Kara Long Roche

Predictive value of the Age-Adjusted Charlson Comorbidity Index on perioperative complications and survival in patients undergoing primary debulking surgery for advanced epithelial ovarian cancer

OBJECTIVE To assess the ability of the Age-Adjusted Charlson Comorbidity Index (ACCI) to predict perioperative complications and survival in patients undergoing primary debulking for advanced epithelial ovarian cancer (EOC). METHODS Data were analyzed for all patients with stage IIIB-IV EOC who underwent primary cytoreduction from 1/2001-1/2010 at our institution. Patients were divided into 3 groups based on an ACCI of 0-1, 2-3, and ≥4. Clinical and survival outcomes were assessed and compared. RESULTS We identified 567 patients; 199 (35%) had an ACCI of 0-1, 271 (48%) had an ACCI of 2-3, and 97 (17%) had an ACCI of ≥4. The ACCI was significantly associated with the rate of complete gross resection (0-1=44%, 2-3=32%, and ≥4=32%; p=0.02), but was not associated with the rate of minor (47% vs 47% vs 43%, p=0.84) or major (18% vs 19% vs 16%, p=0.8) complications. The ACCI was also significantly associated with progression-free (PFS) and overall survival (OS). Median PFS for patients with an ACCI of 0-1, 2-3, and ≥4 was 20.3, 16, and 15.4 months, respectively (p=0.02). Median OS for patients with an ACCI of 0-1, 2-3, and ≥4 was 65.3, 49.9, and 42.3 months, respectively (p<0.001). On multivariate analysis, the ACCI remained a significant prognostic factor for both PFS (p=0.02) and OS (p<0.001). CONCLUSIONS The ACCI was not associated with perioperative complications in patients undergoing primary cytoreduction for advanced EOC, but was a significant predictor of PFS and OS. Prospective clinical trials in ovarian cancer should consider stratifying for an age-comorbidity covariate.

Optimal primary management of bulky stage IIIC ovarian, fallopian tube and peritoneal carcinoma: Are the only options complete gross resection at primary debulking surgery or neoadjuvant chemotherapy?

OBJECTIVE To explore the impact of primary debulking surgery (PDS) to minimal but gross residual disease (RD) in women with bulky stage IIIC ovarian, fallopian tube, or primary peritoneal cancer. METHODS We retrospectively reviewed all patients with the aforementioned diagnosis who underwent PDS at our institution from 01/2001-12/2010. Those with disease of non-epithelial histology or borderline tumors were excluded. Clinicopathologic data were abstracted, and appropriate statistical tests were used. RESULTS We identified 496 eligible patients. Median age was 62years; 91% had disease of serous histology. Patients were grouped by RD status: no gross RD, 184 (37%); RD of 1-5mm, 127 (26%); RD of 6-10mm, 54 (11%); and RD >10mm, 131 (26%). With a median follow-up of 53months, the median progression-free survivals (PFS) were: 26.7, 20.7, 16.2, and 13.6months, respectively (p<0.001). The median overall survivals (OS) were 83.4, 54.5, 43.8, and 38.9months, respectively (p<0.001). Among patients with RD following PDS, those with RD of 1-10mm had improved PFS (p<0.001) and OS (p=0.001) compared with those with RD >10mm. Patients with RD 1-10mm who received intravenous/intraperitoneal (IV/IP) chemotherapy were younger and had prolonged OS compared with those solely exposed to IV chemotherapy (p<0.001 and p=0.002, respectively). CONCLUSIONS PDS to no gross RD was associated with the longest PFS and OS. However, cytoreduction to 1-10mm of RD was also associated with better survival outcomes compared with cytoreduction to >10mm of RD. We conclude that PDS remains an appropriate option for patients with a high likelihood of achieving RD 1-10mm, especially for younger patients who can receive IV/IP chemotherapy after PDS.

Risk‐reducing salpingectomy: Let us be opportunistic

Because there is no screening test for ovarian cancer, effective prevention strategies may be the best way to reduce the mortality of this most lethal gynecologic malignancy. Increasing evidence supports the hypothesis that the fallopian tube is the site of origin for the vast majority of high‐grade serous carcinomas. Our growing understanding of the pathogenesis of this disease offers a rare opportunity to explore new preventive measures, such as bilateral salpingectomy, which may provide great benefit without compromising ovarian function. If the tubal paradigm is accurate, then the impact of bilateral salpingectomy could extend to BRCA1 and BRCA2 mutation carriers, high‐risk noncarriers, and average‐risk women. The authors present a review of the literature on the role of risk‐reducing salpingectomy in all women and in high‐risk groups, with a focus on morbidity, ovarian function, potential clinical applicability, and epidemiological considerations. Cancer 2017;123:1714–1720.

Diverting ileostomy during primary debulking surgery for ovarian cancer: Associated factors and postoperative outcomes

OBJECTIVE To examine the use, as well as postoperative and long-term oncologic outcomes of diverting loop ileostomy (DI) during primary debulking surgery (PDS) for ovarian cancer. METHODS Patients with stage II-IV ovarian, fallopian tube, or primary peritoneal carcinoma who underwent colon resection during PDS from 1/2005-1/2014 were identified. Demographic and clinical data were analyzed. RESULTS Of 331 patients, 320 (97%) had stage III/IV disease and 278 (84%) had disease of high-grade serous histology. Forty-four (13%) underwent a DI. There were no significant differences in age, comorbidity index, smoking status, serum albumin, or attending surgeon between the DI and non-DI groups. Operative time (OR=1.21; 95% CI, 1.03-1.42; p=0.02) and length of rectosigmoid resection (OR=1.04; 95% CI, 1.01-1.08; p=0.02) were predictors of DI on multivariable analysis. The overall anastomotic leak rate was 6%. A comparison of groups (DI vs non-DI) showed no significant differences in major complications (30% vs 23%; p=0.41), anastomotic leak rate (5% vs 7%; p=0.60), hospital length of stay (10 vs 9days; p=0.25), readmission rate (23% vs 17%; p=0.33), or interval to postoperative chemotherapy (41 vs 40days; p=0.20), respectively. Ileostomy reversal was successful in 89% of patients. Median follow-up was 52.6months. There were no differences in median progression-free (17.9 vs 18.6months; p=0.88) and overall survival (48.7 vs 63.8months; p=0.25) between the groups. CONCLUSIONS In patients undergoing PDS, those with longer operative time and greater length of rectosigmoid resection more commonly underwent DI. DI does not appear to compromise postoperative outcomes or long-term survival.

A comparison of primary intraperitoneal chemotherapy to consolidation intraperitoneal chemotherapy in optimally resected advanced ovarian cancer.

OBJECTIVE To compare survival outcomes for patients with advanced epithelial ovarian cancer (EOC) who received primary intravenous/intraperitoneal (IV/IP) chemotherapy to those who received IV followed by consolidation (treatment given to patients in remission) IP chemotherapy. METHODS Data were analyzed and compared for all patients with stage III-IV EOC who underwent optimal primary cytoreduction (residual disease ≤ 1 cm) followed by cisplatin-based consolidation IP chemotherapy (1/2001-12/2005) or primary IV/IP chemotherapy (1/2005-7/2011). RESULTS We identified 224 patients; 62 (28%) received IV followed by consolidation IP chemotherapy and 162 (72%) received primary IV/IP chemotherapy. The primary IP group had significantly more patients with serous tumors. The consolidation IP group had a significantly greater median preoperative platelet count, CA-125, and amount of ascites. There were no differences in residual disease at the end of cytoreduction between both groups. The median progression-free survival (PFS) was greater for the primary IP group; however, this did not reach statistical significance (23.7 months vs 19.7 months; HR 0.78; 95% CI, 0.57-1.06; p=0.11). The median overall survival (OS) was significantly greater for the primary IP group (78.8 months vs 57.5 months; HR 0.56; 95% CI, 0.38-0.83; p=0.004). On multivariate analysis, after adjusting for confounders, the difference in PFS was not significant (HR 0.78; 95% CI, 0.56-1.11; p=0.17), while the difference in OS remained significant (HR 0.59; 95% CI, 0.39-0.89; p=0.01). CONCLUSIONS In our study, primary IV/IP chemotherapy was associated with improved OS compared to IV followed by consolidation IP chemotherapy in patients with optimally cytoreduced advanced EOC.

Feasibility, safety and clinical outcomes of cardiophrenic lymph node resection in advanced ovarian cancer

OBJECTIVES Surgical resection of enlarged cardiophrenic lymph nodes (CPLNs) in primary treatment of advanced ovarian cancer has not been widely studied. We report on a cohort of patients undergoing CPLN resection during primary cytoreductive surgery (CRS), examining its feasibility, safety, and potential impact on clinical outcomes. METHODS We identified all patients undergoing primary CRS/CPLN resection for Stages IIIB-IV high-grade epithelial ovarian cancer at our institution from 1/2001-12/2013. Clinical and pathological data were collected. Statistical tests were performed. RESULTS 54 patients underwent CPLN resection. All had enlarged CPLNs on preoperative imaging. Median diameter of an enlarged CPLN: 1.3cm (range 0.6-2.9). Median patient age: 59y (range 41-74). 48 (88.9%) underwent transdiaphragmatic resection; 6 (11.1%) underwent video-assisted thoracic surgery. A median of 3 nodes (range 1-23) were resected. A median of 2 nodes (range 0-22) were positive for metastasis. 51/54 (94.4%) had positive nodes. 51 (94.4%) had chest tube placement; median time to removal: 4d (range 2-12). 44 (81.4%) had peritoneal carcinomatosis. 19 (35%) experienced major postoperative complications; 4 of these (7%) were surgery-related. Median time to adjuvant chemotherapy: 40d (range 19-205). All patients were optimally cytoreduced, 30 (55.6%) without visible residual disease. Median progression-free survival: 17.2mos (95% CI 12.6-21.8); median overall survival: 70.1mos (95% CI 51.2-89.0). CONCLUSIONS Enlarged CPLNs can be identified on preoperative imaging and may indicate metastases. Resection can identify extra-abdominal disease, confirm Stage IV disease, obtain optimal cytoreduction. In the proper setting it is feasible, safe, and does not delay chemotherapy. In select patients, it may improve survival.

Surgical site infection reduction bundle in patients with gynecologic cancer undergoing colon surgery

OBJECTIVE Surgical site infections (SSIs) can lead to substantial morbidity, prolonged hospitalization, increased costs, and death in patients undergoing colorectal procedures. We sought to investigate the effect of using an SSI reduction bundle on the rate of SSIs in gynecologic cancer patients undergoing colon surgery. METHODS We identified all gynecologic cancer patients who underwent colon resection at our institution from 2014 to 2016, during which time a service-wide SSI reduction bundle was introduced. The intervention included preoperative oral antibiotics with optional mechanical bowel preparation, skin preparation with antibacterial solution, and the use of a separate surgical closing tray. SSI rates were assessed within 30days post-surgery. RESULTS Of 233 identified patients, 115 had undergone colon surgery prior to (PRE) and 118 after (POST) the implementation of the intervention. A low anterior resection was the most common colon surgery in both cohorts. The incidence of SSI within 30days of surgery was 43/115 (37%) in the PRE and 14/118 (12%) in the POST cohorts (p≤0.001). Wound dehiscence was noted in 30/115 (26%) and 2/118 (2%) patients, respectively (p≤0.001). In patients whose operation took longer than 360min, 30-day SSI rates were 37% (28/76) and 12% (8/67), respectively (p≤0.001). In patients with an estimated blood loss >500cm3, SSI rates were 44% (27/62) and 15% (10/67), respectively (p≤0.001). CONCLUSIONS The implementation of an SSI reduction bundle was associated with a significant reduction in 30-day SSIs in these patients. The intervention remained effective in patients undergoing longer operations and in those with increased blood loss.

Primary cytoreductive surgery and adjuvant hormonal monotherapy in women with advanced low-grade serous ovarian carcinoma: Reducing overtreatment without compromising survival?

OBJECTIVES Women with advanced-stage, low-grade serous ovarian carcinoma (LGSC) have low chemotherapy response rates and poor overall survival. Most LGSC tumors overexpress hormone receptors, which represent a potential treatment target. Our study objective was to determine the outcomes of patients with advanced-stage LGSC treated with primary cytoreductive surgery (CRS) and hormone therapy (HT). METHODS A retrospective study was performed at two academic cancer centers. Patients with Stage II-IV LGSC underwent either primary or interval CRS followed by adjuvant HT between 2004 and 2016. Gynecologic pathologists reviewed all cases. Two-year progression-free (PFS) and overall survival (OS) were calculated. RESULTS Twenty-seven patients were studied; primary CRS followed by HT were administered in 26, while 1 patient had neoadjuvant chemotherapy followed by CRS and HT. The median patient age was 47.5, and patients had Stage II (n=2), Stage IIIA (n=6), Stage IIIC (n=18), and Stage IV (n=1) disease. Optimal cytoreduction to no gross residual was achieved in 85.2%. Ninety six percent of tumors expressed estrogen receptors, while only 32% expressed progesterone receptors. Letrozole was administered post operatively in 55.5% cases, anastrozole in 37.1% and tamoxifen in 7.4%. After a median follow up of 41months, only 6 patients (22.2%) have developed a tumor recurrence and two patients have died of disease. Median PFS and OS have not yet been reached, but 2-year PFS and OS were 82.8% and 96.3%, respectively, and 3-year PFS and OS were 79.0% and 92.6%, respectively. CONCLUSIONS Our series describes the initial experience with cytoreductive surgery and hormonal monotherapy for women with Stage II-IV primary ovarian LGSC. While surgery remains the mainstay of treatment, chemotherapy may not be necessary in patients with advanced-stage disease who receive adjuvant hormonal therapy. A cooperative group, Phase III trial is planned to define the optimal therapy for women with this ovarian carcinoma subtype.

Intraperitoneal chemotherapy after interval debulking surgery for advanced-stage ovarian cancer: Feasibility and outcomes at a comprehensive cancer center

OBJECTIVES Intraperitoneal (IP)-based chemotherapy following primary debulking surgery (PDS), although associated with substantial toxicity, is supported by a strong evidence base. We sought to determine feasibility and outcomes of IP chemotherapy after interval debulking surgery (IDS) among patients deemed ineligible for PDS. METHODS We identified all patients with high-grade, stage III/IV ovarian cancer treated at our institution with neoadjuvant chemotherapy (NACT) followed by IDS and postoperative chemotherapy from 1/2008-5/2013. IP and intravenous (IV) regimens were defined; demographic and clinical data were analyzed using appropriate statistics. RESULTS Of 128 evaluable patients, 118 (92%) achieved ≤1cm residual disease at IDS and 74 (58%) achieved a complete gross resection (CGR). An IP port was placed in 54/128 patients (42%), with 89% port utilization. Forty-eight (38%) of 128 patients received IP chemotherapy, 17 (13%) weekly IV paclitaxel/q3week carboplatin, and 63 (49%) q3week IV carboplatin/paclitaxel. Patients completed a median of 3 IP cycles (range, 2-6), with 3 (5.5%) of 54 ports removed due to complications. Overall survival (OS) for patients with a CGR treated with IP and weekly IV chemotherapy was 53.2months (range, 24.7-NE), and 44.2months (range, 30.2-NE) with any visible residual disease (p<0.001). Median OS was 53.2months (range, 44.5-NE) for IP-, not reached for weekly IV-, and 34.2months (range, 27.5-49.8) for q3week IV-treated patients (p=0.1). CONCLUSIONS Patients administered IP after IDS had a high rate of successful port utilization, with few regimen switches. Oncologic outcomes were optimal in patients with a CGR at IDS, regardless of chemotherapy used.

Prognostic significance of the number of postoperative intraperitoneal chemotherapy cycles for patients with advanced epithelial ovarian cancer.

Objective Phase 3 trials have demonstrated a survival advantage for patients with optimally debulked epithelial ovarian cancer who received intravenous (IV) and intraperitoneal (IP) chemotherapy compared with IV therapy alone. This was despite a significant proportion of patients in the IV/IP arms not completing all 6 planned cycles. Our objective was to evaluate the prognostic significance of the number of IV/IP cycles administered. Methods/Materials Data were analyzed for all patients with stage III to IV epithelial ovarian cancer who underwent optimal primary cytoreduction followed by 1 or more cycles of IV/IP chemotherapy from January 2005 to July 2011 at our institution. A landmark analysis was performed to associate progression-free survival (PFS) and overall survival (OS) with the number of IV/IP cycles given. Results We identified 201 patients; 26 (13%) received 1 to 2 cycles of IV/IP chemotherapy, 41 (20%) received 3 to 4 cycles, and 134 (67%) received 5 to 6 cycles. The 5-year PFS for patients who received 1 to 2, 3 to 4, and 5 to 6 cycles was 18%, 29%, and 17%, respectively. The 5-year OS for patients who received 1 to 2, 3 to 4, and 5 to 6 cycles was 44%, 54%, and 57%, respectively. There was no significant difference in PFS (P = 0.31) or OS (P = 0.14) between the 3 groups. The most common reason for discontinuing IV/IP therapy was treatment-related toxicity (77%). Postoperative complications were the most common reason for not initiating IV/IP therapy (42%) in patients who subsequently transitioned to it. Conclusions We did not detect a significant survival difference between patients who received 1 to 2, 3 to 4, or 5 to 6 IV/IP chemotherapy cycles. Women may still derive a survival benefit if they receive fewer than 6 IV/IP cycles.