Specific c-K-ras Gene Mutations as a Tumor-Response Marker in Locally Advanced Rectal Cancer Treated With Preoperative Chemoradiotherapy

Background: Forty percent of patients with colorectal cancer develop mutations in the K-ras gene.Objective: Our objective was to evaluate whether the presence of c-K-ras gene mutations is a useful tumor-response marker in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy.Material and Methods: Thirty seven patients with locally advanced rectal cancer were treated with preoperative chemoradiotherapy. Four to six weeks later, surgery was performed. Specimens were classified according to the UICC-AJC classification. A segment of the tumor was obtained to analyze specific c-K-ras gene mutations. Restriction fragment length polymorphism (RFLP) and single strand confirmation polymorphism (SSCP) techniques were used with a set of probes to detect specific c-K-ras mutations in codons 12, 13, and 61. The 37 patients were divided into Group A (with mutations) and Group B (without mutations).Results: All 37 patients completed the scheduled treatment. Group A consisted of 12 patients, whose tumors were classified and specific c-K-ras mutations were located as follows: eight in codon 12, two in codon 13, and one in codon 61. Group B consisted of 25 patients. The tumors were classified and there were more early-stage tumors in Group A, whereas in Group B there were more advanced-stage tumors (P 5 .05, respectively). The mean follow-up was 36.2 6 18.3 months. All Group A patients survived, whereas 8 of the 25 patients in Group B died due to progressive metastatic disease. Survival in Group A was 100%, whereas in Group B it was 59% (P 5 .03).Conclusions: The presence of specific c-K-ras mutations is an indicator of tumor response in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy and surgery. Therefore, responding patients may be more amenable to less radical surgical procedures based on c-K-ras mutations.     

Preclinical studies with the photon radiosurgery system (PRS)

PURPOSE: Determine the radiobiological effectiveness (RBE) for low-energy X-rays (average energy of 23 KeV) produced by the Photon Radiosurgery System (PRS). METHODS AND MATERIALS: RBE values were assessed by comparison with survival data obtained for cells irradiated with either low-energy X-rays from a GE Maxitron 100 machine or high-energy photons from a clinically used Varian 6 MV LINAC. The output of the GE and PRS sources was determined using Baldwin-Farmer and Markus thin window ionization chambers calibrated with 50 kVp X-rays and cross-checked against figures supplied by Photoelectron Corporation. The dose-rate for the PRS was 1.2 Gy/min at a distance of 35 mm with a field flatness of +/-2%. RESULTS: The RBE for the PRS low-energy X-ray source (at 1-mm depth) was greater than either the GE or Varian machines and varied with cell survival. For Chinese hamster ovary (CHO) cells, the PRS was 1.25 and 3.3 times more effective than 90 kVp X-rays and 6 MeV photons at 0.5% cell survival, respectively; by comparison, the PRS was 1.2 and 1.9 times more effective at 0.05% cell survival, respectively. Similar RBE values of 1.4 and 1.2 were obtained for human U373 and T98 glioblastoma cells grown in vitro irradiated with the PRS or GE sources, respectively. Other studies showed that the RBE for the PRS low-energy X-ray source increased with depth. The RBEs for the PRS source at 1-mm and 4-mm depth were 1.2 and 2.5 (0.5% survival) and 1. 2 and 1.9 (0.05% survival). CONCLUSIONS: The biological and physical properties of the PRS low-energy X-rays offer, under the right conditions, a significant advantage for patient treatment over conventional external beam, stereotactic, or brachytherapy treatment.     

Phase II study of etoposide (VP-16) in patients with thyroid cancer with no prior chemotherapy: an Eastern Cooperative Oncology Group Study (E1385)

This study of etoposide in thyroid cancer was designed to determine the activity and toxicity of etoposide in a variety of inoperable, thyroid hormone insensitive, and radio-iodine resistant primary cancers of the thyroid. The patients were required to have an ECOG performance status of at least 3 and no previous exposure to chemotherapy. The etoposide was given at a dose of 140 mg/m² daily for 3 days and every 3 weeks until progression. The study was closed after 18 months because of poor accrual. There were no responses seen among the 10 patients accrued. The toxicity was primarily hematologic. There was no evidence of activity of etoposide in thyroid carcinoma, although this study lacked significant power because of the poor accrual.