The acceleration of glucose accumulation in renal cell carcinoma assessed by FDG PET/CT demonstrated acquisition of resistance to tyrosine kinase inhibitor therapy.

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.

[A Case of Squamous Cell Carcinoma in Bladder Diverticulum Producing Granulocyte Colony Stimulating Factor].

We report a rare case of squamous cell carcinoma (SCC) in bladder diverticulum producing granulocyte colony stimulating factor (G-CSF). A 59-year-old man complaining of hematuria and right hip pain was admitted with a large cancer in the bladder diverticulum. His laboratory data showed leukocytosis of 20,100/ µ l (neutrophils : 92%) with an elevated G-CSF of 76. 6 pg/ml in the peripheral blood. After neoadjuvant chemotherapy (gemcitabine and cisplatin), radical cystectomy was performed to normalize serum leukocytosis and G-CSF. Histopathological diagnosis was G-CSF-producing SCC pT4N0. He appeared with left pelvic lymph node metastasis and right pulmonary metastasis 3 months after surgery. Therefore, he was treated with four courses of combination chemotherapy (paclitaxel, ifosfamide and nedaplatin) and radiation therapy at left pelvic lymph node metastasis. Computed tomography after these treatments showed complete response. The patient is alive with no evidence of tumor 16 months after surgery.

FDG PET/CT as a prognostic biomarker in the era of molecular-targeting therapies: max SUVmax predicts survival of patients with advanced renal cell carcinoma.

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.

[A Case of Abdominal Wall Desmoid Tumor after Radical Nephrectomy for Renal Cancer].

A 71-year-old man with a right renal tumor underwent nephrectomy. The procedure was converted from laparoscopy to open surgery due to profound bleeding from the renal vein. Pathological diagnosis was clear cell carcinoma G2pT3b v1 ly1 INFα. Three years after surgery, a 5 cm tumor in the abdominal wall was found on computed tomography (CT). A mild uptake was shown on positron emission tomography/CT and as the tumor was located near the surgical wound, recurrence of the renal cell carcinoma was suspected. However, desmoid tumor was suggested by the pathological examination of the tumor biopsy. En-bloc resection of the mass was carried out and the pathological examination showed an array of proliferating and tangling atypical spindle-shaped tumor cells. Immunohistochemical staining of the tumor cells was positive for vimentin, but negative for CD34, c-kit, and s100. Pathological diagnosis was desmoid tumor. There has been no recurrence so far. Desmoid tumor, despite its extremely low incidence, should be considered in a postoperative neoplasm.

[PATHOLOGICAL COMPLETE RESPONSE WITH EVEROLIMUS FOR MULTIPLE LUNG METASTASES OF RENAL CELL CARCINOMA RESISTANT TO SUNITINIB].

A 55-year-old man was referred to our hospital because of a tumor in his right kidney. A Fluorodeoxyglucose-positron emission tomography (PET)/computed tomography (CT) scan revealed strong abnormal uptake by the tumor in the right kidney and a nodule in the right lung. The patient was diagnosed with stage IV renal cell cancer, for which he underwent transperitoneal nephrectomy. Pathological diagnosis revealed the tumor to be a renal cell carcinoma (clear cell carcinoma, G2, pT3a, v (+), INF-ß). Sunitinib was administered because of the occurrence of multiple lung metastases; however, the therapeutic effect was insufficient, and progressive disease was observed on a CT scan. Therefore, everolimus was immediately administered as a second-line therapeutic agent. After treatment, the lung metastases reduced in size, as observed on a CT scan, and partial response continued for 1 year after therapy. One metastatic lesion persisted in the right lung; therefore, he underwent right upper lobe resection after discontinuing everolimus administration. No viable tumor cells were observed on pathological diagnosis, and the patient achieved pathological complete response. 3 month after discontinuing everolimus administration, no metastatic lesions have been observed.

The early response of renal cell carcinoma to tyrosine kinase inhibitors evaluated by FDG PET/CT was not influenced by metastatic organ.

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.

[A case of multiple bony pain due to metastatic malignant pheochromocytoma successfully treated with strontium-89].

A 50-year-old woman complaining of right flank pain visited our hospital. Computed tomography revealed adrenal gland tumor measuring 10 cm in diameter, and multiple bone and liver metastases. It was diagnosed as a malignant pheochromocytoma by means of endocrinological examination and metaiodobenzylguanidine scintigraphy. Although 8 courses of cyclophosphamide, vincristine and dacarbazine therapy were performed, the tumor grew larger gradually, and the bony pain progressed and became uncontrollable with oxycodone hydrochloride. After zoredronic acid and strontium-89 were administered, the bony pain reduced, and the opioid usage could be reduced. In accordance with disease progression, the bony pain progressed again, but the readministration of strontium-89 could diminish the pain again. To our knowledge, this is the first case of malignant pheochromocytoma which strontium-89 was administered, and was effective.

[A case of pneumatosis cystoides intestinalis secondary to sunitinib treatment for renal cell carcinoma].

A 78-year-old man was diagnosed as having right renal cell carcinoma (RCC) with metastasis to the right lung. He received sunitinib and the treatment reduced the size of both RCC and lung metastasis. Then he received right radical nephrectomy. The pathological diagnosis was clear cell RCC. After the initial surgery, he was diagnosed with polymyalgia rheumatic and steroid therapy was started. During follow-up, local recurrence was discovered and sunitinib was then started at a dose of 25 mg/day. Two months after the treatment, abdominal computed tomography (CT) revealed colonic pneumatosis cystoides intestinalis. Administration of sunitinib was stopped and the patient was observed carefully without pursuing surgical intervention. A follow-up CT demonstrated resolution of the colonic pnumatosis.

[Successful combination chemotherapy of gemcitabine plus nedaplatin for invasive ureteral squamous cell carcinoma].

A 77-year-old female was indicated pelvic mass and hydronephrosis when her examination of advanced gastric cancer. Computed tomography revealed left ureteral dilatation and mass around the left ureter. Laparotomy biopsy was abandoned because of her low cardiac function. Thereafter, hemorrhagic stool was observed and colonoscopy revealed hemorrhagic mucosal protrusion at sigmoid colon. This lesion was diagnosed as squamous cell carcinoma by pathology of biopsy specimen. Colonic invasion of other organ carcinoma was suspected by colonoscopic findings. Retrograde pyelogram revealed a defect of left lower ureter. Positron emission tomography revealed the mass excluding sigmoid colon and high value (SUV max was 10.3) at the mass. Therefore, it was diagnosed invasive ureteral squamous cell carcinoma and she was treated with 2 cycles of combination chemotherapy consisting of gemcitabine (800 mg/m2: day 1 and 8) and nedaplatin (60 mg/m2: day 1). During the chemotherapy, only cytopenia (grade 4: CTCAE guidelines) was observed. About 4 months after 2 courses of chemotherapy, the tumor size was reduced by almost 100% (CR; RECIST guidelines). Thereafter, recurrence of pelvic mass was not observed.

[A case of retroperitoneal bronchogenic cyst treated by laparoscopic surgery].

A 51-year-old woman was referred to our hospital because of continuing back pain for 2 weeks. Computed tomography revealed a mass 30x40 mm in diameter adjacent to the left adrenal gland. We performed laparoscopic surgery in order to relieve the symptoms and make a diagnosis. Because there was adhesion between the mass and gastric wall, the mass was resected together with the gastric wall. Histopathological findings revealed the cyst with ciliated columunar epithelium and the final diagnosis was retroperitoneal bronchogenic cyst. There was no evidence of malignancy and the back pain disappeared.

[Retrospective analysis of predicting biochemical recurrence after initial radical prostatectomy].

We evaluated clinical outcomes of radical prostatectomy in 244 patients who had undergone radical prostatectomy as initial treatment from January 2000 to December 2011, and were followed up for more than 6 months. Biochemical recurrence after prostatectomy was defined as prostate-specific antigen (PSA) level of at least 0. 2 ng/ml. We evaluated potential risk factors for significant associations with biochemical recurrence. Median follow-up period after prostatectomy was 49 months (range, 6-144). Of the total, 192, 31, and 20 patients were at pathological stage pT2, pT3a, and pT3b, respectively. In 83 patients with the positive surgical margin, apexes were mostly in the positive area. Of the 68 patients with PSA recurrence, PSA non-relapse rate was 66.6% for 5 years. Multivariate analysis was performed for seminal vesicle invasion, PSA nadir, surgical margins, and Gleason score. Thirty-two patients with PSA recurrence underwent salvage radiotherapy, and the biochemical recurrence rate at 5 years was 73.8%. The group in which the PSA level before salvage radiotherapy was ＜0.5 ng/ml had a low rate of biochemical recurrence. We must consider the recurrence of poorly differentiated or non-confined cancer after radical prostatectomy. These results suggest that early use of salvage radiotherapy is effective for patients with biochemical recurrence after radical prostatectomy.

[A case of secondary Paget's disease of the glans penis originating from bladder cancer].

An 81-year-old man had undergone total cystectomy and bilateral ureterocutaneostomy at the age of 66 years. Furthermore, no recurrence or metastasis was observed; but at the age of 80 years he observed a painless rash around the external urethral orifice. As urothelial cancer was suspected, the urethra and glans were biopsied. Through immunohistochemical staining (cytokeratin 7 and 20), the glans biopsy indicated secondary Paget's disease of transitional epithelial origin. A urethrectomy was performed as progression from the urethra was suspected. The pathological examination revealed Paget cells at the glans, but the tumor was not observed permeating into the corpus cavernosum. This presents a rare case of secondary Paget's disease originating from a bladder tumor, and appearing in the glans without intraurethral progression.

A higher De Ritis ratio (AST/ALT) is a risk factor for progression in high-risk non-muscle invasive bladder cancer.

BACKGROUND: High-risk non-muscle invasive bladder cancer (NMIBC) is thought to be associated with a higher risk of recurrence and progression. A recent study revealed that a high De Ritis ratio was a risk factor in some solid malignancies. This study examined the importance of the De Ritis ratio as a prognostic marker in high-risk NMIBC. MATERIALS AND METHODS: A total of 138 patients who were initially diagnosed with high-risk NMIBC between January 2012 to December 2016 were enrolled in this study. The criteria for the high-risk classification followed the EAU guidelines. The recurrence-free and progression-free survival of the higher and lower De Ritis ratio groups were compared. The cut-off value of the De Ritis ratio was set at 1.35, based on a receiver operator curve analysis. RESULTS: The median observation period was 50.3 months. Among these patients, 32 (23.1%) patients developed recurrent disease and 15 (10.9%) patients showed progression. A multivariate analysis revealed that non-BCG treatment was an independent risk factor for recurrence, and a higher De Ritis ratio was an independent risk factor for cancer progression. CONCLUSIONS: The De Ritis ratio might be a risk factor for progression in high-risk NMIBC.

Impact of maximum standardized uptake value (SUVmax) evaluated by 18-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT) on survival for patients with advanced renal cell carcinoma: a preliminary report.

BACKGROUND: In this era of molecular targeting therapy when various systematic treatments can be selected, prognostic biomarkers are required for the purpose of risk-directed therapy selection. Numerous reports of various malignancies have revealed that 18-Fluoro-2-deoxy-D-glucose (18F-FDG) accumulation, as evaluated by positron emission tomography, can be used to predict the prognosis of patients. The purpose of this study was to evaluate the impact of the maximum standardized uptake value (SUVmax) from 18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) on survival for patients with advanced renal cell carcinoma (RCC). METHODS: A total of 26 patients with advanced or metastatic RCC were enrolled in this study. The FDG uptake of all RCC lesions diagnosed by conventional CT was evaluated by 18F-FDG PET/CT. The impact of SUVmax on patient survival was analyzed prospectively. RESULTS: FDG uptake was detected in 230 of 243 lesions (94.7%) excluding lung or liver metastases with diameters of less than 1 cm. The SUVmax of 26 patients ranged between 1.4 and 16.6 (mean 8.8 ± 4.0). The patients with RCC tumors showing high SUVmax demonstrated poor prognosis (P = 0.005 hazard ratio 1.326, 95% CI 1.089-1.614). The survival between patients with SUVmax equal to the mean of SUVmax, 8.8 or more and patients with SUVmax less than 8.8 were statistically different (P = 0.0012). This is the first report to evaluate the impact of SUVmax on advanced RCC patient survival. However, the number of patients and the follow-up period were still not extensive enough to settle this important question conclusively. CONCLUSIONS: The survival of patients with advanced RCC can be predicted by evaluating their SUVmax using 18F-FDG-PET/CT. 18F-FDG-PET/CT has potency as an "imaging biomarker" to provide helpful information for the clinical decision-making.

[A CASE OF TEMPORARY CARDIAC ARREST FOLLOWING SUDDEN FLUCTUATION OF BLOOD PRESSURE AFTER INITIATION OF PNEUMOPERITONEUM IN LAPAROSCOPIC ADRENALECTOMY FOR ADRENAL PHEOCHROMOCYTOMA].

A 75-year-old man was referred to our hospital with a complaint of difficulty swallowing and was diagnosed with left medullary infarction. Computed tomography and magnetic resonance imaging revealed a right adrenal tumor, 4 cm in size, and a left adrenal tumor, 1.6 cm in size. Abnormally high concentrations of serum catecholamine and urinary total metanephrine were also observed. In addition, 131I-MIBG scintigraphy revealed an abnormal accumulation of 131I in both tumors, which comprehensively led to the diagnosis of bilateral pheochromocytoma. Laparoscopic right adrenalectomy was planned first. After initiating pneumoperitoneum, the systolic blood pressure rose to 270 mmHg. Pneumoperitoneum was suspended briefly, and once resumed, the patient's blood pressure dropped gradually and was followed by cardiac arrest. A decision was made to interrupt surgery and start cardiopulmonary resuscitation. Once blood pressure stabilized above 160 mmHg, the patient was transferred to the intensive care unit with intubation. Subsequently, blood pressure was controlled to around 140 mmHg. He was discharged on the eleventh day after surgery without any major complications. Currently, he is being managed with more aggressive antihypertensive drug treatment.

Primary amelanotic malignant melanoma of the male urethra with inguinal lymph node metastasis successfully controlled by nivolumab: A case report.

We report a rare case of primary amelanotic malignant melanoma of the male urethra. A 65-year-old man with a urethral mass was referred to our hospital. A pathological diagnosis of a biopsy specimen revealed malignant melanoma. Thereafter, the patient underwent partial penectomy. The histopathological diagnosis was amelanotic malignant melanoma of the urethra. The patient had received DAV-Feron in an adjuvant setting; however, PET-CT revealed multiple metastasis. After receiving more than 10 cycles of nivolumab, the accumulation of FDG was no longer observed on PET-CT. The patient is currently free from recurrence at 20 months after nivolumab treatment.

Time-dependent change in relapse sites of renal cell carcinoma after curative surgery.

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.

FDG PET/CT after first molecular targeted therapy predicts survival of patients with renal cell carcinoma.

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.

One-month assessment of renal cell carcinoma treated by everolimus using FDG PET/CT predicts progression-free and overall survival.

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.

Comparison of 11C-4DST and 18F-FDG PET/CT imaging for advanced renal cell carcinoma: preliminary study.

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.