Marc Seltzer

Bexarotene Plus Erlotinib Suppress Lung Carcinogenesis Independent of KRAS Mutations in Two Clinical Trials and Transgenic Models

The rexinoid bexarotene represses cyclin D1 by causing its proteasomal degradation. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib represses cyclin D1 via different mechanisms. We conducted a preclinical study and 2 clinical/translational trials (a window-of-opportunity and phase II) of bexarotene plus erlotinib. The combination repressed growth and cyclin D1 expression in cyclin-E- and KRAS/p53-driven transgenic lung cancer cells. The window-of-opportunity trial in early-stage non–small-cell lung cancer (NSCLC) patients (10 evaluable), including cases with KRAS mutations, repressed cyclin D1 (in tumor biopsies and buccal swabs) and induced necrosis and inflammatory responses. The phase II trial in heavily pretreated, advanced NSCLC patients (40 evaluable; a median of two prior relapses per patient (range, 0–5); 21% with prior EGFR-inhibitor therapy) produced three major clinical responses in patients with prolonged progression-free survival (583-, 665-, and 1,460-plus days). Median overall survival was 22 weeks. Hypertriglyceridemia was associated with an increased median overall survival (P = 0.001). Early PET (positron emission tomographic) response did not reliably predict clinical response. The combination was generally well tolerated, with toxicities similar to those of the single agents. In conclusion, bexarotene plus erlotinib was active in KRAS-driven lung cancer cells, was biologically active in early-stage mutant KRAS NSCLC, and was clinically active in advanced, chemotherapy-refractory mutant KRAS tumors in this study and previous trials. Additional lung cancer therapy or prevention trials with this oral regimen are warranted. Cancer Prev Res; 4(6); 818–28. ©2011 AACR.

The spectrum of positive scan patterns in parathyroid scintigraphy.

Parathyroid scintigraphy provides the clinician treating primary hyperparathyroidism with valuable information regarding the presence and location of parathyroid adenomas. In dual-phase imaging of the parathyroid glands, a widely employed technique that exploits the radiotracer washout characteristics of parathyroid adenomas, images are typically obtained at 20 minutes after administration of the radiotracer (Tc-99m sestamibi or Tc-99m tetrofosmin) and again at 2 hours after injection. Additional imaging of the thyroid is frequently performed to localize thyroid tissue, using Tc-99m pertechnetate or iodine-123. A positive examination can display one of several different patterns; a focus of increased radiotracer activity representing a parathyroid adenoma may be detected on the initial images, on the delayed images, or both. On the thyroid scan, the parathyroid adenoma (if it is discernible) may appear as a cold defect or a persistently hot focus. In our retrospective review of 148 consecutive patients over a 2-year period, 74 examinations were positive and had pathologic confirmation. These examinations were divided into 4 patterns: I (hot focus seen on initial and delayed images, and not on thyroid scan), II (hot focus seen only in initial images), III (hot focus seen only on delayed images), and IV (hot focus seen on initial, delayed and thyroid scan images). Results were as follows: pattern I, 88% (65/74); pattern II, 7% (5/74); pattern III, 3% (2/74); and pattern IV, 3% (2/74). Parathyroid adenomas produce several different patterns on dual-phase scintigraphy. To interpret the examination correctly, it is important for the radiologist to be aware of these patterns of positivity.

Reporting Guidance for Oncologic 18F-FDG PET/CT Imaging

The written report (or its electronic counterpart) is the primary mode of communication between the physician interpreting an imaging study and the referring physician. The content of this report not only influences patient management and clinical outcomes but also serves as legal documentation of services provided and can be used to justify medical necessity, billing accuracy, and regulatory compliance. Generating a high-quality PET/CT report is perhaps more challenging than generating a report for other imaging studies because of the complexity of this hybrid imaging modality. This article discusses the essential elements of a concise and complete oncologic 18F-FDG PET/CT report and illustrates these elements through examples taken from routine clinical practice.

Negative predictive value (NPV) of FDG PET-CT for nodal disease in clinically node-negative early stage lung cancer (AJCC 7 th ed T1-2aN0) and identification of risk factors for occult nodal (pN1-N2) metastasis: implications for SBRT

Non-surgical methods are increasingly employed in the management of early stage lung cancer, but do not afford histological confirmation of nodal status. We sought to assess the incidence, pattern, and predictors of occult nodal involvement (pN1-pN2) in non-small cell lung cancer (NSCLC) patients with negative nodal uptake on fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in early stage lung cancer (clinical stage I AJCC 7 th edition). All patients treated surgically over a 3-year period at Dartmouth Hitchcock Medical Center who were AJCC 7th ed. clinical stage I by pre-operative PET-CT were included in this analysis. The agreement between the clinical stage based on PET-CT and true stage based on pathologic dissection was assessed. Multivariate logistic regression was used to analyze predictors of occult nodal metastasis. Of 144 clinically node-negative patients, 125 were pathologically nodenegative. For all 144 patients, the negative predictive values (NPVs) of PET-CT were 92% for mediastinal disease, 90% for N1 disease, and 87% for overall nodal metastases. The NPVs for mediastinal metastases were 95% in T1 disease and 87% in T2 disease. In multivariate analysis, tumor size (adjusted OR: 3.28, 95% CI: 1.41-7.57), central tumor location (adjusted OR: 7.3, 95% CI: 2.22-24.3), and age at surgery (adjusted OR: 0.95, 95% CI: 0.92-0.98) were significant predictors of occult nodal metastasis. The NPV of PET-CT in nodal staging has implications for the non-surgical treatment of lung cancer, such as stereotactic body radiotherapy, where routine pathologic nodal staging is not performed. Our data suggest PET-CT more accurately rules out the presence of nodal disease in smaller, peripherally located primary tumors.

123I MIBG appearance of severe renal artery stenosis.

We describe a patient with labile hypertension and elevated metanephrines who underwent 123Iodine metaiodobenzylguanidine (MIBG) for the detection of a possible paraganglioma. The scan revealed markedly abnormal diffusely increased activity in the right renal parenchyma. A CT angiogram showed severe renal artery stenosis of an atrophic-appearing right kidney and delayed enhancement of the right kidney, consistent with renal dysfunction due to renal artery stenosis.

Lung cancer metastasis to an adrenal myelolipoma detected by PET/CT.

Abstract: The patient is a 54-year-old woman with squamous cell lung carcinoma, diagnosed bronchoscopically at the bronchus intermedius. Initial staging F-18 fluorodeoxyglucose PET/CT revealed the hypermetabolic primary perihilar right lower lobe malignancy, and a 13-mm hypermetabolic nodule located within a 45-mm fat density structure at the expected location of the right adrenal gland. No normal-appearing adrenal gland was present. This PET/CT demonstrates metastatic squamous cell carcinoma to an adrenal myelolipoma. A CT-guided biopsy of the nodule confirmed squamous cell carcinoma. This is the patients only PET-evident site of disease beyond the primary tumor, compatible with T2N0M1 disease.

Subdiaphragmatic gallstone mimicking hepatic malignancy on FDG PET/CT.

A 70-year-old man underwent an FDG PET/CT for a possible primary liver malignancy or metastasis found on an abdominal MRI obtained as part of a workup for intermittent abdominal pain. The MRI showed an enhancing lesion at the dome of the right lobe of the liver. The lesion was FDG avid with a discrete central calcification. In conjunction with the patients history of laparoscopic cholecystectomy 1 year prior, the findings were consistent with inflammation around a migrated subdiaphragmatic gallstone. One month after the scan, a CT-guided percutaneous biopsy of this lesion revealed chronic inflammatory cells with no evidence of malignancy.

Tracheal metastasis from melanoma detected with 18F-FDG PET/CT.

A 58-year-old man with a history of stage IIIB melanoma of the right arm initially treated 4 years prior presented with new onset cough and hemoptysis. Bronchial washings were positive for melanoma. The PET/CT study showed a hypermetabolic nodule in the posterior mid-trachea. These findings indicate metastatic melanoma to the trachea. No other metastatic foci were evident. This allowed for endoscopic laser ablation of the metastatic focus.

Colon cancer metastatic to a urachus diagnosed by PET/CT.

A 50-year-old man presented with a mass in the transverse colon diagnosed by colonoscopy. He underwent a left hemicolectomy and was diagnosed with a moderately differentiated adenocarcinoma penetrating into the pericolic adipose but no lymph node metastases. His course was uneventful with enrollment in a monoclonal antibody research treatment protocol. Eight years later, he presented with hematuria. A PET/CT demonstrated a hypermetabolic right external iliac lymph node and a hypermetabolic mass within a urachal remnant. The mass was excised and pathologically proven to represent a metastasis from the original primary tumor.

Langerhans cell histiocytosis of the auditory canal detected by 18F-FDG PET/CT.

A 24-year-old woman presented with recurrent bilateral ear infections since childhood and a more recent history of partial hearing loss, discharge, and ear pain. Biopsy of the left external auditory canal revealed Langerhans cell histiocytosis. An F-FDG PET/CT was done to look for additional sites of disease. Increased metabolic activity was seen within both external ear canals.