Study on chemoprevention of hepatocellular carcinoma by ginseng: an introduction to the protocol.
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In patients with chronic hepatitis C virus disease, there is a high incidence of development of hepatocellular carcinoma (HCC) in the process of transition from chronic hepatitis to hepatic cirrhosis. Although ginseng traditionally has been used mainly as a nutritional supplement in Asian countries, a case-control study found that it may inhibit the development of HCC. We therefore planned a clinical study of HCC prevention by medicinal ginseng. The subjects are patients with chronic C virus disease (chronic hepatitis and hepatic cirrhosis), who are high risk group for HCC. This intervention study is a multi-center, double-blind, randomized controlled trial. The participants will be randomly divided into two groups. The test sample (1 g of red ginseng powder per day) will be administered for 5 yr, and ginseng intake will be prohibited during the administration period. The primary endpoint of this study is the development of HCC. Target number of recruiting subjects are 300. The participants should be registered from February 2001 to January 2003. (+info)
Guidelines for the treatment of recurrent and metastatic cervical cancer.
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Although there have been important advances in the management of women with cervical cancer, the optimal treatment for patients with locally recurrent and metastatic disease is still problematic, and there are relatively few randomized trials to guide treatment decisions. This paper reviews the approach to management of patients who relapse after primary treatment for cervical cancer. Patients who are still potentially curable with radical treatment are identified, and the various treatment strategies are discussed. However, most women are treated with palliative intent, and the literature on palliative management is reviewed together with the levels of evidence. (+info)
High-grade extremity soft tissue sarcomas: factors predictive of local recurrence and its effect on morbidity and mortality.
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OBJECTIVE: To identify patient characteristics associated with the development of local recurrence and the effect of local recurrence on subsequent morbidity and mortality in patients with intermediate- to high-grade extremity soft tissue sarcomas. SUMMARY BACKGROUND DATA: Numerous studies on extremity soft tissue sarcomas have consistently shown that presentation with locally recurrent disease is associated with the development of subsequent local recurrences and that large tumor size and high histologic grade are significant factors associated with decreased survival. However, the effect of local recurrence on patient survival remains unclear. METHODS: From 1975 to 1997, 753 patients with intermediate- to high-grade extremity soft tissue sarcomas were treated at UCLA. Treatment outcomes and patient characteristics were analyzed to identify factors associated with both local recurrence and survival. RESULTS: Patients with locally recurrent disease were at a significantly increased risk of developing a subsequent local recurrence. Local recurrence was a morbid event requiring amputation in 38% of the cases. The development of a local recurrence was the most significant factor associated with decreased survival. Once a patient developed a local recurrence, he or she was about three times more likely to die of disease compared to similar patients who had not developed a local recurrence. CONCLUSIONS: Local recurrence in patients with intermediate- to high-grade extremity soft tissue sarcomas is associated with the development of subsequent local recurrences, a morbid event decreasing functional outcomes and the most significant factor associated with decreased survival. Although 85% to 90% of patients with high-grade extremity soft tissue sarcomas are treatable with a limb salvage approach, patients who develop a local recurrence need aggressive treatment and should be considered for trials of adjuvant systemic therapy. (+info)
Neoadjuvant chemotherapy for high-grade central osteosarcoma of the extremity. Histologic response to preoperative chemotherapy correlates with histologic subtype of the tumor.
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BACKGROUND: In primary central high-grade osteosarcoma, a number of distinct subtypes have been identified, but little is known about the response to chemotherapy. METHODS: The authors investigated whether the subtypes correlated with histologic response to chemotherapy in 1058 patients with osteosarcoma of the extremities who were treated with neoadjuvant chemotherapy over the last 20 years. The tumors were classified as osteoblastic (70%), chondroblastic (13%), fibroblastic (9%), and telangiectatic (6%). At diagnosis, 911 patients had localized disease and 147 had resectable lung metastases. RESULTS: The response to preoperative chemotherapy was good (90% or more tumor necrosis) in 59% of patients and poor (< 90% tumor necrosis) in 41% of patients. The rate of good responses was significantly higher (P = 0.0001) in the fibroblastic (83%) and telangiectatic (80%) tumors and significantly lower in chondroblastic tumors (43%). Prognosis was significantly correlated with the histologic subtypes. The 5-year overall survival rate was significantly higher (P = 0.0001) in fibroblastic (83%) and telangiectatic (75%) tumors than in osteoblastic (62%) and chondroblastic (60%) tumors. In all subtypes, except for the chondroblastic subtype, the 5-year overall survival rate was significantly higher (P = 0.0001) in good responders P = 0.0001 (68%) than in poor responders (52%). CONCLUSIONS: The authors concluded that the histologic subtype of primary central high-grade osteosarcoma of the extremity was strictly correlated with histologic response to chemotherapy and probably, as a consequence, also with prognosis. Further studies are needed to establish whether these results justify a specific therapeutic approach based on the histologic subtype of the tumor. (+info)
The influence of central review on outcome associations in childhood malignant gliomas: results from the CCG-945 experience.
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To examine the influence of the pathology review mechanism on the results of analyses of therapeutic efficacy and biological prognostic correlates for pediatric high-grade gliomas, we evaluated the effects of using single-expert review or consensus review, as alternatives to institutional classification, in determining outcome results of a large randomized trial. The study group was the randomized cohort of Children's Cancer Group study 945, which compared efficacy of 2 chemotherapy regimens adjuvant to surgery and radiation. Trial eligibility required institutional histopathologic diagnosis of high-grade glioma. Sections of study tumors also were centrally reviewed, initially by a study review neuropathologist and subsequently by 5 neuropathologists, including the review pathologist. Reviews were independent, and reviewers were masked to clinical factors and outcomes, and consensus diagnoses of the panel were then established. Among 172 eligible patients, 42 tumors were classified as discordant on single-expert review and 51 on consensus review. Progression-free survival probabilities calculated for patients with tumors classified as high-grade gliomas by either single-expert or consensus review were inferior to those for the overall, institutionally diagnosed cohort. However, conclusions of the study regarding relative efficacy of treatment and clinical and molecular outcome correlates were unaffected by diagnosis method. Resection extent, proliferation index, and p53 expression were associated strongly with outcome, regardless of diagnosis method. However, comparisons between arms in which inclusion was determined by different review criteria for each arm caused spurious conclusions about efficacy differences between treatments. We conclude that the pathology review mechanism had little effect on within-trial comparisons of therapeutic effects or prognostic correlates in this randomized study, but strongly influenced survival distributions that were calculated for each treatment arm. These results support the implementation of expedited central review in therapeutic studies involving childhood malignant gliomas as a way to prospectively identify and exclude cases with discordant diagnoses and indicate the need for additional measures, such as molecular assessments, to increase the reproducibility of neuropathologic classification for these tumors. (+info)
Implementing clinical protocols in oncology: quality gaps and the learning curve phenomenon.
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BACKGROUND: The quality improvement effort in clinical practice has focused mostly on 'performance quality', i.e. on the development of comprehensive, evidence-based guidelines. This study aimed to assess the 'conformance quality', i.e. the extent to which guidelines once developed are correctly and consistently applied. It also aimed to assess the existence of quality gaps in the treatment of certain patient segments as defined by age or gender and to investigate methods to improve overall conformance quality. METHODS: A retrospective audit of clinical practice in a well-defined oncology setting was undertaken and the results compared to those obtained from prospectively applying an internally developed clinical protocol in the same setting and using specific tools to increase conformance quality. RESULTS: All indicators showed improvement after the implementation of the protocol that in many cases reached statistical significance, while in the entire cohort advanced age was associated (although not significantly) with sub-optimal delivery of care. A 'learning curve' phenomenon in the implementation of quality initiatives was detected, with all indicators improving substantially in the second part of the prospective study. CONCLUSIONS: Clinicians should pay separate attention to the implementation of chosen protocols and employ specific tools to increase conformance quality in patient care. (+info)
Probabilistic reporting of EUS-FNA cytology: Toward improved communication and better clinical decisions.
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BACKGROUND: The objectives of this study were to determine threshold probabilities needed to perform endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and those needed to treat patients suspected of having malignancy and then to compare these thresholds to the pre- and posttest probabilities of malignancy associated with benign, atypical, suspicious, and malignant diagnoses. The goal was to aid endoscopists in making appropriate clinical decisions based on both quantitative and qualitative approaches. METHODS: The study included 633 consecutive patients. A decision tree was constructed to estimate the "treatment" threshold. Using treatment threshold and likelihood ratios, the authors determined the "no-test-test" and "test-treatment" thresholds. Pretest probability was compared with no-test-test and test-treatment thresholds, and the post-EUS-FNA probability of malignancy for each diagnostic category with the treatment threshold. Results were stratified by lesion site, lesion size, and cytopathologist. RESULTS: EUS-FNA has a wide range of pretest probabilities within which it could be performed (0.06-0.98). The posttest probabilities for malignancy, 0.99 (95% confidence interval [CI], 0.967-0.996) and 0.09 (95% CI, 0.057-0.126), after a positive or a negative result, respectively, were significantly different from the treatment threshold but not those of suspicious, 0.92 (95% CI, 0.767-0.994) diagnosis. The posttest probability of atypical diagnosis, 0.60 (95% CI, 0.407-0.772), was not significantly different from that of pretest probability. Results did not vary by lesion size, organ site, or cytopathologist. CONCLUSION: The authors demonstrated the uncertainty associated with EUS-FNA diagnostic categories and used the threshold approach to qualify quantitatively the decision to perform EUS-FNA and the decision to treat patients suspected of having malignancy. (+info)
Trial on refinement of early stage non-small cell lung cancer. Adjuvant chemotherapy with pemetrexed and cisplatin versus vinorelbine and cisplatin: the TREAT protocol.
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BACKGROUND: Adjuvant chemotherapy has been proven to be beneficial for patients with early stage non-small cell lung cancer. However, toxicity and insufficient dose delivery have been critical issues with the chemotherapy used. Doublet regimens with pemetrexed, a multi-target folate inhibitor, and platin show clear activity in non-small cell lung cancer and are well tolerated with low toxicity rates and excellent delivery. METHODS/DESIGN: In this prospective, multi-center, open label randomized phase II study, patients with pathologically confirmed non-small cell lung cancer, stage IB, IIA, IIB, T3N1 will be randomized after complete tumor resection either to 4 cycles of the standard adjuvant vinorelbine and cisplatin regimen from the published phase III data, or to 4 cycles of pemetrexed 500 mg/m2 d1 and cisplatin 75 mg/m2 d1, q 3 weeks. Primary objective is to compare the clinical feasibility of these cisplatin doublets defined as non-occurrence of grade 4 neutropenia and/or thrombocytopenia > 7 days or bleeding, grade 3/4 febrile neutropenia and/or infection, grade 3/4 non-hematological toxicity, non-acceptance leading to premature withdrawal and no cancer or therapy related death. Secondary parameters are efficacy (time to relapse, overall survival) and drug delivery. Parameters of safety are hematologic and non-hematologic toxicity of both arms. DISCUSSION: The TREAT trial was designed to evaluate the clinical feasibility, i.e. rate of patients without dose limiting toxicities or premature treatment withdrawal or death of the combination of cisplatin and pemetrexed as well as the published phase III regimen of cisplatin and vinorelbine. Hypothesis of the study is that reduced toxicities might improve the feasibility of drug delivery, compliance and the convenience of treatment for the patient and perhaps survival. (+info)