• Korean Journal of Head & Neck Oncology
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• v.37 no.1
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• pp.17-22
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• 2021

Background/Objectives: To evaluate clinical significance of FDG PET-CT for detection of residual cancer cells after curative radiation therapy or chemoradiotherapy for patients with squamous cell carcinoma (SCC) of Head and Neck Materials & Methods: A retrospective analysis of patients with SCC of Head and neck with curative radiotherapy or chemoradiotherpy between June 2011 and Jan. 2019 was performed. Sixty patients were treated with Intensity-modulated radiotherapy (IMRT). The Metabolic responses were evaluated on the post-treatment FDG PET-CT at 12 weeks after curative radiotherapy completion. Results: Median follow up was 51.5 months (3-102). The overall survival (OS), disease free survival (DFS), local control rate (LCR), and Distant metastasis free survival (DMFS) at 5 years were 80.5%, 80.1%, 87.7% and 89.1%. Metabolic CR was found in 43 (71.7%) and partial metabolic response (PR) was noted in 17 (14.6%). Metabolic CR was significantly correlated with OS, DFS, LCR, and DMFS. On multivariate analysis, Metabolic CR remained significant for DFS and LCR. Conclusion: Metabolic CR on post-radiotherapy FDG PET-CT is highly predictive of increased DFS and LCR in patients with head and neck cancer.

• Radiation Oncology Journal
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• v.33 no.2
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• pp.126-133
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• 2015

Purpose: To evaluate the outcomes of adjuvant radiotherapy (RT) and to analyze prognostic factors of survival in the International Federation of Gynecology and Obstetrics (FIGO) IB-IIA uterine cervical cancer. Materials and Methods: We retrospectively reviewed the medical records of 148 patients with FIGO IB-IIA uterine cervical cancer who underwent surgery followed by adjuvant RT at the Yonsei Cancer Center between June 1997 and December 2011. Adjuvant radiotherapy was delivered to the whole pelvis or an extended field with or without brachytherapy. Among all patients, 57 (38.5%) received adjuvant chemotherapy either concurrently or sequentially. To analyze prognostic factors, we assessed clinicopathologic variables and metabolic parameters measured on preoperative 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). To evaluate the predictive performance of metabolic parameters, receiver operating characteristic curve analysis was used. Overall survival (OS) and disease-free survival (DFS) were analyzed by the Kaplan-Meier method. Results: The median follow-up period was 63.2 months (range, 2.7 to 206.8 months). Locoregional recurrence alone occurred in 6 patients, while distant metastasis was present in 16 patients, including 2 patients with simultaneous regional failure. The 5-year and 10-year OSs were 87.0% and 85.4%, respectively. The 5-year and 10-year DFSs were 83.8% and 82.5%, respectively. In multivariate analysis, pathologic type and tumor size were shown to be significant prognostic factors associated with both DFS and OS. In subset analysis of 40 patients who underwent preoperative PET/CT, total lesion glycolysis was shown to be the most significant prognostic factor among the clinicopathologic variables and metabolic parameters for DFS. Conclusion: Our results demonstrated that adjuvant RT following hysterectomy effectively improves local control. From the subset analysis of preoperative PET/CT, we can consider that metabolic parameters may hold prognostic significance in early uterine cervical cancer patients. More effective systemic treatments might be needed to reduce distant metastasis in these patients.

• Journal of the Korean Magnetic Resonance Society
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• v.21 no.1
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• pp.31-43
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• 2017

Together with radiotherapy, chemotherapy using cytotoxic agents is one of the most common therapies in cancer. Metabolic changes in cancer cells are drawing much attention recently, but the metabolic alterations by anticancer agents have not been much studied. Here, we investigated the effects of commonly used cytotoxic agents on lung normal cell MRC5 and lung cancer cell A549. We employed cis-plastin, doxorubicin, and 5-Fluorouracil and compared their effects on the viability and metabolism of the normal and cancer cell lines. We first established the concentration of the cytotoxic reagents that give differences in the viabilities of normal and cancer cell lines. In those conditions, the viability of A549 decreased significantly, whereas that of MRC5 remained unchanged. To study the metabolic alterations implicated in the viability differences, we obtained the metabolic profiles using $^1H$-NMR spectrometry. The $^1H$-NMR data showed that the metabolic changes of A549 cells are more remarkable than that of MRC5 cells and the effect of 5-FU on the A549 cells is the most distinct compared to other treatments. Heat map analysis showed that metabolic alterations under treatment of cytotoxic agents are totally different between normal and cancer cells. Multivariate analysis and weighted correlation network analysis (WGCNA) revealed a distinctive metabolite signature and hub metabolites. Two different analysis tools revealed that the changes of cell metabolism in response to cytotoxic agents were highly correlated with the Warburg effect and Reductive lipogenesis, two pathways having important effects on the cell survival. Taken together, our study addressed the correlation between the viability and metabolic profiles of MRC5 and A549 cells upon the treatment of cytotoxic anticancer agents.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4847-4851
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• 2013

Objectives: To evaluate accuracy of FDG-PET CT in prediction of persistent disease in head and neck cancer cases and to determine prognostic value of metabolic tumor response. Materials and Methods: Between 2009 and 2011, 46 patients with squamous cell carcinoma of head and neck receiving PET-CT were treated with definitive radiotherapy, with or without chemotherapy. There were 29 nasopharyngeal, 11 hypopharyngeal, 3 oropharyngeal and 3 laryngeal cancer patients, with a median age of 50.5 years (range 16-84), 32 males and 14 females. All patients were evaluated with PET-CT median 3-5 months (2.4-9.4) after completion of radiotherapy. Results: After a median 20 months of follow up, complete metabolic response was observed in 63% of patients. Suspicious residual uptake was present in 10.9% and residual metabolic uptake in 26.0% of patients. The overall sensitivity, specificity, positive predictive value and negative predictive value of FDG-PET-CT for detection of residual disease was 91% and 81%, 64% and 96% respectively. Two year LRC was 95% in complete responders while it was 34% in non-complete responders. Conclusions: FDG PET CT is a valuable tool for assessment of treatment response, especially in patients at high risk of local recurrence, and also as an indicator of prognosis. Definitely more precise criteria are required for assessment of response, there being no clear cut uptake value indicating residual disease. Futhermore, repair processes of normal tissue may consume glucose which appear as increased uptake in control FDG PET CT.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.139-146
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• 2012

Obese postmenopausal women increase their risk of developing breast cancer (BC), in particular if they display an android-type pattern of adiposity, which is also associated to increased risks of diabetes mellitus, hypertension and cardiovascular disease. In order to explore the associations among anthropometry (body mass index, body composition, somatotype), some specific items of medical history (diabetes, hypertension, dislypidemias, hyperuricemia) and the risk of BC in Uruguayan women, a case-control study was carried out between 2004-2009 at our Oncology Unit. 912 women of ages between 23-69 years (367 new BC cases and 545 non hospitalized, age-matched controls with a normal mammography) were interviewed. Twenty body measurements were taken in order to calculate body composition and somatotype. Patients were queried on socio-demographics, reproductive history, family history of cancer, a brief food frequency questionnaire and on personal history of diabetes, dislypidemias, hyperuricemia, hypertension and gallbladder stones. Uni- and multivariate analyses were done, generating odds ratios (ORs) as an expression of relative risks. A personal history of diabetes was positively associated to BC risk (OR=1.64, 95% CI 1.00-2.69), being higher among postmenopausal women (OR=1.92, 95% CI 1.04-3.52). The risks of BC for diabetes in postmenopausal women with overweight combined with dislypidemia (OR=9.33, 95% CI 2.10-41.5) and high fat/muscle ratio (OR=7.81, 95% CI 2.01-30.3) were significantly high. As a conclusion, a personal history of diabetes and overweight was strongly associated to BC. The studied sample had a subset of high-risk of BC featured by postmenopausal overweight and diabetic women, who also had a personal history of hypertension and/or dyslipidemia. The present results could contribute to define new high risk groups and individuals for primary as well as for secondary prevention, since this pattern linked to the metabolic syndrome is usually not considered for BC prevention.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.2
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• pp.82-89
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• 2006

Bone metastasis is a common sequelae of solid malignant tumors such as prostate, breast, lung, and renal cancers, which can lead to various complications, including fractures, hypercalcemia, and bone pain, as well as reduced performance status and quality of life it occurs as a result of a complex pathophysiologic process between host and tumor cells leading to cellular invasion, migration adhesion, and stimulation of osteoclastic and osteoblastic activity. Several sequelae occur as a result of osseous metastases and resulting bone pain can lead to significant debilitation. A multidisciplinary approach is usually required not only to address the etiology of the pain and its complicating factors but also to treat the patient appropriately. Pharmaceutical therapy of bone pain, includes non-steroidal analgesics, opiates, steroids, hormones, bisphosphonates, and chemotherapy. While external beam radiation therapy remains the mainstay of pain palliation of a solitary lesions, bone seeking radiopharmaceuticals have entered the therapeutic armamentarium for the treatment of multiple painful osseous lesions. $^{32}P,\;^{89}SrCl,\;^{153}Sm-EDTMP,\;^{188}Re/^{186}Re-HEDP,\;and\;^{177}Lu-EDTMP$ can be used to treat painful osseous metastases. These various radiopharmaceuticals have shown good efficacy in relieving bone pain secondary to bone metastasis. This systemic form of metabolic radiotherapy is simple to administer and complements other treatment options. This has been associated with improved mobility in many patients, reduced dependence on narcotic and non-narcotic analgesics, improved performance status and quality of life, and, in some studios, improved survival. All of these agents, although comprising different physical and chemical characteristics, offer certain advantages in that they are simple to administer, are well tolerated by the patient if used appropriately, and can be used alone or in combination with the other forms of treatment. This article illustrates the salient features of these radiopharmaceuticals, including the usual therapuetic dose, method of administration, and indications for use and also describe about the pre-management checklists, and jndication/contraindication and follow-up protocol.

• Progress in Medical Physics
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• v.21 no.2
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• pp.174-182
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• 2010

In this study, we evaluated feasibility of applying MTV (Metabolic Target Volume) to respiratory gated radiotherapy for more accurate treatment using various SUV (Standard Uptake Value) from PET images. We compared VOI (Volume of Interest) images from 50%, 30% and 5% SUV (standard uptake volume) from PET scan of an artificial target with GTV (Gross Tumor Volume) images defined by percentage of respiratory phase from 4D-CT scan for respiratory gated radiotherapy. It is found that the difference of VOI of 30% SUV is reduced noticeably comparing with that of 50% SUV in longitudinal direction with respect to total GTV of 4D-CT image. Difference of VOI of 30% SUV from 4D-PET image defined by respiratory phase from 25% inhalation to 25% exhalation, and GTV from 4D-CT with the same phase is shown below 0.6 cm in maximum. Thus, it is better to use 4D-PET images than conventional PET images for applying MTV to gated RT. From the result that VOI of 5% SUV from 4D-PET agrees well with reference image of 4D-CT in all direction, and the recommendation from department of nuclear medicine that 30% SUV be advised for defining tumor range, it is found that using less than 30%SUV will be more accurate and practical to apply MTV for respiratory gated radiotherapy.

• Radiation Oncology Journal
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• v.29 no.4
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• pp.243-251
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• 2011

Purpose: To evaluate the prognostic value of metabolic tumor volume (MTV) and maximum standardized uptake value (SUVmax) on initial positron emission tomography-computed tomography (PET-CT) and investigate the clinical value of SUVmax for early detection of locoregional recurrent disease after postoperative radiotherapy in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Materials and Methods: A total of 100 patients with locally advanced HNSCC received primary tumor excision and neck dissection followed by adjuvant radiotherapy with or without chemotherapy. The MTV and SUVmax were measured from primary sites and neck nodes. The prognostic value of MTV and SUVmax were assessed using initial staging PET/CT (study A). Follow-up PET/CT scan available after postoperative concurrent chemoradiotherapy or radiotherapy were evaluated for the SUVmax value and correlated with locoregional recurrence (study B). A receiver operating characteristic (ROC) curve analysis was used to define a threshold value of SUVmax with the highest accuracy for recurrent disease assessment. Results: High MTV (>41 mL) is negative prognostic factor for disease free survival (p = 0.041). Postradiation SUVmax was significantly correlated with locoregional recurrence (hazard ratio, 1.812; 95% confidence interval, 1.361 to 2.413; P < 0.001). A cutoff value of 5.38 from follow-up PET/CT was identified as having maximal accuracy for detecting locoregional recurrence by ROC analysis. Conclusion: MTV at staging work-up was significantly associated with disease free survival. The SUVmax value from follow-up PET/CT showed high diagnostic accuracy for the detection of locoregional recurrence in postoperatively irradiated HNSCC.

• Radiation Oncology Journal
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• v.32 no.1
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• pp.31-42
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• 2014

Purpose: To evaluate the usefulness of positron emission tomography/computed tomography (PET/CT) for field modification during radiotherapy in esophageal cancer. Materials and Methods: We conducted a retrospective study on 33 patients that underwent chemoradiotherapy (CRT). Pathologic findings were squamous cell carcinoma in 32 patients and adenocarcinoma in 1 patient. All patients underwent PET/CT scans before and during CRT (after receiving 40 Gy and before a 20 Gy boost dose). Response evaluation was determined by PET/CT using metabolic tumor volume (MTV), total glycolytic activity (TGA), MTV ratio (rMTV) and TGA ratio (rTGA), or determined by CT. rMTV and rTGA were reduction ratio of MTV and TGA between before and during CRT, respectively. Results: Significant decreases in MTV ($MTV_{2.5}$: mean 70.09%, p < 0.001) and TGA ($TGAV_{2.5}$: mean 79.08%, p < 0.001) were found between before and during CRT. Median $rMTV_{2.5}$ was 0.299 (range, 0 to 0.98) and median $rTGAV_{2.5}$ was 0.209 (range, 0 to 0.92). During CRT, PET/CT detected newly developed distant metastasis in 1 patient, and this resulted in a treatment strategy change. At a median 4 months (range, 0 to 12 months) after completion of CRT, 8 patients (24.2%) achieved clinically complete response, 11 (33.3%) partial response, 5 (15.2%) stable disease, and 9 (27.3%) disease progression. $SUV_{max}$ (p = 0.029), $rMTV_{50%}$ (p = 0.016), $rMTV_{75%}$ (p = 0.023) on intra-treatment PET were found to correlate with complete clinical response. Conclusion: PET/CT during CRT can provide additional information useful for radiotherapy planning and offer the potential for tumor response evaluation during CRT. $rMTV_{50%}$ during CRT was found to be a useful predictor of clinical response.

• Radiation Oncology Journal
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• v.36 no.2
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• pp.95-102
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• 2018

Purpose: To evaluate the prognostic value of $^{18}F$-fluorodeoxyglucose positron-emission tomography (FDG PET) with computed tomography (CT) before and during radiotherapy (RT) in patients with head and neck cancer. Methods: Twenty patients with primary head and neck squamous cell carcinoma were enrolled in this study, of whom 6 had oropharyngeal cancer, 10 had hypopharyngeal cancer, and 4 had laryngeal cancer. Fifteen patients received concurrent cisplatin and 2 received concurrent cetuximab chemotherapy. FDG PET/CT was performed before RT and in the 4th week of RT. The parameters of maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis (TLG) of the primary tumor were measured, and the prognostic significance of each was analyzed with the Cox proportional hazards model. Results: Higher TLG (>19.0) on FDG PET/CT during RT was a poor prognostic factor for overall survival (OS) (p = 0.001) and progression-free survival (PFS) (p = 0.007). In the multivariate analysis, TLG during RT as a continuous variable was significantly associated with OS and PFS rate (p = 0.023 and p = 0.016, respectively). Tumor response worse than partial remission at 1 month after RT was another independent prognostic factor for PFS (p = 0.024). Conclusions: Higher TLG of the primary tumor on FDG PET/CT during RT was a poor prognostic factor for OS and PFS in patients with head and neck cancer.