Key Points
Question
Can a more clinically feasible version of the modified Frailty Index for older patients with cancer be developed?
Findings
In this cohort study of 1137 older patients with cancer, the Memorial Sloan Kettering–Frailty Index (MSK-FI) was associated with aging-related impairments. A higher score on the MSK-FI was also associated with a longer length of stay, higher odds of intensive care unit admission, and lower overall survival.
Meaning
The MSK-FI may be a feasible tool to perioperatively assess frailty in older patients with cancer.
The peritoneal spread of ovarian cancer makes it a potential target for hyperthermic intraperitoneal chemotherapy (HIPEC). Intraperitoneal delivery exposes the tumor to concentrations of cytotoxic drugs much greater than with intravenous delivery, and in vitro studies have also shown that combining hyperthermia and platinum leads to an additive cytotoxic effect. Pharmacokinetic analyses have confirmed very high concentrations of cytotoxic drugs in the peritoneal cavity, with minimal systemic exposure and toxicity.
The majority of historical data evaluating HIPEC in ovarian cancer are based on retrospective research, which included heterogeneous groups of patients and drugs used for HIPEC. Recent publications on the findings of prospective studies, including the first randomized trial in which the only difference in intervention was the addition of HIPEC with cisplatin to interval debulking surgery in stage III patients, have shown a benefit in favor of HIPEC. Yet, a recent prospective study from Korea did not find a benefit.
Opponents of HIPEC have cited higher rates of complications with this approach, yet most of the serious adverse events observed are likely related to the surgery itself, and are comparable to the rates reported in studies evaluating cytoreductive surgery without HIPEC. Findings from a recent randomized controlled trial showed no delays in initiation or completion of postoperative chemotherapy in patients treated with HIPEC.
A growing body of evidence is indicating that it might be time to seriously consider HIPEC as a complementary treatment at the time of cytoreductive surgery for patients with advanced-stage ovarian cancer in the setting of an experienced center. Yet, more research is needed to identify the population of patients who gain the most benefit from this therapy.
Objective: Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) confers similar outcomes as primary debulking surgery and chemotherapy. Little is known about patients who receive NACT but do not undergo debulking surgery. Our aim was to characterize these patients. Methods: We prospectively identified patients with newly diagnosed stage III/IV ovarian cancer treated with NACT from 7/1/15-12/1/17. Fisher exact and Wilcoxon rank-sum tests were used to compare clinical characteristics by surgical status. The Kaplan-Meier method was used to estimate survival outcomes. Log-rank test and Cox proportional hazards model were applied to assess the relationship of covariates to outcome, and time-dependent covariates were applied to variables collected after diagnosis. Results: Of 224 women who received NACT, 162 (72%) underwent IDS and 62 (28%) did not undergo surgery. The non-surgical group was older (p<0.001), had higher Charlson comorbidity index (CCI; p<0.001), lower albumin levels (p=0.007), lower Karnofsky performance scores (p<0.001), and were more likely to have dose reductions in NACT (p<0.001). Reasons for no surgery included poor response to NACT (39%), death (15%), comorbidities (24%), patient preference (16%), and loss to follow-up (6%). The no surgery group had significantly worse overall survival (OS) than the surgery group (hazard ratio=3.34; 95% confidence interval=1.66-6.72; p<0.001), after adjustment for age, CCI, and dose reductions. Conclusions: A significant proportion of women treated with NACT do not undergo IDS, and these women are older, frailer, and have worse OS. More studies are needed to find optimal therapies to maximize outcomes in this high-risk, elderly population.
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