Revathy B. Iyer

Role of Imaging in Pretreatment Evaluation of Early Invasive Cervical Cancer: Results of the Intergroup Study American College of Radiology Imaging Network 6651–Gynecologic Oncology Group 183

PURPOSE To compare magnetic resonance imaging (MRI) and computed tomography (CT) with each other and to International Federation of Gynecology and Obstetrics (FIGO) clinical staging in the pretreatment evaluation of early invasive cervical cancer, using surgicopathologic findings as the reference standard. PATIENTS AND METHODS This prospective multicenter clinical study was conducted by the American College of Radiology Imaging Network and the Gynecologic Oncology Group from March 2000 to November 2002; 25 United States health centers enrolled 208 consecutive patients with biopsy-confirmed cervical cancer of FIGO stage > or = IB who were scheduled for surgery based on clinical assessment. Patients underwent FIGO clinical staging, helical CT, and MRI. Surgicopathologic findings constituted the reference standard for statistical analysis. RESULTS Complete data were available for 172 patients; surgicopathologic findings were consistent with FIGO stages IA to IIA in 76% and stage > or = IIB in 21%. For the detection of advanced stage (> or = IIB), sensitivity was poor for FIGO clinical staging (29%), CT (42%), and MRI (53%); specificity was 99% for FIGO clinical staging, 82% for CT, and 74% for MRI; and negative predictive value was 84% for FIGO clinical staging, 84% for CT, and 85% for MRI. MRI (area under the receiver operating characteristic curve [AUC], 0.88) was significantly better than CT (AUC, 0.73) for detecting cervical tumors (P = .014). For 85% of patients, FIGO clinical staging forms were submitted after MRI and/or CT was performed. CONCLUSION CT and MRI performed similarly; both had lower staging accuracy than in prior single-institution studies. Accuracy of FIGO clinical staging was higher than previously reported. The temporal data suggest that FIGO clinical staging was influenced by CT and MRI findings.

Phase 1b-2a study to reverse platinum resistance through use of a hypomethylating agent, azacitidine, in patients with platinum-resistant or platinum-refractory epithelial ovarian cancer.

Sequential treatment with azacitidine can induce re‐expression of epigenetically silenced genes through genomic DNA hypomethylation and reverse carboplatin resistance of epithelial ovarian cancer cells. A phase 1b‐2a clinical trial of this sequential combination of azacitidine and carboplatin was initiated in patients with platinum‐resistant or platinum‐refractory epithelial ovarian cancer.

CERVIX REGRESSION AND MOTION DURING THE COURSE OF EXTERNAL BEAM CHEMORADIATION FOR CERVICAL CANCER

PURPOSE To evaluate the magnitude of cervix regression and motion during external beam chemoradiation for cervical cancer. METHODS AND MATERIALS Sixteen patients with cervical cancer underwent computed tomography scanning before, weekly during, and after conventional chemoradiation. Cervix volumes were calculated to determine the extent of cervix regression. Changes in the center of mass and perimeter of the cervix between scans were used to determine the magnitude of cervix motion. Maximum cervix position changes were calculated for each patient, and mean maximum changes were calculated for the group. RESULTS Mean cervical volumes before and after 45 Gy of external beam irradiation were 97.0 and 31.9 cc, respectively; mean volume reduction was 62.3%. Mean maximum changes in the center of mass of the cervix were 2.1, 1.6, and 0.82 cm in the superior-inferior, anterior-posterior, and right-left lateral dimensions, respectively. Mean maximum changes in the perimeter of the cervix were 2.3 and 1.3 cm in the superior and inferior, 1.7 and 1.8 cm in the anterior and posterior, and 0.76 and 0.94 cm in the right and left lateral directions, respectively. CONCLUSIONS Cervix regression and internal organ motion contribute to marked interfraction variations in the intrapelvic position of the cervical target in patients receiving chemoradiation for cervical cancer. Failure to take these variations into account during the application of highly conformal external beam radiation techniques poses a theoretical risk of underdosing the target or overdosing adjacent critical structures.

Phase 1–2 study of docetaxel plus aflibercept in patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer

BACKGROUND Biologically targeted therapies have been postulated as a viable strategy to improve outcomes for women with ovarian cancer. We assessed the safety, tolerance, pharmacokinetics, relevant circulating and image-derived biomarkers, and clinical activity of combination aflibercept and docetaxel in this population. METHODS For the phase 1 (pharmacokinetic) study, eligible patients had measurable, recurrent or persistent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma with a maximum of two prior chemotherapy regimens. Aflibercept was administered intravenously over three dose levels (2, 4, or 6 mg/kg; one dose every 21 days) to identify the maximum tolerated dose for the phase 2 study. Pharmacokinetics were assessed and dynamic imaging was done during a lead-in phase with single-agent aflibercept (cycle 0) and during combination therapy with intravenous docetaxel (75 mg/m(2)). Eligibility for the phase 2 study was the same as for phase 1. Patients were enrolled in a two-stage design and given aflibercept 6 mg/kg intravenously and docetaxel 75 mg/m(2) intravenously, every 3 weeks. The primary endpoint was objective response rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors version 1.0. The trial has completed enrolment and all patients are now off study. The trial is registered at ClinicalTrials.gov, number NCT00436501. FINDINGS From the phase 1 study, the recommended phase 2 doses of aflibercept and docetaxel were found to be 6 mg/kg and 75 mg/m(2), respectively. Log-linear pharmacokinetics (for unbound aflibercept) were observed for the three dose levels. No dose-limiting toxicities were noted. 46 evaluable patients were enrolled in the phase 2 trial; 33 were platinum resistant (15 refractory) and 13 were platinum sensitive. The confirmed ORR was 54% (25 of 46; 11 patients had a complete response and 14 had a partial response). Grade 3-4 toxicities observed in more than two patients (5%) were: neutropenia in 37 patients (80%); leucopenia in 25 patients (54%); fatigue in 23 patients (50%); dyspnoea in ten patients (22%); and stomatitis in three patients (7%). Adverse events specifically associated with aflibercept were grade 1-2 hypertension in five patients (11%), and grade 2 proteinuria in one patient (2%). INTERPRETATION Combination aflibercept plus docetaxel can be safely administered at the dose and schedule reported here, and is associated with substantial antitumour activity. These findings suggest that further clinical development of this combination in ovarian cancer is warranted. FUNDING US National Cancer Institute, US Department of Defense, Sanofi-Aventis, Gynecologic Cancer Foundation, Marcus Foundation, and the Commonwealth Foundation.

Cystic retroperitoneal lymphangioma: CT, ultrasound and MR findings

A case of cystic retroperitoneal lymphangioma complicated by hemorrhage is reported in a 7-year-old boy who presented with an abdominal mass. The mass which was partially obstructing the ureter was successfully resected. The imaging findings with emphasis on MR features are described.

Pelvic fractures after radiotherapy for cervical cancer: implications for survivors.

The incidence of pelvic fractures and associated risk factors was determined in women treated with curative‒intent radiotherapy for cervical cancer.

Utility of PET/CT in Differentiating Benign from Malignant Adrenal Nodules in Patients with Cancer

OBJECTIVE The purpose of this retrospective study was to determine the sensitivity and specificity of combined PET/CT in differentiating benign from malignant adrenal nodules measuring at least 1 cm in diameter in patients with cancer. MATERIALS AND METHODS We reviewed the radiology reports and images of patients with known malignant disease who had undergone PET/CT for cancer staging or surveillance and who had adrenal nodules at least 1 cm in diameter. We identified 112 adrenal nodules in 96 patients. Two-dimensional PET had been performed 1 hour after administration of (18)F-FDG. Unenhanced CT was performed for attenuation correction, to determine lesion size, and for coregistration with PET data. Adrenal nodules were considered to have a positive PET result if the average standardized uptake value was greater than that of the liver. Follow-up data and biopsy reports were used to determine the pathologic status of the adrenal nodules. RESULTS Thirty adrenal lesions were malignant. Twenty-five of the 30 malignant nodules had positive PET results. Twelve of 82 benign nodules were PET positive with a sensitivity of 83.3% and specificity of 85.4%. Patients with four of five malignant nodules with negative PET results had received previous therapy. The positive predictive value for detection of malignant lesions was 67%, and the negative predictive value was 93%. CONCLUSION Adrenal masses that are not FDG avid are likely to be benign with a high negative predictive value. Especially in patients undergoing therapy, however, there is a small but statistically significant false-negative rate. A considerable proportion of benign nodules have increased FDG activity.

The quality of cervical cancer brachytherapy implantation and the impact on local recurrence and disease-free survival in Radiation Therapy Oncology Group prospective trials 0116 and 0128

Purpose The objective of the study was to determine the impact of brachytherapy implant quality on outcome among cervical cancer patients treated on Radiation Therapy Oncology Group prospective trials 0116 and 0128. Methods All enrolled patients received concurrent chemoradiation followed by brachytherapy. Individual brachytherapy parameters, including the symmetry of ovoids in relation to the tandem, displacement of ovoids in relation to the cervical os, tandem bisecting the ovoids, tandem in the midpelvis, and appropriateness of packing, were scored for each implant. Multivariate Cox proportional hazards models were constructed for each parameter for local recurrence (LR), regional recurrence, distant recurrence, disease-free survival (DFS), and overall survival. Results Records for 103 patients were analyzed. The median follow-up time was 24.5 months. Patients with unacceptable symmetry of ovoids to the tandem had a significantly higher risk of LR than patients in the acceptable group (hazard ratio [HR], 2.67; 95% confidence interval [CI], 1.11–6.45; P = 0.03). Patients with displacement of ovoids in relation to the cervical os had a significantly increased risk of LR (HR, 2.50; 95% CI, 1.05–5.93; P = 0.04) and a lower DFS rate (HR, 2.28; 95% CI, 1.18–4.41; P = 0.01). Inappropriate placement of packing resulted in a lower DFS rate (HR, 2.06; 95% CI, 1.08–3.92; P = 0.03). Conclusions Assessment of the quality of a brachytherapy implant is imperative, as proper placement has an impact on patient DFS. If feasible, inappropriate placements should be corrected before treatment initiation. Brachytherapy applicators for cervical cancer should preferably be placed and assessed by experienced practitioners.

Ability of integrated positron emission and computed tomography to detect significant colonic pathology: the experience of a tertiary cancer center.

The ability of integrated positron emission tomography and computed axial tomography (PET‐CT) to detect colonic pathology is not fully defined. The purpose of this study was to assess the ability of PET‐CT to detect colonic pathology and to determine the significance of (18F)2‐fluoro‐2‐deoxyglucose (18F‐FDG) activity noted incidentally in the colon on PET‐CT.

Clinical utility of positron emission tomography/computed tomography in the evaluation of suspected recurrent ovarian cancer in the setting of normal CA-125 levels

Objectives: This study was conducted to estimate the accuracy of [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) as compared with contrast-enhanced CT (CECT) in detecting cancer in patients who have normal cancer antigen (CA)-125 (<35 U/dL) but are suspected of having a recurrent disease based on clinical symptoms. Methods: We retrospectively reviewed the records of patients who had undergone primary cytoreductive surgery and subsequently underwent CECT and FDG-PET/CT for suspected recurrence. [18F]-fluorodeoxyglucose positron emission tomography/computed tomography and CECT interpretation to evaluate a recurrent disease was carried out independently by 2 experienced radiologists who were blinded to the final diagnosis for the suspected recurrence. Long-term follow-up imaging (12 months) and biopsy reports were used to assess the true status of the suspected recurrence seen on FDG-PET/CT or CECT. Sensitivity and specificity of all modalities were estimated. McNemar test was used to compare pairs of modalities. All tests were 2-sided, and P ≤ 0.05 was considered statistically significant. Results: Sixty-six patients met the eligibility criteria for inclusion in our analysis. Fifty-eight percent (18/31) and 54% (17/31) of the patients with normal CA-125 levels had evidence of a recurrent disease on FDG-PET/CT and CECT, respectively. Thirty-one percent (6/19) of the patients with no indication of cancer on CECT had evidence of disease on FDG-PET/CT images, which was supported by pathological proof. Conclusion: [18F]-Fluorodeoxyglucose positron emission tomography/computed tomography is capable of detecting ovarian cancer recurrence in symptomatic patients with normal CA-125 levels and, in this setting, has slightly better sensitivity than CECT and can be considered as the frontline modality for all such patients.