Won Park

Pathologic complete response of primary tumor following preoperative chemoradiotherapy for locally advanced rectal cancer: long-term outcomes and prognostic significance of pathologic nodal status (KROG 09-01).

Objective: To investigate long-term outcomes of locally advanced rectal cancer (LARC) patients with postchemoradiotherapy (post-CRT) pathologic complete response of primary tumor (ypT0) and determine prognostic significance of post-CRT pathologic nodal (ypN) status. Background: LARC patients with post-CRT pathologic complete response were suggested to have favorable long-term outcomes, but prognostic significance of ypN status has never been specifically defined in ypT0 patients. Methods: The Korean Radiation Oncology Group collected clinical data for 333 LARC patients with ypT0 following preoperative CRT and curative radical resections between 1993 and 2007. Sphincter preservation surgery and abdominoperineal resection were performed in 283 (85.0%) and 50 (15.0%) patients, respectively. Postoperative chemotherapy was given to 285 (85.6%) patients. Survival was estimated by the Kaplan-Meier method, and the Cox proportional hazard model was used in multivariate analyses. Results: After median follow-up of 43 (range = 14–172) months, 5-year disease-free survival (DFS) was 84.6% and overall survival (OS) was 92.8%. The ypN status was ypT0N0 in 304 (91.3%), ypT0N1 in 22 (6.6%), and ypT0N2 in 7 (2.1%) patients. The ypN status was the most relevant independent prognostic factor for both DFS and OS in ypT0 patients. The 5-year DFS and OS was 88.5% and 94.8% in ypT0N0 patients, and 45.2% and 72.8% in ypT0N+ patients (both, P < 0.001). Conclusions: LARC patients achieving ypT0N0 after preoperative CRT had favorable long-term outcomes, whereas positive ypN status had a poor prognosis even after total regression of primary tumor.

Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients

In patients with human epidermal growth factor receptor-2 (HER2)-overexpressing breast cancer, treatment with trastuzumab has been shown to markedly improve the outcome. We investigated the role of trastuzumab on brain metastasis (BM) in HER2-positive breast cancer patients. From 1999 to 2006, 251 patients were treated with palliative chemotherapy for HER2-positive metastatic breast cancer at Samsung Medical Center. The medical records of these patients were analysed to study the effects of trastuzumab on BM prevalence and outcomes. Patients were grouped according to trastuzumab therapy: pre-T (no trastuzumab therapy) vs post-T (trastuzumab therapy). The development of BM between the two treatment groups was significantly different (37.8% for post-T vs 25.0% for pre-T, P=0.028). Patients who had received trastuzumab had longer times to BM compared with patients who were not treated with trastuzumab (median 15 months for post-T group vs 10 months for pre-T group, P=0.035). Time to death (TTD) from BM was significantly longer in the post-T group than in the pre-T group (median 14.9 vs 4.0 months, P=0.0005). Extracranial disease control at the time of BM, 12 months or more of progression-free survival of extracranial disease and treatment with lapatinib were independent prognostic factors for TTD from BM.

Patterns of failure in gastric carcinoma after D2 gastrectomy and chemoradiotherapy: a radiation oncologist's view

The risk of locoregional recurrence in resected gastric adenocarcinoma is high, but the benefit of adjuvant treatment remains controversial. In particular, after extended lymph node dissection, the role of radiotherapy is questionable. Since 1995, we started a clinical protocol of adjuvant chemoradiotherapy after D2 gastrectomy and analysed the patterns of failure for 291 patients. Adjuvant chemotherapy consisted of five cycles of fluorouracil and leucovorin, and concurrent radiotherapy was given with 4500u2009cGy from the second cycle of chemotherapy. With a median follow-up of 48 months, 114 patients (39%) showed any type of failure, and the local and regional failures were seen in 7% (20 out of 291) and 12% (35 out of 291), respectively. When the recurrent site was analysed with respect to the radiation field, in-field recurrence was 16% and represented 35% of all recurrences. Our results suggest that adjuvant chemoradiotherapy has a potential effect on reducing locoregional recurrence. Moreover, low locoregional recurrence rates could give a clue as to which subset of patients could be helped by radiotherapy after D2 gastrectomy. However, in order to draw a conclusion on the role of adjuvant radiotherapy, a randomised study is needed.

Large-scale graphene micropatterns via self-assembly-mediated process for flexible device application

We report on a method for the large-scale production of graphene micropatterns by a self-assembly mediated process. The evaporation-induced self-assembly technique was engineered to produce highly ordered graphene patterns on flexible substrates in a simplified and scalable manner. The crossed stripe graphene patterns have been produced over a large area with regions consisting of single- and two-layer graphene. Based on these graphene patterns, flexible graphene-based field effect transistors have been fabricated with an ion-gel gate dielectric, which operates at low voltages of < 2 V with a hole and electron mobility of 214 and 106 cm(2)/V·s, respectively. The self-assembly approach described here may pave the way for the nonlithographic production of graphene patterns, which is scalable to large areas and compatible with roll-to-roll system.

Comparative evaluation of magnetite-graphene oxide and magnetite-reduced graphene oxide composite for As(III) and As(V) removal.

Arsenic removal using Fe3O4-graphene oxide composite (M-GO) and Fe3O4-reduced graphene oxide composite (M-rGO) was investigated. The M-GO was more effective to adsorb both As(III) and As(V) than M-rGO, because the more functional groups existing on the M-GO could lead to synthesize more Fe3O4 with M-GO. As(III) was more favorable to be adsorbed than As(V) onto both M-GO and M-rGO. According to the effect of pH on arsenic removal, the electrostatic interaction between the positively charged surface of Fe3O4-graphene based adsorbents and anionic As(V) species was a major factor to adsorb As(V). The adsorption mechanism of As(III), on the other hand, was strongly affected by a surface complexation, rather than electrostatic interactions. Consequently, in terms of the process energy consumption, energy saving could be achieved via omitting the reduction process to fabricate M-rGO from M-GO and the pre-oxidation process to convert As(III) to As(V).

A risk stratification by hormonal receptors (ER, PgR) and HER-2 status in small (≤1 cm) invasive breast cancer: who might be possible candidates for adjuvant treatment?

As the use of screening mammography expands, the proportion of invasive breast cancer ≤1xa0cm is increasing. The aims of this study were: (1) to identify risk factors for systemic metastases in patients with ≤1xa0cm invasive breast cancer and (2) to investigate the patient groups at the greatest risk for metastases with such small tumors. Data were collected retrospectively from the breast cancer registry of our institution for patients with invasive breast cancer from October 1994 to December 2004. Of 4,036 patients who received curative breast cancer surgery, we identified 427 patients who had T1a or T1b breast cancer excluding 39 patients who received neoadjuvant chemotherapy. Ipsilateral axillary lymph node involvement was found in 13% (57/427) of patients at the time of surgery. A multivariate analysis was conducted in 370 (T1aN0, T1bN0) patients without lymph node involvement. In a Cox-regression model, HER-2 positive and triple negative (TN) groups were identified as independent risk factors to predict distant relapse-free survival (DRFS) [Hazard ratio (HR) 8.8, Pxa0=xa00.003 for HER-2 positive group; HR 5.1, Pxa0=xa00.026 for TN group] in T1bN0 tumors. Statistical significance was not maintained when the analysis was limited to T1aN0 tumors. Even though T1aN0 and T1bN0 tumors have a relatively low risk of systemic failure, anti-HER-2-directed therapy for HER-2 group and new innovative adjuvant systemic treatment for TNBC patients with T1bN0 tumors should be considered. Prospective adjuvant trials are warranted in these subgroups of patients.

The role of postmastectomy radiation therapy after neoadjuvant chemotherapy in clinical stage II-III breast cancer patients with pN0: A multicenter, retrospective study (KROG 12-05)

PURPOSEnThe purpose of this study was to investigate the role of postmastectomy radiation therapy (PMRT) after neoadjuvant chemotherapy (NAC) in clinical stage II-III breast cancer patients with pN0.nnnMETHODS AND MATERIALSnWe retrospectively identified 417 clinical stage II-III breast cancer patients who achieved an ypN0 at surgery after receiving NAC between 1998 and 2009. Of these, 151 patients underwent mastectomy after NAC. The effect of PMRT on disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and overall survival (OS) was evaluated by multivariate analysis including known prognostic factors using the Kaplan-Meier method and compared using the log-rank test and Cox proportional regression analysis.nnnRESULTSnOf the 151 patients who underwent mastectomy, 105 (69.5%) received PMRT and 46 patients (30.5%) did not. At a median follow-up of 59 months, 5 patients (3.3%) developed LRR (8 sites of recurrence) and 14 patients (9.3%) developed distant metastasis. The 5-year DFS, LRRFS, and OS rates were 91.2, 98.1, and 93.3% with PMRT and 83.0%, 92.3%, and 89.9% without PMRT, respectively (all P values not significant). By univariate analysis, only age (≤40 vs >40 years) was significantly associated with decreased DFS (P=.027). By multivariate analysis, age (≤40 vs >40 years) and pathologic T stage (0-is vs 1 vs 2-4) were significant prognostic factors affecting DFS (hazard ratio [HR] 0.353, 95% confidence interval [CI] 0.135-0.928, P=.035; HR 2.223, 95% CI 1.074-4.604, P=.031, respectively). PMRT showed no correlation with a difference in DFS, LRRFS, or OS by multivariate analysis.nnnCONCLUSIONSnPMRT might not be necessary for pN0 patients after NAC, regardless of clinical stage. Prospective randomized clinical trial data are needed to assess whether PMRT can be safely omitted in pN0 patients after NAC and mastectomy for clinical stage II-III breast cancer.

Prognostic factor analysis in patients with brain metastases from breast cancer: how can we improve the treatment outcomes?

PurposeWe conducted this study to analyze clinicopathologic features and treatment outcomes for various treatment modalities in breast cancer patients with brain metastases.Patients and methodsRetrospective analysis was performed using medical records of patients who were diagnosed with metastatic brain tumors from breast cancer. The treatment modalities applied included whole-brain radiotherapy (WBRT), surgical resection, stereotactic radiosurgery (SRS) and systemic treatments such as chemotherapy and endocrine therapy.ResultsAmong 125 female breast cancer patients with brain metastases, 87.2% had Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0–2. The median overall survival (OS) was 6.6xa0months (95% CI 3.9–9.2). A multivariate analysis using the Cox-regression test identified three risk factors; poor PS (Pxa0=xa00.023), HER2 positivity (Pxa0=xa00.013), and no additional systemic treatment (Pxa0=xa00.006). Those patients who had no risk factors showed outstanding outcome (median OS 49xa0months). On the contrary, the patients who had all risk factors (poor PS with HER2 positive and did not receive additional systemic chemotherapy) showed dismal prognosis (median OS 2xa0months).ConclusionsOur new classification according to the suggested risk factors for patients with metastatic brain tumor from breast cancer reflects particular characteristics of each subset of the patients with good prognostic capacity.

Blood oxygenation level-dependent MR imaging as a predictor of therapeutic response to concurrent chemoradiotherapy in cervical cancer: a preliminary experience

ObjectivesTo investigate the value of blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) as a predictor of therapeutic response in cervical cancer patients undergoing concurrent chemoradiotherapy (CCRT).MethodsThirty consecutive patients with biopsy-proven cervical cancer were examined by BOLD MRI before (preTx) and after CCRT (postTx). The R2* value (s-1) was calculated in the tumour and normal myometrium for preTx and postTx studies. Final tumour responses, as determined by changes of tumour size or volume on MRI, were correlated with tumour R2* values at preTx.ResultsThe mean R2* values of tumours at preTx (21.1) were significantly lower than those at postTx (39.4xa0s-1) (pu2009<u20090.001), while those of normal myometrium were similar between preTx and postTx (pu2009=u20090.363). At preTx, tumour R2* values showed significantly negative correlation with final tumour size response (pu2009=u20090.022, Spearman’s coefficientu2009=u2009-0.415). However, tumour R2* values at preTx were not associated with final tumour volume response (pu2009=u20090.069).ConclusionsBOLD MRI at 3xa0T, as an imaging biomarker, may have the potential to evaluate therapeutic response in cervical cancers. The association between BOLD MRI findings and CCRT responses warrants further validation.Key points• Hypoxia in cervical cancer is an independent risk factor• BOLD MRI reflect oxygenation status of tissue adjacent to perfused microvessels• Pretreatment tumour R2* reveal negative correlation with final tumour size response• Accurate oxygenation assessment in cervical cancer may help clinical decision making

Quasiclassical trajectory calculations of the reaction C+C2H2-->l-C3H, c-C3H+H, C3+H2 using full-dimensional triplet and singlet potential energy surfaces.

Full-dimensional, density functional theory (B3LYP/6-311g(d,p))-based potential energy surfaces (PESs) are reported and used in quasi-classical calculations of the reaction of C with C(2)H(2). For the triplet case, the PES spans the region of the reactants, the complex region (with numerous minima and saddle points) and the products, linear(l)-C(3)H+H, cyclic(c)-C(3)H+H and c-(3)C(3)+H(2). For the singlet case, the PES describes the complex region and products l-C(3)H+H, c-C(3)H+H and l-(1)C(3)+H(2). The PESs are invariant under permutation of like nuclei and are fit to tens of thousands of electronic energies. Energies and harmonic frequencies of the PESs agree well the DFT ones for all stationary points and for the reactant and the products. Dynamics calculations on the triplet PES find both l-C(3)H and c-C(3)H products, with l-C(3)H being dominant at the energies considered. Limited unimolecular reaction dynamics on the singlet PES find both products in comparable amounts as well as the C(3)+H(2) product.