Materials and Methods
After obtaining institutional review board approval, we conducted a retrospective review of all obese patients with advanced stage (FIGO stage IIIC-IV) epithelial ovarian, fallopian tube, or primary peritoneal carcinoma between January 2005 and December 2010 who were treated by PDS or NACT-IDS. Obesity was defined as a BMI of ≥30 kg/m 2 . For patients who were treated by PDS, the preoperative BMI was used. For patients who were treated by NACT-IDS, the BMI at the time of cancer diagnosis was used. Patients were excluded from analysis for the following reasons: never underwent definitive surgical intervention, nonepithelial histologic condition, synchronous or preexisting primary malignancy, or incomplete medical records. All surgical procedures were performed by gynecologic oncology faculty, with intent to achieve optimal cytoreduction (≤1 cm maximal diameter of the largest residual tumor nodule).
Chemotherapy was largely platinum and paclitaxel based and reflected standard protocols used during the study period. For patients who underwent PDS, the final histologic diagnosis was established after pathologic review of the surgical specimen. For patients who underwent NACT-IDS, the final diagnosis was established with a biopsy or cytologic specimen that was consistent with an ovarian, fallopian tube, or primary peritoneal carcinoma. The decision to perform PDS vs NACT-IDS was left at the discretion of the primary gynecologic oncologist. Patients who received neoadjuvant chemotherapy generally received 3-4 cycles of carboplatin (AUC 6) and paclitaxel (175 mg/m 2 ) every 21 days. Imaging was repeated after 3-4 cycles to evaluate response.
Chemotherapy generally was resumed 3 weeks after surgery with the goal of a total of 6 cycles of chemotherapy. Patients were separated based on PDS or NACT-IDS and compared with respect to preoperative characteristics, surgical procedures performed, and postoperative and oncologic outcomes. To evaluate the impact of the definitive surgical procedure performed, surgical procedures were given a complexity score that reflected the complexity and the number of procedures that were performed as described by Aletti et al. All obese patients (ie, BMI of ≥30 kg/m 2 ) were included in the initial comparison between those who underwent PDS and those who underwent NACT-IDS. We then sought to evaluate PDS vs NACT-IDS among different levels of obesity. The entire obese patient sample was separated into those with a BMI of 30-34.9 kg/m 2 and those with a BMI of ≥35 kg/m 2 . For these separate obesity groups, those women who underwent PDS and those who underwent NACT-IDS were then compared with respect to the previously mentioned variables. A BMI cut-off of 35 kg/m 2 was used to separate the entire obese patient sample because the World Health Organization recognizes this cut-off as the point at which the risk of comorbidities is severe and the point at which treatment options for obese patients often differ.
Differences in clinical and histopathologic factors between patient groups were examined with the χ 2 and Student t test. Progression-free survival (PFS) was calculated from the date of first treatment (surgery or chemotherapy) until the date of first recurrence or last visit. Overall survival (OS) was calculated from the date of first treatment until the date of death, regardless of cause, or the date of last visit if the patient was alive. The Kaplan-Meier method was used to estimate survival curves. Log-rank statistics and Cox proportional hazards regression were used to compare survival data. Associations are shown as hazard ratios (HRs) with 95% confidence intervals (CIs). The SPSS statistical package (version 20.0; SPSS Inc, Chicago, IL) was used for all statistical analyses. A probability value of < .05 was considered to be statistically significant.
Results
Of 117 patient records available for analysis, 95 women (81.2%) underwent PDS and 22 women (18.8%) underwent NACT-IDS. Considering all obese patients, those women who underwent PDS were similar to those who underwent NACT-IDS with respect to BMI, age, CA-125 level, medical comorbidities, previous malignancy, the presence of carcinomatosis, the presence of a pleural effusion (without cytologic evidence), site of origin (ie, ovary, fallopian tube, or peritoneum), histologic type, and histologic grade. The group who underwent NACT-IDS had a greater percentage of patients with stage IV disease (63.6% vs 26.3%; P = .001).
Operative procedure characteristics were then compared between the 2 groups. The group who underwent NACT-IDS had a greater percentage of patients with a low surgical complexity score (63.6% vs 34.7%; P = .016). The rates of optimal cytoreduction and cytoreduction to no gross residual disease (NED) were similar between groups ( Table 1 ). We then compared groups with respect to postoperative morbidity and mortality rates. There were no differences between the PDS and NACT-IDS group with respect to hospital length of stay, number of transfused units of blood, or postoperative complications ( Table 2 ).
| Characteristic | Primary debulking surgery (n = 95) | Neoadjuvant chemotherapy (n = 22) | P value |
|---|---|---|---|
| Estimated blood loss, mL a | |||
| BMI 30-34.9 kg/m 2 | 600 (100–4000) | 300 (200–1100) | .299 |
| BMI ≥35 kg/m 2 | 550 (150–3000) | 400 (50–2300) | .937 |
| Total | 600 (100–4000) | 300 (50–2300) | .294 |
| Low Surgical Complexity Score, n | |||
| BMI 30-34.9 kg/m 2 | 23 (36.5%) | 8 (53.3%) | .175 |
| BMI ≥35 kg/m 2 | 10 (31.3%) | 6 (85.7%) | .013 |
| Total | 33 (34.7%) | 14 (63.6%) | .016 |
| Intermediate Surgical Complexity Score, n | |||
| BMI 30-34.9 kg/m 2 | 29 (46%) | 7 (46.7%) | .175 |
| BMI ≥35 kg/m 2 | 19 (59.4%) | 1 (14.3%) | .044 |
| Total | 48 (50.5%) | 8 (36.4%) | .248 |
| High Surgical Complexity Score, n | |||
| BMI 30-34.9 kg/m 2 | 11 (17.5%) | 0 | .175 |
| BMI ≥35 kg/m 2 | 3 (9.4%) | 0 | .399 |
| Total | 14 (14.7%) | 0 | .069 |
| Optimal cytoreduction (<1cm), n | |||
| BMI 30-34.9 kg/m 2 | 54 (85.7%) | 13 (86.7%) | .924 |
| BMI ≥35 kg/m 2 | 28 (87.5%) | 6 (85.7%) | .898 |
| Total | 82 (86.3%) | 19 (86.4%) | .995 |
| No gross residual disease, n | |||
| BMI 30-34.9 kg/m 2 | 19 (30.2%) | 8 (53.3%) | .227 |
| BMI ≥35 kg/m 2 | 10 (31.3%) | 4 (57.1%) | .569 |
| Total | 29 (30.5%) | 12 (54.5%) | .178 |
| Characteristic | Primary debulking surgery (n = 95) | Neoadjuvant chemotherapy (n = 22) | P value |
|---|---|---|---|
| Hospital length of stay, d a | |||
| BMI 30-34.9 kg/m 2 | 6 (2–35) | 5 (3–10) | .967 |
| BMI ≥35 kg/m 2 | 9 (3–58) | 6 (1–12) | .811 |
| Total | 7 (2–58) | 6 (1–12) | .535 |
| Transfused units of blood, n b | |||
| BMI 30-34.9 kg/m 2 | 1 (0–10) | 0 (0–6) | .642 |
| BMI ≥35 kg/m 2 | 1 (0–12) | 2 (0–5) | .288 |
| Total | 1 (0–12) | 1 (0–6) | .82 |
| Readmission within 30 days of surgery | |||
| BMI 30-34.9 kg/m 2 | 16 (25.4%) | 4 (26.7%) | .919 |
| BMI ≥35 kg/m 2 | 13 (40.6%) | 1 (14.3%) | .188 |
| Total | 29 (30.5%) | 5 (22.7%) | .468 |
| Wound complications | |||
| BMI 30-34.9 kg/m 2 | 17 (27%) | 3 (20%) | .578 |
| BMI ≥35 kg/m 2 | 15 (46.9%) | 3 (42.9%) | .847 |
| Total | 32 (33.7%) | 6 (27.3%) | .563 |
| Deep venous thrombosis/pulmonary embolism | |||
| BMI 30-34.9 kg/m 2 | 2 (3.2%) | 1 (6.7%) | .527 |
| BMI ≥35 kg/m 2 | 4 (12.5%) | 0 | .323 |
| Total | 6 (6.3%) | 1 (4.5%) | .752 |
| Myocardial infarction | |||
| BMI 30-34.9 kg/m 2 | 0 | 0 | N/A |
| BMI ≥35 kg/m 2 | 0 | 0 | N/A |
| Total | 0 | 0 | N/A |
| Pneumonia | |||
| BMI 30-34.9 kg/m 2 | 5 (7.9%) | 2 (13.3%) | .511 |
| BMI ≥35 kg/m 2 | 3 (9.4%) | 0 | .399 |
| Total | 8 (8.4%) | 2 (9.1%) | .919 |
| Ileus/small bowel obstruction | |||
| BMI 30-34.9 kg/m 2 | 13 (20.6%) | 0 | .062 |
| BMI ≥35 kg/m 2 | 4 (12.5%) | 1 (14.3%) | .898 |
| Total | 17 (17.9%) | 1 (4.5%) | .189 |
| Bowel perforation | |||
| BMI 30-34.9 kg/m 2 | 0 | 0 | N/A |
| BMI ≥35 kg/m 2 | 2 (6.3%) | 0 | .497 |
| Total | 2 (2.1%) | 0 | .492 |
a Values represent median (range)
Of the 95 patients in the PDS group, there were 76 recurrences (80%); of the 22 patients in the NACT-IDS group, there were 21 recurrences (95.5%). Compared with those women who underwent NACT-IDS, the group who underwent PDS had a greater median PFS (15 vs 11 months; P = .006). On univariate analysis, factors associated with recurrence included the presence of carcinomatosis (HR, 2.55; 95% CI, 1.55–4.20), the presence of a pleural effusion (HR, 1.79; 95% CI, 1.13–2.83), NACT-IDS (HR, 1.94; 95% CI, 1.18–3.17), stage IV disease (HR, 1.54;95% CI, 1.02–2.34), optimal cytoreduction (HR, 0.53; 95% CI, 0.30–0.93), and cytoreduction to NED (HR, 0.41; 95% CI, 0.22–0.77). On multivariate analysis, the presence of carcinomatosis (HR, 1.87; 95% CI, 0.06–3.30) and the use of NACT-IDS (HR, 2.31; 95% CI, 1.29–4.15) were associated independently with an increased risk of recurrence.
Of the 95 patients in the PDS group, there were 45 deaths (47.4%); of the 22 patients in the NACT-IDS group, there were 13 deaths (59.1%). Compared with those women who underwent NACT-IDS, the group who underwent PDS had a greater median OS (53 vs 32 months; P = .036). The use of NACT-IDS was the only factor that was associated with death on univariate analysis (HR, 1.94; 95% CI, 1.03–3.66).
BMI of 30-34.9 kg/m 2
Table 3 displays a comparison of patient and pathologic characteristics by treatment approach, divided by level of obesity. A total of 78 patients (66.7%) had a BMI of 30-34.9 kg/m 2 . Of these 78 patients, 63 women (80.8%) underwent PDS, and 15 women (19.2%) underwent NACT-IDS. Within this subset of obese patients, those who underwent NACT-IDS had a greater median CA-125 level at diagnosis (1131 vs 334 U/mL; P = .018) and a greater percentage of patients with diabetes mellitus (33.3% vs 11.1%; P = .047), carcinomatosis (93.3% vs 66.7%; P = .039), and stage IV disease (66.7% vs 25.4%; P = .002).
| Characteristic | Body mass index | |||||
|---|---|---|---|---|---|---|
| 30-34.9 kg/m 2 | ≥35 kg/m 2 | |||||
| Primary debulking surgery (n = 63) | Neoadjuvant chemotherapy (n = 15) | P value | Primary debulking surgery (n = 32) | Neoadjuvant chemotherapy (n = 7) | P value | |
| Age, y a | 64 (36–83) | 61 (33–85) | .353 | 63 (50–85) | 68 (47–77) | .94 |
| Cancer antigen 125 at diagnosis, U/mL a | 334 (12–17,700) | 1131 (181–7207) | .018 | 493 (11–3830) | 443 (76–3416) | 1 |
| Hypertension, n | 35 (55.6%) | 7 (46.7%) | .576 | 22 (68.8%) | 4 (57.1%) | .666 |
| Coronary artery disease, n | 6 (9.5%) | 2 (13.3%) | .646 | 2 (6.3%) | 0 | .497 |
| Diabetes mellitus, n | 7 (11.1%) | 5 (33.3%) | .047 | 13 (40.6%) | 1 (14.3%) | .386 |
| Body mass index, kg/m 2 a | 32 (30–34.9) | 32 (30.2–34.9) | 1 | 38 (35–48) | 39 (35–40) | .822 |
| Asthma, n | 1 (1.6%) | 1 (6.7%) | .35 | 2 (6.3%) | 1 (14.3%) | .457 |
| Chronic obstructive pulmonary disease, n | 2 (3.2%) | 2 (13.3%) | .165 | 3 (9.4%) | 0 | .399 |
| Previous malignancy, n | 10 (15.9%) | 5 (33.3%) | .15 | 8 (25.0%) | 0 | .308 |
| Carcinomatosis, n | 42 (66.7%) | 14 (93.3%) | .039 | 22 (68.8%) | 5 (71.4%) | .889 |
| Pleural effusion (without cytology), n | 11 (17.5%) | 4 (26.7%) | .47 | 9 (28.1%) | 4 (57.1%) | .194 |
| Site of origin, n | .829 | .563 | ||||
| Ovary | 56 (88.9%) | 14 (93.3%) | 29 (90.6) | 6 (85.7%) | ||
| Fallopian tube | 6 (9.5%) | 1 (6.7%) | 3 (9.4%) | 1 (14.3%) | ||
| Peritoneum | 1 (1.6%) | 0 | 0 | 0 | ||
| Histologic type, n | .439 | .306 | ||||
| Serous | 46 (73%) | 8 (53.3%) | 26 (81.3%) | 5 (71.4%) | ||
| Mucinous | 1 (1.6%) | 0 | 0 | 0 | ||
| Clear cell | 2 (3.2%) | 2 (13.3%) | 1 (3.1%) | 0 | ||
| Endometrioid | 6 (9.5%) | 1 (6.7%) | 2 (6.3%) | 0 | ||
| Transitional | 1 (1.6%) | 0 | 1 (3.1%) | 0 | ||
| Mixed | 4 (6.3%) | 2 (13.3%) | 1 (3.1%) | 2 (28.6%) | ||
| Unspecified adenocarcinoma | 3 (4.8%) | 2 (13.3%) | 1 (3.1%) | 0 | ||
| Grade, n | .608 | .331 | ||||
| Well-differentiated | 3 (4.8%) | 0 | 1 (3.1%) | 1 (14.3%) | ||
| Moderately differentiated | 3 (4.8%) | 0 | 0 | 0 | ||
| Poorly differentiated | 56 (88.9%) | 15 (100%) | 31 (96.9%) | 6 (85.7%) | ||
| Missing data | 1 (1.6%) | 0 | 0 | 0 | ||
| FIGO stage, n b | .002 | .194 | ||||
| IIIC | 47 (74.6%) | 5 (33.3%) | 23 (71.9%) | 3 (42.9%) | ||
| IV | 16 (25.4%) | 10 (66.7%) | 9 (28.1%) | 4 (57.1%) | ||
a Values represent median (range)
b Patients without cytologic confirmation of a malignant pleural effusion were not grouped as stage IV.
Table 1 displays a comparison of operative procedure characteristics by treatment approach, divided by level of obesity. In this subset of obese patients, PDS and NACT-IDS groups were similar with respect to estimated blood loss, surgical complexity score, rate of optimal cytoreduction, and rate of cytoreduction to NED.
Table 2 displays a comparison of perioperative morbidity by treatment approach, divided by level of obesity. Hospital length of stay, transfused units of blood, readmission within 30 days of surgery, and postoperative complications were similar between the PDS and NACT-IDS groups. There was a trend towards an increased percentage of patients with an ileus/small bowel obstruction within the PDS group (20.6% vs 0%; P = .062), but this did not reach statistical significance.
Of the 63 patients in the PDS group, there were 51 recurrences (81%); of the 15 patients in the NACT-IDS group, there were 15 recurrences (100%). Compared with those women who underwent NACT-IDS, the group who underwent PDS had a greater median PFS (15 vs 10 months; P = .011). Kaplan-Meier curves for PFS between patients who underwent PDS and NACT-IDS are displayed in Figure 1 . On univariate analysis, factors that were associated with recurrence included the presence of carcinomatosis (HR, 2.35; 95% CI, 1.29–4.26), the presence of a pleural effusion (HR, 2.37; 95% CI, 1.28–4.38), NACT-IDS (HR, 2.06; 95% CI, 1.15–3.70), optimal cytoreduction (HR, 0.40; 95% CI, 0.20–0.80), and cytoreduction to NED (HR, 0.42; 95% CI, 0.24–0.74).
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