Radiomics and artificial intelligence analysis by T2-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging to predict Breast Cancer Histological Outcome.

OBJECTIVE: The objective of the study was to evaluate the accuracy of radiomics features obtained by MR images to predict Breast Cancer Histological Outcome. METHODS: A total of 217 patients with malignant lesions were analysed underwent MRI examinations. Considering histological findings as the ground truth, four different types of findings were used in both univariate and multivariate analyses: (1) G1 + G2 vs G3 classification; (2) presence of human epidermal growth factor receptor 2 (HER2 + vs HER2 -); (3) presence of the hormone receptor (HR + vs HR -); and (4) presence of luminal subtypes of breast cancer. RESULTS: The best accuracy for discriminating HER2 + versus HER2 - breast cancers was obtained considering nine predictors by early phase T1-weighted subtraction images and a decision tree (accuracy of 88% on validation set). The best accuracy for discriminating HR + versus HR - breast cancers was obtained considering nine predictors by T2-weighted subtraction images and a decision tree (accuracy of 90% on validation set). The best accuracy for discriminating G1 + G2 versus G3 breast cancers was obtained considering 16 predictors by early phase T1-weighted subtraction images in a linear regression model with an accuracy of 75%. The best accuracy for discriminating luminal versus non-luminal breast cancers was obtained considering 27 predictors by early phase T1-weighted subtraction images and a decision tree (accuracy of 94% on validation set). CONCLUSIONS: The combination of radiomics analysis and artificial intelligence techniques could be used to support physician decision-making in prediction of Breast Cancer Histological Outcome.

Noninvasive strategies for breast cancer early detection.

Breast cancer screening and presurgical diagnosis are currently based on mammography, ultrasound and more sensitive imaging technologies; however, noninvasive biomarkers represent both a challenge and an opportunity for early detection of cancer. An extensive number of potential breast cancer biomarkers have been discovered by microarray hybridization or sequencing of circulating DNA, noncoding RNA and blood cell RNA; multiplex analysis of immune-related molecules and mass spectrometry-based approaches for high-throughput detection of protein, endogenous peptides, circulating and volatile metabolites. However, their medical relevance and their translation to clinics remain to be exploited. Once they will be fully validated, cancer biomarkers, used in combination with the current and emerging imaging technologies, represent an avenue to a personalized breast cancer diagnosis.

¹8F-FLT PET/CT as an imaging tool for early prediction of pathological response in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy: a pilot study.

PURPOSE: We evaluated whether (18)F-3'-deoxy-3'-fluorothymidine positron emission tomography (FLT PET) can predict the final postoperative histopathological response in primary breast cancer after the first cycle of neoadjuvant chemotherapy (NCT). METHODS: In this prospective cohort study of 15 patients with locally advanced operable breast cancer, FLT PET evaluations were performed before NCT, after the first cycle of NCT, and at the end of NCT. All patients subsequently underwent surgery. Variables from FLT PET examinations were correlated with postoperative histopathological results. RESULTS: At baseline, median of maximum standardized uptake values (SUVmax) in the groups showing a complete pathological response (pCR) + residual cancer burden (RCB) I, RCB II or RCB III did not differ significantly for the primary tumour (5.0 vs. 2.9 vs. 8.9, p = 0.293) or for axillary nodes (7.9 vs. 1.6 vs. 7.0, p = 0.363), whereas the Spearman correlation between SUVmax and Ki67 proliferation rate index was significant (r = 0.69, p < 0.001). Analysis of the relative percentage change of SUVmaxin the primary tumour (∆SUVTmax(t1)) and axillary nodes (∆SUVNmax(t1)) after the first NCT cycle showed that the power of ∆SUVTmax(t 1) to predict pCR + RCB I responses (AUC = 0.91, p < 0.001) was statistically significant, whereas ∆SUVNmax(t1) had a moderate ability (AUC = 0.77, p = 0.119) to separate subjects with ΔSUVTmax(t1) > -52.9 % into two groups: RCB III patients and a heterogeneous group that included RCB I and RCB II patients. A predictive score µ based on ΔSUVTmax(t1) and ΔSUVNmax(t1) parameters is proposed. CONCLUSION: The preliminary findings of the present study suggest the potential utility of FLT PET scans for early monitoring of response to NCT and to formulate a therapeutic strategy consistent with the estimated efficacy of NCT. However, these results in a small patient population need to be validated in a larger independent cohort.

Axillary lymph node dissection versus no dissection in patients with T1N0 breast cancer: a randomized clinical trial (INT09/98).

BACKGROUND: Although axillary surgery is still considered to be a fundamental part of the management of early breast cancer, it may no longer be necessary either as treatment or as a guide to adjuvant treatment. The authors conducted a single-center randomized trial (INT09/98) to determine the impact of avoiding axillary surgery in patients with T1N0 breast cancer and planning chemotherapy based on biological factors of the primary tumor on long-term disease control. METHODS: From June 1998 to June 2003, 565 patients aged 30 years to 65 years with T1N0 breast cancer were randomized to either quadrantectomy with (QUAD) or without (QU) axillary lymph node dissection; a total of 517 patients finally were evaluated. All patients received radiotherapy to the residual breast only. Chemotherapy for patients in the QUAD treatment arm was determined based on lymph node status, estrogen receptor status, and tumor grade. Chemotherapy for patients in the QU treatment arm was based on estrogen receptor status, tumor grade, and human epidermal growth factor receptor 2 and laminin receptor status. Overall survival (OS) was the primary endpoint. Disease-free survival (DFS) and rate and time of axillary lymph node recurrence in the QU treatment arm were the secondary endpoints. RESULTS: After a median follow-up of >10 years, the estimated adjusted hazards ratio of the QUAD versus QU treatment arms for OS was 1.09 (95% confidence interval, 0.59-2.00; P = .783) and was 1.04 (95% confidence interval, 0.56-1.94; P = .898) for DFS. Of the 245 patients in the QU treatment arm, 22 (9.0%) experienced axillary lymph node recurrence. The median time to axillary lymph node recurrence from breast surgery was 30.0 months (interquartile range, 24.2 months-73.4 months). CONCLUSIONS: Patients with T1N0 breast cancer did not appear to benefit in terms of DFS and OS from immediate axillary lymph node dissection in the current randomized trial. The biological characteristics of the primary tumor appear adequate for guiding adjuvant treatment.

Ex vivo MRI evaluation of breast tumors: a novel tool for verifying resection of nonpalpable only MRI detected lesions.

A fundamental question in surgery of only magnetic resonance imaging (MRI)-detected breast lesions is to ensure their removal when they are not palpable by clinical examination and surgical exploration. This is especially relevant in the case of small tumors, carcinoma in situ or lobular carcinoma. Thirty-nine patients were enrolled in the study, 21 patients with breast lesions detected by both conventional imaging and breast MRI (bMRI) and 18 patients with bMRI findings only. Preoperative bMRI allowed staging the disease and localizing the lesion. In the operating theater, contrast medium was injected 1 minute before skin incision. After removal, surgical specimens were submitted to ex vivo MRI, performed using a dedicated surface coil and Spair inversion recovery sequences for suppression of fat signal intensity. All MRI enhancing lesions were completely included within the surgical specimen and visualized by ex vivo MRI. In the first 21 patients, bMRI was able to visualize branching margins or satellite nodules around the core lesion, and allowed for better staging of the surrounding in situ carcinoma; in the last 18 patients, eight of whom were breast cancer type 1 susceptibility protein (BRCA) mutation carriers, bMRI identified 12 malignant tumors, otherwise undetectable, that were all visualized by ex vivo MRI. This is the first description of a procedure that re-enhances breast lesions within a surgical specimen, demonstrating the surgical removal of nonpalpable breast lesions diagnosed only with bMRI. This new strategy reproduces the morphology and the entire extension of the primary lesion on the specimen, with potentially better local surgical control, reducing additional unplanned surgery.

MRI versus Mammography plus Ultrasound in Women at Intermediate Breast Cancer Risk: Study Design and Protocol of the MRIB Multicenter, Randomized, Controlled Trial.

In women at high/intermediate lifetime risk of breast cancer (BC-LTR), contrast-enhanced magnetic resonance imaging (MRI) added to mammography ± ultrasound (MX ± US) increases sensitivity but decreases specificity. Screening with MRI alone is an alternative and potentially more cost-effective strategy. Here, we describe the study protocol and the characteristics of enrolled patients for MRIB feasibility, multicenter, randomized, controlled trial, which aims to compare MRI alone versus MX+US in women at intermediate breast cancer risk (aged 40-59, with a 15-30% BC-LTR and/or extremely dense breasts). Two screening rounds per woman were planned in ten centers experienced in MRI screening, the primary endpoint being the rate of cancers detected in the 2 arms after 5 years of follow-up. From July 2013 to November 2015, 1254 women (mean age 47 years) were enrolled: 624 were assigned to MX+US and 630 to MRI. Most of them were aged below 50 (72%) and premenopausal (45%), and 52% used oral contraceptives. Among postmenopausal women, 15% had used hormone replacement therapy. Breast and/or ovarian cancer in mothers and/or sisters were reported by 37% of enrolled women, 79% had extremely dense breasts, and 41% had a 15-30% BC-LTR. The distribution of the major determinants of breast cancer risk profiles (breast density and family history of breast and ovarian cancer) of enrolled women varied across centers.

Inflammatory myofibroblastic tumor of the conjunctiva: response to chemotherapy with low-dose methotrexate and vinorelbine.

Inflammatory myofibroblastic tumor (IMT) is an unusual entity that mainly affects children and young adults, and for which standardized therapies for inoperable cases are still lacking. We report on a 12-year-old patient with an extremely rare and inoperable conjunctival location that was treated with chemotherapy using low-dose methotrexate plus vinorelbine, achieving complete tumor remission. This regimen is usually well tolerated and may be considered as the treatment of choice for cases of unresectable advanced IMT.

Is there a specific magnetic resonance phenotype characteristic of hereditary breast cancer?

AIMS AND BACKGROUND: The aim of the study was to investigate the growth rate of inherited breast cancer, to analyze its T2 signal intensity besides kinetic and morphologic aspects, and to verify whether there is any correlation between magnetic resonance imaging phenotype and BRCA status. METHODS: Between June 2000 and September 2009, we enrolled 227 women at high genetic risk for breast cancer in a surveillance program, within a multicenter project of the Istituto Superiore di Sanità (Rome). RESULTS: Thirty-four cancers were detected among 31 subjects. One patient refused magnetic resonance imaging because of claustrophobia. Compared with sporadic disease, hereditary cancer showed some differences, in terms of biologic attitude and semeiotic patterns. These differences were mainly registered for magnetic resonance imaging, where the most frequent radiological variant was represented by the very high T2 signal intensity (73%). Moreover, the size of 8 of the neoplasms showed a significant increase in less than one year, 5 of them in less than 6 months. Six lesions were in BRCA1 patients and the remaining in BRCA2. Furthermore, cancers with a high growth rate also demonstrated a significant increment in T2 signal intensity. CONCLUSIONS: Our results confirmed the high growth rate within BRCA-related breast cancers, especially for BRCA1 mutation carriers. In our experience, we found a specific imaging phenotype, represented by the high T2 signal intensity of hereditary breast cancer. To our knowledge, this is the first report that points out this new semeiotic parameter, which is usually typical of benign lesions. Considering the correlation between high growth rate and high T2 signal intensity, the former seems to be related to the absence of induction of a desmoplastic reaction that could somehow restrict cancer growth.

Partial breast irradiation with CyberKnife after breast conserving surgery: a pilot study in early breast cancer.

BACKGROUND: Local recurrences after breast conserving treatment are mainly close to the original tumor site, and as such shorter fractionation strategies focused on and nearest mammary gland, i.e. accelerated partial breast irradiation (APBI), have been developed. Stereotactic APBI has been attempted, although there is little experience using CyberKnife (CK) for early breast cancer. METHODS: This pilot study was designed to assess the feasibility of CK-APBI on 20 evaluable patients of 29 eligible, followed for 2 years. The primary endpoint was acute/sub-acute toxicity; secondary endpoints were late toxicity and the cosmetic result. RESULTS: Mean pathological tumor size was 10.5 mm (±4.3, range 3-18), 8 of these patients were classified as LumA-like, 11 as LumB-like, and 1 as LumB-HER2-enriched. Using CK-APBI with Iris, the treatment time was approximately 60 min (range~ 35 to ~ 120). All patients received 30 Gy in five fractions delivered to the PTV. The median number of beams was 180 (IQR 107-213; range:56-325) with a median PTV isodose prescription of 86.0% (IQR 85.0-88.5; range:82-94). The median PTV was 88.1 cm3 (IQR 63.8-108.6; range:32.3-238.8). The median breast V100 and V50 was 0.6 (IQR 0.1-1.5; range:0-13) and 18.6 (IQR 13.1-21.7; range:7.5-37), respectively. The median PTV minimum dose was 26.2 Gy (IQR 24.7-27.6; range 22.3-29.3). Mild side effects were recorded during the period of observation. Cosmetic evaluations were performed by three observers from the start of radiotherapy up to 2 years. Patients' evaluation progressively increase from 60% to 85% of excellent rating; this trend was similar to that of external observer. CONCLUSIONS: These preliminary results showed the safe feasibility of CK-APBI in early breast cancer, with mild acute and late toxicity and very good cosmetic results. TRIAL REGISTRATION: The present study is registered at Clinicaltrial.gov ( NCT02896322 ). Retrospectively egistered August 4, 2016.

Evaluation of Local Oncologic Safety in Nipple-Areola Complex-sparing Mastectomy After Primary Chemotherapy: A Propensity Score-matched Study.

BACKGROUND: Nipple-areola complex-sparing mastectomy (NSM), extending the concept of skin-sparing mastectomy, allows for the provision of a better cosmetic result. Large operable T2-T3 breast cancer might theoretically appear suitable for this surgical option as an alternative to conventional mastectomy or breast-conserving surgery, when a good response to primary chemotherapy has been achieved. PATIENTS AND METHODS: From January 2009 to May 2013, 422 patients with invasive breast cancer were progressively accrued to NSM. Of the 422 patients, 361 underwent NSM as first-line treatment (NSM group), and 61 underwent surgery after primary chemotherapy (NSM-PC group). A total of 151 breast cancer patients, who had undergone PC and conventional total mastectomy (TM-PC group) from 2004 to 2009 were evaluated as comparative group with respect to the NSM-PC group. Using propensity score matching, local disease-free survival (LDFS) was evaluated comparatively. RESULTS: The rate of nipple-areola involvement in the NSM and NSM-PC groups was 13.3% and 9.8%, respectively (P = .539). The nipple-areola involvement in the NSM and NSM-PC groups was significantly associated with the tumor size (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.13-1.95; P = .004), plurifocal or pluricentric tumor (OR, 3.18; 95% CI, 1.72-5.89; P < .001), and the presence of an intraductal component (OR, 2.38; 95% CI, 1.22-4.64; P = .011). The LDFS in the NSM-PC and TM-PC matched cohorts did not show a significant difference, with a 4-year LDFS of 0.89 (95% CI, 0.77-0.95) and 0.93 (95% CI, 0.83-0.97), respectively (hazard ratio [HR], 1.31; 95% CI, 0.40-4.35; P = .655). The NSM-PC cohort was also compared with the NSM cohort in terms of LDFS using 2 different matching criteria, with the tumor size before and after neoadjuvant chemotherapy as the balancing covariate. In the first of the 2 comparisons, the hazards of local relapse were comparable between the 2 matched groups (HR, 1.23; 95% CI, 0.37-4.04; P = .739). In the second comparison, the NSM-PC patients showed a significant greater hazard of local relapse than did the NSM patients (HR, 3.60; 95% CI, 1.10-11.80; P = .035). CONCLUSION: NSM might be a valuable option for large breast cancer treated by primary chemotherapy. The rate of local relapse seemed to be related to the disease stage, and no significant association with the type of surgery was detected.

MRI in the early detection of breast cancer in women with high genetic risk.

AIMS AND BACKGROUND: Women with BRCA1 or BRCA2 germline mutations have an elevated risk of developing breast and/or ovarian cancer. Because of the early onset of the disease, screening of this group of women should start at an earlier age than in the general population. The association of breast magnetic resonance imaging (BMRI) and ultrasonography (US) with mammography (MX) and clinical breast examination (CBE) in the regular surveillance of these individuals has been proposed and seems to improve the early detection of breast cancer. METHODS: Within a multicenter study started by the Istituto Superiore di Sanità (Rome), at the Istituto Nazionale Tumori of Milan (INT) we enrolled 116 women at high genetic risk for breast cancer; they were either BRCA1 or BRCA2 mutation carriers or had a strong family history of breast cancer. They underwent CBE, MX, US and BMRI once a year. RESULTS: Between June 2000 and April 2005, at INT 12 cancers were detected among the 116 screened individuals (10%). In this subgroup, 1 patient refused BMRI and in 2 cases US was not performed. With BMRI we found 11 cancers and 6 of them were detectable only by this technique. In these 6 cases, the size of the disease was less than 1 cm and MX was false negative due to irregularly nodular parenchyma in 4 cases and scar tissue or prosthesis in the other 2. US was not performed in 2 cases and was false negative in 4 cases. Three false positive results were found with BMRI: 1 case was considered suspect but related to hormonal influences; 1 case with the same pattern was sent for second-look US, which gave a negative result and BMRI review after 6 months showed normalization of the parenchyma; in the third case histology revealed the presence of adenosis. No false positive results were registered for MX. CONCLUSIONS: The aim of secondary prevention is the detection of cancer at its earliest stage. BMRI screening in women with BRCA1 or BRCA2 mutations or at high familiar risk appears to be highly sensitive and may detect mammographically occult disease. The accuracy of MR imaging is higher than that of conventional imaging but the technique is flawed by a lower specificity. In order to avoid unnecessary biopsies we believe that the combination of BMRI and conventional imaging can be very useful in screening women with a high genetic risk of breast cancer, especially with second-look evaluation by means of US when BMRI yields the only positive diagnostic result. Second-look US has been demonstrated to be of critical importance both in recognizing false positive BMRI results and in guiding biopsies, when necessary.

Breast metastasis from cutaneous malignant melanoma mimicking a breast cancer.

INTRODUCTION: Breast metastases are very uncommon, either from solid tumors or malignant melanoma. CASE REPORT: We present the case of a 42-year-old woman with a history of cutaneous melanoma of the shoulder excised 21 years ago. She presented with a palpable lump in the upper outer quadrant of the right breast. Ultrasound demonstrated a solid mass within a cystic lesion. A core biopsy was taken and first histology reported a poorly differentiated primary breast cancer suspected to be triple negative. MRI detected a satellite lesion in the same breast, a focus of suspected enhancement in the other breast, and the extramammary finding of an enhancing pulmonary lesion. Staging computed tomography detected widespread metastases to the lungs, brain, subcutaneous left shoulder, liver, pancreas, and hepatorenal recess. A core biopsy was taken from the left breast lesion and the previous slides were reviewed; histopathology and immunohistochemistry were in keeping with metastasis from melanoma. CONCLUSIONS: The possibility of a metastatic lesion to the breast should be taken into account in any patient presenting with a breast lump and a previous history of melanoma. Breast involvement cannot be considered an isolated finding, as it might be the first manifestation of widespread disease.

Breast MRI screening in patients with increased familial and/or genetic risk for breast cancer: a preliminary experience.

AIMS AND BACKGROUND: Breast cancer is the most common cancer affecting women, and it is associated with or due to a genetic predisposition in 5%-10% of the cases. Owing to the higher risk of developing breast cancer and the early onset of the disease in women proved or suspected to be carriers of a breast cancer susceptibility gene, a dedicated screening should be offered as a less invasive approach with the otherwise suggested prophylactic mastectomy. This should be optimized in order to overcome the limitations of conventional breast imaging with the application of new technologies such as breast magnetic resonance imaging. METHODS: A diagnostic protocol for routine control in patients at high risk of developing breast cancer has been prepared. Within a 7-month period, 23 patients suspected or proved to carry a breast cancer susceptibility gene underwent breast magnetic resonance imaging. RESULTS: Four breast cancers were identified with breast magnetic resonance imaging. In these cases, mammography was negative because of the density of the parenchyma or for its fibroglandular pattern. Ultrasound was negative in 2 cases, not specific for malignancy in 1 case, and considered as only possibly malignant but with biopsy recommendation on the basis of magnetic resonance findings in the last one. Clinical analysis was positive for a mass in 2 cases. CONCLUSIONS: The accuracy of breast magnetic resonance imaging is known to be higher than that of conventional imaging in the study of breast parenchyma. High spatial resolution, no breast density influence and multiplanarity can give more detailed information about the smaller lesions and the right extension of the disease. Preliminary studies where breast magnetic resonance imaging is performed in addition to mammography within this group of patients are encouraging. We also believe that the application of breast magnetic resonance imaging can be very useful in the detection of cancer as early as possible with the aim to obtain the highest chance of survival after treatment.

Breast microcalcifications studied with 3D contrast-enhanced high-field magnetic resonance imaging: more accuracy in the diagnosis of breast cancer.

AIMS: To evaluate the reliability of magnetic resonance imaging (MRI) performed with three-dimensional (3D) sequences in mammographically detected breast microcalcifications. METHODS: During an 8-month period, a group of 28 patients with mammographically detected microcalcifications suspicious for malignancy underwent MRI. Their ages ranged from 33 to 65 years. Examinations were performed with a 1.5 Tesia MR unit and a 3D T1 weighted sequence. Images were interpreted on the basis of morphologic parameters and dynamic behavior in the uptake of contrast medium (Gd-DTPA). Histologic findings were considered as the gold reference. RESULTS: Histologic analysis revealed invasive carcinoma in 7 patients, 3 of which were associated with foci of lobular carcinoma in situ. Intraductal carcinoma was diagnosed in 8 patients, 1 of which was associated with a tubular carcinoma. Benign lesions accounted for 13 patients. All the neoplastic conditions showed enhancement on MR images (sensitivity, 100%), whereas early and intense enhancement was noted in 5 of 13 benign lesions (specificity, 61%). The positive predictive value was 75% and negative predictive value, 100%. CONCLUSIONS: Although an overlap in the enhancement behavior of malignant and some benign lesions is clearly evident, a careful interpretation of MR images is helpful in detecting and mainly ruling out breast cancer combined with mammographically suspicious microcalcifications.

A multi-tissue mass-spring model for computer assisted breast surgery.

The aim of this work was to develop and validate a 3D female breast deformation model for computer assisted breast surgery. Magnetic resonance (MR) image data of a patient undergoing breast biopsy, were acquired using two different protocols with the patient in prone position: (i) uncompressed breast and (ii) compressed breast, with lateral single breast compression, realized with a movable slab. The acquired images were then segmented using a semi-automatic procedure and from the extracted volumes of interest tetrahedral meshes representing skin, fat and mammary glands were generated. Tissue deformation was ruled by a mass-spring model: first, an iterative approximation algorithm was implemented to estimate the spring's rest length and stiffness, accounting for gravity force; then the resulting parameters were used to deform the uncompressed breast model in order to reach the real compressed one (ground truth). Results showed that gravity force applied to the mesh was properly compensated by the internal elastic forces, leading to a distance between the deformed mesh and the reference data of 0.036±0.092 mm (median±inter quartile range). The point to mesh residual distance between the deformed mesh and the ground truth was 1.224±2.202 mm (median±inter quartile range). Further investigation on a larger patient dataset is required for a more robust confirmation of model accuracy in predicting breast deformations.

Occurrence of breast cancer after chest wall irradiation for pediatric cancer, as detected by a multimodal screening program.

PURPOSE: To assess the occurrence of breast cancer (BC) after exposure to ionizing radiation for pediatric cancer, by means of a multimodal screening program. PATIENTS AND METHODS: We identified 86 patients who had received chest wall radiation therapy for pediatric cancer. Clinical breast examination (CBE), ultrasound (US), and mammography (MX) were performed yearly. Magnetic resonance imaging (MRI) was added as of October 2007. We calculated the risk of developing BC by radiation therapy dose, patient age, and menarche before or after primary treatment. RESULTS: Eleven women developed a BC from July 2002-February 2010. The sensitivity of the screening methods was 36% for CBE, 73% for MX, 55% for US, and 100% for MRI; the specificity was 91%, 99%, 95%, and 80% for CBE, MX, US, and MRI, respectively. The annual BC detection rate was 2.9%. The median age at BC diagnosis was 33 years. Although age had no influence, menarche before as opposed to after radiation therapy correlated significantly with BC (P=.027): the annual BC detection rate in the former subgroup was 5.3%. CONCLUSIONS: Mammography proved more sensitive and specific in our cohort of young women than CBE or US. Magnetic resonance imaging proved 100% sensitive (but this preliminary finding needs to be confirmed). Our cohort of patients carries a 10-fold BC risk at an age more than 20 years younger than in the general population.

Multicenter surveillance of women at high genetic breast cancer risk using mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (the high breast cancer risk italian 1 study): final results.

OBJECTIVES: : To prospectively compare clinical breast examination, mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (MRI) in a multicenter surveillance of high-risk women. MATERIALS AND METHODS: : We enrolled asymptomatic women aged ≥ 25: BRCA mutation carriers; first-degree relatives of BRCA mutation carriers, and women with strong family history of breast/ovarian cancer, including those with previous personal breast cancer. RESULTS: : A total of 18 centers enrolled 501 women and performed 1592 rounds (3.2 rounds/woman). Forty-nine screen-detected and 3 interval cancers were diagnosed: 44 invasive, 8 ductal carcinoma in situ; only 4 pT2 stage; 32 G3 grade. Of 39 patients explored for nodal status, 28 (72%) were negative. Incidence per year-woman resulted 3.3% overall, 2.1% <50, and 5.4% ≥ 50 years (P < 0.001), 4.3% in women with previous personal breast cancer and 2.5% in those without (P = 0.045). MRI was more sensitive (91%) than clinical breast examination (18%), mammography (50%), ultrasonography (52%), or mammography plus ultrasonography (63%) (P < 0.001). Specificity ranged 96% to 99%, positive predictive value 53% to 71%, positive likelihood ratio 24 to 52 (P not significant). MRI showed significantly better negative predictive value (99.6) and negative likelihood ratio (0.09) than those of the other modalities. At receiver operating characteristic analysis, the area under the curve of MRI (0.97) was significantly higher than that of mammography (0.83) or ultrasonography (0.82) and not significantly increased when MRI was combined with mammography and/or ultrasonography. Of 52 cancers, 16 (31%) were diagnosed only by MRI, 8 of 21 (38%) in women <50, and 8 of 31 (26%) in women ≥ 50 years of age. CONCLUSION: : MRI largely outperformed mammography, ultrasonography, and their combination for screening high-risk women below and over 50.

Comparison of the prognostic value of assessing tumor diameter versus tumor volume at diagnosis or in response to initial chemotherapy in rhabdomyosarcoma.

PURPOSE: In this study on a series of 205 patients with rhabdomyosarcoma, we investigated whether the prognostic effect of tumor size, at diagnosis or in terms of tumor response after induction chemotherapy, differed when tumor diameter or tumor volume were considered. PATIENTS AND METHODS: Tumor size was assessed radiologically at diagnosis and, for the 108 patients with measurable disease, after three courses of chemotherapy. The analysis was based on multivariable models (linear for association between size and patient/tumor characteristics, Cox for association with survival). The predictive performance of the Cox model (estimated by V measure) was compared for the tumor's diameter and volume. RESULTS: Initial tumor size was significantly larger in male or older patients and in T2 or alveolar tumors, but was not associated with the achievement of complete surgical resection. Initial tumor size significantly influenced overall survival. The risk of death was comparable for tumors 10 cm in maximum diameter and 194.0 cm(3) in volume. The predictive performance of the Cox model was much the same when the tumor's diameter or volume was considered. Tumor response was a significant predictor of survival, again irrespective of the type of tumor measurement considered. CONCLUSION: In our analysis, initial tumor size and tumor response were significant prognostic factors in rhabdomyosarcoma, regardless of whether tumor diameter or volume was considered. Three-dimensional tumor assessment was of no greater prognostic value than one-dimensional assessment, neither initially nor after induction treatment.

Radiation-induced thyroid changes: a retrospective and a prospective view.

AIM OF THE STUDY: Incidental/therapeutic thyroid irradiation causes hypothyroidism and nodular disease. Increasing numbers of children are being cured of cancers by treatments that include radiation also involving the thyroid bed: these children warrant an early diagnosis and treatment of any radiation-related thyroid changes. METHODS: In 1998 we retrospectively evaluated thyroid parenchyma/function in all patients irradiated between 1975 and 1997; thereafter, we prospectively evaluated all patients given thyroid irradiation by means of thyroid ultrasound and serum fT3, fT4, TSH and thyroglobulin. RESULTS: Of 596 eligible patients, 468 agreed to the retrospective evaluation: 128/468 had one or more thyroid nodules, and 73 of these 128 had concomitant or previously untreated hypothyroidism, while 22/128 had a differentiated carcinoma. Another 144/157 patients treated between 1998 and 2004 were evaluated and any iatrogenic hypothyroidism was promptly treated: 19/144 had nodules, all smaller than 1cm in diameter. The first patient group was studied retrospectively, so we have no precise record of the time of nodule occurrence or of their initial sizes. We found, however, that both the number of patients with nodules and the sizes of the nodules were significantly lower (p<0.01) in the prospectively studied group (after a median follow-up of 81 months) than in the retrospectively studied group. Among all the patients with nodules, significantly more females developed cancer than males (p<0.04). CONCLUSIONS: Early treatment for hypothyroidism and ultrasound evaluation of the parenchyma are needed to limit nodule onset and growth.