Parenteral nutrition for patients with advanced ovarian malignancy
Brijesh M. Madhok, Academic Unit of Surgery, Level 7 Clinical Sciences Building, St James’s University Hospital, Leeds LS9 7TF, UK.
Tel.: +44 (0)113 2065281
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Background: Parenteral nutrition (PN) in patients with disseminated ovarian cancer remains controversial. The role of PN in providing nutrition and improving quality of life is unclear. The present study aimed to determine the pattern of prescribing in a large teaching hospital, and to identify subgroups where the use of PN was justified.
Methods: Sixty-five patients with advanced ovarian carcinoma received PN between January 2002 and May 2008. A retrospective case note review was undertaken to retrieve data on PN prescribing and outcomes in terms of duration of PN provision, complications, and survival.
Results: Three subgroups were identified. Group I consisted of 18 (28%) patients who received PN for a median [interquartile range (IQR)] of 5 (2–11) days. The majority of these 18 patients (n = 13, 72%) had disease-related terminal bowel obstruction. Out of 18 of these patients, 17 (95%) had poor performance status. The median (IQR) survival was 12 (6–28) days. Group II consisted of 40 (61%) patients who were re-established on enteral nutrition. The median (IQR) duration of PN administration was 10 (6–17) days. The most common indication of PN was protracted ileus (n = 25, 63%). Out of 40 of these patients, 35 (88%) patients had good performance status. The median (IQR) survival was 264 (96–564) days. The third group of patients required home PN (n = 7, 11%). Four (58%) patients had short bowel syndrome and three (42%) had terminal intestinal obstruction. All of the patients had good performance status. The median (IQR) duration of PN administration and survival was 241 (90–305) days.
Conclusions: Administration of PN appears to be justified in those patients with a good performance status (i.e. patients capable of self-care), which constituted three-quarters of this cohort. In the remaining patients with poor performance status, and particularly those with terminal intestinal obstruction, PN administration was difficult to justify. PN should not be denied based purely on the pathology, although cautious judgment is required to select those who are most likely to benefit.
Ovarian cancer accounts for approximately 5000 deaths each year in the UK. Intestinal obstruction is a common manifestation of advanced disease, and represents the cause of death in 25–59% of patients (Copeland et al., 1974; Torelli et al., 1999; Whitworth et al., 2004). The majority of patients with advanced disease develop malnutrition for a variety of reasons, such as cancer-related anorexia, side-effects of chemotherapy, cancer-related intestinal obstruction and complications of surgical intervention (Shike, 1996), which can have a significant impact on survival, quality of life and performance status. Malnutrition also impairs the immunological response to the tumour and reduces the ability to withstand anti-neoplastic therapy (Fan et al., 1994). Accordingly, patients with advanced ovarian cancer are often prescribed nutritional supplementation, sometimes in the form of parenteral nutrition (PN).
The use of PN in such circumstances would appear to be logical for reversing the negative nitrogen balance and maintaining anabolism. However, various randomised studies on different cancers and therapies have reported inconsistent results (Copeland et al., 1974; Holter & Fischer, 1977; Thompson et al., 1981; Brennan et al., 1994; Fan et al., 1994; Torelli et al., 1999). Klein et al. (1986) performed a meta-analysis of 28 randomised controlled clinical trials to assess the use of PN in cancer patients, and concluded that it may be useful perioperatively in patients with gastrointestinal cancer, although there did not appear to be any benefit in patients receiving chemotherapy or radiation. The provision of PN to patients with disseminated solid tumours such as ovarian cancer therefore remains controversial as a result of unclear indications and supported benefits.
PN is currently recommended for patients who cannot use their gut, and have reasonable life expectancy; and malnourished patients who cannot use their gut, and are undergoing surgery, chemotherapy or radiotherapy (Brard et al., 2006). The present study aimed to determine the pattern of PN prescribing in patients with advanced ovarian cancer within the context of a large teaching hospital, with the purpose of identifying subgroups in whom PN use was justified or not, and thus informing prescribing practice.
Materials and methods
A prospectively maintained PN database was used to identify all patients who had been admitted to the St James’ University Hospital (SJUH) between January 2002 and May 2008 with a diagnosis of disseminated ovarian cancer and who were referred for PN. Retrospective case note review was undertaken to retrieve data on patient demographics, disease stage, clinical management, details of PN prescribing, PN-related complications, and outcomes in terms of duration of PN provision, return of normal gut function, and disease survival.
The nutrition team at SJUH comprises of a doctor, nutrition nurse, pharmacist and dietitian. The nutritional state of the patients was assessed by eliciting the history of nutritional intake and recent weight loss, examining their body mass indices, and using the NICE guidelines (NICE, 2006). In cancer patients, performance status is used to measure quality of life as well as to quantify their overall general well being. Performance status was assessed using the WHO scoring (Oken et al., 1982). PN formulation was designed by assessing the macronutritional requirements using body weight, age and sex using the Schofield equation (Schofield et al., 1985) and adjusted by stress factors depending upon clinical condition, activity factor and diet-induced thermogenesis (Parenteral and Enteral Group of the British Dietetic Association, 2004). At SJUH, there is access to a number of precompounded bags and custom formulations, enabling the team to tailor each prescription appropriately.
A total of 65 patients were identified. The median (range) age was 67 (24–92) years. All patients had stage IIIc or IV ovarian carcinoma and had previously received chemotherapy with or without cytoreductive surgery. Of those patients presenting with recurrent disease, 40 (75%) patients had intestinal obstruction, whereas the remainder had other symptoms related to disease progression (ascites, pleural effusion, etc). The majority of patients (n = 34, 64%) underwent surgery and 16 (30%) patients had further chemotherapy. Patient demographics, nutritional status, indications for PN, types of venous access and the complications encountered are summarised in Table 1. The majority of patients (n = 43, 66%) had a good WHO performance status. The median (IQR) duration of PN administration was 10 (5–19) days. The median (IQR) overall survival, from the day of starting PN, was 112 (30–365) days. In an attempt to identify whether PN use was justified, the cohort was subdivided into three categories (Table 2). The majority of patients (n = 40, 61%) were successfully recommenced on enteral feeding. Eighteen (28%) patients died or had active treatment withdrawn when on PN; whereas seven (11%) patients went on to receive home parenteral nutrition (HPN).
Table 1. Patient demographics, indications for parenteral nutrition (PN), types of venous access and complications encountered
| Recurrent disease||53 (82)|
| Newly-diagnosed cancer||13 (18)|
| Poor||27 (42)|
| Moderate||21 (32)|
| Good||17 (26)|
| Peritoneal disease||65 (100)|
| Pleural/lung involvement||11 (17)|
| Liver metastasis||4 (6)|
| Brain metastasis||1 (1.5)|
|Indications for PN|
| Protracted post-operative ileus||30 (46)|
| Intestinal obstruction||23 (36)|
| Enterocutaneous fistulae||4 (6)|
| Short bowel syndrome||4 (6)|
| Uncontrolled nausea and vomiting||4 (6)|
| Nontunnelled central venous catheter||47 (72.5)|
| Tunnelled central venous catheter||13 (20)|
| Peripheral long line||4 (6)|
| Peripherally inserted central catheter||1 (1.5)|
| Line sepsis||11 (17)|
| Hyperglycaemia||3 (4.5)|
| Pneumothorax||2 (3)|
| Electrolyte disturbances||2 (3)|
| Venous thrombosis||1 (1.5)|
Table 2. Outcomes for patients with advanced ovarian cancer commenced on parenteral nutrition (PN)
|Number||18 (28)||40 (61)||7 (11)|
| Recurrent disease||14 (78)||32 (80)||7 (100)|
| Intestinal obstruction||10 (56)||28 (70)||5 (71%)|
| Good (≤1)||1 (5)||35 (88)||7 (100)|
| Poor (≥2)||17 (95)||5 (12)||0 (0)|
|Debulking surgery on same admission||7 (39)||26 (65)||4 (58)|
|Indication for PN|
| Intestinal obstruction||13 (72)||7 (17)||3 (42)|
| Protracted ileus||5 (28)||25 (63)||–|
| Nausea and vomiting||–||4 (10)||–|
| Enterocutaneous fistula||–||4 (10)||–|
| Short bowel syndrome||–||–||4 (58)|
|Median duration of PN (days)||5 (IQR 2–11)||10 (IQR 6–17)||241 (IQR 90–305)|
|Median survival from commencement of PN (days)||12 (IQR 6–28)||264 (IQR 96–564)||241 (IQR 90–305)|
The decision to provide PN to patients with disseminated ovarian cancer is often difficult and controversial (Barber et al., 1998). This is compounded by the lack of good evidence on which to base decision-making because most of the available literature consists of small, single institution series, often containing a heterogeneous cohort of different cancers. Brard et al. (2006) reported a modest survival benefit of 4 weeks in 55 patients receiving PN for terminal intestinal obstruction as a result ovarian cancer. This benefit was reduced in patients receiving concurrent chemotherapy. In another study of 61 patients receiving HPN for gynaecological malignancy (56% as a result of ovarian cancer), a significant improvement in nutritional and quality of life parameters was observed (King et al., 1993).
It is accepted that the present study is also limited by its relatively small cohort and retrospective data collection. However, the findings obtained would tend to support the previous literature. In particular, patients in group I received PN for a median of 5 days, and median survival from commencement of PN was 12 days. Clearly, it is difficult to justify the administration of PN in these patients. The majority of them had terminal intestinal obstruction, and a poor performance status. Second, the group that resumed enteral feeding contained a larger proportion of patients with protracted post-operative ileus rather than intestinal obstruction. Provision of PN in this group was largely an adjunct to surgery, as demonstrated by the median feeding time of 10 days. Although this group appears to do well, it is still not clear how much the addition of PN was beneficial, and whether the same outcome would have been achieved irrespective of its administration.
The only factor that does appear to distinguish the three groups of patients is the WHO performance status. In patients who were relatively independent, with a WHO status of ≤1, the use of PN appears to have been largely justified in terms of a reasonable expectation that some form of enteral nutrition might be re-established or, if not, the patient could be converted to HPN. They are therefore likely to be a self-selecting good prognostic cohort, and most likely will benefit from the enhanced nutritional support and improved quality of life that PN can bring (Chapman et al., 1991; King et al., 1993; Abu-Rustum et al., 1997; Philip & Depczynski, 1997; Whitworth et al., 2004). The importance of performance status when identifying those patients who should receive PN has been previously highlighted, and it has been suggested that PN is not justified in patients with a Karnofsky index of 50% or less (Bachmann et al., 2003). In addition to performance status, it is also critical to have some indication of the likely cancer-related prognosis. In patients with disseminated cancer, it is estimated that life-threatening weight loss will occur in 35–40 days (August et al., 1991). Consequently, if a patient with terminal cancer has an expected survival of >40–60 days, then the use of PN may be appropriate (Duerksen et al., 2004). It is appreciated that an accurate estimation of survival is not always possible, and inter-disciplinary discussion between nutrition teams and oncologists is of paramount importance with respect to properly assessing the relative merits before PN administration. Once PN has been started, it is often difficult to stop because this is frequently considered as a retrograde step by patients and relatives, consistent with the withdrawal of treatment.
In conclusion, patients with advanced ovarian cancer should not be denied the prospect of PN just because of the nature of the disease because even those individuals with terminal intestinal obstruction may derive some benefit. However, cautious judgment is required to select those who are most likely to benefit and should include a clear rationale for PN provision, which can be based on an assessment of the patient’s performance status and an evaluation of disease prognosis, as well as appropriate patient and carer counselling. Further research examining the role of PN in specific subgroup of patients with ovarian cancer, such as in those with terminal intestinal obstruction, is warranted.
Conflicts of interest, sources of funding and authorship
The authors declare that they have no conflicts of interest.
No funding is declared.
BM initiated the study, data collection and analysis and was involved in writing the manuscript; SY, KH and AB undertook the project design and analysis of data; TB edited the manuscript and supported and supervised the study; DGJ was involved in the project design, interpretation of results, manuscript editing, support and supervision. All authors critically reviewed the manuscript and approved the final version submitted for publication.