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Digital workflow expedites the procedure of retrofitting a surveyed crown against an existing removable partial denture (RPD). This article describes a simple and straightforward technique of digital workflow where an existing RPD is scanned as an antagonist to design the rest seat, guide plane, and height of contour of a surveyed crown.

Although the introduction of human epidermal growth factor receptor (HER)2-directed therapy including trastuzumab, pertuzumab, lapatinib and trastuzumab emtansine (T-DM1) in the treatment of HER2-positive metastatic breast cancers (mBCs) favorably changed the natural history of this disease, most cases of HER2-positive mBC will eventually progress. Poziotinib is an oral pan-HER kinase inhibitor showing potent activity through irreversible inhibition of these kinases. This open-label, multicenter phase II study was designed to evaluate the efficacy and safety of poziotinib monotherapy in patients with HER2-positive mBC who had progressed from more than two HER2-directed therapies. Patients received 12 mg poziotinib once daily on a 14-day on/7-day off schedule. Progression-free survival (PFS) as the primary endpoint, the objective response rate (ORR), overall survival (OS) and safety were evaluated. From April 2015 to February 2016, 106 patients were enrolled in the trial from seven institutes in South Korea. They had a median age of 51 years (range 30-76) and had received a median of four prior therapies including two HER2-directed therapies for advanced or metastatic cancers. The median follow-up duration was 12 months. The median PFS was 4.04 months (95% confidence interval [CI], 2.94-4.40 months), and median overall survival has not been reached. The most common treatment-related adverse events were (total/grade ≥3) diarrhea (96.23%/14.15%), stomatitis (92.45%/12.26%) and rashes (63.21%/3.77%). Poziotinib showed meaningful activity in these heavily treated HER2-positive mBCs. Diarrhea and stomatitis were the major toxicities. Biomarker studies analyzed are warranted to support further evaluation of this treatment in such cases.

Aim We evaluated the tumor response and clinical outcomes according to molecular subtypes in stage II–III breast cancer patients who received neo-adjuvant chemotherapy (NAC) followed by surgery and radiotherapy. Methods We retrospectively analyzed 329 patients with clinical stage II–III breast cancer who received NAC followed by surgery and radiotherapy. Luminal A and B, HER2-enriched and triple-negative subgroups were identified. Results The overall pathologic complete response (pCR) rate after NAC was 20.1% and the HER2-enriched subgroup had the highest pCR rate (43.6%), whereas luminal A showed the lowest rate of pCR (4.6%). The median follow-up duration was 55 months (range, 5–98 months). The 5-year overall survival (OS) and disease-free survival (DFS) rates were 88.9% and 72.9%, respectively. In subgroup analysis, according to the pathologic response (pCR vs non-pCR), the triple-negative subtype exhibited a significant difference in 5-year OS rate (100.0% vs 71.6%, P = 0.005) and 5-year DFS rate (93.1% vs 55.1%, P < 0.001). A distinct survival difference according to molecular subtype was found, particularly in the non-pCR group (5-year OS and DFS, P < 0.001, respectively). Conclusions The non-pCR group showed significantly decreased 5-year OS and DFS rates compared to the pCR group, especially in triple negative and HER2-enriched breast cancer patients. A significant difference in survival rates and molecular subtypes was found in patients who failed to attain pCR.

The aim of this study was to investigate candidate genes that might function as biomarkers to differentiate triple negative breast cancers (TNBCs) among patients, who received adjuvant chemotherapy after curative surgery. We tested whether the results of a NanoString expression assay that targeted 250 prospectively selected genes and used mRNA extracted from formalin-fixed, paraffin-embedded would predict distant recurrence in patients with TNBC. The levels of expression of seven genes were used in a prospectively defined algorithm to allocate each patient to a risk group (low or high). NanoString expression profiles were obtained for 203 tumor tissue blocks. Increased expressions of the five genes (SMAD2, HRAS, KRT6A, TP63 and ETV6) and decreased expression of the two genes (NFKB1 and MDM4) were associated favorable prognosis and were validated with cross-validation. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low- and high-risk groups according to gene expression signature were 62% [95% confidence interval (CI), 48.6-78.9%] and 85% (95% CI, 79.2-90.7%), respectively. When adjusting for TNM stage, the distant recurrence-free survival (DRFS)s in the low-risk group was significantly longer than that in the high-risk group (p

Background A phase II clinical trial of the comparison between eribulin plus gemcitabine (EG) and paclitaxel plus gemcitabine (PG) as first-line chemotherapy for patients with metastatic breast cancer (MBC) found that the EG regimen was less neurotoxic, but was similar in efficacy to the PG regimen. In the present study, we analyzed functional assessment of cancer therapy-taxane (FACT-Taxane) questionnaires from patients in this clinical trial to determine their quality of life (QoL). Methods QoL was assessed using the Korean version of the FACT-Taxane questionnaires. After baseline assessment, QoL was assessed every 2 cycles for 12 cycles and every 3 cycles thereafter. The linear mixed model was used to evaluate the difference in QoL between the EG and PG arms. Results Of the 118 enrolled patients, 117 responded to the FACT-Taxane questionnaires at baseline, 1 in the PG arm did not. Baseline QoL scores were not different between the EG and PG arms. During treatment, taxane subscale scores were significantly higher in the PG arm than in the EG arm after 2–13 cycles of chemotherapy (all P

BACKGROUND: In patients with nonsmall cell lung cancer (NSCLC), several studies have demonstrated a positive correlation between somatic mutation in the epidermal growth factor receptor (EGFR) tyrosine kinase domain and clinical outcomes with the use of EGFR tyrosine kinase inhibitors (TKIs). However, some patients with wild-type (WT) EGFR also responded to EGFR TKIs and remained stable. Recently, amphiregulin (AR) has been suggested as a predictive marker for EGFR TKIs in patients with WT EGFR-positive NSCLC. The objective of the current study was to evaluate the association between AR expression and the efficacy of using EGFR TKIs in the treatment of patients with WT EGFR-positive NSCLC. METHODS: Seventy-three patients with WT EGFR-positive NSCLC received treatment with gefitinib or erlotinib between May 2005 and December 2008. AR expression was assessed by immunohistochemistry. RESULTS: The clinical response to EGFR TKIs was reassessed for all patients as follows: 16 of 73 patients had a partial response (21.9%), 12 patients had stable disease (16.5%), and 45 patients had progressive disease (61.6%). AR expression was positive in 24 of 40 patients (60%). The ability to achieve disease control did not differ significantly between AR-positive patients and AR-negative patients (P = .188). At a median follow-up of 25.4 months (range, 10.5-53.3 months), progression-free survival was 8.1 weeks in AR-positive patients and 4 weeks in AR-negative patients (P = .025), and overall survival was significantly longer in AR-positive patients than in AR-negative patients (12.2 months vs 4.1 months; P = .001). CONCLUSIONS: The current results suggested that patients with WT EGFR-positive NSCLC who have AR-positive tumors may benefit clinically from treatment with EGFR TKIs, indicating that AR expression may be a potential marker for the selection of EGFR-TKI treatment for patients with WT EGFR-positive NSCLC. Cancer 2011. © 2010 American Cancer Society.

Insulin-like growth factor receptor-1 (IGFR-1) is a cellular membrane receptor which is overexpressed in many tumors and seems to play a critical role in anti-apoptosis. The insulin-like growth factor binding protein-3 (IGFBP-3) is known as a growth suppressor in multiple signaling pathways. The aim of this study was to determine IGFR-1 and IGFBP-3 expression in small-cell lung cancer (SCLC) and analyze the prognostic value in patients with SCLC. We analyzed IGFR-1 and IGFBP-3 expression in 194 SCLC tissues by immunohistochemical staining. Correlative analyses between IGFR-1 and IGFBP-3 expression in SCLC and clinicopathologic factors were performed. A total of 117 patients had extensive disease (ED) (60.3%) and 77 had limited disease (39.7%). With the median follow-up duration of 49.5 months (24-82 months), the median progression-free survival (PFS) and overall survival (OS) were 7.2 months [95% confidence interval (CI): 6.4-8.0 months] and 14.4 months (95% CI: 12.7-16 months), respectively. IGFR-1 expression was observed in 154 of the 190 tumor tissues, whereas there was no IGFBP-3 expression. Multivariate analysis showed that stage (p < 0.001), response rate (p < 0.001), and lactate dehydrogenase (LDH) levels (p < 0.001) were the independent prognostic factors for PFS, and age (p = 0.014), LDH level (p < 0.001), and stage (p < 0.001) for OS. The IGFR-1 positivity was not associated with PFS or OS in the entire cohort. Subgroup analysis revealed that OS was significantly longer in patients with IGFR-1-positive tissue than IGFR-1-negative tissue in SCLC-ED (p = 0.034). These results suggest that IGFR-1 expression may be useful as a prognostic marker in patients with SCLC-ED.

Background Recently PET is emerged as a method to estimate the response of neoadjuvant chemotherapy (NAC) in advanced breast cancer. This study is aimed to estimate the predictive role of PET CT and other imaging modalities (ultrasound, MRI) through NAC. Methods PET CT was acquired before and after NAC from 41 patients. Pathologic results were classified as pathological complete response (pCR) and non-pCR. The results of clinical responses were assessed with imaging indexes (postTx, postchemotherapy size or peak standardized uptake values (pSUV); delta, the size difference between treatment; RR, reduction rate of tumor size or pSUV), and they were compared with pathologic results. Results Seven patients (17.1%) showed pCR. As a result of comparison of the image index, all image indexes of MRI were predictive for pCR (P

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 = 0.037) and overall survival (OS) (21 vs. 56 months, p = 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.

This study evaluated the applicability of prognostic factors commonly used for diagnosis of classical lymphoma outcomes to extranodal NK/T cell lymphoma, nasal type (NTCL). Clinical features and their associations with lactate dehydrogenase (LDH) were evaluated in 70 patients. RLDH was defined as the ratio of LDH to the upper normal limit. RLDH was associated with stage (I-II vs. III-IV), lymph node involvement (LNI), and International Prognostic Index score ( or =2). Poor performance status and advanced stage were common in patients with local tumor invasiveness (LTI). LDH level, classified into three levels (low, high, and very high) was associated with survival (P < 0.001). In multivariate analysis, the predictive values of LDH level, B symptom, performance status, and stage remained significant whereas those of LTI and LNI did not. Scoring was performed by weighting each factor with 0.5 or 1.0 according to its hazard ratio. Scores were classified into four groups. Groups with high scores were associated with unfavorable outcomes (P < 0.001). Current study suggests that prognostic factors for NHL may be useful to predict the outcome of NTCL but the model should take LDH level and the prognostic weight of each factor into account.

Nongastric marginal zone B-cell lymphoma (NG-MZL) is a relatively uncommon indolent lymphoma. From 1990 to 2005, a total of 247 patients with histologically confirmed NG-MZL were analyzed. Ann Arbor stage I/II disease was present in 78% (167 out of 215). One hundred eighty-six patients out of two hundred eight were categorized into the low/low-intermediate risk group (89%) according to International Prognostic Index (IPI). Eighty percent (172/215) were in low risk group according to Follicular Lymphoma International Prognostic Index (FLIPI). Complete and partial remissions (CR and PR) were achieved in 140 (92.7%) and 8 (5.3%) of the 151 stage I/II patients. Especially, radiation containing treatment achieved 96% CR rate (108 out of 113). In 38 patients with stage III/IV, CR and PR were achieved in 17 (44.7%) and 11 (26.3%), respectively. The estimated five-year overall survival (OS) and progression-free survival (PFS) were 93.8% and 70.1%, respectively. Although anthracycline-containing regimen could achieve higher CR rate, it did not improve PFS. Stage III/IV, low hemoglobin, poor performance status, high/high-intermediate IPI, poor risk FLIPI, and nodal MZL were poor prognostic factors for PFS. NG-MZL is an indolent disease. FLIPI has strong power to predict the prognosis of NG-MZL.

Objectives: We conducted a clinical risk factors analysis to define a prognostic model for high-grade primary gastric lymphoma (HG-PGL). Methods and Results: The median event-free survival and overall survival of 214 HG-PGL patients were 54 and 104.5 months, respectively, after a median follow-up duration of 60 months. According to the prognostic factor analysis, survival, advanced age, male gender, higher LDH levels and the presence of ascites were identified as independent prognostic factors for HG-PGL. We identified four groups at different risk: group 1, no adverse effect; group 2, one factor; group 3, two factors; group 4, three or four factors. The new prognostic model showed excellent prognostic capacity to differentiate subgroups according to their risk stratification. Conclusions: The proposed new prognostic model for HG-PGL demonstrated a balanced distribution of patients into four groups with good prognostic capacity.

On the basis of inhibitory activity of truncated cyclopentenyl cytosine against S-adenosylhomocysteine hydrolase (SAH), its fluorocyclopentenyl pyrimidine derivatives were efficiently synthesized from D-ribose via electrophilic fluorination as a key step. The final nucleosides were evaluated for SAH inhibitory activity, among which the uracil derivative 9 showed significant inhibitory activity (IC50 = 8.53 μM). They were also evaluated for cytotoxic effects in several human cancer cell lines such as fibro sarcoma, stomach cancer, leukemia, and colon cancer, but they did not show any cytotoxic effects up to 100 μM, indicating that 4′-hydroxymethyl groups are essential for the anticancer activity.

Synthesis of fluorocyclopentenyl pyrimidine nucleosides 6–9 was enantiopurely accomplished employing oxidative rearrangement, RCM reaction and electrophilic fluorination starting from d-ribose. Cytosine analog 8 was found to exhibit significant anticancer activity in various human tumor cell lines.