Indicators of Survival Duration in Ovarian Cancer and Implications for Aggressiveness of Care

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1 2221 Indicators of Survival Duration in Ovarian Cancer and Implications for Aggressiveness of Care Vivian von Gruenigen, MD 1,2 Barbara Daly, PhD 3 Heidi Gibbons, MS 1,2 Jessica Hutchins, MD 1,2 Andrew Green, MD 1,2 1 Department of Obstetrics and Gynecology, University Hospitals Case Medical Center, Cleveland, Ohio. 2 Department of Reproductive Biology, Case Western Reserve University, Cleveland, Ohio. 3 School of Nursing, Case Western Reserve University, Cleveland, Ohio. BACKGROUND. Ovarian cancer patients frequently receive chemotherapy near the end of life. The purpose of the current study was to develop indicators that characterize those ovarian cancer patients who have a short life span. METHODS. The medical charts of deceased epithelial ovarian cancer patients were retrospectively reviewed from 2000 through All patients received primary debulking surgery and adjuvant chemotherapy. Aggressiveness of cancer care within the last month of life was measured by chemotherapy regimens, emergency room visits, and hospitalizations. Significant clinical events (SCE) were defined as ascites, bowel obstruction, and pleural effusion. Survival quartiles were compared using chi-square and Student t test statistics. Multiple regression analysis was performed using survival duration as a dependent variable. RESULTS. In all, 113 patients with epithelial ovarian cancer were reviewed. Patients had increased hospitalizations (P <.001) and SCE (P <.001) as they approached the end of life. There was no difference in the pattern of hospitalizations and SCE between the top and bottom survival quartiles. Patients with a shorter survival time had a trend toward increased chemotherapy during their last 3 months of life (P 5.057) and had increased overall aggressiveness of care (P 5.013). In patients with a disease remission, the length of initial remission time was found to be significant in predicting survival (P <.01). Time to second disease recurrence was also significant in predicting survival time (P < 0.01). CONCLUSIONS. Patients who received aggressive care did not have improvement in survival. Short disease remissions and increasing hospitalizations with SCE should be indicators of the appropriateness of reducing cure-oriented therapies and increasing palliative interventions. Cancer 2008;112: Ó 2008 American Cancer Society. Presented in part at the American Society of Clinical Oncology 54th Annual Meeting, Atlanta, GA, June 2-6, Address for reprints: Vivian von Gruenigen, MD, Division of Gynecologic Oncology, University Hospitals Case Medical Center, Euclid Avenue, Room 7128, Cleveland, OH 44106; Fax: (216) ; vivian.vongruenigen@uhhospitals.org Received September 18, 2007; revision received November 16, 2007; accepted November 27, KEYWORDS: aggressiveness of care, chemotherapy, end of life, ovarian cancer, survival. Quality of life at the end of life (EOL) in ovarian cancer patients may be hindered by chemotherapy and aggressive care. Previous investigations of the clinical care of cancer patients at the EOL reveal substantial amounts of chemotherapy being provided along with increased hospitalizations. 1,2 Although the importance of quality of EOL care is a major focus, the trajectory of the disease process, or rapidity to terminal stage, is something that can affect care at the EOL as well. 3 Prognostic indicators such as performance status, clinical symptoms, and laboratory values have been explored to predict the EOL in cancer patients. 4 While exploring diagnostic and procedure codes in ovarian cancer patients, we found that admissions for bowel obstruction, pleural effusion, and ascites increased toward the EOL. 2 A subsequent publication on aggressive care in cancer patients near ª 2008 American Cancer Society DOI /cncr Published online 17 March 2008 in Wiley InterScience (

2 2222 CANCER May 15, 2008 / Volume 112 / Number 10 the EOL revealed new chemotherapy regimens, emergency room visits, hospital admissions, and short hospice enrollment increasing over the past decade. 5 Earle et al. s 5 indicators of aggressive cancer care are very similar to those of the National Quality Forum s (NQF) 6 consensus standards for symptom management and EOL care for patients with cancer. There is growing consensus that these standards can be used as targets for improving the quality of care in patients with advanced cancer. Because palliative care and hospice services have become an increasingly crucial part of our healthcare systems, the guidelines endorse a framework for care that is intended to develop a comprehensive quality measurement and reporting system. Because not all cancer patients have the same clinical symptoms and clinical course, it is important to explore what happens to ovarian cancer patients at the EOL. Because the majority of patients with recurrent ovarian cancer receive palliative chemotherapy at the time of disease recurrence, an effective strategy to guide patients and physicians with regard to when to withdraw therapy is imperative to improve quality care near the EOL. Thus, we believe that focusing research on clinical care patterns is crucial to improving quality of life. The purpose of the current study was to develop indicators that characterize those ovarian cancer patients who have a short life and evaluate trends in hospice transfer. We hypothesized that those patients with a short trajectory between diagnoses and death received more aggressive care and chemotherapy at the EOL. MATERIALS AND METHODS The medical charts of patients diagnosed with epithelial ovarian cancer who died during the years between 2000 and 2006 were retrospectively reviewed. For the years 2000 and 2001, charts were reviewed at Akron General Medical Center, SUMMA Heath System, Aultman Health Foundation, and University Hospitals Case Medical Center (UHCMC) (n 5 62). From 2002 through 2006, charts were reviewed only at UHCMC (n 5 51). Institutional Review Board approval was obtained for this retrospective study. Patients who never received chemotherapy or underwent primary debulking surgery or those who had a survival duration of <30 days were not included. Details of the method collections have been previously published. 2 Aggressiveness of cancer care (ACE) was defined according to Earle et al. 5 and includes occurrence of any of the following events: start of a new chemotherapy within 30 days of death, last chemotherapy within 14 days of death, >1 emergency room visit within the last month of life, >14 days in the hospital within the last month of life, >1 hospital admission within the last month of life, admission to the intensive care unit within the last month of life, and hospice patients with a length of stay of 3 days. These definitions are also used by the NQF as standards for assessing quality of care in cancer patients, with a lower incidence representing better EOL care. 6 Significant clinical events (SCE) were defined as hospitalizations for bowel obstruction, pleural effusion requiring thoracentesis, and abdominal ascites requiring paracentesis. 2 Palliative procedures not requiring hospitalization were not included. Data were analyzed in 3-month intervals within the last year of life. Only 1 event (primary SCE) per hospitalization was counted if multiple SCEs occurred within the same hospitalization. Repetitive SCEs were defined as the same SCE event occurring repeatedly within a time period of 2 months. Hospitalizations (including emergency room visits) were documented according to International Classification of Diseases (9th revision) (ICD-9) diagnosis codes and categorized into system management categories. To determine the number of patients hospitalized within each quarter, hospitalizations were counted only once during each quarterly interval, even if a woman was hospitalized more than once per interval. To determine the total number of hospitalizations and reasons for hospitalization for each quarterly interval, all hospitalizations and codes were counted. Statistical Analysis Descriptive statistics were used to summarize patient demographic and clinical variables and ACE. Hospice care and ACE indicators were compared between 2000 and 2002 (timeframe of prior publication) versus 2003 and 2006 by the chi-square or Fisher exact test. When pertinent, patients were stratified according to survival quartiles and variables were compared by use of the chi-square and Student t test between the upper and lower quartiles. The number of SCEs and hospitalizations in all patients were compared using the Mantel-Haenszel chi-square test for trend for quarterly time periods during the last year of life. In charts reviewed from UHCMC for patients who died between 2000 and 2006 (n 5 56 because of the availability of charts), multiple regression analysis was performed to examine the length of survival (dependent variable) and independent variables of age, number of SCEs, ACE, stage of disease, and time to first and second recurrence as independent variables. Patients were assigned a score of 0 to 6 according to

3 Ovarian CA and Aggressiveness of Care/von Gruenigen et al TABLE 1 Patient Demographic and Clinical Characteristics (n 5 113) Mean age at death (range), y 62.5 (21 89) Stage of disease I/II 10 (9%) III/IV 103 (91%) Median survival time (range), mo 33 (4 142) Median no. of chemotherapy regimens (range) 3.0 (1 8) Hospice care (home or center) 61 (54%) Median length of hospice care, d 25 Location of death Home 52 (46%) Hospice center 24 (21%) Hospital 19 (17%) Nursing home/skilled facility 6 (5%) Unknown 12 (11%) Chemotherapy during last 3 mo 65 (57.5%) Values are presented as the number (%) unless otherwise specified. the number of ACEs they experienced. Similarly, each patient was given a score of 0, 1, 2, or 3 representing the number of SCEs they experienced during the last year of life (at any timepoint). Regression analysis was repeated with time to second disease recurrence (defined as the time from original diagnosis until the second disease recurrence) as well. Pearson correlation coefficients, variance inflation factor, and tolerance were used to examine correlations and multicollinearity between variables. SPSS statistical software (version 14.0; SPSS Inc, Chicago, Ill) was used for analysis. RESULTS The medical records from 113 patients who received primary debulking surgery and adjuvant chemotherapy with a death date during the years 2000 through 2006 were reviewed. Patient characteristics are presented in Table 1. The median age of the patients at death was 62.5 years; 32 patients were aged >70 years. Approximately 91% of the women had stage III or stage IV disease (determined according to the Federation of Gynecology and Obstetrics grading system). The median survival from the date of diagnosis was 33 months and the median number of chemotherapy regimens administered was 3. Forty-six percent of patients died in their home (with or without hospice support). Approximately 54% of patients had some form of hospice support either in their home or at a hospice center. Twenty-six of 63 patients (41%) who died between 2000 and 2002 received hospice care (either home care or at a center) compared with 35 of 50 patients (70%) who died between 2003 and 2006 (P 5.002). Eighteen of 65 patients (27.7%) who received chemotherapy during the last 3 months of life died in the hospital compared with only 1 of 48 patients who did not receive chemotherapy during this time (P <.001). Approximately 31% of patients received aggressive care at the EOL (Table 2). Death in an acute hospital setting and starting a new chemotherapy regimen within the last 30 days were the most common indicators at 16.8% and 11.5%, respectively. There was no difference overall in ACE indicators noted over the study period because 33% of patients who died between 2000 and 2002 and 28% of patients who died between 2003 and 2006 had positive ACE indicators (Table 2, P 5.542). However, patients from 2000 through 2002 died more frequently at the hospital than those who died between 2003 and 2006 (P 5.026). In patients with an ACE indicator (excluding death at a hospital), 10 of 27 patients (37%) died in the hospital compared with 9 of 86 patients (10.5%) without any ACE measures (P ). There was no statistically significant difference (P 5.981) noted with regard to the proportion receiving hospice care among patients with at least 1 ACE indicator (15 of 27 patients; 55.6%) and those with no ACE indicators (48 of 86 patients; 55.8%). Approximately 14% of ACE patients had 2 indicators. Data from patients in the lower (n 5 28) and upper (n 5 28) survival quartiles were compared (Table 3). Patients with a shorter survival time had a trend toward receiving more chemotherapy during their last 3 months of life (P 5.057) and received more aggressive care (P 5.013). Approximately 53% of patients in the lower survival quartile had at least 1 ACE indicator compared with 21% of patients in the upper survival quartile. Administering a new chemotherapy regimen within the last 30 days of life resulted in many other interactions. Six of 13 patients (46%) who received a new chemotherapy regimen within the last 30 days before death had >1 hospital admission during the last month of life or were hospitalized 14 days during the last month of life compared with 11 of 100 patients (11%) who did not receive a new chemotherapy regimen during this time (P <.001). The number of SCEs increased in all patients during the last year of life (Table 4). SCEs were not found to be significantly different between patients in the lower and upper survival quartiles and the frequency of these events occurred equally in the upper and lower survival quartiles. Increased aggressiveness of care, indicated by ACE, was not associated with a decrease in SCE. Twenty-three of 113 patients (20.4%) had repetitive SCEs, with the most common being ascites requiring paracentesis. Hospitalizations increased as patients approached the EOL and there

4 2224 CANCER May 15, 2008 / Volume 112 / Number 10 TABLE 2 Aggressiveness of Care Indicators for Versus Overall P* Aggressiveness of care 35 (30.9%) 21 (33.3%) 14 (28%) NS 1. Last chemotherapy within 14 d of death 10 (8.8%) 7.9% 10% NS 2. New chemotherapy regimen in last mo of life 13 (11.5%) 7.9% 16% NS 3. Emergency room visit(s) in last mo of life 0 0% 0% NS 4. Hospital admission(s) in the last mo of life 10 (8.8%) 9.5% 6% NS d or more in hospital during last mo of life 11 (9.7%) 7.9% 10% NS 6. Intensive care unit admission in last mo of life 4 (3.5%) 3.2% 4% NS 7. Hospice patients with length of stay 3 d 4 (3.5%) 3.2% 4% NS 8. Death at a hospital 19 (16.8%) 23.8% 8%.026 NS indicates not significant. Values are presented as the number (%). * The chi-square or Fisher exact tests were used to compare years versus years TABLE 3 Clinical and Demographic Characteristics in the Upper and Lower Survival Quartiles Lower survival quartile (n 5 28) Upper survival quartile (n 5 28) P* Stage.111 I/II 0 4 (14.3%) III/IV 28 (100%) 24 (85.7%) No. of chemotherapy regimens, mean SEM <.001 Hospice care (either home or at center) 10 (35.7%) 14 (50.0%).280 Hospice care (median, range), d 21.5 (1 126) 27 (2 180).320 Chemotherapy during last 3 mo 20 (71.4%) 8 (46.4%).057 Aggressiveness of care 15 (53.6%) 6 (21.4%) Last chemotherapy within 14 d of death New chemotherapy regimen in last mo of life Emergency room visit(s) in last mo of life Hospital admission(s) in the last mo of life days or more in hospital during last mo of life Intensive care unit admission in last mo of life Hospice patients with length of stay 3 d Death at a hospital 7 5 Significant clinical events during last year of life, mean Hospitalizations during last y, mean SEM indicates standard error of the mean. Values are presented as the number (%) unless otherwise specified. * The chi-square or Fisher exact test was used for proportions and the Student t-test was used for comparisons. TABLE 4 Specific SCE Events and Hospitalizations in All Patients (n 5 113) Months prior to death P * No. of patients hospitalized <.001 Total no. of hospitalizations Ascites y 0 (1) 3 (4) 8 (21) 11 (41) <.001 Bowel obstruction y 1 (3) 2 (3) 8 (7) 25 (40) <.001 Pleural effusion y 2 (2) 1 (1) 4 (5) 11 (23).001 SCE indicates significant clinical event. * The Mantel-Haenszel chi-square test for trend was used to determine the P value. y Number of patients (total number of events) who had a SCE. was no significant difference noted between the number of hospitalizations over time between patients in the upper and lower survival quartiles. During the last 6 months of life, the 3 most common reasons for hospital admissions included digestive (47 of 113 patients; 41.6%), circulatory (32 of 113 patients; 28.3%), and infectious disease (22 of 113 patients; 19.5%) system categories. There was no difference in reasons for hospitalizations between patients in the upper and lower quartiles (data not shown). Multiple regression analysis was performed with data from the 56 patients who died between 2000

5 Ovarian CA and Aggressiveness of Care/von Gruenigen et al TABLE 5 Multiple Regression Analysis for Duration of Survival Time (n 5 56) Standardized beta t value P Time to second disease recurrence <.001 Age SCE (no. of events) Stage Aggressiveness of care (points) SCE indicates significant clinical event. F , P <.001; adjusted r and 2006 at UHCMC. In patients with a disease remission, the length of initial remission time was found to be significant in predicting survival (P <.01). Because the majority of ovarian cancer patients go into a first disease remission, time to second disease recurrence was used for prediction of survival over first disease remission. Duration from diagnosis to second disease recurrence was found to be statistically significant in predicting the duration of survival in these patients (Pearson correlation coefficient [r] 5.57; P <.01) (Table 5). Because this variable included the time from diagnosis to the first disease recurrence (initial disease remission time), only time to second disease recurrence was used in the final regression model. Age, stage, and ACE trended toward significance in predicting the duration of survival, but the number of SCEs experienced was not found to be significant. Increasing age and number of ACEs experienced was associated with a trend toward a decrease in the duration of survival. DISCUSSION A substantial number of ovarian cancer patients are receiving aggressive care at the EOL, including frequent hospitalizations, significant clinical events, and chemotherapy. It is interesting to note that those patients with a short trajectory of disease appeared to have the same significant clinical events, which increased over time in all patients, suggesting that the characteristics of patients in the terminal phase of illness is similar to those with longer survival duration. Not surprisingly, time to second disese recurrence was found to be predictive of survival. ACE, age, and stage of disease were not found to be significant contributors to the model, highlighting that increasing aggressive care does not improve survival. Approximately 31% of the patients in the current study had positive indicators of ACE within the last month of life. Earle et al. 5 analyzed Medicare claims in nearly 30,000 patients who died within 1 year of an initial diagnosis of lung, breast, colorectal, or other gastrointestinal cancers. Through their previously identified indicators, they found a 30% incidence of ACE. Because our patient population included many patients who were >1 year from diagnosis, it would be anticipated that the percentage of patients in this study with positive indicators of aggressive care would have been <30% because they have a more predictable course of disease recurrences and remissions. According to the NQF, all the aggressiveness of care measures reflect deviations from quality indicators. Because palliative care and hospiceserviceshavebecomeanincreasinglycrucial part of our healthcare systems, the guidelines endorse a framework for care that is intended to develop a comprehensive quality measurement and reporting system. Others have attempted to identify ovarian cancer patients unlikely to benefit from palliative chemotherapy. In what to our knowledge is 1 of the largest studies published to date, Hoskins and Le 7 described a model for survival in 120 patients for whom data were available after first disease recurrence. This was done with the purpose of guiding chemotherapy decisions after the patients developed disease recurrence. A predictive model based on the length of time between diagnosis to second disease recurrence was found to be predictive of which patients would survive <6 months. In particular patients, however, they found that multiple episodes of retreatment were of value. Of interest, expected prognostic variables such as age, residual tumor at the time of original surgery, grade, stage, and pleural effusions were not significant predictors of survival after the first disease recurrence. We also found age and stage to be nonsignificant variables after the first disease recurrence, with ACE being similarly nonsignificant. A recent article determined that more chemotherapy in ovarian cancer patients may not translate into longer survival but does increase morbidity. 8 We found that patients who progress and die rapidly are more likely to receive therapy shortly before death. This is more likely a measure of the aggressive nature of the disease and not a function of chemotherapy treatment. Tumor biology and platinum resistance all play a part in the aggressiveness of ovarian cancer. However, our findings do suggest that in the presence of rapidly progressive disease, aggressive care measures such as new chemotherapy regimens within the last month of life and the administration of chemotherapy within the last 2 weeks of life are not associated with a survival benefit.

6 2226 CANCER May 15, 2008 / Volume 112 / Number 10 It is well known that for some individuals, continuing the fight, regardless of effectiveness, has great meaning and adds value to existence. 9 For example, Brown et al. 10 reported that only 5% of their sample of 108 women with gynecologic malignancies predicted that they would give up the fight if the time came that their treatment was no longer working. The study by Donovan et al. 11 examining treatment preferences using a decision board found that 25% of recently diagnosed ovarian cancer patients indicated that they would never switch to palliative care, but would choose salvage therapy even if the anticipated median survival time was <1 week. Although it is the patient s decision to continue therapy, physicians do have some influence on this course of action. Studies have shown that cancer physicians consistently overestimate the duration of survival. 12,13 In the current study, the upper and lower quartiles of survival differed with regard to chemotherapy patterns and aggressiveness of care, but were similar with regard to hospice patterns and SCEs or clinical pattern of death. Those patients who received the most aggressive care within the last month of life did not have the longest survival. In all patients, regardless of quartile, SCE events were rarely observed before 6 months before death. However, in the 6 months before death and especially within the last 3 months, there was a marked increase in the number of events and repetitive occurrences. Absence of SCE should not be viewed as indicating that conversations about goals of care do not need to occur. The occurrence of these events, however, does suggest an increased likelihood of the onset of the terminal phase and should prompt discussions regarding goals and transitions to a comfort-oriented plan of care. Unfortunately, the majority of women died without hospice support despite our improvements in hospice transfers. Recent evidence from Connor et al. 14 indicates that there may be a survival benefit to patients enrolled in hospice. Since the initiation of this study in 2002, our division has developed a heightened awareness to this issue and, as illustrated in this report, our practice patterns have changed over time. However, continued improvement, both at our center and in the community, is still needed. Trajectories have been used to describe functional decline before death. 15 Patient groups differ in the slope of decline between sudden death, organ failure, frailty, and terminal illness. Based on hospitalizations, we hypothesize that the trajectory of death in ovarian cancer patients undulates with a steady decline (Fig. 1). It may also be described as entryreentry, a pattern in which individuals decline but return home, or receive further therapy between FIGURE 1. Theoretic trajectory of dying in patients with recurrent ovarian cancer. stays in the hospital. 15 Although this is a retrospective descriptive report, it should evoke thoughtful consideration in the cancer care provider. Our data source was a retrospective review of medical records with inherent limitations, including the lack of a quality-of-life component and cost measures. In general, the majority of our patients are treated in our health system, but there is always the possibility of unknown events (hospitalizations and SCE) that occurred at other facilities and are not included in our medical charts. Patients with advanced cancer may be directly admitted to a hospital floor instead of being directed to the emergency room; therefore, our ACE numbers related to emergency room admissions may be falsely low. In addition, there are those circumstances in which patients are admitted to the hospital for palliative reasons, although this dataset revealed that the most common reasons for hospital admission were related to digestive and circulatory problems. Finally, our regression analysis included only 56 patients. Prospective studies of ovarian cancer patients at the EOL would ensure the capture of these events. There is a difference between palliative chemotherapy administered early in the trajectory of disease and near the EOL. It is unknown whether chemotherapy was given in these study patients with the goal of palliation of symptoms or the prolongation of life; however, we suspect the latter. Regardless, time to second disease recurrence should be a trigger for less chemotherapy, less aggressive care, and EOL discussions with the patient. The goal of EOL care should be to avoid interventions, such as cytotoxic chemotherapy, that are likely to decrease the quality of life while failing to increase survival. Despite the lack of prospective randomized trials,

7 Ovarian CA and Aggressiveness of Care/von Gruenigen et al there is evidence indicating that specific procedures, such as paracentesis and thoracentesis, relieve symptoms more than chemotherapy at the EOL. 2 In addition, these definitions may blend further as noncytotoxic therapies, such as bevacizumab (Avastin; Genentech, San Francisco, Calif) may be a viable palliative care option for ascites. 16 Although these data do not provide definitive guidelines regarding when to withdraw aggressive care and chemotherapy, the current study does provide a prescriptive message as cancer care providers, we have an obligation for improvement. Finally, this information should be shared with patients and their families. It is also the hope that cooperative cancer research groups embark on prospective trials near the EOL so that clinical cancer research is not limited to pharmacologic agents. REFERENCES 1. Emanuel EJ, Young-Xu Y, Levinsky NG, Gazelle G, Saynina O, Ash AS. Chemotherapy use among medicare beneficiaries at the end of life. Ann Intern Med. 2003;138: von Gruenigen VE, Frasure HE, Reidy AM, Gil KM. Clinical disease course during the last year in ovarian cancer. Gynecol Oncol. 2003;90: LoCoco S, Covens A, Carney M, et al. Does aggressive therapy improve survival in suboptimal stage IIIc/IV ovarian cancer? A Canadian-American comparative study. Gynecol Oncol. 1995;59: Vigano A, Bruera E, Jhangri GS, Newman SC, Fields AL, Suarez-Almazor ME. Clinical survival predictors in patients with advanced cancer. Arch Intern Med. 2000;160: Earle CC, Neville BA, Landrum MB, Ayanian JZ, Block SD, Weeks JC. Trends in the aggressiveness of cancer care near the end of life. J Clin Oncol. 2004;22: Specifications of national voluntary consensus standards for symptom management and end-of-life care in cancer patients. The National Quality Forum. Available at: Accessed January 15, Hoskins PJ, Le N. Identifying patients unlikely to benefit from further chemotherapy: a descriptive study of outcome at each relapse in ovarian cancer. Gynecol Oncol. 2005;97: Silber JH, Rosenbaum PR, Polsky D, et al. Does ovarian cancer treatment and survival differ by the specialty providing chemotherapy? J Clin Oncol. 2007;25: Matsuyama R, Reddy S, Smith TJ. Why do patients choose chemotherapy near the end of life? A review of the perspective of those facing death from cancer. J Clin Oncol. 2006;24: Brown D, Roberts JA, Elkins TE, Larson D, Hopkins M. Hard choices: the gynecologic cancer patient s end-of-life preferences. Gynecol Oncol. 1994;55(3 pt 1): Donovan KA, Greene PG, Shuster JL, Partridge EE, Tucker DC. Treatment preferences in recurrent ovarian cancer. Gynecol Oncol. 2002;86: Glare P, Virik K, Jones M, et al. A systematic review of physicians survival predictions in terminally ill cancer patients. BMJ. 2003;327: Gripp S, Moeller, Bolke E, et al. Survival prediction in terminally ill cancer patients by clinical estimates, laboratory tests, and self-rated anxiety and depression. J Clin Oncol. 2007;25: Connor SR, Pyenson B, Fitch K, Spence C, Iwasaki K. Comparing hospice and nonhospice patient survival among patients who die within a 3-year window. J Pain Symptom Manage. 2007;33: Lunney JR, Lynn J, Foley DJ, Lipson S, Guralnik JM. Patterns of functional decline at the end of life. JAMA. 2003; 289: Numnum TM, Rocconi RP, Whitworth J, Barnes MN. The use of bevacizumab to palliate symptomatic ascites in patients with refractory ovarian carcinoma. Gynecol Oncol. 2006;102: