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Seminars in Diagnostic Pathology May 2018The identification of at-risk kindreds facilitates screening and risk reduction strategies for patients with hereditary cancer predisposition syndromes. Recently,... (Review)
Review
The identification of at-risk kindreds facilitates screening and risk reduction strategies for patients with hereditary cancer predisposition syndromes. Recently, immunohistochemistry (IHC) has emerged as a cost-effective strategy for detecting or inferring the presence of mutations in both tumors and the germline of patients presenting with tumors associated with hereditary cancer predisposition syndromes. In this review we discuss the use of novel IHC markers, including PRKAR1A, β-catenin, SDHB, fumarate hydratase and 2SC, HRASQ61R, BAP1, parafibromin and glucagon, which have either established applications or show promise for surgical pathologists to complement morphological or clinical suspicion of hereditary cancer predisposition syndromes. Specifically, we focus on Carney complex, familial adenomatous polyposis (FAP)-associated cribriform-morular variant of papillary thyroid carcinoma, familial succinate dehydrogenase-related pheochromocytoma/paraganglioma syndromes, hereditary leiomyomatosis and renal cell cancer (HLRCC), medullary thyroid cancer and Multiple Endocrine Neoplasia 2 (MEN2), BAP1 hereditary cancer predisposition syndrome, Hyperparathyroidism-Jaw Tumor Syndrome (HPT-JT), and Pancreatic Neuroendocrine Tumor Syndrome (Mahvash disease).
Topics: Biomarkers, Tumor; DNA Mutational Analysis; Genetic Predisposition to Disease; Genetic Testing; Heredity; High-Throughput Screening Assays; Humans; Immunohistochemistry; Mutation; Neoplastic Syndromes, Hereditary; Pathology, Molecular; Pedigree; Phenotype; Predictive Value of Tests; Risk Assessment; Risk Factors
PubMed: 28662997
DOI: 10.1053/j.semdp.2017.05.004 -
European Radiology Nov 2017To determine the clinical relevance of incidentally-found hypervascular micronodules (IHM) on cone-beam computed tomography angiography (CBCTA) in patients with liver...
PURPOSE
To determine the clinical relevance of incidentally-found hypervascular micronodules (IHM) on cone-beam computed tomography angiography (CBCTA) in patients with liver metastasis undergoing transarterial (chemo)embolization (TACE/TAE).
MATERIAL AND METHODS
This was a HIPAA-compliant institutional review board-approved single-institution retrospective review of 95 non-cirrhotic patients (52 men; mean age, 60 years) who underwent CBCTA prior to (chemo)embolic delivery. IHM were defined by the presence of innumerable subcentimetre hepatic parenchymal hypevascular foci not detected on pre-TACE/TAE contrast-enhanced cross-sectional imaging. Multivariate analysis was performed to compare time to tumour progression (TTP) between patients with and without IHM.
RESULTS
IHM were present in 21 (22%) patients. Patients with IHM had a significantly shorter intrahepatic TTP determined by a higher frequency of developing new liver metastasis (hazard ratio [HR]: 1.99; 95% confidence interval [CI] 1.08-3.67, P= 0.02). Patients with IHM trended towards a shorter TTP of the tumour(s) treated with TACE/TAE (HR: 1.72; 95% CI: 0.98-3.01, P= 0.056). Extrahepatic TTP was not significantly different between the two cohorts (P= 0.27).
CONCLUSION
Patients with IHM on CBCTA have worse prognosis due to a significantly higher risk of developing new hepatic tumours. Further work is needed to elucidate its underlying mechanisms of pathogenesis.
KEY POINTS
• 21% of liver metastasis patients undergoing TACE/TAE have IHM on CBTA. • IHM are associated with a high risk of developing new hepatic tumours. • IHA are also associated with a trend toward poorer response to TACE/TAE.
Topics: Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Computed Tomography Angiography; Cone-Beam Computed Tomography; Female; Humans; Liver Neoplasms; Male; Middle Aged; Prognosis; Proportional Hazards Models; Retrospective Studies
PubMed: 28484824
DOI: 10.1007/s00330-017-4847-3 -
The Lancet. Oncology Apr 2017Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for...
BACKGROUND
Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA.
METHODS
We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA. We enrolled patients with treatment-refractory metastatic SCCA, who were given nivolumab every 2 weeks (3 mg/kg). The primary endpoint was response according to Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. At the time of data cutoff, the study was ongoing, with patients continuing to receive treatment. The study is registered with ClinicalTrials.gov, number NCT02314169.
RESULTS
We screened 39 patients, of whom 37 were enrolled and received at least one dose of nivolumab. Among the 37 patients, nine (24% [95% CI 15-33]) had responses. There were two complete responses and seven partial responses. Grade 3 adverse events were anaemia (n=2), fatigue (n=1), rash (n=1), and hypothyroidism (n=1). No serious adverse events were reported.
INTERPRETATION
To our knowledge, this is the first completed phase 2 trial of immunotherapy for SCCA. Nivolumab is well tolerated and effective as a monotherapy for patients with metastatic SCCA. Immune checkpoint blockade appears to be a promising approach for patients with this orphan disease.
FUNDING
National Cancer Institute/Cancer Therapy Evaluation Program, the HPV and Anal Cancer Foundation, the E B Anal Cancer Fund, The University of Texas MD Anderson Moon Shots Program, and an anonymous philanthropic donor.
Topics: Aged; Antibodies, Monoclonal; Antineoplastic Agents; Anus Neoplasms; Carcinoma, Squamous Cell; Case-Control Studies; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Nivolumab; Prognosis; Prospective Studies; Response Evaluation Criteria in Solid Tumors; Salvage Therapy; Survival Rate
PubMed: 28223062
DOI: 10.1016/S1470-2045(17)30104-3 -
Journal of Hepatocellular Carcinoma 2016Hepatocellular carcinoma (HCC) is the fifth most frequently occurring cancer globally and predominantly develops in the setting of various grades of underlying chronic... (Review)
Review
Hepatocellular carcinoma (HCC) is the fifth most frequently occurring cancer globally and predominantly develops in the setting of various grades of underlying chronic liver disease, which affects management decisions. Image-guided percutaneous ablative or transarterial therapies have acquired wide acceptance in HCC management as a single treatment modality or combined with other treatment options in patients who are not amenable for surgery. Recently, such treatment modalities have also been used for bridging or downsizing before definitive treatment (ie, surgical resection or liver transplantation). This review focuses on the use of minimally invasive image-guided locoregional therapies for HCC. Additionally, it highlights recent advancements in imaging and catheter technology, embolic materials, chemotherapeutic agents, and delivery techniques; all lead to improved patient outcomes, thereby increasing the interest in these invasive techniques.
PubMed: 27785450
DOI: 10.2147/JHC.S92732 -
Journal of Hepatocellular Carcinoma 2016The safety and efficacy of the combined use of sorafenib and yttrium-90 resin microspheres (Y90 RMS) to treat advanced hepatocellular carcinoma (HCC) is not well...
PURPOSE
The safety and efficacy of the combined use of sorafenib and yttrium-90 resin microspheres (Y90 RMS) to treat advanced hepatocellular carcinoma (HCC) is not well established. We determined the incidence of adverse events with this combination therapy in patients with advanced HCC at our institution and analyzed the treatment and survival outcomes.
MATERIALS AND METHODS
We reviewed the records of 19 patients with Barcelona Clinic Liver Cancer class B or C HCC who underwent treatment with Y90 RMS (for 21 sessions) while receiving full or reduced doses of sorafenib between January 2008 and May 2010. Therapy response was evaluated using Response Evaluation Criteria in Solid Tumors. We evaluated median overall survival (OS) and progression-free survival (PFS) as well as hepatic and extrahepatic disease PFS and incidence of adverse events.
RESULTS
The median patient age was 67 years, and portal or hepatic venous invasion was present in eight patients (42%). Ten patients received reduced doses of sorafenib. The median Y90 radiation activity delivered was 41.2 mCi. The partial response of Response Evaluation Criteria in Solid Tumors was observed in four patients (19%). The median hepatic disease PFS was 7.82 months, extrahepatic disease PFS was 8.94 months, OS was 19.52 months, and PFS was 6.63 months. Ninety days after treatment with Y90 RMS, five patients (26%) had grade II adverse events and four patients (21%) had grade III adverse events.
CONCLUSION
OS and PFS outcomes were superior to those observed in prior studies evaluating sorafenib alone in patients with a similar disease status, warranting further study of this treatment combination.
PubMed: 27574586
DOI: 10.2147/JHC.S62261 -
Journal of Gastrointestinal Surgery :... Jun 2016The risk of colorectal liver metastases (CLM) disappearing on cross-sectional imaging has increased with advances in preoperative chemotherapy, but <50 % of...
BACKGROUND
The risk of colorectal liver metastases (CLM) disappearing on cross-sectional imaging has increased with advances in preoperative chemotherapy, but <50 % of disappearing CLM demonstrate complete pathological response.
OBJECTIVE
The aim of this study was to evaluate the role of fiducial marker placement before potentially curative treatment of CLM at risk of disappearing with chemotherapy.
METHODS
All consecutive patients who underwent fiducial placement for tracking of CLM at a tertiary center were reviewed.
RESULTS
Among 1377 patients undergoing CLM resection between 2005 and 2015, 35 patients underwent fiducial placement. Three patients were excluded due to disease progression. The study population comprised 32 patients who underwent fiducial placement in 41 CLM. Among the 41 marked CLM, 34 (83 %) were located >10 mm deep in the liver parenchyma, 25 (61 %) were in the right liver, and median size was 12 mm (range, 6-20 mm). No complication occurred after fiducial placement. After chemotherapy, 19 (46 %) of the 41 marked metastases disappeared on cross-sectional imaging. All fiducial-tracked CLM were treated with resection (n = 31) or ablation (n = 10). After median follow-up of 14 months (range, 0-64 months), no local recurrences were observed.
CONCLUSION
Fiducial placement represents a safe procedure that facilitates accurate localization for resection or ablation of small CLM at risk of disappearing with chemotherapy.
Topics: Antineoplastic Agents; Chemotherapy, Adjuvant; Colorectal Neoplasms; Fiducial Markers; Follow-Up Studies; Hepatectomy; Humans; Liver Neoplasms; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Retrospective Studies; Treatment Outcome
PubMed: 26791387
DOI: 10.1007/s11605-016-3079-1