Scott R. Gerst

Prostate cancer: sextant localization at MR imaging and MR spectroscopic imaging before prostatectomy--results of ACRIN prospective multi-institutional clinicopathologic study.

PURPOSE To determine the incremental benefit of combined endorectal magnetic resonance (MR) imaging and MR spectroscopic imaging, as compared with endorectal MR imaging alone, for sextant localization of peripheral zone (PZ) prostate cancer. MATERIALS AND METHODS This prospective multicenter study, conducted by the American College of Radiology Imaging Network (ACRIN) from February 2004 to June 2005, was institutional review board approved and HIPAA compliant. Research associates were required to follow consent guidelines approved by the Office for Human Research Protection and established by the institutional review boards. One hundred thirty-four patients with biopsy-proved prostate adenocarcinoma and scheduled to undergo radical prostatectomy were recruited at seven institutions. T1-weighted, T2-weighted, and spectroscopic MR sequences were performed at 1.5 T by using a pelvic phased-array coil in combination with an endorectal coil. Eight readers independently rated the likelihood of the presence of PZ cancer in each sextant by using a five-point scale-first on MR images alone and later on combined MR-MR spectroscopic images. Areas under the receiver operating characteristic curve (AUCs) were calculated with sextant as the unit of analysis. The presence or absence of cancer at centralized histopathologic evaluation of prostate specimens was the reference standard. Reader-specific receiver operating characteristic curves for values obtained with MR imaging alone and with combined MR imaging-MR spectroscopic imaging were developed. The AUCs were estimated by using Mann-Whitney statistics and appropriate 95% confidence intervals. RESULTS Complete data were available for 110 patients (mean age, 58 years; range, 45-72 years). MR imaging alone and combined MR imaging-MR spectroscopic imaging had similar accuracy in PZ cancer localization (AUC, 0.60 vs 0.58, respectively; P > .05). AUCs for individual readers were 0.57-0.63 for MR imaging alone and 0.54-0.61 for combined MR imaging-MR spectroscopic imaging. CONCLUSION In patients who undergo radical prostatectomy, the accuracy of combined 1.5-T endorectal MR imaging-MR spectroscopic imaging for sextant localization of PZ prostate cancer is equal to that of MR imaging alone.

Phase II Study of Sunitinib in Patients With Metastatic Urothelial Cancer

PURPOSE No standard therapy exists for metastatic urothelial cancer (UC) that has progressed after initial chemotherapy. This trial was designed to assess the efficacy and tolerability of sunitinib in patients with advanced, previously treated UC. PATIENTS AND METHODS In this phase II trial, 77 patients received sunitinib between September 2006 and January 2009 on one of two schedules (50 mg per day for 4 weeks on and 2 weeks off [cohort A], 37.5 mg per day continuously [cohort B]), using a Simon 2 stage design in each cohort separately. RESULTS A partial response was seen in three of 45 patients (95% CI, 1% to 18%) in cohort A, and in one of 32 patients (95% CI, 0% to 16%) in cohort B. Clinical regression or stable disease was achieved in 33 of 77 patients (43%). Tumor regression lasted between 0.6 and 23.4 months with 29% of patients achieving response lasting longer than 3 months. The progression-free survival (2.4 v 2.3 months; P = .4) and overall survival (7.1 v 6.0 months; P = .4) were similar in both cohorts. There was one treatment-related death, and 47 patients (33 cohort A, 24 cohort B) experienced grade 3 or 4 toxicity. CONCLUSION Sunitinib did not achieve the predetermined threshold of >or= 20% activity defined by Response Evaluation Criteria in Solid Tumors. However, antitumor responses were observed, identifying the vascular endothelial growth factor axis as a viable pathway for UC treatment. The reported clinical benefit in previously treated patients warrants further investigation in a disease for which there is no US Food and Drug Administration-approved treatment.

Phase II study of everolimus in metastatic urothelial cancer

No recent advances have been made in the treatment of patients with advanced bladder cancer and, to date, targeted therapies have not resulted in an improvement in outcome. The mammalian target of rapamycin pathway has been shown to be up‐regulated in bladder cancer and represents a rational target for therapeutic intervention. In the present phase II study of everolimus, one near‐complete response, one partial response and several minor responses suggest that everolimus possesses biological activity in a subset of patients with bladder cancer. To maximize benefit from targeted agents such as everolimus, the preselection of patients based on molecular phenotype is required.

A phase II study of cetuximab/paclitaxel/carboplatin for the initial treatment of advanced-stage ovarian, primary peritoneal, or fallopian tube cancer

OBJECTIVE Determine the safety and efficacy of cetuximab plus paclitaxel and carboplatin as initial treatment of stage III/IV ovarian cancer. METHODS An initial intravenous [IV] dose of cetuximab (400 mg/m(2)) was administered over 120 min followed by weekly IV infusions of cetuximab (250 mg/m(2)) administered over 60 min. Paclitaxel (175 mg/m(2)) and carboplatin (area under the curve [AUC] of 6) were administered IV every 21 days for 6 cycles. The order of administration was cetuximab followed by paclitaxel and then carboplatin. Patients achieving a clinical complete response after 6 cycles were eligible to continue weekly cetuximab for 6 months or until toxicity or disease progression. Safety was evaluated using NCI Common Toxicity Criteria version 2.0. Progression-free survival (PFS) at 18 months was determined and compared with historical controls. RESULTS Forty-one patients were enrolled in this study; 40 received treatment and were evaluable for toxicity, and 38 were evaluable for PFS. Grade 3/4 treatment-related toxicities included febrile neutropenia (12.5%), rash (2.5%), hypersensitivity reaction (7.5%), and hypomagnesemia (12.5%). Common grade 1/2 toxicities attributed to cetuximab included acneiform rash (82.5%), hirsutism (7.5%) or abnormal hair growth (25%), and nail disorders (22.5%), which in 3 cases resulted in the patients discontinuation from the study. Median PFS was 14.4 months, and PFS at 18 months was 38.8%. CONCLUSIONS The combination of cetuximab with paclitaxel and carboplatin is adequately tolerated as primary therapy for ovarian cancer but did not demonstrate prolongation of PFS when compared to historical data.

Evaluation of Renal Masses With Contrast-Enhanced Ultrasound: Initial Experience

OBJECTIVE Nearly 25% of solid renal tumors are indolent cancer or benign and can be managed conservatively in selected patients. This prospective study was performed to determine whether preoperative IV microbubble contrast-enhanced ultrasound can be used to differentiate indolent and benign renal tumors from more aggressive clear cell carcinoma. SUBJECTS AND METHODS Thirty-four patients with renal tumors underwent preoperative gray-scale, color, power Doppler, and octafluoropropane microbubble IV contrast-enhanced ultrasound. Three blinded radiologists reading in consensus compared rate of contrast wash-in, grade and pattern of enhancement, and contrast washout compared with adjacent parenchyma. Contrast ultrasound findings were compared with surgical histopathologic findings for all patients. RESULTS The 34 patients had 23 clear cell carcinomas, three type 1 papillary carcinomas, one chromophobe carcinoma, one clear rare multilocular low-grade malignant tumor, two unclassified lesions, three oncocytomas, and one benign angiomyolipoma. The combination of heterogeneous lesion echotexture and delayed lesion washout had 85% positive predictive value, 43% negative predictive value, 48% sensitivity, and 82% specificity for predicting whether a lesion was conventional clear cell carcinoma or another tumor. Diminished lesion enhancement grade had 75% positive predictive value, 81% negative predictive value, 55% sensitivity, and 91% specificity for non-clear cell histologic features, either benign or low-grade malignant. Combining delayed washout with quantitative lesion peak intensity of at least 20% of kidney peak intensity had 91% positive predictive value, 40% negative predictive value, 63% sensitivity, and 80% specificity in the prediction of clear cell histologic features. CONCLUSION Ultrasound features of gray-scale heterogeneity, lesion washout, grade of contrast enhancement, and quantitative measure of peak intensity may be useful for differentiating clear cell carcinoma and non-clear cell renal tumors.

Implementation of Evidence-Based Guidelines for Thyroid Nodule Biopsy: A Model for Establishment of Practice Standards

OBJECTIVE Multiple studies have defined criteria for the selection of thyroid nodules for biopsy. No set of criteria is sufficiently sensitive and specific. The aim of this study is to develop a method for assessing consistency of practice in an ultrasound group and to determine whether a 5-point malignancy rating scale can be used to select patients for biopsy. MATERIALS AND METHODS One hundred one nodules (50 benign and 51 malignant) were selected from a thyroid biopsy database. Seven radiologists were educated on evidence-based criteria used to select nodules for biopsy. Using this information, readers graded the likelihood of malignancy using a 5-point malignancy rating scale, where 1 equals the lowest probability of malignancy and 5 equals the highest probability of malignancy, on the basis of overall impression of sonographic findings. Interobserver agreement on biopsy recommendation, reader sensitivity, specificity, and accuracy were determined. RESULTS The sensitivity and specificity of biopsy recommendation were 96.1% and 52%, respectively. The misclassification rate was 25.7%, and accuracy was 74.3%. Interobserver agreement on biopsy recommendation was fair to substantial (κ, 0.38-0.69). The proportion of agreement was excellent for malignant nodules (0.88-1.0). The risk of malignancy increased with increasing malignancy rating: 4.3% of nodules with a malignancy rating of 1 were malignant versus 93.4% of those assigned a rating of 5. CONCLUSION Our study illustrates a method to evaluate the standard of practice for thyroid nodule assessment among radiologists within an ultrasound group. Application of a 5-point malignancy rating scale to select nodules for biopsy is feasible and shows good diagnostic accuracy.

Phase II Study of Intraperitoneal Paclitaxel Plus Cisplatin and Intravenous Paclitaxel Plus Bevacizumab As Adjuvant Treatment of Optimal Stage II/III Epithelial Ovarian Cancer

PURPOSE Intraperitoneal (IP) cisplatin and intravenous (IV) or IP paclitaxel constitute a standard therapy for optimally debulked ovarian cancer. Bevacizumab prolongs progression-free survival (PFS) when included in first-line IV chemotherapy. In this study, the safety and feasibility of adding bevacizumab to a first-line IP regimen were assessed. PATIENTS AND METHODS Treatment was as follows: paclitaxel 135 mg/m(2) IV over 3 hours day 1, cisplatin 75 mg/m(2) IP day 2, and paclitaxel 60 mg/m(2) IP day 8. Bevacizumab 15 mg/kg IV was given after paclitaxel on day 1 beginning in cycle 2. After six cycles of chemotherapy, bevacizumab was given every 3 weeks for 17 additional treatments. The primary end point was safety and tolerability determined by whether 60% of patients completed six cycles of IV/IP chemotherapy. RESULTS Of 41 treated patients, 30 (73%) received six cycles of IV/IP chemotherapy and 35 (85%) received at least four cycles. Three (27%) of those who discontinued chemotherapy did so because of complications related to bevacizumab (hypertension, n = 2; perforation, n = 1). Grades 3 to 4 toxicities included neutropenia (34%), vasovagal syncope (10%), hypertension (7%), nausea/vomiting (7%), hypomagnesemia (7%), and abdominal pain (7%). There were three grade 3 small bowel obstructions (7%) during cycles 3, 9, and 15. One patient died following rectosigmoid anastomotic dehiscence during cycle 4. Estimated median PFS is 28.6 months (95% CI, 19.1 to 38.9 months). Three patients (7%) had IP port malfunction. CONCLUSION The addition of bevacizumab to this IP regimen is feasible; however, bevacizumab may increase the risk of bowel obstruction/perforation. The observed median PFS is similar to that seen with IP/IV chemotherapy alone.

Extended pelvic resections for recurrent or persistent uterine and cervical malignancies: An update on out of the box surgery

OBJECTIVE To update our report on the outcome of patients who underwent extended pelvic resection (EPR) for recurrent or persistent uterine and cervical malignancies. METHODS We reviewed the records of all patients who underwent EPR between 6/2000 and 07/2011. EPR was defined as an en-bloc resection of a pelvic tumor with sidewall muscle, bone, major nerve, and/or major vascular structure. Complications up to 180 days post surgery were analyzed. Survivals were estimated using the Kaplan-Meier method. RESULTS We identified 22 patients. Median age at the time of EPR was 58 years (range, 36-74). Median tumor diameter was 5.4 cm (range, 1.5-11.2). Primary tumor sites included: uterus, 13; cervix, 7; synchronous uterus/cervix, 1; and synchronous uterus/ovary, 1. The EPR structures were: muscle, 13; nerve, 10; bone, 8; vessel, 5. Complete gross resection with microscopically negative margins (R0 resection) was achieved in 17 patients (77%). There were no perioperative mortalities. Major postoperative complications occurred in 14 patients (64%). The two most common morbidities were pelvic abscesses and peripheral neuropathies. Median follow-up time was 28 months (range, 6-99). The 5-year overall survival (OS) for the entire cohort was 34% (95% CI, 13-57). For the 17 patients who had an R0 resection, the 5-year OS was 48% (95% CI, 19-73). In patients with positive pathologic margins (n=5), the 5-year OS was 0%. CONCLUSION EPR was associated with prolonged survival when an R0 resection was achieved. The high rate of postoperative complications remains a hallmark of these procedures and properly selected patients should be extensively counseled preoperatively.

Imaging Appearance of Granulomatous Disease After Intravesical Bacille Calmette-Guérin (BCG) Treatment of Bladder Carcinoma

OBJECTIVE The purpose of our study is to present the radiographic findings in a series of 16 patients with complications associated with intravesical bacille Calmette-Guérin (BCG) treatment of bladder cancer. CONCLUSION Intravesical BCG-related complications such as granulomatous disease may show imaging findings mimicking primary or metastatic tumors in patients with bladder cancer. Radiologists should consider this possibility when imaging abnormalities are encountered in bladder cancer patients treated with intravesical BCG so that appropriate management can be administered and unnecessary procedures avoided.

Anterior pelvic exenteration with total vaginectomy for recurrent or persistent genitourinary malignancies: Review of surgical technique, complications, and outcome

OBJECTIVE To describe the surgical technique, complications, and outcomes after anterior pelvic exenteration with total vaginectomy (AETV) for recurrent or persistent genitourinary malignancies. METHODS We reviewed the medical records of all patients who underwent AETV between 12/2002 and 07/2011. Relevant demographic, clinical, and pathological information was collected. Postoperative complications and rates of readmission and reoperation (up to 180 days after surgery) were examined, and preliminary survival data were obtained. RESULTS We identified 11 patients who underwent AETV. The median age at the time of the surgery was 55 years (range, 36-71). The median tumor size was 0.9 cm (range, microscopic - 4). Primary tumor sites included: cervix, 6; uterus, 3; vagina, 1; and urethra, 1. Complete surgical resection with negative pathologic margins was achieved in all 11 patients. Major postoperative complications occurred in 4 patients (36%). Six patients (55%) required readmission to the hospital. No operative mortalities were observed, and none of the patients required a re-operation. With a median follow-up after the procedure of 25 months (range, 6-95), none of the patients developed a pelvic recurrence. Ten patients (91%) were alive without evidence of disease and one patient (9%) developed a pancreatic recurrence. CONCLUSION AETV sparing the rectosigmoid and anus is feasible in highly selected patients with central pelvic recurrences. Compared to previously reported studies on total pelvic exenteration, data from this case series suggest that AETV may be associated with a lower rate of complications without compromising the oncologic outcome, while also preserving rectal function.