Long-term results of intraoperative multicatheter breast implant (IOMBI) for accelerated partial breast irradiation (APBI) on early breast cancer patients.

BACKGROUND AND PURPOSE: Multicatheter breast brachytherapy is a standard technique for accelerated partial breast irradiation (APBI) in early breast cancer patients. Intraoperative multicatheter breast implant (IOMBI) followed by perioperative high-dose-rate brachytherapy (PHDRBT) offers a novel and advantageous approach. We present long-term oncological, toxicity, and cosmesis outcomes for a well-experienced single institution. MATERIALS AND METHODS: Eligible women aged ≥ 40 years with clinically and radiologically confirmed unifocal invasive or in situ ≤ 3 cm breast tumors underwent IOMBI during breast-conserving surgery. Patients meeting APBI criteria by definitive pathologic results received 3.4 Gy × 10fx with PHDRBT. Patients not suitable for APBI received PHDRBT-boost followed by WBRT. RESULTS: A total of 171 patients underwent IOMBI during BCS, 120 patients (70.1 %) were suitable for APBI and 51 (29.8 %) for anticipated PHDRBT-boost. The median age was 61 years (range: 40-78), the median tumor size was 1.1 cm (range: 0.2-3.5), with a histological diagnosis of invasive ductal carcinoma in 78.9 % and ductal in situ in 21.1 %. A median of 9 catheters (range: 4-14) were used. For APBI, the median CTV and V100 were 40.8 cc (range: 8.6-99) and 35.4 cc (range: 7.2-94). The median of healthy breast tissue irradiated represents 7.2 % (range: 2.3-28 %) and the median local treatment duration was 10 days (range: 7-16). With a median follow-up of 8.8 years (range: 0.3-16.25), the 8-year local, locoregional, and distant control rates were 99 %, 98.1 %, and 100 %. G1-G2 late-toxicity rate was 53.4 %. Long-term cosmetic evaluation was excellent-good in 90.8 %. CONCLUSION: IOMBI&PHDRBT program reports excellent long-term oncological outcomes, with a reduction from unnecessary irradiation exposure which translates into low long-term toxicity and good cosmesis outcomes, especially on well-selected APBI patients.

Four-fraction ultra-accelerated minimal breast irradiation in early breast cancer: The initial feasibility results of an institutional experience.

PURPOSE: To evaluate the feasibility, early toxicity, and clinical outcomes of early-breast cancer patients in a single-arm, phase I/II study of an ultra-accelerated, four-fraction schedule of minimal breast irradiation (4f-AMBI) using a multicatheter, minimally-invasive, intraoperative tumor bed implant (MITBI) during breast-conserving surgery (BCS). METHODS AND MATERIALS: Eligible women aged >40 years with clinically and radiologically confirmed, unifocal invasive or in situ ≤3 cm tumors were considered as potential candidates for MITBI during BCS. After the pathology report, patients who met APBI criteria received ultra-accelerated four-fractions irradiation (6.2 Gy BID x 4fx over 2 days) with perioperative HDR-brachytherapy (PHDRBT). Early complications, toxicity, clinical outcomes, and cosmetic results were analyzed. RESULTS: Of 89 patients initially implanted, 60(67.4%) were definitively included in the 4f-AMBI-protocol. The median age was 64.4 years; the median CTV was 32.1 cc (6.9-75.4 cc), and the external-V100 was 43.1 cc (12.87-107 cc), representing 5% of the breast tissue irradiated with a median CTV D90 of 6.2 Gy (5.6-6.28 Gy). The entire local treatment (BCS&MITBI-4f-AMBI) was completed at a median of 8 days (4-10 days). The rate of early complications was 11%. There were no major complications. Acute skin-subcutaneous G1 toxicity was reported in 11.7%, and late G1 toxicity on 36.7%. After a median follow-up of 27 months (11-51 months), the local, elsewhere, locoregional and distant-control rates were 100%, 98.3%, 100%, and 100% respectively. The early-cosmetic evaluation was excellent-good in 94.5% of patients evaluated. CONCLUSIONS: Ultra-accelerated, four-fraction, minimal breast irradiation (4f-AMBI) using a minimally-invasive tumor bed implant procedure is safe, dosimetrically feasible, and shows small irradiated volumes. This program provides low toxicity rates and excellent short-term clinical and cosmesis outcomes.

Final results regarding the addition of dendritic cell vaccines to neoadjuvant chemotherapy in early HER2-negative breast cancer patients: clinical and translational analysis.

BACKGROUND: Primary breast cancer (BC) has shown a higher immune infiltration than the metastatic disease, justifying the optimal scenario for immunotherapy. Recently, neoadjuvant chemotherapy (NAC) combined with immune checkpoint inhibitors has demonstrated a gain in pathological complete responses (tpCR) in patients with BC. The aim of our study is to evaluate the safety, feasibility, and efficacy of the addition of dendritic cell vaccines (DCV) to NAC in HER2-negative BC patients. METHODS: Thirty-nine patients with early BC received DCV together with NAC conforming the vaccinated group (VG) and compared with 44 patients as the control group (CG). All patients received anthracyclines and taxanes-based NAC (ddECx4→Dx4) followed by surgery ± radiotherapy ± hormonotherapy. RESULTS: The tpCR rate was 28.9% in the VG and 9.09% in the CG (p = 0.03). Pathological CR in the triple negative (TN) BC were 50.0% versus 30.7% (p = 0.25), 16.6% versus 0% in luminal B (p = 0.15), and none among luminal A patients in VG versus CG, respectively. Impact of DCV was significantly higher in the programmed cell death ligand 1 (PD-L1) negative population (p < 0.001). PD-L1 expression was increased in patients with residual disease in the VG as compared with the CG (p < 0.01). No grade ⩾3 vaccine-related adverse events occurred. With a median follow-up of 8 years, no changes were seen in event-free survival or overall survival. Phenotypic changes post DCV in peripheral blood were observed in myeloid-derived suppressor cells (MDSC), NK, and T cells. Increase in blood cell proliferation and interferon (IFN)-γ production was detected in 69% and 74% in the VG, respectively. Humoral response was also found. Clonality changes in TCR-ß repertoire were detected in 67% of the patients with a drop in diversity index after treatment. CONCLUSION: The combination of DCV plus NAC is safe and increases tpCR, with a significant benefit among PD-L1-negative tumors. DCV modify tumor milieu and perform cellular and humoral responses in peripheral blood with no impact in outcome. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01431196. EudraCT 2009-017402-36.

Minimally invasive tumor bed implant (MITBI) and peri-operative high-dose-rate brachytherapy (PHDRBT) for accelerated minimal breast irradiation (AMBI) or anticipated boost (A-PHDRBT-boost) in breast-conserving surgery for ductal carcinoma in situ.

PURPOSE: To evaluate our institutional experience of minimally invasive tumor bed implantation (MITBI) during breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) to deliver peri-operative high-dose-rate brachytherapy (PHDRBT) as accelerated minimal breast irradiation (AMBI) or anticipated boost (A-PHDRBT-boost). MATERIAL AND METHODS: Patients older than 40, with clinical and radiological unifocal DCIS < 3 cm were considered potential candidates for accelerated partial breast irradiation (APBI) and were implanted during BCS using MITBI-technique. Patients who in final pathology reports showed free margins and no other microscopic tumor foci, received AMBI with PHDRBT (3.4 Gy BID in 5 days). Patients with adverse features received A-PHDRBT-boost with post-operative external beam radiotherapy (EBRT). RESULTS: Forty-one patients were implanted, and 36 were treated and analyzed. According to final pathology, 24 (67%) patients were suitable for AMBI and 12 (33%) were qualified for A-PHDRBT-boost. Reoperation rate for those with clear margins was 16.6% (6/36); this rate increased to 33% (4/12) for G3 histology, and 66% (4/6) were rescued using AMBI. Early complications were documented in 5 patients (14%). With a median follow-up of 97 (range, 42-138) months, 5-year rates of local, elsewhere, locoregional, and distant control were all 97.2%. 5-year ipsilateral breast tumor recurrence rates (IBTR) were 5.6% (2/36), 8.3% (2/24) for AMBI, and 0% (0/12) for A-PHDRBT-boost patients. Both instances of IBTR were confirmed G3 tumors in pre-operative biopsies; no IBTR was documented in G1-2 tumors. Cosmetic outcomes were excellent/good in 96% of AMBI vs. 67% in A-PHDRBT-boost (p = 0.034). CONCLUSIONS: The MITBI-PHDRBT program allows selection of patients with excellent prognoses (G1-2 DCIS with negative margins and no multifocality), for whom AMBI could be a good alternative with low recurrence rate, decrease of unnecessary radiation, treatment logistics improvement, and over-treatment reduction. Patients whose pre-operative biopsy showed G3 tumor, presents with inferior local control and more risk of reoperation due to positive margins.

Multicatheter breast implant during breast conservative surgery: Novel approach to deliver accelerated partial breast irradiation.

PURPOSE: To assess the safety, feasibility, and efficacy of free-hand intraoperative multicatheter breast implant (FHIOMBI) and perioperative high-dose-rate brachytherapy (PHDRBT) in early breast cancer. METHODS AND MATERIALS: Patients with early breast cancer candidates for breast conservative surgery (BCS) were prospectively enrolled. Patients suitable for accelerated partial breast irradiation (APBI) (low or intermediate risk according GEC-ESTRO criteria) received PHDRBT (3.4 Gy BID × 10 in 5 days). Patients not suitable for APBI (high risk patients according GEC-ESTRO criteria) received PHDRBT boost (3.4 Gy BID × 4 in 2 days) followed by whole breast irradiation. RESULTS: From June 2007 to November 2014, 119 patients were treated and 122 FHIOMBI procedures were performed. Median duration of FHIOMBI was 25 minutes. A median of eight catheters (range, 4-14) were used. No severe intraoperative complications were observed. Severe early postoperative complications (bleeding) were documented in 2 patients (1.6%), wound healing complications in 3 (2.4%), and infection (mastitis or abscess) in 2 (1.6%). PHDRBT was delivered as APBI in 88 cases (72.1%) and as a boost in 34 (27.8%). The median clinical target volume T was 40.8 cc (range, 12.3-160.5); median D90 was 3.32 Gy (range, 3.11-3.85); median dose homogeneity index was 0.72 (range, 0.48-0.82). With a median followup of 38.4 months (range, 8.7-98.7) no local, elsewhere, or regional relapses were observed; there was only one distant failure in PHDRBT boost. No major (acute or late) RTOG grade 3 or higher were documented in any of the 119 patients treated with PHDRBT. Cosmetic outcome in APBI patients was excellent or good in (87.0%) and fair or poor in (11.9%) while in boost patients was excellent or good in (76.4%) and fair in (23.5%). CONCLUSION: The FHIOMBI-PHDRBT program does not add complications to conservative surgery. It allows precise selection of APBI patients and offers excellent results in disease control and cosmetics. It also offers logistic advantages because it dramatically shortens the time of local treatment and avoids further invasive procedures.

Diagnostic performance of IOTA simple rules for adnexal masses classification: a comparison between two centers with different ovarian cancer prevalence.

OBJECTIVE: The aim of this study was to compare the diagnostic performance of the IOTA simple rules for classifying adnexal masses when used in two centers with different ovarian cancer prevalence. STUDY DESIGN: A prospective study was performed between June 2012 and December 2013 at two different centers with different ovarian cancer prevalence. Center A had high ovarian malignancy prevalence and Center B had low malignancy rates. Eligible patients were all women diagnosed as having a persistent adnexal mass. Examiners had to analyze the masses according to IOTA simple rules (SR) providing a diagnosis of malignant, benign or inconclusive. Those cases classified as inconclusive were then examined by an expert examiner (the same examiner in center A, a different examiner in center B), who had to classify the mass as malignant, benign or uncertain according to his subjective impression (SI). Definitive histologic diagnosis from tumors removed surgically was used as gold standard. The diagnostic performance was assessed by calculating the sensitivity and specificity, positive and negative likelihood ratios, for SR and SR+SI assessments. McNemar test was used for comparing sensitivity and specificity. RESULTS: During this period, 247 women were eligible for this study. The rate of inconclusive masses was 18.4% and 18.0% for centers A and B, respectively (p>0.05). Ovarian malignancy rate was significantly higher in center A as compared with center B (27.2% versus 11.3%), (p=0.001). When analyzing only cases classifiable by SR, sensitivity in center A was significantly higher (100% versus 84.6% p=0.001), but specificity was similar in both centers (93.9% and 95.8% respectively). When analyzing SR plus SI, sensitivity in center A was significantly higher (100% versus 86.7% p=0.001), but specificity was similar in both centers (89.9% and 88.8%, respectively). CONCLUSIONS: The diagnostic performance in terms of sensitivity of IOTA rules is higher in a center with higher prevalence of ovarian malignancy.

Reproducibility of two different methods for performing mean gray value evaluation of cyst content in endometriomas using VOCAL.

OBJECTIVE: To compare two different methods (manual sampling of the entire cyst and semi-automated spherical sampling from the central part of the cyst) for calculating the mean gray value (MGV) from the cystic content in endometriomas using virtual organ computer-aided analysis (VOCAL). METHODS: Forty-one volumes from histologically confirmed endometriomas were retrieved from our database and the volumes were analyzed to compare the MGVs obtained via the two modalities. In addition, to evaluate the reproducibility in a sample of 20 volumes, two different observers calculated the MGV from cyst content using VOCAL software. For each method, each examiner analyzed the volumes twice, 3 weeks apart, for assessment of intra-observer agreement. First, manual sampling of the internal contour of all the cysts was performed, and 1 week later semi-automated 2-cm sphere sampling from the central part of the cyst was carried out. In addition, the observers recorded the time spent performing each analysis. Inter- and intra-observer reproducibility was evaluated for each method using intra-class correlation coefficients (ICC). RESULTS: There was no difference in the mean MGV between manual sampling (22.211 ± 7.541) and the semi-automated modality of sampling (23.840 ± 8.621, p = 0.439). The correlation between manual and semi-automated sampling measurement was high (r = 0.92). According to the ICCs, there was no significant difference in interobserver reliability between manual sampling (0.931; 95 % CI, 0.824-0.973) and the semi-automated modality of sampling (0.924; 95 % CI, 0.809-0.970). Intra-observer reproducibility for both examiners was good (ICC > 0.94). Semi-automated measurements were obtained faster than those obtained by manual evaluation (p = 0.0001 for observer 1 and p = 0.083 for observer 2). CONCLUSIONS: Both methods seem to be reliable, but the semi-automated method using the sphere should be preferred because it is a less time-consuming procedure.

Assessing the reproducibility of the IOTA simple ultrasound rules for classifying adnexal masses as benign or malignant using stored 3D volumes.

OBJECTIVE: To analyze the reproducibility of the IOTA simple ultrasound rules for classifying adnexal masses as benign or malignant among examiners with different level of expertise using stored 3D volumes of adnexal masses. STUDY DESIGN: Five examiners, with different levels of experience and blinded to each other, evaluated 100 stored 3D volumes from adnexal masses and looked for the presence or absence of malignant or benign features according to the IOTA definitions. Multiplanar view and virtual navigation were used. All examiners had to assess the 3D volume of each adnexal mass and classify it as benign or malignant. To analyze intra-observer agreement each examiner performed the assessment twice with a two-week interval between the first and second assessments. To analyze the inter-observer agreement, the second assessment from each examiner was used. Reproducibility was assessed calculating the weighted Kappa index. RESULTS: Intra-observer reproducibility was moderate or good for all observers (Kappa index ranging from 0.59 to 0.74). Inter-observer reproducibility was moderate to good (Kappa index range: 0.46-0.67). CONCLUSIONS: The simple rules are reasonably reproducible among observers with different level of expertise when assessed in stored 3D volumes.

Clinical and sonographic features of uncommon primary ovarian malignancies.

PURPOSE: To describe the gray-scale and color Doppler ultrasound features of uncommon (<5% prevalence) primary malignant ovarian tumors. METHODS: Retrospective analysis of 98 masses in 89 patients (median age: 50.4 years old, ranging from 15 to 81 years) diagnosed as having an uncommon primary ovarian malignancy. All patients had undergone transvaginal color Doppler ultrasound according to a standardized protocol prior to surgical tumor removal. Ultrasound features analyzed were laterality, presence of ascites, tumor volume, morphologic appearance (unilocular, multilocular, unilocular-solid, multilocular-solid, and solid), and color Doppler score (subjective assessment of the amount of flow as absent, scanty, moderate, or abundant). RESULTS: Pathological diagnoses included uncommon epithelial tumors (n = 59), germ cell tumors (n = 10), sex cord-stromal tumors (n = 11), sarcoma (n = 9), and lymphoma (n = 9). Germ cell tumors presented in younger women (p < 0.001). Germ cell tumors, sex cord-stromal tumors, sarcomas, and lymphomas were significantly more often solid as compared with epithelial malignancies, which appeared more frequently as complex (cystic-solid) tumors (p < 0.001). There were no differences in color Doppler score between the various types of tumors. CONCLUSIONS: Germ cell tumors, sex cord-stromal tumors, sarcomas, and lymphomas tend to appear as unilateral solid tumors. Color Doppler score is not useful for discriminating among uncommon primary ovarian malignancies.

Different injection sites of radionuclide for sentinel lymph node detection in breast cancer: single institution experience.

OBJECTIVE: The sentinel node is defined as the first lymph node in a regional basin that receives lymph flow from the primary tumor. There is still a controversy over deep versus superficial injection administration in the breast. STUDY DESIGN: From June 2006 to June 2008, 133 patients with biopsy proven breast carcinoma and clinically negative axilla have been treated with conservative surgery and a study of their axillary sentinel lymph nodes (SLN) has been conducted. RESULTS: The median number of SLN detected was significantly higher in the periareolarly injected (PA) group (2.43) than in the intratumorally injected (IT) group (1.92) (p=0.008). The incidence of positive SLN in the PA group was not significantly different from the incidence observed in the IT group (p=0.22). CONCLUSION: Both techniques seem to reliably identify the true SLN in the axilla. Although intradermal as compared with intratumoral injection has numerous advantages, including ease of injection, shorter time between injection and sentinel node identification, and increased radiotracer nodal uptake, nevertheless, intradermal injection allows almost exclusive identification of axillary nodes, and only on rare occasions, of non-axillary nodes. We therefore think that intratumoral injection must be preferred to intradermal when possible to identify the node that is the first draining step of the tumoral tissue.

Thrombospondin-1 serum levels do not correlate with pelvic pain in patients with ovarian endometriosis.

OBJECTIVE: Thrombospondin-1 serum levels is correlate with pelvic pain in patients with ovarian endometriosis. PATIENTS: Thrombospondin-1 serum levels were prospectively analysed in 51 patients (group A asymptomatic patients or patients presenting mild dysmenorrhea and women comprised group B severe dysmenorrhea and/or chronic pelvic pain and/or dyspareunia) who underwent surgery for cystic ovarian endometriosis to asses whether a correlation exists among thrombospondin-1 serum levels and pelvic pain. RESULTS: From 56 patients, five cases were ultimately excluded, because the histological diagnosis was other than cystic ovarian endometriosis (2 teratomas and 3 haemorrhagic cysts). The mean thrombospondin-1 serum levels in group A was 256,69 pg/ml_+37,07 and in group B was 291,41 pg/ml + 35,59. CONCLUSION: Pain symptoms in ovarian endometriosis is not correlated with thrombospondin-1 serum levels.

The value of minilaparotomy for total hysterectomy for benign uterine disease: a comparative study with conventional Pfannenstiel and laparoscopic approaches.

BACKGROUND: The aim of this paper is to review and compare the results obtained using the Pfannenstiel, laparoscopy and minilaparotomy approaches for total hysterectomy procedure in relation to benign uterine diseases. METHODS: A retrospective data analysis was performed on 165 patients who underwent hysterectomy for benign uterine diseases at our centre during the period 2004 to 2006. FINDINGS: The minilaparotomy procedure was the fastest procedure with a mean time of 73.4 minutes (range: 67.85 to 78.94 minutes, p < 0.001). Hospital stay was shortest for laparosopic procedure (mean time: 3.24 days, range: 2.86 to 3.61 days) (p < 0.001). The rate of intraoperative and postoperative complications were not statistical different among three procedures. CONCLUSION: The minilaparotomy procedure offers a minimally invasive option for total hysterectomy due to benign uterine disease.

Two-dimensional power Doppler-three-dimensional ultrasound imaging of a cesarean section dehiscence with utero-peritoneal fistula: a case report.

INTRODUCTION: An imaging diagnosis after an iterative cesarean delivery is reviewed demonstrating a fine ultrasound-pathologic correlation. CASE PRESENTATION: A 33-year-old woman (G3, P3) presented referring intense dysmenorrhea and intermenstrual spotting since her third cesarean delivery, 1 year before. A cesarean section dehiscence with utero-peritoneal fistula was diagnosed by transvaginal ultrasound. CONCLUSION: We can conclude that transvaginal two-dimensional power Doppler and three-dimensional ultrasound are highly accurate in detecting cesarean section dehiscence and uterine fistula.

Endometriosis in a postmenopausal woman without previous hormonal therapy: a case report.

INTRODUCTION: The prevalence of pelvic endometriosis is high, affecting approximately 6% to 10% of women of reproductive age. Although endometriosis has been associated with the occurrence of menstrual cycles, it can affect between 2% to 5% of postmenopausal women. CASE PRESENTATION: We present a case of ovarian endometriosis in a 62-year-old Spanish Caucasian woman with no previous use of hormonal therapy and no history of endometriosis or infertility. CONCLUSION: ALTHOUGH THE REPORTED SITUATION IS RARE, IT IS IMPORTANT TO BE AWARE OF ENDOMETRIOSIS AFTER THE MENOPAUSE: post-menopausal endometriosis confers a risk of recurrence and malignant transformation.