hirty-four patients were included in this study. The demographic and clinicopathologic characteristics of the patients in this study are shown in Table 1. The median age of diagnosis was 56.5 years (range, 31-74 years). The majority of patients had serous tumors (28, 82%) with the remainder having clear cell (1, 3%), endometrioid (1, 3%), mucinous (3, 9%), and adenosquamous (1, 3%) histologies. At the time of presentation, the majority of patients had advanced stage disease (28, 82%). Three patients (9%) had early stage disease at presentation. In another three (9%) patients the initial disease stage was unknown because the patient either received neoadjuvant chemotherapy prior to undergoing surgery or because the patient did not undergo a complete staging procedure. One patient initially presented with a mucinous tumor of low malignant potential that recurred as a low-grade mucinous tumor that was treated with HIPEC.
The most common indication for treatment with HIPEC was treatment of first recurrence (14, 41%). Other indications for HIPEC include primary treatment (3, 9%), treatment of second recurrence (9, 26%), consolidative treatment following treatment of primary disease (5, 15%), and consolidative treatment following treatment of disease recurrence (3, 9%). The median number of chemotherapy regimens prior to undergoing treatment with HIPEC (including front-line regimens) was two. At the time of surgical cytoreduction prior to HIPEC, 26 (76%) patients underwent optimal cytoreduction (defined as 1 cm or less of residual disease). Fifteen (44%) of patients required resection of at least one abdominal visceral organ. Mitomycin C was the most commonly used agent (21, 62%) followed by cisplatin (10, 29%), oxaliplatin (2, 6%), and carboplatin (1, 3%). Mitomycin C was most commonly given as a total dose of 40 mg while cisplatin was most commonly given at a dose of 100 mg/m2.
The median length of stay following HIPEC administration was 9 days (range, 3-39 days). It is common practice in our institution for all patients receiving HIPEC to be pre-emptively admitted to the ICU following surgery. The most common post-operative complications were hematologic with 13 (37%), 5 (14%), and 1 (3%) of patients experiencing anemia requiring blood transfusion, grade 3 or 4 neutropenia, and grade 3 or 4 thrombocytopenia, respectively (Table 2). Two (6%) patients experienced post-operative sepsis during their post-operative stay. Only two (13%) of those patients undergoing visceral resection developed an intra-abdominal abscess or fistula in the first 30 days from surgery. Seven (21%) patients developed transient renal dysfunction, defined as >50% rise in serum creatinine value over baseline as defined by the Acute Kidney Injury Criteria (26), all of which, resolved by 30 days post-operatively. One patient (3%) experienced renal dysfunction that persisted for longer than 30 days post-operatively but did not go on to require dialysis. Of the eight patients who suffered some degree of renal dysfunction, all but one had received HIPEC with a platinum agent. Of those patients who received HIPEC with cisplatin, 70% experienced some degree of renal dysfunction. When comparing toxicity profiles between mitomycin C and platinum-containing agents, only transient renal dysfunction was significantly different between the two groups (P=0.007). Of note, one patient in each the mitomycin C and platinum groups had an elevated creatinine at baseline, defined as a serum of creatinine of >1.3 mg/dL.
(To view a larger version of Table 2, click here.)
Eight (24%) patients were re-admitted within 30 days of discharge. The most common reason for re-admission was infection (six patients) with the remaining two patients being readmitted for dehydration. There were no post-operative deaths in this cohort. Following recovery from surgery, 11 (32%) patients received additional therapy. Seven of those patients received cytotoxic agents while four received treatment with tamoxifen. Two additional patients were recommended to receive additional chemotherapy, however one patient declined additional therapy and one patient was never medically well enough to receive additional therapy. At a median follow-up of 20 months (range, 3-87 months), eight patients are alive with disease, seven have no evidence of disease, 14 have died of their disease, and five patients have been lost to follow-up. Median time to progression for the group of patients receiving mitomycin C is 9 months and median time to progression for the group of patients receiving platinum is 7 months. This difference is not statistically significant (P=0.23).