Xiao Ping Lin

Prospective Study of Tailoring Whole-Body Dual-Modality [18F]Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography With Plasma Epstein-Barr Virus DNA for Detecting Distant Metastasis in Endemic Nasopharyngeal Carcinoma at Initial Staging

PURPOSE To evaluate which patients with nasopharyngeal carcinoma (NPC) obtained the greatest benefits from the detection of distant metastasis with [(18)F]fluorodeoxyglucose positron emission tomography and computed tomography (PET/CT) combined with plasma Epstein-Barr virus (EBV) DNA levels. PATIENTS AND METHODS Consecutive patients with NPC were prospectively enrolled. PET/CT, conventional work-up (CWU), and quantification of plasma EBV DNA were performed before treatment. The accuracy of these strategies for distant metastases was assessed. The costs of the diagnostic strategies were compared. RESULTS Eighty-six (14.8%) of the 583 eligible patients were found to have distant metastases; 71 patients (82.6%) by PET/CT and 31 patients (36.0%) by CWU. In the multivariable analysis, advanced N stage (odds ratio, 2.689; 95% CI, 1.894 to 3.818) and pretreatment EBV DNA level (odds ratio, 3.344; 95% CI, 1.825 to 6.126) were significant risk factors for distant metastases. PET/CT was not superior to CWU for detecting distant metastases in very low-risk patients (N0-1 with EBV DNA < 4,000 copies/mL; P = .062), but was superior for the low-risk patients (N0-1 with EBV DNA ≥ 4,000 copies/mL and N2-3 with EBV DNA < 4,000 copies/mL; P = .039) and intermediate-risk patients (N2-3 disease with EBV DNA ≥ 4,000 copies/mL; P < .001). The corresponding patient management changes based on PET/CT were 2.9%, 6.3%, and 16.5%, respectively. The costs per true-positive case detected by PET/CT among these groups were ¥324,138 (≈

Use of subsequent PET/CT in diffuse large B-cell lymphoma patients in complete remission following primary therapy

47,458), ¥96,907 (≈

Knockdown of PKM2 and GLS1 expression can significantly reverse oxaliplatin-resistance in colorectal cancer cells

14,188), and ¥34,182 (≈

Complementary roles of squamous cell carcinoma antigen and 18F-FDG PET/CT in suspected recurrence of cervical squamous cell cancer

5,005), respectively. CONCLUSION PET/CT detects more distant metastases than conventional staging in patients with NPC. The largest benefit in terms of cost and patient management was observed in the subgroup with N2-3 disease and EBV DNA ≥ 4,000 copies/mL.

Cervical lymph node hyperplasia on [18F]-fluorodeoxyglucose positron emission tomography/computed tomography scan after treatment of children and adolescents with malignant lymphoma

Interim 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (I-PET/CT) is a powerful tool for monitoring the response to therapy in diffuse large B-cell lymphoma (DLBCL). This retrospective study aimed to determine when and how to use I-PET/CT in DLBCL. A total of 197 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were enrolled between October 2005 and July 2011; PET/CT was performed at the time of diagnosis (PET/CT0), after 2 and 4 cycles of chemotherapy (PET/CT2 and PET/CT4, respectively), and at the end of treatment (F-PET/CT). According to the International Harmonization Project for Response Criteria in Lymphoma, 110 patients had negative PET/CT2 scans, and 87 had positive PET/CT2 scans. The PET/CT2-negative patients had significantly higher 3-year progression-free survival rate (75.8% vs. 38.2%) and 3-year overall survival rate (93.5% vs. 55.6%) than PET/CT2-positive patients. All PET/CT2-negative patients remained negative at PET/CT4, but 3 were positive at F-PET/CT. Among the 87 PET/CT2-positive patients, 57 remained positive at F-PET/CT, and 32 progressed during chemotherapy (15 at PET/CT4 and 17 at F-PET/CT). Comparing PET/CT4 with PET/CT0, 7 patients exhibited progression, and 8 achieved partial remission. Comparing F-PET/CT with PET/CT0, 10 patients exhibited progression, and 7 achieved partial remission. In conclusion, our results indicate that I-PET/CT should be performed after 2 rather than 4 cycles of immunochemotherapy in DLBCL patients. There is a limited role for subsequent PET/CT in the detection of relapse in PET/CT2-negative patients, but repeat PET/CT is required if the PET/CT2 findings are positive.

Advantage of PET/CT in target delineation of MRI negative cervical lymph nodes in intensity-modulated radiation therapy planning for nasopharyngeal carcinoma

Clinical treatment for colorectal cancer (CRC) thus far encounters a huge challenge due to oxaliplatin-resistance. As crucial rate-limiting enzymes in aerobic glycolysis and glutaminolysis, pyruvate kinase M2 type (PKM2) and kidney-type glutaminase (GLS1) are proposed to carry important implications in colorectal carcinogenesis and drug-resistance. This study aimed to explore the possible association of oxaliplatin-resistance with aerobic glycolysis/glutaminolysis indexed by PKM2/GLS1 expression. PKM2 and GLS1 expression was quantified by polymerase chain reaction (PCR) and Western blot techniques in CRC cell lines. The abilities of cell formation, kinetics, migration, invasion, survival and apoptosis, as well as permeability glycoprotein (Pgp) expression were inspected before and after knocking-down PKM2/GLS1 expression. In addition, the influence of knocking-down PKM2/GLS1 expression was evaluated in vivo. Differentiated PKM2 and GLS1 expression in both THC8307 and THC8307/Oxa cell lines was identified. In the THC8307 cell line, PKM2 and GLS1 can accelerate malignant behaviors, increase oxaliplatin-resistance, upregulate Pgp expression, and inhibit cell apoptosis. Contrastingly in the THC8307/Oxa cell line, knockdown of PKM2/GLS1 expression can restrain malignant behaviors, reestablish oxaliplatin-sensitivity, downregulate Pgp expression, and induce cell apoptosis. In xenograft, knockdown of PKM2/GLS1 expression can significantly inhibit tumor growth, reduce Pgp expression, and increase tumor apoptosis. Taken together, the present findings enriched our knowledge by demonstrating a significant association of PKM2 and GLS1 with oxaliplatin-resistance in CRC. We further propose that knockdown of PKM2/GLS1 expression may constitute a novel therapeutic strategy toward effective treatment for CRC.

Optimal modality for detecting distant metastasis in primary nasopharyngeal carcinoma during initial staging: A systemic review and meta-analysis of 1774 Patients

Purpose: To assess the clinical value of FDG PET/CT and evaluate the complementary roles of serum squamous cell carcinoma antigen (SCCAg) and FDG PET/CT in the diagnosis of suspected recurrent of cervical squamous cell cancer. Methods: Serum SCCAg levels were retrospectively reviewed in patients previously treated for cervical squamous cell carcinoma, who had suspected recurrence of cervical cancer and who had undergone FDG PET/CT scans. The clinical impact of elevated SCCAg (>1.5 ng/ml) and negative SCCAg (≤1.5 ng/ml) levels were analyzed based on the results of PET/CT and final diagnosis. Results: The overall patient-based sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of PET/CT for the detection of tumor recurrence or malignancy were 100% (86/86), 80.8% (21/26), 95.5% (107/112), 94.5% (86/91) and 100% (21/21), respectively. Of the 112 patients included in this study, recurrence or malignancy was detected by PET/CT in 62 of the 64 patients with elevated SCCAg, compared to 24 of the 48 patients with negative SCCAg levels. The overall patient-based PPV, NPV, sensitivity and accuracy of SCCAg for the detection of tumor recurrence or malignancy were 96.9% (62/64), 50% (24/48), 72.1% (62/86) and 76.8% (86/112), respectively. The five false-positive PET/CT results were all associated with patients with negative SCCAg levels. The PPV of positive PET/CT-associated elevated SCCAg for the detection of tumor recurrence or malignancy was 100% (62/62). The NPV of negative SCCAg-associated negative PET/CT was 100% (19/19). Conclusions: Serum SCCAg evaluation and FDG PET/CT imaging can be complementary techniques in cases of suspected recurrent cervical squamous cancer. Positive PET/CT with elevated SCCAg can predict recurrence. Although PET/CT cannot confidently be deferred due to a negative SCCAg test, the possibility of a false-positive PET/CT in those cases may have diagnostic importance.

[Role of 18F-FDG PET/CT in diagnosis and staging of nasopharyngeal carcinoma].

PURPOSE To define imaging manifestations and clinical prognosis of cervical lymph node hyperplasia using [(18)F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scanning after treatment of children and adolescents with malignant lymphoma. METHODS Children and adolescent patients with malignant lymphoma who had high FDG uptake in their cervical lymph nodes via PET/CT after treatment, which was not due to tumor recurrence or residue, were retrospectively analyzed. RESULTS Twenty-seven patients with a median age of 12 years were included; 11 had Hodgkins disease and 16 had non-Hodgkins lymphoma. The time from PET/CT scan to completion of therapy was 1-36 months, 85.2% (23/27) of which took place within 12 months. Three patients had confirmed lymph node follicular hyperplasia by biopsy, while all 27 patients achieved disease-free survival during the follow-up period. The maximum standardized uptake values (SUVmax) of cervical lymph nodes were 2.2-16.2 and the maximum short axis ranged from 0.3 to 1.2 cm. Cervical lymph node hyperplasia was noted in neck levels I-V, and neck level II bilaterally had the highest incidence (100%). Bilateral cervical lymph node hyperplasia was symmetrical in terms of both the SUVmax and affected locations. Thymic hyperplasia and nasopharyngeal lymphoid hyperplasia were both observed in 24 patients (88.9%). There was no relationship in terms of the SUVmax between cervical lymph nodes and thymic tissue, cervical nodes or nasopharyngeal lymphoid tissue. CONCLUSION Cervical lymph node hyperplasia with high FDG uptake on PET/CT scans found after treating children and adolescents with malignant lymphoma can be benign processes. Awareness of this possibility may help avoid invasive procedures and over-treatment.

18F-FDG PET/CT for the detection of primary tumors metastasizing to lymph nodes of the neck

Introduction: In intensity-modulated radiation therapy (IMRT) planning for nasopharyngeal carcinoma (NPC), cervical lymph nodes (CLNs) that appear negative on magnetic resonance imaging (MRI) scans can be difficult to target. The purpose of this study was to assess the advantage of 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) for distinguishing MRI-negative CLNs and the effect of 18F-FDG PET/CT on diagnosis, target delineation, and dose prescription in IMRT planning for NPC. Methods: Thirty-five NPC patients with 37 MRI-negative CLNs underwent 18F-FDG PET/CT imaging before treatment. Ultrasonography-guided fine-needle aspiration cytology (USgFNAC) was performed to examine the pathology of CLNs. The 18F-FDG PET/CT and cytopathological results were compared, and the diagnostic accuracy of 18F-FDG PET/CT was calculated. The cytopathologically confirmed CLNs were delineated and treated as the gross tumor volume of lymph nodes (denoted as GTVnd). Results: Nineteen of the 37 MRI-negative CLNs were positive on 18F-FDG PET/CT, and metastasis was confirmed by USgFNAC in 16 CLNs. Of the remaining 18 18F-FDG PET/CT-negative lymph nodes, metastasis was confirmed in one. The diagnostic accuracy, sensitivity, and specificity of 18F-FDG PET/CT were 89.2%, 94.1%, and 85.0%, respectively. The positive and negative predictive values were 84.2% and 94.4%, respectively. With a median follow-up of 48.3 months, no relapse was observed among the 18F-FDG PET/CT-positive CLNs with metastasis confirmed by USgFNAC and treated as GTVnd. Conclusion: 18F-FDG PET/CT had high accuracy, sensitivity, and specificity for distinguishing MRI-negative CLNs. 18F-FDG PET/CT-positive CLNs could reasonably be categorized as high-risk clinical tumor volume in IMRT planning for NPC.

Application of 18F-FDG PET/CT in cervical cancer with elevated levels of serum squamous cell carcinoma antigen during the follow-up

Purpose: To compare the diagnostic performance of two modalities commonly used for detecting distant metastasis in primary nasopharyngeal carcinoma (NPC): 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and conventional work-ups (CWUs). Methods: All topic-related studies were comprehensively searched and included. We determined sensitivities and specificities across studies, calculated negative and positive likelihood ratios (LR- and LR+, respectively), and constructed summary receiver operating characteristic curves. Moreover, we compared the diagnostic performance of PET/CT and CWUs by analyzing studies that reported the results of these diagnostic methods on the same patients. Results: The pooled sensitivity and specificity were 85.7% and 98.1% for PET/CT (1474 patients), and 38.0% and 97.6% for CWUs (1329 patients). In the head-to-head comparison of PET/CT and CWUs (1029 patients), PET/CT showed a significantly higher sensitivity (83.7% vs. 40.1%, P < 0.001) and lower LR- (0.169 vs. 0.633, P < 0.001) than CWUs on a per-patient basis; no significant difference was observed in pooled specificity (97.7% vs. 97.8%, P = 0.892) or LR+ (36.416 vs. 16.845, P = 0.149). The superiority of PET/CT over CWUs was due mainly to the better diagnostic performance on bone metastasis. However, suboptimal sensitivity of PET/CT was reported in the aspect of detection of liver metastasis. Sensitivity analyses showed relatively poor sensitivity and LR- of PET/CT compared to the original analysis. Conclusions: PET/CT was superior to CWUs in detecting distant metastasis in primary NPC. However, the efficacy of PET/CT in detecting liver metastasis still requires further optimization.