The effect of combined chemoradiotherapy versus chemotherapy alone on the survival of ⅣB stage esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Objective:To investigate the survival benefit of radiotherapy on the basis of systemic treatment for stage ⅣB esophageal squamous cell carcinoma (ESCC).Methods:Based on inclusion and exclusion criteria, we collected the treatment information of 298 patients with newly diagnosed stage ⅣB ESCC admitted to Affiliated Cancer Hospital of Zhengzhou University from January 2016 to February 2021. All patients were divided into two groups based on treatment: early radiotherapy intervention group (CRT group, n=197) and salvage radiotherapy intervention or no intervention group (CT group, n=101). Propensity score matching (PSM) was used to balance baseline characteristics between two groups. Kaplan-Meier method was used to calculate the survival rate and log-rank was used to test the difference. Cox model was used to analyze the multivariate prognosis. Results:In the CRT and CT groups, the objective response rate (ORR) and disease control rate (DCR) were 52.8% vs. 31.5%( P=0.006) and 98.9% vs. 85.4%( P=0.001) respectively, and the 1-, 2- and 3-year survival rates were 74.2% vs. 52.8%、31.5% vs. 10.1% and 15.7% vs. 2.2%, respectively. Median progression-free survival (PFS) was 8.5 months (95% CI: 6.7-10.3 months) vs. 4.4 months (95% CI: 3.5-5.3 months)( P<0.001). Median overall survival (OS) were 17.1 months (95% CI: 14.9-19.3 months) vs. 12.7 months (95% CI: 8.0-17.4 months)( P<0.001). The difference of adverse reactions was mainly in hematology. Conclusions:For newly diagnosed stage ⅣB patients with ESCC, radiotherapy should be combined with systemic therapy as early as possible. It yields longer PFS and OS, and effectively improves dysphagia. Adverse reactions are tolerated. Further validation is recommended in larger prospective studies.

Response Assessment with MRI after Chemoradiotherapy in Rectal Cancer: Current Evidences

Baseline magnetic resonance imaging (MRI) has become the primary staging modality for surgical plans and stratification of patient populations for more efficient neoadjuvant treatment. Patients who exhibit a complete response to chemoradiotherapy (CRT) may achieve excellent local tumor control and better quality of life with organ-preserving treatments such as local excision or even watch-and-wait management. Therefore, the evaluation of tumor response is a key factor for determining the appropriate treatment following CRT. Although post-CRT MRI is generally accepted as the first-choice method for evaluating treatment response after CRT, its application in the clinical decision process is not fully validated. In this review, we will discuss various oncologic treatment options from radical surgical technique to organ-preservation strategies for achieving better cancer control and improved quality of life following CRT. In addition, the current status of post-CRT MRI in restaging rectal cancer as well as the main imaging features that should be evaluated for treatment planning will also be described for the tailored treatment.

Single nucleotide polymorphism of GSTP1 and pathological complete response in locally advanced rectal cancer patients treated with neoadjuvant concomitant radiochemotherapy

PURPOSE: Standard treatment for locally advanced rectal cancer consists of neoadjuvant radiochemotherapy with concomitant fluoropyrimidine or oxaliplatin and surgery with curative intent. Pathological complete response has shown to be predictive for better outcome and survival; nevertheless there are no biological or genetic factors predictive for response to treatment. We explored the correlation between the single nucleotide polymorphisms (SNPs) GSTP1 (A313G) and XRCC1 (G28152A), and the pathological complete response and survival after neoadjuvant radiochemotherapy in locally advanced rectal cancer patients. MATERIALS AND METHODS: Genotypes GSTP1 (A313G) and XRCC1 (G28152A) were determined by pyrosequencing technology in 80 patients affected by locally advanced rectal cancer. RESULTS: The overall rate of pathological complete response in our study population was 18.75%. Patients homozygous AA for GSTP1 (A313G) presented a rate of pathological complete response of 26.6% as compared to 8.5% of the AG+GG population (p = 0.04). The heterozygous comparison (AA vs. AG) showed a significant difference in the rate of pathological complete response (26.6% vs. 6.8%; p = 0.034). GSTP1 AA+AG patients presented a 5- and 8-year cancer-specific survival longer than GSTP1 GG patients (87.7% and 83.3% vs. 44.4% and 44.4%, respectively) (p = 0.014). Overall survival showed only a trend toward significance in favor of the haplotypes GSTP1 AA+AG. No significant correlations were found for XRCC1 (G28152A). CONCLUSION: Our results suggest that GSTP1 (A313G) may predict a higher rate of pathological complete response after neoadjuvant radiochemotherapy and a better outcome, and should be considered in a more extensive analysis with the aim of personalization of radiation treatment.

Early evaluation of tumor radiation response by medical imaging / 中华放射肿瘤学杂志

Response evaluation criteria in solid tumors is widely used for assessing tumor response to radiotherapy in clinical practice.However,it is clearly insufficient.Currently there is no ideal method for early evaluation of tumor radiation response.This paper reviews studies on early evaluation of radiotherapy efficacy by positron emission tomography-computed tomography (CT),magnetic resonance imaging,and CT.This paper also further explores the necessity and feasibility of CT values of megavoltage CT scans in early evaluation of the radiosensitivity of tumor during tomotherapy.

Genetic Variations of Drug Transporters Can Influence on Drug Response in Patients Treated with Docetaxel Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Dose-limiting toxicities of docetaxel are widely considered to be neutropenia, anemia, skin toxicity, and nausea. One of the factors that limit the use of docetaxel is its unpredictability of inter-individual variation in toxicity. MATERIALS AND METHODS: In order to identify the genetic factors that affect the risk of docetaxel-induced toxicities, we recruited patients who received docetaxel chemotherapy. We genotyped 92 patients with single-nucleotide polymorphisms (SNPs) in 5 genes: CYP3A4 (CYP3A4*1B, CYP3A4*18, and CYP3A4*3), CYP3A5 (CYP3A5*2 and CYP3A5*3), ABCB1 (C1236T, G2677G/T, and C3435T), SLCO1B3 (rs11045585), and ABCC2 (rs12762549). RESULTS: Out of 92 patients, 70 had grade 3 or 4 neutropenia; 4 had grade 1 or 2; and 18 had no toxicity (76.1%, 4.3%, and 19.6%, respectively). The findings of the SNP analysis showed that patients with TT genotype of ABCB1 3435C>T polymorphism showed significantly higher risk of neutropenia and anemia (p=0.029 and p=0.044, respectively). There were significant associations between docetaxel-induced leucopenia and 2677G/T of ABCB1 and rs12762549 of ABCC2 (p=0.025 and p=0.028, respectively). In a multivariate analysis, we observed that patients carrying 2677G>T in ABCB1might be associated with higher risk of chemo-resistance when treated with docetaxel (odds ratio [OR], 6.48; confidence interval, 1.92 to 21.94; p=0.003). In a subgroup analysis of non-small cell lung cancer patients, a significant association of tumor response with G2677T/A (OR, 4.54) in ABCB1 and SLCO1B3 (OR, 9.44) was observed. CONCLUSION: Our data suggest that ABCB1 (2677G/T) and SLCO1B3 (rs11055585) might be major genetic predictors of docetaxel-related toxicities in patients receiving docetaxel chemotherapy.

Clinical predictive factors of pathologic tumor response after preoperative chemoradiotherapy in rectal cancer

PURPOSE: The aim of this study was to identify clinical predictive factors for tumor response after preoperative chemoradiotherapy (CRT) in rectal cancer. MATERIALS AND METHODS: The study involved 51 patients who underwent preoperative CRT followed by surgery between January 2005 and February 2012. Radiotherapy was delivered to the whole pelvis at a dose of 45 Gy in 25 fractions, followed by a boost of 5.4 Gy in 3 fractions to the primary tumor with 5 fractions per week. Three different chemotherapy regimens were used (5-fluorouracil and leucovorin, capecitabine, or tegafur/uracil). Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and pathologic complete response (ypCR). Statistical analyses were performed to identify clinical factors associated with pathologic tumor response. RESULTS: Tumor downstaging was observed in 28 patients (54.9%), whereas ypCR was observed in 6 patients (11.8%). Multivariate analysis found that predictors of downstaging was pretreatment relative lymphocyte count (p = 0.023) and that none of clinical factors was significantly associated with ypCR. CONCLUSION: Pretreatment relative lymphocyte count (%) has a significant impact on the pathologic tumor response (tumor downstaging) after preoperative CRT for locally advanced rectal cancer. Enhancement of lymphocyte-mediated immune reactions may improve the effect of preoperative CRT for rectal cancer.

Imaging-Based Tumor Treatment Response Evaluation: Review of Conventional, New, and Emerging Concepts

Tumor response may be assessed readily by the use of Response Evaluation Criteria in Solid Tumor version 1.1. However, the criteria mainly depend on tumor size changes. These criteria do not reflect other morphologic (tumor necrosis, hemorrhage, and cavitation), functional, or metabolic changes that may occur with targeted chemotherapy or even with conventional chemotherapy. The state-of-the-art multidetector CT is still playing an important role, by showing high-quality, high-resolution images that are appropriate enough to measure tumor size and its changes. Additional imaging biomarker devices such as dual energy CT, positron emission tomography, MRI including diffusion-weighted MRI shall be more frequently used for tumor response evaluation, because they provide detailed anatomic, and functional or metabolic change information during tumor treatment, particularly during targeted chemotherapy. This review elucidates morphologic and functional or metabolic approaches, and new concepts in the evaluation of tumor response in the era of personalized medicine (targeted chemotherapy).

Dual-Energy CT in Patients Treated with Anti-Angiogenic Agents for Non-Small Cell Lung Cancer: New Method of Monitoring Tumor Response?

OBJECTIVE: To evaluate tumor responses in patients treated with anti-angiogenic agents for non-small cell lung cancer (NSCLC) by assessing intratumoral changes using a dual-energy CT (DECT) (based on Choi's criteria) and to compare it to traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria. MATERIALS AND METHODS: Ten NSCLC patients treated with bevacizumab underwent DECT. Tumor responses to anti-angiogenic therapy were assessed and compared with the baseline CT results using both RECIST (size changes only) and Choi's criteria (reflecting net tumor enhancement). Kappa statistics was used to evaluate agreements between tumor responses assessed by RECIST and Choi's criteria. RESULTS: The weighted kappa value for the comparison of tumor responses between the RECIST and Choi's criteria was 0.72. Of 31 target lesions (21 solid nodules, 8 lymph nodes, and two ground-glass opacity nodules [GGNs]), five lesions (16%) showed discordant responses between RECIST and Choi's criteria. Iodine-enhanced images allowed for a distinction between tumor enhancement and hemorrhagic response (detected in 14% [4 of 29, excluding GGNs] of target lesions on virtual nonenhanced images). CONCLUSION: DECT may serve as a useful tool for response evaluation after anti-angiogenic treatment in NSCLC patients by providing information on the net enhancement of target lesions without obtaining non-enhanced images.

Clinical Impact of Tumor Regression Grade after Preoperative Chemoradiation for Locally Advanced Rectal Cancer: Subset Analyses in Lymph Node Negative Patients

BACKGROUND: We investigated the prognostic significance of tumor regression grade (TRG) after preoperative chemoradiation therapy (preop-CRT) for locally advanced rectal cancer especially in the patients without lymph node metastasis. METHODS: One-hundred seventy-eight patients who had cT3/4 tumors were given 5,040 cGy preoperative radiation with 5-fluorouracil/leucovorin chemotherapy. A total mesorectal excision was performed 4-6 weeks after preop-CRT. TRG was defined as follows: grade 1 as no cancer cells remaining; grade 2 as cancer cells outgrown by fibrosis; grade 3 as a minimal presence or absence of regression. The prognostic significance of TRG in comparison with histopathologic staging was analyzed. RESULTS: Seventeen patients (9.6%) showed TRG1. TRG was found to be significantly associated with cancer-specific survival (CSS; P = 0.001) and local recurrence (P = 0.039) in the univariate study, but not in the multivariate analysis. The ypN stage was the strongest prognostic factor in the multivariate analysis. Subgroup analysis revealed TRG to be an independent prognostic factor for the CSS of ypN0 patients (P = 0.031). TRG had a stronger impact on the CSS of ypN (-) patients (P = 0.002) than on that of ypN (+) patients (P = 0.521). In ypT2N0 and ypT3N0, CSS was better for TRG2 than for TRG3 (P = 0.041, P = 0.048), and in ypN (-) and TRG2 tumors, CSS was better for ypT1-2 than for ypT3-4 (P = 0.034). CONCLUSION: TRG was found to be the strongest prognostic factor in patients without lymph node metastasis (ypN0), and different survival was observed according to TRG among patients with a specific histopathologic stage. Thus, TRG may provide an accurate prediction of prognosis and may be used for f tailoring treatment for patients without lymph node metastasis.

Molecularly Targeted Therapy Using Bevacizumab for Non-Small Cell Lung Cancer: a Pilot Study for the New CT Response Criteria

OBJECTIVE: We wanted to compare the efficacy of the new CT response evaluation criteria for predicting the tumor progression-free survival (PFS) with that of RECIST 1.1 in non-small cell lung cancer (NSCLC) patients who were treated with bevacizumab. MATERIALS AND METHODS: Sixteen patients (M:F = 11:5; median age, 57 years) treated with bevacizumab and combined cytotoxic chemotherapeutic agents were selected for a retrospective analysis. The tumor response was assessed by four different methods, namely, by using RECIST 1.1 (RECIST), RECIST but measuring only the solid component of tumor (RECISTsolid), the alternative method reflecting tumor cavitation (the alternative method) and the combined criteria (the combined criteria) that evaluated both the changes of tumor size and attenuation. To evaluate the capabilities of the different measurement methods to predict the patient prognosis, the PFS were compared, using the log rank test, among the responder groups (complete response [CR], partial response [PR], stable disease [SD] and progressive disease [PD]) in terms of the four different methods. RESULTS: The overall (CR, PR or SD) response rates according to RECIST, RECISTsolid, the alternative method and the combined criteria were 81%, 88%, 81% and 85%, respectively. The confirmed response rates (CR or PR) were 19%, 19%, 50% and 54%, respectively. Although statistically not significant, the alternative method showed the biggest difference for predicting PFS among the three response groups (PR, SD and PD) (p = 0.07). RECIST and the alternative method showed a significant difference for predicting the prognosis between the good (PR or SD) and poor overall responders (p = 0.02). CONCLUSION: The response outcome evaluations using the three different CT response criteria that reflect tumor cavitation, the ground-glass opacity component and the attenuation changes in NSCLC patients treated with bevacizumab showed different results from that with using the traditional RECIST method.

The Usefulness of 18F-FDG PET/CT for Predicting the Response of Locally Advanced Rectal Cancer to Neoadjuvant Chemoradiation Therapy / 대한방사선종양학회지

PURPOSE: This study aimed at assessing the value of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) for predicting the response of locally advanced rectal cancer to neoadjuvant CRT. MATERIALS AND METHODS: Between August 2006 and January 2008, we prospectively enrolled 20 patients with locally advanced rectal cancer and who were treated with neoadjuvant CRT at the Korea Institute of Radiological and Medical Sciences. The treatment consisted of radiation therapy and chemotherapy, and this was followed by curative resection 6 weeks later. All the patients underwent 18F-FDG PET/CT both before CRT and 6 weeks after completing CRT. The measurements of the FDG uptake (SUV(max)), the absolute difference (DeltaSUV(max)) and the percent SUV(max) difference (response index, RI(SUV)) between the pre- and post-CRT 18F-FDG PET/CT scans were assessed. The measurements of the metabolic volume, the absolute difference (Delta metabolic volume) and the percent metabolic volume difference (response index, RI(metabolic volume)) were also assessed. RESULTS: Of the 20 patients who underwent surgery, 11 patients (55%) were classified as responders according to Dworak's classification. The post-CRT SUV(max) was significantly lower than the pre-CRT SUV(max). However, there were no significant differences in the SUV(max) and the metabolic volume reduction between the responders and non-responders. We used a minimum SUV(max) reduction of 67% as the cut-off value for defining a response, with a sensitivity of 45.5%, a specificity of 88.9%, a positive predictive value of 77% and a negative predictive value of 53.8%. CONCLUSION: Although there were no statistically significant results in this study, other studies have revealed that 18F-FDG PET/CT has the potential to assess the tumor response to neoadjuvant CRT in patients with locally advanced rectal cancer.

The Effect of Cyclooxygenase-2 Expression on Tumor Volume Response in Patients Treated with Radiotherapy for Uterine Cervical Cancer

We investigated the correlation between Cyclooxygenase-2 (COX-2) expression and the tumor response in patients with cervical cancer that were treated with curative radiotherapy (RT). Fifty-seven patients with squamous cell carcinoma were treated with concurrent radiochemotherapy (CRCT, n=29) or RT alone (n=28). The response of each patient was evaluated by three serial Magnetic Resonance Imaging examinations: before the start of RT, at four weeks after the start of RT (mid-RT) and at four weeks after the completion of RT (post-RT). Forty-three patients had positive COX-2 expression. The COX-2 negative patients achieved a higher rate of complete response (CR) at mid-RT than did the COX-2 positive patients (28.6% vs. 7.0%, P=0.054), but not at post-RT (64.3% vs. 69.8%). The initial tumor volume was a significant predictor of CR at mid-RT (P=0.003) and post-RT (P=0.004). The multivariate analysis showed that the initial tumor volume (at mid-RT and post-RT) and CRCT (at post-RT) were significant predictors of CR; however, the COX-2 expression was not. In conclusion, the COX-2 expression status has no significant correlation with the tumor response. Further studies on the changes in COX-2 expression levels during RT may be helpful for determination of its role in the tumor response to treatment and patient prognosis.

The Efficacy of UGT1A1 Polymorphism in Chemoradiation Therapy Using Irinotecan in Patients with Locally Advanced Rectal Cancer

PURPOSE: Irinotecan (CPT-11) is hydrolyzed to an active SN-38, which is further detoxicated to SN-38G through conjugation by uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) enzymes. There are many reports that UGT1A1 polymorphisms are associated with irinotecan related dose-limiting toxicity. The aim of the present study is to determine whether UGT1A1 polymorphisms affect individual variations of the toxicity due to and the tumor response to irinotecan via the alteration of bioavailability of SN-38 in Korean patients with locally advanced rectal cancer. METHODS: Twenty patients with locally advanced rectal cancer, who had received surgery after irinotecan-containing chemoradiation from 2003 to 2006, were enrolled. We analyzed the association of UGT1A1 genotypes with toxicity and tumor response to chemoradiation therapy. A tumor response was assumed when a tumor regression grade I or II was obtained. Toxicity was graded in accordance with the NCI common toxicity criteria. RESULTS: The frequence of square53(TA)6>7 (UGT1A1*28), 211G>A (UGT1A1*6), 686C>A (UGT1A1*27), square3279T>G (UGT1A1*60), and square3156G>A were 25% (5/20), 25% (5/20), 0% (0/20), 55% (11/20), and 20% (4/20), respectively. There were five grade III neutropenia and one severe diarrhea. Patients with UGT1A1*28 and square3156G>A showed higher complete tumor response rates (40% vs. 6.7%, P=0.07; 50% vs. 6.3%, P=0.08), but there was no differences in toxicity and tumor response between responders and non-responders. Patients with square3279T>G (UGT1A1*60) showed a tendency for lower tumor response in tumor responders, but there was no statistically significant difference (P=0.07). CONCLUSIONS: This study suggested that square3279T>G (UGT1A1*60) may be useful in predicting tumor response of irinotecan. In the future, further study is warranted using large numbers of cases to reach statistical significance.

Comparison of WHO and RECIST Criteria for Response in Metastatic Colorectal Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study compared the WHO criteria with the response evaluation criteria in solid tumors (RECIST) in the same patients with metastatic colorectal cancer in order to determine the significance of the RECIST. In addition, this study compared the estimations of medical oncologists with those of a radiologist. MATERIALS AND METHODS: Between 2002 and 2005, a total of 48 patients (male: female ratio, 29: 19; median age, 58 years) with measurable lesions receiving chemotherapy for metastatic colorectal carcinoma were enrolled in this study. Two medical oncologists and one radiologist, who were blinded to the patients' condition, independently reviewed all the CT images. The results were compared using a kappa test. RESULTS: The kappa test for concordance between the WHO and RECIST criteria of the medical oncologists and the radiologist were 0.908 and 0.841, respectively. The level of concordance between the investigators using the WHO and RECIST were 0.722 and 0.753, respectively. CONCLUSIONS: The RECIST criteria are comparable to the WHO criteria in evaluating the response of colorectal carcinoma, but have simple and reproducible guidelines. The use of RECIST is recommended for evaluating the treatment efficacy in clinical trials and practice.

Study of Clinical Features of Cutaneous Side Effects Associated with ZD 1839 / 대한피부과학회지

BACKGROUND: ZD1839 (Iressa(R)Gefitinib) is an orally active, selective epidermal growth factor (EGF) receptor tyrosine kinase inhibitor that blocks signal production pathways in cell proliferation. It is currently used in the treatment of advanced stage non-small cell lung cancer. Cutaneous side effects commonly associated with ZD 1839 treatment include acneiform eruption, dry skin and hair growth abnormalities. Cutaneous eruptions result from direct interference with functions of EGF receptor signaling in the skin. OBJECTIVE: The purpose of our study was to investigate the clinical features of cutaneous side effects of ZD 1839 in Korean with literature review. We also analysed the relationship between skin rash severity, onset and objective tumor response. METHOD: We retrospectively reviewed medical records and the histologic materials of 23 Korean patients who had been treated with ZD 1839 at Ajou University Hospital from March 2002 to September 2003 . RESULTS: The results are summarized as follows. 1. The most common cutaneous side effect was acneiform skin rash (56%) which is a well known complication of ZD 1839. 2. Acneiform eruptions were easily controlled by oral antibiotics, such as minocycline and topical retinoid ointment. 3. The second common side effect was dry scaly skin (43%). 4. We also found acute paronychia, finger tip desquamation, alopecia and intertrigo. 5. The severity of the skin rash correlated well with the treatment response of ZD 1839. 6. When the skin rash appeared within 1 week after taking ZD 1839, the skin rash was severe, and the tumor responded well to the ZD 1839. CONCLUSION: The results of this study suggest that acneiform eruption and dry skin are the most common cutaneous side effects of ZD 1839. The association between rash severity and onset of tumor response suggests that the rash may serve as a marker of response to ZD1839 therapy and may be used to guide treatment to obtain optimal response. However, further prospective studies on the potentially important association between rash severity or onset and outcome of treatment with ZD 1839 are needed.

p53, Bcl-2 and Ki-67 Expression according to Tumor Response after Concurrent Chemoradiation Treatment for Advanced Rectal Cancer

PURPOSE: Concurrent chemoradiation treatment (CCRT) for locally advanced rectal cancer is an important modality for curative resection, but its tumor response shows wide spectrum. The aim of study is to investigate any correlation between a related genetic mutations, proliferative index and tumor response after CCRT. METHODS: A twenty three patients with rectal cancer, which preoperatively staged as over T3N1 or T4 determined by transrectal ultrasonography and MRI. Enrolled patients were given 5 FU 450 mg/m2 and leucovorin 20 mg/m2 intravenously for 5 days during the first and fifth weeks of radiation therapy (45~54 Gy). 4 weeks after completion of scheduled treatment, surgical resection was performed. Tumor response was classified into CR (complete remission), PR (partial response: 50% of diminution of tumor volume and downstaging), NR (no response). Paraffin-embedded tissues obtained before chemoradiation treatment were studied with immunohistochemical staining of p53, Bcl-2 and Ki-67. The extent of tumor response was correlated with proliferative activity as measured by immunostaining of Ki-67 proliferative antigen and expression of p53 and bcl-2 oncoproteins (less than 10%: negative, 10~25%: , 25~50%: , more than 50%: , Ki-67: to count a labeled cells per 1,000 cells). RESULTS: All patients were resectable. CR was obtained in 4 (17.4%), PR in 10 (43.3%) and NR in 9 (39.2%). p53 mutation was noted in 16 (70%). p53 mutation was found in NR: 5 (31.3%), PR: 9 (56.2%), CR: 2 (12.5%), respectively. Bcl-2 expression was noted in 11 (48%). NR as in 4 (36.3%), PR: 3 (28.4%) and CR: 4 (36.3%), respectively. Ki-67 labeling index was NR: 615.4 446.2, PR: 663.2 296.4, CR: 765.5 188.3, respectively (CR PR Vs NR, p=0.029). CONCLUSIONS: Immunohistochemical Expression of p53 and bcl-2 does not correlate with tumor response after CCRT, but Ki-67 labeling may be useful parameters for good radiosensitive tumor selected for CCRT.