The other recorded reasons were suspicion of a second primary, differential diagnosis of metastasis from a second primary, the time from early diagnosis, and patient desire. Significant, but undocumented, considerations for repeat biopsy were low stage at early diagnosis, year of recurrence, interval to recurrence, and site of recurrence. Only for 165 of 295 patients (56%) was the full HR and HER2 status from the new biopsy specimen obtained. CONCLUSION: Nondocumented factors influence physicians' decisions for referring patients for rebiopsy. This might reflect a low rate of patient involvement in their disease management and decision making.

Cancer-related fatigue and depression in breast cancer patients postchemotherapy: Different associations with optimism and stress appraisals.

OBJECTIVE: Symptoms of depression and cancer-related fatigue (CRF) are common among breast cancer patients postchemotherapy and may seriously impair quality of life (QoL). This study aimed to assess the relationship between depression and CRF in breast cancer patients postchemotherapy and to examine their relationships to optimism and to threat and challenge appraisals. METHOD: Participants included 95 breast cancer patients (stages 1-3) 1 to 6 months after completion of chemotherapy. Patients submitted personal and medical details and completed the following: physical symptom questionnaires (EORTC QLQ-C30, and QLQ-BR23), a symptoms of depression questionnaire (CES-D), the Fatigue Symptom Inventory (FSI), the Life Orientation Test (LOT-R), and a stress appraisals questionnaire. RESULTS: We found levels of depression, CRF, and appraisals of cancer as a threat to bemoderate and levels of optimism and appraisals of cancer as a challenge to be high. Depression and CRF were positively associated. A multivariate regression analysis revealed that 51% of the CRF variancewas explained; physical symptoms and threat appraisal were significantly associated with CRF. A 67% of the CRF variance of depression was explained; challenge and threat appraisals were significantly associated with depression [corrected]. SIGNIFICANCE OF RESULTS: Although CRF and depression were often experienced simultaneously and both were found to be higher among individuals who gave higher appraisals of cancer as a threat, only depression was related to optimism and challenge appraisals, while CRF was related mainly to intensity of physical symptoms. The different pattern of associations between optimism and appraisals warrants further clinical attention as well as future study.

Spermatocytic variant of classic seminoma: a report of five cases and a brief review of the literature.

BACKGROUND: Spermatocytic seminoma is a rare testicular malignancy, appearing in the adult population. It has a good prognosis and a low rate of metastatic potential. OBJECTIVES: We present five cases diagnosed and treated with radiotherapy at Rambam Health Care Campus in Haifa, Israel. METHODS: Between 1974 and 1996, five patients with stage I spermatocytic seminoma were referred post-orchiectomy to the Northern Israel Oncology Center. All five patients presented with the typical pathological features of the spermatocytic variant of classic seminoma, and all were staged clinically and radiologically. RESULTS: Mean age at diagnosis was 44 years (range 30-58 years). Main symptoms included a palpable testicular mass and/or testicular enlargement. Mean duration of symptoms was 9 months (range 0.5-24 months). Three patients were irradiated to the para-aortic/ipsilateral iliacal lymph nodes (mean total dose 2,500 cGy), one patient with 4,000 cGy. One patient was irradiated to the bilateral iliacal lymph nodes (2,600 cGy). With a median follow-up of 15 years, four patients are alive with no evidence of disease or severe late side effects. One patient developed severe lymphedema and symptomatic peripheral vascular disease, stage IIA prostate carcinoma (hormonal and brachytherapy treatment) and a non-secretory hypophyseal adenoma (surgically removed); he died at the age of 75 due to severe peripheral vascular and coronary heart disease with no evidence of his first or second primaries. CONCLUSIONS: Prognosis is excellent and does not differ from classic seminoma. As in the accumulated experience in early-stage, low-risk classic seminoma, we suggest surveillance as the preferred policy.

GABP transcription factor (nuclear respiratory factor 2) is required for mitochondrial biogenesis.

Mitochondria are membrane-bound cytoplasmic organelles that serve as the major source of ATP production in eukaryotic cells. GABP (also known as nuclear respiratory factor 2) is a nuclear E26 transformation-specific transcription factor (ETS) that binds and activates mitochondrial genes that are required for electron transport and oxidative phosphorylation. We conditionally deleted Gabpa, the DNA-binding component of this transcription factor complex, from mouse embryonic fibroblasts (MEFs) to examine the role of Gabp in mitochondrial biogenesis, function, and gene expression. Gabpα loss modestly reduced mitochondrial mass, ATP production, oxygen consumption, and mitochondrial protein synthesis but did not alter mitochondrial morphology, membrane potential, apoptosis, or the expression of several genes that were previously reported to be GABP targets. However, the expression of Tfb1m, a methyltransferase that modifies ribosomal rRNA and is required for mitochondrial protein translation, was markedly reduced in Gabpα-null MEFs. We conclude that Gabp regulates Tfb1m expression and plays an essential, nonredundant role in mitochondrial biogenesis.

Anaplastic variant of classical seminoma of the testis: northern Israel oncology center experience and brief review of literature.

OBJECTIVES: There are only sporadic reports on the clinical behavior and appropriate treatment of anaplastic seminoma. This retrospective study summarizes our experience with the anaplastic variant of classical (typical) seminoma. METHODS: Between 1986 and 2006, seven anaplastic seminoma patients were staged and treated at the Northern Israel Oncology Center. Staging procedures included meticulous physical and neurological examinations, complete blood count, full biochemistry profile, specific tumor markers, testicular ultrasound, and other radiological measures. All patients underwent inguinal orchiectomy and were staged properly. Six patients had stage I disease, and one patient had stage IIA disease. Patients were irradiated with doses ranging from 2,500 to 3,000 cGy, and the stage IIA patient received an additional 1,000 cGy boost to radiographically involved lymph nodes. RESULTS: After a mean follow-up of 11 years, six patients are alive with no evidence of disease. One patient died due to an unknown, non-oncological, cause, unrelated to his previous testicular tumor, while in complete remission. CONCLUSIONS: Despite the low patient numbers and the retrospective nature of our study, it can be concluded that radiotherapy treatment for early-stage anaplastic seminoma patients might achieve the same excellent survival as for classical seminoma. However, the general consensus achieved through large-scale studies suggests that active surveillance should be offered to all stage I seminoma patients, regardless of the pathologic variant.

Platinum-based Chemotherapy in Primary Advanced Seminoma-a Retrospective Analysis: Treatment Results at the Northern Israel Oncology Center (1989-2010).

OBJECTIVE: Over the past 30 years, great strides have been made in the treatment of disseminated testicular tumors. Despite the low number of patients and the rarity of studies concerning primary advanced seminoma, the efficacy of chemotherapy is clear, mainly 3-4-cisplatin-based chemotherapy. Aiming to contribute to the understanding and implementation of proper chemotherapeutic management in advanced seminoma patients, we retrospectively summarized our experience with 26 patients who were referred for platinum-based chemotherapy, post-orchiectomy to the Northern Israel Oncology Center between 1989 and 2010. Response rate, side effects, and long-term outcome were investigated. METHODS: Before chemotherapy, meticulous staging was done, including tumor markers (B-human chorionic gonadotropin (B-HCG), alpha-fetoprotein (AFP), and lactic dehydrogenase (LDH)), and abdominal and pelvic computerized tomography (CT) scans were carried out. RESULTS: All 26 treated patients achieved complete remission, clinically and symptomatically, with normalization of their CT scans. At a median follow-up of 120 months (range, 24-268 months) all patients are alive, without evidence of recurrent disease. One patient whose disease recurred twice achieved a third complete remission following salvage treatment with high-dose chemotherapy and autologous peripheral stem cell transplantation. Another patient, who preferred surveillance, relapsed abdominally after 9 months but achieved long-standing complete remission with cisplatin-based chemotherapy. Both these patients are alive with no evidence of disease. Three patients recovered uneventfully from bleomycin-induced pneumonitis. CONCLUSIONS: Advanced seminoma is a highly curable disease using platinum-based chemotherapy. Our study confirms the efficacy and safety of cisplatin-based chemotherapy in the treatment of advanced seminoma.

Computerized morphometry as an aid in distinguishing recurrent versus nonrecurrent meningiomas.

OBJECTIVE: To use novel digital and morphometric methods to identify variables able to better predict the recurrence of intracranial meningiomas. STUDY DESIGN: Histologic images from 30 previously diagnosed meningioma tumors that recurred over 10 years of follow-up were consecutively selected from the Rambam Pathology Archives. Images were captured and morphometrically analyzed. Novel algorithms of digital pattern recognition using Fourier transformation and fractal and nuclear texture analyses were applied to evaluate the overall growth pattern complexity of the tumors, as well as the chromatin texture of individual tumor nuclei. The extracted parameters were then correlated with patient prognosis. RESULTS: Kaplan-Meier analyses revealed statistically significant associations between tumor morphometric parameters and recurrence times. Tumors with less nuclear orientation, more nuclear density, higher fractal dimension, and less regular chromatin textures tended to recur faster than those with a higher degree of nuclear order, less pattern complexity, lower density, and more homogeneous chromatin nuclear textures (p < 0.01). CONCLUSION: To our knowledge, these digital morphometric methods were used for the first time to accurately predict tumor recurrence in patients with intracranial meningiomas. The use of these methods may bring additional valuable information to the clinician regarding the optimal management of these patients.

GABP transcription factor is required for myeloid differentiation, in part, through its control of Gfi-1 expression.

GABP is an ets transcription factor that regulates genes that are required for myeloid differentiation. The tetrameric GABP complex includes GABPα, which binds DNA via its ets domain, and GABPß, which contains the transcription activation domain. To examine the role of GABP in myeloid differentiation, we generated mice in which Gabpa can be conditionally deleted in hematopoietic tissues. Gabpa knockout mice rapidly lost myeloid cells, and residual myeloid cells were dysplastic and immunophenotypically abnormal. Bone marrow transplantation demonstrated that Gabpα null cells could not contribute to the myeloid compartment because of cell intrinsic defects. Disruption of Gabpa was associated with a marked reduction in myeloid progenitor cells, and Gabpα null myeloid cells express reduced levels of the transcriptional repressor, Gfi-1. Gabp bound and activated the Gfi1 promoter, and transduction of Gabpa knockout bone marrow with Gfi1 partially rescued defects in myeloid colony formation and myeloid differentiation. We conclude that Gabp is required for myeloid differentiation due, in part, to its regulation of the tran-scriptional repressor Gfi-1.

Phyllodes tumor of the breast.

PURPOSE: To better identify prognostic factors for local control and survival, as well as the role of different therapeutic options, for phyllodes tumors, a rare fibroepithelial neoplasm of the breast. METHODS AND MATERIALS: Data from 443 women treated between 1971 and 2003 were collected from the Rare Cancer Network. The median age was 40 years (range, 12-87 years). Tumors were benign in 284 cases (64%), borderline in 80 cases (18%), and malignant in 79 cases (18%). Surgery consisted of breast-conserving surgery (BCS) in 377 cases (85%) and total mastectomy (TM) in 66 cases (15%). Thirty-nine patients (9%) received adjuvant radiotherapy (RT). RESULTS: After a median follow-up of 106 months, local recurrence (LR) and distant metastases rates were 19% and 3.4%, respectively. In the malignant and borderline group (n = 159), RT significantly decreased LR (p = 0.02), and TM had better results than BCS (p = 0.0019). Multivariate analysis revealed benign histology, negative margins, and no residual disease (no RD) after initial treatment and RT delivery as independent favorable prognostic factors for local control; benign histology and low number of mitosis for disease-free survival; and pathologic tumor size < or = 3 cm and no tumor necrosis for overall survival. In the malignant and borderline subgroup multivariate analysis TM was the only favorable independent prognostic factor for disease-free survival. CONCLUSIONS: This study showed that phyllodes tumor patients with no RD after treatment have better local control. Benign tumors have a good prognosis after surgery alone. In borderline and malignant tumors, TM had better results than BCS. Thus, in these forms adjuvant RT should be considered according to histologic criteria.

Retinoic acid signaling in myelopoiesis.

PURPOSE OF REVIEW: For decades, retinoic acid has been known to alter the proliferation and differentiation of myeloid cells. Currently, retinoic acid is a front-line agent in the treatment of certain forms of acute myelogenous leukemia. In this review, we focus on recent advances in our understanding of the mechanisms by which retinoids affect growth and proliferation of myeloid cells and contribute to the pathogenesis of leukemia. We have not attempted to summarize the related clinical literature. RECENT FINDINGS: The past 2 years have yielded important understanding of the mechanisms by which retinoids and their nuclear receptors interact with other signal transduction pathways and transcription factors to modify chromatin, alter gene expression, and participate in normal myeloid differentiation and leukemogenesis. Important advances regarding cell biology, molecular biology, biochemistry, and animal studies of retinoids and myeloid differentiation are reviewed. SUMMARY: Greater understanding of the role of retinoids and their receptors in myeloid cell growth and differentiation provides important insight into normal myelopoiesis. These findings have resulted in successful rational approaches to the treatment of acute leukemia and provide the promise of improved treatments in the near future.

Genetic predictors of adverse radiotherapy effects: the Gene-PARE project.

PURPOSE: The development of adverse effects resulting from the radiotherapy of cancer limits the use of this treatment modality. The validation of a test capable of predicting which patients would be most likely to develop adverse responses to radiation treatment, based on the possession of specific genetic variants, would therefore be of value. The purpose of the Genetic Predictors of Adverse Radiotherapy Effects (Gene-PARE) project is to help achieve this goal. METHODS AND MATERIALS: A continuously expanding biorepository has been created consisting of frozen lymphocytes and DNA isolated from patients treated with radiotherapy. In conjunction with this biorepository, a database is maintained with detailed clinical information pertaining to diagnosis, treatment, and outcome. The DNA samples are screened using denaturing high performance liquid chromatography (DHPLC) and the Surveyor nuclease assay for variants in ATM, TGFB1, XRCC1, XRCC3, SOD2, and hHR21. It is anticipated that additional genes that control the biologic response to radiation will be screened in future work. RESULTS: Evidence has been obtained that possession of variants in genes, the products of which play a role in radiation response, is predictive for the development of adverse effects after radiotherapy. CONCLUSIONS: It is anticipated that the Gene-PARE project will yield information that will allow radiation oncologists to use genetic data to optimize treatment on an individual basis.

Peripheral lymphadenopathy as the initial manifestation of pericardial mesothelioma: a case report.

Lymphadenopathy is an unusual initial presentation of malignant mesothelioma. We describe a case of extrathoracic lymphadenopathy as the only initial manifestation of primary pericardial malignant mesothelioma. The diagnosis of metastatic malignant mesothelioma was made by excisional biopsy of the supraclavicular lymph node and later confirmed by cytologic examination of pericardial fluid. The clinical and pathological features of this case, including positron-emission tomography (PET), immunohistochemistry, and electron microscopy, are discussed.

Efficacy of I131 ablation therapy using different doses as determined by postoperative thyroid scan uptake in patients with differentiated thyroid cancer.

PURPOSE: The optimal dose of I(131) for ablation of functioning residual thyroid tissue after surgery is controversial. The current study was conducted to determine the optimal dose of I(131) for remnant postoperative ablation. A review of the literature is included. METHODS AND MATERIALS: A total of 238 patients with papillary and follicular carcinoma were treated with I(131) for ablation of a postoperative thyroid remnant. The I(131) dose was based on the 24-h percentage of neck uptake in the postoperative thyroid scans. Patients with < 5% uptake received a median of 85 mCi; 6-10% uptake, a median of 80 mCi; 11-15% uptake, a median of 60 mCi; 16-20% uptake, a median of 50 mCi; and > or =21% uptake, a median of 30 mCi. The ablation results were compared with the prognostic factors. RESULTS: Complete ablation was observed in 40 (92%) of 43 patients receiving 85 mCi, in 31 (94%) of 33 who received 80 mCi, in 39 (95%) of 41 who received 60 mCi, in 51 (93%) of 55 who received 50 mCi, in 37 (94%) of 39 who received 30 mCi, and in 18 (96%) of 19 who received 30 mCi. The overall successful ablation rate was 94% (95% confidence interval, 89-100%). CONCLUSION: Our findings suggest that patients with differentiated thyroid cancer can be treated with doses of I(131) according to the percentage of neck uptake of postoperative total body scan, with high complete ablation rates, without exposing patients to higher dose levels of I(131).

Interstitial brachytherapy in soft tissue sarcomas: the Rambam experience.

BACKGROUND: There are radiobiologic and technical advantages to the use of interstitial brachytherapy alone or as an adjunct to external beam radiotherapy in the postoperative treatment of soft tissue sarcomas. OBJECTIVES: To review the experience of the Rambam Medical Center in implementing interstitial brachytherapy in the treatment of 32 patients with soft tissue sarcomas. METHODS: Thirty-two patients with variously located soft tissue sarcomas were managed with a combination of surgery and brachytherapy of the tumor bed, with or without EBRT. In 27 of 32 patients, brachytherapy catheters were placed intraoperatively, while in 5 patients the implant was performed as a separate postoperative procedure. Twenty-seven patients received low dose-rate brachytherapy with Iridium-192 seeds. Five patients received fractionated high dose-rate brachytherapy using the microSelectron machine. RESULTS: With a median follow-up of 36 months, the overall local control rate was 87.5%. Four of 32 patients (13%) failed locally at the implant site, and 6 (19%) developed lung metastasis. Two of the five patients with lung metastasis had a local recurrence as well. At the time of analysis, eight patients had died of sarcoma (disease-specific mortality rate was 25%), while three had died of intercurrent causes. The 5 year actuarial disease-free survival rate was 56%, and the 5 year actuarial overall survival 70%. Five patients (16%) developed severe wound complications following surgery/brachytherapy, and six patients (19%) developed late local toxicity (fibrosis and telangiectasia). CONCLUSIONS: Wide local excision followed by interstitial brachytherapy has resulted in an 87.5% local control rate with a 16% local complication rate.