記述言語：英語   掲載種別：研究論文（学術雑誌）  

High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecological malignancy. New evidence supports a hypothesis that HGSOC can originate from fallopian tube epithelium (FTE). It is unclear how genetic alterations and pathophysiological processes drive the progression of FTE tumor precursors into widespread HGSOCs. In this study, we uncovered that brain-derived neurotrophic factor (BDNF) in the follicular fluid stimulates the tropomyosin receptor kinase B (TrkB)-expressing FTE cells to promote their survival, migration, and attachment. Using in vitro and in vivo models, we further identified that the acquisition of common TP53 gain-of-function (GOF) mutations in FTE cells led to enhanced BDNF/TrkB signaling compared to that of FTE cells with TP53 loss-of-function (LOF) mutations. Different mutant p53 proteins can either increase TrkB transcription or enhance TrkB endocytic recycling. Our findings have demonstrated possible interplays between genetic alterations in FTE tumor precursors (i.e., p53 GOF mutations) and pathophysiological processes (i.e., the release of follicular fluid upon ovulation) during the initiation of HGSOC from the fallopian tube. Our data revealed molecular events underlying the link between HGSOC tumorigenesis and ovulation, a physiological process that has been associated with risk factors of HGSOC.

DOI： 10.1038/s41389-020-0243-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Molecular chaperone heat shock protein 90 (HSP90) is involved in oncogenic signaling pathways including epithelial-mesenchymal transition (EMT), a key process in tumor initiation, progression, metastasis, and chemoresistance. The molecular mechanisms underlying the involvement of HSP90 in EMT are still under investigation. In this study, we identified a previously unrecognized role of HSP90 in cooperating with signal transducer and activator of transcription 3 (STAT3) to regulate TWIST1 transcription in cancer cells. The HSP90 inhibitor 17-N-allylamino-17-demethoxygeldanamycin suppressed TWIST1 mRNA expression and promoter activity in epithelial ovarian cancer, renal clear cell cancer, and nasopharyngeal cancer cell lines. The interactions between HSP90 and transcription factors were visualized in cancer cell lines and tumor tissues using proximity ligation assays. Our findings reveal that HSP90 promotes the binding of STAT3 to the TWIST1 promoter, leading to the transcription of TWIST1. The inhibition of HSP90 downregulates STAT3 activity and TWIST1 transcription, thereby suppressing EMT and potentially inhibiting tumor progression, metastasis, and chemoresistance in different types of cancers. SIGNIFICANCE STATEMENT: Our study provides new evidence that HSP90 promotes EMT through enhancing TWIST1 transcription, which can be suppressed by HSP90 inhibitors. The HSP90 inhibitor inhibits EMT, thus potentially slowing down tumor growth, invasion, dissemination, metastasis, and drug resistance. These findings will hopefully pave the way for new therapeutic opportunities to target EMT and metastasis using HSP90 inhibitors.

DOI： 10.1124/mol.119.116137

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記述言語：英語  

DOI： 10.1016/j.eururo.2019.01.015

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

PURPOSE: When working on fluoroscopy and patient assistance in a healthcare facility, workers need to understand how to properly protect scattered radiation. In this study, we examined a four-dimensional visualization method to make it easy to understand the spread of scattered radiation visually, and proposed its application to radiation protection education. METHODS: We constructed the X-ray room, X-ray CT room, and angiography room using Particle Heavy Ion Transport code System (PHITS), and calculated the scattered radiation distribution when the patient was irradiated with X-rays. The three-dimensional distribution of each moment was continuously displayed to create a four-dimensional distribution. Using the created data, we conducted radiation protection education including exercises to make the students confirm the scatter distribution from any direction. The effectiveness of the scattered radiation visualization data was evaluated by a questionnaire. RESULTS: The position of assistance for standing chest radiograph was less scattered radiation at the side and below the patient. As a result of the questionnaire, this education has confirmed the effect of attracting attention about radiation protection. The fourdimensional visualization allowed students to understand the behavior of radiation and the source of scattered radiation. CONCLUSION: Visualization of three- and four-dimensional scattered radiation distribution in the radiological examination room can intuitively enhance the understanding of the invisible radiation spread and appropriate aids.

DOI： 10.6009/jjrt.2019_JSRT_75.11.1297

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: Tumor heterogeneity may represent a barrier to preoperative genomic characterization by needle biopsy in clear cell renal cell carcinoma (ccRCC). The extent of heterogeneity in small renal tumors remains unknown. Therefore, we set out to evaluate heterogeneity in resected large and small renal tumors.Experimental Design: We conducted a study from 2013 to 2016 that evaluated 47 consecutive ccRCC tumors resected during radical or partial nephrectomy. Cases were designated as small (<4 cm) and large (>7 cm) tumors. Each tumor had three regions sampled. Copy-number variation (CNV) was assessed and gene expression analysis was performed to characterize the clear-cell A and B (ccA/ccB) profile and the cell-cycle progression (CCP) score. Genomic heterogeneity between three regions was evaluated using CNV subclonal events, regional expression profiles, and correlation between gene expression.Results: Twenty-three small and 24 large tumors were analyzed. Total CNVs and subclonal CNVs events were less frequent in small tumors (P < 0.001). Significant gene expression heterogeneity was observed for both CCP scores and ccA/ccB classifications. Larger tumors had more variance in CCP scores (P = 0.026). The distribution of ccA/ccB differed between small and large tumors with mixed ccA/ccB tumors occurring more frequently in the larger tumors (P = 0.024). Analysis of five mixed tumors (with both ccA/ccB regions) demonstrated the more aggressive ccB phenotype had greater CNV events (P = 0.014).Conclusions: Small renal tumors have much less genomic complexity and fewer subclonal events. Pretreatment genomic characterization with single-needle biopsy in small tumors may be useful to assess biologic potential and may influence therapy. Clin Cancer Res; 24(17); 4137-44. ©2018 AACR.

DOI： 10.1158/1078-0432.CCR-18-0214

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The hereditary cancer syndromes hereditary leiomyomatosis and renal cell cancer (HLRCC) and succinate dehydrogenase-related hereditary paraganglioma and pheochromocytoma (SDH PGL/PCC) are linked to germline loss-of-function mutations in genes encoding the Krebs cycle enzymes fumarate hydratase and succinate dehydrogenase, thus leading to elevated levels of fumarate and succinate, respectively1-3. Here, we report that fumarate and succinate both suppress the homologous recombination (HR) DNA-repair pathway required for the resolution of DNA double-strand breaks (DSBs) and for the maintenance of genomic integrity, thus rendering tumor cells vulnerable to synthetic-lethal targeting with poly(ADP)-ribose polymerase (PARP) inhibitors. These results identify HLRCC and SDH PGL/PCC as familial DNA-repair deficiency syndromes, providing a mechanistic basis to explain their cancer predisposition and suggesting a potentially therapeutic approach for advanced HLRCC and SDH PGL/PCC, both of which are incurable when metastatic.

DOI： 10.1038/s41588-018-0170-4

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記述言語：英語  

DOI： 10.1016/j.eururo.2018.03.033

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: We investigated prospectively whether 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) can predict the overall survival (OS) of patients with advanced renal cell carcinoma (RCC) previously treated by molecular targeted therapies. METHODS: Between 2009 and 2016, 81 patients who had received single molecular targeted therapies (43 sorafenib, 27 sunitinib, 8 temsirolimus and others) and were scheduled for second line molecular targeted therapies for advanced RCC were enrolled in this prospective study. FDG PET/CT was performed after first line molecular targeted therapies, the max SUVmax (highest standardized uptake value for each patient) recorded, and its association with OS compared with those of known risk factors. The median follow-up was 15.4 months (range 0.9-97.4 months). RESULTS: The max SUVmax of the 81 subjects ranged from undetectable to 23.0 (median 7.1). Patients with high max SUVmax had a poor prognosis and multivariate analysis with established risk factors showed that it was an independent predictor of survival (p < 0.001; hazard ratio 1.156; 95% confidence interval 1.080-1.239). Subclassification of patients by max SUVmax showed that the median OS of patients with max SUVmax < 7.0 (39), 7.0-12.0 (30), and ≥ 12.0 (12) were 32.8, 15.2, and 6.0 months, respectively. These differences are statistically significant (< 7.0 versus 7.0-12.0: p = 0.0333, 7.0-12.0 versus ≥ 12.0: p = 0.0235). CONCLUSIONS: The max SUVmax by FDG PET/CT of patients with RCC evaluated after their first molecular targeted therapy predicts OS. FDG PET/CT is a useful "imaging biomarker" for patients with advanced RCC planning sequential molecular targeted therapies.

DOI： 10.1007/s00280-018-3542-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We investigated time-dependent changes in the relapse features of renal cell carcinoma (RCC) after curative surgery. Between 1985 and 2015, 1398 patients with RCC (1226 clear cell RCC, 89 papillary RCC, and 53 chromophobe RCC) underwent curative surgery at Yokohama City University Hospital and its affiliated hospitals. We retrospectively reviewed the clinicopathologic factors of patients with relapse after surgery. Median follow-up was 56.3 months. Recurrence occurred in 245 patients (217 clear cell RCC, 12 papillary RCC, and 3 chromophobe RCC). Papillary RCC and chromophobe RCC had no recurrence beyond 5 years after surgery, but 20 cases of clear cell carcinoma had recurrence beyond 10 years after surgery. The typical recurrence sites of clear cell RCC were lung (46.6%), bone (17.9%), liver (7.6%), and lymph nodes (6.5%). The proportion of recurrences at these typical sites was 83.9% for recurrences within 5 years, 76.3% between 5 and 10 years, and 40.0% beyond 10 years. In contrast, the proportion of retroperitoneal organ recurrence, including contralateral kidney, pancreas, and adrenal glands, increased with increasing time after surgery. Interestingly, the hazard ratio of typical site relapse decreased whereas that of retroperitoneal organ relapse increased in a time-dependent manner. In summary, clear cell RCC showed potential to relapse beyond 10 years after surgery. Recurrence at typical sites decreased whereas retroperitoneal organ recurrence increased in a time-dependent manner. Clinicians should check for recurrence at various sites beyond 10 years, especially in clear cell RCC.

DOI： 10.1007/s10585-018-9883-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: We evaluated 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) results as outcome predictors for patients with metastatic renal cell carcinoma (RCC) treated by everolimus (EVL), an inhibitor of mammalian target of rapamycin. METHODS: We retrospectively reviewed 30 patients who were treated with EVL for metastatic RCC between May 2010 and March 2015, by evaluating their FDG PET/CT result before and 1 month after starting EVL treatment. We examined the relationships between each patient's maximum standardized uptake value (max SUVmax) assessed by FDG PET/CT on progression-free survival (PFS) and overall survival (OS). RESULTS: Median PFS for all 30 patients was 3.77 months (range 0.72-24.56 months) and median OS after EVL treatment of all 30 patients was 11.67 months (range 1.0-62.98 months). Enrolled patients were divided into two groups by max SUVmax prior to EVL (median = 7.6) and at 1 month after EVL treatment (median = 5.7). PFS were significantly shorter in higher max SUVmax prior to EVL (<7.6, PFS 7.8 vs 3.5 months, log-rank P = 0.017) and at 1 month after EVL (<5.7, PFS 10.6 vs 2.7 months, log-rank P = 0.002) than lower max SUVmax. OS were also significantly shorter in higher max SUVmax prior to EVL (<7.6, OS 18.1 vs 7.5 months, log-rank P = 0.010) and at 1 month after EVL (<5.7, OS 17.2 vs 7.5 months, log-rank P = 0.009) than lower max SUVmax. Multivariate Cox hazard regression analysis indicated that max SUVmax at 1 month after EVL is an independent predictor of both PFS and OS in patients treated with EVL although univariate regression analysis showed max SUVmax before EVL is a possible predictor. CONCLUSIONS: Max SUVmax assessed by FDG PET/CT prior to EVL and at 1 month after EVL treatment can accurately predict PFS and can guide decisions on whether to continue or change treatments for patients with EVL-treated RCC who suffer from adverse events.

DOI： 10.1007/s00280-017-3275-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Laparoscopic surgical techniques are difficult to learn, and developing such skills involves a steep learning curve. To ensure surgeons achieve a high skill level, it is important to be able to measure and assess their skills. Therefore, it is necessary to understand the performance differences between experienced and novice surgeons, as such information could be used to help surgeons learn laparoscopic skills. We examined the differences in gripping and reaction force between experienced and novice surgeons during laparoscopic surgery. METHODS: We measured the gripping force generated during laparoscopic surgery performed on pigs using forceps with pressure sensors. Several sensors, including strain gauges, accelerometers, and a potentiometer, were attached to the forceps. This study included 4 experienced and 4 novice surgeons. Each subject was asked to elevate the kidney in order to approach the renal hilus using the forceps. Throughout the experiment, we measured the gripping force and reaction force generated during the movement of the forceps in real time. RESULTS: The experienced and novice surgeons exhibited similar reaction force levels. Conversely, gripping force differed significantly between the groups. The experienced and novice surgeons exhibited mean gripping force levels of 3.06 and 7.15 N, respectively. The gripping force standard deviation values for the experienced and novice surgeons were 1.43 and 3.54 N, respectively. The mean and standard deviation gripping force values of the experienced surgeons were significantly lower than those of the novice surgeons (P = 0.015 and P = 0.011, respectively). CONCLUSIONS: This study indicated that experienced surgeons generate weaker but more stable gripping force than novice surgeons during laparoscopic procedures.

DOI： 10.1007/s00464-016-5153-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Tyrosine-kinase inhibitor (TKI) targeting angiogenesis improves the prognosis of patients with metastatic renal cell carcinoma (RCC), but its effect is temporary. In order to understand the mechanism by which RCC acquires resistance to TKI, we investigated the change of glucose accumulation in RCC by FDG PET/CT when they demonstrated progression disease (PD) against TKI. METHODS: We monitored the FDG accumulation in RCC of 38 patients treated with TKI by 162 PET/CT sequentially until they were judged to demonstrate PD. Standardized uptake value (SUV), a simplified index of tissue FDG accumulation rate, was measured, and the sequential changes of max SUVmax (the highest SUV in an individual patient) was analyzed. Additionally, the expression of glucose transporter 1 (GLUT-1) and associated proteins in 786-O cells cultured under hypoxia were analyzed. RESULTS: The 10 patients with RCC which FDG accumulation was accelerated after beginning of TKI treatment demonstrated PD soon. The other 28 patients with RCC which FDG accumulation was suppressed by TKI showed longer progression-free survival (3.6 months vs 6.5 months, P = 0.0026), but this suppression in most cases (96%) was temporary and FDG accumulation was accelerated when tumor demonstrated PD. Interestingly, the FDG accumulation at PD was higher than that before TKI treatment in the half cases. The acceleration of FDG accumulation was suppressed by following treatment by mammalian target of rapamycin (mTOR) inhibitor. Additionally, in vitro assay demonstrated that the expression of GLUT-1 was increased in the RCC cells surviving under hypoxia condition via mTOR pathway. CONCLUSIONS: The acceleration of glucose accumulation dependent on mTOR in RCC assessed by FDG PET/CT demonstrated acquisition of resistance to TKI. FDG PET/CT had potential as an assessment method monitoring not only the initial response but also following status of RCC during TKI treatment. TRIAL REGISTRATION: UMIN0000008141 , 11 Jun 2012. This trial was retrospectively registered.

DOI： 10.1186/s12885-016-3044-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: 4'-[Methyl-(11)C]-thiothymidine (4DST) has been developed as an in vivo cell proliferation marker based on its DNA incorporation mechanism. This study evaluated the potential of 4DST PET/CT for imaging cellular proliferation in advanced clear cell renal cell carcinoma (RCC), compared with FDG PET/CT. Both 4DST and FDG uptake were compared with biological findings based on surgical pathology. METHODS: Five patients (3 men and 2 women; mean (±SD) age 64.8 ± 11.0 years) with a single RCC (mean diameter: 9.3 ± 3.2 cm) were examined by PET/CT using 4DST and FDG. The dynamic emission scan of 4DST for RCC over 35 min followed by a static emission scan of the body for 4DST and FDG. Then we compared the maximum standardized uptake value (SUVmax) of 20 areas of RCC on both 4DST and FDG images with (1) the Ki-67 index of cellular proliferation (2) Fuhrman grade system for nuclear grade (G) in RCC and (3) pathological phosphorylated grade of mammalian target of rapamycin (pmTOR). RESULTS: All patient cases showed clear uptake of FDG and 4DST in RCC tumors, with mean 4DST SUVmax of 7.3 ± 2.2 (range 4.3-9.4) and mean FDG SUVmax of 6.0 ± 2.8 (range 3.4-10.4). The correlation coefficient between SUVmax and Ki-67 index was higher with 4DST (r = 0.61) than with FDG (r = 0.43). Tumor 4DST uptake (G0: 1.4, G2: 2.6, G2 5.6, G4: 5.7) and tumor FDG uptake (G0: 1.8, G2: 2.9, G2 3.7, G4: 4.1) were both related to Fuhrman grade system. The 4DST uptake increased as the pmTOR grade increases (G0: 3.1, G1: 4.8, G2: 4.7, G3: 6.2); in contrast FDG uptake was unrelated to pmTOR grade (G0: 2.8, G2: 4.0, G2 3.3, G4: 3.6). CONCLUSION: A higher correlation with the proliferation of RCC was observed for 4DST than for FDG. The 4DST uptake exhibits the possibility to predict pmTOR grade, indicating that 4DST has potential for the evaluation of therapeutic effect with mTOR inhibitor in patients with RCC.

DOI： 10.1007/s00261-015-0601-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Various molecular-targeting therapies have become available for the treatment of advanced renal cell carcinoma (RCC). Accurate prognostication is desirable for choosing the appropriate treatment for individual patients. (18)F-2-fluoro-2-deoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) is a non-invasive tool for evaluating glucose accumulation, which can be an index of biological characteristics of cancer. We prospectively evaluated FDG PET/CT as a prognostic indicator in patients with advanced RCC. METHODS: A total of 101 patients slated for different systematic therapies for advanced RCC were enrolled between 2008 and 2014. A total of 61 patients had recurrent RCC (58 metastatic and 3 regional) and 40 patients had stage IV RCC (36 metastatic and 4 locoregional). Sixteen patients had not undergone nephrectomy. Pre-treatment FDG PET/CT was performed, and the max SUVmax (the highest SUV measurement in each patient) was recorded. The max SUVmax was compared with different clinical risk factors as prognostic indicators. The median observation period was 18 months (range 1-70 months). RESULTS: The max SUVmax of the 101 subjects ranged from undetectable to 23.0 (median 6.9). Patients with high max SUVmax had a poor prognosis. Multivariate analysis with standard risk factors revealed that max SUVmax was an independent predictor of survival (p < 0.001; hazard ratio 1.265; 95% confidence interval 1.159-1.380). A cutoff of 8.8 for max SUVmax advocated in our previous report was highly significant (p < 0.0001). When we subclassified the max SUVmax values, the median overall survival of subjects with max SUVmax < 7.0 was 41.9 months. That of subjects with max SUVmax between 7.0 and 12.0 was 20.6 months. That of subjects with max SUVmax ≥ 12.0 was 4.2 months. The differences were statistically significant. CONCLUSIONS: Pretreatment max SUVmax assessed by FDG PET/CT is a useful prognostic marker for patients with advanced RCC, providing helpful information for clinical decision making.

DOI： 10.1186/s12885-016-2097-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: To describe and to validate a novel patient-specific virtual-reality based simulator for laparoscopic surgery. METHODS: Three surgeons carried out 13 preoperative simulations at Yokohama City University Hospital, Yokohama, Kanagawa, Japan, from 2011 to 2012. The procedures included seven nephrectomies, four partial nephrectomies and two pyeloplasties. We evaluated whether the anatomies reproduced by the simulator matched those encountered during the actual operations. Furthermore, the surgeons were asked to use visual analog scales (from 1 to 5; higher scores are better) to evaluate the anatomical integrity and utility of the simulations, and their intraoperative confidence during the subsequent surgical procedures. RESULTS: The simulator reproduced the patients' anatomies almost perfectly. Only a few minor mistakes were identified. Regarding the surgeons' evaluations of the system, the mean scores for the anatomical integrity and utility of the simulations, and the surgeons' intraoperative confidence were 3.4, 4.2 and 4.1, respectively. In all 13 cases, the surgeons were able to carry out preoperative training with ease, and they stated that the simulator was useful for producing preoperative images. CONCLUSIONS: A patient-specific simulator for laparoscopic renal surgery has been successfully developed. This system correctly reproduces anatomical structures, and it seems to be a useful preoperative training tool.

DOI： 10.1111/iju.12737

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The purpose of this study is presenting a method to predict the presence of an open urinary tract and the position of the opening in laparoscopic partial nephrectomy from three dimensional (3D) computed tomography (CT) images by using novel image segmentation and visualization techniques. METHODS: From CT images of patients who underwent laparoscopic partial nephrectomy, 3D regions of the kidney, urinary tract, and tumor were segmented. For each patient, multiple virtual resection planes of the kidney with different surgical margins (1 mm to 5 mm, every 1 mm) were generated and the presence of an open urinary tract and the position of the opening were predicted from the images. RESULTS: We compared the predictions with actual operations in 5 cases by using recorded video of the operations and operative notes. In terms of the presence of an open urinary tract, agreement of the predictions and the intraoperative results was obtained in all patients. The expected positions of the openings were close to those in the actual operations. CONCLUSIONS: We have developed a method to virtually visualize the resection plane of laparoscopic partial nephrectomy. Image segmentation methods used in this study were precise and effective. The comparison indicated that our method accurately predicted the presence of an open urinary tract and the position of the opening and provided useful preoperative information.

DOI： 10.1186/1471-2490-14-47

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have become the mainstay of treatment for advanced renal cell carcinoma (RCC), but it has been unclear whether the antitumor effect of TKIs depends on the organ where the RCC metastasis is located. We previously reported that the FDG accumulation assessed by FDG PET/CT, was a powerful index for evaluating the biological response to TKI. In this study we investigated the differences in FDG accumulation and the response to TKI as assessed by FDG PET/CT among various organs where RCC were located. METHODS: A total of 48 patients with advanced RCC treated with a TKI (25 with sunitinib and 23 with sorafenib) were evaluated by FDG PET/CT before and at 1 month after a TKI treatment initiation. The maximum standardized uptake value (SUVmax) of all RCC lesions were measured and analyzed. RESULTS: We evaluated 190 RCC lesions. The pretreatment SUVmax values (mean ± SD) were as follows: in the 49 lung metastases, 4.1 ± 3.3; in the 40 bone metastases, 5.4 ± 1.6; in the 37 lymph node metastases, 6.7 ± 2.7; in the 29 abdominal parenchymal organ metastases, 6.6 ± 2.7; in the 26 muscle or soft tissue metastases, 4.4 ± 2.6; and in the nine primary lesions, 8.9 ± 3.9. Significant differences in the SUVmax were revealed between metastases and primary lesions (p = 0.006) and between lung metastases and non-lung metastases (p < 0.001). The SUVmax change ratios at 1 month after TKI treatment started were -14.2 ± 48.4% in the lung metastases, -10.4 ± 23.3% in the bone metastases, -9.3 ± 47.4% in the lymph node metastases, -24.5 ± 41.7% in the abdominal parenchymal organ metastases, -10.6 ± 47.4% in the muscle or soft tissue metastases, and -24.2 ± 18.3% in the primary lesions. There was no significant difference among the organs (p = 0.531). CONCLUSIONS: The decrease ratio of FDG accumulation of RCC lesions evaluated by PET/CT at 1 month after TKI treatment initiation was not influenced by the organs where the RCC metastasis was located. This result suggests that TKIs can be used to treat patients with advanced RCC regardless of the metastatic site.

DOI： 10.1186/1471-2407-14-390

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We reported previously that (18)F-2-fluoro-2-deoxyglucose positron emission tomography/ computed tomography (FDG PET/CT) had potential for evaluating early response to treatment by tyrosine kinase inhibitors (TKIs) in advanced renal cell carcinoma (RCC). This time we investigated the relation of the early assessment by FDG PET/CT to long-term prognosis with an expanded number of patients and period of observation. METHODS: Patients for whom TKI treatment for advanced RCC was planned were enrolled. FDG PET/CT was performed before TKI treatment and after one month of TKI treatment. The relations of the FDGPET/CT assessment to progression free survival (PFS) and overall survival (OS) were investigated. RESULTS: Thirty-five patients were enrolled (sunitinib 19 cases, sorafenib 16 cases). The patients with RCC showing high SUVmax in pretreatment FDG PET/CT demonstrated short PFS (P =0.024, hazard ratio 1.137, 95% CI 1.017-1.271) and short OS (P =0.004, hazard ratio 1.210 95% CI 1.062-1.379). Thirty patients (sunitinib 16 cases, sorafenib 14 cases) were evaluated again after 1 month. The PFS of the patients whose SUVmax decreased<20% was shorter than that of the patients whose SUVmax decreased<20% (P = 0.027, hazard ratio 3.043, 95% CI 1.134-8.167). The PFS of patients whose tumor diameter sum increased was shorter than that of the patient with tumors whose diameter sum did not (P =0.006, hazard ratio 4.555, 95% CI 1.543-13.448). The patients were classified into three response groups: good responder (diameter sum did not increase, and SUVmax decreased ≥ 20%), intermediate responder (diameter sum did not increase, and SUVmax decreased<20%), and poor responder (diameter sum increased, or one or more new lesions appeared). The median PFS of good, intermediate, and poor responders were 458 ± 146 days, 131 ± 9 days, and 88 ± 26 days (good vs. intermediate P = 0.0366, intermediate vs. poor P = 0.0097, log-rank test). Additionally the mean OSs were 999 ± 70 days, 469 ± 34 days, and 374 ± 125 days, respectively (good vs. intermediate P = 0.0385, intermediate vs. poor P = 0.0305, log-rank test). CONCLUSIONS: The evaluation of RCC response to TKI by tumor size and FDG uptake using FDG PET/CT after 1 month can predict PFS and OS.

DOI： 10.1186/1471-2407-12-162

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