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BACKGROUNDThe hypervascular nature of hepatocellular carcinoma (HCC) is well characterized. Recent data have suggested that thalidomide possesses antiangiogenic and immunomodulatory activity. Therefore, the authors initiated a study to assess the efficacy and toxicity of thalidomide in patients with advanced HCC as primary and secondary endpoints, respectively.METHODSInclusion criteria were unresectable HCC with bidimentionally measurable disease, age ≥ 18 years, Eastern Cooperative Oncology Group performance status ≤ 2, and adequate organ function. Thalidomide was administered at a starting dose of 200 mg per day in a 100‐mg‐per‐week dose escalation regimen, up to the maximum tolerated dose or to 800 mg per day. Toxicity was monitored according to the National Cancer Institute Common Toxicity Criteria.RESULTSTwenty‐six of 27 patients were eligible and assessable for toxicity and response. A median daily dose of 300 mg was achieved. One patient experienced near‐complete recovery of α‐fetoprotein levels and a partial radiographic response on computed tomography. Two patients had stable disease during the 16‐week study period. The median duration of progression‐free survival was 42 days. The overall median survival was 123 days. Fatigue and somnolence were the most common side effects, occurring in 81% and 62% of patients, respectively. No Grade 4 hematologic toxicity was observed. Three patients experienced Grade 4 hepatic toxicity (namely, hyperbilirubinemia).CONCLUSIONSWith gradual dose escalation, thalidomide was tolerated in most patients with advanced HCC. However, treatment with thalidomide alone was associated with only a modest response in the treatment of HCC. Cancer 2005. © 2004 American Cancer Society.

Purpose: The experimental verification of the Acuros XB (AXB) algorithm was conducted in a heterogeneous rectangular slab phantom, and compared to the Anisotropic Analytical Algorithm (AAA). The dosimetric impact of the AXB for stereotactic body radiation therapy (SBRT) and RapidArc planning for 16 non-small-cell lung cancer (NSCLC) patients was assessed due to the dose recalculation from the AAA to the AXB. Methods: The calculated central axis percentage depth doses (PDD) in a heterogeneous slab phantom for an open field size of 3 × 3 cm 2 were compared against the PDD measured by an ionization chamber. For 16 NSCLC patients, the dose-volume parameters from the treatment plans calculated by the AXB and the AAA were compared using identical jaw settings, leaf positions, and monitor units (MUs). Results: The results from the heterogeneous slab phantom study showed that the AXB was more accurate than the AAA; however, the dose underestimation by the AXB (up to −3.9%) and AAA (up to −13.5%) was observed. For a planning target volume (PTV) in the NSCLC patients, in comparison to the AAA, the AXB predicted lower mean and minimum doses by average 0.3% and 4.3% respectively, but a higher maximum dose by average 2.3%. The averaged maximum doses to the heart and spinal cord predicted by the AXB were lower by 1.3% and 2.6% respectively; whereas the doses to the lungs predicted by the AXB were higher by up to 0.5% compared to the AAA. The percentage of ipsilateral lung volume receiving at least 20 and 5 Gy (V20 and V5 respectively) were higher in the AXB plans than in the AAA plans by average 1.1% and 2.8% respectively. The AXB plans produced higher target heterogeneity by average 4.5% and lower plan conformity by average 5.8% compared to the AAA plans. Using the AXB, the PTV coverage (95% of the PTV covered by the 100% of the prescribed dose) was reduced by average 8.2% than using the AAA. The AXB plans required about 2.3% increment in the number of MUs in order to achieve the same PTV coverage as in the AAA plans. Conclusion: The AXB is more accurate to use for the dose calculations in SBRT lung plans created with a RapidArc technique; however, one should also note the reduced PTV coverage due to the dose recalculation from the AAA to the AXB.

The primary objectives of this phase II study were to evaluate the use of preirradiation temozolomide followed by concurrent temozolomide and radiotherapy (RT) in patients with newly diagnosed anaplastic oligodendroglioma (AO) and mixed anaplastic oligoastrocytoma (MOA). Preirradiation temozolomide (150 mg/m(2)/day) was given on a 7-day-on/7-day-off schedule for up to six cycles. The primary end point was the response rate during the 6-month, pre-RT chemotherapy. Tumor tissue was analyzed for the presence of chromosomal deletions on 1p and 19q and for MGMT-promoter methylation. Forty-two patients were enrolled; 39 were eligible. The objective response rate was 32% (6% [complete response, CR], 26% [partial response PR]), and the rate of progression during pre-RT chemotherapy was 10%. The worst nonhematological toxicity was grade 4 in three patients (8%). Twenty-two patients completed concurrent chemotherapy and RT. There were no grade 4 nonhematological toxicities during the concurrent chemotherapy and RT. Seventeen of 28 (60.7%) evaluable cases had codeletion of 1p/19q; all 17 were free from progression at 6 months. Sixteen of 20 (80%) evaluable cases had MGMT-promoter methylation; all 16 were free from progression at 6 months. In conclusion, the rate of progression of 10% during pre-RT temozolomide chemotherapy for newly diagnosed AO and MAO compared favorably with prior experience with pre-RT PCV chemotherapy (20% in RTOG 9402). The toxicity of the dose-intense pre-RT regimen used in this study may warrant evaluation of other, less intense dosing strategies. Future studies will need to prospectively stratify patients according to the presence of deletions of chromosomes 1p and 19q.