T. Tillmanns

A multi-institutional experience with robotic-assisted radical hysterectomy for early stage cervical cancer

OBJECTIVE The purpose of the study is to report a multi-institutional experience with robotic-assisted radical hysterectomy to treat patients with early stage cervical cancer with respect to perioperative outcomes. METHODS A multi-institutional robotic surgical consortium consisting of five board-certified gynecologist oncologist in distinct geographical regions of the United States was created to evaluate the utility of robotics for gynecologic surgery (benign and malignant). Between April 2003 and August 2008, a total of 835 patients underwent robotic surgery for benign gynecologic disorders and/or gynecologic malignancies by a surgeon in the consortium. IRB approval was obtained and data was collected in a prospective fashion at each institution. For the purposes of the study, a multi-institutional HIPPA compliant database was then created for all patients that underwent robotic-assisted surgery between the April 2003 and August 2008. This database was queried for all patients who underwent a robotic-assisted type II or III radical hysterectomy for Stage IA1 (+vsi)-IB2 cervical carcinoma. Forty-two patients were identified. Records were then reviewed for demographic data, medical conditions, prior abdominal or pelvic surgeries, and follow-up. The perioperative outcomes analyzed included: operative time (skin-skin), estimated blood loss (EBL), length of hospital stay, total lymph node count, conversion to laparotomy, and operative complications. RESULTS From a database of 835 patients who underwent robotic surgery by a gynecologic oncologist, a total of 42 patients who underwent a robotic-assisted type II (n=10) or type III (n=32) radical hysterectomy for early stage cervical cancer were identified. Demographic data demonstrated a median age of 41 and a median BMI of 25.1. With regard to stage, seven patients (17%) were Stage IA2, twenty-eight patients (67%) were Stage IB1 and six patients (14%) were Stage IB2. There was a single patient with Stage IA1 cervical cancer with vascular space invasion who underwent a type II radical hysterectomy. The overall median operative time was 215 min. The overall median estimated blood loss was 50 cc. No patient received a blood transfusion. The median lymph node count was 25. The median hospital stay was 1 day. Positive lymph nodes were detected in 12% of the patients. Pelvic radiotherapy or chemo-radiation was given to 14% of the patients based on final surgical pathology. Intraoperative complications occurred in 4.8% of the patients and included one conversion to laparotomy (2.4%) and one ureteral injury (2.4%). Postoperative complications were reported in 12% of the patients and included a DVT (2.4%), infection (7.2%), and bladder/urinary tract complication (2.4%) The conversion rate to laparotomy was 2.4%. CONCLUSIONS Robotic-assisted radical hysterectomy is associated with minimal blood loss, a shortened hospital stay, and few operative complications. Operative time and lymph node yields are acceptable. This data suggests that robotic-assisted radical hysterectomy may offer an alternative to traditional radical hysterectomy. This series contributes to the growing literature on robotic-assisted radical hysterectomy and prospective comparisons with traditional radical hysterectomy are needed.

A Multiinstitutional Experience With Robotic-Assisted Hysterectomy With Staging for Endometrial Cancer

OBJECTIVE: To report perioperative outcomes and learning curve characteristics from a multiinstitutional experience with robotic-assisted surgical staging for endometrial cancer. METHODS: A multiinstitutional robotic surgical consortium was created to evaluate the usefulness of robotics for gynecologic oncology surgery. An analysis of a multiinstitutional database of all patients who underwent robotic surgery for endometrial carcinoma between April 2003 and January 2009 was performed. Records were reviewed for demographic data and perioperative outcomes. Individual surgeon outcomes were analyzed as well in an attempt to evaluate characteristics of learning with incorporation of robotic technology. RESULTS: Four hundred five patients were identified who underwent robotic surgery for endometrial cancer. Mean age was 62.2 years and mean body mass index was 32.4. Fifty-five percent of patients reported a prior abdominal surgery. Final pathologic analysis demonstrated that 89.6% of all patients had stage I and II disease. Mean operative time was 170.5 minutes. Mean estimated blood loss was 87.5 mL. Mean lymph node count was 15.5. Mean hospital stay was 1.8 days. Intraoperative complications occurred in 3.5% of the patients and conversion to laparotomy occurred in 6.7%. Postoperative complications were reported in 14.6% of the patients. For the group, fewer than 10 cases were required to achieve proficiency with the procedure. CONCLUSION: Robotic technology may level the playing field between the novice and expert laparoscopist for endometrial cancer staging. Prospective trials should be undertaken to compare robotic and laparoscopic approaches to treat endometrial cancer. LEVEL OF EVIDENCE: III

Impact of individual physicians on enrollment of patients into clinical trials.

&NA; The National Cancer Institute is committed to increasing enrollment of cancer patients in clinical treatment trials. The factors that achieve successful results are poorly understood. This study analyzes the role of individual physicians in recruitment of patients in clinical trials. A retrospective review was undertaken of all patients with untreated endometrial, cervical, or ovarian cancer potentially eligible for a multi‐institutional phase III trial cared for by the Section of Gynecologic Oncology at the University of Oklahoma from July 1, 1998 to September 30, 1999. Patient variables assessed included age, insurance status, cancer diagnosis, and enrollment onto clinical trial. There was no difference in faculty patients with regard to cancer type, age, or insurance status. There was a significant difference (p < 0.01) between faculty in offering protocol therapy and likelihood of successfully enrolling patients. Successful enrollment was correlated with faculty experience and principal investigator status. This study shows that availability of patients, patient variances, support staff, and institutional commitment are secondary to individual physician factors in determining successful enrollment of patients onto clinical trials.

Use of the Female Sexual Function Index in Women with Vulvar Intraepithelial Neoplasia

The present investigation extends the validation of the Female Sexual Function Index (FSFI; Rosen et al., 2000) to include women with vulvar excisions for vulvar intraepithelial neoplasia (VIN). No instrument previously has been validated in this population. We administered the instrument to 43 women (n = 43) with VIN treated with vulvar excision and age-matched healthy controls (n = 43). We found the FSFI to have high reliability and validity in the VIN excision population. Discriminant validity and internal consistency were within acceptable ranges. Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C-30; Agronson et al., 1993) and the FSFI in this population, we found a correlation between a related construct of quality of life and sexual function.

Phase II clinical trial of bevacizumab with albumin-bound paclitaxel in patients with recurrent, platinum-resistant primary epithelial ovarian or primary peritoneal carcinoma

OBJECTIVE We examined the safety and efficacy of combining bevacizumab with albumin-bound (ab-) paclitaxel to treat patients with recurrent, platinum-resistant primary epithelial ovarian or peritoneal carcinoma. METHODS Patients had measurable disease per RECIST guidelines, progressing within 6 months after a prior course of platinum-based treatment. Patients received ab-paclitaxel 100mg/m(2) given by intravenous infusion over 30 min on days 1, 8, and 15 of a 28-day cycle with bevacizumab 10mg/kg given on days 1 and 15. RESULTS Forty-eight patients with an average 1.8 prior lines of treatment participated. The overall response rate was 50% (24/48) (95% CI, 34.8% - 65.1%), with 4 complete and 20 partial responses. Fourteen patients (29%) had stable disease, whereas eight (17%) had progressive disease, and two (4%) were not evaluable. Patients received a median of 6 treatment cycles (range, 1 - 31 cycles). The median progression-free survival was 8.08 months (95% CI, 5.78 - 10.15 months); 6 month progression-free rate was 62.5% (95% CI, 47.8%-77.2%); median overall survival was 17.15 months (95% CI, 13.57 - 23.82 months). Grade 3-4 adverse events included gastrointestinal disorders (18.8%), neutropenia (8.3%), and hypertension (6.3%). CONCLUSIONS Ab-paclitaxel with bevacizumab clearly demonstrates antitumor activity and manageable toxicity profile in patients with recurrent, platinum-resistant ovarian carcinoma. This regimen should be evaluated in a larger randomized trial.

Lymph node counts in uterine cancer: A randomized double blind trial

OBJECTIVE Higher number of lymph nodes counts may suggest a more accurate cancer staging. We wish to study whether sending lymph nodes to pathologist in four containers, instead of a single container, yields a higher nodal count. METHODS Patients with uterine cancer who underwent abdominal hysterectomy and lymphadenectomy were recruited. The right and left pelvic lymph nodes were collected from four locations (common, external and internal iliac, and obturator). Blinded randomization ex vivo allocated the side of the pelvic nodes specimen which was sent to pathology as one versus four containers. Each patient served as her own control by having the other side of her pelvic nodes sent as four different specimens. The surgeons and pathologists were blinded. RESULTS 104 consecutive patients were enrolled. The average age was 61 years old. The patients were predominately Caucasians (69%). The average total pelvic and aortic nodes per patients was 17.8. 54 patients, whose right-sided pelvic nodes were randomized to be sent in a single container, yielded an average of 7.2 right pelvic nodes versus 8.6 left pelvic nodes (p=0.026). 50 patients, whose left-sided pelvic nodes were randomized to be sent in a single container, yielded an average 8.1 right pelvic nodes versus 6.9 left pelvic nodes (p=0.042). CONCLUSION The lymph nodes count are higher when surgical nodes were sent as multiple separated instead of single specimens, regardless of the side of the pelvis.

Outpatient laparoscopic extraperitoneal aortic nodal dissection for locally advanced cervical carcinoma.

The detection of aortic nodal metastasis via radiologic methods is limited with our current technology, although improvements have been made with newer imaging techniques such as positron emission tomography (PET). Surgical staging has shown to alter radiation treatment fields up to 43% of the time in patients with negative preoperative imaging. This limitation has led some investigators to approach the detection of aortic nodal metastasis via a laparoscopic extraperitoneal surgical approach. In this article, we describe step by step our adaptation of this novel minimally invasive procedure for outpatient surgical staging of patients with locally advanced cervical cancer.

A prognostic nomogram to predict overall survival in women with recurrent ovarian cancer treated with bevacizumab and chemotherapy.

OBJECTIVE To develop a nomogram to predict overall survival (OS) in women with recurrent ovarian cancer treated with bevacizumab and chemotherapy. METHODS A multicenter retrospective study was conducted. Potential prognostic variables included age; stage; grade; histology; performance status; residual disease; presence of ascites and/or pleural effusions; number of chemotherapy regimens, treatment-free interval (TFI) prior to bevacizumab administration, and platinum sensitivity. Multivariate analysis was performed using Cox proportional hazards regression. The predictive model was developed into a nomogram to predict five-year OS. RESULTS 312 women with recurrent ovarian cancer treated with bevacizumab and chemotherapy were identified; median age was 59 (range: 19-85); 86% women had advanced stage (III-IV) disease. The majority had serous histology (74%), high grade cancers (93.5%), and optimal cytoreductions (69.5%). Fifty-one percent of women received greater than two prior chemotherapeutic regimens. TFI (AHR=0.98, 95% CI 0.97-1.00, p=0.022) was the only statistically significant predictor in a multivariate progression-free survival (PFS) analysis. In a multivariate OS analysis, prior number of chemotherapy regimens, TFI, platinum sensitivity, and presence of ascites were significant. A nomogram to predict five-year OS was constructed and internally validated (bootstrap-corrected concordance index=0.737). CONCLUSION Our multivariate model identified prior number of chemotherapy regimens, TFI, platinum sensitivity, and the presence of ascites as prognostic variables for OS in women with recurrent ovarian cancer treated with bevacizumab combined with chemotherapy. Our nomogram to predict five-year OS may be used to identify women who may benefit from bevacizumab and chemotherapy, but further validation is needed.

Comparison of bevacizumab alone or with chemotherapy in recurrent ovarian cancer patients

BACKGROUND To compare the efficacy of chemotherapy (C) combined with bevacizumab (Bev) versus Bev alone in recurrent, heavily pretreated epithelial ovarian cancer (EOC). METHODS A multicenter analysis of patients treated from 2004 to 2011 was performed. Demographic, treatment, response, and adverse event information were obtained. Progression-free (PFS) and overall survival (OS) were analyzed. RESULTS Of 277 patients (median age: 58years), the majority had Stage III and IV (86%) disease, and 72% had serous histology. 244 (88%) were treated with C+Bev and 33 (12%) with Bev. Corresponding median progression-free survival (PFS) was 8.7 and 6.7months, and median overall survival (OS) was 14.3 and 10.5months, respectively. The chemotherapeutic agents combined with Bev and the median OS include: pegylated liposomal doxorubicin (n=19, OS of 20.4months), taxanes (n=55, OS of 20.2months), gemcitabine (n=106, OS of 14.1months), topotecan (n=43, OS of 13months), and cyclophosphamide (n=21, OS of 13months). There was no significant difference in toxicities between the C+Bev vs. Bev alone group. CONCLUSION This retrospective analysis supports that combination chemotherapy and bevacizumab prolongs PFS and OS compared with bevacizumab alone.

Update on minimally invasive surgery in the management of gynecologic malignancies: focus on robotic laparoscopic systems

Laparoscopic management of gynecologic malignancies has experienced an unparalled expansion in the last 10–15 years, driven by tremendous advances in technology, medicine and surgical techniques. The best example of this comes from the adoption of robotic technology for minimally invasive procedures. These procedures and other minimally invasive laparoscopic procedures are now being explored, defi ned and are gaining wide acceptance for treatment of endometrial, cervical, and ovarian cancer treatment. When compared with standard open techniques in large studies, minimally invasive procedures seem to offer similar or improved survival with the added benefi ts of faster recovery, decreased blood loss, decreased pain, and improved quality of life. Ongoing clinical trials will undoubtedly encourage future and current laparoscopic surgeons to deploy this exciting technology to fulfi ll the surgical extirpation of malignant disease while providing patients with the most minimally invasive approach.