Jun-Sang Kim

Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer

PURPOSEnCapecitabine (Xeloda) is a new orally administered fluoropyrimidine carbamate that was rationally designed to exert its effect by tumor-selective activation. We attempted to evaluate the efficacy and toxicity of preoperative chemoradiation using capecitabine in locally advanced rectal cancer.nnnMETHODS AND MATERIALSnBetween July 1999 and March 2001, 45 patients with locally advanced rectal cancer (cT3/T4 or N+) were treated with preoperative chemoradiation. Radiation of 45 Gy/25 fractions was delivered to the pelvis, followed by a 5.4 Gy/3 fractions boost to the primary tumor. Chemotherapy was administered concurrent with radiotherapy and consisted of 2 cycles of 14-day oral capecitabine (1650 mg/m(2)/day) and leucovorin (20 mg/m(2)/day), each of which was followed by a 7-day rest period. Surgery was performed 6 weeks after the completion of chemoradiation.nnnRESULTSnThirty-eight patients received definitive surgery. Primary tumor and node downstaging occurred in 63% and 90% of patients, respectively. The overall downstaging rate, including both primary tumor and nodes, was 84%. A pathologic complete response was achieved in 31% of patients. Twenty-one patients had tumors located initially 5 cm or less from the anal verge; among the 18 treated with surgery, 72% received sphincter-preserving surgery. No Grade 3 or 4 hematologic toxicities developed. Other Grade 3 toxicities were as follows: hand-foot syndrome (7%), fatigue (4%), diarrhea (4%), and radiation dermatitis (2%).nnnCONCLUSIONnThese preliminary results suggest that preoperative chemoradiation with capecitabine is a safe, well-tolerated, and effective neoadjuvant treatment modality for locally advanced rectal cancer. In addition, this preoperative treatment has a considerable downstaging effect on the tumor and can increase the possibility of sphincter preservation in distal rectal cancer.

Hyperfractionated radiotherapy with concurrent chemotherapy for para-aortic lymph node recurrence in carcinoma of the cervix.

PURPOSEnTo evaluate efficacy, toxicity, and patterns of relapse in patients treated with hyperfractionated radiotherapy (HFRT) with concurrent chemotherapy for para-aortic lymph node (PALN) recurrence of cervical carcinoma.nnnMETHODS AND MATERIALSnBetween September 1997 and October 2000, 12 cervical carcinoma patients with isolated PALN recurrence who had previously received radical or postoperative radiotherapy were treated with HFRT and concurrent chemotherapy. The initial FIGO stage was Stage IB in 4 (33%) patients, Stage IIA in 2 (17%), and Stage IIB in 6 (50%). The radiation field encompassed the gross recurrent PALN with the superior margin at the upper end of the T12 body and the inferior margin between L5 and S1. The fractionated dose was 1.2 Gy in 2 daily fractions, and the median total dose was 60 Gy. The weekly concurrent chemotherapy consisted of paclitaxel in 11 patients and cisplatin in 1. The median number of cycles of chemotherapy was 5.nnnRESULTSnThe latent period to PALN recurrence from the time of initial treatment for all patients ranged from 2 to 92 months (median: 12 months). One month after treatment, the clinical tumor response evaluated was complete in 33% (4/12) and partial in 67% (8/12). The 3-year overall survival rate and median survival were 19% and 21 months, respectively. The latent period to PALN recurrence was the only significant prognostic factor; the median survival of patients who relapsed in < or =24 months from the initial treatment of cervical carcinoma was 13 months vs. 45 months for those relapsed at >24 months (p = 0.026). Grade 3-4 hematologic toxicity developed in 2 patients. Six (50%) patients experienced Grade 2 nausea. There were no late gastrointestinal or neurologic complications during the follow-up period. Subsequent distant metastases after PALN treatment developed in 58% (7/12).nnnCONCLUSIONnHFRT of 60 Gy to PALN with concurrent chemotherapy could be regarded as an effective treatment modality without significant acute or late toxicity. Patients with a latent period >24 months until PALN recurrence had a more favorable survival rate than those with a latent period </=24 months. Subsequent distant metastasis after PALN recurrence was the main cause of death and is a problem to overcome in the future.

Comparison of the Efficacy of Oral Capecitabine versus Bolus 5-FU in Preoperative Radiotherapy of Locally Advanced Rectal Cancer

The effects of treatment with oral capecitabine vs. bolus 5-FU, administered concurrently with preoperative radiotherapy, were compared in the treatment of locally advanced rectal cancer (LARC). One hundred and twenty-seven patients with LARC received concurrent preoperative chemoradiation using two cycles bolus 5-FU (500 mg/m2/day) plus leucovorin (LV, 20 mg/m2/day) (Group I). Another LARC group received concurrent chemoradiation using two cycles 1,650 mg/m2/day of oral capecitabine and 20 mg/m2/day of LV (Group II, 97 patients). Radiation was delivered to the primary tumor at 50.4 Gy in both groups. Definitive surgery was performed 6 weeks after the completion of chemoradiation. A pathologic complete remission was achieved in 11.4% of patients in Group I and in 22.2% of patients in Group II (p=0.042). The down-staging rates of the primary tumor and lymph nodes were 39.0/68.7% in Group I and 61.1/87.5% in Group II (p=0.002/0.005). Sphincter-preserving surgery was possible in 42.1% of patients in Group I and 66.7% of those in Group II (p=0.021). Grade 3 or 4 leucopenia, diarrhea, and radiation dermatitis were statistically more prevalent in Group I than in Group II, while the opposite was true for grade 3 hand-foot syndrome. Preoperative chemoradiation using oral capecitabine was better tolerated than bolus 5-FU and was more effective in the promotion of both down-staging and sphincter preservation in patients with LARC.

Isocenter accuracy in frameless stereotactic radiotherapy using implanted fiducials

PURPOSEnThe stereotactic radiotherapy (SRT) system verifies isocenter accuracy in patient space. In this study, we evaluate isocenter accuracy in frameless SRT using implanted cranial gold markers.nnnMATERIALS AND METHODSnWe performed frameless SRT on 43 intracranial tumor patients between August 1997 and December 2000. The treatment technique was determined by the tumor shape and volume, and by the location of critical organs. The coordinates of anterior-posterior and lateral port film were inputted to ISOLOC software, which calculated (1) the couch moves translation distance required to bring the target point to the isocenter, and (2) the intermarker distance comparisons between the CT study and the treatment machine films. We evaluated the isocenter deviation based on the error between orthogonal film target coordinates and isocenter coordinates.nnnRESULTSnThe mean treatment isocenter deviations (x, y, z) were -0.03, 0.14, and -0.04 mm, respectively. The systematic component isocenter standard deviations were 0.28, 0.31, and 0.35 mm (1 SD), respectively, and the random component isocenter standard deviations were 0.53, 0.52, and 0.50 mm (1 SD), respectively.nnnCONCLUSIONSnThe isocenter accuracy in the frameless SRT-implanted fiducial system is highly reliable and is comparable to that of other stereotactic radiosurgery systems.

Extremely low intrinsic non-axisymmetric field in KSTAR and its implications

A surprisingly low level of intrinsic non-axisymmetric field (called error field) has been measured in KSTAR, suggesting at least an order of magnitude lower than in other major tokamaks. Specifically, the KSTAR was found to have an extremely low level of pitch resonant intrinsic error field at the m/n = 2/1 surface in the order of 10−5 of the magnetic field at the geometric centre, instead of 10−4 typically observed in other devices. Using a single array of in-vessel control coils (IVCCs) at the outboard midplane, the n = 1 intrinsic error field was diagnosed. Such a low level of intrinsic non-axisymmetric field as measured in KSTAR is less than or comparable to the Earths magnetic field or a remanent field in the KSTAR plasma chamber. Considering that a very low level of n = 1 intrinsic error field (mostly associated with kink-resonance) helps the plasma to be less vulnerable to mode-locking, this might have allowed the n = 1 resonant magnetic perturbation (RMP) currents (configured to be dominantly pitch-resonant for edge localized mode (ELM) suppression) to increase without invoking a kink-resonant mode-locking, consistent with experimental observation and poloidal mode spectra calculations in KSTAR. Further clarification of the influence of the intrinsic error field in terms of a 3D structure is expected to provide a solid foundation to understand the n = 1 RMP-driven ELM suppression uniquely observed in KSTAR.

Radiation-induced thymidine phosphorylase upregulation in rectal cancer is mediated by tumor-associated macrophages by monocyte chemoattractant protein-1 from cancer cells.

PURPOSEnThe mechanisms of thymidine phosphorylase (TP) regulation induced by radiation therapy (XRT) in various tumors are poorly understood. We investigated the effect and mechanisms of preoperative XRT on TP expression in rectal cancer tissues.nnnMETHODS AND MATERIALSnTP expression and CD68 and monocyte chemoattractant protein-1 (MCP-1) levels in rectal cancer tissues and cancer cell lines were evaluated before and after XRT in Western blotting, immunohistochemistry, enzyme-linked immunoassay, and reverse transcription-polymerase chain reaction studies. Isolated peripheral blood monocytes were used in the study of chemotaxis under the influence of MCP-1 released by irradiated colon cancer cells.nnnRESULTSnExpression of TP was significantly elevated by 9 Gy of XRT in most rectal cancer tissues but not by higher doses of XRT. In keeping with the close correlation of the increase in both TP expression and the number of tumor-associated macrophages (TAMs), anti-TP immunoreactivity was found in the CD68-positive TAMs and not the neoplastic cells. Expression of MCP-1 was increased in most cases after XRT, and this increase was strongly correlated with TP expression. However, this increase in MCP-1 expression occurred in tumor cells and not stromal cells. The XRT upregulated MCP-1 mRNA and also triggered the release of MCP-1 protein from cultured colon cancer cells. The supernatant of irradiated colon cancer cells showed strong chemotactic activity for monocyte migration, but this activity was completely abolished by neutralizing antibody.nnnCONCLUSIONSnUse of XRT induces MCP-1 expression in cancer cells, which causes circulating monocytes to be recruited into TAMs, which then upregulate TP expression in rectal cancer tissues.

Retrospective analysis of treatment outcomes after postoperative chemoradiotherapy in advanced gastric cancer

Purpose To evaluate retrospectively the survival outcome, patterns of failure, and complications in patients treated with postoperative chemoradiotherapy (CRT) in advanced gastric cancer. Materials and Methods Between January 2000 and December 2006, 80 patients with advanced gastric cancer who received postoperative concurrent CRT were included. Pathological staging was IB-II in 9%, IIIA in 38%, IIIB in 33%, and IV in 21%. Radiotherapy consisted of 45 Gy of radiation. Concurrent chemotherapy consisted of a continuous intravenous infusion of 5-fluorouracil and leucovorin on the first 4 days and last 3 days of radiotherapy. Results The median follow-up period was 48 months (range, 3 to 83 months). The 5-year overall survival, disease-free survival, and locoregional recurrence-free survivals were 62%, 59%, and 80%, respectively. In the multivariate analysis, significant factors for disease-free survival were T stage (hazard ratio [HR], 0.278; p = 0.038), lymph node dissection extent (HR, 0.201; p = 0.002), and maintenance oral chemotherapy (HR, 2.964; p = 0.004). Locoregional recurrence and distant metastasis occurred in 5 (6%) and 18 (23%) patients, respectively. Mixed failure occurred in 10 (16%) patients. Grade 3 leukopenia and thrombocytopenia were observed in 4 (5%) and one (1%) patient, respectively. Grade 3 nausea and vomiting developed in 8 (10%) patients. Intestinal obstruction developed in one (1%). Conclusion The survival outcome of the postoperative CRT in advanced gastric cancer was similar to those reported previously. Our postoperative CRT regimen seems to be a safe and effective method, reducing locoregional failure without severe treatment toxicity in advanced gastric cancer patients.

Effects of pressure on the pore formation of carbon/carbon composites during carbonization

In this study, porosity and graphitizability of coal tar pitch with the treatment pressure were investigated. 4-directional carbon/carbon composites (4D C/C) were made from the matrix precursor of coal tar pitch through the process of impregnation and carbonization. Then the effects of applied pressure during the densification on the composites were observed. The matrix pitch which had 600 bar applied during the carbonization process had one and a half times less pore area ratio than that treated at 1 bar. When the pitch was heat treated up to 2300°C after the high pressure carbonization, the degree of graphitization was improved on a small scale and the crystal size tended to reduce. As the applied pressures to 4D C/C composites increased from 1 to 600 bar, the densification ratio was greatly improved. In the pore size distribution of the 4D C/C composites, the macropore portion was decreased while the mesopore portion increased, when high pressures were applied.

Excision repair cross-complementation group 1 expression predicts response and survival in locally advanced cervical carcinoma patients treated with concurrent chemoradiotherapy

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Prognostic significance of human apurinic/apyrimidinic endonuclease (APE/Ref-1) expression in rectal cancer treated with preoperative radiochemotherapy.

PURPOSEnHuman apurinic endonuclease/redox factor 1 (APE/Ref-1) mediates repair of radiation-induced DNA lesions and regulates transcription via redox-based activation. We investigated the predictive and prognostic significance of APE/Ref-1 expression in pretreatment biopsy specimens in locally advanced rectal cancer (LARC) (cT3-T4 or N+).nnnMETHODS AND MATERIALSnAPE/Ref-1 expression was analyzed by immunohistochemistry in pretreatment biopsy specimens obtained from 83 patients with LARC. Patients received preoperative radiotherapy of 50.4 Gy in 28 fractions, combined with oral capecitabine and leucovorin chemotherapy, followed by curative surgery. The prognostic significance of various clinicopathologic characteristics, including APE/Ref-1 protein expression, was evaluated.nnnRESULTSnAPE/Ref-1 was expressed in 97% of patient samples. Exclusive APE/Ref-1 nuclear staining was observed in 49 of 83 samples (59%), and mixed nuclear and cytoplasmic staining was observed in 31 samples (37%). APE/Ref-1 nuclear expression levels were low in 49 patients (59%) and high in 34 patients (41%). The level of APE/Ref-1 nuclear expression was not a prognostic factor for overall and disease-free survival. Cytoplasmic expression of APE/Ref-1 was a borderline-significant predictive factor for pathologic tumor response (p = 0.08) and a significant prognostic factor for disease-free survival, as shown by univariate analysis (p = 0.037). Multivariate analysis confirmed that cytoplasmic localization of APE/Ref-1 is a significant predictor of disease-free survival (hazard ratio, 0.45; p = 0.046).nnnCONCLUSIONSnAPE/Ref-1 was expressed in a majority of pretreatment biopsy specimens from patients with LARC. The level of APE/Ref-1 nuclear expression was not a significant predictive and prognostic factor; however, cytoplasmic localization of the protein was negatively associated with disease-free survival. These results indicate that cytoplasmic expression of APE/Ref-1 represents an adverse prognostic factor for LARC patients who receive preoperative radiochemotherapy.