Patients triaged to neoadjuvant chemotherapy have higher rates of sarcopenia: An opportunity for prehabilitation.

OBJECTIVE: To compare baseline body composition measures (BCM), including sarcopenia, between patients with advanced epithelial ovarian cancer (EOC) undergoing primary cytoreductive surgery (PCS) versus neoadjuvant chemotherapy/interval cytoreductive surgery (NACT/ICS) and evaluate changes in BCM pre-NACT versus pre-ICS. METHODS: Patients with stage IIIC/IV EOC who underwent PCS or NACT with curative intent between 1/1/2012 and 7/31/2016 were included. Computed tomography scans were evaluated via a semi-automated program to determine BCM. Measures evaluated include skeletal muscle area (SMA), skeletal muscle density (SMD), skeletal muscle index (SMI), and skeletal muscle gauge (SMG). Sarcopenia was defined as SMI <39.0 cm2/m2. RESULTS: The study included 200 PCS patients and 85 NACT/ICS patients, of which 76 had both pre-NACT and pre-ICS scans. NACT patients were significantly more likely to be sarcopenic compared to PCS patients (40.0% vs 27.5%, p = 0.04). Mean SMA (107.3 vs 113.4 cm2, p = 0.004) and mean SMG (1344.6 vs. 1456.9 (cm2 x HU)/m2, p = 0.06) were lower in NACT patients. Among NACT/ICS patients, mean SMI significantly decreased -1.4 cm2/m2 (p = 0.005) at the time of surgery, resulting in a non-statistically significant increase in the percentage of sarcopenic patients from baseline (40.8% vs. 50.0%, p = 0.09). CONCLUSIONS: Sarcopenia is more common in patients with advanced EOC undergoing NACT compared to PCS when using an evidence-based triage system for triage decisions. Body composition changes significantly over the course of NACT. Sarcopenia may be an indicator of debility and another factor for consideration in treatment planning. Further research into body composition's effects on prognosis and altering sarcopenia is necessary.

Risk-scoring system for the individualized prediction of lymphatic dissemination in patients with endometrioid endometrial cancer.

OBJECTIVE: To develop a risk-scoring system (RSS) for the prediction of lymphatic dissemination after hysterectomy in endometrioid endometrial carcinoma (EC). METHODS: Patients who underwent surgery from 1/1/1999-12/31/2008 were evaluated. Patients with non-endometrioid histology, stage IV with macroscopic extrauterine disease, or receiving adjuvant therapy (excluding brachytherapy) without pelvic and/or paraaortic (P/PA) lymphadenectomy (LND) were excluded. Lymph node dissemination was defined as nodal metastasis when P/PA LND was performed or P/PA lymph node recurrence after negative LND or when LND was not performed. Logistic regression analysis was used to identify predictors for lymphatic dissemination and develop a RSS and nomogram. The RSS was assessed for calibration and verified for discrimination. RESULTS: Overall, 883 patients were assessed of which 521 (59.0%) underwent P/PA LND and 57 (10.9%) had positive lymph nodes. Of patients who did not undergo P/PA LND (N=362) or had negative nodes (N=464), 10 (1.2%) patients had P/PA lymph node recurrence. Myometrial invasion, tumor diameter (TD), FIGO grade, cervical stromal invasion and lymphovascular space invasion were significant on univariable analysis. All preceding variables were included in a multivariable logistic model. A parsimonious model and an alternative full model not including TD were considered. The full model with TD (illustrated in nomogram) had the highest predictive ability (concordance index 0.88). CONCLUSION: Our RSS allows accurate quantification of the probability of lymphatic dissemination and can be used as an adjunct to clinical decision-making after hysterectomy in the absence of staging. TD is an important component of the RSS and should be routinely assessed.

Evaluating the prognostic significance of preoperative thrombocytosis in epithelial ovarian cancer.

OBJECTIVE: Preoperative thrombocytosis has been implicated as a negative prognostic marker for epithelial ovarian cancer (EOC). We assessed whether thrombocytosis is an independent risk factor for EOC recurrence and death. METHODS: Perioperative patient characteristics and process-of-care variables (National Surgical Quality Improvement Program (NSQIP)-defined) were retrospectively abstracted from 587 women who underwent EOC staging between 1/2/03-12/29/08. Thrombocytosis was defined as platelet count > 450 × 10(9)/L. Disease-free survival (DFS) and overall survival (OS) were determined using Kaplan-Meier methods. Associations were evaluated with Cox proportional hazards regression and hazard ratios (HR). RESULTS: The incidence of preoperative thrombocytosis was 22.3%. DFS was 70.8% and 36.0% at 1 and 3 years. OS was 83.3% and 54.3% at 1 and 3 years. Ascites, lower hemoglobin, advanced disease, and receipt of perioperative packed red blood cell transfusion were independently associated with thrombocytosis. Older age and the presence of coronary artery disease were associated with lower likelihood of thrombocytosis. Overall, thrombocytosis was an independent predictor of increased risk of recurrence. Among early stage (I/II) cases, there was a 5-fold increase in the risk of death and nearly 8-fold risk of disease recurrence independently associated with thrombocytosis. CONCLUSION: Preoperative thrombocytosis portends worse DFS in EOC. In early stage disease, thrombocytosis is a potent predictor of worse DFS and OS and further assessment of the impact of circulating platelet-derived factors on EOC survival is warranted. Thrombocytosis is also associated with extensive initial disease burden, measurable residual disease, and postoperative sequelae. Preoperative platelet levels may have value in primary cytoreduction counseling.

Risk factors that mitigate the role of paraaortic lymphadenectomy in uterine endometrioid cancer.

OBJECTIVE: Paraaortic lymph node (PA) dissemination in endometrial cancer (EC) is uncommon and a systematic infrarenal PA dissection carries morbidity. Our objective was to identify a subgroup of EC patients who may potentially forego PA lymphadenectomy (LND). METHODS: The study endpoint (PA Metastasis or Recurrence; PAMR) was defined as detection of metastasis to PA nodes (among those with any type of PA LND) or PA recurrence within 2 years (among patients without PA LND or those with negative nodes in the context of an inadequate (<5 nodes) PA LND). Patients with non-endometrioid histology, stage IV disease, synchronous cancers, gross extrauterine or gross adnexal disease, neoadjuvant therapy, or insufficient follow-up were excluded. Multivariable logistic regression analysis identified predictors of PAMR. RESULTS: Of the 946 patients, PAMR was observed in 4% (36/946). Multivariable analysis identified positive pelvic nodes (odds ratio (OR) 24.2; p<0.001), >50% MI (OR 5.3; p<0.001) and lymphovascular space invasion (LVSI) (OR 3.7; p=0.005) as the only three independent predictors of PAMR. When all three factors were absent (77% of study cohort), the predicted probability of PAMR was 0.6%. If intraoperative frozen section is not available on pelvic lymph nodes and LVSI, omitting PA LND in all patients with ≤ 50% MI would affect 84% (792/946) of the total cohort, with a 1.1% risk of PAMR (9/792). CONCLUSION: The majority of patients with endometrioid EC may potentially forgo PA LND with expected reductions in surgical morbidity and cost. This cohort may be identified by a combined absence of: positive pelvic nodes, >50% MI and LVSI.

Prospective assessment of survival, morbidity, and cost associated with lymphadenectomy in low-risk endometrial cancer.

OBJECTIVE: Since 1999, patients with low risk endometrial cancer (EC) as defined by the Mayo criteria have preferably not undergone lymphadenectomy (LND) at our institution. Here we prospectively assess survival, sites of recurrence, morbidity, and cost in this low risk cohort. METHODS: Cause-specific survival (CSS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Complications were graded per the Accordion Classification. Thirty-day cost analyses were expressed in 2010 Medicare dollars. RESULTS: Among 1393 consecutive surgically managed cases, 385 (27.6%) met inclusion criteria, accounting for 34.1% of type I EC. There were 80 LND and 305 non-LND cases. Complications in the first 30 days were significantly more common in the LND cohort (37.5% vs. 19.3%; P<0.001). The prevalence of lymph node metastasis was 0.3% (1/385). Over a median follow-up of 5.4 years only 5 of 31 deaths were due to disease. The 5-year CSS in LND and non-LND cases was 97.3% and 99.0%, respectively (P=0.32). None of the 11 total recurrences occurred in the pelvic or para-aortic nodal areas. Median 30-day cost of care was $15,678 for LND cases compared to $11,028 for non-LND cases (P<0.001). The estimated cost per up-staged low-risk case was $327,866 to $439,990, adding an additional $1,418,189 if all 305 non-LND cases had undergone LND. CONCLUSION: Lymphadenectomy dramatically increases morbidity and cost of care without discernible benefits in low-risk EC as defined by the Mayo criteria. In these low-risk patients, hysterectomy with salpingo-oophorectomy alone is appropriate surgical management and should be standard of care.