Using computer-aided detection in mammography as a decision support

Contains fulltext : 87548.pdf (publisher's version ) (Closed access)OBJECTIVE: To evaluate an interactive computer-aided detection (CAD) system for reading mammograms to improve decision making. METHODS: A dedicated mammographic workstation has been developed in which readers can probe image locations for the presence of CAD information. If present, CAD findings are displayed with the computed malignancy rating. A reader study was conducted in which four screening radiologists and five non-radiologists participated to study the effect of this system on detection performance. The participants read 120 cases of which 40 cases had a malignant mass that was missed at the original screening. The readers read each mammogram both with and without CAD in separate sessions. Each reader reported localized findings and assigned a malignancy score per finding. Mean sensitivity was computed in an interval of false-positive fractions less than 10%. RESULTS: Mean sensitivity was 25.1% in the sessions without CAD and 34.8% in the CAD-assisted sessions. The increase in detection performance was significant (p = 0.012). Average reading time was 84.7 +/- 61.5 s/case in the unaided sessions and was not significantly higher when interactive CAD was used (85.9 +/- 57.8 s/case). CONCLUSION: Interactive use of CAD in mammography may be more effective than traditional CAD for improving mass detection without affecting reading time.1 oktober 201

One-day core needle biopsy in a breast clinic: 4 years experience

Contains fulltext : 118897pub.pdf (publisher's version ) (Closed access) Contains fulltext : 118897pos.pdf (postprint version ) (Open Access)Many attempts have been made to combine the high diagnostic accuracy and conclusive rate of core needle biopsy (CNB) with the speed of fine needle aspiration cytology in evaluation of solid breast lesions. Multiple hybrid techniques have been developed to achieve this. We describe a cohort of patients for whom we used a relatively new, accelerated method of CNB processing, allowing for a definitive diagnosis the same day. All patients visiting the Radboud University Nijmegen Medical Centre breast clinic during a 4-year period were reviewed to identify all CNBs in this period performed in a same-day diagnosis track. CNB result was compared to post-operative pathology reports when available, and to follow-up when patients were not surgically treated. 1,060 patients underwent CNB of 1,383 lesions, 898 of which in a same-day diagnosis track with a sensitivity of 96.9 % and a specificity of 99.4 %. The inconclusive rate was 9.2 %. For a same-day diagnosis for solid breast lesions, we could give a conclusive diagnosis with accelerated CNB processing in 65 % of our patients requiring CNB. This technique can be used reliably in a same-day diagnosis breast clinic with a very high sensitivity, specificity, and conclusive rate

Prophylactic vaccines are potent activators of monocyte-derived dendritic cells and drive effective anti-tumor responses in melanoma patients at the cost of toxicity

Dendritic cell (DC)-based immunotherapy is explored worldwide in cancer patients, predominantly with DC matured with pro-inflammatory cytokines and prostaglandin E2. We studied the safety and efficacy of vaccination with monocyte-derived DC matured with a cocktail of prophylactic vaccines that contain clinical-grade Toll-like receptor ligands (BCG, Typhim, Act-HIB) and prostaglandin E2 (VAC-DC). Stage III and IV melanoma patients were vaccinated via intranodal injection (12 patients) or combined intradermal/intravenous injection (16 patients) with VAC-DC loaded with keyhole limpet hemocyanin (KLH) and mRNA encoding tumor antigens gp100 and tyrosinase. Tumor antigen-specific T cell responses were monitored in blood and skin-test infiltrating-lymphocyte cultures. Almost all patients mounted prophylactic vaccine- or KLH-specific immune responses. Both after intranodal injection and after intradermal/intravenous injection, tumor antigen-specific immune responses were detected, which coincide with longer overall survival in stage IV melanoma patients. VAC-DC induce local and systemic CTC grade 2 and 3 toxicity, which is most likely caused by BCG in the maturation cocktail. The side effects were self-limiting or resolved upon a short period of systemic steroid therapy. We conclude that VAC-DC can induce functional tumor-specific responses. Unfortunately, toxicity observed after vaccination precludes the general application of VAC-DC, since in DC maturated with prophylactic vaccines BCG appears to be essential in the maturation cocktai

Effective clinical responses in metastatic melanoma patients after vaccination with primary myeloid dendritic cells

\u3cp\u3ePURPOSE: Thus far, dendritic cell (DC)-based immunotherapy of cancer was primarily based on in vitro-generated monocyte-derived DCs, which require extensive in vitro manipulation. Here, we report on a clinical study exploiting primary CD1c(+) myeloid DCs, naturally circulating in the blood.\u3c/p\u3e\u3cp\u3eEXPERIMENTAL DESIGN: Fourteen stage IV melanoma patients, without previous systemic treatment for metastatic disease, received autologous CD1c(+) myeloid DCs, activated by only brief (16 hours) ex vivo culture and loaded with tumor-associated antigens of tyrosinase and gp100.\u3c/p\u3e\u3cp\u3eRESULTS: Our results show that therapeutic vaccination against melanoma with small amounts (3-10 × 10(6)) of myeloid DCs is feasible and without substantial toxicity. Four of 14 patients showed long-term progression-free survival (12-35 months), which directly correlated with the development of multifunctional CD8(+) T-cell responses in three of these patients. In particular, high CD107a expression, indicative for cytolytic activity, and IFNγ as well as TNFα and CCL4 production was observed. Apparently, these T-cell responses are essential to induce tumor regression and promote long-term survival by stalling tumor growth.\u3c/p\u3e\u3cp\u3eCONCLUSIONS: We show that vaccination of metastatic melanoma patients with primary myeloid DCs is feasible and safe and results in induction of effective antitumor immune responses that coincide with improved progression-free survival. Clin Cancer Res; 22(9); 2155-66. ©2015 AACR.\u3c/p\u3

Effective Clinical Responses in Metastatic Melanoma Patients after Vaccination with Primary Myeloid Dendritic Cells

Thus far, dendritic cell (DC)-based immunotherapy of cancer was primarily based on in vitro-generated monocyte-derived DCs, which require extensive in vitro manipulation. Here, we report on a clinical study exploiting primary CD1c(+) myeloid DCs, naturally circulating in the blood. Fourteen stage IV melanoma patients, without previous systemic treatment for metastatic disease, received autologous CD1c(+) myeloid DCs, activated by only brief (16 hours) ex vivo culture and loaded with tumor-associated antigens of tyrosinase and gp100. Our results show that therapeutic vaccination against melanoma with small amounts (3-10 × 10(6)) of myeloid DCs is feasible and without substantial toxicity. Four of 14 patients showed long-term progression-free survival (12-35 months), which directly correlated with the development of multifunctional CD8(+) T-cell responses in three of these patients. In particular, high CD107a expression, indicative for cytolytic activity, and IFNγ as well as TNFα and CCL4 production was observed. Apparently, these T-cell responses are essential to induce tumor regression and promote long-term survival by stalling tumor growth. We show that vaccination of metastatic melanoma patients with primary myeloid DCs is feasible and safe and results in induction of effective antitumor immune responses that coincide with improved progression-free survival. Clin Cancer Res; 22(9); 2155-66. ©2015 AAC

MR-guided breast biopsy at 3T: diagnostic yield of large core needle biopsy compared with vacuum-assisted biopsy.

Item does not contain fulltextOBJECTIVE: The purpose of this study was to evaluate two MR-guided biopsy techniques at 3 T, large core needle breast biopsy (LCNB) and vacuum-assisted breast biopsy (VAB) and to compare the diagnostic yield and rate of complications to determine the optimal biopsy technique at 3 T. METHODS: 55 LCNB and 64 VAB were consecutively performed. Benign biopsy results were verified by retrospective correlation of histology, with pre-interventional, post-interventional MRI studies and follow-up and were classified as representative or non-representative. Time to follow-up was up to 2 years for the considered non-representative benign lesions. Statistical analysis was performed using the Chi-squared test. RESULTS: LCNB was technically successful in 100% of patients (55/55) and VAB in 98% of patients (63/64). Histopathological analysis resulted in 45 (82%) benign, 3 (5%) high-risk and 7 (13%) malignant lesions for LCNB and 43 (67%) benign, 3 (5%) high-risk and 18 (28%) malignant lesions. Distribution was significantly different (p < 0.001), favouring VAB over LCNB. CONCLUSION: Because of the substantially higher diagnostic yield and certainty of a benign diagnosis, VAB is the optimal biopsy technique at 3 T. LCNB should be considered when VAB is not feasible.1 februari 201