Soojung Hong

Elevated Serum C-Reactive Protein as a Prognostic Marker in Small Cell Lung Cancer

Purpose Elevated C-reactive protein (CRP) is associated with poor prognosis in several tumor types. The purpose of this study was to investigate serum CRP as a prognostic marker in small cell lung cancer (SCLC). Materials and Methods The pretreatment serum CRP level was measured in 157 newly diagnosed SCLC patients, and correlation between serum CRP level and other clinical parameters was analyzed. Multivariate analyses were performed to find prognostic markers using Coxs proportional hazards model. Results The initial CRP concentration was within the normal range in 72 (45.9%) patients and elevated in 85 (54.1%) patients. There was a significant correlation between serum CRP level and the extent of disease (p<0.001), weight loss (p=0.029) and chest radiation (p=0.001). Median overall survival (OS) in the normal CRp group was significantly longer than with the high CRp group (22.5 months vs. 11.2 months, p<0.001). Extent of disease (p<0.001), age (p=0.025), and performance status (p<0.001) were additional prognostic factors on univariate analysis. On multivariate analysis, elevated serum CRp level was an independent prognostic factor for poor survival (HR=1.8; p=0.014), regardless of the extent of disease (HR=3.7; p<0.001) and performance status (HR=2.2; p<0.001). Conclusion High level of CRP was an independent poor prognostic serum marker in addition to previously well-known prognosticators in patients with SCLC.

Prognostic and Predictive Value of Carcinoembryonic Antigen and Cytokeratin-19 Fragments Levels in Advanced Non-Small Cell Lung Cancer Patients Treated with Gefitinib or Erlotinib

Purpose The prognostic and predictive value of pretreatment serum levels of carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) were assessed in advanced non-small cell lung cancer (NSCLC) patients treated with gefitinib or erlotinib. Materials and Methods Pretreatment CEA and CYFRA 21-1 were measured in 123 advanced NSCLC patients receiving gefitinib or erlotinib. High CEA levels (h-CEA) were significantly associated with females, patients with adenocarcinoma, and non-smokers. Results Low CYFRA 21-1 levels (l-CYFRA) were significantly associated with a good performance status (ECOG PS 0-1). The overall response rate (RR) was 27.6%, and higher RR was associated with adenocarcinoma, h-CEA, and epidermal growth factor receptor (EGFR) mutation. Patients with h-CEA had significantly longer progression-free survival (PFS) (p=0.021). Patients with l-CYFRA had significantly longer PFS and overall survival (p=0.006 and p<0.001, respectively). Of note, h-CEA and l-CYFRA had good prognosis in patients with unknown EGFR mutation status or patients with squamous cell carcinoma (p=0.021 and p=0.015, respectively). A good ECOG PS (HR=0.45, p=0.017), h-CEA (HR=0.41, p=0.007), l-CYFRA 21-1 (HR=0.52, p=0.025), and an EGFR mutation (HR=0.22, p<0.001) were independently predictive of a longer PFS. Conclusion h-CEA and l-CYFRA 21-1 may be prognostic and predictive serum markers for higher response and longer survival in patients with advanced NSCLC receiving gefitinib or erlotinib, especially in patients with unknown EGFR mutation status or patients with squamous cell carcinoma.

Overexpression of Class III Beta Tubulin and Amplified HER2 Gene Predict Good Response to Paclitaxel and Trastuzumab Therapy

Through this study, we aimed to validate several biomarkers that have been known to possibly predict the outcomes of the trastuzumab and paclitaxel (TP). Human epidermal growth factor 2 (HER2) positive metastatic breast cancer (MBC) patients who had been treated with TP in single institute from 2006 to 2009 were included in this study. For procured formalin fixed paraffin embedded tumor tissues, HER2 amplification index (AI) and polymorphisms of the immunoglobulin G fragment C receptors (FCGR) were assessed as biomarkers to the trastuzumab and expression of class III beta tubulin (bTubIII) was evaluated as a predictive factor to the paclitaxel. Of 46 patients treated with TP, 27 patients could be evaluated for HER2 AI, 31 for bTubIII, and 26 for FCGR gene polymorphism. The median of the HER2 AI was 5.0 (range, 1.4−15.5) and a higher HER2 AI (≥5.0) was significantly correlated with better response rate (RR) (80% vs. 42%, P = 0.049) and longer progression-free survival (PFS) (13.6 vs. 6.9 months, P = 0.023). High bTubIII expression showed higher RRs than did low expression (81% vs. 40%, P = 0.040) in addition to longer PFS (16.2 months vs. 8.8 months, P = 0.04). However, polymorphisms in FCGR 2A-H131R or FCGR 3A-V158F were not predictive of RR or PFS. Our results suggest that a high HER2 AI and high bTubIII expression could be predictive of the outcomes to TP therapy but no evidence was found in terms of FCGR polymorphisms.

Prognostic factors in small cell lung cancer: a new prognostic index in Korean patients.

Objective: The aims of this study were to identify prognostic factors for overall survival (OS) in patients with small cell lung cancer (SCLC) and to construct a prognostic index on the basis of their expected OS. Long-term survivors were also given special attention. Methods: We retrospectively analyzed 295 patients diagnosed with SCLC from January 2002 to September 2007 at the Severance Hospital, Seoul, Republic of Korea. Patient history was reviewed regarding both clinical and tumor-related markers, and treatment-related factors were also evaluated. Results: There were 131 (44.4%) patients with limited disease (LD) and 164 (55.6%) with extensive disease (ED). Median follow-up lasted 9.4 months. Objective response to chemotherapy was 66.8%. The median survival time (MST) was 11.2 months in all patients, 20.4 months in LD patients, and 7.7 months in ED patients. The median progression-free survival was 9.4 months. Independent prognostic factors for overall survival (OS) were extent of disease, performance status, and CYFRA 21-1 level. We classified all patients into four groups based on the results of multivariate analysis using classification and regression tree analysis. Median survival times were 22.7, 13.7, 8.5, and 3.2 months, respectively. A total of 51 (17.3%) patients from the entire study population were evaluated for long-term survival, which was defined as survival >2 years. Their MST was 43.1 months, and extent of disease, performance status, and CYFRA 21-1 were independent prognostic factors for long-term survival. Conclusions: We confirmed the well-known prognosticators, disease extent and performance status, in our patients, but further identified CYFRA 21-1 as independent prognostic factor. A prognostic index was constructed to create four classifications of SCLC considering these variables.

Comparison of Long-Term Outcome between Doublet and Triplet Neoadjuvant Chemotherapy in Non-Metastatic Osteosarcoma of the Extremity

Objective: This study compared outcomes between doublet (AP) and triplet (IAP) neoadjuvant chemotherapy for nonmetastatic osteosarcoma of the extremity. Methods: A total of 124 patients were enrolled. In the AP group, a doublet regimen of intraarterial cisplatin and intravenous doxorubicin was given to 77 patients from 1991 to 1999. In the IAP group, a triplet regimen of additional intravenous ifosfamide was given to 47 patients from 2000 to 2007. After completion of 3 cycles of chemotherapy, patients underwent surgery. We assessed tumor response according to pathologic tumor necrosis, and treated patients with further adjuvant chemotherapy. Results: The overall pathologic response was excellent with more than 90% tumor necrosis in 74.8% of patients. Total necrosis of tumors was also found in 46 (37.4%) patients. There was no difference between the 2 groups in pathologic response (75.3 vs. 72.3%; p = 0.52) or other clinicopathologic parameters. There was no difference between the 2 groups in recurrence rate (31.2 vs. 31.9%; p = 0.17) or lung metastasis (28.6 vs. 23.4%; p = 0.53). Moreover, there were no statistical differences in median disease-free survival and overall survival between the groups. There was more hematologic toxicity in the IAP group (neutropenia, p = 0.002; thrombocytopenia, p = 0.001; febrile neutropenia, p < 0.001). Conclusions: The addition of ifosfamide to doxorubicin and cisplatin in neoadjuvant chemotherapy did not show improved outcomes in this study. Further trials are required to elucidate optimal neoadjuvant chemotherapy and effective salvage regimens.

Value of specimen radiographs in diagnosing multifocality of thyroid cancer

Specimen radiography has been used widely to evaluate the complete excision of calcified breast lesions but has not been evaluated for thyroid cancer.

Predicting cumulative incidence of adverse events in older patients with cancer undergoing first-line palliative chemotherapy: Korean Cancer Study Group (KCSG) multicentre prospective study

BackgroundOlder patients have increased risk of toxicity from chemotherapy. Current prediction tools do not provide information on cumulative risk.MethodsPatients aged ≥ 70 years with solid cancer were prospectively enrolled. A prediction model was developed for adverse events (AEs) ≥ Grade 3 (G3), based on geriatric assessment (GA), laboratory, and clinical variables.Results301 patients were enrolled (median age, 75 years). Median number of chemotherapy cycles was 4. During first-line chemotherapy, 53.8% of patients experienced AEs ≥ G3. Serum protein < 6.7 g/dL, initial full-dose chemotherapy, psychological stress or acute disease in the past 3 months, water consumption < 3 cups/day, unable to obey a simple command, and self-perception of poor health were significantly related with AEs ≥ G3. A predicting model with these six variables ranging 0–8 points was selected with the highest discriminatory ability (c-statistic= 0.646), which could classify patients into four risk groups. Predicted cumulative incidence of AEs ≥ G3 was discriminated according to risk groups.ConclusionsThis prediction tool could identify the risk of AEs ≥ G3 after chemotherapy and provide information on the cumulative incidence of AEs in each cycle.Clinical Trial IdWHO ICTRP number, KCT0001071

Kaposi's Varicelliform-Like Eruption in a Patient Treated with Everolimus for Metastatic Renal Cell Carcinoma: Report of a Rare Case.

Kaposis varicelliform eruption is a cutaneous eruption caused by the herpes simplex virus and a few other viruses that infect persons with pre-existing dermatosis such as atopic dermatitis. We report the case of a 56-year-old man who was treated with the mammalian target of rapamycin inhibitor, everolimus, for metastatic renal cell carcinoma. He presented with painful, umbilicated vesicles and pustules on his face, genital region, forearms, and legs suggestive of Kaposis varicelliform eruption. He did not have a history of any visceral viral disease and pre-existing dermatosis. The diagnosis was based on the clinical features. He was treated with acyclovir for 7 days, with improvement of his skin lesions. We discuss the clinical manifestations of the Kaposi varicelliform-like eruption in an immunocompromised patient treated with everolimus.

Retraction: Prognostic and Predictive Value of Carcinoembryonic Antigen and Cytokeratin-19 Fragments Levels in Advanced Non-Small Cell Lung Cancer Patients Treated with Gefitinib or Erlotinib. Yonsei Med J 2012;53:931-9.

Dear Editor We deeply regret to inform you that our paper was submitted twice to two different Journals, and was already published in another Journal1; therefore, we are requesting to retract our paper that has been published in YMJ.2 We mistakenly submitted our paper to the other journal. As the corresponding author, I will take full responsibility for this error and respectfully request for the retraction of our paper from YMJ.

Venous thromboembolism in patients with renal cell carcinoma: Incidence, risk factors, and prognostic implication.

446 Background: Renal cell ca (RCC) is one of solid tumor with relatively highest incidence of venous thromboembolism (VTE). But, there have been to no large-scale studies that focused on VTE in RCC. The aim of this study was to investigate the incidence, time course of VTE, risk factors, and prognosis associated with VTE in RCC patients in Korea. METHODS The medical records of RCC patients (n=1248) histologically diagnosed at Severance Hospital, Yonsei University College of Medicine, Seoul, Korea from Jan 2005 to Mar 2011 were retrospectively reviewed. RESULTS Among 1248 RCC patients, 69.6% were men, median age was 56years (range: 4∼89), and stage distribution was stage I 65.1%, stage II 9.2%, stage III 10.4%, stage IV 12.5%. The 2-year cumulative incidences of tumor induced VTE (tVTE) was detected in 78 patients (6.3%), while 1-month, 6-months and 1-year cumulative incidence of tVTE were 5.3%, 5.7% and 6.0%, retrospectively. Two-year cumulative incidence of tVTE seemed to increase with stage (0.6%, 3.5%, 22.3% and 24.3% in stages I, II, III and IV, retrospectively). Almost tVTE events developed in the first few months after diagnosis. Stage and metastatic disease were independent risk factors for developing tVTE. In multivariate analysis, the development of tVTE was a significant predictor of survival (P=0.004) and stage, age, ECOG PS was also independent predictor of survival. CONCLUSIONS This is the first study that specially focused on tVTE in RCC. The 2-year cumulative incidence of tVTE in Korean patients with RCC was 6.3%, which is similar to other ethnic group. As tVTE related to poorer survival, RCC patients with advanced stage and metastasis with higher risk of tVTE, close follow-up is recommended and proactive prophylaxis of VTE might be needed.