Hong-Gyun Wu

Class III β-tubulin, but not ERCC1, is a strong predictive and prognostic marker in locally advanced head and neck squamous cell carcinoma

BACKGROUNDnRecent researches revealed that class III beta-tubulin (TUBB3) is a prognostic marker in various tumors and role of TUBB3 in head and neck squamous cell carcinoma (HNSCC) is not defined yet. We analyzed the significance of TUBB3 expression along with p53 and ERCC1 in locally advanced HNSCC patients receiving cisplatin-based induction chemotherapy.nnnMATERIALS AND METHODSnRetrospective review of medical records at Seoul National University Hospital between 1998 and 2007 was carried out. Immunohistochemical stain of TUBB3, p53, and ERCC1 was done in paraffin-embedded tumor tissue. We assessed response to treatment, progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS).nnnRESULTSnEighty-five patients with oropharyngeal, hypopharyngeal, and laryngeal cancers received induction chemotherapy with 5-fluorouracil (5-FU) and cisplatin (n = 55), or 5-FU, cisplatin, and docetaxel (Taxotere) (n = 30). Eighty-three received definitive treatment after induction chemotherapy, where 62 received radiotherapy and 21 received surgery. TUBB3-positive patients showed lower response rate than TUBB3-negative patients (69% versus 88%, P = 0.039). Shorter median PFS was observed in TUBB3-positive group (12 versus 47 months, P = 0.001). Shorter median OS was observed in TUBB-positive group not reaching statistical significance (30 versus 59 months, P = 0.072). TUBB3 status significantly influenced CSS (35 months versus not reached, P = 0.017). Positive p53 status was related to poorer OS and CSS. ERCC1 showed no influence on chemotherapy response, PFS, OS, and CSS.nnnCONCLUSIONnTUBB3 is a predictive and prognostic marker along with well-known p53 in HNSCC patients receiving cisplatin-based induction chemotherapy. Clinical impact of ERCC1 is not evident in this setting.

Predictive and prognostic value of PET/CT imaging post-chemoradiotherapy and clinical decision-making consequences in locally advanced head & neck squamous cell carcinoma: a retrospective study

BackgroundThe accuracy of 18F-fluorodeoxygluocose positron emission tomography/computed tomography (PET/CT) in predicting immediate failure after radical chemoradiotherapy (CRT) for HNSCC is poorly characterized at present. The purpose of this study was to examine PET/CT as a predictive and prognostic gauge of immediate failure after CRT and determine the impact of these studies on clinical decision making in terms of salvage surgery.MethodsMedical records of 78 consecutive patients receiving radical CRT for locally advanced HNSCC were reviewed, analyzing PET/CTs done before and 3xa0months after CRT. Immediate failure was defined as residual disease or locoregional and/or systemic relapse within 6xa0months after CRT.ResultsMaximum standard uptake value (SUV) of post CRT PET/CT (postSUVmax) was found optimal for predicting immediate failure at a cutpoint of 4.4. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were 90.0xa0%, 83.8xa0%, 98.3xa0%, and 45.0xa0%, respectively. Of 78 patients studied, postSUVmax ≥4.4 prevailed in 20 (25.6xa0%), with postSUVmax <4.4 in 58 (74.4xa0%). At postSUVmax ≥4.4 (vs. postSUVmax <4.4) OS was poorer by comparison (3-year OS: 56.9 vs. 87.7xa0%; Pu2009=u20090.005), as was progression-free survival (3-year PFS: 42.9 vs. 81.1xa0%; Pu2009<u20090.001). At postSUVmax ≥4.4, OS with and without immediate salvage surgery did not differ significantly (3-year OS: 60.0 vs. 55.6xa0%; Log-rank Pu2009=u20090.913).ConclusionPost CRT PET/CT imaging has prognostic value in terms of OS and PFS and is useful in predicting immediate therapeutic failure, given its high NPV. However, OS was not significantly altered by early salvage surgery done on the basis of post CRT PET/CT findings.

Additional prognostic role of EGFR activating mutations in lung adenocarcinoma patients with brain metastasis: Integrating with lung specific GPA score

OBJECTIVEnWhile several prognostic models have been presented in NSCLC patients with brain metastasis, none of these models have included molecular markers as an index. The aim of our study was to evaluate the prognostic value of EGFR mutations and to integrate these EGFR mutations into the prognostic index in NSCLC patients with brain metastasis.nnnMATERIALS AND METHODSnWe analyzed retrospectively 292 lung adenocarcinoma patients with brain metastasis. Clinico-pathological features and overall survival (OS) were compared between patients with EGFR mutations and patients with EGFR wild type. EGFR mutation status was integrated with lung specific graded prognostic assessment (GPA) score.nnnRESULTSnAmong 292 patients, EGFR mutation status was tested in 183 patients. One hundred and five patients (57.4%) had EGFR activating mutations, 14 (7.7%) had EGFR non-activating mutations and 64 (35.0%) had EGFR wild type. OS was significantly longer in patients with EGFR activating mutations than in those with EGFR wild type patients (20.4 vs. 10.1 months, p = 0.002). However, patients with EGFR non-activating mutations did not show superior OS compared with EGFR wild type patients (14.6 vs. 10.1 months, p = 0.83). Multivariate analysis revealed that the presence of EGFR activating mutation is an independent positive prognostic factor for OS (adjusted hazard ratio 0.56, p = 0.002).nnnCONCLUSIONSnEGFR activating mutations have a prognostic role in lung adenocarcinoma patients with brain metastasis that is independent of other known prognostic factors. The frequency of EGFR mutation was higher than expected. The presence of EGFR activating mutations should be included as an index in the prognostic models for lung adenocarcinoma patients with brain metastasis.

The Role of Neoadjuvant Chemotherapy in the Treatment of Nasopharyngeal Carcinoma: A Multi-institutional Retrospective Study (KROG 11-06) Using Propensity Score Matching Analysis

Purpose We compared the treatment results and toxicity in nasopharyngeal carcinoma (NPC) patients treated with concurrent chemotherapy (CCRT) alone (the CRT arm) or neoadjuvant chemotherapy followed by CCRT (the NCT arm). Materials and Methods A multi-institutional retrospective study was conducted to review NPC patterns of care and treatment outcome. Data of 568 NPC patients treated by CCRT alone or by neoadjuvant chemotherapy followed by CCRT were collected from 15 institutions. Patients in both treatment arms were matched using the propensity score matching method, and the clinical outcomes were analyzed. Results After matching, 300 patients (150 patients in each group) were selected for analysis. Higher 5-year locoregional failure-free survival was observed in the CRT arm (85% vs. 72%, p=0.014). No significant differences in distant failure-free survival (DFFS), disease-free survival (DFS), and overall survival were observed between groups. In subgroup analysis, the NCT arm showed superior DFFS and DFS in stage IV patients younger than 60 years. No significant difference in compliance and toxicity was observed between groups, except the radiation therapy duration was slightly shorter in the CRT arm (50.0 days vs. 53.9 days, p=0.018). Conclusion This study did not show the superiority of NCT followed by CCRT over CCRT alone. Because NCT could increase the risk of locoregional recurrences, it can only be considered in selected young patients with advanced stage IV disease. The role of NCT remains to be defined and should not be viewed as the standard of care.

Identification of genomic mutations associated with clinical outcomes of induction chemotherapy in patients with head and neck squamous cell carcinoma

PurposeWe performed deep sequencing of target genes in head and neck squamous cell carcinoma (HNSCC) tumors to identify somatic mutations that are associated with induction chemotherapy (IC) response.MethodsPatients who were diagnosed with HNSCC were retrospectively identified. Patients who were treated with IC were divided into two groups: good responders and poor responders by tumor response and progression-free survival. Targeted gene sequencing for 2404 somatic mutations of 44 genes was performed on HNSCC tissues. Mutations with total coverage of <500 were excluded, and the cutoff for altered allele frequency was >10xa0%.ResultsOf the 71 patients, 45 were treated upfront with IC. Mean total coverage was 1941 per locus, and 42.2xa0% of tumors had TP53 mutations. Thirty-three mutations in TP53, NOTCH3, FGFR2, FGFR3, ATM, EGFR, MET, PTEN, FBXW7, SYNE1, and SUFU were frequently altered in poor responders. Among the patients who were treated with IC, those with unfavorable genomic profiles had significantly poorer overall survival than those without unfavorable genomic profiles (hazard ratio 6.45, 95xa0% confidence interval 2.07–20.10, Pxa0<xa00.001).ConclusionsComprehensive analysis of mutation frequencies identified unfavorable genomic profiles, and the patients without unfavorable genomic profiles can obtain clinical benefits from IC in patients with HNSCC.

Clinical outcomes of radiation-based locoregional therapy in locally advanced head and neck squamous cell carcinoma patients not responding to induction chemotherapy.

OBJECTIVEnThe purpose of this study was to evaluate the efficacy of radiation-based locoregional therapy for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) patients who did not respond to induction chemotherapy (IC).nnnSTUDY DESIGNnOutcomes after radiation-based locoregional therapy were retrospectively analyzed.nnnRESULTSnAmong a total of 208 patients treated with IC, 46 (22.1%) did not respond. After IC, patients were treated with radiotherapy (RT), concurrent chemoradiotherapy (CCRT), or surgery with or without postoperative RT. Among the 46 nonresponders, 17 (37.8%) patients underwent surgery and 28 (62.2%) were treated with RT or CCRT. Responses to subsequent RT or CCRT for 26 evaluable patients were as follows: complete response=7 (26.9%), partial response=9 (34.6%), stable disease=4 (15.4%), and progressive disease=6 (23.1%).nnnCONCLUSIONnA significant proportion of LA-HNSCC patients who did not respond to IC can benefit from subsequent RT or CCRT.

Effect of mesenchymal stem cells and platelet-derived growth factor on the healing of radiation induced ulcer in rats

Radiation-induced skin ulceration is a frequent complication of radiation therapy. This study investigated the effects of rat mesenchymal stem cells (rMSCs) and platelet-derived growth factor (PDGF) on the healing of radiation-induced soft tissue injury. Sprague-Dawley rats (n=17) were irradiated on the right and left buttocks with a single dose of 50 Gy. The right buttocks were administered with phosphatebuffered solution as a control. The left buttocks were administered with either rMSCs (2×106 cells), PDGF (8 µg), or PDGF combined with rMSCs. Administration was done at three weeks after irradiation. Wound healing was analyzed by calculating the percentage of residual ulcerated skin area compared to the total irradiated area during the five week healing period after administration. Modified skin scores were also assessed. Finally, skin lesions were histologically evaluated. More than 40% of the irradiated skin area within the irradiated zone underwent ulceration within 16 days postirradiation, with peak ulceration exceeding 50% around three weeks post-irradiation. Administration of rMSCs or PDGF alone did not confer any significant healing effect. The combined rMSCs+PDGF treatment significantly reduced the wound size compared with the nontreated control up to two weeks postinjection. Regarding the histological examination, lesions administered with PDGF (either alone or mixed with rMSCs) resulted in a greater deposition of highly organized collagen fibers throughout the dermis layer, compared with the control. In conclusion, the combined administration of rMSCs and PDGF efficiently enhanced the healing of radiation-induced skin ulceration.

Effect of induction chemotherapy on survival in locally advanced head and neck squamous cell carcinoma treated with concurrent chemoradiotherapy: Single center experience

Although induction chemotherapy can reduce distant metastases in locally advanced head and neck squamous cell carcinoma (HNSCC), overall survival (OS) improvement because of induction chemotherapy has not been confirmed.

Clinical outcomes of stereotactic ablative radiotherapy in patients with pulmonary metastasis

Backgrounds In addition to its curative use for early stage lung cancer, stereotactic ablative radiotherapy is also indicated for pulmonary metastatic disease. Aims of this study were to retrospectively analyze treatment outcomes and to find prognostic factors for survivals. Methods Treatment outcomes and toxicities of 85 cases of SABR in 72 patients were retrospectively reviewed from September 2012 to April 2015. Prognostic factors were analyzed using Cox proportional hazards regression. Results The local failure-free survival rate at 2 years was 98%. Of the case, 1-year and 2-year progression-free survival rates were 62% and 48%, and overall survival rates were 90% and 72%, respectively. Multivariate analyses demonstrated that controlled primary cancer (P = 0.01), absence of extra-pulmonary metastatic disease (P < 0.01) and disease-free interval longer than 1 year (P < 0.01) favorably affected progression-free survival. Furthermore, the absence of extra-pulmonary metastatic disease (P < 0.01) increased overall survival as well. Grade 1 or 2 radiation pneumonitis was found in 37 cases, and Grade 1 chest wall pain was found in 1 case. Conclusions Stereotactic ablative radiotherapy demonstrated good local control with tolerable adverse effects for pulmonary metastasis. The presence or absence of extra-pulmonary metastasis was found to be prognostic factor of mortality after stereotactic ablative radiotherapy treatment.

Clinical significance of downstaging in patients with limited-disease small-cell lung cancer.

BACKGROUNDnWe investigated the effect of downstaging on OS in LD-SCLC patients treated with first-line treatment.nnnPATIENTS AND METHODSnWe retrospectively reviewed 210 LD-SCLC patients who were treated with first-line treatment at Seoul National University Hospital between April 1999 and November 2012. Compared with initial tumor, node, metastases (TNM) stage, cases that showed a lower TNM stage after treatment were defined as downstaging. The relationship between downstaging and OS was analyzed, and a subgroup analysis on the responders was performed.nnnRESULTSnAfter first-line treatment, 78 (37.1%) patients achieved complete response, 97 (46.2%) achieved PR, and 35 (16.7%) experienced stable disease or progressive disease. A hundred and fifty one patients (71.9%) showed downstaging of their diseases, and the remaining 59 patients (28.1%) showed no change or upstaging. The median OS for patients achieving downstaging and no change/upstaging were 32.8 months and 13.1 months, respectively (P < .001). Of the 97 patients who achieved PR, the OS was significantly longer in patients who showed downstaging than those who did not (25.8 months vs. 13.8 months, respectively; P = .004). In multivariate analyses, female sex, downstaging, lower initial TNM stage, and prophylactic cranial irradiation were independent good prognostic factors for OS.nnnCONCLUSIONnDownstaging might be an independent good prognostic factor in LD-SCLC. Specifically, downstaging is expected to be useful for stratification of patients achieving PR. Further prospective studies are warranted to verify whether patients who achieved PR without downstaging can be candidates for consolidation treatments after first-line treatment.