Scott D. Richard

Does Aggressive Surgery Improve Outcomes? Interaction Between Preoperative Disease Burden and Complex Surgery in Patients With Advanced-Stage Ovarian Cancer: An Analysis of GOG 182

PURPOSE To examine the effects of disease burden, complex surgery, and residual disease (RD) status on progression-free (PFS) and overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC) and complete surgical resection (R0) or < 1 cm of RD (MR) after surgical cytoreduction. PATIENTS AND METHODS Demographic, pathologic, surgical, and outcome data were collected from 2,655 patients with EOC or PPC enrolled onto the Gynecologic Oncology Group 182 study. The effects of disease distribution (disease score [DS]) and complexity of surgery (complexity score [CS]) on PFS and OS were assessed using the Kaplan-Meier method and multivariable regression analysis. RESULTS Consistent with existing literature, patients with MR had worse prognosis than R0 patients (PFS, 15 v 29 months; P < .01; OS, 41 v 77 months; P < .01). Patients with the highest preoperative disease burden (DS high) had shorter PFS (15 v 23 or 34 months; P < .01) and OS (40 v 71 or 86 months; P < .01) compared with those with DS moderate or low, respectively. This relationship was maintained in the subset of R0 patients with PFS (18.3 v 33.2 months; DS moderate or low: P < .001) and OS (50.1 v 82.8 months; DS moderate or low: P < .001). After controlling for DS, RD, an interaction term for DS/CS, performance status, age, and cell type, CS was not an independent predictor of either PFS or OS. CONCLUSION In this large multi-institutional sample, initial disease burden remained a significant prognostic indicator despite R0. Complex surgery does not seem to affect survival when accounting for other confounding influences, particularly RD.

Hyperthermic intraperitoneal chemotherapy in ovarian cancer: first report of the HYPER-O registry.

Introduction: An analysis of experience of surgical and gynecologic oncologists in the United States with the use of hyperthermic intraperitoneal chemotherapy for women with invasive epithelial ovarian cancer (EOC). Methods: An Internet-based registry (HYPER-O) collected data from collaborating institutions. Eligibility included women with EOC treated with hyperthermic intraperitoneal chemotherapy. Borderline and nonepithelial cancers were excluded. Results: As of July 1, 2008, 141 women were eligible for analysis treated at the following time points: frontline (n = 26), interval debulking (n = 19), consolidation (n = 12), and recurrence (n = 83). The mean perfusion temperatures were 38.5 to 43.6°C (median, 41.9°C) for inflow and 36.9 to 42.9°C (median, 41°C) for outflow for 30 to 120 minutes. Treatment was with a platinum agent (n = 72), mitomycin (n = 53), or a combination (n = 14). Median follow-up was 18 months (range, 0.3-140.5 months) and median overall survival 30.3 months (95% confidence interval, 23.0-37.6) with 2-, 5-, and 10-year overall survival probabilities of 49.1%, 25.4%, and 14.3%, respectively. Of the 141 patients, 110 (78%) experienced recurrence of ovarian cancer and 87 died, 3 (0.5%) dying within 30 days of surgery. In the multivariable analysis, the factors significant for increased survival were sensitivity to platinum response (P = 0.048), completeness of cytoreduction scores of 1 or 0 (P = 0.025), carboplatin alone or a combination of 2 or more chemotherapy agents used (P = 0.011), and duration of hospital stays of 10 days or less (P = 0.021). Conclusions: Hyperthermic intraperitoneal chemotherapy is a viable additional treatment option for patients with invasive EOC and may extend life in selected groups. It warrants further study in randomized controlled trials.

Three-dimensional High Dose Rate Intracavitary Image-guided Brachytherapy for the Treatment of Cervical Cancer Using a Hybrid Magnetic Resonance Imaging/Computed Tomography Approach: Feasibility and Early Results

AIMS To evaluate the feasibility and outcome of image-guided brachytherapy (IGBT) for treating cervical cancer using magnetic resonance imaging (MRI)-based planning for the first fraction followed by computed tomography (CT)-based planning for subsequent fractions. MATERIALS AND METHODS Forty-four patients with cervical cancer were treated with three-dimensional high dose rate IGBT. The brachytherapy dose was 5.0-6.0 Gy × five fractions. All but five patients received concurrent weekly cisplatinum at 40 mg/m(2). All patients received external beam radiotherapy (EBRT) with a median dose of 45Gy over 25 fractions. Total doses for the high-risk clinical target volume (HRCTV) and organs at risk, including the rectum, bladder and sigmoid, from EBRT and brachytherapy were summated and normalised to a biologically equivalent dose of 2Gy per fraction (EQD(2)). At 3 months after therapy, any early response was assessed with positron emission tomography (PET)/CT imaging. RESULTS The mean D(90) for the HRCTV was 83.3 (3.0) Gy. The mean 2 cm (3) dose to the bladder, rectum and sigmoid colon organs was 79.7 (5.1), 57.5 (4.4) and 66.8 (5.7) Gy, respectively. All but one (2.3%) patient had a complete response. Follow-up PET/CT was carried out in 41 (93.0%) patients, of whom 38 (92.5%) had a complete response. Of the 38 patients with a complete response on PET/CT, two had local recurrences at 6 and 8 months, respectively. Actuarial 2 year local control, disease-specific and overall survival rates were 88, 85 and 86%, respectively. CONCLUSION This is the first report of three-dimensional high dose rate IGBT for the treatment of cervical cancer using a hybrid MRI/CT approach. Early results have shown the feasibility of this approach with excellent local control. Additional studies are needed to assess long-term outcomes of local control and associated morbidities.

Impact of facility volume on therapy and survival for locally advanced cervical cancer

OBJECTIVE Chemosensitizing radiation with brachytherapy is standard of care for treatment of locally advanced cervical cancer, an increasingly rare disease. Treatment facility volume has been correlated with outcome in many diseases. Treatment outcome and likelihood of receiving standard therapy in locally advanced cervical cancer based on facility volume were examined using a large national cancer database. METHODS The National Cancer Data Base was queried for patients with stage IIB - IIIB cervical cancer from 1/1998 through 12/2010. Facility volumes were tallied. Overall survival was estimated using Kaplan-Meier method. Univariate and multivariable analyses were performed to determine variables affecting survival, receiving standard therapy, and total duration of radiotherapy. RESULTS We identified a total of 27,660 patients who were treated at 1361 facilities. Thirty of the facilities (2.2%) treated the highest quartile volume of patients (>9.4 patients annually) while 1072 facilities (78.8%) treated <2.4 patients annually. The median age of patients was 53, the majority were Caucasian, treated in a metropolitan area, and of squamous cell histology. Median survival of patients treated at lowest- and highest-volume centers were 42.3 months (95% CI 39.8-44.8) and 53.8 months (50.1-57.5), respectively (p < 0.001). The proportions of patients receiving brachytherapy and chemotherapy were 54.8% and 79.9%, respectively. On multivariable analysis, higher facility volume independently predicted improved survival (p = 0.022), increased likelihood of receiving brachytherapy (p < 0.0005) and chemotherapy (p = 0.013), and shorter time to radiotherapy completion (p < 0.0005). CONCLUSIONS Patients with locally advanced cervical cancer treated at high volume centers are more likely to receive standard therapy, complete therapy sooner, and experience better survival.

Completion of intraperitoneal chemotherapy in advanced ovarian cancer and catheter-related complications

OBJECTIVE Combination intravenous/intraperitoneal (IV/IP) chemotherapy has been shown in three randomized trials to be superior to IV therapy alone in the treatment of advanced ovarian cancer with respect to overall survival (OS). We sought to evaluate the effect of dose modification of IP therapy on completion rates. METHODS From November 1999 until August 2008, all optimally debulked, advanced stage ovarian cancer patients who received adjuvant IP chemotherapy at a single institution were reviewed. The primary endpoint was completion of 6 cycles of IP chemotherapy. This rate was compared to published results from GOG 172. A secondary analysis evaluated completion of chemotherapy based on IP catheter type. Statistical analysis was performed with a chi square test with a significance level of p<0.05. RESULTS One hundred and three patients received IP chemotherapy during this period. Seventy-five patients received the modified IV/IP chemotherapy regimen. Sixty-two patients (83%) completed all 6 cycles in our cohort compared to 119 patients (42%) reported in GOG 172 (p=0.0001). Fifty-five patients had a fenestrated catheter (F) and 48 had a non-fenestrated (NF) catheter. Eight patients in each cohort discontinued treatment, for a completion rate of 85.5% in NF and 82.3% in F (p=0.79). CONCLUSIONS The dose modifications utilized in this study allowed for completion of 6 cycles of adjuvant IP chemotherapy in 83% of patients. Choice of catheter type did not affect completion rates. Continued monitoring of outcomes is planned to compare PFS and OS. The high completion rate may increase acceptance of IP chemotherapy in the community setting.

Dual-console robotic surgery compared to laparoscopic surgery with respect to surgical outcomes in a gynecologic oncology fellowship program

OBJECTIVE Minimally invasive surgical techniques decrease surgical morbidity and recovery time. Studies demonstrate similar surgical outcomes comparing robotic to laparoscopic surgery. These studies have not accounted for the incorporation of fellow education. With the dual-console da Vinci Si Surgical System®, a two surgeon approach could be performed. We sought to compare surgical outcomes at a gynecologic oncology fellowship program of traditional laparoscopic to robotic surgeries using the dual-console system. METHODS We identified patients who underwent laparoscopic or robotic surgery performed by a gynecologic oncologist from November 2009-November 2010. Robotic surgeries were conducted using the dual-console, utilizing a two surgeon approach. Surgeries involved a staff physician with a gynecologic oncology fellow. Statistical analysis was performed using student t-test and chi-squared analysis. RESULTS A total of 222 cases were identified. Cases were analyzed in groups: all cases identified, all cancer cases, and endometrial cancer cases only. When analyzing all cases, no statistical difference was noted in total operating room time (172 vs. 175 min; p=0.6), pelvic lymph nodes removed (10.1 vs. 9.6; p=0.69), para-aortic lymph nodes dissected (3.7 vs. 3.8; p=0.91), or length of stay (1.5 vs. 1.3 days; p=0.3). There was a significant difference in total surgical time (131 vs.110 min; p<0.0001) and EBL (157 vs.94 ml; p<0.0001), favoring robotic surgery. When analyzing all cancer cases, the advantage in total surgical time for robotic surgery was lost. Complications were similar between cohorts. CONCLUSION Incorporating fellow education into robotic surgery does not adversely affect outcomes when compared to traditional laparoscopic surgery.

Survival for stage IB cervical cancer with positive lymph node involvement : a comparison of completed vs. abandoned radical hysterectomy

PURPOSE Management for stage IB cervical cancer with intraoperative positive pelvic lymph nodes (LNs) is controversial. We compare 5-year survival rates for women with completed vs. abandoned radical hysterectomy (RH) who were treated with postoperative radiation therapy (RT). PATIENTS AND METHODS We identified all women diagnosed with stage IB cervical carcinoma from the Surveillance, Epidemiology, and End Results database from 1988-1998. Women with positive LN involvement who had undergone a complete pelvic and para-aortic lymphadenectomy were compared for 5-year survival based on whether a RH was completed or abandoned at the time of surgery. All women then received postoperative RT. Survival rates were calculated using the Kaplan-Meier method, and the Chi square test was used for all univariate analysis. RESULTS From a cohort of 3116 women diagnosed with stage IB cervical cancer, 265 (8.7%) had positive pelvic LNs and a complete pelvic and para-aortic lymphadenectomy. Of these women, 163 had completion of their RH while RH was abandoned in 55. Positive pelvic LNs averaged 2.58+/-2.37 in the completed RH group and 2.42+/-1.63 in the abandoned RH group. Median follow-up was 6.42 years in the completed RH group and 5.75 years in the abandoned RH group. Five-year survival for the completed RH group was 69% compared with 71% in patients with abandoned RH (p=0.46). CONCLUSIONS Treatment for patients with positive pelvic LNs at the time of RH should be determined by overall morbidity of therapy since equivalent 5-year survival was found between the completed and abandoned RH groups.

Radical hysterectomy for early stage cervical cancer: laparoscopy versus laparotomy.

Laparoscopic radical hysterectomy appears to be a feasible alternative to laparotomy for early stage cervical cancer with similar surgical outcomes and lessened morbidity.

Upper abdominal procedures in advanced stage ovarian or primary peritoneal carcinoma patients with minimal or no gross residual disease: An analysis of Gynecologic Oncology Group (GOG) 182

PURPOSE To examine the utility of upper abdominal procedures (UAPs) performed in a cohort of optimally cytoreduced patients with advanced stage epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC) and identify potential areas where aggressive surgery may impact survival. PATIENTS AND METHODS We reviewed 2655 patients enrolled in Gynecologic Oncology Group (GOG) 182 who had complete resection (CR) or minimal residual (MR) disease <1cm. Demographic, pathologic, surgical, and outcome data were collected. UAPs included diaphragm stripping or resection, liver resection, splenectomy, pancreatectomy, and porta hepatis surgery. Effect of UAP and CR on PFS/OS was assessed by Kaplan-Meier and proportional hazards methods. RESULTS Four-hundred eighty-two patients (18.1%) underwent a total of 590 UAPs. There were 351 (13.1%) diaphragm surgeries, 112 (4.2%) liver surgeries, 108 (4%) splenectomies, 12 (0.5%) pancreatectomies, and 7 (0.2%) porta hepatis surgeries. Comparing patients who did not have UAPs to patients who had UAPs, the PFS was 18.2 months (mos) and 14.8 mos (p < 0.01) and OS was 49.8 mos v. 43.7 mos (p = 0.01), respectively. However, in the multivariable analysis this survival benefit did not remain (PFS HR = 1.03, 95% CI 0.91-1.15; OS HR=0.92, 95%CI 0.81-1.04). The OS of the 141 patients who had an UAP and achieved CR compared to the 341 patients who had an UAP with MR was 54.6 compared to 40.4 mos (p=0.0005). CONCLUSIONS UAP procedures should only be performed when CR is attainable. A significant proportion of patients with MR were left with diaphragmatic disease that could potentially be completely resected.

Does the number of nodes removed impact survival in vulvar cancer patients with node-negative disease?

OBJECTIVE To determine if the extent of lymphadenectomy as determined by lymph node count from an inguinal-femoral lymph node dissection for vulvar cancer impacts overall survival (OS) and disease-specific survival (DSS) in patients with node-negative disease. METHODS Patients with stage I, II and III squamous cell carcinoma of the vulva who underwent primary inguinal-femoral nodal dissection were identified from the Surveillance, Epidemiology and End Results Program between 1988 and 2003. Patients were divided into 2 groups, those with <or=10 nodes and those with >10 nodes removed, and analyzed according to stage. All patients with histologically positive nodes were excluded. Log-rank test was done for univariate analysis. Cox regression method was used for multivariate analysis. RESULTS Squamous cell vulvar cancer was identified in 1030 patients. Statistically significant differences were seen on univariate analysis of OS between stage II and III patients with <or=10 and >10 nodes removed. The difference in 5-year DSS survival was statistically significant only for patients with stage III disease. On multivariate analysis age, stage and number of lymph nodes removed were all found to be significant variables affecting OS and DSS. CONCLUSIONS The removal of greater than 10 lymph nodes was associated with a significant improvement in DSS in patients with stage III vulvar carcinoma. This improvement in survival may be due to removal of micrometastatic disease in the inguinal lymph nodes. These data suggest that a thorough inguinal-femoral lymph node dissection should be performed in patients with advanced-stage node-negative vulvar carcinoma.