What is the indication for sorafenib in hepatocellular carcinoma? A clinical challenge

The incidence of hepatocellular carcinoma is rising in many countries, including the United States. Approval of sorafenib (Nexavar) as the first targeted therapy for treatment of advanced hepatocellular carcinoma (HCC) represents a milestone in the treatment of this disease. The approval was based on two large randomized phase III trials from the Western and Eastern hemispheres that showed an overall survival benefit compared with placebo in patients with well-preserved liver function. The exact indication for sorafenib is unclear, however. The U.S. Food and Drug Administration (FDA) authorized use of sorafenib for "unresectable HCC", an indication which is very broad, vague, and confusing. Less is known about the effects of sorafenib in patients with decompensated liver disease, or of sorafenib in combination with local therapy or in a transplant setting. Prospective trials are lacking in these areas. We will review current data on use of sorafenib in HCC.     

What is the best schedule for administration of gemcitabine-taxane?

Until recently, standard adjuvant chemotherapy for metastatic breast cancer (MBC) consisted of anthracycline-based regimens, followed by a taxane. However, data suggest that taxane-based combinations can be more effective than taxanes alone for the second part of treatment. Synergy between paclitaxel and gemcitabine was demonstrated in vitro when paclitaxel was followed by gemcitabine. Dose-dense regimens administered every 2 weeks are more effective than standard 3 weekly regimens. In a phase II study, gemcitabine plus paclitaxel every 2 weeks as first-line chemotherapy of MBC was associated with an overall response rate (ORR) of 71%. Women with HER2 ECD-positive tumours have a poor ORR (40%) to first-line chemotherapy. The addition of trastuzumab to dose-dense paclitaxel-gemcitabine as first-line chemotherapy in women with HER2-positive MBC was associated with a dramatic increase in ORR to 78%, with no serious toxicity observed. Two phase III clinical trials of gemcitabine-paclitaxel as adjuvant chemotherapy in women with histologically-confirmed MBC are currently underway. Preliminary data show that this drug combination is well-tolerated, and the efficacy results are eagerly awaited.     

Extrahepatic spread from hepatocellular carcinoma: who are candidates for aggressive anti-cancer treatment?

BACKGROUND: There is no standard treatment for patients with extrahepatic spread from hepatocellular carcinoma. The aim of this retrospective study was to identify candidates for aggressive intervention or new drug trial among such patients. METHODS: Retrospective exploration was performed to extract a patient cohort step by step using univariate and multivariate analyses. RESULTS: There were 201 subjects from the past 12 years. The 1-, 3- and 5-year survival rates were 31.0, 9.2 and 4.5%, respectively. The upper limit of the 95% confidence interval of median survival time did not reach 3 months in patients with a performance status of 2 or worse, or with Child-Pugh grades B or C. After excluding those, univariate and multivariate analyses were performed in the remaining 124 subjects. Three independent prognostic factors--brain metastasis, number of metastatic tumors and primary tumor status--were identified. The final cohort was set at 121 after excluding three with brain metastasis. Among these 121, there were 11 with a solitary metastatic tumor and T1/2 primary tumor. In this subgroup, 10 underwent complete removal of the metastatic tumor, and the median survival time exceeded 5 years. CONCLUSION: Candidates for anti-cancer treatment should meet the following requirements: a performance status of 0 or 1, a Child-Pugh grade A and no brain metastasis. Among these, challenging locoregional intervention was acceptable only for patients with solitary metastatic tumor and T1/2 primary tumor.     

What is the optimal initial treatment for chronic lymphocytic leukemia?

For decades, initial therapy for chronic lymphocytic leukemia (CLL) consisted of alkylators such as chlorambucil (Leukeran). The introduction of nucleoside analogs such as fludarabine and monoclonal antibodies such as rituximab (Rituxan) markedly changed the initial therapy of CLL, particularly in the United States. Fludarabine and combination regimens such as fludarabine/cyclophosphamide (FC) have achieved higher complete response (CR) rates and progression-free survival (PFS) than chlorambucil in previously untreated CLL, but long-term overall survival has not improved, due to concurrent improvement in salvage therapy of relapsed CLL patients. Upfront chemoimmunotherapy regimens such as fludarabine/rituximab (FR) and fludarabine/cyclophosphamide/rituximab (FCR) have similarly improved CR rates and PFS in previously untreated CLL patients, but it is unclear whether overall survival is improved. Advances in cytogenetic analysis and other biologic prognostic factors have greatly enhanced clinicians' ability to risk-stratify newly diagnosed CLL patients, and knowledge of such prognostic factors is necessary to properly interpret results of clinical treatment studies. The choice of initial therapy for an individual patient should depend upon the patient's age and medical condition, cytogenetic and other prognostic factors, and whether the goal of therapy is maximization of CR and PFS or palliation of symptoms with minimal toxicity.     

What can we learn from the phenomenon of preferential lymph node metastasis in carcinoma?

Lymph nodes are the most common and earliest site of malignancies arising in epithelia. However, the reason for this pattern of preferential metastasis is not clear. This article reviews features of the metastatic process and lymph node microenvironment which might potentiate lymph node metastases. There is intriguing evidence that preferential lymph node metastasis is due to (1) the efficiency of lymph nodes as filters of the tumor cells which arrive there, and (2) the probability that adhesive interactions, normally governing the generation of different T-cell immune responses, are responsible for this efficiency and may also promote invasion and proliferation of tumor cells in the lymph node. Manipulation of the cytokine environment in a lymph node draining a primary epithelial tumor may alter both the expression of cell adhesion molecules within the node and the subsequent metastatic ability of the tumor cells arriving at it.     

Laparoscopic approach for hepatocellular carcinoma： where is the limit？

Hepatocellular cancer （HCC） is the sixth most common malignant tumor worldwide and the most common primary liver cancer （1）. Liver resection or liver transplantation is the therapeutic gold standards in patient with HCC. Due to advanced disease, extrahepatic metastases, or inadequate liver reserve, only 15% to 30% of patients with HCC can undergo to surgery （2）. Five-year risk of recurrence of HCC after resection is as high as 70% because the underlying chronic liver disease continues to put the patient at risk for the development of new cancer nodules （3）. Starting from the assumption that recurrence may be newly treated with surgery, laparoscopic approach is recommended,     

Well-differentiated neurocytoma: what is the best available treatment?

Most neurocytomas are well differentiated, being associated with better long-term survival than the more aggressive atypical lesions. Atypical neurocytomas are characterized by an MIB-1 labeling index >3% or atypical histologic features. This analysis focuses on well differentiated neurocytomas in order to define the optimal treatment. A case with a follow-up of 132 months is presented. The patient developed two recurrences two and four years after first surgery, each showing an increasing proliferation activity. Furthermore, all published well-differentiated neurocytoma cases were reviewed for surgery, radiotherapy, and prognosis. Additional relevant data were obtained from the authors. Complete resection (CTR), complete resection plus radiotherapy (CTR + RT), incomplete resection (ITR), and incomplete resection plus radiotherapy (ITR + RT) were compared for outcome by using the Kaplan-Meier method and the log-rank test. Data were complete in 301 patients (CTR, 108; CTR + RT, 27; ITR, 81; ITR + RT, 85). Local control and survival were better after CTR than after ITR (P < 0.0001 and P = 0.0085, respectively). Radiotherapy improved local control after ITR (P < 0.0001) and after CTR (P = 0.0474), but not survival (P = 0.17 and P = 1.0, respectively). In the ITR + RT group, doses < or =54 Gy (n = 33) and >54 Gy (n = 32) were not significantly different for local control (P = 0.88) and survival (P = 0.95). The data demonstrated CTR to be superior to ITR for local control and survival. After CTR and ITR, radiotherapy improved local control, but not survival. A radiation dose of 54 Gy appeared sufficient. Application of postoperative radiotherapy should be decided individually, taking into account the risk of local failure, the need for another craniotomy, and potential radiation toxicity.     

What is the best position of the arms in mantle field for Hodgkin's disease?

PURPOSE: To evaluate the best position of the arms in mantle field for Hodgkin's disease. METHODS AND MATERIALS: In 12 patients, with surgical clips placed at the time of an axillary dissection for breast cancer, the radiological projection of the clips according to three arm positions was prospectively evaluated: akimbo (A), extended (E), and up over the head (U). The surgical clips were arbitrarily separated into two groups: lower and upper. In each patient, the distance between the surgical clips and chest wall was measured, and the possibility of shielding the lungs and humeral heads was evaluated. RESULTS: The mean displacement of the lower clips away from the chest wall when the patients were in A, E, and U positions was 2.5, 3.0, and 4.6 cm, respectively. The upper group clips showed a lower difference in distance from chest wall. In the U position, there was always a clip of the lower group that projected over the humeral head, making it impossible to block this structure. CONCLUSION: In the A position, there is the possibility of blocking the humeral head, but it is necessary to irradiate more lung parenchyma. Type E treatment setup allows the shielding of both lung and humeral head, while maintaining adequate margins around the axillary nodes. In the U position, there is a greater possibility of shielding the lung parenchyma, but it is impossible to block the humeral heads.