Optimal treatment strategies for small cell carcinoma of the uterine cervix: A retrospective multi-center study (KROG 19-03).

OBJECTIVE: This multi-institutional study aimed to identify the optimal treatment strategy for small cell carcinoma of the cervix. STUDY DESIGN: We retrospectively collected the medical records of 166 patients diagnosed with small cell carcinoma of the uterine cervix from January 2000 to December 2015 from 13 institutions of the Korean Radiation Oncology Group. After excluding 18 (10.8 %) patients who initially had distant metastasis, the treatment outcomes of 148 patients were analyzed. RESULTS: After a median 46.4 (1.4-231.9) months of follow-up, the 5-year progression-free survival (PFS) and overall survival (OS) rates of all patients were 45.9 % and 63.5 %, respectively. Distant metastasis was the dominant pattern of failure occurring in 67 patients (45.3 %). We stratified the patients according to the primary local treatment: primary surgery (n = 119), primary radiotherapy (RT) (n = 26), and no local treatment group (n = 3). Although the primary RT group had advanced disease (FIGO stage ≧ IIB) more frequently than the primary surgery group (80.8 % vs. 47.9 %), the PFS and OS did not differ between the groups in multivariate analysis. CONCLUSION: Definitive RT is a reasonable local treatment option for small cell cervical cancer, particularly for advanced cases. Given the high rates of distant relapse, an effective systemic therapy protocol is warranted for small cell cervical cancer patients.

Preclinical platform for long-term evaluation of immuno-oncology drugs using hCD34+ humanized mouse model.

BACKGROUND: Well-characterized preclinical models are essential for immune-oncology research. We investigated the feasibility of our humanized mouse model for evaluating the long-term efficacy of immunotherapy and biomarkers. METHODS: Humanized mice were generated by injecting human fetal cord blood-derived CD34+ hematopoietic stem cells to NOD-scid IL2rγnull (NSG) mice myeloablated with irradiation or busulfan. The humanization success was defined as a 25% or higher ratio of human CD45+ cells to mice peripheral blood mononuclear cells. RESULTS: Busulfan was ultimately selected as the appropriate myeloablative method because it provided a higher success rate of humanization (approximately 80%) and longer survival time (45 weeks). We proved the development of functional T cells by demonstrating the anticancer effect of the programmed cell death-1 (PD-1) inhibitor in our humanized mice but not in non-humanized NSG mice. After confirming the long-lasting humanization state (45 weeks), we further investigated the response durability of the PD-1 inhibitor and biomarkers in our humanized mice. Early increase in serum tumor necrosis factor α levels, late increase in serum interleukin 6 levels and increase in tumor-infiltrating CD8+ T lymphocytes correlated more with a durable response over 60 days than with a non-durable response. CONCLUSIONS: Our CD34+ humanized mouse model is the first in vivo platform for testing the long-term efficacy of anticancer immunotherapies and biomarkers, given that none of the preclinical models has ever been evaluated for such a long duration.

STING activation reprograms tumor vasculatures and synergizes with VEGFR2 blockade.

The stimulator of interferon genes (STING) signaling pathway is a critical link between innate and adaptive immunity, and induces anti-tumor immune responses. STING is expressed in vasculatures, but its role in tumor angiogenesis has not been elucidated. Here we investigated STING-induced tumor vascular remodeling and the potential of STING-based combination immunotherapy. Endothelial STING expression was correlated with enhanced T-cell infiltration and prolonged survival in human colon and breast cancer. Intratumoral STING activation with STING agonists (cGAMP or RR-CDA) normalized tumor vasculatures in implanted and spontaneous cancers, but not in STING-deficient mice. These were mediated by upregulation of type I/II interferon genes and vascular stabilizing genes (e.g., Angpt1, Pdgfrb, and Col4a). STING in non-hematopoietic cells is as important as STING in hematopoietic cells to induce a maximal therapeutic efficacy of exogenous STING agonist. Vascular normalizing effects of STING agonists were dependent on type I interferon signaling and CD8+ T cells. Notably, STING-based immunotherapy was maximally effective when combined with VEGFR2 blockade and/or immune checkpoint blockade (αPD-1 or αCTLA-4), leading to complete regression of immunotherapy-resistant tumors. Our data show that intratumoral STING activation can normalize tumor vasculature and the tumor microenvironment, providing a rationale for combining STING-based immunotherapy and anti-angiogenic therapy.

Radiation-Induced Phosphorylation of Serine 360 of SMC1 in Human Peripheral Blood Mononuclear Cells.

In the event of a mass casualty radiation scenario, biodosimetry has the potential to quantify individual exposures for triaging and providing dose-appropriate medical intervention. Structural maintenance of chromosomes 1 (SMC1) is phosphorylated in response to ionizing radiation. The goal of this study was to develop a new biodosimetry method using SMC1 phosphorylation as a measure of exposure to radiation. In the initial experiments, two normal human cell lines (WI-38VA-13 and HaCaT) and four lymphoblastoid cell lines were irradiated, and the levels of SMC1 phosphorylation at Ser-360 and Ser-957 were assessed using Western blotting. Subsequently, similar experiments were performed using peripheral blood mononuclear cells (PBMCs) obtained from 20 healthy adults. Phosphorylation of SMC1 at Ser-957 and Ser-360 was increased by exposure in a dose-dependent manner, peaked at 1-3 h postirradiation and then decreased gradually. Ser-360 was identified as a new phosphorylation site and was more sensitive to radiation than Ser-957, especially at doses below 1 Gy. Our results demonstrate a robust ex vivo response of phospho-SMC1-(Ser-360) to ionizing radiation in human PBMCs. Detection of phosphorylation at Ser-360 in SMC1 could be used as a marker of radiation exposure. Our findings suggest that it is feasible to measure blood cell-based changes in the phosphorylation level of a protein as an ex vivo radiation exposure detection method, even after low-dose exposure.

Clinical significance of the post-radiotherapy 18F-fludeoxyglucose positron emission tomography response in nasopharyngeal carcinoma.

OBJECTIVE: The aim of the present study was to evaluate the clinical significance of the post-radiotherapy 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) response for detecting residual disease and predicting survival outcome in patients with nasopharyngeal cancer. METHODS: We reviewed 143 patients with nasopharyngeal cancer who underwent 18F-FDG PET within 6 months after completion of radiotherapy between 2001 and 2012. 18F-FDG PET findings at the primary tumor (T-) and regional lymph nodes (N-) were separately assessed and considered negative [PET (-)] or positive [PET (+)] depending on the remaining focal increased uptake of 18F-FDG that was greater than that of the surrounding muscle or blood vessels. The standard of reference was histopathological confirmation or clinical/imaging follow-up. Overall survival (OS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRRFS) rates were estimated from the date of the start of radiotherapy. RESULTS: The median follow-up period was 73 months (range, 9-182 months). Overall, 83 and 66% of patients achieved T-PET (-) and N-PET (-) responses, and the negative-predictive values (NPVs) for T- and N- were 100 and 99%, respectively. The sensitivity, specificity, and positive-predictive value were 100, 84, and 8% for T-, and 67, 80, and 7% for N-, respectively. The 5-year OS, DMFS, and LRRFS rates were 83, 83, and 87%, respectively, and patients with N-PET (+) with SUVmax >2.5 showed significantly inferior 5-year OS and DMFS rates than patients with N-PET (-) or N-PET (+) with SUVmax ≤2.5 (44 vs 86%, p = 0.004; 36 vs 85%, p < 0.001). CONCLUSION: In patients that have received definitive (chemo)radiotherapy for nasopharyngeal cancer, 18F-FDG PET within 6 months of completion of treatment has a high NPV for predicting residual disease and is prognostic for long-term treatment outcomes. Patients with remaining focal increased uptake of 18F-FDG at lymph nodes may benefit from more aggressive treatments, and further studies are needed to validate the clinical significance of post-radiotherapy 18F-FDG PET. ADVANCES IN KNOWLEDGE: We found that post-radiotherapy 18F-FDG PET findings have a high NPV for detecting residual disease and are a significant prognostic factor for treatment outcomes.

Evaluation of predictive factors of vertebral compression fracture after conventional palliative radiotherapy for spinal metastasis from colorectal cancer.

OBJECTIVE Delayed consequences of spinal radiotherapy (RT), including vertebral compression fracture (VCF), are critical complications. However, the predisposing factors that contribute to VCF after conventional RT are unclear. The aim of this study was to assess the incidence of VCF and to determine the predictors of VCF following conventional spinal RT specific to colorectal cancer (CRC). METHODS The authors retrospectively reviewed 237 spinal segments (147 metastatic and 90 nonmetastatic) in 53 patients with CRC who underwent RT with a median total dose of 30 Gy in 10 fractions between January 2007 and December 2014. The primary end point was the development of a VCF following RT, either de novo VCF or the progression of a baseline VCF. VCFs were assessed using the spinal instability neoplastic score (SINS) criteria. RESULTS Among all 237 spinal segments, 22 VCFs (9.3%) were observed following RT, including 13 de novo and 9 progressive fractures, and the median time to VCF was 4 months. All VCFs developed in metastatic spines. Among 147 metastatic spinal segments, 22 fractures were observed, with a 12-month cumulative incidence of VCF of 14.8%. Results of multivariable analysis indicated sex (p = 0.023) and SINS class II/III (p < 0.001) as risk factors related to development of a VCF in metastatic spinal segments. Among the SINS criteria, a lytic tumor and the presence of a baseline VCF were identified as predictors of VCF in metastatic spinal segments. CONCLUSIONS In osteolytic or mixed lesions that were predominant in spinal metastases of CRC, the incidence of VCF was not negligible, even in patients treated with conventional spinal RT. This was especially evident in patients with spinal metastases with a SINS score ≥ 7. Presence of a baseline VCF after spinal RT is a predictor of VCF development and should be observed carefully.

Tumor Boost Using External Beam Radiation in Cervical Cancer Patients Unable to Receive Intracavitary Brachytherapy: Outcome From a Multicenter Retrospective Study (Korean Radiation Oncology Group 1419).

PURPOSE: We conducted this study to evaluate the outcomes of external-beam radiotherapy tumor boost (EBRT-B) in cervical cancer patients who could not receive intracavitary brachytherapy. METHODS: A total of 11 hospitals provided the data of patients who received EBRT-B during the period from January 2005 through October 2012. RESULTS: A total of 75 patients were included. The median radiotherapy dose was 46 Gy (range, 40-54 Gy) for whole pelvis and 24 Gy (range, 9-35 Gy) for EBRT-B. Initial tumor responses assessed at 2 to 6 months after radiotherapy were as follows: 46 with complete response, 22 with partial response, 2 with stable disease, and 3 with progressive disease. After a median follow-up time of 33 months, 30 patients (40.0%) showed disease progression including 21 (28.0%) with local progression. The 5-year local failure-free survival rate was 70.0%. Achieving complete response at the first follow-up visit and an overall treatment time of 53 days or less were significantly related to favorable local failure-free survival. The rate of grade 3 or higher toxicity was 2.6%. CONCLUSIONS: Approximately 70% of patients had local tumor control after curative radiotherapy using EBRT-B. Early tumor response and overall treatment time of 53 days or less were closely associated with favorable local control.

The Prognostic Impact of the Number of Metastatic Lymph Nodes and a New Prognostic Scoring System for Recurrence in Early-Stage Cervical Cancer with High Risk Factors: A Multicenter Cohort Study (KROG 15-04).

PURPOSE: We aimed to assess prognostic value of metastatic pelvic lymph node (mPLN) in early-stage cervical cancer treated with radical surgery followed by postoperative chemoradiotherapy. Also, we sought to define a high-risk group using prognosticators for recurrence. MATERIALS AND METHODS: A multicenter retrospective study was conducted using the data from 13 Korean institutions from 2000 to 2010. A total of 249 IB-IIA patients with high-risk factors were included. We evaluated distant metastasis-free survival (DMFS) and disease-free survival (DFS) in relation to clinicopathologic factors including pNstage, number of mPLN, lymph node (LN)ratio (number of positive LN/number of harvested LN), and log odds of mPLNs (log(number of positive LN+0.5/number of negative LN+0.5)). RESULTS: In univariate analysis, histology (squamous cell carcinoma [SqCC] vs. others), lymphovascular invasion (LVI), number of mPLNs (≤ 3 vs. > 3), LN ratio (≤ 17% vs. > 17%), and log odds of mPLNs (≤ ‒0.58 vs. > ‒0.58) were significant prognosticators for DMFS and DFS. Resection margin involvement only affected DFS. No significant survival difference was observed between pN0 patients and patients with 1-3 mPLNs. Multivariate analysis revealed that mPLN > 3, LVI, and non-SqCC were unfavorable index for both DMFS (p < 0.001, p=0.020, and p=0.031, respectively) and DFS (p < 0.001, p=0.017, and p=0.001, respectively). A scoring system using these three factors predicts risk of recurrence with relatively high concordance index (DMFS, 0.69; DFS, 0.71). CONCLUSION: mPLN > 3 in early-stage cervical cancer affects DMFS and DFS. A scoring system using mPLNs > 3, LVI, and non-SqCC could stratify risk groups of recurrence in surgically resected early-stage cervix cancer with high-risk factors.

Clinical outcomes of multileaf collimator-based CyberKnife for spine stereotactic body radiation therapy.

OBJECTIVE: Stereotactic body radiotherapy (SBRT) for spinal metastases is becoming a prevalent therapeutic option. We aimed to evaluate the clinical feasibility and outcomes of the recently developed multileaf collimator (MLC)-based CyberKnife (CK-M) for spine SBRT. METHODS: We reviewed 119 patients of 144 cases with 229 lesions treated with CK between November 2014 and March 2016. The lesion features, dosimetric parameters and clinical outcomes were compared between fixed cone collimator based CK (CK-F) and CK-M. RESULTS: Of 144 cases, 78 and 66 were treated with CK-F and CK-M, respectively. CK-M achieved an adequate target volume coverage that was comparable with CK-F (median 92 vs 90%; p = 0.03) even in larger targets (median 64.2 vs 46.7 cm3; p = 0.01), respectively. CK-M showed an improvement in the gradient index (p < 0.001) and no difference in conformity (p = 0.16). With CK-M, the median beam delivery time was significantly reduced by 30% (to 34 vs 48 min; p < 0.001). CK-M showed 1 year local control rates that were comparable to CK-F (77 vs 78%, respectively; p = 0.83). CONCLUSION: CK-M exhibits dosimetric data and local control that are comparable with CK-F, but with significant treatment time reduction. CK-M could be widely used in spine SBRT. Advances in knowledge: Given the recently developed MLC in CK, we aimed to evaluate the clinical feasibility and outcomes of MLC compared with fixed cone-based CK. MLC showed equivalent plan quality and significant treatment time reduction with comparable radiological control. We report here MLC as an effective and tolerable treatment option in CK.

Adjuvant Treatment after Surgery in Stage IIIA Endometrial Adenocarcinoma.

PURPOSE: We evaluated the role of adjuvant therapy in stage IIIA endometrioid adenocarcinoma patients who underwent surgery followed by radiotherapy (RT) alone or chemoradiotherapy (CTRT) according to risk group. MATERIALS AND METHODS: A multicenter retrospective study was conducted including patients with surgical stage IIIA endometrial cancertreated by radical surgery and adjuvant RT or CTRT. Disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: Ninety-three patients with stage IIIA disease were identified. Nineteen patients (20.4%) experienced recurrence, mostly distant metastasis (17.2%). Combined CTRT did not affect DFS (74.1% vs. 82.4%, p=0.130) or OS (96.3% vs. 91.9%, p=0.262) in stage IIIA disease compared with RT alone. Patients with age ≥ 60 years, grade G2/3, and lymphovascular space involvement had a significantly worse DFS and those variables were defined as risk factors. The high-risk group showed a significant reduction in 5-year DFS (≥ 2 risk factors) (49.0% vs. 88.0%, p < 0.001) compared with the low-risk group (< 2). Multivariate analysis confirmed that more than one risk factor was the only predictor of worse DFS (hazard ratio, 5.45; 95% confidence interval, 2.12 to 13.98; p < 0.001). Of patients with no risk factors, a subset treated with RT alone showed an excellent 5-year DFS and OS (93.8% and 100%, respectively). CONCLUSION: We identified a low-risk subset of stage IIIA endometrioid adenocarcinoma patients who might be reasonable candidates for adjuvant RT alone. Further randomized studies are needed to determine which subset might benefit from combined CTRT.

A multicenter analysis of adjuvant therapy after surgery for stage IIIC endometrial adenocarcinoma: A Korean Radiation Oncology Group study (KROG 13-17).

OBJECTIVE: To investigate whether combined chemoradiotherapy (CTRT) confers a benefit for survival outcome over radiotherapy (RT) alone after primary surgery in patients with FIGO stage IIIC endometrial adenocarcinoma. METHODS: We conducted a multicenter retrospective study of patients with surgical stage IIIC endometrial cancer from 1990 to 2011. Adjuvant RT alone was performed in 85 patients (40.3%) and adjuvant CTRT in 126 patients (59.7%). Disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox proportional hazards model. RESULTS: Stage IIIC1 and stage IIIC2 accounted for 63% and 37%, respectively. FIGO IIIC2 had a higher recurrence rate than FIGO IIIC1 (38.5% vs. 29.3%, p=0.172). Five-year OS and DFS were lower in FIGO IIIC2 than FIGO IIIC1 (85.1% vs. 76.9%, p=0.417; 71.0% vs. 59.2%, p=0.108, respectively). Eighteen patients (13.5%) in stage IIIC1 developed PALN recurrence, whereas only one (3.3%) in stage IIIC2 had PALN recurrence (p=0.001). In multivariate analysis, predictors of DFS were parametrial invasion (HR, 3.49; 95% CI, 1.83-6.64; p<0.001), higher grade (HR, 2.78; 95% CI, 1.31-5.89; p=0.008), and >3 positive pelvic nodes (HR, 1.84; 95% CI, 1.11-3.05; p=0.019). Combined CTRT did not affect DFS or OS in IIIC1 and IIIC2 compared with RT alone. CONCLUSION: CTRT showed comparable survival outcome to RT alone. Half of relapses (46%) in stage IIIC1 occurred in PALN region, whereas relapse in stage IIIC2 primarily occurred in distant metastasis (90%). Future randomized studies are needed to determine which subgroup may be most likely to benefit from CCRT.

Risk factors for distant metastasis as a primary site of treatment failure in early-stage breast cancer.

The aim of this study was to evaluate the risk factors for distant metastasis (DM) as a primary site of failure in early-stage breast cancer. Data from 294 patients diagnosed with pathologic stage I or II breast cancer between January 2000 and December 2005 were reviewed retrospectively. Median follow-up duration was 81.0 months (range, 18-135 months). The total number of patients with DM without evidence of locoregional recurrence was 20 and the median time between surgery and DM was 29 months (range, 9-79 months). Median survival time was 38 months (range, 22-77 months) after operation. HER-2 positivity (p=0.015), T stage of tumor (p=0.012), and number of involved lymph nodes (p=0.008) were significant predictors of DM in the univariable analysis. Number of involved lymph nodes [p=0.005, hazards ratio (HR): 1.741; 95% confidence interval (CI): 1.178-2.574] and HER-2 positivity (p=0.018, HR: 2.888; 95% CI: 1.201-6.941) had a statistically significant effect on DM-free survival in the multivariable analysis. A cautious evaluation may be helpful when patients with risk factors for DM have symptoms implying the possibility of DM. To reduce DM, applying intensive therapy is needed after curative surgery for patients with high risk for DM.

Placenta-derived mesenchymal stem cells have an immunomodulatory effect that can control acute graft-versus-host disease in mice.

BACKGROUND AND AIMS: Immunomodulatory properties of mesenchymal stem cells (MSCs) have been applied to reduce the incidence of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). Among the various sources of MSCs that have immunomodulatory effects in vitro, only placenta-derived MSCs (PD-MSCs) have not been evaluated in an in vivo model of GVHD. In this study, we investigated the immunomodulatory properties of PD-MSCs in vitro and evaluated their clinical potential for controlling GVHD in an animal model. METHODS: A GVHD animal model was established by transplanting C57BL/6 donor bone marrow cells and spleen cells into lethally irradiated BALB/c recipient mice. To control GVHD, human PD-MSCs were transplanted into recipient mice (5 × 10(5) or 1 × 10(6) cells). RESULTS: PD-MSCs suppressed mitogen-stimulated T cell proliferation in vitro in a dose-dependent manner. Moreover, PD-MSCs inhibited cytokine secretion (interleukin-12, tumor necrosis factor-α and interferon-γ) of activated T cells. In vivo, the survival rate in the PD-MSC group (transplanted with 1 × 10(6) cells) was higher than that in the control group and histological scores were low in the PD-MSC group. CONCLUSION: We present the first evidence that human PD-MSCs can efficiently control GVHD in an HSCT in vivo model.

Esophageal tolerance to high-dose stereotactic radiosurgery.

PURPOSE: Esophageal tolerance is needed to guide the safe administration of stereotactic radiosurgery (SRS). We evaluated comprehensive dose-volume parameters of acute esophageal toxicity in patients with spinal metastasis treated with SRS. MATERIALS AND METHODS: From May 2008 to May 2011, 30 cases in 27 patients with spinal metastasis received single fraction SRS to targets neighboring esophagus. Endpoints evaluated include length (mm), volume (mL), maximal dose (Gy), and series of dose-volume thresholds from the dose-volume histogram (volume of the organ treated beyond a threshold dose). RESULTS: The median time from the start of irradiation to development of esophageal toxicity was 2 weeks (range, 1 to 12 weeks). Six events of grade 1 esophageal toxicity occurred. No grade 2 or higher events were observed. V15 of external surface of esophagus was found to predict acute esophageal toxicity revealed by multivariate analysis (odds radio = 1.272, p = 0.047). CONCLUSION: In patients with spinal metastasis who received SRS for palliation of symptoms, the threshold dose-volume parameter associated with acute esophageal toxicity was found to be V15 of external surface of esophagus. Restrict V15 to external surface of esophagus as low as possible might be safe and feasible in radiosurgery.

Treatment outcome in patients with triple negative early stage breast cancers compared with other molecular subtypes.

PURPOSE: To determine whether triple negative (TN) early stage breast cancers have poorer survival rates compared with other molecular types. MATERIALS AND METHODS: Between August 2000 and July 2006, patients diagnosed with stage I, II early stage breast cancers, in whom all three markers (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor [HER]-2) were available and treated with modified radical mastectomy or breast conserving surgery followed by radiotherapy, were retrospectively reviewed. RESULTS: Of 446 patients, 94 (21.1%) were classified as TN, 57 (12.8%) as HER-2 type, and 295 (66.1%) as luminal. TN was more frequently associated with young patients younger than 35 years old (p = 0.002), higher histologic grade (p < 0.0001), and nuclear (p < 0.0001). The median follow-up period was 78 months (range, 4 to 130 months). There were 9 local relapses (2.0%), 15 nodal (3.4%), 40 distant metastases (9.0%), and 33 deaths (7.4%) for all patients. The rates of 5-year OS, DFS, LFS, and DMFS for all patients were 95.5%, 89.9%, 95.4%, and 91.7%, respectively. There were no significant differences in OS, DFS, LFS, and DMFS between triple negative and other subtypes (p > 0.05). CONCLUSION: We found that patients with TN early stage breast cancers had no difference in survival rates compared with other molecular subtypes. Prospective study in homogeneous treatment group will need for a prognosis of TN early stage breast cancer.

Diagnostic value of neck node status using 18F-FDG PET for salivary duct carcinoma of the major salivary glands.

UNLABELLED: (18)F-FDG PET and PET/CT have shown clinical usefulness in the initial staging and follow-up of patients with salivary malignancy. Therefore, we evaluated the utility of (18)F-FDG PET in preoperative staging, determining the extent of neck node involvement, and surgical planning for patients with salivary duct carcinoma (SDC) of the major salivary gland. METHODS: We evaluated 18 patients with SDC who were assessed by (18)F-FDG PET and CT before surgery. The sensitivity, specificity, accuracy, and predictive values of CT and PET/CT for predicting the primary tumor site and determining the extent of neck node involvement at each dissected neck level were evaluated by comparing imaging findings with pathologic nodal stage. RESULTS: The median maximum standardized uptake value of the primary lesions and cervical nodes were 4.7 (range, 1.8-12.1) and 5.8 (range, 1.7-13.0), respectively. The sensitivities of (18)F-FDG PET and CT for predicting the primary tumor site were 100% (18/18) and 94.4% (17/18), respectively. In analyzing cervical lymph nodes at 73 dissected neck levels, (18)F-FDG PET had a sensitivity of 76.1%, a specificity of 96.3%, a positive predictive value of 97.2%, and a negative predictive value of 70.3%; the corresponding values for CT were 39.1%, 92.6%, 90.0%, and 47.2%, respectively. The sensitivity and negative predictive value were significantly higher for (18)F-FDG PET than for CT (P < 0.001 and P = 0.03, respectively).(18)F-FDG PET determination of the extent of neck node involvement changed the neck dissection regimen in 5 patients (27.8%). CONCLUSION: SDC of the major salivary gland is a highly metabolic tumor with high (18)F-FDG uptake. (18)F-FDG PET is useful for evaluating neck node status and for determining surgical planning in patients with major salivary gland SDC.

A comparison of preplan MRI and preplan CT-based prostate volume with intraoperative ultrasound-based prostate volume in real-time permanent brachytherapy.

PURPOSE: The present study compared the difference between intraoperative transrectal ultrasound (iTRUS)-based prostate volume and preplan computed tomography (CT), preplan magnetic resonance imaging (MRI)-based prostate volume to estimate the number of seeds needed for appropriate dose coverage in permanent brachytherapy for prostate cancer. MATERIALS AND METHODS: Between March 2007 and March 2011, among 112 patients who underwent permanent brachytherapy with (125)I, 60 image scans of 56 patients who underwent preplan CT (pCT) or preplan MRI (pMRI) within 2 months before brachytherapy were retrospectively reviewed. Twenty-four cases among 30 cases with pCT and 26 cases among 30 cases with pMRI received neoadjuvant hormone therapy (NHT). In 34 cases, NHT started after acquisition of preplan image. The median duration of NHT after preplan image acquisition was 17 and 21 days for cases with pCT and pMRI, respectively. The prostate volume calculated by different modalities was compared. And retrospective planning with iTRUS image was performed to estimate the number of (125)I seed required to obtain recommended dose distribution according to prostate volume. RESULTS: The mean difference in prostate volume was 9.05 mL between the pCT and iTRUS and 6.84 mL between the pMRI and iTRUS. The prostate volume was roughly overestimated by 1.36 times with pCT and by 1.33 times with pMRI. For 34 cases which received NHT after image acquisition, the prostate volume was roughly overestimated by 1.45 times with pCT and by 1.37 times with pMRI. A statistically significant difference was found between preplan image-based volume and iTRUS-based volume (p < 0.001). The median number of wasted seeds is approximately 13, when the pCT or pMRI volume was accepted without modification to assess the required number of seeds for brachytherapy. CONCLUSION: pCT-based volume and pMRI-based volume tended to overestimate prostate volume in comparison to iTRUS-based volume. To reduce wasted seeds and cost of the brachytherapy, we should take the volume discrepancy into account when we estimate the number of (125)I seeds for permanent brachytherapy.

Rationale for radiotherapy as a treatment modality in gastric mucosa-associated lymphoid tissue lymphoma.

PURPOSE: To provide a rationale for the use of local radiotherapy (RT) for the treatment of low-grade mucosa-associated lymphoid tissue lymphoma of the stomach (MLS). In addition, the clinicopathologic characteristics were analyzed. METHODS AND MATERIALS: The data of 72 patients with MLS, who underwent radical surgery between 1991 and 2001, were retrospectively reviewed. The depth of invasion into the gastric wall and the pattern of lymph node spread according to pathologic grade were analyzed. RESULTS: The patient age range was 24-77 years (median, 51 years). Of the 72 patients, 45 (62.5%) had low-grade and 27 (37.5%) had high-grade MLS; 44 (61%) had Stage I and 28 (39%) Stage II. The tumors were confined to the mucosa or submucosa in 43 patients (58.9%). Sixty-seven percent of low-grade tumors and 48% of high-grade tumors were confined to the mucosa and submucosa. Lymph node involvement was identified in 24.4% of the low-grade MLS patients and 63.0% of the high-grade MLS patients. In the low-grade group, lymph node involvement was limited to the perigastric lymph nodes in all cases except for one. One patient with tumor infiltration beyond the serosa had extensive lymph node involvement into the paraaortic and omental lymph nodes. CONCLUSION: Local RT to the stomach and regional lymphatics can be applied preferably instead of gastrectomy in patients with low-grade MLS who are negative for Helicobacter pylori or are refractory to anti-H. pylori therapy. The timing of RT and the exclusion criteria for RT should be determined in the future.

Primary NK/T cell lymphoma of the testis. A case report and review of the literature.

We report a case of aggressive 'nasal type' natural killer (NK)/T cell lymphoma initially presenting as a testicular tumor in a Korean man, which quickly took a fatal course by widespread dissemination. Histologically, the testicular mass showed a diffuse dense infiltrate of medium-sized and atypical large lymphoid cells with angiocentric and angiodestructive infiltration and areas of coagulative necrosis on hematoxylin-eosin stained sections. Immunophenotyping by immunohistochemistry yielded surface markers consistent with NK/T cell lymphoma. The Epstein-Barr virus genome was detected by in situ hybridization. During involved-field irradiation and chemotherapy following radical orchiectomy, the tumor disseminated shortly to the skin and soft tissue of his anterior chest wall and central nervous system (CNS). Identical lymphoid infiltrates were present in the patient's skin. CNS involvement was interpreted as having a leptomeningeal seeding. To the best of our knowledge, this is the 9th reported case of confirmed NK/T cell lymphoma arising from the testis. Relevant literature is reviewed, and the clinicopathologic features, natural history, and treatment options for primary testicular NK/T cell lymphoma are discussed.

Overexpression of cyclooxygenase-2 is associated with a poor prognosis in patients with squamous cell carcinoma of the uterine cervix treated with radiation and concurrent chemotherapy.

BACKGROUND: The objective of this study was to determine whether cyclooxygenase-2 (COX-2) overexpression was an indicator of prognosis in patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IIB uterine cervical carcinoma who underwent radiation and concurrent chemotherapy. METHODS: Seventy-five patients with FIGO Stage IIB squamous cell carcinoma (SCC) of the uterine cervix who were treated with radiotherapy and concurrent chemotherapy between 1991 and 1996 were divided into two groups according to their COX-2 level in an immunohistochemical study: the COX-2 negative group (n = 54 patients) and the COX-2 positive group (n = 21 patients). The clinicopathologic features, patterns of treatment failure, and survival data for patients in the COX-2 positive group were compared with data from the patients in the COX-2 negative group. Univariate and multivariate analyses were performed to determine the prognostic factors that influenced patient survival. RESULTS: In the immunohistochemical study, COX-2 overexpression was observed in approximately 30% of patients with FIGO Stage IIB SCC of the uterine cervix. With delayed regression to the initial treatment, the treatment failure rate of patients in the COX-2 positive group was much higher compared with the treatment failure rate of patients in the COX-2 negative group. The higher incidence of central failure and lymph node failure for patients in the COX-2 positive group was statistically significant (48% for the COX-2 positive group vs. 13% for the COX-2 negative group). However, there was no difference in the incidence of hematogenous metastases between the two groups (5% for the COX-2 positive group vs. 7% for the COX-2 negative group). In addition, increased COX-2 expression in tumor cells also was correlated with a shorter interval to tumor recurrence (median interval to recurrence, 9 months in the COX-2 positive group vs. 26 months in the COX-2 negative group). Compared with patients in the COX-2 negative group, patients in the COX-2 positive group had lower overall actuarial and disease free survival rates (overall 5-year actuarial survival rates: 56% for the COX-2 positive group vs. 94% for the COX-2 negative group; P = 0.003). Univariate and multivariate analyses showed that COX-2 overexpression was an independent prognostic factor that surpassed other well-known clinicopathologic parameters. CONCLUSIONS: COX-2 overexpression can be used as a potent molecular risk factor in patients with FIGO Stage IIB SCC of the uterine cervix who are treated with radiotherapy and concurrent chemotherapy.