Poor ECOG Performance Status Research Articles

1350 - Metastatic Nsclc Outcomes at a Single Canadian Institution Over a Decade

ABSTRACT Background In the past 10 years, the standard of care in non small cell lung cancer has seen the adoption of several less toxic and better tolerated therapies, allowing a greater proportion of metastatic patients the opportunity to receive 2nd and even 3rd line treatment. We investigated whether this improvement in the number of available therapies for metastatic NSCLC had any bearing on overall patient survival, by retrospectively analyzing patients diagnosed in 1999, 2004 and 2009 at our centre. Methods Demographic details, clinical variables and outcome data were gathered retrospectively via chart review, on NSCLC patients diagnosed at the Tom Baker Cancer Centre (TBCC) in 1999, 2004 and 2009 (Glans-Look Lung Cancer Database). All patients were restaged according to the new 7th Edition of the American Joint Committee on Cancer TNM system for NSCLC staging. Survival was analyzed using the Kaplan-Meier method and differences measured by a log rank test. Results 807 patients were included in the analysis (649 who were stage IV at diagnosis, 158 who recurred with metastatic disease). Of these patients, 22.1% received palliative systemic therapy (18.9% in 1999, 23.0% in 2004 and 23.1% in 2009). During this time, the proportion of patients who received 2 or more lines of treatment almost doubled (6.9% in 1999, 9.0% in 2004 and 12.7% in 2009). In addition, there was a trend towards increasing median overall survival (MOS) of systemically treated patients over 1999-2009, from 10.8 months (95% CI: 8.4-13.3) in 1999 to 14.7 months (95%CI: 9.6-14.4) in 2009 (p = 0.2). Conclusions Our analysis suggests that there is an increasing proportion of metastatic NSCLC patients being treated systemically at our centre, specifically, the proportion of patients being treated with two or more lines of systemic therapy has increased over the decade from 1999-2009. This study also suggests a trend toward an increased MOS for systemically treated patients diagnosed in 2009 compared to those diagnosed in 1999. However, the vast majority of patients (>3/4) are still not being treated with systemic therapy, despite the increase in available therapies now compared to a decade ago. The reasons for this are not clear but may include poor ECOG performance status, rapid decline, sub-optimal referral pathways and rural residence. Disclosure All authors have declared no conflicts of interest.

Baby-step chemotherapy as a way to deliver chemotherapy in poor PS small cell lung cancer.

e17500 Background: Majority of patients with SCLC present with advanced stage and poor ECOG performance status. Hence delivery of adequate dose of chemotherapy is compromised. We hypothesized that initial low-dose chemotherapy might improve PS and enable administration of standard-dose chemotherapy, thus extending benefit of chemotherapy to otherwise ineligible patients. Methods: 30 patients with ECOG performance status 2-4 received low-dose chemotherapy consisting of either single agent carboplatin at AUC 2 or an abbreviated course of platinum-etoposide. Patients whose PS improved got full-dose chemotherapy with the standard regimen of platinum-etoposide. Demographic details, toxicity, time to progression and overall survival were analyzed. Univariate and multivariate analysis was performed to determine factors associated with TTP and OS. Results: Median age was 58 years with male predominance. The PS was IV in 9, III in 20 and II in 1 patient. Extensive-stage and limited-stage disease was seen in 24 and 6 patients respectively.15 patients received single-agent carboplatin, 10 patients abbreviated cisplatin-etoposide, 1 patient each cyclophosphamide and cisplatin-etoposide and 3 patients refused chemotherapy. Major grade 3-4 toxicity was mucositis in 1, loose motions in 1 and hyponatremia in 4 patients. There was no grade 3- 4 haematological toxicity. The median number of dose-reduced cycles was 1 and 3 patients received more than 2 cycles. 22 patients were eligible and willing for full-dose chemotherapy. The median time to start of full-dose chemotherapy was 11.5 days (4-26 days). The median number of cycles of standard-dose chemotherapy was 5 (1-6) with 16 completing planned schedule. Grade 3-4 toxicity was neutropenia in 50%, febrile neutropenia in 25%, loose motions in 25% and hyponatremia in 40%. The overall TTP and OS was 182 days and 263 days respectively. Presence of SIADH (p = 0.02) and completion of standard treatment (p = 0.001) had a positive impact on TTP while completion of treatment (p = 0.01) and normal LDH (p = 0.03) had a positive impact on OS. Conclusions: Low-dose chemotherapy is well-tolerated and might help in extending the benefit of standard-dose chemotherapy to otherwise ineligible patients.

Outcomes of a Cancer Clinical Trial Matching Service

The American Cancer Society (ACS) and Coalition of Cancer Cooperative Groups (CCCG) provide a clinical trial (CT) information/matching/eligibility service (Clinical Trials Matching Service [CTMS]). Patients' demographic and clinical data, enrollment status, and self-reported barriers to CT participation were analyzed to assess enrollment rates and determinants of enrollment. During 3 years beginning October 1, 2007, the CTMS served 6,903 patients via the ACS call center. Among the 1,987 patients with follow-up information on enrollment, 219 (11.0%) enrolled in a CT; 48 of these 219 enrollees chose a CT they found via the CTMS. Patients were less likely to enroll if they had poor ECOG performance status (P = 0.032); were African American (P = 0.0003), were uninsured or had Medicaid coverage (P = 0.024), or had lower stage disease (P = 0.018). Enrollment varied by trial type/cancer site/system (P = .026). Several barriers significantly predicted nonenrollment. Broader availability of a CTMS might help improve patient participation in cancer clinical trials.

Baseline Quality of Life Assessed with the EORTC QLQ-C30 Predicts the Treatment Outcome of Patients with Diffuse Large B-Cell Lymphoma: Results of a Prospective Cohort Study

Abstract 1595 Background:The self-reported Quality of life (QoL) assessment has been widely used as an endpoint for clinical trials along with traditional endpoints of response and survival because the QoL can provide the health-related information, and it should be considered another parameter to estimate the efficacy of treatment. However, there is growing evidence that the QoL assessment can be used as a prognostic factor in cancer patients. Thus, the prognostic value of baseline QoL was reported in several different types of cancers independent of other clinical prognostic factors. Considering the performance status of patients is an important prognostic factor in lymphoma, the assessment of QoL at diagnosis might be an informative tool for predicting treatment outcome of lymphoma. However, few data exists regarding the prognostic relevance of baseline QoL in patients with lymphoma. Thus, we evaluated the prognostic impact of baseline QoL on the outcome of patients with diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma. Methods:The Samsung Medical Center Lymphoma Cohort Study (SMCLCS) is a prospective cohort study registering patients diagnosed with Hodgkin and non-Hodgkin lymphoma at the Samsung Medical Center (NCT00822731). All patients completed the version 3.0 of the European Organization for Research and Treatment of Cancer (EORTC) Core Questionnaire (QLQ-C30) after they provided written inform consents. Among patients registered in the SMCLCS, we analyzed the baseline QoL and clinical data of 263 patients consecutively diagnosed with DLBCL between September 2008 and February 2011. Primary CNS lymphoma was excluded, thus, all patients were treated with rituximab-CHOP. We made a prognostic model according to the scores of three items: (1) Global health status representing general health condition, (2) Functional scale representing physical function, (3) Symptom scales representing symptoms and signs. Each item was counted as one point if the score of each item was higher than 50. Thus, patients were classified as good (3 points), moderate (2 points) and poor QoL (score =0 or 1) groups. The QoL scores of patients with marginal zone B-cell lymphoma (MZL, n = 110) were used as a control. Results:The median score of Global health status was 50 (range 0–100) while the median scores of Functional and Symptom scales were 78.4 (24.1–100.0) and 79 (25.9–100.0), respectively in patients with DLBCL. These scores were significantly lower than a control group, MZL (P < 0.05). When patients were categorized into three groups, the good and moderate QoL groups accounted for 43.0% (n = 113) and 41.1% (n = 108) of patients, respectively. The proportion of poor QoL group of DLBCL was 16.0% (n = 42), and it was higher than that of MZL (2.7%). When the QoL at diagnosis was compared with other clinical factors, the poor QoL was significantly associated with poor ECOG performance status (≤ grade 2) whereas age older than 60 years was not significantly related with the poor QoL. The clinical factors representing high tumor burden such as elevated serum LDH, the number of extranodal involvement and Ann Arbor stage were significantly associated with the QoL model, thus, patients with high tumor burden showed poor QoL (P < 0.05). In consistent with this, patients with high or high-intermediate International Prognostic Index showed worse QoL scores than low or low-intermediate risk group. The frequency of treatment-related mortality was significantly higher in patients belonging to moderate and poor QoL groups than good QoL group (P < 0.05). As a result, more than 20% of the moderate or poor QoL group failed to complete the planned treatment schedule of rituximab-CHOP while only 10% of patients of the good QoL group could not finish the treatment. As a result, the overall survival of the good QoL group was significantly better than moderate and poor QoL groups (p < 0.05). This risk stratification based on the baseline QoL assessment was independently prognostic for overall survival in the multivariate analysis after controlling for International Prognostic Index. Conclusion:The baseline quality of life assessed with the EORTC QLQ-C30 is significantly associated with high tumor burden and worse overall survival of DLBCL. Thus, this prospective result suggests that the it may become a feasible prognostic factor in patients with DLBCL. Disclosures:No relevant conflicts of interest to declare.

A prospective, observational study of medication use among outpatients with common solid tumors.

9055 Background: In addition to treatment for their primary disease, cancer patients (pts) receive medications (meds) for relief of symptoms arising from the disease or its treatment and for prevention and treatment of other concurrent conditions. As part of the ECOG Symptom Outcomes and Practice Patterns study (SOAPP), we explored the number and type of agents pts receive and examined factors associated with taking more than 10 meds. Methods: Eligible pts were seen in outpatient academic or community cancer clinics and agreed to complete a survey at two time points 28 to 35 days apart. Data on current meds were collected through health care providers at both time points. Descriptive statistics, Fisher's exact test, and logistic regression (LR) were used to summarize the findings. Results: In 2,795/3,106 evaluable pts responding to the question at baseline (90% response rate), 32% were taking 0-4 meds, 43% were taking 5-9 meds, and 25% were taking >10 meds. The 5 most frequently prescribed categories of med among 3099 pts with available data were anti-hypertensives (46%), non-opioid pain meds (38%), GI meds other than antiemetics (38%), psychiatric meds (35%), antiemetics (32%). In addition, 48% of pts were taking nutrition supplements. A multivariable LR model showed that Non-Hispanic white pts, older pts, pts with poor ECOG performance status, pts with diagnoses of lung and prostate cancer, and pts with advanced stage of disease were more likely to be taking 10 or more meds. These pts were as prevalent in community practices as in academic settings (p=0.63). Conclusions: Outpatient management of solid tumor patients is complex due to co-morbidities and the need for pharmaceutical intervention of both symptoms of disease and side effects of treatment. The strongest predictor of polypharmacy is race/ethnicity. Factors asssociated with > 10 meds Odds ratio 95% CI P Female 1.13 0.89 – 1.43 0.31 White/non-Hispanic 2.84 2.15 – 3.76 <0.0001 Primary site lung/prostate 1.78 1.40 – 2.25 <0.0001 ECOG PS 2-4 vs PS 0 1.63 1.13 – 2.34 0.001 ECOG PS 2-4 vs. PS 1 1.17 0.83 – 1.64 0.43 Advanced disease 1.41 1.15 – 1.72 0.001 Age > 65 1.72 1.40 – 2.12 <0.0001 Number of moderate to severe symptoms 1.06 1.06 – 1.12 <0.0001

Biologic Features and Clinical Outcomes According to Age Groups In Myelodysplastic Syndrome

AbstractAbstract 4963Myelodysplastic syndrome (MDS) is a disease of the elderly, but can also affect younger people. Age is known to be an important prognostic factor in MDS but age variable is not included in most prognostic scoring systems because it is not thought as a disease-related variable. Many reports have showed that MDS is seen one to two decades earlier in Far Eastern countries than Western countries. We retrospectively investigated the differences in biologic features and clinical outcomes according to different age groups in Korean patients with MDS. Primary end points of our study were overall survival (OS) and progression-free survival (PFS). PFS was defined as time from diagnosis to AML progression or death. About one third of the patients received intensive treatment including chemotherapy, hypomethylating treatment or hematopoietic cell transplantation. Therefore, all survival data were censored at the start of intensive treatment to eliminate the influence of the treatments on clinical outcomes. A total of 403 patients, 248 males and 155 females, were included in this study. Median age was 54 years. We divided the patients into three age groups: ≤50 years (n=181), 51 to 60 (n=81), and over 60 (n=141). Baseline biologic features were significantly different according to three age groups: with increasing age, more male preponderance (P=0.009), more BM blast percentage (P<0.001), more advanced WHO subtype (P<0.001), higher proportion of high risk cytogenetic features (P=0.052; ≤60 vs. >60, P=0.011), poorer ECOG performance status (P=0.004), higher IPSS risk group (P=0.019). Five-year survival probabilities were significantly different according to age groups (≤ 50 vs. 51–60 vs. > 60; OS, 66.8% vs. 28.5% vs. 12.2%, P<0001; PFS, 58.5% vs. 37.9% vs. 12.3%, P<0.001). Survivals were also significantly different according to age groups in both IPSS Low/INT-1 (P<0.001 for OS, P=0.001 for PFS) and IPSS INT-2/High risk group (P=0.026 for OS, P=0.069 for PFS). Cox proportional hazards models also demonstrated that age group was an independent prognostic factor for survivals: ≤ 50 vs. 51–60 and > 60; OS, RR 2.3 (P=0.037) and RR 4.6 (P<0.001); PFS, RR 1.3 (P=0.449) and RR 2.0 (P=0.012). Conclusion:Biologic features and clinical outcomes were significantly different among age groups in MDS. Clinical outcomes were better in younger age group independently of biologic features. Survivals (OS & PFS) were better in younger age group and survival differences by age groups were observed in both lower and higher risk MDS, suggesting that age stratification should be considered in treatment decision and clinical trial design. Disclosures:No relevant conflicts of interest to declare.

An analysis of prognostic factors of comprehensive geriatric assessment (CGA) and development of a clinical scoring system in elderly Asian cancer patients.

9165 Background: Certain components of the comprehensive geriatric assessment (CGA) correlate with survival in elderly cancer patients. The purpose of this study was to determine the impact of each CGA domain on overall survival and to develop a prognostic scoring system to stratify elderly cancer patients into risk groups. Methods: A retrospective analysis of CGA data collected from 318 consecutive cancer patients who attended the outpatient geriatric oncology clinic at the National Cancer Center Singapore, aged 70 years and above was performed. Univariate and multivariate analyses were done using Cox proportional hazard method to identify significant prognostic factors within the CGA. A simple scoring algorithm to predict overall survival was developed using the regression coefficients from the multivariate model with total clinical scores ranging from 0 to 6. Results: Median age of the 318 patients was 77 years old (range: 70-94 years). ECOG performance status, functional status (ADL/IADL) and presence of geriatric syndromes were shown to be highly co-dependent variables. In our model, poor ECOG performance status (≥ 2 vs. < 2: HR=2.28, 95% CI= 1.44 - 3.61), high malnutrition risk (high risk vs. low risk: HR=2.59, 95% CI= 1.64 -4.10) and advance stage of disease (late vs. early: HR=2.14, 95% CI= 1.25–3.67) were independent predictors of survival. The patients with high risk clinical score 5-6 (HR=4.92, 95%CI = 2.72–8.87) and moderate risk score 3-4 (HR=2.09, 95%CI = 1.09–4.02) had significantly higher mortality rates compared to those classified as low risk score 0-2. The 2-year survival rate for low, moderate and high risk groups were 74.9% (95%CI 58.9-85.4), 50.9% (95% CI 37.0–63.3) and 23.2% (95% CI 16.8–30.1) respectively. Longer term follow-up and a larger sample size may identify factors that will significantly distinguish the low and moderate risk groups. Conclusions: The results confirm the importance of the CGA in the assessment of the elderly cancer patient. The development of the risk scoring system incorporating few key prognostic factors helps stratify patients into risk groups for further intervention. No significant financial relationships to disclose.

The Effect of Disease Progression on Patient Reported Outcomes in HER-2 Negative Metastatic Breast Cancer Patients.

Abstract Background: Patients with HER-2 neg metastatic breast cancer (MBC) often experience a wide range of cancer related symptoms, which may impact their quality of life (QoL). We conducted a retrospective analysis to characterize the differences between patient-reported outcomes (PROs) of MBC patients prior to progression of disease (PD) and following PD, and examined the effect of metastases in bone, lung, liver, peritoneum and central nervous system (CNS) on PROs.Methods: 102 HER-2 neg MBC patients were enrolled from 7 community oncology practices within the U.S. The source data comprised data abstracted from medical records and PROs from the 38-item Patient Care Monitor (PCM). The PCM consists of 6 indices including impaired ambulation, impaired performance, general physical symptoms, treatment-related side effects, despair and depression, and acute distress. Linear mixed-effect models were used to analyze change in PCM index scores over time, controlling for individual, disease, and treatment characteristics. Minimum important difference for PCM index scores was estimated to be 1.5 to 3 points (Ringash 2000).Results: The sample (n=102) consists of 72% Caucasian, 25% African American, 3% other race patients, with mean age of 57 years. The ECOG performance status (PS) was unknown in 58% of the cases. Among those with known PS, 79% had a status of 0 or 1. Most patients (87%) had previous surgery, and 62% had received adjuvant chemotherapy. The mean time from metastatic diagnosis to first PD was 14 months. The predominant sites of metastasis were bone (66%), lung (35%), and liver (33%). First line treatment was hormone therapy only for 29%, no treatment recorded for 4%, taxane based for 42%, and non-taxane based for 25%. Linear mixed-effect model results showed modest but statistically significant (p&amp;lt;0.005) worsening for General Physical Symptoms (2.4 points), Acute Distress (2.3 points), and Impaired Performance (1.7 points) scores following PD. The effect of PD was non significant for other index scores. Changes in symptoms severity following PD varied depending on metastasis location, being on chemotherapy, and ECOG status at baseline. There were marked detrimental effects of liver metastasis on Treatment related Side Effects, and of brain metastasis on Acute Distress. The most consistent effect on PROs was associated with PS. Patients with PS of 2 – 4 had worse scores in all areas except Acute Distress and Treatment Side effects.Conclusions: PD was associated with modest but significant worsening of general physical symptoms, acute distress, and impaired performance scores. Patients with poor ECOG PS at baseline were most affected. These findings suggest that delaying disease progression may have a positive impact on patients' QoL.Reference: Ringash J et al. Minimal important difference for quality of life measures is about five to ten percent of the instrument range. Presented at Proc Am Soc Clin Oncol. May 20-23, 2000. New Orleans, LA. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5050.

Statistical Correlations Between Quantifiable Disease Variables and Prognosis in Hematological Malignancy Patients Treated with Itraconazole as An Empirical Antifungal Therapy: A Prospective Multicenter Observational Study in Korea

We identified the clinical characteristics including disease status for expecting success outcome of empirical antifungal therapy for invasive fungal infection (IFI) using itraconazole in immunocompromised patients with hematological malignancies. The prospective multicenter observational study was performed at 26 medical centers for 9 months. Three hundred seventy six patients with hematological malignancies (median age 48) had been enrolled and analyzed. The patients with possible and probable categories for IFI according to the EORTC/MSG criteria were included. We excluded the patients with proven IFI. IV itraconazole was administered as routine schedule. Oral itraconazole solution was used after the IV itraconazole. Underlying disease consisted of 61% of AML and 15% of ALL. Overall success rate of empirical antifungal therapy with itraconazole was 196/376 (51%). Acute leukemia in non-CR status and advanced stage of MDS patients showed a lower trend of success rate. Combined co-morbidities, underlying lung disease, poor ECOG performance status (≥2), abnormal chest X-ray at the time of initiation of empirical antifungal therapy, no early initiation of empirical antifungal therapy (the duration of baseline neutropenic fever ≥3 days) and antifungal prophylaxis other than itraconazole were associated with decreased overall success rate. Multivariate analysis revealed that poor ECOG performance status (≥2) (P=0.01, HR = 1.90, 95% CI 1.17–3.06) and abnormal chest X-ray (P=0.02, HR = 2.00, 95% CI 1.12–3.58) were significantly associated with poor outcome of empirical antifungal therapy with itraconazole. Overall success rate of empirical antifungal therapy was not affected by antifungal prophylaxis. Defervescence in setting of neutropenia was 70% (264/276). Higher rate of defervescence was observed in the patients with early stage of MDS (92% vs. 40%, P = 0.02). Median time to defervescence after empirical itraconazole therapy was 3 days. Short mean time to defervescence was observed in the patients with acute leukemia in CR status (P = 0.002) or early stage of lymphoid malignancies (P = 0.03). Baseline fungal infections were diagnosed in 13 patients (3%). Of the patients with baseline fungal infections, 7 patients (54%) had a successful outcome. All 7 patients with successful outcome had baseline fungal infection with candidemia. The rate of breakthrough fungal infection was 4% (16/376). Breakthrough aspergillus infection was documented in the half of theses patients (8/16). The rate of breakthrough fungal infection also was not different according to the different disease status. Premature discontinuation of itraconazole therapy because of toxicity or lack of efficacy occurred in 35% (131/376). The proportion of patients who survived for at least 7 days after completion of itraconazole therapy was 90% (338/376). IV itraconazole followed by oral itraconazole solution is an effective regimen for empirical antifungal therapy in the haematological malignancy patients with persistent neutropenic fever. Poor performance status and abnormal chest X-ray were predictive factors for failure of empirical antifungal therapy with itraconazole in the patients with hematological malignancies.Table 1. Outcomes (overall success rate) according to the clinical characteristicsYesNoPCo-morbidities37/90 (41%)156/286 (55%)0.03Diabetes mellitus6/20 (30%)187/356 (53%)0.07Lung disease3/14 (21%)190/362 (53%)0.03ECOG performance status -≥2 (vs. 0 or 1)45/123 (37%)148/253 (59%)< 0.001Galactomannan test – positive3/9 (33%)33/74 (45%)0.73Abnormal chest X-ray23/70 (33%)156/278 (56%)0.001Abnormal chest CT14/51 (28%)5/8 (63%)0.10Duration of baseline neutropenia≥7 days (vs. <7 days)101/206 (49%)92/170 (54%)0.35>10 days (vs. ≤10 days)60/122 (49%)133/254 (52%)0.58Duration of baseline neutropenic fever≥3 days (vs. <3 days)89/193 (46%)104/183 (57%)0.04≥5 days (vs. <5 days)55/124 (44%)138/252 (55%)0.06Antifungal prophylaxis95/183 (52%)98/193 (51%)0.84Other drugs (vs. itraconazole)51/114 (45%)44/69 (64%)0.02

The Symptom Burden of Chronic Myelogenous Leukemia (CML)

Symptom burden is the combined impact of all disease-related and therapy-related symptoms on one's ability to function as one did before onset of disease or therapy. Lack of understanding of symptoms may result in failure to address symptoms and return patients to optimum functioning. This is critical for patients with chronic diseases who are receiving continuing therapy, such as patients with chronic myeloid leukemia (CML). Additionally patient-reported outcome measures are becoming primary endpoints in clinical trials to test results such as reduction in symptom burden that establish treatment benefits from the patient's perspective. No patient-reported outcome measure for CML currently exists, and there is little understanding or knowledge of the symptom burden of CML and its treatment. The purpose of this study was to initially explore the symptom burden of CML.Methods: Retrospective analysis of 29 patients with CML who participated in two larger cross-sectional studies exploring cancer-related symptoms. Patients used the M. D. Anderson Symptom Inventory (MDASI) to rate the severity of their symptoms (13 items) and the degree to which their symptoms interfered with daily living (6 items) on a 0–10 scale.Results: Patient/treatment characteristics are summarized in Table 1.Table 1: Patient/Treatment CharacteristicsN=29MeanSDAge53.914.6Highest Grade Completed14.452.08n%Sex–Male1758.6%Race–White, non-Hispanic2793.1%Employment Status–Employed or Homemaker1344.8%ECOG Performance Status–< 22172.4%Treatment TypeInterferon-Based Therapy931.0%Tyrosine Kinase Inhibitor1034.5%Mean global symptom severity was 1.86 (SD 1.76) and mean global interference was 1.79 (SD 2.05). Cronbach alpha for the symptom scores was 0.916 and for the interference scores was 0.922, indicating that the MDASI is reliable in this sample. The 6 most severe symptoms (mean severity score > 2.5) were fatigue, drowsiness, lack of appetite, disturbed sleep, difficulty remembering things, and dry mouth. Symptoms interfered most with work and general activities. Mean symptom severity scores and standard deviations for the top most severe symptoms and most bothersome interference items are reported in Table 2.Table 2: Symptom and Interference Means and SDThere was no significant difference in mean symptom severity or interference between patients receiving interferon-based therapies and patients receiving tyrosine kinase inhibitors. There were significant differences in mean symptom severity (p = .001) and interference (p < .001) scores between patients with good (0 or 1) and poor (≥ 2) ECOG performance status. Preliminary analysis has encouraged us to investigate further relationships among the 13 symptom items, the 6 interference items, and demographic, disease, and treatment related factors. This further, more-detailed analysis will be presented.nMinimumMaximumMeanSDSymptom ItemFatigue29094.622.691Drowsiness290103.003.151Lack of Appetite29082.832.916Sleep disturbance290102.662.595Difficulty Remembering29072.622.162Dry mouth290102.522.681Interference ItemWork28093.143.003Activity280103.112.897Conclusion: Methods for patients with CML to report symptom burden to clinicians and researchers are needed. Based on preliminary results, the MDASI is a reliable instrument that captures many symptoms of CML and differentiates between levels of severity of illness. Further work is ongoing to identify and add symptom items to the MDASI that will capture CML-specific and treatment-specific symptoms.

Compliance to consensus recommendations, surgeon's experience and introduction of a quality assurance and management program. – Influence on therapy of early-stage ovarian carcinoma

State of the art surgical staging and adjuvant chemotherapy in early-stage ovarian carcinoma has an impact on patient's outcome, but compliance to guidelines and consensus recommendations is still poor. This study reports on our results before and after introduction of a quality assurance and management program in our clinic in 2001. Patients with ovarian carcinoma limited to the pelvis who underwent primary surgery in our hospital from 1997 to October 2007 were eligible for this study. Univariate and multivariate logistic regression analyses were performed to evaluate the impact of compliance with our management program and physician's experience in ovarian carcinoma surgery on achieving both standards of surgery and chemotherapy. In a total of 117 women a significant impact on adherence to guideline defined comprehensive surgical staging was found for poor ECOG performance status (OR 22.16; CI 3.2–152.0; p=0.002) and year of surgery before 2001 (OR 47.60; CI 9.20–245.22; p<0.001). Tumor grading < G3 (OR 4.14; CI: 1.20–14.22; p=0.02) was a statistically significant predictor for receiving standard adjuvant chemotherapy. Survival analyses showed a trend towards improved survival for patients having received guidelines adopted therapy, but event numbers were too low for adequate analyses. The introduction of a quality assurance program for treatment of ovarian carcinoma represents a major improvement of patient care. It led to a higher compliance with consensus recommendations and showed already a trend towards improved survival. Further outcome research should focus on methods for implementation of guidelines in daily practice in institutions caring for patients with ovarian carcinoma.

Combination chemotherapy with irinotecan and cisplatin in elderly patients (≥65 years) with extensive-disease small-cell lung cancer

Combination chemotherapy with irinotecan and cisplatin is one of the standard treatments for patients with small-cell lung cancer (SCLC). In elderly patients, however, its efficacy and toxicity has not been well documented. In this Phase II study, we assessed the efficacy and toxicity of combination chemotherapy with irinotecan and cisplatin and examined whether advanced age compromises it in elderly patients with previously untreated extensive-disease small-cell lung cancer (ED-SCLC). In this study, 46 previously untreated elderly patients (65 years or older) with ED-SCLC were given combination chemotherapy consisting of irinotecan 60 mg/m(2) on days 1, 8 and 15 and cisplatin 60 mg/m(2) on day 1. The treatment was repeated every 4 weeks until patients completed the maximum six cycles. Patients consisted of 37 men and 9 women, whose median age was 70 years (range 65-81 years). A complete response and a partial response were observed in 19.6% (9/46) and 56.5% (26/46), respectively. The overall response rate was 76.1% (95% C.I; 63.8-88.4%). The overall median survival was 10.4 months (range 7.6-13.2 months). The median progression-free survival was 8.32 months (range 6.8-9.8 months). Major toxicities included neutropenia (grade 3-4, 58.7%), leukopenia (grade 3-4, 49.9%), infection (grade 3-4, 39.1%) and diarrhea (grade 3-4, 30.4%). Incidence of febrile neutropenia was significantly higher in patients with ECOG performance status 2-3 compared with ECOG performance status 0-1 (70.4% vs. 5.2%; p<0.001). There were two treatment related deaths in patients ECOG performance status 3. Our results indicate that combination chemotherapy with irinotecan and cisplatin is an effective treatment for elderly patients with ED-SCLC who have good ECOG performance status and physicians should be aware of the mortality and morbidity due to myelosuppression following this treatment in elderly ED-SCLC patients with poor ECOG performance status.

A Conditional Risk Model for Chemotherapy-Induced Anemia (CIA) in Cancer Patients.

Anemia represents the most common hematological toxicity in cancer patients receiving systemic chemotherapy and is associated with considerable morbidity and cost. Current guidelines for chemotherapy-induced anemia call for intervention at a hemoglobin <10 g/dL with treatment options including transfusion or an erythropoietic-stimulating agent (ESA). A meta-analysis of randomized controlled trials has demonstrated the clinical value of early versus late intervention with an ESA (Lyman Cancer, 2006). While anemia risk models based on pretreatment characteristics have recently been validated, recent safety concerns have limited use of the ESAs to patients with moderate or severe anemia. The gradual onset of anemia and response to ESAs over time provides a rationale for selecting patients for ESA support early in the course of chemotherapy.Methods: 3640 patients with solid tumors or malignant lymphoma initiating a new regimen have been prospectively registered at 110 randomly selected U.S. practice sites. A logistic regression risk model for hemoglobin <10 g/dL based on pretreatment characteristics and hematolgic events during cycle 1 was developed and model predictive performance characteristics estimated.Results: Over a median of 3 cycles of chemotherapy, hemoglobin <10 g/dL was reported one or more times in 1072 (29.5%) patients. Significant independent baseline characteristics associated with subsequent hemoglobin <10 g/dL include: female gender, poor ECOG performance status, history of congestive heart failure, vascular disease or chronic pulmonary disease, cancer type, treatment with an anthracycline-, platinum- or etoposide-based regimen and baseline hemoglobin <12 g/dL or platelet count <150000/mm3. In addition, significant independent predictive hematologic changes during cycle 1 include: decrease in hemoglobin >1 g/dL (OR=4.48; P<.0001), decrease in platelet count >100000/mm3 (OR=1.54;P<.0001) or neutrophil count <500/mm3 (OR=1.94; P<.001) as well as hemoglobin <12 g/dL (OR=2.0;P<.001) at the start of cycle 2. Model R2 = 0.581 and c-statistic = 0.901 [95% CI: .89–.91, P<.0001]. The predicted risk of hemoglobin <10 g/dL ranged from 0 to 100% with mean and median probabilities of 0.16 and 0.30, respectively. Based on a risk cutpoint at the mean, 1290 patients (38%) were classified as high risk. The risks of hemoglobin <10 g/dL in high and low risk subjects were 66% and 9%, respectively. Model test performance characteristics [± 95% CLs] included: sensitivity: 82%[80–84]; specificity: 82%[80–83]; positive predictive value: 66%[63–68]; negative predictive value: 91%[90–93] and diagnostic odds ratio: 20.4[16.8–24.6]. Of note, risk of hemoglobin <11 g/dL in high and low risk subjects based on this model were 95% and 34%, respectively. Validation of the model in a separate population of patients is currently under way.Discussion: This conditional risk model based on both pretreatment characteristics and first cycle events identified cancer patients receiving chemotherapy at substantial risk for clinically significant anemia. The use of ESAs early in the course of treatment based on individual risk assessment must consider both the potential benefit and risks and careful monitoring is essential.

Distress and its correlates in Korean cancer patients: pilot use of the distress thermometer and the problem list

The distress thermometer (DT), a one-item measure for distress, provides a means for rapidly and effectively screening psychological distress in cancer patients. In this pilot study, a screening efficacy of the DT was investigated in a mixed cohort of 108 Korean cancer patients. Participants completed the DT, the problem list (PL), and the Hospital Anxiety and Depression Scale (HADS), and answered questions regarding supportive needs and their degree of satisfaction with several aspects of care. Receiver operating characteristic (ROC) curve analyses indicated that a DT cutoff score of 4 yielded an area under the ROC curve of 0.75 with a sensitivity of 0.83 and a specificity of 0.59 for HADS-total score defined cases (> or =15). HADS--Anxiety and Depression subscale scores explained 27% of the variability in the DT scores, implying that 'distress' is a broader concept that includes anxiety and depressive symptoms but has a more comprehensive meaning that encompasses multiple contributory factors. Regarding the PL, distressed patients (DT> or =4) reported significantly more problems (23 of 35) in all categories, suggesting, although degrees differ, that a wide variety of problems contribute to distress in cancer patients. Distress as defined by DT and HADS subscale scores was also significantly associated with higher supportive needs, a poor ECOG performance status (both physician and patient-rated), and a reduced level of satisfaction with treatment, staff, and communications. In conclusion, the DT and the PL were found to be simple yet effective screening instruments for detecting psychosocial distress in Korean cancer patients, and for identifying problems that warrant intervention.

Clinical variables are associated with treatment satisfaction in patients with breast, lung, and colorectal cancer

6608 Background: The association between clinical variables (e.g. disease stage/type, side effects, ECOG performance status (PS)) and patient-reported treatment satisfaction has received little attention, despite the potential implications for treatment adherence and decision-making. We examined the relation between clinical variables and treatment satisfaction in a U.S. sample of patients with breast (BC), lung (LC), or colorectal (CRC) cancer using the Cancer Treatment Satisfaction Questionnaire (CTSQ), a recently validated 16-item measure designed to assess expectations of therapy (ET), feelings about side effects (FSE), and satisfaction with therapy (SWT). Methods: Cancer stage, line of therapy, physician-reported ECOG PS, presence vs. absence of medication side effects, and perceived change in cancer over the last two weeks were obtained on patients. These clinical variables were examined in relation to the ET, FSE, and SWT scales of the CTSQ. Higher scale scores indicated better outcomes (e.g., better satisfaction). Group means were compared using one-way ANOVAs; trends of scale scores across clinical variables were also examined. Results: Participants were 349 patients with early and late stage BC (n=137), CRC (n=121), or LC (n=91) who had ≥ 1 cycles of chemo-, bio-, or hormonal therapy in the last 6 months. In all cancer types, FSE differed by presence of side effects (BC&lt;.03; CRC&lt;.01; LC&lt;.02). In BC patients, FSE differed by stage, and ET differed significantly depending on ECOG PS (p&lt;.006) and perceived change (p&lt;.05). For CRC patients, ET significantly differed by stage (p&lt;.05) and perceived change (p&lt;.02); and SWT by presence of side effects (p&lt;.01). SWT also differed by perceived change (p&lt;.01) for LC patients. Most trends were in the expected direction. Conclusions: These results indicate that patient-reported satisfaction with therapy is correlated with clinical variables. On average, patients who perceive less improvement in their cancer, have side effects, and poorer ECOG PS are less satisfied with their current cancer therapy. Unknown is the impact of this relation on adherence and decision-making. Recent changes in healthcare suggests that treatment satisfaction may become an increasingly important measure of clinical outcome. No significant financial relationships to disclose.

Prognostic Factors in Hodgkin's Disease - Analysis of 211 Patients from a Single Institution.

The treatment adaptation to individual risks of patients with Hodgkin's disease is closely connected to the prognostic factors identification. The goal of the study was to identify prognostic factors related to survival of patients with Hodgkin's disease in the population of Plovdiv district (South Bulgaria).Patients and methods: The retrospective study involved 151 patients with Hodgkin's disease, diagnosed and treated in the University Clinic of Hematology, Plovdiv, Bulgaria, from 1995 to 2005. The prognostic value of several pretreatment parameters with regard to the survival time was analyzed:Sex,Ann-Arbor clinical staging,ECOG Performance status,Histological type,Extranodal localization,Systemic B symptoms,Abdominal lymphadenopathy andInfradiaphragmatic disease.The patient's survival was analyzed by using the Kaplan-Meier method. The log-rank test was used to compare cumulative survival functions.Results: The mean survival period of patients was 13,35 years (95% C.I. 10,35–16,36). The most important prognostic factors for survival were: ECOG Performance status (P<0,001), Ann-Arbor clinical stages (P=0,0046), extranodal localization (P=0,0009), abdominal lympadenopathy (P=0,0025), B symptoms (P=0,0145) and histological type (P=0,02). The factors with negative impact on survival time were: advanced III/IV clinical stage; poor ECOG performance status 3/4; mixed cellularity/lymphocyte depletion histological type; presence of abdominal lymphadenopathy and B symptoms and more than one extranodal localization. There is a tendency of poorer survival in patients in clinical stage I/II and infradiaphragmatic initial presentation of disease (P=0,185).Conclusion: Prognostic factors identified in the present study can be easily applied in the routine clinical practice and may be used as a basis for mathematical prognostic models.

Non-Hodgkin's lymphoma in patients 80 years of age or older

BackgroundVery elderly patients (≥80 years old) with non-Hodgkin's lymphoma (NHL) frequently have co-morbid conditions and are generally excluded from clinical trials or even from treatment. The optimal treatment of these patients is unknown. Patients and methodsWe reviewed the records of 109 patients ≥80 years at diagnosis of NHL (65 F/44 M; median age: 84 years, range; 80–95). ResultsSeventy-eight patients (72%) had aggressive NHL, 25 (23%) had indolent and NHL, eight had unclassified disease. Advanced-stage disease was noted in 54%. Forty patients (39%) had a poor ECOG performance status (PS), and 52 (49%) had an intermediate or high risk International Prognostic Index (IPI). Seventy-nine patients (72%) were treated with chemotherapy and 37 (34%) with radiotherapy. Initial chemotherapy consisted of chlorambucil in 15, oral etoposide in 2, and combination protocol in 62. Only 16% of patients received full-dose therapy, and only 50% completed ≥6 cycles of combination chemotherapy. The overall response rate for the 69 evaluable patients was 84% (complete 56.5%, partial 27.5%). Overall 5-year survival for the whole group was 39%, and median survival time was 26 months. ConclusionA high response rate can be achieved in very elderly NHL patients despite aggressive histology, poor prognostic features, and reduced doses of chemotherapy. Age alone should not be a contraindication to treatment.

Reduced-Intensity Cord Blood Transplantation (RICBT) Is a Feasible Approach for Advanced Adult T-Cell Leukemia (ATL).

Introduction:ATL in advanced stage is a lymphoid malignancy with poor prognosis, its mean survival time being a few months. Allogeneic hematopoietic stem cell transplantation has been shown to be potentially curative approach, but the availability of HLA-matched donor, either of related or unrelated, limits its application to many of the patients. Cord blood has been widely used as an alternative donor cells. We report here the feasibility of RICBT for patients with advanced ATL.Patients and Methods:Eighteen patients with advanced ATL, including 11 acute type and 7 lymphoma type, who underwent RICBT between March 2002 and June 2005 at our institution, were retrospectively analyzed. Eighty percent of them were chemo-refractory at the time of transplant. Median age of the patients was 59 years (27–79). Pretransplant conditioning regimen consisted of fludarabine 125 mg/m2, melphalan 80 mg/m2 and TBI 4 Gy. GVHD prophylaxis was either cyclosporine (CSP, n=11) or tacrolimus (TAC, n=7) alone. The median number of infused nucleated cells and CD34 positive cells were 2.83 (1.95–4.83) x 107 and 1.00 (0.40–2.91) x 105, respectively. All the patients received CB units with HLA mismatches at 1 (n=8) or 2 (n=10) loci.Results:Neutrophil and platelet engraftment were observed in 15 (83.3%, median 16 days) and 14 patients (77.8 %, median 42 days). Two died before engraftment. Five of the engrafted patients (30%) developed acute GVHD (grade II–IV). Although 14 out of 15 patients who survived over 30 days achieved complete remission, 6 died of non-relapse mortality (NRM) within 100 days post-transplant (5 sepsis, 1 encephalitis), and another 6 died of relapse (median 225 days post-transplant). Five of the 7 patients who were alive beyond 100 days developed chronic GVHD (4 limited, 1 extensive). One patient experienced rapid tumor regression along with the chronic GVHD after cessation of TAC at day 146 post-transplant, indicating possible GvATL effect. Estimated 1-year overall and progression-free survival rates were 27.9 +/− 9.0 % and 17.2 +/− 12.8 %, respectively. Among 9 survivors beyond 100 days post-transplant, 5 remain alive at median follow-up of 17 months but only 2 of them remain progression free. Univariate analyses revealed high age (over 60), poor ECOG performance status (over 2) and high sIL-2R level (over 10000IU/L) as poor factors for survival. TAC dramatically decreased the day 100 mortality (14.3%) compared with CSP (45.5%).Conclusion:This pilot study indicates that our RICBT is feasible even for the ATL patients in advanced stage. Day 100 mortality was improved by using TAC but eventually the overall survival decreased to comparable level with CSP. To further improve the outcome, RICBT should be investigated for patients in early stage of the disease, or new approach to prevent late relapse should be explored.

Neoadjuvant chemotherapy for stage III and IV epithelial ovarian cancer: A comparative study

5117 Background: The aim of this study was to compare the outcome of patients with advanced ovarian carcinoma treated with neoadjuvant chemotherapy with those treated conventionally with primary debulking surgery. Methods: From February 1994 to October 2003, all consecutive cases of advanced stage epithelial ovarian carcinoma treated with neoadjuvant chemotherapy (NACT) at the University of Bari were identified. A well-balanced group of women who underwent primary debulking surgery followed by platinum-based chemotherapy was selected as controls. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors for survival. Results: Thirty women with advanced stage epithelial ovarian carcinoma were treated with neoadjuvant chemotherapy and were compared to other 30 patients who underwent primary debulking surgery. Patients in the neoadjuvant chemotherapy were significantly older (p=0.03) and had a poorer ECOG performance status (p=0.02) compared to the controls. However, no statist...

Neoadjuvant chemotherapy for stage III and IV epithelial ovarian cancer: A comparative study

5117 Background: The aim of this study was to compare the outcome of patients with advanced ovarian carcinoma treated with neoadjuvant chemotherapy with those treated conventionally with primary debulking surgery. Methods: From February 1994 to October 2003, all consecutive cases of advanced stage epithelial ovarian carcinoma treated with neoadjuvant chemotherapy (NACT) at the University of Bari were identified. A well-balanced group of women who underwent primary debulking surgery followed by platinum-based chemotherapy was selected as controls. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors for survival. Results: Thirty women with advanced stage epithelial ovarian carcinoma were treated with neoadjuvant chemotherapy and were compared to other 30 patients who underwent primary debulking surgery. Patients in the neoadjuvant chemotherapy were significantly older (p=0.03) and had a poorer ECOG performance status (p=0.02) compared to the controls. However, no statistical difference was observed in overall disease-specific survival (p=0.66) and disease-free survival (p=0.25) between the two groups. Conclusions: Despite patients in the neoadjuvant chemotherapy group are significantly older and have a poorer performance status, this treatment modality does not compromise survival. Prospective randomised trials comparing neoadjuvant chemotherapy to conventional treatment to determine the quality of life and cost/benefit outcomes are now appropriate for women presenting advanced epithelial ovarian cancer. No significant financial relationships to disclose.