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Tracking administered natural killer (NK) cells in vivo is critical for developing an effective NK cell-based immunotherapy against human hepatocellular carcinoma (HCC). Here the authors established a new molecular imaging using ex vivo -activated NK cells and investigated real-time biodistribution of administered NK cells during HCC progression. Ex vivo -expanded NK cells from healthy donors were labeled with a near-infrared lipophilic cytoplasmic dye, and their proliferation, surface receptor expression and cytotoxicity activity were evaluated. Human HCC HepG2 cells were implanted into the livers of NOD.Cg- Prkdcscid IL2rgtm1Wjl/ SzJ (NSG) mice. The authors administered 1,1'-dioctadecyltetramethyl indotricarbocyanine iodide (DiR)-labeled NK cells intravenously to non-tumor-bearing and intrahepatic HCC tumor-bearing NSG mice. Fluorescent imaging was performed using a fluorescence-labeled organism bioimaging instrument. Single cell suspensions from the resected organs were analyzed using flow cytometry. The fluorescent DiR dye was nontoxic and did not affect the proliferation or surface receptor expression levels of the NK cells, even at high doses. The administered DiR-labeled NK cells immediately migrated to the lungs of the non-tumor-bearing NSG mice, with increased NK cell signals evident in the liver and spleen after 4 h. NK cells migrated to the intrahepatic tumor-bearing livers of both early- and late-stage HCC mice within 1 h of injection. In early-stage intrahepatic tumor-bearing mice, the fluorescence signal increased in the liver until 48 h post-injection and decreased 7 days after NK injection. In late-stage HCC, the NK cell fluorescence signal was the highest in the liver for 7 days after NK injection and persisted for 14 days. The purity of long-term persistent CD45+CD56+CD3− NK cells was highest in early- and late-stage HepG2-bearing liver compared with normal liver 2 weeks after NK injection, whereas highest purity was still observed in the lungs of non-tumor-bearing mice. In addition, Ki-67 expression was detected in migrated human NK cells in the liver and lung up to 72 h after administration. With HepG2 tumor progression, NK cells reduced the expression of NKp30 and NKG2D. Administered NK cells were successfully tracked in vivo by labeling the NK cells with near-infrared DiR dye. Highly expanded, activated NK cells migrated rapidly to the tumor-bearing liver, where they persisted for 14 days after administration, with high purity of CD45+CD56+CD3− NK cells. Liver biodistribution and persistence of administered NK cells showed significantly different accumulation patterns during HCC progression. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: To predict tumor regression in pre-operative chemoradiotherapy (CRT) using 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) and serum carcinoembryonic antigen (CEA) in patients with rectal cancer. Materials and methods: The metabolic response of the tumor was assessed by determining the maximal standardized uptake value (SUVmax), absolute difference (ΔSUVmax), and SUV reduction ratio (SRR) on pre- and post-CRT PET/CT scans. The serum CEA, absolute difference (ΔCEA), and the CEA reduction ratio (CRR) were also determined. A receiver-operating characteristic (ROC) curve was generated. Results: Of all seventy two patients, mean pre- and post-CRT SUVmax was 14.9 and 5.8, respectively. The mean pre- and post-CRT CEA level was 15.5ng/ml and 5.4ng/ml, respectively. Forty-three patients (59.8%) were classified as responders (Dworak’s tumor regression grade 3–4) and 36 patients (50%) achieved tumor down-staging. ROC analysis showed that both post-CRT SUVmax and SRR were predictive factors for responders (p =0.03 and p =0.02, respectively). A threshold of post-CRT SUVmax was 5.4 and that of SRR was 53.1%. Pre-CRT SUVmax, ΔSUVmax, and all parameters in regard to CEA were not significant in ROC analysis. Conclusions: The post-CRT SUVmax and SRR are potential factors for predicting tumor response in pre-operative CRT. The patients with lower post-CRT SUVmax and higher SRR could be expected to achieve maximum tumor regression after pre-operative CRT in this study. [ABSTRACT FROM AUTHOR]

Purpose: We designed the Korean Radiation Oncology Group 09-03 phase III clinical trial to compare accelerated hypofractionated radiation therapy (RT) using a concomitant boost to the gross tumor volume (GTV) with conventionally fractionated 60-Gy RT in patients with stage III unresectable non-small cell lung cancer (NSCLC).Methods and Materials: A conventionally fractionated RT group (arm 1; 124 patients) received a 2-Gy daily dose to a total cumulative dose of 44 Gy to the planning target volume (PTV) in 22 fractions and 60 Gy to the GTV in 30 fractions over 6 weeks. A hypofractionated RT group (arm 2; 142 patients) received a 1.8-Gy daily dose to the PTV with a synchronous boost of 0.6 Gy to the GTV, for total cumulative doses of 45 Gy to the PTV and 60 Gy to the GTV in 25 fractions over 5 weeks. All patients received concurrent weekly chemotherapy consisting of paclitaxel and cisplatin.Results: The objective response rate of all patients was 86.5% (arm 1, 84.6%; arm 2, 88.1%; P = .612). The median overall survival was 26 months (arm 1, 26 months; arm 2, 27 months; P = .508). The median progression-free survival was 11 months (arm 1, 10 months; arm 2, 13 months; P = .295). The local tumor control rates at 2 and 5 years were 58.3% and 50.7%, respectively (arm 1, 62.4% and 51.0%, respectively; arm 2, 54.0% and 48.6%, respectively; P = .615). There were no significant between-group differences in the cumulative incidence of grade ≥3 radiation pneumonitis (P = .134) or radiation esophagitis (P = .539).Conclusions: This clinical trial did not confirm the superiority of accelerated 2.4-Gy hypofractionated RT compared with conventional 2-Gy fractionation in patients with unresectable stage III NSCLC undergoing concurrent chemoradiation therapy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the metabolic response of uterine cervix and pelvic lymph nodes (LNs) using consecutive 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) immediately after RT and to correlate survival outcome with the metabolic response. Methods and Materials: We retrospectively reviewed 48 patients with cervical cancer who had positive pelvic LNs by preradiation therapy (pre-RT) PET/CT. All patients underwent PET/CT scans immediately after RT (inter-RT PET/CT) after median 63 Gy to the gross LNs. The metabolic response of the LNs was assessed quantitatively and semiquantitatively by measurement of the maximal standardized uptake value (SUVmax). Results: Classifying the metabolic response of all nodal lesions, 37 patients (77%) had LNs with complete metabolic response on the inter-RT PET/CT (LNCMRi), and 11 patients had a non-LNCMRi, including 4 patients with progressive metabolic disease. The overall 3-year survival rates were 83% for the patients with LNCMRi and 73% for the non-LNCMRi group (P=.038). The disease-free survival for patients with LNCMRi were significantly better than that for the non-LNCMRi group (71% vs 18%, respectively, P<.001). The 3-year distant metastasis-free survival rates were 79% for the patients with LNCMRi and 27% for the non-LNCMRi group (P<.001). There were no statistically significant differences in overall survival (76% vs 86%, respectively, P=.954) and disease-free survival rates (58% vs 61%, respectively, P=.818) between the CMR of primary cervical tumor and the non-CMR groups. Conclusions: The results showed a significant correlation between survival outcome and the interim metabolic response of pelvic LNs. CMR of nodal lesion on inter-RT PET/CT had excellent overall survival, disease-free survival and distant metastasis-free survival rates. This suggested that PET/CT immediately after RT can be a useful tool for the evaluation of the interim response of the LNs and identify a subset of patients with a high risk of recurrence and poor survival in patients with cervical cancer with initial positive LNs. [Copyright &y& Elsevier]

Background and purpose The efficacy of prophylactic extended-field irradiation (EFI) plus concomitant cisplatin in patients with locally advanced uterine cervical cancer (LAUCC) is unknown, nor is it known whether tumor carbonic anhydrase IX (CA9) expression level, a hypoxia marker, influences survival outcome. Material and methods We recruited patients with UCC, FIGO stage IB1 with pelvic lymph node (LN) metastases to IVA with negative para-aortic LN on PET/CT. CA9 expression was examined and patients were randomized to either EFI or pelvic only radiotherapy (PRT) in each CA9 group. The primary outcomes were para-aortic recurrence-free survival (PARFS) and disease-free survival (DFS). Results Between 2006 and 2011, 79 patients with CA9-positive and 37 with CA9-negative tumors were enrolled, respectively. The median follow-up period was 69.2 months (range 6.8–102.1). For CA9-positive patients, 5-year PARFS was 100% and 81.7% for those receiving EFI and PRT ( p = 0.007), respectively. DFS was 78.6% for EFI and 71.3% for PRT patients ( p = 0.353). For CA9-negative patients, 5y PARFS was 100% and 94.1% for EFI and PRT ( p = 0.317), respectively. DFS was 100% for EFI and 70.7% for PRT ( p = 0.018). Conclusion EFI significantly reduced recurrences in PAN in patients with CA9-positive tumors, but survival outcome was not improved, due to high local recurrence and high distant metastases rates. This study indicates the necessity for new therapeutic strategies for LAUCC patients whose tumors show high CA9 expression. [ABSTRACT FROM AUTHOR]

The use of natural killer (NK) cells is a promising approach in the field of cancer immunotherapy; however, combination treatments are required to enhance the effects of NK cell immunotherapy. In this study, we assessed the potential of irradiation and cisplatin as a chemoradiotherapy (CRT) regimen to augment the effects of NK cell immunotherapy in head and neck squamous cell carcinoma (HNSCC). NK cells were expanded using our recently established K562-OX40 ligand and membrane-bound interleukin (IL)-18 and IL-21 feeder cells in the presence of IL-2/IL-15 from peripheral blood of healthy donors. The results showed an increase in the purity of NK cells and expression of activation markers such as NKG2D and lymphocyte function–associated antigen 1 during the expansion process, which is positively correlated to the NK cell infiltration and overall survival in patients with HNSCC. CRT induced NK cell activation ligand (ULBP2) and adhesion molecules (ICAM-1, -2 and -3) on HNSCC, leading to enhanced cytotoxicity of NK cells against HNSCC. Our findings suggest that the NK cells have a potent anti-tumor effect in combination with CRT against HNSCC. We hypothesized that NK cells expanded by our recently established K562-OX40L-mbIL-18/21 feeder cells can increase the expression of NKG2D and LFA-1, thereby increasing the recognition and adhesion, respectively. In contrast, the treatment of cancer cells with irradiation (RT) and cisplatin not only directly killed HNSCC but also upregulated the expression levels of MICA and MICB, ULBP 1 and ULBP 2, and ICAM-1, 2 and 3 on HNSCC. The upregulation of these markers will enhance NK cells–HNSCC interaction, thereby leading to enhanced NK cell killing activity against HNSCC cells. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: We investigated whether adoptive cell therapy with ex vivo-activated natural killer (NK) cells enhances the therapeutic efficacy of local tumor radiation therapy (RT) using a human triple-negative breast cancer xenograft model.Methods and Materials: NK cells from healthy donors were expanded ex vivo. MDA-MB-231/Luc-GFP cells were subcutaneously implanted into the thighs of NSG mice. The animals were divided into 4 experimental groups: control, RT, NK, and RT + NK. On day 17 after tumor implantation, tumors from the RT groups were irradiated. The ex vivo-expanded NK cells were intravenously administered twice, on days 17 and 19. Primary and secondary tumors were evaluated using long-term bioluminescence imaging, and histopathology was performed on resected tumor tissue specimens.Results: The luciferase signals of the primary tumors in the RT + NK group were significantly lower than those of comparably sized primary tumors in the RT group. The long-term migration and infiltration of NK cells into the primary tumor sites were significantly higher in RT + NK than in NK mice. Moreover, lymphatic metastasis to the axillary lymph nodes and liver and lung metastases were highly suppressed in the RT + NK group, as demonstrated by BLI and p53 immunohistochemistry. The long-term survival of the RT + NK group was significantly higher than that of the RT or NK groups.Conclusions: Reduction in tumor burden by combining RT and systemic NK cell therapy improved the suppression of primary tumor growth, with efficient NK cell migration and penetration into the primary tumor site. Administered NK cells were maintained in the primary tissue for a significantly longer time in RT + NK group compared with NK group. Both lymphatic spread and distant metastasis to the lungs and liver were effectively suppressed by the combined therapy. [ABSTRACT FROM AUTHOR]

Background aims Irradiation enhances the adhesion between natural killer (NK) cells and target cells by up-regulating intercellular adhesion molecule-1 (ICAM-1) on target cells. Therefore, we investigated the effect of irradiation-induced ICAM-1 expression on human cancer cells on NK cell–mediated cytotoxicity. Methods Expression levels of ICAM-1 on the target cell surface before and after irradiation of six human cancer cell lines (HL60, SKBR-3, T47D, HCT-116, U937 and U251) were analyzed by flow cytometry. Ex vivo expansion of NK cells from human peripheral blood mononuclear cells was performed by co-culture with irradiated K562 cells. The related adhesion molecule lymphocyte function–associated antigen 1 (LFA-1) on NK cells was analyzed by flow cytometry. An enzyme-linked immunosorbent assay was used to detect interferon-γ (IFN-γ), and WST-8 assays were performed to check NK cell cytotoxicity. Finally, blocking assays were performed using monoclonal antibodies against ICAM-1 or LFA-1. Results LFA-1 expression increased on NK cells after expansion ( P  <   0.001). The expression of ICAM-1 was significantly upregulated by irradiation after 24 h in various cell lines, including HL60 ( P  <   0.001), SKBR-3 ( P  <   0.001), T47D ( P  <   0.001) and U937 ( P  <   0.001), although the level of expression depended on the cell line. ICAM-1 expression was extremely low before and after irradiation in U251 cells. NK cell–mediated cytotoxicity increased after irradiation of HL60 ( P  <   0.001), SKBR-3 ( P  <   0.001), T47D ( P  = 0.003), and U937 ( P  = 0.004) cells, in which ICAM-1 expression was significantly increased after irradiation. IFN-γ production by NK cells in response to HL60 ( P  <   0.001) and T47D ( P  = 0.011) cells significantly increased after irradiation. NK cell–mediated cytotoxicity against irradiated SKBR-3 ( P  <   0.001) and irradiated T47D cells ( P  = 0.035) significantly decreased after blocking of ICAM-1. Blocking of LFA-1 on NK cells resulted in reduced cytotoxicity against irradiated HL60 ( P  <   0.001) and irradiated SKBR-3 ( P  <   0.001). Conclusions Irradiation upregulates ICAM-1 expression on the surface of human cancer cells and enhances activated NK cell–mediated cytotoxicity. Therefore, irradiation combined with NK cell therapy may improve the antitumor effects of NK cells. [ABSTRACT FROM AUTHOR]

Background and purpose To evaluate the pre-treatment clinical factors affecting recurrence and survival in rectal cancer patients who receive preoperative chemoradiotherapy (CRT) and curative surgery. Methods and materials The clinical data of 1782 patients from 8 institutions in Korea were analyzed. The potential prognostic factors that could be acquired before radical surgery were patient age, gender, clinical T and N stages, tumor size and location, tumor grade, carcinoembryonic antigen (CEA) level, and the concurrent chemotherapy regimen. The relapse-free survival (RFS), overall survival (OS), and cumulative incidence of locoregional and distant recurrence were analyzed according to the clinical factors. Results Among the pre-treatment clinical factors, tumor grade, pre-CRT CEA level, tumor location, and clinical N stage were significant prognostic factors affecting the RFS. The high-grade tumor was the hazardous factor for RFS on the multivariate analysis [Hazard ratio (HR), 1.83; 95% confidence interval (CI), 1.29–2.58; p = 0.001]. The 5-year RFS rate for high-grade tumors was significantly lower than that for low-grade tumors (63.8% vs. 78.8%, p < 0.001). The tumor grade was a significant prognostic factor for distant recurrence (HR, 1.83, 95% CI, 1.29–2.58; p < 0.001), but not for locoregional recurrence (HR, 1.49, 95% CI, 0.68–3.26; p = 0.320) on the multivariate analysis. The 5-year OS rate for high-grade tumors was significantly lower than that for low-grade tumors (70.6% vs. 85.5%, p < 0.001). Conclusion The tumor grade is the significant pre-treatment clinical factor for recurrence and survival in rectal cancer patients who receive preoperative CRT and curative surgery. [ABSTRACT FROM AUTHOR]

Background and purpose The Korean Radiation Oncology Group evaluated the significance of carcinoembryonic antigen (CEA) levels both as a predictor of tumor response after CRT and as a prognosticator for recurrence-free survival. Methods and materials 1804 rectal cancer patients, staged cT3–4N0–2M0, participated in a multicenter study. The patients were administered preoperative radiation of 50.4 Gy in 28 fractions with 5-FU or capecitabine, followed by total mesorectal excision. Patients with elevated CEA levels (>5 ng/mL) were matched at a 1 ( n = 595):1 ( n = 595) ratio with patients with normal CEA (⩽5 ng/mL). The tumor response after CRT and the recurrence-free survival (RFS) rates were evaluated and compared between two arms. Results An elevated CEA level ( p < 0.001) was determined to be a significant negative predictor of downstaging after CRT. The downstaging rate was 42.9% for normal CEA and 23.4% for elevated CEA. A multivariate analysis also revealed that cT ( p = 0.021) and cN classification ( p = 0.001), tumor size ( p = 0.002), and tumor location from the anal verge ( p = 0.006) were significant predictors for tumor downstaging. The 5-year RFS rates were significantly higher for the normal CEA arm than for the elevated CEA arm (74.2 vs. 63.5%, p < 0.001). Conclusions Elevated CEA (>5 ng/mL) is a negative predictor of tumor downstaging after CRT and also has a negative impact on RFS in rectal cancer. [ABSTRACT FROM AUTHOR]

Abstract: Based on per-field data, 3 dose-volume histogram (DVH) is designed to calculate 3-dimensional (3D) dose using patient-computed tomography (CT) for an intensity-modulated radiation therapy (IMRT) delivery quality assurance (DQA) process measured with diode detector arrays. In this study, the characteristics and suitability of 3DVH for an IMRT DQA process were evaluated by assessment of clinically applied results. The DQA plans were prepared with a 2D diode detector array (MapCHECK 2) for 20 IMRT patients (10 with head and neck cancer and 10 with prostate cancer), and the matching rate between the calculated dose and the measured dose was analyzed. The relative dose differences between the original IMRT plan and the recalculated plan by 3DVH were evaluated for tumor target and organs at risk (OARs). Confidence limits (CLs) were determined for quantification of the degree of agreement that should be expected in each DQA method. The individual CLs for DQA accuracy of 3D dosimetric evaluation in the tumor target and OARs were also calculated to evaluate the differences compared with conventional 2D-based DQA results. The matching rates were sufficient to validate the accuracy of IMRT DQA analyses and the calculated CL values were reasonable values considering the normal criteria of our institution. The 3DVH analysis generally had better matching rate than per-field measurement analysis and the CL values for OARs were better than those for the planning target volume (PTV). The usefulness of the 3DVH tool was verified for IMRT DQA from the point of view of dose evaluation in the corresponding patient's CT data. It also enables dosimetric evaluation in each important structure (PTV and OARs), which can promote more effective evaluation of DQA error in terms of tumor treatment and side effects. [Copyright &y& Elsevier]

Purpose: To perform a prospective phase II study to investigate the efficacy and safety of preoperative pelvic radiation therapy and concomitant small-field boost irradiation with 5-fluorouracil and leucovorin for 5 weeks in locally advanced rectal cancer patients. Methods and Materials: Sixty-nine patients with locally advanced, nonmetastatic, mid-to-lower rectal cancer were prospectively enrolled. They had received preoperative chemoradiation therapy and total mesorectal excision. Pelvic radiation therapy of 43.2 Gy in 24 fractions plus concomitant boost radiation therapy of 7.2 Gy in 12 fractions was delivered to the pelvis and tumor bed for 5 weeks. Two cycles of 5-fluorouracil and leucovorin were administered for 3 days in the first and fifth week of radiation therapy. The pathologic response, survival outcome, and treatment toxicity were evaluated for the study endpoints. Results: Of 69 patients, 8 (11.6%) had a pathologically complete response. Downstaging rates were 40.5% for T classification and 68.1% for N classification. At the median follow-up of 69 months, 36 patients have been followed up for more than 5 years. The 5-year disease-free survival (DFS) and overall survival rates were 66.0% and 75.3%, respectively. Higher pathologic T (P = .045) and N (P = .032) classification were significant adverse prognostic factors for DFS, and high-grade histology was an adverse prognostic factor for both DFS (P = .025) and overall survival (P = .031) on the multivariate analysis. Fifteen patients (21.7%) experienced grade 3 or 4 acute toxicity, and 7 patients (10.1%) had long-term toxicity. Conclusion: Preoperative pelvic radiation therapy with concomitant boost irradiation with 5-fluorouracil and leucovorin for 5 weeks showed acceptable acute and long-term toxicities. However, the benefit of concomitant small-field boost irradiation for 5 weeks in rectal cancer patients was not demonstrated beyond conventional irradiation for 6 weeks in terms of tumor response and survival. [Copyright &y& Elsevier]

Purpose: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with curative intent in patients with stage IVB cervical cancer initially presenting with paraortic and left supraclavicular lymph node metastases. Methods and Materials: The medical records of 25 patients with both paraortic and left supraclavicular lymph nodal metastases (group I) were reviewed and compared with those of 101 women with paraortic lymph node metastases alone (group II). Group I received a mean 59.4 Gy to the paraortic and left supraclavicular areas and 50.4 Gy to the pelvis, followed by 30 Gy of high-dose-rate brachytherapy in 6 fractions. Group II received the same dose to the paraortic area and pelvis followed by intracavitary brachytherapy. All patients received platinum-based chemotherapy simultaneously. Results: Of the 25 patients in group I, 16 (64%) experienced acute grade 3-4 hematologic toxicities, and 1 had a late grade 3 genitourinary toxicity. Complete responses, including the primary mass and pelvic, paraortic, and left supraclavicular lymph nodes, were observed in 13 patients (52%). At a median follow-up of 32 months for surviving patients, 3 experienced in-field failure, 6 showed distant failure, and 9 showed both. The 3-year overall and disease-free survival rates were 49% and 33%, respectively. In comparison, of the 101 patients in group II, 16 showed in-field failure, 14 experienced distant failure, and 11 showed both. The 3-year overall and disease-free survival rates were 69% and 57%, respectively. Conclusions: Curative CCRT is feasible in patients with stage IVB cervical cancer presenting with paraortic and left supraclavicular lymph nodal metastases, with acceptable late toxicity and high response rates, despite high rates of acute hematologic toxicity. [Copyright &y& Elsevier]

Abstract: The cone-beam CT (CBCT), which is acquired using an on-board imager (OBI) attached to a linear accelerator, is used effectively in the verification of setup accuracy for lung radiation surgery. In this study, the respiratory organ motional effect on the CBCT was evaluated with a properly devised phantom system, and the level of possible error in conditions of a real clinical process was assessed. In a comparison study between the CBCT in static status and CBCT images acquired in 20 different motional cases, we confirmed that the image quality and information of CBCT were degraded, with an increase of motional ranges in the region of inhomogeneous structures. The 4D-CT MIP (50∼55%) for the planning of lung radiation surgery and the 4D-CT MIP (full phase) were compared with CBCT in the various motional cases for the evaluation of the influence of the motional effect on CBCT in the process of the setup error correction. The average ratio of relative difference between plan CT: 4D-CT MIP (50%∼55%) and CBCT was 5.79% and between plan CT: 4D-CT MIP (50%∼55%) and 4D-CT MIP (full phase) was 42.95% in the phantom study. In the analysis of clinical cases of lung radiation surgery, the gross tumor volumes were compared in each CT image. The average ratio of relative difference between plan CT: 4D-CT MIP (50∼55%) and CBCT was 10.72% and between plan CT: 4D-CT MIP (50∼55%) and 4D-CT MIP (full phase) was 28.19%. These results showed that, although a respiratory organ motional effect on CBCT introduced variation in image quality, the error as a result of this variation could be estimated relatively low in the setup error correction for a gated-lung radiation surgery when the planning was performed in 4D-CT MIP (50∼55%), which already included a related signal of motional effect. [Copyright &y& Elsevier]

Abstract: The present study evaluated the pretreatment expression patterns of hMLH1, MDM2, p53, and pRb protein to determine whether these could predict the outcome of definitive concurrent chemoradiotherapy (CCRT) in 51 patients with stage I–IVa esophageal squamous cell carcinoma. High immunoreactivies of hMLH1, MDM2, p53, and pRb were detected in 90.2%, 19.6%, 27.5%, and 66.7% of entire patients, respectively. High hMLH1 expression was found to favor earlier stage, less locoregional failure, and longer cause-specific survival, and all were with significance. However, the expressions of MDM2, p53, and pRb were not found to be clinically significant. Thirty-three patients with high hMLH1 and pRb expression tended to survive longer than four patients with low hMLH1 and pRb expression. We suggest that the expression of hMLH1 is a potential marker of tumor response and survival. Determinations of this protein expression might be useful for selecting esophageal squamous cell carcinoma patients for definitive CCRT. [Copyright &y& Elsevier]

Purpose: To evaluate the metabolic response of uterine cervix and pelvic lymph nodes (LNs) using consecutive 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) immediately after RT and to correlate survival outcome with the metabolic response. Methods and Materials: We retrospectively reviewed 48 patients with cervical cancer who had positive pelvic LNs by preradiation therapy (pre-RT) PET/CT. All patients underwent PET/CT scans immediately after RT (inter-RT PET/CT) after median 63 Gy to the gross LNs. The metabolic response of the LNs was assessed quantitatively and semiquantitatively by measurement of the maximal standardized uptake value (SUVmax). Results: Classifying the metabolic response of all nodal lesions, 37 patients (77%) had LNs with complete metabolic response on the inter-RT PET/CT (LNCMRi), and 11 patients had a non-LNCMRi, including 4 patients with progressive metabolic disease. The overall 3-year survival rates were 83% for the patients with LNCMRi and 73% for the non-LNCMRi group (P=.038). The disease-free survival for patients with LNCMRi were significantly better than that for the non-LNCMRi group (71% vs 18%, respectively, P<.001). The 3-year distant metastasis-free survival rates were 79% for the patients with LNCMRi and 27% for the non-LNCMRi group (P<.001). There were no statistically significant differences in overall survival (76% vs 86%, respectively, P=.954) and disease-free survival rates (58% vs 61%, respectively, P=.818) between the CMR of primary cervical tumor and the non-CMR groups. Conclusions: The results showed a significant correlation between survival outcome and the interim metabolic response of pelvic LNs. CMR of nodal lesion on inter-RT PET/CT had excellent overall survival, disease-free survival and distant metastasis-free survival rates. This suggested that PET/CT immediately after RT can be a useful tool for the evaluation of the interim response of the LNs and identify a subset of patients with a high risk of recurrence and poor survival in patients with cervical cancer with initial positive LNs. [ABSTRACT FROM AUTHOR]