Fluorescent humanized anti-CEA antibody specifically labels metastatic pancreatic cancer in a patient-derived orthotopic xenograft (PDOX) mouse model.

Pancreatic cancer is a highly lethal disease in part due to incomplete tumor resection. Targeting by tumor-specific antibodies conjugated with a fluorescent label can result in selective labeling of cancer in vivo for surgical navigation. In the present study, we describe a patient-derived orthotopic xenograft model of pancreatic cancer that recapitulated the disease on a gross and microscopic level, along with physiologic clinical manifestations. We additionally show that the use of an anti-CEA antibody conjugated to the near-infrared (NIR) fluorescent dye, IRDye800CW, can selectively highlight the pancreatic cancer and its metastases in this model with a tumor-to-background ratio of 3.5 (SEM 0.9). The present results demonstrate the clinical potential of this labeling technique for fluorescence-guided surgery of pancreatic cancer

Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer.

Background:Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer. Methods:The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Rao's quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. Results:A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P < .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio [HR] = 1.98, 95% confidence interval [CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI = 1.18 to 4.99). Conclusions:Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors

Fluorescent humanized anti-CEA antibody specifically labels metastatic pancreatic cancer in a patient-derived orthotopic xenograft (PDOX) mouse model.

Pancreatic cancer is a highly lethal disease in part due to incomplete tumor resection. Targeting by tumor-specific antibodies conjugated with a fluorescent label can result in selective labeling of cancer in vivo for surgical navigation. In the present study, we describe a patient-derived orthotopic xenograft model of pancreatic cancer that recapitulated the disease on a gross and microscopic level, along with physiologic clinical manifestations. We additionally show that the use of an anti-CEA antibody conjugated to the near-infrared (NIR) fluorescent dye, IRDye800CW, can selectively highlight the pancreatic cancer and its metastases in this model with a tumor-to-background ratio of 3.5 (SEM 0.9). The present results demonstrate the clinical potential of this labeling technique for fluorescence-guided surgery of pancreatic cancer

Molecular Tumor Board: The University of California San Diego Moores Cancer Center Experience

ObjectiveDNA sequencing tests are enabling physicians to interrogate the molecular profiles of patients' tumors, but most oncologists have not been trained in advanced genomics. We initiated a molecular tumor board to provide expert multidisciplinary input for these patients.Materials and methodsA team that included clinicians, basic scientists, geneticists, and bioinformatics/pathway scientists with expertise in various cancer types attended. Molecular tests were performed in a Clinical Laboratory Improvement Amendments environment.ResultsPatients (n = 34, since December 2012) had received a median of three prior therapies. The median time from physician order to receipt of molecular diagnostic test results was 27 days (range: 14-77 days). Patients had a median of 4 molecular abnormalities (range: 1-14 abnormalities) found by next-generation sequencing (182- or 236-gene panels). Seventy-four genes were involved, with 123 distinct abnormalities. Importantly, no two patients had the same aberrations, and 107 distinct abnormalities were seen only once. Among the 11 evaluable patients whose treatment had been informed by molecular diagnostics, 3 achieved partial responses (progression-free survival of 3.4 months, ≥6.5 months, and 7.6 months). The most common reasons for being unable to act on the molecular diagnostic results were that patients were ineligible for or could not travel to an appropriately targeted clinical trial and/or that insurance would not cover the cognate agents.ConclusionGenomic sequencing is revealing complex molecular profiles that differ by patient. Multidisciplinary molecular tumor boards may help optimize management. Barriers to personalized therapy include access to appropriately targeted drugs

Molecular Tumor Board: The University of California San Diego Moores Cancer Center Experience

OBJECTIVE. DNA sequencing tests are enabling physicians to interrogate the molecular profiles of patients’ tumors, but most oncologists have not been trained in advanced genomics. We initiated a molecular tumor board to provide expert multidisciplinary input for these patients. MATERIALS AND METHODS. A team that included clinicians, basic scientists, geneticists, and bioinformatics/pathway scientists with expertise in various cancer types attended. Molecular tests were performed in a Clinical Laboratory Improvement Amendments environment. RESULTS. Patients (n = 34, since December 2012) had received a median of three prior therapies. The median time from physician order to receipt of molecular diagnostic test results was 27 days (range: 14–77 days). Patients had a median of 4 molecular abnormalities (range: 1–14 abnormalities) found by next-generation sequencing (182- or 236-gene panels). Seventy-four genes were involved, with 123 distinct abnormalities. Importantly, no two patients had the same aberrations, and 107 distinct abnormalities were seen only once. Among the 11 evaluable patients whose treatment had been informed by molecular diagnostics, 3 achieved partial responses (progression-free survival of 3.4 months, ≥6.5 months, and 7.6 months). The most common reasons for being unable to act on the molecular diagnostic results were that patients were ineligible for or could not travel to an appropriately targeted clinical trial and/or that insurance would not cover the cognate agents. CONCLUSION. Genomic sequencing is revealing complex molecular profiles that differ by patient. Multidisciplinary molecular tumor boards may help optimize management. Barriers to personalized therapy include access to appropriately targeted drugs

A Consensus Curriculum for Laboratory Management Training for Pathology Residents

Through the combined efforts of the American Pathology Foundation (APF), the American Society for Clinical Pathology (ASCP), and the Program Directors Section (PRODS) of the Association of Pathology Chairs (APC), a needs assessment was performed via a survey on the PRODS listserv, workshops at the APC/PRODS annual meetings in 2009 and 2010, and a Work Group of representatives of APF, ASCP, and PRODS. Residency program needs and resource constraints common to training pathology residents in practice and laboratory management were identified. In addition, a consensus curriculum for management training was created to serve as a resource for residency training program directors and others. The curriculum was converted into a wiki design tool for use by program directors, residents, and faculty