Longitudinal Changes in Bone Mineral Measurements Inside and Outside Radiation Fields Used for Cervical Cancer Treatment.

PURPOSE: We compared the magnitude of changes in bone mineral density (BMD), within and outside the radiation field, among women who received pelvic radiation therapy (RT) with or without chemotherapy for cervical cancer. METHODS AND MATERIALS: In this secondary analysis of a prospective study, we analyzed serial computed tomography scans and dual-energy x-ray absorptiometry scans from 78 patients who received definitive RT or chemoradiation therapy (CRT) for cervical cancer at a single institution from 2008 to 2015. BMD values at L1, L2, L3, and L4 were measured. We compared changes in BMD within the radiation field (ie, at L4) with those outside the field (ie, at L1). Linear mixed models were also used to examine the effect of RT on changes in BMD over time and covariate adjustment. RESULTS: The median age of the 78 patients was 45.5 years (range, 23-88 years); all received RT and 76 (97%) received concurrent CRT. Treatment was associated with significant declines in BMD in all 4 lumbar vertebral bodies over time (P < .05), with nadir at 3 months for L4 and at 1 year for L1. Pairwise comparisons at 3 months and 2 years after treatment indicated that BMD in L4 (within the RT field) had improved (P = .037), but BMD in L1 (outside the RT field) was no different at 3 months and 2 years. CONCLUSIONS: Significant BMD declines were observed in all lumbar vertebral bodies immediately after RT. However, in-field vertebral bodies reached nadir BMD earlier than those located outside the RT field. Our results suggest that treatment and patient-related factors other than RT may contribute to declines in BMD after treatment for cervical cancer. Routine bone density screening and post-RT therapy with hormones may be beneficial for selected patients who receive CRT for cervical cancer.

Comprehensive review of imaging features of sex cord-stromal tumors of the ovary.

Sex cord-stromal tumors of the ovary (SCST) are uncommon ovarian tumors arising from sex cord and/or stromal cells of the ovaries. They may be nonfunctional and asymptomatic or functional presenting with hyperestrogenic, hyperandrogenic or cushingoid symptoms. They present in a wide age group of women, mostly in early stages and follow a nonaggressive clinical course after surgical resection. They differ from more prevalent epithelial ovarian tumors which tend to present in older women in advanced stages with poor prognosis. Some of SCSTs are associated with clinical syndromes. We will review imaging features on ultrasound, computed tomography and magnetic resonance imaging, epidemiology and clinical presentations of these tumors.

Pelvic fractures and changes in bone mineral density after radiotherapy for cervical, endometrial, and vaginal cancer: A prospective study of 239 women.

BACKGROUND: Advances in radiotherapy (RT) have led to improved oncologic outcomes for women with gynecologic cancers; however, the long-term effects and survivorship implications need further evaluation. The purpose of this study was to determine the incidence of pelvic fractures and changes in bone mineral density (BMD) after pelvic RT. METHODS: Two hundred thirty-nine women who had pelvic RT for cervical, endometrial, or vaginal cancer between 2008 and 2015 were prospectively studied. BMD scans and biomarkers of bone turnover were obtained at the baseline and 3 months, 1 year, and 2 years after RT. Imaging studies were assessed for pelvic fractures for up to 5 years. Patients with osteopenia, osteoporosis, or pelvic fractures at any point were referred to the endocrinology service for evaluation and treatment. RESULTS: The median age at diagnosis was 51 years; 132 patients (56%) were menopausal. The primary diagnoses were cervical (63.6%), endometrial (30.5%), and vaginal cancer (5.9%). Sixteen patients (7.8%; 95% confidence interval, 4.5%-12.4%) had pelvic fractures with actuarial rates of 3.6%, 12.7%, and 15.7% at 1, 2, and 3 years, respectively. Fractures were associated with baseline osteoporosis (P < .001), higher baseline bone-specific alkaline phosphatase (P < .001), and older age (P = .007). The proportion of patients with osteopenia/osteoporosis increased from 50% at the baseline to 58%, 59%, and 70% at 3 months, 1 year, and 2 years, respectively. CONCLUSIONS: A high proportion of women had significant decreases in BMD after pelvic RT, with 7.8% diagnosed with a pelvic fracture. BMD screening and pharmacologic intervention should be strongly considered for these high-risk women.

Patterns of treatment failure in patients undergoing adjuvant or definitive radiotherapy for vulvar cancer.

OBJECTIVES: Knowledge of the detailed pattern of failure can be useful background knowledge in clinical decision making and potentially drive the development of new treatment strategies by increasing radiotherapy dose prescription to high-risk sub-regions of the target. Here, we analyze patterns of recurrence in patients with vulvar cancer treated with radiotherapy according to original planning target volumes and radiation dose delivered. METHODS: We analyzed dose-planning and post-treatment recurrence scans from patients with vulvar cancer treated at two institutions from January 2009 through October 2014. We delineated the recurrences and merged the dose-planning and recurrence scans for each patient by using deformable co-registration. We estimated the center of each recurrence on the merged scans with the goal of relating them to the original dose plan. RESULTS: We evaluated 157 patients who received radiotherapy for vulvar cancer. Median age was 68 years (range 29-91). Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA-IVB were included. Twenty-nine patients had recurrent disease; 156 patients had squamous cell carcinoma and one patient had adenosquamous carcinoma of the vulva. Among the 157 patients, 37 patients with recurrent disease had recurrence scans available for review, for a total of 80 recurrence sites; 53% of the recurrences were located in the region to which the highest dose (60-70 Gy) had been prescribed. Patients who received definitive radiotherapy developed failure primarily in the high-dose region (80.5%), whereas patients who received adjuvant radiotherapy had a more scattered failure pattern (p<0.0001). Among the latter group, 29.5% failed in the high-dose region. CONCLUSIONS: Patients who received definitive versus adjuvant radiotherapy had different failure patterns, indicating that separate approaches are needed to improve both adjuvant and definitive radiotherapy for vulvar cancer.

[18F]-2-Fluoro-2-Deoxy-D-glucose-PET Assessment of Cervical Cancer.

This article provides an overview of PET in cervical cancer, primarily with regard to the use of 18F-2-fluoro-2-deoxy-d-glucose-PET/computed tomography. A brief discussion of upcoming technologies, such as PET/MR imaging, is presented.

A multicenter assessment of the ability of preoperative computed tomography scan and CA-125 to predict gross residual disease at primary debulking for advanced epithelial ovarian cancer.

OBJECTIVE: To assess the ability of preoperative computed tomography scan and CA-125 to predict gross residual disease (RD) at primary cytoreduction in advanced ovarian cancer. METHODS: A prospective, non-randomized, multicenter trial of patients who underwent primary debulking for stage III-IV epithelial ovarian cancer previously identified 9 criteria associated with suboptimal (>1cm residual) cytoreduction. This is a secondary post-hoc analysis looking at the ability to predict any RD. Four clinical and 18 radiologic criteria were assessed, and a multivariate model predictive of RD was developed. RESULTS: From 7/2001-12/2012, 350 patients met eligibility criteria. The complete gross resection rate was 33%. On multivariate analysis, 3 clinical and 8 radiologic criteria were significantly associated with the presence of any RD: age≥60years (OR=1.5); CA-125≥600U/mL (OR=1.3); ASA 3-4 (OR=1.6); lesions in the root of the superior mesenteric artery (OR=4.1), splenic hilum/ligaments (OR=1.4), lesser sac >1cm (OR=2.2), gastrohepatic ligament/porta hepatis (OR=1.4), gallbladder fossa/intersegmental fissure (OR=2); suprarenal retroperitoneal lymph nodes (OR=1.3); small bowel adhesions/thickening (OR=1.1); and moderate-severe ascites (OR=2.2). All ORs were significant with p<0.01. A 'predictive score' was assigned to each criterion based on its multivariate OR, and the rate of having any RD for patients who had a total score of 0-2, 3-5, 6-8, and ≥9 was 45%, 68%, 87%, and 96%, respectively. CONCLUSIONS: We identified 11 criteria associated with RD, and developed a predictive model in which the rate of having any RD was directly proportional to a predictive score. This model may be helpful in treatment planning.

Potential Application of Dual-Energy CT in Gynecologic Cancer: Initial Experience.

OBJECTIVE: The purpose of this article is to review the use of dual-energy CT (DECT) in the assessment of gynecologic cancer. CONCLUSION: DECT has the potential to improve diagnostic performance, may improve the ability to differentiate between simple cystic lesions and primary ovarian cancer, and may also improve the detection of musculoskeletal and liver metastases. Additional studies will be needed to determine the direction of future developments and the degree to which DECT will affect the imaging and management of gynecologic cancer.

Ovarian Cancer, the Revised FIGO Staging System, and the Role of Imaging.

OBJECTIVE: It is now recognized that ovarian cancer includes a heterogeneous group of malignant epithelial tumors originating from the ovaries, fallopian tubes, or peritoneum. This development has prompted the International Federation of Gynecology and Obstetrics (FIGO) to issue a revised staging system that can provide prognostic information and guidance on personalized management of ovarian cancer. CONCLUSION: We review the epidemiology of ovarian cancer, the new FIGO staging system, and the role of imaging in the assessment, staging, and follow-up of ovarian cancer.

Survival outcomes for patients with stage IVB vulvar cancer with grossly positive pelvic lymph nodes: time to reconsider the FIGO staging system?

OBJECTIVE: To evaluate treatment outcomes for patients with vulvar cancer with grossly positive pelvic lymph nodes (PLNs). METHODS: From a database of 516 patients with vulvar cancer, we identified patients with grossly positive PLNs without distant metastasis at initial diagnosis. We identified 20 patients with grossly positive PLNs; inclusion criteria included PLN 1.5cm or larger in short axis dimension on CT/MRI (n=11), FDG-avid PLN on PET/CT (n=3), or biopsy-proven PLN disease (n=6). Ten patients were treated with chemoradiation therapy (CRT), 4 with RT alone, and 6 with various combinations of surgery, RT or CRT. Median follow-up time for patients who had not died of cancer was 47months (range, 4-228months). RESULTS: Mean primary vulvar tumor size was 6.4cm; 12 patients presented with 2009 AJCC T2 and 8 with T3 disease. All patients had grossly positive inguinal nodes, and the mean inguinal nodal diameter was 2.8cm. The 5-year overall survival and disease specific survival rates were 43% and 48%, respectively. Eleven patients had recurrences, some at multiple sites. There were 9 recurrences in the vulva, but no isolated nodal recurrences. Four patients developed distant metastasis within 6months of starting radiation therapy. CONCLUSIONS: Aggressive locoregional treatment can lead to favorable outcomes for many patients with grossly involved PLNs that is comparable to that of grossly involved inguinal nodes only. We recommend modification of the FIGO stage IVB classification to more accurately reflect the relatively favorable prognosis of patients with PLN involvement.

CT colonography for the detection of nonpolypoid adenomas: sensitivity assessed with restricted national CT colonography trial criteria.

OBJECTIVE: The purpose of this study was to determine the prevalence of nonpolypoid adenomas and the sensitivity of CT colonography (CTC) in their detection by use of the restricted criteria of height-to-width ratio<50% and height elevation≤3 mm. MATERIALS AND METHODS: In the National CT Colonography Trial (American College of Radiology Imaging Network protocol 6664), a cohort of 2531 participants without symptoms underwent CTC and screening colonoscopy. The CTC examinations were interpreted with both 2D and 3D techniques. Nonpolypoid adenomatous polyps identified with CTC or colonoscopy were retrospectively reviewed to determine which polyps met the restricted criteria. The prevalence of nonpolypoid adenomas and the prospective sensitivity of CTC were determined. Descriptive statistics were used to report the prevalence, size, and histologic features. The sensitivities (with 95% CIs) for nonpolypoid and polypoid lesions were compared by two-sided Z test for independent binomial proportions. RESULTS: The retrospective review confirmed 21 nonpolypoid adenomas, yielding a prevalence of 0.83% (21 of 2531 participants). Eight (38.1%) were advanced adenomas, many (50% [4/8]) only because of large size (≥10 mm). The overall per polyp sensitivity of CTC (combined 2D and 3D interpretation) for detecting nonpolypoid adenomas≥5 mm (n=21) was 0.76; ≥6 mm (n=16), 0.75; and ≥10 mm (n=5), 0.80. These values were not statistically different from the sensitivity of detecting polypoid adenomas (p>0.37). CONCLUSION: In this large screening population, nonpolypoid adenomas had a very low prevalence (<1%), and advanced pathologic features were uncommon in polyps<10 mm in diameter. Most nonpolypoid adenomas are technically visible at CTC. The prospective sensitivity is similar to that for polypoid adenomas when the interpretation combines both 2D and 3D review.

A multicenter prospective trial evaluating the ability of preoperative computed tomography scan and serum CA-125 to predict suboptimal cytoreduction at primary debulking surgery for advanced ovarian, fallopian tube, and peritoneal cancer.

OBJECTIVE: To assess the ability of preoperative computed tomography (CT) scan of the abdomen/pelvis and serum CA-125 to predict suboptimal (>1cm residual disease) primary cytoreduction in advanced ovarian, fallopian tube, and peritoneal cancer. METHODS: This was a prospective, non-randomized, multicenter trial of patients who underwent primary cytoreduction for stage III-IV ovarian, fallopian tube, and peritoneal cancer. A CT scan of the abdomen/pelvis and serum CA-125 were obtained within 35 and 14 days before surgery, respectively. Four clinical and 20 radiologic criteria were assessed. RESULTS: From 7/2001 to 12/2012, 669 patients were enrolled; 350 met eligibility criteria. The optimal debulking rate was 75%. On multivariate analysis, three clinical and six radiologic criteria were significantly associated with suboptimal debulking: age ≥ 60 years (p=0.01); CA-125 ≥ 500 U/mL (p<0.001); ASA 3-4 (p<0.001); suprarenal retroperitoneal lymph nodes >1cm (p<0.001); diffuse small bowel adhesions/thickening (p<0.001); and lesions >1cm in the small bowel mesentery (p=0.03), root of the superior mesenteric artery (p=0.003), perisplenic area (p<0.001), and lesser sac (p<0.001). A 'predictive value score' was assigned for each criterion, and the suboptimal debulking rates of patients who had a total score of 0, 1-2, 3-4, 5-6, 7-8, and ≥ 9 were 5%, 10%, 17%, 34%, 52%, and 74%, respectively. A prognostic model combining these nine factors had a predictive accuracy of 0.758. CONCLUSIONS: We identified nine criteria associated with suboptimal cytoreduction, and developed a predictive model in which the suboptimal rate was directly proportional to a predictive value score. These results may be helpful in pretreatment patient assessment.

Anatomic distribution of fluorodeoxyglucose-avid para-aortic lymph nodes in patients with cervical cancer.

PURPOSE: Conformal treatment of para-aortic lymph nodes (PAN) in cervical cancer allows dose escalation and reduces normal tissue toxicity. Currently, data documenting the precise location of involved PAN are lacking. We define the spatial distribution of this high-risk nodal volume by analyzing fluorodeoxyglucose (FDG)-avid lymph nodes (LNs) on positron emission tomography/computed tomography (PET/CT) scans in patients with cervical cancer. METHODS AND MATERIALS: We identified 72 PANs on pretreatment PET/CT of 30 patients with newly diagnosed stage IB-IVA cervical cancer treated with definitive chemoradiation. LNs were classified as left-lateral para-aortic (LPA), aortocaval (AC), or right paracaval (RPC). Distances from the LN center to the closest vessel and adjacent vertebral body were calculated. Using deformable image registration, nodes were mapped to a template computed tomogram to provide a visual impression of nodal frequencies and anatomic distribution. RESULTS: We identified 72 PET-positive para-aortic lymph nodes (37 LPA, 32 AC, 3 RPC). All RPC lymph nodes were in the inferior third of the para-aortic region. The mean distance from aorta for all lymph nodes was 8.3 mm (range, 3-17 mm), and from the inferior vena cava was 5.6 mm (range, 2-10 mm). Of the 72 lymph nodes, 60% were in the inferior third, 36% were in the middle third, and 4% were in the upper third of the para-aortic region. In all, 29 of 30 patients also had FDG-avid pelvic lymph nodes. CONCLUSIONS: A total of 96% of PET positive nodes were adjacent to the aorta; PET positive nodes to the right of the IVC were rare and were all located distally, within 3 cm of the aortic bifurcation. Our findings suggest that circumferential margins around the vessels do not accurately define the nodal region at risk. Instead, the anatomical extent of the nodal basin should be contoured on each axial image to provide optimal coverage of the para-aortic nodal compartment.

Anatomic distribution of [(18)F] fluorodeoxyglucose-avid lymph nodes in patients with cervical cancer.

PURPOSE: Current information about the anatomic distribution of lymph node (LN) metastases from cervical cancer is not precise enough for optimal treatment planning for highly conformal radiation therapy. To accurately define the anatomic distribution of these LN metastases, we mapped [(18)F] fluorodeoxyglucose positron emission tomography (FDG PET)-positive LNs from 50 women with cervical cancer. METHODS AND MATERIALS: Records of patients with cervical cancer treated from 2006 to 2010 who had pretreatment PET/computed tomography (CT) scans available were retrospectively reviewed. Forty-one consecutive patients (group 1) with FDG-avid LNs were identified; because there were few positive paraortic LNs in group 1, 9 additional patients (group 2) with positive paraortic LNs were added. Involved LNs were contoured on individual PET/CT images, mapped to a template CT scan by deformable image registration, and edited as necessary by a diagnostic radiologist and radiation oncologists to most accurately represent the location on the original PET/CT scan. RESULTS: We identified 190 FDG-avid LNs, 122 in group 1 and 68 in group 2. The highest concentrations of FDG-avid nodes were in the external iliac, common iliac, and paraortic regions. The anatomic distribution of the 122 positive LNs in group 1 was as follows: external iliac, 78 (63.9%); common iliac, 21 (17.2%); paraortic, 9 (7.4%); internal iliac, 8 (6.6%); presacral, 2 (1.6%); perirectal, 2 (1.6%); and medial inguinal, 2 (1.6%). Twelve pelvic LNs were not fully covered when the clinical target volume was defined according to Radiation Therapy Oncology Group guidelines for intensity modulated radiation therapy for cervical cancer. CONCLUSIONS: Our findings clarify nodal volumes at risk and can be used to improve target definition in conformal radiation therapy for cervical cancer. Our findings suggest several areas that may not be adequately covered by contours described in available atlases.

Early postoperative CT as a prognostic biomarker in patients with advanced ovarian, tubal, and primary peritoneal cancer deemed optimally debulked at primary cytoreductive surgery.

OBJECTIVE: The purpose of this article is to determine whether early postoperative CT provides prognostic information in patients with advanced ovarian, tubal, or primary peritoneal carcinoma with optimal debulking reported at primary cytoreduction. MATERIALS AND METHODS: Our study included 63 patients who underwent primary cytoreductive surgery for presumed advanced ovarian cancer, who had optimal debulking (residual disease ≤ 1 cm) reported at surgery, and who underwent CT before and 7-49 days after surgery. Two radiologists independently retrospectively interpreted all postoperative CT scans and scored lesions on a 5-point scale, where 1 indicates normal and 5 indicates definitely malignant. Lesions larger than 1 cm with a CT score of 4 or 5 were considered suboptimally debulked residual disease. RESULTS: Suboptimally debulked residual disease on CT (range, 1.1-5.8 cm) was reported by reader 1 for 29 of 63 patients (46%) and by reader 2 for 31 of 63 patients (49%), with substantial interobserver agreement (κ = 0.75). Patients with suboptimally debulked residual disease on CT had significantly worse median progression-free survival (p = 0.001, both readers) and overall survival (p ≤ 0.010, both readers). By univariate and multivariate analyses, suboptimally debulked residual disease on CT remained a significant independent predictor of progression-free survival (p = 0.001, both readers) and overall survival (p ≤ 0.006, both readers). CONCLUSION: Our study showed that residual disease larger than 1 cm was present on early postoperative CT in almost half of the patients deemed to have optimally debulked disease at primary cytoreduction. Residual disease larger than 1 cm detected on early postoperative CT was associated with significant decreases in both progression-free and overall survival.

Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or peritoneum.

OBJECTIVE: To determine whether hormonal therapies have efficacy in patients with recurrent low-grade serous carcinoma of the ovary or peritoneum. METHODS: We searched departmental databases for patients with histologically-confirmed, evaluable, recurrent low-grade serous ovarian or peritoneal carcinoma who received hormonal therapy at our institution between 1989 and 2009. We retrospectively reviewed patients' medical records for demographic, disease, hormonal therapy, and estrogen receptor and progesterone receptor expression data. We used the Response Evaluation Criteria in Solid Tumors version 1.1 to determine patients' responses to hormonal therapy. Because patients could have received more than one evaluable hormonal therapy regimen, we chose to define the outcome metric as "patient-regimens." Median time to disease progression (TTP) and overall survival (OS) were also calculated. Regression analysis was also performed. RESULTS: We identified 64 patients with recurrent low-grade serous carcinoma of the ovary or peritoneum. Patients' median TTP and median OS were 7.4 and 78.2 months, respectively. Patients received 89 separate hormonal patient-regimens, which produced an overall response rate of 9% (6 complete responses and 2 partial responses). Sixty-one percent of the patient-regimens resulted in a progression-free survival duration of at least 6 months. Patient-regimens involving ER+/PR+ disease produced a longer median TTP (8.9 months) than patient-regimens involving ER+/PR- disease did (6.2 months; p=0.053). This difference approached but did not reach statistical significance. CONCLUSIONS: Hormonal therapies have moderate anti-tumor activity in patients with recurrent low-grade serous carcinoma of the ovary or peritoneum. Further study to determine whether ER/PR expression status is a predictive biomarker for this rare cancer subtype is warranted.

The National CT Colonography Trial: assessment of accuracy in participants 65 years of age and older.

PURPOSE: To conduct post-hoc analysis of National CT Colonography Trial data and compare the sensitivity and specificity of computed tomographic (CT) colonography in participants younger than 65 years with those in participants aged 65 years and older. MATERIALS AND METHODS: Of 2600 asymptomatic participants recruited at 15 centers for the trial, 497 were 65 years of age or older. Approval of this HIPAA-compliant study was obtained from the institutional review board of each site, and informed consent was obtained from each subject. Radiologists certified in CT colonography reported lesions 5 mm in diameter or larger. Screening detection of large (≥10-mm) histologically confirmed colorectal neoplasia was the primary end point; screening detection of smaller (6-9-mm) colorectal neoplasia was a secondary end point. The differences in sensitivity and specificity of CT colonography in the two age cohorts (age < 65 years and age ≥ 65 years) were estimated with bootstrap confidence intervals (CIs). RESULTS: Complete data were available for 477 participants 65 years of age or older (among 2531 evaluable participants). Prevalence of adenomas 1 cm or larger for the older participants versus the younger participants was 6.9% (33 of 477) versus 3.7% (76 of 2054) (P < .004). For large neoplasms, mean estimates for CT colonography sensitivity and specificity among the older cohort were 0.82 (95% CI: 0.644, 0.944) and 0.83 (95% CI: 0.779, 0.883), respectively. For large neoplasms in the younger group, CT colonography sensitivity and specificity were 0.92 (95% CI: 0.837, 0.967) and 0.86 (95% CI: 0.816, 0.899), respectively. Per-polyp sensitivity for large neoplasms for the older and younger populations was 0.75 (95% CI: 0.578, 0.869) and 0.84 (95% CI: 0.717, 0.924), respectively. For the older and younger groups, per-participant sensitivity was 0.72 (95% CI: 0.565, 0.854) and 0.81 (95% CI: 0.745, 0.882) for detecting adenomas 6 mm in diameter or larger. CONCLUSION: For most measures of diagnostic performance and in most subsets, the difference between senior-aged participants and those younger than 65 years was not statistically significant.

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.

National CT colonography trial (ACRIN 6664): comparison of three full-laxative bowel preparations in more than 2500 average-risk patients.

OBJECTIVE: The purpose of our study was to compare the effect of three different full-laxative bowel preparations on patient compliance, residual stool and fluid, reader confidence, and polyp detection at CT colonography (CTC). SUBJECTS AND METHODS: A total of 2531 patients underwent CTC followed by colonoscopy for the American College of Radiology Imaging Network (ACRIN) National CTC Trial. Of this total, 2525 patients used one of three bowel preparations with bisacodyl tablets and stool and fluid tagging: 4 L of polyethylene glycol (PEG); 90 mL of phosphosoda; or 300 mL of magnesium citrate. Patients reported percent compliance with the bowel preparation and radiologists graded each CTC examination for the amount of residual fluid and stool on a scale from 1 (none) to 4 (nondiagnostic). Reader confidence for true-positive findings was reported on a 5-point scale: 1 (low) to 5 (high). Sensitivity and specificity for detecting polyps ≥ 6 mm and ≥ 1 cm compared with colonoscopy were calculated for each preparation. RESULTS: The most commonly prescribed preparation was phosphosoda (n = 1403) followed by PEG (n = 1020) and magnesium citrate (n = 102). Phosphosoda had the highest patient compliance (p = 0.01), least residual stool (p < 0.001), and highest reader confidence versus PEG for examinations with polyps (p = 0.06). Magnesium citrate had significantly more residual fluid compared with PEG and phosphosoda (p = 0.006). The sensitivity and specificity for detecting colon polyps ≥ 6 mm and ≥ 1 cm did not differ significantly between preparations. CONCLUSION: Polyp detection was comparable for all three preparations, although phosphosoda had significantly higher patient compliance and the least residual stool.

ACRIN CT colonography trial: does reader's preference for primary two-dimensional versus primary three-dimensional interpretation affect performance?

PURPOSE: To determine whether the reader's preference for a primary two-dimensional (2D) or three-dimensional (3D) computed tomographic (CT) colonographic interpretation method affects performance when using each technique. MATERIALS AND METHODS: In this institutional review board-approved, HIPAA-compliant study, images from 2531 CT colonographic examinations were interpreted by 15 trained radiologists by using colonoscopy as a reference standard. Through a survey at study start, study end, and 6-month intervals, readers were asked whether their interpretive preference in clinical practice was to perform a primary 2D, primary 3D, or both 2D and 3D interpretation. Readers were randomly assigned a primary interpretation method (2D or 3D) for each CT colonographic examination. Sensitivity and specificity of each method (primary 2D or 3D), for detecting polyps of 10 mm or larger and 6 mm or larger, based on interpretive preference were estimated by using resampling methods. RESULTS: Little change was observed in readers' preferences when comparing them at study start and study end, respectively, as follows: primary 2D (eight and seven readers), primary 3D (one and two readers), and both 2D and 3D (six and six readers). Sensitivity and specificity, respectively, for identifying examinations with polyps of 10 mm or larger for readers with a primary 2D preference (n = 1128 examinations) were 0.84 and 0.86, which was not significantly different from 0.84 and 0.83 for readers who preferred 2D and 3D (n = 1025 examinations) or from 0.76 and 0.82 for readers with a primary 3D preference (n = 378 examinations). When performance by using the assigned 2D or 3D method was evaluated on the basis of 2D or 3D preference, there was no difference among those readers by using their preferred versus not preferred method of interpretation. Similarly, no significant difference among readers or preferences was seen when performance was evaluated for detection of polyps of 6 mm or larger. CONCLUSION: The reader's preference for interpretive method had no effect on CT colonographic performance.

Multidetector computed tomography follow-up of hypoattenuating small liver lesions in patients with rectal cancer.

OBJECTIVE: To study the behavior of hypoattenuating liver lesions, deemed too small to characterize at baseline scanning with multidetector computed tomography (CT), in patients with rectal cancer. METHODS: Retrospective review of locally advanced rectal cancer patients from a radiation oncology therapy database was conducted. Patients who presented before neoadjuvant chemoradiation without metastases at baseline CT and with follow-up scans for at least 1 year after therapy were evaluated. CT studies were reviewed for the presence and change in size of hypoattenuating liver lesions (<15 mm) at baseline and follow-up. RESULTS: A total of 616 consecutive patients from the radiotherapy database were reviewed. Of these, 70 patients with a total of 163 hepatic lesions met the selection criteria. The mean patient age was 62.4 years (range, 26-85 years). All patients subsequently underwent surgery and adjuvant chemotherapy. The mean time of radiographic imaging from baseline CT to most recent surveillance CT was 3.3 years (range, 1.1-7.4 years). Two radiologists independently reviewed the CTs. The lesions were stable in 56 of 70 (80.0%, 95% confidence interval: 69%, 89%) patients. Of 163 lesions, 148 (90.8%) were stable, 8 (4.9%) regressed, and 7 (4.3%) progressed in size. No significant difference in results was found for patients stratified according to T-stage (P = 0.41) and N-stage (P > 0.99). CONCLUSION: In patients with rectal cancer, majority of small hypoattenuating liver lesions remain stable and are treated as benign lesions, at multidetector CT follow-up of more than a year. Nevertheless, hepatic lesion stability during systemic therapy should still be interpreted with caution and closely followed for at least 1 year after completion of therapy.