Cytokines, GM-CSF and IFNγ administered by priming and post-chemotherapy cycling in recurrent ovarian cancer patients receiving carboplatin

BACKGROUND: Monocyte/macrophages (MO/MA), a polymorphic population of innate immune cells, have the potential to mediate antitumor effects, and may also contribute to protumor effects. A priming and post-chemotherapy schedule of the myeloid cell mobilizing and immune stimulatory growth factor, granulocyte monocyte stimulating factor (GM-CSF, Leukine(®)) and the MO/MA activating cytokine recombinant interferon gamma 1b (rIFN-γ1b, Actimmune(®)) has been developed. The pre- and post-chemotherapy design is based upon known in vivo kinetics and immune modulatory effects of these molecules. Carboplatin (Paraplatin(®)) was selected as the cornerstone of treatment of epithelial ovarian cancer (EOC). METHODS: We studied hematopoietic and immunologic effects of GM-CSF and rIFN-γ1b before and after carboplatin in patients with recurrent EOC. Potentially chemotherapy-sensitive patients with recurrent measurable tumors received subcutaneous GM-CSF (starting at 400 μg/day) for 7 days plus subcutaneous rIFN-γ1b (100 μg) on days 5 and 7, before and after intravenous carboplatin (area under the curve of 5). We performed standard hematologic assessment and monitored monocyte (MO), dendritic cell, major cell subset counts, and antibody-dependent cell-mediated cytotoxicity (ADCC) against a Her2neu(+ )tumor cell line, as well as selected plasma inflammatory cytokine, chemokine and growth factor levels. RESULTS: Our analysis comprised only the first 3 months of treatment in the initial 25 patients. Relative to pretreatment baseline values, white blood cell, neutrophil, MO, and eosinophil counts increased (P ≤ .001 for each); the proportion of platelets increased 9 days after the second (P ≤ .002) and third (P ≤ .04) carboplatin treatments; and the number of cells in the activated MO subsets CD14+HLA-DR+, CD14+CD64+, and CD14(+)CXCR3(+ )increased (P ≤ .04 for each); plasma levels of the proangiogenic interleukins 1α, 6, and 8 were lower (P ≤ .03 for each); M-CSF, a product of activated MO/MA, was increased on day 9 (P = .007); and GM-CSF was increased in plasma after GM-CSF administration (P ≤ .04). Quality of life measurements were reduced during the GM-CSF/IFN-γ1b cycle while recovering at pre-chemotherapy baseline for FACT-G scores only. CONCLUSION: A novel regimen of GM-CSF plus IFN-γ1b administered to 25 EOC patients receiving carboplatin increased myeloid cells, platelets and total activated MO populations during the initial 3 months; however, ADCC responses were not consistently enhanced during this period

Accuracy of CT Colonography for Detection of Large Adenomas and Cancers

Background Computed tomographic (CT) colonography is a noninvasive option in screening for colorectal cancer. However, its accuracy as a screening tool in asymptomatic adults has not been well defined. Methods We recruited 2600 asymptomatic study participants, 50 years of age or older, at 15 study centers. CT colonographic images were acquired with the use of standard bowel preparation, stool and fluid tagging, mechanical insufflation, and multidetector-row CT scanners (with 16 or more rows). Radiologists trained in CT colonography reported all lesions measuring 5 mm or more in diameter. Optical colonoscopy and histologic review were performed according to established clinical protocols at each center and served as the reference standard. The primary end point was detection by CT colonography of histologically confirmed large adenomas and adenocarcinomas (10 mm in diameter or larger) that had been detected by colonoscopy; detection of smaller colorectal lesions (6 to 9 mm in diameter) was also evaluated. Results Complete data were available for 2531 participants (97%). For large adenomas and cancers, the mean (±SE) per-patient estimates of the sensitivity, specificity, positive and negative predictive values, and area under the receiver-operating-characteristic curve for CT colonography were 0.90±0.03, 0.86±0.02, 0.23±0.02, 0.99± Conclusions In this study of asymptomatic adults, CT colonographic screening identified 90% of subjects with adenomas or cancers measuring 10 mm or more in diameter. These findings augment published data on the role of CT colonography in screening patients with an average risk of colorectal cancer. (ClinicalTrials.gov number, NCT00084929; American College of Radiology Imaging Network [ACRIN] number, 6664.

PET/CT imaging in the diagnosis, staging, and follow-up of colorectal cancer

Colorectal cancer is a common malignancy that afflicts many in the western world. Imaging studies are frequently used to evaluate patients in the screening, staging and surveillance of colorectal cancer. Cross sectional imaging studies such as ultrasound, computed tomography and magnetic resonance imaging provide anatomic and morphologic information about tumor and patterns of spread. Positron emission tomography (PET) differs in that it provides information about tumor metabolism.[18F]Fluorodeoxyglucose PET has been clinically used for the evaluation of patients with a wide variety of cancers since most malignancies, including colorectal cancer, typically show increased glucose metabolism. This review present the positron emission tomography/computed tomography imaging findings that may be encountered in the diagnosis, staging and follow-up of patients with colorectal cancer

PET/CT and hepatic radiation injury in esophageal cancer patients

This paper evaluates the imaging appearance of radiation injury in the liver on positron emission tomography (PET)/computed tomography (CT) in patients with distal esophageal cancer who underwent pre-operative chemoradiation therapy. Twenty-six patients with distal esophageal cancer who received chemoradiotherapy before esophagectomy were included. All patients had baseline and follow-up PET/CT. Fluorodeoxyglucose (FDG) uptake in both left and right lobes of the liver was evaluated. CT findings suggesting radiation damage were documented. Abnormal FDG uptake in the liver was observed in 5 (19%) patients after therapy. These abnormalities were in the left lobe (12%) and right lobe (12%) of the liver. In the irradiated left lobe, FDG uptake increased focally greater than 50% over baseline in two patients (54% and 133%); in one of these patients, biopsy confirmed radiation injury. In the non-irradiated right lobe, standard uptake values (SUV) increased diffusely in two different patients. In one patient, SUV decreased by at least 50% in both the right and left lobes. In the remaining patients, there were no significant changes in FDG uptake. Atrophy and attenuation changes of irradiated liver on CT were found in 15 (58%) patients. In patients receiving chemoradiotherapy, PET/CT may identify metabolic abnormalities in irradiated liver. Such abnormalities should be correlated with other imaging, clinical and laboratory findings to avoid confusion with hepatic metastases