Optimized breast MRI functional tumor volume as a biomarker of recurrence-free survival following neoadjuvant chemotherapy.

PURPOSE: To evaluate optimal contrast kinetics thresholds for measuring functional tumor volume (FTV) by breast magnetic resonance imaging (MRI) for assessment of recurrence-free survival (RFS). MATERIALS AND METHODS: In this Institutional Review Board (IRB)-approved retrospective study of 64 patients (ages 29-72, median age of 48.6) undergoing neoadjuvant chemotherapy (NACT) for breast cancer, all patients underwent pre-MRI1 and postchemotherapy MRI4 of the breast. Tumor was defined as voxels meeting thresholds for early percent enhancement (PEthresh) and early-to-late signal enhancement ratio (SERthresh); and FTV (PEthresh, SERthresh) by summing all voxels meeting threshold criteria and minimum connectivity requirements. Ranges of PEthresh from 50% to 220% and SERthresh from 0.0 to 2.0 were evaluated. A Cox proportional hazard model determined associations between change in FTV over treatment and RFS at different PE and SER thresholds. RESULTS: The plot of hazard ratios for change in FTV from MRI1 to MRI4 showed a broad peak with the maximum hazard ratio and highest significance occurring at PE threshold of 70% and SER threshold of 1.0 (hazard ratio = 8.71, 95% confidence interval 2.86-25.5, P < 0.00015), indicating optimal model fit. CONCLUSION: Enhancement thresholds affect the ability of MRI tumor volume to predict RFS. The value is robust over a wide range of thresholds, supporting the use of FTV as a biomarker.

Screening mammography: does ethnicity influence patient preferences for higher recall rates given the potential for earlier detection of breast cancer?

PURPOSE: To prospectively survey the preferences of an underserved and predominantly minority population of women regarding their understanding of screening mammography, desire for recall and early detection, and willingness to continue with annual screening mammography once given a false-positive result. MATERIALS AND METHODS: A total of 1011 women who were going to undergo mammography completed a HIPAA-compliant, Institutional Review Board-approved, validated survey in one of three languages: English, Spanish, or Haitian-Creole. Data were analyzed across three groups (ie, white, black, Hispanic) by using chi(2) analysis. RESULTS: Of 911 women included in the final analysis, 378 (41%) were white, 439 (48%) were black, and 94 (10%) were Hispanic. Income and education levels varied significantly across ethnicities (P < .0001). A higher percentage of white women (40%) correctly identified the sensitivity of mammography (P < .0001), while black (42%) and Hispanic (50%) participants thought mammography to have a higher sensitivity than it truly does. After a false-positive result, only 80% of black women and 71% of Hispanic women were likely to continue with screening in the future, compared with 93% of white women (P < .0001). Only 54% of black women and 59% of Hispanic women were willing to return for a second noninvasive procedure despite the possibility of a higher cancer detection rate, compared with 76% of white women (P < .0001). Black women (53%) were also more reluctant to be recalled for invasive studies, and Hispanic women (65%) were slightly less willing to take this risk than were white women (75%) (P < .0001). CONCLUSION: Differences in ethnic background appear to influence women's understanding of mammography, compliance with recall, and preference for early detection of breast cancer.

Use of radiologic imaging to enhance physical diagnosis instruction in the preclinical curriculum.

RATIONALE AND OBJECTIVES: To expose students in the premedical years to imaging and its indications, to enhance their understanding of pathologic processes by allowing direct visualization, and to teach physical diagnosis through an integrated, multispecialty approach. MATERIALS AND METHODS: A total of 166 second-year medical students participated in a novel imaging session that accompanied the physical diagnosis course they were concurrently enrolled in. Students were provided a didactic orientation to imaging and taught how to use Picture Archiving and Communications System software. The students then participated in interactive imaging sessions in which they were able to scroll through entire imaging cases of real, anonymized patients with accompanying clinical scenarios and physical examination findings. RESULTS: Of 89 students responding to an online curricular feedback questionnaire, 41% believed that the imaging correlated with the other information taught in the course and 46% found it was helpful to their learning. The majority of students (64%) believed that the sessions helped challenge them to think about physical diagnosis in a different way. CONCLUSION: Physical diagnosis on the wards requires a multispecialty approach and the early introduction of this technique through the integrated mode of teaching we present will benefit students in their clinical years and future careers.

Epidermal growth factor receptor - mediated signal transduction in the development and therapy of gliomas.

The epidermal growth factor receptor (EGFR) and its ligands figure prominently in the biology of gliomas, the most common tumors of the central nervous system (CNS). Although their histologic classification seems to be straightforward, these tumors constitute a heterogeneous class of related neoplasms. They are associated with a variety of molecular abnormalities affecting signal transduction, transcription factors, apoptosis, angiogensesis, and the extracellular matrix. Under normal conditions, these same interacting factors drive CNS growth and development. We are now recognizing the diverse molecular genetic heterogeneity that underlies tumors classified histologically into three distinct grades. This recognition is leading to new therapeutic strategies targeted directly at specific molecular subtypes. In this article, we will review the role of EGFR and related molecular pathways in the genesis of the normal CNS and their relationship to glial tumorigenesis. We will discuss barriers to effective treatment as they relate to anatomic specialization of the CNS. We will also consider the ways in which specific EGFR alterations common to glioma reflect outcomes following treatment with targeted therapies, all with an eye towards applying this understanding to improved patient outcomes.

Mechanisms of metastasis as related to receptor tyrosine kinases in small-cell lung cancer.

Small-cell lung cancer (SCLC) is an aggressive, malignant neoplasm with a 5-year survival of less than 10%. This poor survival rate is related to a high propensity for recurrence and a high rate of metastases. Metastases initially occur in the lymph nodes and thereafter in other organs such as the lung itself, liver, adrenal glands, brain, bone, and bone marrow. The mechanisms of metastases have been better understood recently and are described in this review. Receptor tyrosine kinases (RTKs) have been identified as important therapeutic targets in non-small-cell lung cancer (such as the EGF-receptor). We have begun to identify RTKs in SCLC and have shown that c-Kit and c-Met are expressed and functional in SCLC. RTKs have also been shown to be important in the metastasis of cancer cells. The roles of RTKs in the mechanism of metastasis are detailed in this review, with special emphasis on downstream signal transduction from RTK signaling.

Relationship of glioblastoma multiforme to the subventricular zone is associated with survival.

The subventricular zone (SVZ) lines the lateral ventricles and represents the origin of neural and some cancer stem cells. Tumors contacting the SVZ may be more invasive with higher potential to recruit migratory progenitor cells. Our specific aim was to determine whether SVZ involvement in glioblastoma multiforme (GBM) is associated with a higher recurrence rate and shorter overall survival. MR imaging and clinical data from 91 patients with GBM treated at our institution were retrospectively reviewed. Tumors were classified as type I if the contrast-enhancing lesion contacted both the SVZ and cortex on pre-operative MRI, type II if only the SVZ was involved, type III if only cortex was involved, and type IV if the lesion did not contact either the SVZ or cortex. Progression-free survival (PFS) and overall survival were estimated based on Kaplan-Meier calculations. When comparing type I tumors with types II-IV, only 39% of patients with type I tumors were free of recurrence and alive at 6 months, significantly fewer than for all other types combined (67%; P = .01). PFS at 6 months was also less, at only 47% among patients with SVZ-positive tumors, compared with 69% in the SVZ-negative group (P = .002). Patients with SVZ involvement also demonstrated a more rapid time to progression, compared with those not involving the SVZ (P = .003). Patients with GBM involving the SVZ have decreased overall survival and PFS, which may have prognostic and therapeutic implications.

Student-facilitated radiology-pathology correlation conferences: an experiential educational tool to teach multidisciplinary patient care.

PURPOSE: The aim of this study was to provide an experiential educational activity during the fourth-year radiology clerkship through a student-facilitated radiology-pathology correlation conference held as part of the radiology departmental conference to increase students' exposure to the longitudinal, multidisciplinary care of a patient and to enhance undergraduate medical education in radiology, pathology, and oncology. METHODS: During July 2006, a formal radiology-pathology correlation conference held by medical students was added to the core curriculum for residents and fellows. A total of 141 students, in groups of 3 to 5, collaborated with an attending radiologist to choose an interesting case with radiology and pathology correlation and subsequently met with a fellow or attending physician in the pathology department to review the slides and pathologic diagnosis. A 1-hour departmental conference in the fourth week of the clerkship was devoted to the students' presentations. Formal evaluation was performed from March 2007 to March 2008, through completion of an anonymized questionnaire evaluating the logistics and content of this educational activity. RESULTS: One hundred seventeen students (83%) felt that the session taught them about the longitudinal care of patients. A majority of the students, 118 (84%), preferred the student-facilitated format to a resident-run conference. In addition, 124 (88%) thought that this type of activity should continue to be part of the clerkship, and 119 (84%) thought that this type of exercise would be a valuable addition to other core clerkships. CONCLUSION: Student-facilitated radiology-pathology departmental conferences are an effective means to provide students an opportunity to integrate imaging into the longitudinal care of patients and to expose students to the multidisciplinary approach to patient care.

The Shrinking Breast: An Unusual Mammographic Finding of Invasive Lobular Carcinoma.

We report two cases of invasive lobular carcinoma of the breast that were initially missed on first mammographic interpretation because of an uncommon, easily overlooked, and unreported imaging presentation. The abnormality in the cases manifested as an apparent decrease in breast glandular tissue volume when compared with the patients' previous mammograms, observed as "shrinking" of the breast on mammography. Invasive lobular carcinoma is considered one of the most difficult subtypes of breast cancer to identify on mammography because the changes that occur are often nonspecific and subtle. Microcalcifications that are usually associated with breast masses on imaging are rarely seen in this subtype of breast cancer. Although magnetic resonance imaging and computer-aided detection have somewhat improved the detection of invasive lobular carcinoma, radiologic and clinical detection remains a challenge.