Long-Term Results of Intraoperative Radiation Therapy for Early Breast Cancer Using a Nondedicated Linear Accelerator.

Purpose: To present the long-term results of intraoperative radiation therapy (IORT) for early breast cancer using a nondedicated linear accelerator. Methods and Materials: The eligibility criteria were biopsy-proven invasive carcinoma, age ≥40 years, tumor size ≤3 cm, and N0M0. We excluded multifocal lesions and sentinel lymph node involvement. All patients had previously undergone breast magnetic resonance imaging. Breast-conserving surgery with margins and sentinel lymph node evaluation using frozen sections were performed in all cases. If there were no margins or involved sentinel lymph nodes, the patient was transferred from the operative suite to the linear accelerator room, where IORT was delivered (21 Gy). Results: A total of 209 patients who were followed up for ≥1.5 years from 2004 to 2019 were included. The median age was 60.3 years (range, 40-88.6), and the mean pT was 1.3 cm (range, 0.2-4). There were 90.5% pN0 cases (7.2% of micrometastases and 1.9% of macrometastases). Ninety-seven percent of the cases were margin free. The rate of lymphovascular invasion was 10.6%. Twelve patients were negative for hormonal receptors, and 28 patients were HER2 positive. The median Ki-67 index was 29% (range, 0.1-85). Intrinsic subtype stratification was as follows: luminal A, 62.7% (n = 131); luminal B, 19.1% (n = 40); HER2 enriched 13.4% (n = 28); and triple negative, 4.8% (n = 10). Within the median follow-up of 145 months (range, 12.8-187.1), the 5-year, 10-year, and 15-year overall survival rates were 98%, 94.7%, and 88%, respectively. The 5-year, 10-year, and 15-year disease-free rates were 96.3%, 90%, and 75.6%, respectively. The 15-year local recurrence-free rate was 76%. Fifteen local recurrences (7.2%) occurred throughout the follow-up period. The mean time to local recurrence was 145 months (range, 12.8-187.1). As a first event, 3 cases of lymph node recurrence, 3 cases of distant metastasis, and 2 cancer-related deaths were recorded. Tumor size >1 cm, grade III, and lymphovascular invasion were identified as risk factors. Conclusions: Despite approximately 7% of recurrences, we may infer that IORT may still be a reasonable option for selected cases. However, these patients require a longer follow-up as recurrences may occur after 10 years.

Peritumoral infiltration of local anesthetic before surgery in early breast cancer: a comment

This is a comment on a study recently published about peritumoral infiltration of local anesthetic before surgery in early breast cancer. Previously, animal models and a randomized study for stage IV breast cancer patients inferred that the removal of the primary tumor resulted in increased growth factors and worse distant disease control. Therefore, breast cancer surgery might not be a strictly local intervention. In this new randomized study, the intervention was a peritumoral infiltration of local anesthetic ­ lidocaine 0.5% in the six tumor margins, as an attempt to limit the systemic repercussions of surgery. Although the adjuvant treatment available for the study seems outdated, leading us to question the external validation, limited resources may have increased the power of surgery. Unknown mechanisms during surgery can change the patient's journey, and it is our duty to look at surgical studies with due seriousness

Effectiveness of different accelerated partial breast irradiation techniques for the treatment of breast cancer patients: Systematic review using indirect comparisons of randomized clinical trials.

AIM: This systematic review was conducted to compare the effectiveness of different accelerated partial breast irradiation (APBI) techniques for the treatment of breast cancer patients. BACKGROUND: Numerous (APBI) techniques are available for clinical practice. METHODS AND MATERIALS: Systematic review of randomized controlled trials of APBI versus whole breast irradiation (WBI). The data from APBI studies were extracted for the analyses. Indirect comparisons were used to compare different APBI techniques. RESULTS: Ten studies fulfilled the inclusion criteria. A total of 4343 patients were included, most of them with tumor stage T1-T2 and N0. Regarding APBI techniques, six trials used external beam radiation therapy; one intraoperative electrons; one intraoperative low-energy photons; one brachytherapy; and one external beam radiation therapy or brachytherapy. The indirect comparisons related to 5-years local control and 5-years overall survival were not significantly different between APBI techniques. CONCLUSIONS: Based on indirect comparisons, no differences in clinical outcomes were observed among diverse APBI techniques in published clinical trials that formally compared WBI to APBI. However wide confidence intervals and high risk of inconsistency precluded a sound conclusion. Further head-to-head clinical trials comparing different APBI techniques are required to confirm our findings. Studies comparing different techniques using individual participant data and/or real-life data from population-based studies/registries could also provide more robust results.

Suspicious amorphous microcalcifications detected on full-field digital mammography: correlation with histopathology.

OBJECTIVE: To evaluate suspicious amorphous calcifications diagnosed on full-field digital mammography (FFDM) and establish correlations with histopathology findings. MATERIALS AND METHODS: This was a retrospective study of 78 suspicious amorphous calcifications (all classified as BI-RADS® 4) detected on FFDM. Vacuum-assisted breast biopsy (VABB) was performed. The histopathological classification of VABB core samples was as follows: pB2 (benign); pB3 (uncertain malignant potential); pB4 (suspicion of malignancy); and pB5 (malignant). Treatment was recommended for pB5 lesions. To rule out malignancy, surgical excision was recommended for pB3 and pB4 lesions. Patients not submitted to surgery were followed for at least 6 months. RESULTS: Among the 78 amorphous calcifications evaluated, the histopathological analysis indicated that 8 (10.3%) were malignant/suspicious (6 classified as pB5 and 2 classified as pB4) and 36 (46.2%) were benign (classified as pB2). The remaining 34 lesions (43.6%) were classified as pB3: 33.3% were precursor lesions (atypical ductal hyperplasia, lobular neoplasia, or flat epithelial atypia) and 10.3% were high-risk lesions. For the pB3 lesions, the underestimation rate was zero. CONCLUSION: The diagnosis of precursor lesions (excluding atypical ductal hyperplasia, which can be pB4 depending on the severity and extent of the lesion) should not necessarily be considered indicative of underestimation of malignancy. Suspicious amorphous calcifications correlated more often with precursor lesions than with malignant lesions, at a ratio of 3:1.

OBJETIVO: Correlacionar o achado mamográfico de calcificações amorfas suspeitas diagnosticadas na mamografia digital com seus diagnósticos anatomopatológicos. MATERIAIS E MÉTODOS: Setenta e oito casos de calcificações amorfas suspeitas (todas classificadas como BI-RADS® 4) detectadas na mamografia digital e submetidas a biópsia percutânea assistida à vácuo foram retrospectivamente avaliados. A classificação anatomopatológica utilizada na biópsia foi: pB2 para lesão benigna, pB3 para lesão com potencial incerto de malignidade, pB4 para lesão suspeita, e pB5 para lesão considerada maligna. O tratamento foi recomendado para as lesões pB5, a exérese cirúrgica foi indicada para lesões pB3 e pB4, para descartar malignidade, e o seguimento evolutivo foi adotado para as demais pacientes. RESULTADOS: A histologia demonstrou 8 (10,3%) casos malignos (6 lesões pB5 e 2 lesões pB4) e 36 (46,2%) casos benignos (pB2). As demais 34 (43,6%) lesões foram classificadas como pB3 (33,3% foram lesões precursoras - hiperplasia ductal atípica, neoplasia lobular ou atipia epitelial plana - e 10,3% foram lesões de alto risco). A taxa de subestimação das lesões pB3 foi zero. CONCLUSÃO: O diagnóstico de lesões precursoras (excluindo hiperplasia ductal atípica, que pode corresponder a lesão pB4 dependendo da severidade e extensão dos achados) na biópsia percutânea assistida à vácuo por calcificações amorfas suspeitas não necessariamente representa lesão subestimada. Calcificações amorfas suspeitas se associaram a lesões precursoras numa proporção de 3:1 em relação às lesões malignas.

Suspicious amorphous microcalcifications detected on full-field digital mammography: correlation with histopathology / Microcalcificações amorfas suspeitas detectadas na mamografia digital: correlação histológica

Abstract Objective: To evaluate suspicious amorphous calcifications diagnosed on full-field digital mammography (FFDM) and establish correlations with histopathology findings. Materials and Methods: This was a retrospective study of 78 suspicious amorphous calcifications (all classified as BI-RADS® 4) detected on FFDM. Vacuum-assisted breast biopsy (VABB) was performed. The histopathological classification of VABB core samples was as follows: pB2 (benign); pB3 (uncertain malignant potential); pB4 (suspicion of malignancy); and pB5 (malignant). Treatment was recommended for pB5 lesions. To rule out malignancy, surgical excision was recommended for pB3 and pB4 lesions. Patients not submitted to surgery were followed for at least 6 months. Results: Among the 78 amorphous calcifications evaluated, the histopathological analysis indicated that 8 (10.3%) were malignant/suspicious (6 classified as pB5 and 2 classified as pB4) and 36 (46.2%) were benign (classified as pB2). The remaining 34 lesions (43.6%) were classified as pB3: 33.3% were precursor lesions (atypical ductal hyperplasia, lobular neoplasia, or flat epithelial atypia) and 10.3% were high-risk lesions. For the pB3 lesions, the underestimation rate was zero. Conclusion: The diagnosis of precursor lesions (excluding atypical ductal hyperplasia, which can be pB4 depending on the severity and extent of the lesion) should not necessarily be considered indicative of underestimation of malignancy. Suspicious amorphous calcifications correlated more often with precursor lesions than with malignant lesions, at a ratio of 3:1.

Resumo Objetivo: Correlacionar o achado mamográfico de calcificações amorfas suspeitas diagnosticadas na mamografia digital com seus diagnósticos anatomopatológicos. Materiais e Métodos: Setenta e oito casos de calcificações amorfas suspeitas (todas classificadas como BI-RADS® 4) detectadas na mamografia digital e submetidas a biópsia percutânea assistida à vácuo foram retrospectivamente avaliados. A classificação anatomopatológica utilizada na biópsia foi: pB2 para lesão benigna, pB3 para lesão com potencial incerto de malignidade, pB4 para lesão suspeita, e pB5 para lesão considerada maligna. O tratamento foi recomendado para as lesões pB5, a exérese cirúrgica foi indicada para lesões pB3 e pB4, para descartar malignidade, e o seguimento evolutivo foi adotado para as demais pacientes. Resultados: A histologia demonstrou 8 (10,3%) casos malignos (6 lesões pB5 e 2 lesões pB4) e 36 (46,2%) casos benignos (pB2). As demais 34 (43,6%) lesões foram classificadas como pB3 (33,3% foram lesões precursoras - hiperplasia ductal atípica, neoplasia lobular ou atipia epitelial plana - e 10,3% foram lesões de alto risco). A taxa de subestimação das lesões pB3 foi zero. Conclusão: O diagnóstico de lesões precursoras (excluindo hiperplasia ductal atípica, que pode corresponder a lesão pB4 dependendo da severidade e extensão dos achados) na biópsia percutânea assistida à vácuo por calcificações amorfas suspeitas não necessariamente representa lesão subestimada. Calcificações amorfas suspeitas se associaram a lesões precursoras numa proporção de 3:1 em relação às lesões malignas.

Measuring plasma levels of three microRNAs can improve the accuracy for identification of malignant breast lesions in women with BI-RADS 4 mammography.

A BI-RADS category of 4 from a mammogram indicates suspicious breast lesions, which require core biopsies for diagnosis and have an approximately one third chance of being malignant. Human plasma contains many circulating microRNAs, and variations in their circulating levels have been associated with pathologies, including cancer. Here, we present a novel methodology to identify malignant breast lesions in women with BI-RADS 4 mammography. First, we used the miRNome array and qRT-PCR to define circulating microRNAs that were differentially represented in blood samples from women with breast tumor (BI-RADS 5 or 6) in comparison to controls (BI-RADS 1 or 2). Next, we used qRT-PCR to quantify the level of this circulating microRNAs in patients with mammograms presenting with BI-RADS category 4. Finally, we developed a machine learning method (Artificial Neural Network - ANN) that receives circulating microRNA levels and automatically classifies BI-RADS 4 breast lesions as malignant or benign. We identified a minimum set of three circulating miRNAs (miR-15a, miR-101 and miR-144) with altered levels in patients with breast cancer. These three miRNAs were quantified in plasma from 60 patients presenting biopsy-proven BI-RADS 4 lesions. Finally, we constructed a very efficient ANN that could correctly classify BI-RADS 4 lesions as malignant or benign with approximately 92.5% accuracy, 95% specificity and 88% sensibility. We believe that our strategy of using circulating microRNA and a machine learning method to classify BI-RADS 4 breast lesions is a non-invasive, non-stressful and valuable complementary approach to core biopsy in women with BI-RADS 4 lesions.

Radiotherapy for a breast cancer patient with Schnitzler syndrome: Report of acute toxicity and early follow-up.

This article provides description about acute toxicity and early follow-up of one patient treated for breast cancer and Schnitzler syndrome. There are no previously reported cases exploring this interaction on medical literature. The expected radiodermitis to occur in the region treated with radiotherapy along with urticarial-like lesions might be challenging in view of the interaction between symptoms and therapeutic measures.

Popliteal sentinel lymph node involvement in melanoma patients.

BACKGROUND: Sentinel lymph nodes (SLN) in popliteal basins are rare, and there is controversy in literature regarding their origin, management, and outcomes. OBJECTIVES: To correlate clinical and pathological features of popliteal basin drainage and analyze the impact of popliteal lymph node drainage on survival. MATERIALS AND METHODS: Retrospective analysis of SLN biopsies performed at a single institution between 2000 and 2010. RESULTS: SLN biopsies were performed in 254 patients with melanoma in lower limbs, 247 of which were evaluated. In this group, there were 59 patients (24%) with a positive SLN. Twenty-seven cases (11%) presented with popliteal drainage, one of which lacked concurrent groin drainage. Among these 27 patients, three (11%) had popliteal metastasis, one of which had exclusive involvement of this basin. Popliteal drainage was associated with worse 5-year disease-free survival (DFS) (P = 0.028) but not 5-year overall survival (OS) (P = 0.219) in univariate analysis. In multivariate analysis, Breslow thickness, mitotic index, and positive SLN were prognostic factors for DFS. Only mitotic index correlated significantly with OS (P = 0.044). CONCLUSIONS: Popliteal drainage seems to be associated with worse prognostic features of the primary tumor.

Magnetic resonance imaging-guided occult breast lesion localization and simultaneous sentinel lymph node mapping.

BACKGROUND: Radio-guided occult lesion localization is a valid technique for the diagnosis of suspicious non-palpable lesions. Here we determine the feasibility of pre-operative localization of occult suspect non-palpable breast lesions using radio-guided occult lesion localization, as well as for identifying the sentinel lymph node. METHODS: This is a descriptive study of data collected retrospectively. Pre-operative mapping of 34 breast lesions in 25 patients suspected of being malignant was performed using conventional imaging methods with a magnetic resonance imaging-guided radiopharmaceutical injection. RESULTS: The mean time required to perform the localization was 25 minutes. After resection of the lesions using a gamma probe, malignancy was confirmed in fifteen patients (60.0%), with nine invasive ductal carcinomas, two invasive lobular carcinomas, and four in situ ductal carcinomas The resection was confirmed by the complete removal of the radioactive material. The pathologic results and images were concordant in all but two cases, which were submitted for new magnetic resonance imaging examinations and surgery that confirmed the malignancies. Of the 15 patients with confirmed malignancies, 10 had sentinel lymph node resection. Of these, eight were negative for metastases, one had micro-metastases and one had confirmed metastases. Three patients had full axillary node dissection, with metastases found in only one. No side effects were observed with magnetic resonance-guided radiopharmaceutical injection. CONCLUSIONS: The sentinel node occult lesion localization technique is a simple, reproducible and effective alternative approach to occult lesions compared to other methods, such as mammotomy and the hook-wire localization technique, for mapping suspect breast lesions and identifying lymph node metastasis.

Intraoperative radiation therapy in early breast cancer using a linear accelerator outside of the operative suite: an "image-guided" approach.

PURPOSE: To present local control, complications, and cosmetic outcomes of intraoperative radiation therapy (IORT) for early breast cancer, as well as technical aspects related to the use of a nondedicated linear accelerator. METHODS AND MATERIALS: This prospective trial began in May of 2004. Eligibility criteria were biopsy-proven breast-infiltrating ductal carcinoma, age >40 years, tumor <3 cm, and cN0. Exclusion criteria were in situ or lobular types, multicentricity, skin invasion, any contraindication for surgery and/or radiation therapy, sentinel lymph node involvement, metastasis, or another malignancy. Patients underwent classic quadrantectomy with intraoperative sentinel lymph node and margins evaluation. If both free, the patient was transferred from operative suite to linear accelerator room, and IORT was delivered (21 Gy). Primary endpoint: local recurrence (LR); secondary endpoints: toxicities and aesthetics. Quality assurance involved using a customized shield for chest wall protection, applying procedures to minimize infection caused by patient transportation, and using portal films to check collimator-shield alignment. RESULTS: A total of 152 patients were included, with at least 1 year follow-up. Median age (range) was 58.3 (40-85.4) years, and median follow-up time was 50.7 (12-110.5) months. The likelihood of 5-year local recurrence was 3.7%. There were 3 deaths, 2 of which were cancer related. The Kaplan-Meier 5-year actuarial estimates of overall, disease-free, and local recurrence-free survivals were 97.8%, 92.5%, and 96.3%, respectively. The overall incidences of acute and late toxicities were 12.5% and 29.6%, respectively. Excellent, good, fair, and bad cosmetic results were observed in 76.9%, 15.8%, 4.3%, and 2.8% of patients, respectively. Most treatments were performed with a 5-cm collimator, and in 39.8% of the patients the electron-beam energy used was ≥12 MeV. All patients underwent portal film evaluation, and the shielding was repositioned in 39.9% of cases. No infection or anesthesia complications were observed. CONCLUSIONS: Local control with IORT was adequate, with low complication rates and good cosmetic outcomes. More than one-third of patients benefited from the "image-guidance" approach, and almost 40% benefited from the option of higher electron beam energies.