Young Chan Lee

The importance of postoperative radiation therapy in multimodality management of locally advanced breast cancer: a phase II trial of neoadjuvant MVAC, surgery, and radiation.

PURPOSE To determine the impact of postoperative radiation on locoregional relapse and overall survival rate in a multimodality protocol for locally advanced breast cancer (LABC). MATERIAL AND METHODS Of the patients entered in the protocol, 55 were evaluable. Treatment consisted of: neoadjuvant MVAC (methotrexate, vinblastine, adriamycin, and cisplatin) until a maximum response had been achieved; modified radical mastectomy; 6 courses of postoperative adjuvant MVAC chemotherapy, and chest wall irradiation (CWXRT). Multivariate analysis of locoregional response and overall survival was done. RESULTS Of the total, 42 patients received chest wall radiation; 28 of these also received radiation to regional lymph nodes. Chest wall doses ranged from 45 Gy to 50.4 Gy to the whole chest wall, with 31 patients receiving an additional chest-wall boost. The incidence of locoregional relapse with and without radiation was 7% vs. 31%, respectively (p = 0.026). An overall survival benefit was seen in those receiving radiation, with a mean overall survival of 50 months vs. 20 months, and a 3-year overall survival of 88% vs. 46% with and without radiation, respectively (p = 0.003). Multivariate analysis showed that overall survival was affected by the presence of pathological CR (p = .047), the number of pre-operative chemotherapy cycles (p = .036) and whether or not they received radiation (p = 0.003). Neither the interval between surgery and radiation, technique of radiation, nor radiation modality significantly affected local control. CONCLUSION The significant improvement in local regional control and overall survival with the addition of radiation suggests that radiation should be an integral part of multimodality management of locally advanced breast cancer.

X-ray excision repair replication and radiation survival in placental mammal cells.

Abstract X-ray induced excision repair replication (ER) has been studied in two cell lines, HeLa cells and rat REQ cells. It was found that ER was essentially absent in REQ cells when BUdR-substituted DNA was studied and that REQ cells showed about 3596 of the amount of ER noted in HeLa cells when non-substituted DNA was studied. Both cell lines were essentially identical in their radiobiological parameters and recovery patterns suggesting that X-ray ER is not involved in the repair of sub-lethal X-ray damage in rat cells and presumably in other placental mammal cells. The results do not indicate that base damage (and its repair) per se is non-important since other forms of repair (e.g. post-replication repair) may remove X-ray products, thereby contributing to cell survival in a clonogenic assay. Bromouracil products may be handled by different repair enzyme systems than thymine radiation products and the mechanisms may vary between species.

SOX2 activation predicts prognosis in patients with head and neck squamous cell carcinoma

SOX2 copy number and mRNA expression were analysed to examine the clinical significance of SOX2 activation in HNSCC. Gene expression signatures reflecting SOX2 activation were identified in an HNSCC cohort. Patients with HNSCC were classified into two subgroups according to the gene expression signature: SOX2-high and SOX2-low. The clinical significance of SOX2 activation was further validated in two independent cohorts. Moreover, clinical significance of SOX2 activation in response to radiotherapy was assessed in patients with HNSCC. The relationship between SOX2 activation and radiotherapy was validated in an in vitro experiment. Patients in the SOX2-high subgroup had a better prognosis than patients in the SOX2-low subgroup in all three patient cohorts. Results of multivariate regression analysis showed that SOX2 signature was an independent predictor of the overall survival of patients with HNSCC (hazard ratio, 1.45; 95% confidence interval, 1.09–1.92; P = 0.01). Interestingly, SOX2 activation was a predictor of therapy outcomes in patients receiving radiotherapy. Moreover, SOX2 overexpression enhanced the effect of radiotherapy in HNSCC cell lines. SOX2 activation is associated with improved prognosis of patients with HNSCC and might be used to predict which patients might benefit from radiotherapy.

Lymph node irradiation in carcinoma of the prostate: necessity of computerized tomography and three dimensional treatment planning in portal design

Twenty consecutive patients with localized adenocarcinoma of the prostate received whole pelvic radiation followed by a reduced field of radiation directed at the prostate and periprostatic tissues. The four-field pelvic volumes were designed using standard bony landmarks on simulator films. All patients had treatment planning CT scans which were utilized to define the prostatic tumor volume for the prostate boost treatment.

Clinical significance of YAP1 activation in head and neck squamous cell carcinoma

By analyzing the genomic data of head and neck squamous cell cancer (HNSCC), we investigated clinical significance of YAP1 activation. Copy number and mRNA expression of YAP1 were analyzed together to assess clinical relevance of YAP1 activation in HNSCC. The clinical significance of YAP1 activation was further validated in four independent test cohorts. We also assessed the correlation of YAP1 activation with genomic alterations such as copy number alteration, somatic mutation, and miRNA expression. The YAP1-activated (YA) subgroup showed worse prognosis for HNSCC as tested and validated in five cohorts. In a multivariate risk analysis, the YAP1 signature was the most significant predictor of overall survival. The YAP1-inactivated (YI) subgroup was associated with HPV-positive status. In multiplatform analysis, YA tumors had gain of EGFR and SNAI2; loss of tumor-suppressor genes such as CSMD1, CDKN2A, NOTCH1, and SMAD4; and high mutation rates of TP53 and CDKN2A. YI tumors were characterized by gain of PIK3CA, SOX2, and TP63; deletion of 11q23.1; and high mutation rates of NFE2L2, PTEN, SYNE1, and NSD1. YA tumors also showed weaker immune activity as reflected in low IFNG composite scores and YAP1 activity is negatively associated with potential response to treatment of pembrolizumab. In conclusion, activation of YAP1 is associated with worse prognosis of patients with HNSCC and potential resistance to immunotherapy.

Factors Affecting the Result of Intralesional Corticosteroid Injection in Patients With Oral Lichen Planus

Objectives To examine the factors which affect the improvement or the recurrence of disease after intralesional steroid injection in patients with oral lichen planus (OLP). Methods Sixty-two patients diagnosed as OLP were treated with intralesion corticosteroid injection. To evaluate the objective severity of OLP, total severity score of OLP was assessed. To examine the factors affecting the therapeutic effect of intralesional steroid injection, factors were compared between the symptom-improved group and symptom-not-improved group. To assess the symptom of patients, patients filled in 10-cm visual analogue scale, along with an Oral Health Impact Profile-14. Results Symptoms improved in 50 patients (80.6%, symptom-improved group), but not in 12 patients (symptom-not-improved group). In a comparison between both group, OLP with lip involvement was the only variable which showed significant difference (P=0.008). Twenty-nine of 50 patients had recurrence of OLP (58%, recurrence group) and 21 of 50 patients did not have recurrence (42%, no-recurrence group). Statistically significant differences were not found between both groups. Conclusion This study suggested that patients suffering from OLP with lesion on the lip might not be effective in treating with intralesional corticosteroid injection.

Prevalence and Predictors of Sjögren's Syndrome in Patients with Burning Mouth Symptoms

AIMS To investigate the prevalence and predictive factors of Sjögrens syndrome (SS) in a cohort of patients with burning mouth symptoms. METHODS A total of 125 patients with burning mouth symptoms were enrolled in a prospective study and assessed for the presence of SS. The severity of oral symptoms was evaluated by using questionnaires. Salivary flow rates and salivary scintigraphy were used to evaluate salivary function. Patient laboratory work-ups were reviewed, and SS was diagnosed by a rheumatologist based on the American-European Consensus Group criteria. The differences between the SS patient group and the non-SS patient group were analyzed with chi-square test or t test. RESULTS A total of 12 of the 125 enrolled patients (9.5%) had a positive autoimmune antibody test, and 6 (4.8% of the entire cohort) had SS (4 [3.2%] primary and 2 [1.6%] secondary). Patients with SS exhibited significantly decreased hemoglobin levels, an increased erythrocyte sedimentation rate, and an increased prevalence of autoantibody positive results compared to non-SS patients. Salivary scintigraphy showed that the uptake ratio of the submandibular gland in SS patients was decreased significantly. CONCLUSION The prevalence of SS in patients with burning mouth symptoms was 4.8%. Therefore, clinicians who treat patients with burning mouth symptoms should evaluate laboratory findings and salivary functions to identify patients with SS.