Abstract
This study assesses survival outcomes among patients with gastric adenocarcinoma who received hyperthermic intraperitoneal chemotherapy combined with cytoreductive surgery at US academic centers.
Gastric cancer (GC) with peritoneal metastases is associated with a poor prognosis. Median overall survival (OS) is less than 1 year with systemic chemotherapy alone.1 Hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) has been used for various peritoneal surface malignant tumors, and there has been marked interest in its application to GC because a small randomized clinical trial demonstrated improved OS among patients who underwent CRS-HIPEC compared with CRS alone.2 Although widespread adoption of HIPEC for GC has been limited because of poor oncologic outcomes and high perioperative morbidity,3 interest in the use of intraperitoneal chemotherapy for patients with advanced GC persists.1 We assessed survial outcomes among patients with gastric adenocarcinoma who received CRS-HIPEC at academic centers across the United States.
Methods
Patients with gastric adenocarcinoma identified on final pathology reports were identified from the US HIPEC Collaborative, a multi-institutional data set composed of more than 2300 patients from 12 academic medical centers. Institutional review board approval was obtained at each participating institution. A retrospective analysis of baseline demographic, clinicopathologic, operative, and postoperative factors was performed using descriptive statistics. Both OS and recurrence-free survival were analyzed using the Kaplan-Meier method. No informed consent was required because a waiver of informed consent was requested for this study given that it was a retrospective medical record review of data with no direct patient contact. Deidentified data were used for all distribution and analysis.
Results
Overall, 28 patients (17 [61%] female; mean [SD] age, 48.5 [14.2] years) with GC underwent HIPEC at 7 institutions between January 1, 2010, and December 31, 2017. Baseline demographic and clinicopathologic factors are given in the Table. Twenty-five patients (89%) had overt peritoneal dissemination, whereas 3 (11%) had positive cytologic findings on peritoneal washings. The median peritoneal carcinomatosis index (PCI) of those with peritoneal disease was 12 (interquartile range, 4-17). Curative-intent resection was performed in 23 patients; 5 patients underwent palliative HIPEC. In the curative-intent population, complete cytoreduction was achieved in 16 (70%) of 23 patients. Twenty-seven patients (96%) received neoadjuvant or adjuvant chemotherapy. Although 17 chemotherapy regimens (63%) were fluorouracil based, 15 distinct regimens were observed. In the curative-intent population, median recurrence-free survival was 7 months (95% CI, 4.9-9.1 months) and OS was 10 months (95% CI, 6.5-13.5 months) (Figure, A and B). Improved median OS was observed among the 11 curative-intent patients with a PCI of 9 or less compared with the 12 patients with PCI scores greater than 9 (26 vs 8 months; P = .01). After palliative HIPEC, the median OS was only 2 months (range, 2-13 months).
Table. Characteristics of the Patients Undergoing Gastric Hyperthermic Intraperitoneal Chemotherapya .
| Characteristic | Finding (N = 28) |
|---|---|
| Demographics | |
| Female | 17 (61) |
| Age, mean (SD), y | 48.5 (14.2) |
| BMI, median (range) | 22.5 (20-25) |
| ECOG status 0/1 | 26 (93) |
| Tumor characteristics | |
| PCI, median (range) | 12 (4-17) |
| Pathologic T stage | |
| T1 | 3 (11) |
| T2 | 3 (11) |
| T3 | 7 (25) |
| T4 | 13 (46) |
| Pathologic N stage | |
| N0 | 8 (29) |
| N1 | 6 (21) |
| N2 | 6 (21) |
| N3 | 5 (20) |
| Macroscopic peritoneal involvement | 25 (89) |
| Cytologic test results positive on washings | 3 (11) |
| Signet ring cells | 18 (64) |
| Additional therapy | |
| Neoadjuvant systemic therapy | 26 (93) |
| Adjuvant systemic therapy | 9 (32) |
| Neoadjuvant radiotherapy | 3 (11) |
| Adjuvant radiation | 0 |
| EPIC or IP catheter therapy | 0 |
| Operative factors | |
| Curative intent | 23 (82) |
| Palliative intent | 5 (18) |
| CCR 0/1 | 24 (86) |
| Total gastrectomy | 16 (57) |
| Estimated blood loss, median (range), mL | 300 (162-475) |
| HIPEC performed | 28 (100) |
| Closed technique | 27 (96) |
| IP mitomycin | 26 (9) |
| IP platinum agents | 2 (7) |
| Outcomes | |
| Any complication | 21 (75) |
| Clavien-Dindo score ≥3 | 5 (18) |
| Superficial SSI | 3 (11) |
| Intra-abdominal infection | 3 (11) |
| Anastomotic leak | 2 (7) |
| Enterocutaneous fistula | 1 (4) |
| Subsequent operation | 5 (18) |
| Postoperative TPN | 13 (46) |
| Supplemental tube feeds | 9 (32) |
| ICU admission | 24 (86) |
| Length of stay, median (range), d | 11 (8-15) |
| Readmission | 7 (25) |
| Perioperative deaths (≤90 d from surgery) | 2 (7) |
| Overall survival, % | |
| 1 y | 38 |
| 5 y | 8 |
Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); CCR, completeness of cytoreduction; EPIC, early postoperative intraperitoneal chemotherapy; HIPEC, hyperthermic intraperitoneal chemotherapy; ICU, intensive care unit; IP, intraperitoneal; PCI, peritoneal carcinomatosis index; SSI, surgical site infection; TPN, total parenteral nutrition.
Data are provided as number (percentage) of patients unless otherwise indicated.
Figure. Overall and Recurrence-Free Survival Among 23 Patients Who Underwent Curative-Intent Hyperthermic Intraperitoneal Chemotherapy.
Perioperative morbidity among all patients was high: 21 (75%) experienced at least 1 complication, 5 (18%) of which were Clavien-Dindo grade 3 or higher. Five patients required a subsequent operation for indications, including anastomotic leak, intra-abdominal infection, or obstruction. The need for nutritional support was common; total parenteral nutrition was required for 13 patients (46%), whereas 9 (32%) of 28 needed supplemental tube feeds. The median length of stay was 11 days (interquartile range, 8-15 days), and 7 patients (25%) required readmission. Two patients (7%) died within 90 days of surgery.
Discussion
The optimal role for HIPEC in the treatment of advanced GC remains poorly defined.1 Because of the lack of high-quality evidence, unclear criteria for patient selection, and biological differences among patients, no standardized approach has emerged. In addition, no clear survival advantage exists compared with results reported with standard chemotherapy alone, and little progress has been made in patient outcomes. More than a decade ago, published reviews3,4 of European and US patients undergoing CRS-HIPEC for GC reported a median OS of 8.0 to 9.2 months, with a perioperative morbidity ranging from 27.8% to 35.0%. Comparable mortality and morbidity rates from our current series suggest that outcomes remain poor, even among experienced centers. Although multiple studies indicate there may be a survival benefit among patients with lower PCI scores, a consensus cutoff has not been determined.1 Clear criteria to aid in patient selection remain elusive given the lack of high-quality evidence. Our study is limited by the overall low number of patients, selection bias arising from the retrospective design, and the lack of standardized treatment protocols across participating centers. Innovative approaches to this population, such as neoadjuvant laparoscopic HIPEC or combination intraperitoneal and intravenous chemotherapy, should be evaluated prospectively.5,6 In the meantime, our findings suggest that HIPEC for GC should be limited to clinical trials and preferably restricted to patients with low PCI scores (scores ≤9).
References
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