Takehito Kishino

Usefulness of 3′-Deoxy-3′-18F-Fluorothymidine PET for Predicting Early Response to Chemoradiotherapy in Head and Neck Cancer

This study compared the utility of 3′-deoxy-3′-18F-fluorothymidine PET (18F-FLT PET) with that of 18F-FDG PET for assessment of the early locoregional clinical outcomes of chemoradiotherapy for head and neck squamous cell carcinomas. Methods: From May 2006 to September 2010, 28 patients with head and neck squamous cell carcinomas underwent 18F-FLT and 18F-FDG PET before radiation therapy (RT), 4 wk after the initiation of RT, and 5 wk after completion of RT. PET images were evaluated qualitatively for regions of focally increased metabolism and were analyzed in relation to residual accumulation and local disease control. Results: During RT, 18F-FLT uptake decreased more significantly than 18F-FDG uptake. 18F-FLT accumulations disappeared in 34 of 54 lesions (63%), and negative predictive value was 97%. 18F-FDG PET during RT also had a high negative predictive value (100%), but only 9 lesions (16%) showed complete absence of accumulation. The specificity and overall accuracy of 18F-FLT PET were significantly higher than those of 18F-FDG PET both during and after RT. In particular, high significance was attributable to the results of the evaluations of primary lesions. There were significant differences in 3-y local control between the residual-accumulation and no-accumulation groups on both posttreatment 18F-FLT PET (P < 0.0001) and posttreatment 18F-FDG PET (P = 0.0081). Conclusion: 18F-FLT PET during RT and early follow-up facilitates the selection of optimal further therapy and the prediction of outcomes.

Prognostic value comparison between (18)F-FLT PET/CT and (18)F-FDG PET/CT volume-based metabolic parameters in patients with head and neck cancer.

Purpose The present study compared the potential of pretreatment 3′-deoxy-3′-[18F]-fluorothymidine (18F-FLT) uptake parameters and those of 18F-FDG to predict the clinical outcome of head and neck squamous cell carcinoma treated with chemoradiotherapy. Methods A total 53 patients undergoing pretreatment 18F-FLT PET/CT and 18F-FDG PET/CT from May 2006 to April 2013 were evaluated. The SUVmax, metabolic tumor volume (MTV), total lesion glycolysis, and total lesion proliferation (TLP) were determined semiquantitatively. Associations between clinical factors and PET/CT parameters and prognostic value were analyzed. Results In univariate analyses, 18F-FLT SUVmax, MTV, TLP, 18F-FDG MTV, and total lesion glycolysis correlated with locoregional control (P = 0.02, P = 0.0007, P = 0.0001, P = 0.007, and P = 0.013, respectively). Clinical T stage, 18F-FLT SUVmax, MTV, TLP, and 18F-FDG SUVmax correlated with overall survival (P = 0.012, P = 0.0057, P = 0.0018, P = 0.0012, and P = 0.047, respectively). On multivariate analyses, 18F-FLT TLP was an independent factor for locoregional control (P = 0.002; hazards ratio [HR], 5.13; 95% confidence interval [CI], 1.81-14.54), as were 18F-FLT SUVmax and MTV for overall survival (P = 0.021; HR, 3.47; 95% CI, 1.2–10.01 and P = 0.029; HR, 3.17; 95% CI, 1.12–8.95). Conclusions Pretreatment 18F-FLT PET/CT volume-based metabolic parameters are superior prognostic predictors to those of 18F-FDG PET/CT. 18F-FLT SUVmax and MTV can provide important prognostic information for patients with head and neck squamous cell carcinomas administered with chemoradiotherapy.

Comparison of 18 F-FLT PET and 18 F-FDG PET for detection of cervical lymph node metastases in head and neck cancers

Abstract Conclusion: Despite low uptake of tracer, 3′-deoxy-3′-18F-fluorothymidine (FLT) PET could detect cervical lymph node metastases as well as 2-deoxy-2-18F-fluoro-d-glucose (FDG) PET. Objective: The diagnostic efficacy of FLT PET was compared with that of FDG PET regarding nodal staging of head and neck squamous cell cancers. Methods: Twenty-three patients were examined with FLT PET and FDG PET. PET images were evaluated qualitatively for regions of focally increased metabolism and maximum standardized uptake values (SUV) were calculated for semiquantitative analysis. Results: The mean (± SD) FLT SUV in visualized metastatic lymph nodes was 4.8 ± 2.9 as compared with 6.9 ± 4.9 for FDG SUV (p < 0.001). Significant correlations were found between the area of metastatic lymph nodes and both FLT SUV (r = 0.8; p < 0.0001) and FDG SUV (r = 0.84; p < 0.0001). The false-positive (over-staged) and false-negative (under-staged) rates for lymph node staging by FLT PET were 4% (1/23) and 17% (4/23), respectively. Those for FDG PET were 9% (2/23) and 13% (3/23). All metastatic lymph nodes measuring more than 9 mm in short-axis diameter were correctly detected by FLT PET. However, both FLT and FDG PET had low sensitivity for detecting the lymph node metastases ≤ 9 mm in short-axis diameter and tumor deposits < 5 mm.

Early prediction of local control in head and neck cancer after chemoradiotherapy by FDG-PET.

ObjectiveTo determine the utility of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) for assessment of early locoregional clinical outcome of chemoradiotherapy for head and neck squamous cell carcinomas (HNSCCs). MethodsFrom July 2002 to July 2008, a total of 35 patients with HNSCCs underwent FDG-PET before and between 4 and 7 weeks (median: 5 weeks) after the end of concurrent chemoradiotherapy. FDG uptake of primary sites and metastatic lymph nodes was measured as standardized uptake values (SUVs) and was analyzed in relation to local control. ResultsVisual inspection showed a sensitivity of 88.2% and a negative predictive value of 93.1%, but the positive predictive value was only 37.5%. Setting a posttreatment SUV of 3.0 and percentage change of 60 as cut-off values, positive predictive value increased to 81.3% and overall accuracy increased to 89.9% using the combined analysis of these two parameters. The local control rate was not associated with T, the N category, or the tumor node metastasis stage. In contrast, combined analysis of the posttreatment SUV and the percentage change in SUV was a useful indicator of locoregional control. In particular, combined evaluation of SUVs was very effective for assessment of therapeutic effects with reference to metastatic lymph nodes. ConclusionEarly follow-up with FDG-PET is thus considered helpful further in choosing optimal therapy and for making an accurate prognosis.

The value of 18F-FLT PET for detecting second primary cancers and distant metastases in head and neck cancer patients.

Objective Diagnostic efficacy of 18F-FLT PET was compared with that of 18F-FDG PET regarding second primary cancers and distant metastases of head and neck squamous cell cancers (HNSCCs). Methods A total of 88 patients with HNSCCs were qualitatively examined with FLT PET and FDG PET for regions of focally increased metabolism. Final diagnoses of second primary cancer and distant metastasis were established on the basis of histological findings or clinical follow-up. Results FDG PET had 1 false-negative finding with lung metastasis, and FLT PET had 4 false-negative findings with 1 liver metastasis, 1 bone metastasis, and 2 lung metastases. There were no false-positive findings with FLT PET in contrast to 9 with FDG PET (1 in lung, 4 in mediastinum, 1 in rectum, and 3 in stomach). Overall accuracy of FDG PET and FLT PET for pretreatment metastasis staging was 92% and 98%, respectively. Five distant metastases in 3 patients occurred after the initiation of chemoradiotherapy. FLT PET missed 2 metastatic lesions (1 in liver and 1 in lung), whereas FDG PET could not discriminate intracranial metastasis because of FDG uptake in the brain. Conclusions FLT PET does not appear to be recommendable to replace FDG PET for pretreatment metastasis staging in HNSCC cases because of its lower sensitivity and higher background activity in the liver and bone marrow. However, it might provide additional diagnostic specificity and biological information.

Clinical outcomes of nedaplatin and S-1 treatment with concurrent radiotherapy in advanced head and neck cancer.

Abstract Conclusion: Nedaplatin and S-1 treatment with concurrent radiotherapy was effective, with acceptable toxicities. This regimen does not require extensive intravenous hydration and continuous infusion. Nedaplatin and S-1 may contribute to better clinical outcomes and improve quality of life for patients. Objectives: We retrospectively analyzed the clinical efficacy and toxicity of concurrent chemoradiotherapy with nedaplatin and S-1 for head and neck squamous cell cancer. Methods: Forty-six patients with oropharyngeal, hypopharyngeal, and laryngeal cancer were treated with S-1 on days 1 through 14 and nedaplatin on day 1 every 4 weeks for two cycles of radiotherapy. Therapeutic responses and adverse events were assessed. Results: Primary site tumors and neck lymph nodes exhibited complete response rates of 91% and 64.3%, respectively. The 4-year relapse-free survival and overall survival rates were 76.2% and 85.3%, respectively. The main grade 3 and 4 toxicities were mucositis (30%), leukopenia (30%), anorexia (22%), dermatitis (15%), and thrombocytopenia (9%).

The Feasibility of 18-FLT PET for the Detection of Metastatic Lymph Node of Head and Neck Cancer

Objective: Investigate the diagnostic efficacy of FLT PET for evaluating the nodal metastatic lymph nodes in head and neck cancers. Method: The diagnosis of metastatic lymph nodes was based on CT findings. The sensitivity, specificity, positive predictive value, and negative predictive value with FLT PET were determined based on CT findings. Ten patients underwent surgical treatment, and those cases were all evaluated histopathologically. Results: The sensitivity, specificity, positive predictive value, and negative predictive value with FLT PET were 90%, 91%, 96%, and 80%, respectively. While the accuracy was 98% in the lymph nodes with a minimum diameter greater than 10 mm, the accuracy decreased to 80% in lymph nodes with a minimum diameter less than 10mm. A histopathological examination of 191 lymph nodes from 10 patients revealed that FLT PET had a sensitivity, specificity, positive predictive value, and negative predictive value for lymph node of 61%, 99%, 90%, and 93%, respectively. Conclusion: FLT PET was found to have a high sensitivity for detecting metastatic lymph nodes with a minimum diameter greater than 10 mm. However, it was difficult to detect the occult metastatic lymph nodes which could not be detected with CT imaging.

A Case of Invasive Paranasal-Skull Base Mycosis

Paranasal mycosis is divided into non-invasive and invasive types. The invasive type is rare, but sometimes fatal; it can extend up to the skull base and affect the orbital cavity with bone destruction. We encountered a case of invasive paranasal-skull base mycosis resistant to surgical and pharmacological treatments. A 78-year-old man developed persistent headache and retro-ocular pain in June, 2004, and consulted the Department of Neurosurgery and Otorhinolaryngology, Ritsurin Hospital on July 20. CT scan demonstrated a soft tissue shadow in the ethmoid and sphenoid sinus with bone destruction of the skull base. We performed endonasal endoscopic biopsy on July 30, but we could not open the sphenoid sinus because of bleeding. Therefore, we only opened the bilateral ethmoid sinuses. The result of biopsy showed granulation tissue. On August 11, endonasal endoscopic surgery was performed to obtain biopsy and culture as well as to drain the sphenoid sinus. The second histopathological examination demonstrated a fungus ball. Culture of this fungus ball demonstrated Aspergillus fumigatus. Post-operative CT scan showed the persistent residue of a soft tissue shadow and expansion of a bone defect of the skull base. The patient was referred to Kagawa University for further treatment. Endonasal endoscopic surgery was performed again to remove residual fungus on August 20. Antifungal drug therapies had been administered throughout the treatment period, but we failed to control the fungal disease. The patient died on September 21.