Prognostic values of EORTC QLQ-C30 and QLQ-HCC18 index-scores in patients with hepatocellular carcinoma - clinical application of health-related quality-of-life data.

BACKGROUND: Health-related quality-of-life (HRQOL) assessment with EORTC QLQ-C30 was prognostic for overall survival (OS) in patients with advance-stage hepatocellular carcinoma (HCC), but no data existed for early-stage patients. The HCC-specific QLQ-HCC18 has not been evaluated for prognostic value in HCC patients. Utilization of raw HRQOL data in clinical setting has been impractical and non-meaningful. Therefore we developed index scores of QLQ-C30 and QLQ-HCC18 in an attempt to enable clinical utilization of these HRQOL measurements. This study investigates the prognostic significance of QLQ-C30, QLQ-HCC18 and C30/HCC18 index-scores in patients with newly diagnosed HCC which encompasses all stages. METHODS: From 2007-2011, 517 patients were prospectively recruited. HRQOL was assessed at diagnosis using QLQ-C30 and QLQ-HCC18; C30 and HCC18 index-scores were calculated from raw HRQOL data. Cox regression was performed using continuous, dichotomized QLQ-C30 and QLQ-HCC18 variables, or index-scores, together with clinical factors to identify independent factors for OS. Various multivariate models were validated with c-index and bootstrapping for 1000 replications. RESULTS: Four hundred and seventy two patients had complete HRQOL data. Their median OS was 8.6 months. In multivariate analysis, independent prognostic HRQOL variables for OS were QLQ-C30 pain (HR 1.346 [1.092-1.661], p = 0.0055), QLQ-C30 physical functioning (HR 0.652 [0.495-0.860], p = 0.0024); QLQ-HCC18 pain (HR 1.382 [1.089-1.754], p = 0.0077) and QLQ-HCC18 fatigue (HR 1.441 [1.132-1.833], p = 0.0030). C30 index-score (HR 2.143 [1.616-2.841], p < 0.0001) and HCC18 index-score (HR 1.957 [1.411-2.715], p < 0.0001) were highly significant factors for OS. The median OS of patients with C30 index-score of 0-20, 21-40, 41-60, 61-100 were 16.4, 7.3, 3.1, 1.8 months respectively (p < 0.0001); while for HCC18 index-score: 16.4, 6.0, 2.8, 1.8 months respectively (p < 0.0001). All the multivariate models were validated, with mean optimism <0.01. The bootstrap validated c-index was 0.78. CONCLUSIONS: QLQ-C30 and QLQ-HCC18 were prognostic for OS in patients with newly diagnosed HCC irrespective of stage. Both C30 and HCC18 index-scores were highly significant prognostic factors for OS in newly diagnosed HCC patients. Index-scoring provides an effective way to summarize, analyze and interpret raw HRQOL data, and renders QLQ-C30 and QLQ-HCC18 meaningful and communicable in clinical practice. Index-scores could potentially serve as a standardized tool for future HRQOL research.

Intermittent versus continuous erlotinib with concomitant modified "XELOX" (q3W) in first-line treatment of metastatic colorectal cancer: correlation with serum amphiregulin and transforming growth factor alpha.

BACKGROUND: This study evaluated the activity of 2 schedules of erlotinib in combination with chemotherapy, and the prognostic significance of serum amphiregulin (AREG) and transforming growth factor alpha (TGFa) in metastatic colorectal cancer. METHODS: A total of 60 untreated patients were randomized to a "continuous" (CON; erlotinib 100 mg daily) or an "intermittent" (INT; erlotinib 150 mg on alternate day on day 2 to 14, then 150 mg daily on days 15 to 21) schedule of erlotinib with a modified XELOX (capecitabine plus oxaliplatin) regimen. Serum levels of AREG and TGFa were determined serially. RESULTS: Baseline characteristics were similar between the 2 arms. Of the 58 patients evaluated for response, there was a nonsignificant trend toward a slightly higher overall response rate in the INT arm (66.7%) versus the CON arm (56.7%). At a median follow-up of 2.8 years, the median overall survival was 18.8 months (95% confidence interval = 11.3-22.9 months) and 20.7 months (95% confidence interval = 12.5-31 months, P = .19) for the CON and INT arm, respectively. KRAS mutation did not predict drug response. The 2 arms did not differ significantly in toxicity. Baseline serum TGFa was an independent predictor of progression-free survival, whereas a drop in serum TGFa and AREG levels following 3 to 4 cycles of treatment were associated with shorter progression-free survival and overall survival, respectively. CONCLUSIONS: The intermittent erlotinib schedule was associated with a higher response rate, although this is not statistically significant. Serum TGFa and AREG levels have prognostic significance in erlotinib-treated patients with colorectal cancer, and further studies are warranted.

Prediction of outcome in cancer patients with febrile neutropenia: a prospective validation of the Multinational Association for Supportive Care in Cancer risk index in a Chinese population and comparison with the Talcott model and artificial neural network.

PURPOSE: We aimed to validate the Multinational Association for Supportive Care in Cancer (MASCC) risk index, and compare it with the Talcott model and artificial neural network (ANN) in predicting the outcome of febrile neutropenia in a Chinese population. METHODS: We prospectively enrolled adult cancer patients who developed febrile neutropenia after chemotherapy and risk classified them according to MASCC score and Talcott model. ANN models were constructed and temporally validated in prospectively collected cohorts. RESULTS: From October 2005 to February 2008, 227 consecutive patients were enrolled. Serious medical complications occurred in 22% of patients and 4% died. The positive predictive value of low risk prediction was 86% (95% CI = 81-90%) for MASCC score ≥ 21, 84% (79-89%) for Talcott model, and 85% (78-93%) for the best ANN model. The sensitivity, specificity, negative predictive value, and misclassification rate were 81%, 60%, 52%, and 24%, respectively, for MASCC score ≥ 21; and 50%, 72%, 33%, and 44%, respectively, for Talcott model; and 84%, 60%, 58%, and 22%, respectively, for ANN model. The area under the receiver-operating characteristic curve was 0.808 (95% CI = 0.717-0.899) for MASCC, 0.573 (0.455-0.691) for Talcott, and 0.737 (0.633-0.841) for ANN model. In the low risk group identified by MASCC score ≥ 21 (70% of all patients), 12.5% developed complications and 1.9% died, compared with 43.3%, and 9.0%, respectively, in the high risk group (p < 0.0001). CONCLUSIONS: The MASCC risk index is prospectively validated in a Chinese population. It demonstrates a better overall performance than the Talcott model and is equivalent to ANN model.

Food Avoidance Beliefs and Behaviors Among Chinese Cancer Patients: Validation of a New Measurement Tool.

OBJECTIVE: Restrictive food avoidance behavior among Chinese cancer patients is common. Yet, to the authors' knowledge, no study has investigated factors associated with such behavior. This study attempted to validate a new measurement tool, the Cancer Patients Food Avoidance Behaviors Scale (CPFAB), that assessed cancer patients' belief regarding 5 perceived benefits of practicing food avoidance, and to test its applicability. DESIGN: Cross-sectional face-to-face interviews. SETTING: Two outpatient oncology clinics in 2 different districts of Hong Kong. PARTICIPANTS: A total of 245 patients with nasopharyngeal and colorectal cancer. MAIN OUTCOME MEASURES: Assessment of psychometric properties of the CPFAB. ANALYSIS: Principal components method with oblique (Promax) rotations was performed to investigate the factor structure of the CPFAB. RESULTS: Psychometric properties, which included test-retest intraclass correlations (mean = 0.72; SD = 0.12), Cronbach α (.88-.94), floor (0.4% to 5.7%) and ceiling (0% to 7.3%) effects, and item-subscale (0.67-0.79) and subscale-total (0.68-0.89) correlations, were satisfactory. CONCLUSIONS AND IMPLICATIONS: The CPFAB, a new instrument used to assess food avoidance, was developed and validated. It showed satisfactory psychometric properties and can be used to evaluate interventions that seek to modify food avoidance attitudes among cancer patients.

Evaluation of a single-tube multiplex polymerase chain reaction screen for detection of common alpha-thalassemia genotypes in a clinical laboratory.

We prospectively compared a single-tube multiplex polymerase chain reaction (PCR) for detecting alpha-thalassemia with our current approach using 452 blood samples. Initial evaluation of 89 specimens revealed sensitivity and specificity, respectively, for the hemoglobin H inclusion body test (HbH prep) vs PCR for detecting alpha0-thalassemia carriers of 0.79 and 0.96 and for a mean corpuscular volume (MCV) of 82 microm3 (82 fL) or less, 1.0 and 0.45. Detection of all alpha-thalassemia genotypes was significantly lower for HbH prep and MCV (sensitivity and specificity, respectively: HbH prep, 0.48 and 0.96; MCV, 0.87 and 0.47). In a follow-up evaluation of patients with positive HbH prep results or suspected alpha-thalassemia prescreened by low MCV, the sensitivity and specificity, respectively, of HbH prep vs PCR increased to 0.97 and 0.93 for alpha0-thalassemia and 0.83 and 0.92 for any alpha-thalassemia. PCR detected alpha-thalassemia in 37.2% of 298 suspected alpha-thalassemia cases with suggestive indices but negative HbH prep results and no detectable hemoglobinopathy. This multiplex approach was more sensitive than the HbH prep for detecting all alpha-thalassemia genotypes, particularly alpha+-thalassemia; was particularly valuable for identifying carriers of alpha0-thalassemia at risk for offspring with hemoglobin Bart hydropsfetalis, regardless of other diagnosed hemoglobinopathies; and is an ideal adjunct to standard clinical screening protocols for detecting alpha-globin deletions.

A practical, comprehensive classification for pediatric myelodysplastic syndromes: the CCC system.

PURPOSE: Pediatric myelodysplastic syndromes (MDS) are biologically diverse. The French-American-British (FAB) classification of adult forms of MDS is not always applicable because many pediatric patients do not fit into any of the categories. To circumvent the FAB schema and other flawed formats, the authors developed a practical classification system for childhood MDS. PATIENTS AND METHODS: The authors analyzed 40 children with MDS diagnosed in Toronto between 1988 and 1998 to test the utility of the classification. Children were classified according to three main features: category, cytology, and cytogenetics. RESULTS: Using this system the authors were able to classify all 40 patients; about half could not be unclassified by FAB. Patients could also be longitudinally classified by serial analysis to show progression of disease. Juvenile myelomonocytic leukemia was excluded because of its known myeloproliferative pathogenesis. Chronic myelomonocytic leukemia, which almost never occurs in children, was also omitted. Also excluded were other chronic myeloproliferative disorders and any cytopenias without malignant potential. CONCLUSIONS: Based on these data, the CCC system appears to have prognostic potential; children with advanced class and cytogenetic abnormalities had a poorer outcome. The authors urge international adoption of this system for uniformity in clinical practice and reporting purposes.

A practical, comprehensive classification for pediatric myelodysplastic syndromes: the CCC system.

PURPOSE: Pediatric myelodysplastic syndromes (MDS) are biologically diverse. The French-American-British (FAB) classification of adult forms of MDS is not always applicable because many pediatric patients do not fit into any of the categories. To circumvent the FAB schema and other flawed formats, the authors developed a practical classification system for childhood MDS. PATIENTS AND METHODS: The authors analyzed 40 children with MDS diagnosed in Toronto between 1988 and 1998 to test the utility of the classification. Children were classified according to three main features: category, cytology, and cytogenetics. RESULTS: Using this system the authors were able to classify all 40 patients; about half could not be classified by FAB. Patients could also be longitudinally classified by serial analysis to show progression of disease. Juvenile myelomonocytic leukemia was excluded because of its known myeloproliferative pathogenesis. Chronic myelomonocytic leukemia, which almost never occurs in children, was also omitted. Also excluded were other chronic myeloproliferative disorders and any cytopenias without malignant potential. CONCLUSIONS: Based on these data, the CCC system appears to have prognostic potential; children with advanced class and cytogenetic abnormalities had a poorer outcome. The authors urge international adoption of this system for uniformity in clinical practice and reporting purposes.

Brain metastasis responding to gefitinib alone.

A woman with stage IIIb non-small cell lung cancer (NSCLC) developed disease progression with brain metastases during chemotherapy. Due to unusual circumstances, the patient received gefitinib alone, without the use of corticosteroid treatment or radiotherapy. There was a dramatic clinical improvement within 1 week. Follow-up magnetic resonance imaging of the brain 1 month later showed decreases in both the size and number of brain metastases. The patient remains well 9 months after initiation of gefitinib. It is proposed that gefitinib may have a role in treatment of brain metastases from NSCLC.