Yeon-Sil Kim

Fractionated stereotactic radiotherapy as reirradiation for locally recurrent head and neck cancer.

PURPOSE We report early preliminary experience with CyberKnife radiosurgery (RS) as salvage treatment for locally recurrent head and neck cancer (HNC). METHODS AND MATERIALS Between March 2004 and August 2006, 36 patients (44 sites) were treated with CyberKnife RS as reirradiation for locally recurrent HNC. Treatment sites were as follows: nasopharynx (8), maxillary sinus (8), neck lymph nodes (8), skull base (7), nasal cavity (4), retropharyngeal lymph nodes (3), orbit (2), and others (4). Total doses administered were 18-40 Gy (median, 30 Gy) in 3 to 5 fractions to the 65%-85% isodose line for 3-5 consecutive days. Previous external radiation dose ranged from 39.6 to 134.4 Gy (median, 70.2 Gy). Gross tumor volume ranged from 0.2 to 114.9 cm(3) (median, 22.6 cm(3)). Median follow-up was 17.3 months. RESULTS Thirty-five of 44 sites were evaluated for response. Fifteen (42.9%) sites achieved complete response, 13 sites (37.1%) achieved a partial response, 3 (8.6%) sites maintained stable disease, and 4 sites (11.4%) showed tumor progression. Grade III acute complications were noted in 13 patients. Late complications were observed in three patients (1 bone necrosis, 2 soft tissue necrosis) during follow-up. CONCLUSION These preliminary results suggest that fractionated stereotactic radiosurgery is an effective treatment modality as a salvage treatment with good short-term local control. The early overall response rate is encouraging. However, more experience and a longer follow-up are necessary to determine the role of fractionated stereotactic radiosurgery as a salvage treatment of locally recurrent HNC and to define long-term complications.

The TGF-β1 dynamics during radiation therapy and its correlation to symptomatic radiation pneumonitis in lung cancer patients

BackgroudThe underlying molecular and cellular mechanisms of radiation pneumonitis (RP) are very complex. Several biological factors need to be considered together with the well known dosimetric parameters for understanding the molecular events in developing RP in lung cancer patients. The aim of this study was to correlate the variations of the cytokine levels in lung cancer patients during radiation therapy (RT) with the occurrence of symptomatic RP.MethodsThirty-four lung cancer patients who received three-dimensional conformal radiation therapy were evaluated prospectively. Serial blood samples before, at the beginning, in the middle of, at the end of RT and 2 and 4 weeks after RT were analyzed for IL-1α, IL-6, IL-10, TNF-α and TGF-β1 by performing enzyme-linked immunosorbent assay. The predictive values of dosimetric factors for RP were evaluated, too.ResultsOverall, 8 patients (23.5%) had grade ≥ 2 RP. By serial measurement of cytokines level, only the TGF-β1 level showed a correlation to the symptomatic RP. None of the other cytokines, IL-1α, IL-6, IL-10 and TNF-α level was correlated with the risk of RP. The mean pretreatment TGF-β1 level did not differ between RP and non-RP groups. However, during the period of radiation treatment, the TGF-β1 level began to increase at the end of RT in the RP group and became significantly higher 4 weeks after RT (p = 0.007). Using an ANOVA model for repeated-measures, we found significant associations between the changes of TGF-β1 during the time course of the RT and the risk of developing RP (p < 0.001). Most of the dosimetric factors showed a significant association with RP.ConclusionOur results show that the changes of TGF-β1 could be correlated with RP and the incorporation of the biological parameters into the dosimetric data could be useful for predicting symptomatic RP.

Difference in expression of EGFR, pAkt, and PTEN between oropharyngeal and oral cavity squamous cell carcinoma.

OBJECTIVES The aims of this study were to evaluate the expression of EGFR, PI3K, Akt, mTOR, and PTEN in the oral cavity and oropharyngeal cancers, and to investigate their clinical significance as prognostic markers. MATERIALS AND METHODS One hundred twenty-one patients who underwent curative surgery for oral cavity or oropharyngeal squamous cell carcinoma in Seoul St. Marys Hospital between January 1995 and September 2009 were evaluated. The level of protein expression of EGFR, PIK3CA, pAkt, mTOR, and PTEN was assessed by immunohistochemistry. In situ hybridization was used to detect the existence of human papillomavirus (HPV). RESULTS Nineteen of 61 patients with oropharyngeal cancer showed HPV-positive tumors, and two of 60 patients with oral cavity cancer showed HPV-positive tumors. EGFR and pAkt expression was significantly higher in oral cavity cancers than in oropharyngeal cancers. Loss of PTEN occurred significantly more frequently in oral cavity cancers than in oropharyngeal cancers. The expression levels of PIK3CA, mTOR, and p53 did not differ significantly between the two cancers. Overexpression of EGFR and pAkt and loss of PTEN were observed more frequently in HPV-negative tumors. Multivariate Cox regression analysis showed that pAkt expression had a significantly unfavorable impact on relapse-free survival in oropharyngeal cancer. CONCLUSION We conclude that the expression levels of EGFR, pAkt, and PTEN differ between oropharyngeal and oral cavity cancer and it may be attributed to HPV-related molecular pathogenesis. The expression of pAkt might be an unfavorable prognostic marker for relapse-free survival in oropharyngeal cancer.

The relevance of serum carcinoembryonic antigen as an indicator of brain metastasis detection in advanced non-small cell lung cancer

Although many biomarkers have emerged in non-small cell lung cancer (NSCLC), the predictive value of site-specific spread is not fully defined. We designed this study to determine if there is an association between serum biomarkers and brain metastasis in advanced NSCLC. We evaluated 227 eligible advanced NSCLC patients between May 2005 and March 2010. Patients who had been newly diagnosed with stage IV NSCLC but had not received treatment previously, and had available information on at least one of the following pretreatment serum biomarkers were enrolled: carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA 21-1), cancer antigen 125 (CA 125), cancer antigen 19-9, and squamous cancer cell antigen. Whole body imaging studies and magnetic resonance imaging of the brain were reviewed, and the total number of metastatic regions was scored. Brain metastasis was detected in 66 (29.1%) patients. Although serum CEA, CYFRA 21-1, and CA 125 levels were significantly different between low total metastatic score group (score 1–3) and high total metastatic score group (score 4–7), only CEA level was significantly different between patients with brain metastasis and those without brain metastasis (p < 0.0001). The area under the receiver operating curve of serum CEA for the prediction of brain metastasis was 0.724 (p = 0.0001). The present study demonstrated that the pretreatment serum CEA level was significantly correlated with brain metastasis in advanced NSCLC. These findings suggested the possible role of CEA in the pathogenesis of brain invasion. More vigilant surveillance would be warranted in the high-risk group of patients with high serum CEA level and multiple synchronous metastasis.

Stereotactic radiosurgery for brain metastasis in non-small cell lung cancer

Purpose Stereotactic radiosurgery (SRS) has been introduced for small-sized single and oligo-metastases in the brain. The aim of this study is to assess treatment outcome, efficacy, and prognostic variables associated with survival and intracranial recurrence. Materials and Methods This study retrospectively reviewed 123 targets in 64 patients with non-small cell lung cancer (NSCLC) treated with SRS between January 2006 and December 2012. Treatment responses were evaluated using magnetic resonance imaging. Overall survival (OS) and intracranial progression-free survival (IPFS) were determined. Results The median follow-up was 13.9 months. The median OS and IPFS were 14.1 and 8.9 months, respectively. Fifty-seven patients died during the follow-up period. The 5-year local control rate was achieved in 85% of 108 evaluated targets. The 1- and 2-year OS rates were 55% and 28%, respectively. On univariate analysis, primary disease control (p < 0.001), the Eastern Cooperative Oncology Group (ECOG) performance status (0-1 vs. 2; p = 0.002), recursive partitioning analysis class (1 vs. 2; p = 0.001), and age (<65 vs. ≥65 years; p = 0.036) were significant predictive factors for OS. Primary disease control (p = 0.041) and ECOG status (p = 0.017) were the significant prognostic factors for IPFS. Four patients experienced radiation necrosis. Conclusion SRS is a safe and effective local treatment for brain metastases in patients with NSCLC. Uncontrolled primary lung disease and ECOG status were significant predictors of OS and intracranial failure. SRS might be a tailored treatment option along with careful follow-up of the intracranial and primary lung disease status.

Radiation Therapy Combined with (or without) Cisplatin-based Chemotherapy for Patients with Nasopharyngeal Cancer: 15-years Experience of a Single Institution in Korea

PURPOSE This retrospective study was carried out to evaluate the efficacy and toxicity of radiation therapy (RT) with/without cisplatin-based chemotherapy in nasopharyngeal cancer (NPC). MATERIALS AND METHODS One hundred forty six patients with NPC received curative RT and/or cisplatin-based chemotherapy. Thirty-nine patients were treated with induction chemotherapy (IC), including cisplatin and 5-fluorouracil followed by RT. Another 63 patients were treated with concurrent chemoradiotherapy (CCRT) using cisplatin, and 22 patients were treated with IC followed by CCRT. The remaining 22 patients were treated with RT alone. RESULTS One hundred four (80.0%) patients achieved complete response (CR), and 23 (17.7%) patients achieved partial response (PR). The patterns of failure were: locoregional recurrences in 21.2% and distant metastases in 17.1%. Five-year overall survival (OS) and progression free survival (PFS) were 50.7% and 45.0%, respectively. Multivariate Cox stepwise regression analysis revealed CR to chemoradiotherapy to be a powerful prognostic factor for OS. CR to chemoradiotherapy and completion of radiation according to the time schedule were favorable prognostic factors for PFS. A comparison of each treatment group (IC --> RT vs. CCRT vs. IC --> CCRT vs. RT alone) revealed no significant differences in the OS or PFS. However, subgroup analysis showed significant differences in both OS and DFS in favor of the combined chemoradiotherapy group compared with RT alone, for stage IV and T3-4 tumors. Grade 3-4 toxicities were more common in the combined chemoradiotherapy arm, particularly in the CCRT group. CONCLUSIONS This study was limited in that it was a retrospective study, much time was required to collect patients, and there were imbalances in the number of patients in each treatment group. Combined chemoradiotherapy remarkably prolonged the OS and PFS in subgroup patients with stage IV or T3-4 NPC.

Adjuvant Postoperative Radiotherapy with or without Chemotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck: The Importance of Patient Selection for the Postoperative Chemoradiotherapy

Purpose We wanted to evaluate the role of postoperative chemoradiotherapy (CRT) for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Materials and Methods From March 1993 to July 2008, 101 patients with advanced SCCHN and who had undergone macroscopically complete resection were enrolled. Survival and the cumulative incidence of local or regional relapse, metastasis, and acute toxicity were analyzed. Results There was a marginally significant difference of disease-free survival at five years in favor of the CRT arm (51.3% vs. 41.8%, respectively; p=0.10). However, there was no significant difference in overall survival between the two treatment arms (p=0.20). The rate of locoregional failure only for the radiotherapy arm was significantly higher than that for the CRT arm (23.2% vs. 4.4%, respectively; p=0.01). The incidence of grade 3 or 4 hematologic toxicity was significantly higher in the CRT arm than that in the radiotherapy arm (37.7% vs. 1.7%, respectively; p=0.01). In CRT arm, early mortality group within 1 year had low performance status and old age over sixty compared with those of the others. Conclusion After curative-intent surgery, adjuvant CRT is more effective in locoregional tumor control than radiotherapy alone for patients with advanced SCCHN. However, compared with radiotherapy alone, this combined modality treatment had no survival benefit, and was significantly associated with increased toxicity. Thus, patients with low performance status and old age must be cautious in selection of toxic trimodality treatment.

Prognostic significance of expression of vegf and cox-2 in nasopharyngeal carcinoma and its association with expression of C-erbB2 and EGFR

This study evaluated several tumor angiogenesis‐related markers to examine their expression pattern and relation to clinicopathologic implications of nasopharyngeal carcinoma.

Interdigitating dendritic cell sarcoma of the tonsil

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare malignancy derived from antigen‐presenting cells, with 55 cases reported thus far. A standard treatment modality is still being debated. This report describes a 56‐year‐old female who presented with right tonsillar enlargement and right submandibular swelling for 6 months. Treatment with empiric antibiotics did not result in improvement of her symptoms. Fine needle aspiration of the tonsil revealed no malignant cells. Tonsillectomy was eventually performed due to persistent symptoms. Based on microscopic findings, immunohistochemical stains, and review of the literature, the present case was finally diagnosed as IDCS of the tonsil with cervical lymph node involvement. The patient received four cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy, and a clinically complete response was achieved followed by adjuvant radiation.

Treatment Outcome of Cisplatin-based Concurrent Chemoradiotherapy in the Patients with Locally Advanced Nasopharyngeal Cancer

PURPOSE The standard treatment of locally advanced nasopharyngeal cancer is a concurrent chemoradiotherapy (CCRT), and cisplatin has been used as the most popular chemotherapeutic agent. But many different doses and schedules for cisplatin administration such as daily, weekly and 3 week cycles have been proposed. We compared and analyzed the tumor response, the overall survival, the toxicity and the chemotherapy dose intensity in the patients with locally advanced nasopharyngeal cancer who were treated with CCRT. MATERIALS AND METHODS We performed a retrospective study on 55 patients with locally advanced nasopharyngeal cancer, and they were treated with CCRT as a front-line treatment from Jan 1996 to Jun 2007 at Kangnam Saint Marys Hospital. RESULTS The patients had a median age of 53 years (range: 19 approximately 75 years). Of the total 55 patients, a 3-week cycle of 100mg cisplatin was administered in 31 patients and 30 mg weekly cisplatin was administered in 24 patients combined with radiotherapy. Twenty one patients had a complete response and four patients had a partial response for a response rate of 71.4% (95% CI: 59.5 approximately 83.3) after CCRT and followed by adjuvant chemotherapy. The complete response rates for the 30 mg and 100 mg cisplatin groups were 72.7% (95% CI: 54.9 approximately 90.5) and 54.2% (95% CI: 36.7 approximately 71.7), respectively (p=0.23). The duration of CCRT in the 100mg cisplatin group was significantly longer than that of the 30mg cisplatin group (11.1+/-2.9 weeks vs. 9.0+/-1.2 weeks, p=0.003). The major deviation group, which was defined as prolongation of the radiotherapy duration for more than 2 weeks, had a significantly lower objective response rate than did the non-deviation group (56.3% vs 84.2%, respectively, p=0.002). The major severe toxicities were leucopenia (49.1%), pharyngoesophagitis (49.1%), anorexia (43.6%), nausea (41.8%) and vomiting (40%). CONCLUSIONS Weekly 30mg cisplatin-based CCRT is a practical, feasible cisplatin schedule for the patients with locally advanced nasopharyngeal cancer in regard to decreasing the interruption of radiation treatment and decreasing the treatment-related acute toxicities.