Faculty Bibliography

Objective: The Gynecologic Oncology Group (GOG) study 240 demonstrated a 3.5-month improvement in overall survival when bevacizumab (bev) was added to a combination chemotherapy regimen. This study established a bev-containing regimen as standard therapy for women with recurrent, persistent, or metastatic cervical cancer (CC). Gastrointestinal fistula (GIF) formation is a known complication of bev, and the long-term data of GOG 240 reported that a GIF rate of 15% in women who were treated with bev compared to 1% in the control group women. We sought to evaluate our experience with women treated with bev for CC and to identify associated risk factors for GIF formation.
Method(s): All patients who have received bev for CC from 2012 to 2018 at two academic institutions were identified, and their records were reviewed. Standard two-sided statistical analyses were performed.
Result(s): A total of 43 women were treated with a bev-containing chemotherapy regimen; among them, 34 (79.1%) were treated for CC recurrence, and the remaining were treated for metastatic disease at initial presentation or persistent disease following primary treatment. Thirty-three women (76.6%) received prior radiation therapy (RT); of these, 10 (32.3%) received external beam radiation therapy (EBRT), and 21 (67.7%) had prior EBRT and brachytherapy (BT). The median dose of bev was 15 mg/kg for both EBRT only and EBRT and BT groups. Eleven women developed GIF after bev treatment (11/43, 25.6%). All 11 (100%) had been previously treated with RT, and six (54.5%) had received EBRT plus BT. This resulted in rates of 33.3% (11/33) for GIF formation among women who received EBRT, and 28.6% (6/21) for GIF formation among women who received EBRT plus BT. The median number of bev cycles prior to GIF development was 8 (1-29), and 7 (7/11, 63.6%) received the dose of bev (15 mg/kg) as prescribed in GOG 240. See Table 1.
Conclusion(s): In our cohort of women with CC who were treated with bev, over 25% developed GIF. This is more than expected based on the 15% seen in GOG 240. Notably almost all who developed GIF had recurrent disease and were treated with prior RT. A third of women treated with RT followed by bev formed GIF, representing a considerable proportion of the cohort. GIF development and the possibility of requiring a colostomy should be a part of counseling prior to bev initiation especially in those who have had prior RT. [Figure presented]
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Objective: Cost-effective postoperative care for endometrial cancer relies on addressing complications and lowering emergency department visits and readmissions. Patients seen in the emergency department but subsequently released without hospital admission present an opportunity for cost savings. Patients seen in safety net hospitals may have less social support, leading to higher emergency department visits and readmissions. We sought to evaluate factors associated with postoperative emergency department visits following surgery for endometrial cancer.
Method(s): All patients undergoing hysterectomy for endometrial cancer by gynecologic oncologists between 2013 and 2016 at both a private and a public hospital were included in the study. Outcomes clinically associated with emergency department visits during the 30- and 60-day postoperative periods were analyzed using comparative and multivariate analyses.
Result(s): Four hundred and twelve patients were included. During the 30-day postoperative period, 38 patients were seen in the emergency department: 19 (4.6%) were readmitted to the hospital (RAH) and 19 (4.6%) patients were treated and released (TAR). During the 60-day postoperative period, 49 patients were seen in the emergency department: 26 (6.3%) were RAH and 23 (5.6%) were TAR. RAH patients had the highest number of phone calls and outpatient visits both 30 and 60 days postoperatively (Table 1). In the 30-day postoperative period, compared to patients who did not present to the emergency department, TAR patients had fewer clinic visits than RAH patients (1.33 +/- 0.03 vs 1.16 +/- 0.12, respectively). Receiving care at a private hospital was associated with decreased rates of TAR visits within 30 days (OR = 0.351, 95% CI 0.129-0.956), adjusting for number of clinic visits, home nursing services at time of discharge, and American Society of Anesthesiologists' classification system.
Conclusion(s): Readmitted patients have the highest number of phone calls and outpatient visits, which may reflect the true acuity of these patients. Patients who were TAR had a lower number of clinic visits within 30 days. These data can aid in care planning as well as cost modeling for payment models in endometrial cancer.
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Objective: Enhanced Recovery Protocols (ERPs) minimize the stress response associated with surgery, decrease postoperative opioid consumption, and reduce length of stay (LOS). However, several of the medications on standard ERPs are expensive, which may limit their availability in low-resource settings. Our gynecologic oncology service takes care of patients at both an academic tertiary care center and a safety net hospital. We sought to examine whether a modified ERP at the safety net hospital led to comparable patient outcomes when compared to a standard protocol.
Method(s): From January 2016 to June 2017, patients undergoing scheduled laparotomy by 1 team of gynecologic oncologists who cover 2 hospital networks were placed on a perioperative ERP. Hospital A is an academic medical center; hospital B is a safety net public hospital. ERP was modified at hospital B because of the high cost of several medications (Figure 1). Demographics and perioperative outcomes including LOS, complication, and readmission rates were compared.
Result(s): One hundred and four patients at hospital A and 45 patients at hospital B were included. Patients at hospital B were younger on average (49.0 +/- 13.2 years vs 55.7 +/- 14.4 years, P < 0.001), more likely to be nonwhite (93.3% vs 40.4%, P < 0.001), utilize public insurance (48.9% vs 26.0%, P < 0.001), and be unmarried (55.7% vs 33.7%, P < 0.001). There were no statistically significant differences in LOS, postoperative complications, final pathology, estimated blood loss, 30-day readmission, or 30-day complication rates. Compared to patients at hospital A, patients at hospital B were less likely to receive intraoperative transfusions (0% vs 11.5%, P = 0.018) and had fewer inpatient complications (6.7% vs 21.2%, P = 0.032)
Conclusion(s): Despite the lack of several medications, patients on a modified ERP had similar outcomes to patients on a standard ERP protocol. A lower cost ERP is feasible, effective, and may represent an opportunity for cost reduction. [Figure presented]
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Objective: Obesity is a significant risk factor for perioperative morbidity and mortality. Outcomes can be improved with standardized protocols including preventive measures and specialized surgical equipment and personnel. We sought to evaluate the outcomes of a surgical safety protocol for all patients with a body mass index (BMI) of >=40 undergoing planned gynecologic surgery.
Method(s): The high BMI pathway (HBP) was developed by a multidisciplinary team of gynecologic oncologists (GO), anesthesiologists, and ancillary surgical and nursing staff based on the most current recommendations from the literature and instituted as a quality improvement project. It was implemented for all morbidly obese patients undergoing planned surgery by a GO. Patients who underwent robotic hysterectomies (RH) on the HBP from 2016 to 2018 were compared with consecutive historical controls who had RHs from 2014 to 2015 prior to HBP implementation. Standard two-sided statistical analyses were performed.
Result(s): Of the 80 patients who successfully completed surgery on the HBP, 55 patients (68.8%) underwent RH and were included in this analysis. These patients were compared to 48 historical controls prior to HBP initiation. There were no significant differences in patient factors or perioperative times between pre- and post-HBP groups (Table 1). Since implementing HBP, there were fewer anesthesia-related complications (ARC) in HBP patients after RH compared to pre-HBP patients (0.0% vs 12.5%, P = 0.02). Among the control patients with ARC, two had respiratory distress requiring pharmacologic intervention, two had increased postoperative nausea and vomiting, and two had intractable postoperative pain. There was also an increase in same-day discharges among patients who underwent RH (65.5% vs 41.7%, P = 0.03), but no difference in hospital readmission rates. There were no differences in intraoperative and 30-day postoperative complications.
Conclusion(s): A HBP to improve perioperative safety for morbidly obese patients undergoing RH resulted in fewer ARCs and increased rates of same-day discharge without increasing perioperative times or intraoperative and postoperative complications. [Figure presented]
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Objective: Few effective treatment options exist for women with advanced or recurrent endometrial cancer (EC). To explore a modification of the standard systemic treatment for advanced or recurrent EC, we sought to determine the feasibility of completing 6 cycles of nab-paclitaxel (Nab-P) and carboplatin. Unlike paclitaxel, Nab-P does not require any steroid or other premedication, an important consideration for patients with diabetes mellitus and in the investigation of combinations with immunotherapy. We prospectively evaluated safety and efficacy of a day 1, 8-dose schedule of Nab-P in combination with carboplatin day 1 q3weeks in patients with chemotherapy naive EC.
Method(s): Patients with early-stage and high-risk, advanced primary, or recurrent EC with no prior platinum and taxane exposure were enrolled at a single institution. Patients received 6 cycles of day 1 Nab-P 100 mg/m² IV with carboplatin AUC 6 IV and day 8 Nab-P 100 mg/m² IV q21days. We evaluated percentage completion of 6 cycles with standard dose reductions, as well as toxicity per CTCAE v.4. Measurable disease was not required, and efficacy was assessed by PFS rate at 6 months.
Result(s): From 2016 to 2018, 23 subjects were enrolled; median age was 65 (43-73) years. Nineteen (82%) completed 6 cycles of the doublet therapy. Eight subjects (35%) were dose-reduced 1 level, and 5 (22%) were reduced 2 levels; only 1 subject withdrew due to toxicity. Twelve subjects (52%) had at least 1 grade 3/4 treatment-related adverse event, the most common being anemia, 6 (26%); neutropenia, 4 (17%); and diarrhea, 2 (9%). Pre-existing neuropathy was an exclusion criteria, and 13 (57%) reported at least grade 1 neuropathy with treatment. After treatment, 3 (13%) deaths occurred with 2 due to disease progression and 1 to pulmonary embolism. At 6 months after treatment initiation, 19 (83%) had no evidence of disease or its progression; 4 (17%) had progressed. Kaplan-Meier analysis revealed a 6-month PFS rate of 80.5% (95% CI 65.1%-99.7%) (Figure 1).
Conclusion(s): The Nab-P/carboplatin day 1, 8 regimen met the prespecified criteria of feasibility with acceptable toxicity and efficacy. Use of Nab-P obviates steroid premedications, ideal for immune checkpoint inhibitors that target mismatch repair deficient advanced EC. A future phase II feasibility trial combining an anti-PD-1 agent with Nab-P and carboplatin is planned. [Figure presented]
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The carboplatin/paclitaxel doublet remains the chemotherapy backbone for the initial treatment of ovarian cancer. This two-drug regimen, with carboplatin dosed using the Calvert formula, yielded convincing noninferior outcomes when compared with the prior, more toxic, regimen of cisplatin/paclitaxel. Carboplatin's dose-limiting toxicity is thrombocytopenia; however, when this drug is properly dosed and combined with paclitaxel, the doublet's cycle 1 dose in chemotherapy-naive women is generally safe. Carboplatin (unlike cisplatin) contributes minimally to the cumulative sensory neuropathy of paclitaxel, thus ensuring noticeable reversibility of neuropathy symptoms following completion of 6 cycles and only occasionally requiring cessation or substitution of the taxane. Paclitaxel is responsible for the hair loss associated with the carboplatin/paclitaxel doublet; preventive measures must be considered for patients who would otherwise refuse treatment. Several first-line phase III trials, as well as ongoing trials for which only preliminary results have been published, have fueled debates on the optimal dose and schedule; these have focused not only on weekly vs q3-weeks paclitaxel, but also on other modifications and the advisability of adding bevacizumab. Our view is that results of this doublet in the first-line treatment of ovarian cancer are driven primarily by carboplatin, given that ovarian cancer is a platinum-sensitive disease. Consequently, the roles of the accompanying paclitaxel dose and schedule and the addition of bevacizumab are currently unsettled, and questions regarding these issues should be decided based on patient tolerance and comorbidities until additional data are available.