Survival without adjuvant chemotherapy for selected patients with stage II and III nasopharyngeal carcinoma after concurrent chemoradiotherapy alone.

BACKGROUND: The role of adjuvant chemotherapy after concurrent chemoradiotherapy (CRT) for nasopharyngeal carcinoma (NPC) is controversial. We report our phase II prospective study of withholding adjuvant chemotherapy in a subgroup of patients with American Joint Committee on Cancer (AJCC) stage II and III NPC with low risk for metastasis. METHODS: Between April 1998 and December 2008, 263 patients with stage II (AJCC 1997 T2aN0, T1-T2aN1; AJCC 2010 T1N1) NPC or stage III (AJCC 1997 T1-T2aN2; AJCC 2010 T1N2) NPC were enrolled. Patients received standard concurrent CRT with cisplatin and 5-fluorouracil (5-FU) but without adjuvant chemotherapy. RESULTS: With a median follow-up of 107 months, the 5-year overall survival (OS), disease-free survival (DFS), and distant metastasis-free survival (DMFS) were 92.4%, 84.4%, and 90.7% for all patients; 94.1%, 85.9%, and 92.9% for patients with stage II NPC; and 90.9%, 83.2%, and 88.9% for patients with stage III NPC, respectively. CONCLUSION: It is safe to withhold adjuvant chemotherapy for selected patients with stage II and III NPC.

Gene expression profiling in prognosis of distant recurrence in HR-positive and HER2-negative breast cancer patients.

There had been several studies using gene-expression profiling in predicting distant recurrence in breast cancer. In this study, we developed an 18-gene classifier (18-GC) to predict distant recurrence of breast cancer and compared it with the 21-gene panel (Oncotype DX®, ODx) in performance. Included were 224 breast cancer patients with positive hormonal receptor (HR+) and negative human epidermal growth factor receptor 2 (HER2-). We compared the demographic, clinical, and survival information of the patients, and further compared the prediction of recurrence risk obtained by using the 18-GC with that by ODx. To have the best combined sensitivity and specificity, receiver operating characteristics (ROC) curve analysis was performed to determine the cutoff values for several breakpoint scores. For the new 18-GC, a breakpoint score of 21 was adopted to produce a combined highest sensitivity (95%) and specificity (39%) in detecting distant recurrence. At this breakpoint score, 164 of the 224 patients were classified by the 18-GC in the same risk level as by ODx, giving a concordance rate of 73%. Along with patient age and tumor stage, this 18-GC was found to be an independent significant prognostic factor of distant metastasis of breast cancer. We have thus created a new gene panel assay for prediction of distant recurrence in HR+ and HER2- breast cancer patients. With a high concordance rate with ODx, this new assay may serve as a good tool for individual breast cancer patients to make an informed decision on whether adjuvant chemotherapy should be performed post-surgery.

Patterns of failure after use of (18)F-FDG PET/CT in integration of extended-field chemo-IMRT and 3D-brachytherapy plannings for advanced cervical cancers with extensive lymph node metastases.

BACKGROUND: The study is to evaluate the patterns of failure, toxicities and long-term outcomes of aggressive treatment using (18)F-FDG PET/CT-guided chemoradiation plannings for advanced cervical cancer with extensive nodal extent that has been regarded as a systemic disease. METHODS: We retrospectively reviewed 72 consecutive patients with (18)F-FDG PET/CT-detected widespread pelvic, para-aortic and/or supraclavicular lymph nodes treated with curative-intent PET-guided cisplatin-based extended-field dose-escalating intensity-modulated radiotherapy (IMRT) and adaptive high-dose-rate intracavitary 3D-brachytherapy between 2002 and 2010. The failure sites were specifically localized by comparing recurrences on fusion of post-therapy recurrent (18)F-FDG PET/CT scans to the initial PET-guided radiation plannings for IMRT and brachytherapy. RESULTS: The median follow-up time for the 72 patients was 66 months (range, 3-142 months). The 5-year disease-free survival rate calculated by the Kaplan-Meier method for the patients with extensive N1 disease with the uppermost PET-positive pelvic-only nodes (26 patients), and the patients with M1 disease with the uppermost PET-positive para-aortic (31 patients) or supraclavicular (15 patients) nodes was 78.5 %, and 41.8-50 %, respectively (N1 vs. M1, p = 0.0465). Eight (11.1 %), 18 (25.0 %), and 3 (4.2 %) of the patients developed in-field recurrence, out-of-field and/or distant metastasis, and combined failure, respectively. The 6 (8.3 %) local failures around the uterine cervix were all at the junction between IMRT and brachytherapy in the parametrium. The rate of late grade 3/4 bladder and bowel toxicities was 4.2 and 9.7 %, respectively. When compared to conventional pelvic chemoradiation/2D-brachytherapy during 1990-2001, the adoption of (18)F-FDG PET-guided extended-field dose-escalating chemoradiation plannings in IMRT and 3D-brachytherapy after 2002 appeared to provide higher disease-free and overall survival rates with acceptable toxicities in advanced cervical cancer patients. CONCLUSIONS: For AJCC stage M1 cervical cancer with supraclavicular lymph node metastases, curability can be achieved in the era of PET and chemo-IMRT. However, the main pattern of failure is still out-of-field and/or distant metastasis. In addition to improving systemic treatment, how to optimize and integrate the junctional doses between IMRT and 3D-brachytherapy in PET-guided plannings to further decrease local recurrence warrants investigation.

Logistic-AFT location-scale mixture regression models with nonsusceptibility for left-truncated and general interval-censored data.

In conventional survival analysis there is an underlying assumption that all study subjects are susceptible to the event. In general, this assumption does not adequately hold when investigating the time to an event other than death. Owing to genetic and/or environmental etiology, study subjects may not be susceptible to the disease. Analyzing nonsusceptibility has become an important topic in biomedical, epidemiological, and sociological research, with recent statistical studies proposing several mixture models for right-censored data in regression analysis. In longitudinal studies, we often encounter left, interval, and right-censored data because of incomplete observations of the time endpoint, as well as possibly left-truncated data arising from the dissimilar entry ages of recruited healthy subjects. To analyze these kinds of incomplete data while accounting for nonsusceptibility and possible crossing hazards in the framework of mixture regression models, we utilize a logistic regression model to specify the probability of susceptibility, and a generalized gamma distribution, or a log-logistic distribution, in the accelerated failure time location-scale regression model to formulate the time to the event. Relative times of the conditional event time distribution for susceptible subjects are extended in the accelerated failure time location-scale submodel. We also construct graphical goodness-of-fit procedures on the basis of the Turnbull-Frydman estimator and newly proposed residuals. Simulation studies were conducted to demonstrate the validity of the proposed estimation procedure. The mixture regression models are illustrated with alcohol abuse data from the Taiwan Aboriginal Study Project and hypertriglyceridemia data from the Cardiovascular Disease Risk Factor Two-township Study in Taiwan.

Validating a prognostic scoring system for postmastectomy locoregional recurrence in breast cancer.

PURPOSE: This study is designed to validate a previously developed locoregional recurrence risk (LRR) scoring system and further define which groups of patients with breast cancer would benefit from postmastectomy radiation therapy (PMRT). METHODS AND MATERIALS: An LRR risk scoring system was developed previously at our institution using breast cancer patients initially treated with modified radical mastectomy between 1990 and 2001. The LRR score comprised 4 factors: patient age, lymphovascular invasion, estrogen receptor negativity, and number of involved lymph nodes. We sought to validate the original study by examining a new dataset of 1545 patients treated between 2002 and 2007. RESULTS: The 1545 patients were scored according to the previously developed criteria: 920 (59.6%) were low risk (score 0-1), 493 (31.9%) intermediate risk (score 2-3), and 132 (8.5%) were high risk (score ≥4). The 5-year locoregional control rates with and without PMRT in low-risk, intermediate-risk, and high-risk groups were 98% versus 97% (P=.41), 97% versus 91% (P=.0005), and 89% versus 50% (P=.0002) respectively. CONCLUSIONS: This analysis of an additional 1545 patients treated between 2002 and 2007 validates our previously reported LRR scoring system and suggests appropriate patients for whom PMRT will be beneficial. Independent validation of this scoring system by other institutions is recommended.

Implementing an evidence-based risk assessment tool to predict chemotherapy-induced neutropenia in women with breast cancer.

BACKGROUND: Several studies have documented the efficacy of prophylactic granulocyte colony-stimulating factor in reducing rates of infections and risk of febrile neutropenia. An appropriate risk assessment model is pivotal to identify high-risk patients who would require granulocyte colony-stimulating factor prophylaxis. OBJECTIVE: The objectives of the study were to develop, implement, and evaluate a risk assessment model for neutropenic events in breast cancer patients who were receiving myelosuppressive chemotherapy. METHODS: During the study period, neutropenia risk was assessed for breast cancer patients by using an innovative risk model before the first cycle of chemotherapy. A stepwise logistic regression model was performed to determine significant factors for the prediction. RESULTS: A total of 119 patients were evaluated for neutropenia risk between August 2010 and December 2010. Twenty-nine percent (35/119) of the patients have experienced at least 1 neutropenic event during the initial 3 cycles of chemotherapy. Based on the logistic regression model, only the risk score was retained as the significant predictor; the probability of an individual patient developing neutropenic events increased 1.24 times by increasing 1 score number (odds ratio, 1.24; with 95% confidence interval, 1.063-1.457). CONCLUSIONS: Based on the examination of different cutoff points, the performance of the risk model is best when the risk threshold is set at 6, which was found to have a sensitivity of 0.49 and a specificity of 0.69; the misclassification rate was 0.37, with a positive predictive value of 0.40 and a negative predictive value of 0.76. IMPLICATIONS FOR PRACTICE: The results of this project support incorporating the discussed risk assessment model into routine nursing assessments to prevent neutropenic complications.

Rab5A is associated with axillary lymph node metastasis in breast cancer patients.

The expression of Rab proteins has been associated with cancer. However, few data are available on Rab5A expression in human breast cancer or its impact on disease progression. First, we examined the functional role of Rab5A in breast cancer cells. The expression of Rab5A in MDA-MB-231 cells can be stimulated by epidermal growth factor in a dose-dependent manner. The epidermal growth factor-induced increase of Rab5A expression correlated well with enhanced migration in wound healing migration assays in these cells. Furthermore, we evaluated the expression of Rab5A in breast cancer specimens using immunohistochemical staining, then analyzed the relationship between the expression of Rab5A and clinicopathological parameters. The increased expression of Rab5A protein in 123 breast cancer samples was associated with higher histological grade (P = 0.004), more lymphovascular invasion (P = 0.027), more axillary lymph node (LN) metastasis (P = 0.008), and a higher number of axillary LN metastases (P = 0.043). Among 218 axillary LNs of more than 10 breast cancer patients with node metastases, 167 metastatic LNs were found to have increased Rab5A expression. Rab5A is associated with axillary LN metastasis in breast cancer patients.

Radiotherapy can decrease locoregional recurrence and increase survival in mastectomy patients with T1 to T2 breast cancer and one to three positive nodes with negative estrogen receptor and positive lymphovascular invasion status.

PURPOSE: To define a subgroup of patients at high risk of locoregional recurrence (LRR) who might be benefit from postmastectomy radiotherapy in invasive breast cancer and tumor size <5 cm with one to three involved axillary lymph nodes (T1-2 N1). METHODS AND MATERIALS: Between April 1991 and December 2005, 544 patients with T1-2 N1 invasive breast cancer were treated with modified radical mastectomy. Of the 544 patients, 383 patients (70.4%) had no radiotherapy, and 161 patients (29.6%) received radiotherapy. We retrospectively compared these two patient groups. RESULTS: With a median follow-up of 40.3 months, LRR occurred in 40 (7.4%) of 544 patients. On univariate analysis, high nuclear grade (p = 0.04), negative estrogen receptor (ER) status (p = 0.001), presence of lymphovascular invasion (LVI) (p = 0.003), and no radiotherapy (p = 0.0015) were associated with a significantly higher rate of LRR. Negative ER status (hazard ratio = 5.1) and presence of LVI (hazard ratio = 2.5) were the risk factors for LRR with statistical significance in the multivariate analysis. Radiotherapy reduced the LRR in patients with the following characteristics: age <40 years, T2 stage, high nuclear grade, negative ER status, and presence of LVI. For 41 patients with negative ER and positive LVI status, radiotherapy can reduce LRR from 10 of 25 (40%) to 2 of 16 (12.5%) and increase the 5-year overall survival from 43.7% to 87.1%. CONCLUSION: Radiotherapy can reduce LRR and increase survival in T1-2 N1 breast cancer patients with negative ER status and presence of LVI.

Adherence to quality indicators and survival in patients with breast cancer.

BACKGROUND: International initiatives increasingly advocate physician adherence to clinical protocols that have been shown to improve outcomes, yet the process-outcome relationship for adhering to breast cancer care protocol is unknown. OBJECTIVE: This study explores whether 100% adherence to a set of quality indicators applied to individuals with breast cancer is associated with better survival. RESEARCH DESIGN AND SUBJECTS: Ten quality indicators (4 diagnosis-related and 6 treatment-related indicators) were used to measure the quality of care in 1378 breast cancer patients treated from 1995 to 2001. Adherence to each indicator was based on the number of procedures performed divided by the number of patients eligible for that procedure. The main analysis of adherence was dichotomous (ie, 100% adherence vs. <100% adherence). MEASURES: The outcome measures studied were 5-year overall survival and progression-free survival, calculated using the Kaplan-Meier method. The Cox's proportional hazard regression model was used for univariate and multivariate analyses. RESULTS: Most patients received care that demonstrated good adherence to the quality indicators. Multivariate analysis revealed that 100% adherence to entire set of quality indicators was significantly associated with better overall survival [hazard ratio (HR): 0.46; 95% confidence interval (CI): 0.33-0.63] and progression-free survival (HR 0.51; 95% CI, 0.39-0.67). One hundred percent adherence to treatment indicators alone was also associated with statistically significant improvements in overall and progression-free survivals. CONCLUSIONS: Our study strongly supports that 100% adherence to evidence supported quality-of-care indicators is associated with better survival rates for breast cancer patients and should be a priority for practitioners.

Use of combined molecular biomarkers for prediction of clinical outcomes in locally advanced tonsillar cancers treated with chemoradiotherapy alone.

BACKGROUND: Environmental exposures to tobacco, alcohol, human papillomavirus (HPV) and/or Epstein-Barr virus (EBV), all of which can perturb multiple cell cycle proteins or tumor suppressors, have been implicated in the pathogenesis of different subsets of head and neck cancers. The aim of this study was to investigate to which extent the virus infection by itself, and/or the altered cell cycle proteins, contributes to prognosis in locally advanced tonsillar squamous cell carcinomas (TSCCs) treated with concurrent chemoradiotherapy (CCRT) alone. METHODS: Serial tumor tissue arrays from archival samples were tested for the presence of HPV genome integration or EBV episome by means of DNA sequencing, real-time polymerase chain reaction (PCR), and in situ hybridization. Alterations of cell cycle proteins (p53, pRb, and p21) were evaluated by immunohistochemical staining. The association of viral presence with altered cell cycle proteins was correlated to clinical outcomes. RESULTS: Of the 46 patients with the same T2N2bM0 stage IVA among consecutive patients with TSCC, 23 (50%) had integrated HPV DNA and only 1 (2%) had EBV episome. The HPV types detected were almost all HPV-16. A reduced expression pattern of p53, pRb, and p21 was noted in HPV-positive tumors, and the incremental number of alterations in the 3 proteins was significantly associated with HPV-negative tumors. The presence or absence of HPV together with the number of altered expression of the 3 cell cycle markers resulted in further identification of 4 biologically and clinically distinct subgroups with different outcomes after CCRT. CONCLUSIONS: Use of combined biomarkers of oncogenic HPV and tumor suppressors of p53, pRb, and p21 in advanced TSCC provides prognostic molecular classification superior to the TNM stage system and identifies low-risk patients for organ preservation by CCRT alone and high-risk patients who might benefit from planned tonsillectomy and neck dissection before or after CCRT.

CT-guided needle biopsy: value of on-site cytopathologic evaluation of core specimen touch preparations.

PURPOSE: To examine the diagnostic effect of immediate on-site cytopathologic evaluation of tissue core touch preparations in computed tomographic (CT)-guided coaxial needle biopsy. MATERIALS AND METHODS: The authors reviewed the records of 430 patients and included 413 patients with 432 biopsies (210 in the lungs, 222 in other locations). Each time the guiding needle was moved to a new location in the lesion for tissue core procurement with the cutting needle, it represented a new session. Core specimen touch preparations were obtained and immediately evaluated on-site for specimen adequacy and preliminary diagnosis. New sessions were considered and/or executed in the case of inconclusive cytopathologic readings. Each final diagnosis was reached according to the pathology report showing "positive for malignancy," "negative but with a specific diagnosis," or "unclear" for further surgical resection specimen or radiologic follow-up. RESULTS: The accuracy of on-site cytopathologic examination of touch preparations was 80.6% for the first session and increased to 85.9% and 86.3%, respectively, for the second and third sessions. The corresponding accuracies for biopsy were 88.2%, 93.8%, and 94.9%. The overall accuracy was 97.1% for lesions in the lungs and 92.8% for lesions at other sites. More biopsy sessions were deemed necessary in lesions measuring 2 cm or smaller (P = .0045). During CT-guided lung biopsy, 10 patients (4.8%) had major complications that necessitated chest tube insertion. CONCLUSIONS: The diagnostic accuracy of CT-guided needle biopsy can be increased through repeated sessions with immediate on-site cytologic evaluation, especially for lesions of 2 cm or smaller and those from nonpulmonary sites.

Is final TNM staging a predictor for survival in locally advanced rectal cancer after preoperative chemoradiation therapy?

BACKGROUND: Neoadjuvant chemoradiation therapy has improved the local control rate and overall survival in locally advanced rectal cancers. The purpose of this retrospective study is to evaluate the correlation between the final pathologic stage and survival in these patients. METHODS: Patients with biopsy-proven rectal carcinoma, pretreatment staging by magnetic resonance imaging such as T3 or T4 tumors, or node-positive disease were treated with preoperative concomitant 5-fluorouracil-based chemotherapy and radiation, followed by radical surgical resection. Clinical outcome with survival, disease-free survival, recurrence rate, and local recurrence rate were compared with each T and N findings using the American Joint Committee on Cancer Tumor-Node-Metastasis (TNM) staging system. RESULTS: A total of 248 patients were enrolled in this study. Overall survival and disease-free survival at 1, 3, and 5 years were 97.1, 92, and 89.9% and 87.5, 71.1, and 69.5%, respectively. Thirty-six patients (14.5%) had a pathologic complete response after neoadjuvant therapy. The recurrence rate was significantly different between the pathologic complete response group and residual group (5.6 vs 31.1%; P = .002). Five-year disease-free survival was significantly better in the complete response group than the residual tumor group (93 vs 66%; P = .0045). There was no statistical difference in survival or locoregional recurrence rate between these two groups. CONCLUSIONS: Posttreatment pathologic TNM stage is correlated to disease-free survival and tumor recurrence rate in locally advanced rectal cancer after preoperative chemoradiation. Also, pathologic complete response to neoadjuvant treatment has its oncologic benefit in both overall recurrence and disease-free survival.

Study of prostate cancer pathologic features in Chinese populations.

OBJECTIVES: To report the pathologic features of prostate cancer and its clinical outcome in the Chinese population in Taiwan. METHODS: A total of 139 radical prostatectomy specimens removed at Koo Foundation Sun Yat-Sen Cancer Center from 1993 to 2001 were reviewed. RESULTS: The median patient age was 69 years. The histologic type was acinar adenocarcinoma in 137, mucinous adenocarcinoma in 1, and ductal adenocarcinoma in 1. The median tumor number in each prostate gland was 2. The main tumor location was distributed in peripheral zone (76.3%), followed by the transitional zone (15.1%). The Gleason score of the largest tumor was 2 to 4 in 1.5%, 5 to 6 in 7.9%, 7 in 48.9%, and 8 to 10 in 41.7%. Extraprostatic tumor extension, seminal vesicle invasion, and lymph node metastasis were found in 59.0%, 28.8%, and 13.7% of the patients, respectively. Of the 139 specimens, 56 (40.3%), 64 (46.1%), and 19 (13.7%) were pathologic Stage T2, T3, and T4, respectively. The clinical stage (P = 0.0059), serum prostate-specific antigen (PSA) level (greater than 20 ng/mL versus 10 ng/mL or less, P = 0.002), extraprostatic extension (P = 0.0012), seminal vesicle invasion (P <0.0001), and surgical margin status (P <0.0001) were all significant factors for disease progression on univariate analysis. On multivariate analysis, the serum PSA level (greater than 20 ng/mL versus 10 ng/mL or less, P = 0.03), seminal vesicle invasion (P = 0.02), and surgical margin status (P = 0.02) remained significant. CONCLUSIONS: The patients with prostate cancer cared for at the Koo Foundation Sun Yat-Sen Cancer Center were older and had greater PSA levels, a more advanced stage, higher grade tumors, and high positive surgical margin rates. Increased public awareness and implementing a PSA screening program in Taiwan are of crucial importance.

Genomic prediction of locoregional recurrence after mastectomy in breast cancer.

PURPOSE: This study aims to explore gene expression profiles that are associated with locoregional (LR) recurrence in breast cancer after mastectomy. PATIENTS AND METHODS: A total of 94 breast cancer patients who underwent mastectomy between 1990 and 2001 and had DNA microarray study on the primary tumor tissues were chosen for this study. Eligible patient should have no evidence of LR recurrence without postmastectomy radiotherapy (PMRT) after a minimum of 3-year follow-up (n = 67) and any LR recurrence (n = 27). They were randomly split into training and validation sets. Statistical classification tree analysis and proportional hazards models were developed to identify and validate gene expression profiles that relate to LR recurrence. RESULTS: Our study demonstrates two sets of gene expression profiles (one with 258 genes and the other 34 genes) to be of predictive value with respect to LR recurrence. The overall accuracy of the prediction tree model in validation sets is estimated 75% to 78%. Of patients in validation data set, the 3-year LR control rate with predictive index more than 0.8 derived from 34-gene prediction models is 91%, and predictive index 0.8 or less is 40% (P = .008). Multivariate analysis of all patients reveals that estrogen receptor and genomic predictive index are independent prognostic factors that affect LR control. CONCLUSION: Using gene expression profiles to develop prediction tree models effectively identifies breast cancer patients who are at higher risk for LR recurrence. This gene expression-based predictive index can be used to select patients for PMRT.

A prognostic scoring system for locoregional control in nasopharyngeal carcinoma following conformal radiotherapy.

PURPOSE: This study established a prognostic scoring system for nasopharyngeal carcinoma (NPC), which estimates the probability of locoregional (LR) control following definitive conformal radiotherapy. METHODS AND MATERIALS: Patients with nondisseminated NPC at initial presentation (n = 630) were enrolled in this study. All patients had magnetic resonance imaging of the head and neck and were treated with conformal radiotherapy. Among them, 93% had concurrent chemotherapy, and 76% had postradiation chemotherapy. The extent of the primary tumor, age at diagnosis, primary tumor size, tumor and nodal classification, histology, and serum lactate dehydrogenase (LDH) level before treatment were included in the analysis for building a prognostic scoring system. The end point for this study was LR control. RESULTS: The prognostic score was defined as the number of adverse prognostic factors present at diagnosis. Four factors had similarly independent prognostic effects (hazard ratio, 2.0-2.6): age >40 years, histologic WHO type I-II, serum LDH level > or =410 U/L, and involvement of two or more sites of the following anatomic structures, i.e., sphenoid floor, clivus marrow, clivus cortex, prevertebral muscles, and petrous bone. The score predicted the 5-year probability of LR control as follows: 0 (15% of the patients), 100%; 1 (42% of the patients), 93%; 2 (29% of the patients), 83%; 3 or higher (13% of the patients), 71%. CONCLUSION: This scoring system is useful in the decision-making for individual patients and the design of clinical trials to improve LR control for advanced-stage NPC.

Sublethal irradiation induces vascular endothelial growth factor and promotes growth of hepatoma cells: implications for radiotherapy of hepatocellular carcinoma.

PURPOSE: To investigate the clinical benefit of additional radiotherapy to patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoembolization (TACE) and the molecular effects of radiation on gene expression in hepatoma cells. EXPERIMENTAL DESIGN: Between August 1996 and August 2003, 276 and 64 patients with American Joint Committee on Cancer stage T3N0M0 hepatocellular carcinoma receiving TACE alone and TACE followed by three-dimensional conformal radiotherapy, respectively, at our institution were studied. Clinical outcome and pattern of failure were analyzed for the association of survival benefit with radiotherapy. The molecular effects of radiotherapy were studied in vitro and in vivo using human hepatoma cells with different p53 mutation and hepatitis B virus infection status. RESULTS: Median follow-up and survival time in the TACE alone and TACE + radiotherapy groups were 39 and 19 months, and 51 and 17 months, respectively. Additional radiotherapy to TACE did not improve overall survival (P = 0.65). However, different failure patterns were noted after TACE and after radiotherapy. Although all irradiated tumors regressed substantially, radiotherapy rapidly enhanced both intrahepatic and extrahepatic tumor progression outside the radiotherapy treatment field in a significant portion of patients, which offset the benefit of radiotherapy on overall survival. In molecular analysis of the radiation effects on human hepatoma cells, radiotherapy rapidly induced p53-independent transcriptional up-regulation of vascular endothelial growth factor (VEGF), increased VEGF secretion in a dose-, time-, and cell type-dependent manner, and promoted hepatoma cell growth in vivo with enhanced intratumor angiogenesis, which correlated well with elevated levels of serum VEGF. CONCLUSIONS: Radiotherapy to eradicate a primary hepatocellular carcinoma might result in the outgrowth of previously dormant microtumors not included in the radiotherapy treatment field. Radiotherapy-induced VEGF could be a paracrine proliferative stimulus. Therapeutic implications of the study justify the combination of three-dimensional conformal radiotherapy with anti-VEGF angiogenic modalities for the treatment of unresectable hepatocellular carcinoma to reduce relapses.

Prognostic index score and clinical prediction model of local regional recurrence after mastectomy in breast cancer patients.

PURPOSE: To develop clinical prediction models for local regional recurrence (LRR) of breast carcinoma after mastectomy that will be superior to the conventional measures of tumor size and nodal status. METHODS AND MATERIALS: Clinical information from 1,010 invasive breast cancer patients who had primary modified radical mastectomy formed the database of the training and testing of clinical prognostic and prediction models of LRR. Cox proportional hazards analysis and Bayesian tree analysis were the core methodologies from which these models were built. To generate a prognostic index model, 15 clinical variables were examined for their impact on LRR. Patients were stratified by lymph node involvement (<4 vs. >or =4) and local regional status (recurrent vs. control) and then, within strata, randomly split into training and test data sets of equal size. To establish prediction tree models, 255 patients were selected by the criteria of having had LRR (53 patients) or no evidence of LRR without postmastectomy radiotherapy (PMRT) (202 patients). RESULTS: With these models, patients can be divided into low-, intermediate-, and high-risk groups on the basis of axillary nodal status, estrogen receptor status, lymphovascular invasion, and age at diagnosis. In the low-risk group, there is no influence of PMRT on either LRR or survival. For intermediate-risk patients, PMRT improves LR control but not metastases-free or overall survival. For the high-risk patients, however, PMRT improves both LR control and metastasis-free and overall survival. CONCLUSION: The prognostic score and predictive index are useful methods to estimate the risk of LRR in breast cancer patients after mastectomy and for estimating the potential benefits of PMRT. These models provide additional information criteria for selection of patients for PMRT, compared with the traditional selection criteria of nodal status and tumor size.

Prognostic accuracy of Acute Physiology and Chronic Health Evaluation II scores in critically ill cancer patients.

BACKGROUND: The predictive accuracy of scores on the Acute Physiology and Chronic Health Evaluation II (APACHE II) for in-hospital mortality among critically ill cancer patients varies. OBJECTIVE: To evaluate the predictive accuracy of APACHE II scores for severity of illness in critically ill cancer patients and to find clinical indicators to improve the accuracy. METHODS: Actual hospital mortality rates were compared with predicted rates. Data were collected prospectively from 1263 cancer patients admitted to the intensive care unit during a 5-year period in a cancer center in Taiwan. The APACHE II score for each patient was calculated at admission. Stepwise logistic regression was used to identify clinical predictors associated with increased mortality. RESULTS: The scores ranged from 2 to 54. The mortality rates were 19% overall, 45% for medical patients, and 1% for surgical patients. The fit of the scores was good for the medical patients (Hosmer-Lemeshow statistic 8.2, P = .41). The estimated odds ratios for mortality of presence of metastasis and respiratory failure were 4.18 (95% CI 2.65-6.59) and 2.03 (95% CI 1.22-3.38), respectively. When metastasis and respiratory failure were incorporated into the APACHE II model, the area under the receiver operating characteristic curve for medical patients increased from 0.82 to 0.86. The fit of the modified model was excellent (Hosmer and Lemeshow statistic 6.57, P=.58). CONCLUSIONS: APACHE II scores are predictive of hospital mortality in critically ill cancer patients. The presence of metastasis and respiratory failure at admission are also associated with outcome.

Breast cancer and dietary factors in Taiwanese women.

OBJECTIVES: To examine the effect of the consumption of dietary factors on the risk of breast cancer in a case-control study in Taiwan. METHODS: Two-hundred-and-fifty cases and 219 age-matched controls between the ages of 25 and 74 were interviewed in person between 1996 and 1999. Usual consumption of dietary habits including 100 foods was assessed using a food frequency questionnaire and a nutrient database developed and validated in Taiwanese populations. RESULTS: Cases consumed significantly more fat than controls. Cases also consumed statistically significant less supplements such as vitamins and mineral than controls. Food group analyses showed that highest quartile of beef and pork intake significantly increased risk in younger women (OR = 2.5, 95% CI = 1.0-6.0) and all women (OR = 2.5, 95% CI = 1.1-3.3). The age- education- and total calorie-adjusted odds ratio (OR) of breast cancer risk comparing the highest and second highest quartile of fat intake to the lowest quartile was 5.1, 95% confidence interval (CI): 2.1-13 and 3.5, 95% CI: 1.4-8.7 among those younger cases (< or =40). A multiple regression model indicates a protective effect of supplements (OR: 0.40, 95% CI: 0.3-07) and a harmful effect of dietary fat (OR: 2.6, 95% CI: 1.4-5.0) for the highest versus lowest quartile in all women. CONCLUSIONS: Our results indicate a strong protective effect of dietary supplements and a harmful effect of dietary fats on the risk of breast cancer among women in Taiwan. These findings should be confirmed in future follow-up studies. Specific amount of dietary supplements and dietary fats should be quantified for a more accurate evaluation on the risk for breast cancer in this population.

Extended-field radiotherapy and high-dose-rate brachytherapy with concurrent and adjuvant cisplatin-based chemotherapy for locally advanced cervical cancer: a phase I/II study.

OBJECTIVE: The purpose of this prospective study was to investigate the toxicity and efficacy of integrating extended-field para-aortic and pelvic external radiation, high-dose-rate intracavity brachytherapy, and concurrent and adjuvant cisplatin-based chemotherapy for locally advanced cervical cancer. METHOD: A phase I/II study was performed from 1998 to 2003 including sixty-three patients with both clinical FIGO and MRI/CT-based TNM stage IIB-IVA cervical cancer. Patients were treated with extended-field external radiation to the para-aortic and pelvic regions with 45 Gy in 25 fractions, and an additional boost to the gross nodes to 50.4 Gy and the parametrium to 59.4 Gy. Patients also received a high-dose-rate (HDR) intracavity brachytherapy with doses of 22-31 Gy to point A in 4-6 fractions. Concurrently, two cycles of cisplatin (50-80 mg/m(2)) were administered in weeks 1 and 5 during radiotherapy, as well as two cycles of cisplatin (60-80 mg/m(2)) for 1 day and 5-fluorouracil (600-800 mg/m(2)) for 4 days at 1 and 2 months after completion of radiotherapy. The treatment-related acute and late side effects were evaluated using RTOG criteria, and the disease control and survival rate were calculated using the Kaplan-Meier method. The median follow-up interval was 36 months. RESULTS: All sixty-three patients completed the planned extended-field radiotherapy and high-dose-rate brachytherapy with 2 concurrent cycles of cisplatin. Fifty-eight (92%) patients received 2 cycles of the post-radiation adjuvant chemotherapy of cisplatin and 5-fluorouracil. RTOG grade III acute toxicity was gastrointestinal (2%) and hematological (10%). No patient had grade IV acute toxicity. Late grades III-IV morbidity actuarial risk of 6% at 6.5 years primarily involved the injuries to the bowels requiring surgical intervention for intestinal obstruction or fistula formation. Initial sites of recurrence were locoregional failure alone (pelvic and para-aortic regions within the radiation field), 3%; distant metastases only, 8%; and locoregional failure plus distant metastases, 8%. The observed rates at 3-year and 5-year of locoregional control, freedom from distant metastasis, and overall survival were 86% and 86%, 81% and 81%, and 81% and 77%, respectively. CONCLUSION: Incorporating HDR brachytherapy into a regimen including concurrent chemotherapy and extended radiation appears safe and effective.