Woong Sub Koom

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.

Synchronous Coexpression of Epidermal Growth Factor Receptor and Cyclooxygenase-2 in Carcinomas of the Uterine Cervix A Potential Predictor of Poor Survival

Purpose: To evaluate the potential of the new prognostic information gained by analyzing the coexpression of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in cervical cancer patients. Experimental Design: Sixty-eight patients with International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix, who underwent concurrent chemoradiotherapy between 1993 and 1996, were divided into the following four groups according to their immunoreactivities for EGFR and COX-2 in paraffin-embedded sections: (a) the EGFR-negative/COX-2-negative group (n = 11); (b) the EGFR-negative/COX-2-positive group (n = 8); (c) the EGFR-positive/COX-2-negative group (n = 27); and (d) the EGFR-positive/COX-2-positive group (n = 22). The clinical features, patterns of treatment failure, and survival data in the four groups were compared. Results: Positive immunoreactivity for EGFR and COX-2 was observed in 49 of 68 (72%) and 19 of 68 (28%), respectively. However, no strong correlation was found between the levels of EGFR and COX-2 immunopositivity (R2 = 0.05, P = 0.07). Patients in the EGFR-positive/COX-2-positive group had a higher likelihood of locoregional recurrence than those in the other three groups (P = 0.02). Of the patients in the four groups, patients positive for both oncoproteins were found to have the worst prognosis with an overall 5-year disease-free survival rate of 55% compared with 91% for the EGFR-negative/COX-2-negative patients, 88% for the EGFR-negative/COX-2-positive patients, and 69% for the EGFR-positive/COX-2-negative patients (P = 0.05, log-rank test). In addition, the synchronous coexpression of the EGFR and COX-2 oncoproteins was found to be an independent prognostic factor by univariate and multivariate analyses (relative risk = 4.0, P = 0.03). Conclusions: Given these observations, we conclude that the coexpression of EGFR and COX-2 immunoreactivity may be used as a potent molecular risk factor for predicting the poor survival of patients with the International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix.

Risk Factors and Dose-Effect Relationship for Mandibular Osteoradionecrosis in Oral and Oropharyngeal Cancer Patients

PURPOSE To analyze risk factors and the dose-effect relationship for osteoradionecrosis (ORN) of the mandible after radiotherapy of oral and oropharyngeal cancers. MATERIALS AND METHODS One-hundred ninety-eight patients with oral (45%) and oropharyngeal cancer (55%) who had received external radiotherapy between 1990 and 2000 were retrospectively reviewed. All patients had a dental evaluation before radiotherapy. The median radiation dose was 60 Gy (range, 16-75 Gy), and the median biologically effective dose for late effects (BED(late)) in bone was 114 Gy(2) (range, 30-167 Gy(2)). RESULTS The frequency of ORN was 13 patients (6.6%). Among patients with mandibular surgery, eight had ORN at the surgical site. Among patients without mandibular surgery, five patients had ORN on the molar area of the mandible. The median time to ORN was 22 months (range, 1-69 months). Univariate analysis revealed that mandibular surgery and Co-60 were significant risk factors for ORN (p = 0.01 and 0.04, respectively). In multivariate analysis, mandibular surgery was the most important factor (p = 0.001). High radiation doses over BED 102.6 Gy(2) (conventional dose of 54 Gy at 1.8 Gy/fraction) were also a significant factor for ORN (p = 0.008) and showed a positive dose-effect relationship in logistic regression (p = 0.04) for patients who had undergone mandibular surgery. CONCLUSIONS Mandibular surgery was the most significant risk factor for ORN of mandible in oral and oropharyngeal cancers patients. A BED of 102.6 Gy(2) or higher to the mandible also significantly increases the risk of ORN.

Clinical relevance of three subtypes of primary sinonasal lymphoma characterized by immunophenotypic analysis

The purpose of this study was to investigate the clinical relevance of subtypes categorized by immunophenotypic analysis in primary sinonasal lymphomas.

Clinical outcomes for T1-2N0-1 oral tongue cancer patients underwent surgery with and without postoperative radiotherapy.

BackgroundThe aim of this study was to assess the results of curative surgery with and without radiotherapy in patients with T1-2N0-1 oral tongue squamous cell carcinoma (OSCC) and to evaluate survival and prognostic factors.MethodsRetrospective analysis of 86 patients with T1-2N0-1 OSCC who received surgery between January 2000 and December 2006. Fourteen patients (16.3%) received postoperative radiotherapy (PORT). Patient characteristics, tumor characteristics, treatment modality, failure patterns, and survival rates were analyzed.ResultsThe median follow-up was 45 months. The five-year overall survival (OS) and disease-free survival (DFS) rates were 80.8% and 80.2%, respectively. Higher tumor grade and invasion depth ≥ 0.5 cm were the significant prognostic factors affecting five-year OS and DFS (OS rate; 65% vs. 91%, p = 0.001 for grade; 66% vs. 92%, p = 0.01 for invasion depth: DFS rate; 69% vs. 88%, p = 0.005 for grade; 66% vs. 92%, p = 0.013 for invasion depth). In the risk group, there was no local failure in patients with postoperative radiotherapy.ConclusionsIn T1-2N0-1 OSCC, factors that affected prognosis after primary surgery were higher tumor grade and deep invasion depth over 0.5 cm. Postoperative radiotherapy should be considered in early oral tongue cancer patients with these high-risk pathologic features.

Reirradiation to the pelvis for recurrent rectal cancer

This study investigated late toxicity and infield progression‐free survival in patients with locally recurrent rectal cancer (LRRC) who had previously received irradiation to the pelvis.

CA 19-9 as a Predictor for Response and Survival in Advanced Pancreatic Cancer Patients Treated With Chemoradiotherapy

PURPOSE To investigate the significance of carbohydrate antigen 19-9 (CA 19-9) levels for predicting response and survival in pancreatic cancer (PC) treated with concurrent chemoradiotherapy. METHODS AND MATERIALS We retrospectively reviewed data from 69 patients with PC between 1999 and 2005. All patients had elevated CA 19-9 levels before treatment. CA 19-9 levels (pre- and posttreatment CA 19-9) and their decline were analyzed for radiologic response and overall survival. RESULTS Seventeen patients (25%) had a 50% or greater reduction in tumor size within 3 months of chemoradiotherapy (1 complete response, 16 partial responses). CA 19-9 decline was significantly correlated with radiologic response (p = 0.03). The median survival time (MST) was 12 months (range, 4-48 months), and 1-year survival rate was 44%. Pretreatment CA 19-9 > 1,200 U/mL (MST, 13 vs. 8 months; p = 0.002), posttreatment CA 19-9 >100 U/mL (MST, 17 vs. 10 months; p = 0.0003), and CA 19-9 decline <or=40% (MST, 13 vs. 10 months; p = 0.005) were the strongest and most unfavorable prognostic factors. In addition, patients with multiple unfavorable CA 19-9 levels had significantly worse outcomes than those without. CONCLUSIONS CA 19-9 decline shows a correlation with radiologic response. The combination of pretreatment CA 19-9 >1,200 U/mL, posttreatment CA 19-9 >100 U/mL, and CA 19-9 decline <or=40% may possibly serve as a surrogate marker for poor survival in advanced PC receiving chemoradiotherapy.

Patterns of regional recurrence after curative D2 resection for stage III (N3) gastric cancer: Implications for postoperative radiotherapy

BACKGROUND AND PURPOSE To analyze patterns of regional recurrence after curative gastrectomy and D2 lymph node dissection in patients with stage III (N3) gastric cancer. MATERIALS AND METHODS Between 2004 and 2008, 2918 patients with primary gastric cancer underwent D2 resection at a single institution. A retrospective review was performed on 382 patients in stage III with N3 disease. Of these, 357 patients (93.5%) received adjuvant chemotherapy. None of the patients received pre- or postoperative radiotherapy. RESULTS Median follow-up was 56.3 months. The 5-year regional failure free-survival (RFFS) rate was 63.6%. Regional failure (RF) as any component of first recurrence occurred in 91 patients (23.8%), with isolated regional failure occurring in 49 (12.8%). The most commonly involved lymph nodes were the No. 16b, No. 16a, No. 12, No. 14, No. 13, and No. 9 nodes. RFFS was adversely affected by advanced nodal stage (N3b vs. N3a). The 5-year progression-free survival rate was 32.1% and overall survival was 41.5%. CONCLUSION The most prevalent nodal recurrence in patients with advanced gastric cancer was in the nodal basin outside the D2 dissection field. Our findings may help physicians construct a lymph node target volume for radiation treatment of gastric cancer after D2 dissection.

A Phase II Study of Synchronous Three-Dimensional Conformal Boost to the Gross Tumor Volume for Patients With Unresectable Stage III Non–Small-Cell Lung Cancer: Results of Korean Radiation Oncology Group 0301 Study

PURPOSE We evaluated the efficacy of synchronous three-dimensional (3D) conformal boost to the gross tumor volume (GTV) in concurrent chemoradiotherapy for patients with locally advanced non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS Eligibility included unresectable Stage III NSCLC with no pleural effusion, no supraclavicular nodal metastases, and Eastern Cooperative Oncology Group performance score of 0-1. Forty-nine patients with pathologically proven NSCLC were enrolled. Eighteen patients had Stage IIIA and 31 had Stage IIIB. By using 3D conformal radiotherapy (RT) techniques, a dose of 1.8 Gy was delivered to the planning target volume with a synchronous boost of 0.6 Gy to the GTV, with a total dose of 60 Gy to the GTV and 45 Gy to the planning target volume in 25 fractions during 5 weeks. All patients received weekly chemotherapy consisting of paclitaxel and carboplatin during RT. RESULTS With a median follow-up of 36.8 months (range, 29.0-45.5 months) for surviving patients, median survival was 28.1 months. One-, 2- and 3-year overall survival rates were 77%, 56.4%, and 43.8%, respectively. Corresponding local progression-free survival rates were 71.2%, 53.7%, and 53.7%. Compliance was 90% for RT and 88% for chemotherapy. Acute esophagitis of Grade 2 or higher occurred in 29 patients. Two patients with T4 lesions died of massive bleeding and hemoptysis during treatment (Grade 5). Overall late toxicity was acceptable. CONCLUSIONS Based on the favorable outcome with acceptable toxicity, the acceleration scheme using 3D conformal GTV boost in this trial is warranted to compare with conventional fractionation in a Phase III trial.

Upfront systemic chemotherapy and preoperative short-course radiotherapy with delayed surgery for locally advanced rectal cancer with distant metastases

BackgroundChoosing the most effective approach for treating rectal cancer with mesorectal fascia (MRF) involvement or closeness and synchronous distant metastases is a current clinical challenge. The aim of this retrospective study was to determine if upfront systemic chemotherapy and short-course radiotherapy (RT) with delayed surgery enables R0 resection.MethodsBetween March 2009 and October 2009, six patients were selected for upfront chemotherapy and short-course RT (5 × 5 Gy) with delayed surgery. The patients had locally advanced primary tumors with MRF involvement or closeness, as well as synchronous and potentially resectable distant metastases. Chemotherapy was administered to five patients between the end of the RT and surgery. All patients underwent total mesorectal excision (TME).ResultsThe median patient age was 54 years (range 39-63). All primary and metastatic lesions were resected simultaneously. The median duration between short-course RT and surgery was 13 weeks (range, 7-18). R0 resection of rectal lesions was achieved in 5 patients. One patient, who had a very low-lying tumor, had an R1 resection. The median follow-up duration for all patients was 16.7 months (range, 15.5-23.5). One patient developed liver metastasis at 15.7 months. There have been no local recurrences or deaths.ConclusionsUpfront chemotherapy and short course RT with delayed surgery is a valuable alternative treatment approach for patients with MRF involvement or closeness of rectal cancer with distant metastases.