The predictive value of serum myeloma protein in solitary plasmacytoma

Purpose@#To identify the clinical usefulness of serum M protein and to establish a rationale for regular follow-up with serum protein electrophoresis in solitary plasmacytoma. @*Materials and Methods@#Sixty-nine patients with solitary plasmacytoma and solitary plasmacytoma with minimal marrow involvement according to the International Myeloma Working Group criteria were retrospectively reviewed. @*Results@#At a median follow-up of 6.2 years, 5-year local control (LC), 5-year multiple myeloma-free survival (MMFS), 5-year failure-free survival (FFS), and 5-year overall survival (OS) were 82.6%, 44.1%, 41.8%, and 85.1%, respectively. Among the patients whose initial serum M protein was present or not evaluated, 37.3% of patients showed disappearance of serum M protein after various treatment. MMFS of these patients were comparable to non-secretory plasmacytoma with undetectable levels of M protein, and significantly better than patients with persistent M protein. Increase of serum M protein ≥0.1 g/dL was most predictive of treatment failure with area under the curve of 0.731. @*Conclusion@#Patients who eventually showed persistence of serum M protein after treatment showed worse MMFS and FFS compared to those whose serum M protein disappeared or who had initially non-secretory disease. The increase of serum M protein level ≥0.1 g/dL from current nadir was predictive of treatment failure. Therefore, regular follow-up with serum M protein is highly recommended especially unless the patient had initially non-secretory disease.

Disulfiram, a Re-positioned Aldehyde Dehydrogenase Inhibitor, Enhances Radiosensitivity of Human Glioblastoma Cells In Vitro / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Glioblastoma, the most common brain tumor in adults, has poor prognosis. The purpose of this study was to determine the effect of disulfiram (DSF), an aldehyde dehydrogenase inhibitor, on in vitro radiosensitivity of glioblastoma cells with different methylation status of O⁶-methylguanine-DNA methyltransferase (MGMT) promoter and the underlying mechanism of such effect. MATERIALS AND METHODS: Five human glioblastoma cells (U138MG, T98G, U251MG, U87MG, and U373MG) and one normal human astrocyte (NHA) cell were cultured and treated with DSF or 6MV X-rays (0, 2, 4, 6, and 8 Gy). For combined treatment, cells were treated with DSF before irradiation. Surviving fractions fit from cell survival based on colony forming ability. Apoptosis, DNA damage repair, and cell cycle distributionwere assayed bywestern blot for cleaved caspase-3, γH2AX staining, and flow cytometry, respectively. RESULTS: DSF induced radiosensitization in most of the glioblastoma cells, especially, in the cells with radioresistance as wildtype unmethylated promoter (MGMT-wt), but did not in normal NHA cell. DSF augmented or induced cleavage of caspase-3 in all cells after irradiation. DSF inhibited repair of radiation-induced DNA damage in MGMT-wt cells, but not in cells with methylated MGMT promoter. DSF abrogated radiation-induced G2/M arrest in T98G and U251MG cells. CONCLUSION: Radiosensitivity of glioblastoma cells were preferentially enhanced by pre-irradiation DSF treatment compared to normal cell, especially radioresistant cells such as MGMT-wt cells. Induction of apoptosis or inhibition of DNA damage repair may underlie DSF-induced radiosensitization. Clinical benefit of combining DSF with radiotherapy should be investigated in the future.

Effect of Time Interval between Breast-Conserving Surgery and Radiation Therapy on Outcomes of Node-Positive Breast Cancer Patients Treated with Adjuvant Doxorubicin/Cyclophosphamide Followed by Taxane / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study evaluated the effect of surgery-radiotherapy interval (SRI) on outcomes in patients treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) and adjuvant four cycles of doxorubicin/cyclophosphamide (AC) followed by four cycles of taxane. MATERIALS AND METHODS: From 1999 to 2007, 397 eligible patients were diagnosed. The effect of SRI on outcomes was analyzed using a Cox proportional hazards model, and a maximal chi-square method was used to identify optimal cut-off value of SRI for each outcome. RESULTS: The median SRI was 6.7 months (range, 5.6 to 10.3 months). A SRI of 7 months was the significant cut-off value for distant metastasis-free survival (DMFS) and disease-free survival (DFS) using a maximal chi-square method. For overall survival, a significant cut-off value was not found. The patients with SRI > 7 months had worse 6-year DMFS and DFS than those with SRI ≤ 7 months on univariate analysis (DMFS, 81% vs. 91%, p=0.003; DFS, 78% vs. 89%, p=0.002). On multivariate analysis, SRI > 7 months did not affect DMFS and DFS. CONCLUSION: RT delayed for more than 7 months after BCS and adjuvant four cycles of AC followed by four cycles of taxane did not compromise clinical outcomes.

Proton Beam Radiotherapy for Pediatric Gliomas: Early Outcomes and Dose Comparison / 임상소아혈액종양

BACKGROUND: Proton beam radiotherapy (PBT) has shown to provide high radiation dose to tumors and to save surrounding normal tissues because of its physical characteristics, Bragg peak. In the current study, we report the early outcomes for pediatric patients with intracranial gliomas treated with PBT and compared PBT plan (pencil beam scanning and double scattering) with intensity modulated radiotherapy (IMRT) plan and three dimensional-conformal radiotherapy (3D-CRT) plan. METHODS: Clinical data from 18 consecutive children with intracranial gliomas who underwent PBT from May 2007 to April 2012 was collected. The median follow-up duration was 16 months (range 6-69). RESULTS: There were 9 patients with brain stem glioma, 2 patients with optic pathway glioma, 2 patients with low grade glioma (LGG), 2 patients with anaplastic astrocytoma (AA) and 3 patients with glioblastoma multiforme (GBM). The median overall survival for patients with brain stem glioma was 11 months. Patients with optic pathway glioma, LGG or AA were all alive without progression except one patient. Among patients with GBM, one patient had no evidence of disease 25 months after PBT. When PBT plan was compared to those of IMRT and 3D-CRT for patients with LGG or AA and one patient with brain stem glioma by DVH analysis, PBT showed better sparing effect on normal tissue compared to IMRT and 3D-CRT, especially in low dose area. CONCLUSION: PBT could be delivered safely and effectively to pediatric patients with gliomas. For confirming the clinical benefits of PBT, further follow-up is necessary.

Proton Beam Radiotherapy for Pediatric Gliomas: Early Outcomes and Dose Comparison / 임상소아혈액종양

BACKGROUND: Proton beam radiotherapy (PBT) has shown to provide high radiation dose to tumors and to save surrounding normal tissues because of its physical characteristics, Bragg peak. In the current study, we report the early outcomes for pediatric patients with intracranial gliomas treated with PBT and compared PBT plan (pencil beam scanning and double scattering) with intensity modulated radiotherapy (IMRT) plan and three dimensional-conformal radiotherapy (3D-CRT) plan.METHODS: Clinical data from 18 consecutive children with intracranial gliomas who underwent PBT from May 2007 to April 2012 was collected. The median follow-up duration was 16 months (range 6-69).RESULTS: There were 9 patients with brain stem glioma, 2 patients with optic pathway glioma, 2 patients with low grade glioma (LGG), 2 patients with anaplastic astrocytoma (AA) and 3 patients with glioblastoma multiforme (GBM). The median overall survival for patients with brain stem glioma was 11 months. Patients with optic pathway glioma, LGG or AA were all alive without progression except one patient. Among patients with GBM, one patient had no evidence of disease 25 months after PBT. When PBT plan was compared to those of IMRT and 3D-CRT for patients with LGG or AA and one patient with brain stem glioma by DVH analysis, PBT showed better sparing effect on normal tissue compared to IMRT and 3D-CRT, especially in low dose area.CONCLUSION: PBT could be delivered safely and effectively to pediatric patients with gliomas. For confirming the clinical benefits of PBT, further follow-up is necessary.

Salvage radiotherapy for lymph node recurrence after radical surgery in cervical cancer / 부인종양

OBJECTIVE: This study was to evaluate the treatment outcomes and prognostic factors of patients treated with salvage radiotherapy for the treatment of isolated lymph node recurrence of cervical cancer. METHODS: Between 1990 and 2009, 22 cervical cancer patients with lymph node recurrence who had previously undergone radical hysterectomy and pelvic lymph node dissection were treated with salvage radiotherapy with (n=18) or without (n=4) chemotherapy. Of the 22 patients, 10 had supraclavicular lymph node recurrence, 9 had para-aortic lymph node, and 3 had inguinal lymph node. The median total radiotherapy dose was 60 Gy (range, 40 to 70 Gy). Initial pathologic findings, latent period to lymph node recurrence and other clinical parameters such as squamous cell carcinoma antigen (SCC-Ag) level and concurrent chemotherapy were identified as prognostic factors for survival. RESULTS: The median follow-up period after salvage radiotherapy was 31.2 months (range, 12.1 to 148.9 months). The 5-year progression-free and overall survival rates of all patients were 32.7% and 30.7%, respectively. Concurrent chemoradiotherapy (p=0.009) and longer latent period to lymph node recurrence (>18 months vs. 8 ng/dL vs. < or =8 ng/dL, p=0.008) and longer latent period to lymph node recurrence (p=0.040) for overall survival. Treatment failure after salvage radiotherapy occurred in 14 (63.6%) for the 22 patients (in field, 2; out of field, 10; both in and out field, 2). Grade 3 acute skin (n=2) and hematologic toxicity (n=1) developed in 3 patients. CONCLUSION: For isolated lymph node recurrence of cervical cancer, salvage radiotherapy with concurrent chemotherapy should be considered, especially in patients with a long-term progression-free period.

Molecular biomarkers in extrahepatic bile duct cancer patients undergoing chemoradiotherapy for gross residual disease after surgery

PURPOSE: To analyze the outcomes of chemoradiotherapy for extrahepatic bile duct (EHBD) cancer patients who underwent R2 resection or bypass surgery and to identify prognostic factors affecting clinical outcomes, especially in terms of molecular biomarkers. MATERIALS AND METHODS: Medical records of 21 patients with EHBD cancer who underwent R2 resection or bypass surgery followed by chemoradiotherapy from May 2001 to June 2010 were retrospectively reviewed. All surgical specimens were re-evaluated by immunohistochemical staining using phosphorylated protein kinase B (pAKT), CD24, matrix metalloproteinase 9 (MMP9), survivin, and beta-catenin antibodies. The relationship between clinical outcomes and immunohistochemical results was investigated. RESULTS: At a median follow-up of 20 months, the actuarial 2-year locoregional progression-free, distant metastasis-free and overall survival were 37%, 56%, and 54%, respectively. On univariate analysis using clinicopathologic factors, there was no significant prognostic factor. In the immunohistochemical staining, cytoplasmic staining, and nuclear staining of pAKT was positive in 10 and 6 patients, respectively. There were positive CD24 in 7 patients, MMP9 in 16 patients, survivin in 8 patients, and beta-catenin in 3 patients. On univariate analysis, there was no significant value of immunohistochemical results for clinical outcomes. CONCLUSION: There was no significant association between clinical outcomes of patients with EHBD cancer who received chemoradiotherapy after R2 resection or bypass surgery and pAKT, CD24, MMP9, survivin, and beta-catenin. Future research is needed on a larger data set or with other molecular biomarkers.