The excision repair cross-complementation group 1 (ERCC1) enzyme plays a rate-limiting role in the nucleotide excision repair pathway and is associated with resistance to platinum-based chemotherapy. The purpose of this study was to evaluate the role of ERCC1 expression as a predictive marker of survival in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) treated with cisplatin-based concurrent chemoradiotherapy (CCRT). ERCC1 expression was assessed by immunohistochemical staining. The median age of the 45 patients analysed was 56 years (range 27–75 years), and 82% were men; 73% of all specimens showed high expression of ERCC1. The overall tumour response rate after CCRT was 89%. The median follow-up was 53.6 months (95% CI, 34.5–72.7 months). The 3-year progression-free survival (PFS) and overall survival (OS) rates were 58.7 and 61.3%, respectively. Univariate analyses showed that patients with low expression of ERCC1 had a significantly higher 3-year PFS (83.3 vs 49.4%, P=0.036) and OS (91.7 vs 45.5%, P=0.013) rates. Multivariate analysis showed that low expression of ERCC1 was an independent predictor for prolonged survival (HR, 0.120; 95% CI, 0.016–0.934, P=0.043). These results suggest that ERCC1 expression might be a useful predictive marker of locally advanced SCCHN in patients treated with cisplatin-based CCRT.

Background: Gastric cancer with bone marrow metastases is known to pursue a rapidly deteriorating clinical course. We conducted a retrospective analysis to evaluate clinical manifestations and prognosis of gastric cancer patients with bone marrow metastases. Methods: Between September 1994 and February 2006, 39 gastric cancer patients with pathologically confirmed bone marrow dissemination were selected. Results: The majority of the patients showed younger age, poorly differentiated adenocarcinoma or signet ring cell carcinoma, thrombocytopenia, anemia, elevated lactate dehydrogenase and alkaline phosphatase. Poor prognostic factors for survival were serum sodium ≤133 mmol/l [relative risk (RR) 4.57; 95% CI 1.99–10.52; p < 0.001], the presence of lung metastasis (RR 3.47; 95% CI 1.48–8.15; p = 0.007) and the presence of peritoneal seeding (RR 2.17; 95% CI 1.06–4.43; p = 0.036). Median survival durations after bone marrow metastases for patients without any adverse factors (n = 19, 48.7%) and those with 1–3 adverse factors (n = 20, 51.3%) were 67 and 23 days, respectively (p = 0.013). Patients without any adverse factors did benefit from palliative chemotherapy (p = 0.048). Conclusion: We suggest that gastric cancer patients with bone marrow metastases should receive more tailored therapies according to different risk factors in order to enhance survival.

Background and purposePigmented villonodular synovitis (PVNS) is a rare proliferative disorder involving synovial membranes, and patients with PVNS have a variable prognosis. We retrospectively analyzed clinical outcomes after synovectomy plus low-dose external beam radiotherapy for diffuse PVNS of the knee.MethodsWe reviewed the medical records of 23 patients who underwent postoperative radiotherapy between 1998 and 2007. 19 patients had primary disease and 4 had recurrent disease with an average of 2.5 prior surgeries. After synovectomy (17 arthroscopic surgeries; 6 open), all 23 patients received 4-MV or 6-MV external beam radiotherapy with a median dose of 20 (12–34) Gy in 10 fractions.ResultsAt a median follow-up of 9 (0.8–12) years, 4 patients had recurrent disease, with a median disease-free interval of 5 years. Of these 4 patients, 3 received salvage synovectomy and regained local control. Univariate analysis showed that age, sex, history of trauma, and total dose of radiation were not predictive of local control. 22 patients reported excellent or good joint function, and 1 who refused salvage synovectomy had poor joint function. None of the patients experienced grade 3 or higher radiation-related toxicity or radiation-induced secondary malignancies.InterpretationPostoperative external beam radiotherapy is an effective and acceptable modality to prevent local recurrence and preserve joint function in patients with diffuse PVNS of the knee. Low-dose (20 Gy) radiotherapy appears to be as effective as moderate-dose treatment (around 35 Gy).

Hematopoietic stem cell transplantation (HSCT) recipients frequently develop opportunistic infections, including paranasal sinusitis. Paranasal sinusitis in post-transplant recipients can be complicated by life-threatening infections. Accordingly, we analyzed risk factors for development of paranasal sinusitis following HSCT and reviewed our experiences for analysis of the role of management of paranasal sinusitis prior to HSCT. A retrospective review was performed for patients who had received HSCT at Samsung Medical Center (Seoul, South Korea) from 1996 to 2003. A total of 252 patients were analyzed. While 23 patients (9.1%) had sinusitis prior to HSCT, its occurrence rate increased to 15.9% after HSCT. Patients with pre-HSCT sinusitis showed a high occurrence rate of post-HSCT sinusitis (34.8 vs. 14.0%, p = 0.015). However, when pre-HSCT radiological abnormality alone was compared to no evidence of sinusitis prior to HSCT, there was no significant difference in the occurrence rates of post-HSCT sinusitis (15.6 vs. 12.8%, p = 0.541). Although statistical significance was not demonstrated, the occurrence rate of post-HSCT sinusitis was relatively low in patients who received autologous HSCT compared to those who received allogeneic HSCT (11.3 vs. 20.3%, p = 0.060). Use of total body irradiation and presence of graft-versus-host disease did not correlate with development of post-HSCT sinusitis. Compared to the observation group, occurrence of post-HSCT sinusitis showed a slight reduction with medical or surgical intervention targeting radiological abnormalities of the paranasal sinuses (10.0 vs. 25.0%, p = 0.057). In conclusion, pre-HSCT sinusitis and allogeneic HSCT are associated with development of post-HSCT sinusitis. Although asymptomatic radiological abnormalities of the sinus do not increase the risk of post-HSCT sinusitis, optimal treatment prior to HSCT tends to decrease the risk of post-HSCT sinusitis.

The aim of this study was to evaluate the role of platinum-containing chemotherapy for metastatic triple-negative breast cancer (TNBC) patients in terms of the response rate (RR) and progression-free survival. A second aim was to characterize the clinical behavior at the time of relapse of TNBC. We retrospectively analyzed the clinical outcomes of patients with metastatic breast cancer who received taxane-platinum chemotherapy as the first-or second-line treatment, focusing on the TN phenotype. In total, 257 patients with metastatic breast cancer received platinum-containing chemotherapy at Samsung Medical Center from 1999 to 2006. Of these patients, 106 patients with available data on estrogen (ER), progesterone (PgR) and human epidermal growth factor receptor-2 (HER2) receptor status received taxane-platinum regimen as the first-or second-line treatment. The overall RR of patients with TNBC was 39%. This rate did not differ significantly from those of patients with other phenotypes. The time to death after chemotherapy (19 vs. 50 months, p 5 0.037) and overall survival (OS) (21 vs. 56 months, p 5 0.030) differed significantly between patients with TNBC and non-TNBC. TNBC showed a unique locoregional infiltration pattern at relapse, which might reflect its aggressive clinical behavior. Despite the similar response to platinum-containing chemotherapy, patients with TNBC had a shorter OS than patients with non-TNBC. The implication of TN phenotype as poor prognostic factor is uncertain, because it needs to be defined whether poor outcome is related to the rapid growing characteristics of tumor itself or the resistance to drug therapy. Further prospective studies are warranted. ' 2008 Wiley-Liss, Inc.Key words: triple-negative breast cancer; platinum chemotherapy; BRCA1 Human breast cancer is a heterogeneous group of diseases, encompassing a number of distinct biological entities that differ in their behavior, outcome and response to therapy.1,2 DNA microarray analysis has revealed 5 subtypes of breast cancer: luminal A, luminal B, basal cell-like, human epidermal growth factor receptor-2 (HER2) positive and estrogen receptor (ER) negative, and normal-like. These subtypes have different prognoses and need different systemic treatment strategies.3,4 The basal cell-like tumors typically lack or show low expression of HER2 and ER, and exhibit a high expression level of genes characteristic of basal epithelial cells.1,4-7 These tumors might share many clinical and biologic behaviors with triple-negative breast cancers (TNBCs), which lack of expression of ER, progesterone receptor (PgR) and HER2. 5,8 However, although most basal cell-like cancers do not express ER, PgR or HER2, there is incomplete overlap between basal cell-like breast cancer and TNBC. 5,[8][9][10] The TN phenotype of breast cancer is characterized by more aggressive clinical behavior and poorer prognosis compared with the other subtypes, which likely reflect this subtype's high proliferative capacity and the lack of targeted therapies such as convent...

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Malignant melanoma, a neoplastic disorder produced by malignant transformation of the melanocyte, is considered to be resistant to chemotherapy. Dacarbazine is one of the standard chemotherapeutic agents in Korea. This study is designed to analyze treatment outcome and delineate prognostic factors based on clinical parameters for patients with advanced malignant melanoma who had received dacarbazine-based chemotherapy. This is a multicenter, retrospective analysis of 95 patients with metastatic malignant melanoma who had received dacarbazine-based chemotherapy, from January 1997 to June 2010. After a median follow-up duration of 41 months (range, 2-191 months), median survival time from the start of treatment was 12.1 months [95% confidence interval (CI): 10.9-13.5]. The overall response rate was 26.3% (95% CI: 17.8-36.4). On univariate analysis, primary site [mucosa of head and neck, gastrointestinal (GI)/genitourinary tract > cutaneous+acral melanoma], metastases to liver, GI tract, and elevated lactate dehydrogenase adversely influenced on survival. At a multivariate level, independent poor prognostic factors were mucosal melanoma [P=0.001; hazard ratio (HR): 2.988; 95% CI: 1.534-5.821], metastasis to GI tract [P=0.040; HR: 2.108; 95% CI: 1.036-4.288], and elevated lactate dehydrogenase (P=0.047; HR: 1.695; 95% CI: 1.007-2.854). Dacarbazine-based chemotherapy seems to be a reasonable option in Asia where mucosal melanoma is more prevalent than in the West. The dacarbazine-based chemotherapy showed an overall response rate of 26.3% and an overall survival of 12.1 months without a significant difference in response rates between noncutaneous or cutnaeous melanoma.

Deletion of CDKN2A (p16) or amplification of CCND1 (cyclin D1) occurs commonly in head and neck squamous cell carcinoma (HNSCC) and induces sustained cyclin-dependent kinase (CDK) 4/6 activation. Here, we report the antiproliferative activity of LY2835219, a selective CDK4/6 inhibitor through inhibition of CDK4/6-dependent Ser780 phosphorylation in retinoblastoma (RB) and induction of cell cycle arrest in HNSCC cells. In addition, we demonstrated the antitumor effects of HNSCC xenografts to LY2835219 in vivo. Given the limited effect in HNSCC as a single-agent treatment with LY2835219, a combinational strategy is required to enhance antitumor activity. At the molecular level, we found that LY2835219 inhibited activation of AKT and ERK, but not mTOR. The combination of LY2835219 with mTOR inhibitor was found to be more effective than either drug alone in vitro and in vivo. Taken together, our findings suggest that a combinational treatment with LY2835219 and mTOR inhibitor is a promising therapeutic approach for HNSCC.