¹⁸F-fluoro-deoxyglucose positron emission tomography in assessment of myeloma-related bone disease: a systematic review

BACKGROUND:

The goal of this study was to conduct a comparative analysis of whole body X‐ray (WBXR) and ¹⁸F‐fluoro‐deoxyglucose positron emission tomography (¹⁸FDG PET) in staging and response assessment of multiple myeloma.

METHODS:

We performed a systematic review of studies comparing ¹⁸FDG PET with WBXR and/or magnetic resonance imaging in terms of sensitivity for myeloma‐related bone disease at staging and during follow‐up.

RESULTS:

Eighteen studies involving 798 patients met the inclusion criteria. The mean Quality Assessment of Diagnostic Accuracy Studies (QUADAS) score, expressed as a percentage of the maximum score, was 61%. In 7 studies (n = 242 patients), concordance assessment between WBXR and ¹⁸FDG PET scan was possible, showing a higher sensitivity of the ¹⁸FDG PET in the detection of myeloma bone lesions in 6 studies. The only study reporting on the prognostic value of ¹⁸FDG PET at staging found that the number of FDG‐avid focal lesions was an independent prognostic parameter. In addition, the limited studies on response monitoring showed that normalization of ¹⁸FDG PET during treatment correlated with a superior clinical outcome.

CONCLUSIONS:

In general, ¹⁸FDG PET has a superior sensitivity for myeloma bone lesions compared with WBXR. Future studies have to validate the additive value of myeloma‐related bone disease detected on ¹⁸FDG PET–computed tomography (CT) in predicting outcome. Response monitoring with the use of ¹⁸FDG PET‐CT during treatment is promising, allowing more precise prediction of prognosis compared with the standard response monitoring. In view of the expanding treatment options for multiple myeloma, this may provide important information for treatment decisions in the future. Cancer 2012. © 2011 American Cancer Society.     

Early 18F-labeled fluoro-2-deoxy-D-glucose positron emission tomography scanning in the lymphomas: changing the paradigms of treatments?

The identification of refractory or nonresponding tumors at an early period during therapy may lead to abbreviation of the current therapy regimen or timely institution of an alternative therapy protocol. Nevertheless, evaluation of treatment response is consequential clinically if the tumor potentially is curable and if effective treatment alternatives exist, so that change in treatment ultimately may increase the probability of response and survival. Hodgkin disease (HD) and diffuse large cell lymphoma (LCL) fit in this model well. However, a subset of patients is either refractory to first-line treatment or develops recurrent disease after an initial remission. Improvements in the treatment of these diseases rely not only on new therapy modalities and accurate assessment of disease extent but also on the assessment of disease extent and on timely and accurate therapy response to enable a more effective management plan. Although the International Prognostic Score for HD and International Prognostic Index for LCL have proved valuable for the stratification of patients in clinical trials, there is variability in outcome within the individual risk groups. Recently, positron emission tomography using (18)F-labeled fluoro-2-deoxy-D-glucose (FDG-PET) imaging has been suggested as a sensitive and relatively more specific means to reflect tumor biologic changes after therapy. With increasingly compelling evidence, early FDG-PET provides a reliable means to assess tumor response accurately that may lead to better management with an effective therapeutic approach.     

Which is the best monitoring study (tumor marker, computed tomography or 18F-fluoro-2-deoxy-D-glucose positron emission tomography) to evaluate efficacy of chemotherapy on unresectable pancreatic cancer ?

The objective of this study was to clarify the clinical features of long-time survivors with unresectable pancreatic cancer treated by gemcitabine(GEM)alone and to predict survival time by carbohydrate antigen(CA)19-9, enhanced computed tomography(CT), and 18F-fluoro-2-deoxy-D-glucose positron emission tomography(FDG-PET) in monitoring the response to chemotherapy. Twenty-one patients with unresectable pancreatic cancer were enrolled in this study. All patients were evaluated by serum CA19-9 level, tumor size of CT, maximum standardized uptake value (SUVmax)with FDG-PET and other factors before chemotherapy(GEM alone at a dose of 1,000 mg/m(2) weekly x 3 followed by 1 week of rest), and they received chemotherapy until obviously progressive disease. Serum CA19-9, tumor size of CT and SUVmax with PET were measured after three courses of chemotherapy in ten patients. We compared these three modalities in terms of two points: Which is the best modality to predict survival time ? Which is the best monitoring modality to evaluate the efficacy of chemotherapy on unresectable pancreatic cancer ? A significant difference in survival time was not found between high level group and low level group of serum CA19-9 level and SUVmax with FDG-PET and also longest length of tumor by enhanced CT. In ten patients we evaluated the response rate of each parameter CA19-9(IU/mL), CT(longest length of tumor), and SUVmax with FDG-PET. We defined the response rate(pretreatment level of CA19-9 or longest length of tumor or SUVmax-after 3 courses chemotherapy level of CA19-9 or longest length of tumor or SUVmax/pretreatment level of CA19-9 or longest length of tumor or SUVmax). Response rate of CA19-9 was significantly correlated with survival time(r=0.633, p=0.0481). However, the response rate of SUVmax with FDG-PET had no significant correlation with survival time(r=0.019, p=0.9630). In the present study, the response rate of CA19-9 is the best monitoring modality to evaluate the efficacy of chemotherapy.     

Prognostic value of plasma Epstein–Barr virus DNA level during posttreatment follow-up in the patients with nasopharyngeal carcinoma having undergone intensity-modulated radiotherapy

Background: The value of Epstein–Barr virus (EBV) DNA assay during posttreatment follow-up of the patients with nasopharyngeal carcinoma (NPC) presenting with different pretreatment plasma EBV DNA levels remains unclear. In the present study, we aimed to evaluate the prognostic value of plasma EBV DNA assay during posttreatment follow-up in the patients with NPC who have undergone intensity-modulated radiotherapy. Methods: The medical records of 385 NPC patients treated with intensity-modulated radiotherapy between Novem-ber 2009 and February 2012 were reviewed. All patients underwent plasma EBV DNA assays before treatment, within 3 months after treatment, and then every 3–12 months during posttreatment follow-up period. The recurrence rates for patients with different pretreatment and posttreatment follow-up plasma EBV DNA levels were analyzed. Results: Of the 385 patients, 267 (69.4％) had detectable pretreatment plasma EBV DNA (> 0 copy/mL) and 93 (24.2％) had detectable posttreatment EBV DNA during a median follow-up of 52.8 months (range 9.3–73.8 months). Detectable EBV DNA during posttreatment follow-up was found in 14.4％ (17/118) and 28.5％ (76/267) of patients with undetectable and detectable pretreatment EBV DNA, respectively, and was significantly associated with tumor recurrence in both patient groups. EBV DNA was detectable in 12.8％ (40/313) of patients who remained disease-free, 56.4％ (22/39) of patients with locoregional recurrence alone, and 93.9％ (31/33) of patients with distant metastasis as the first recurrence event (P < 0.001); 6.5％ (19/292) of patients with undetectable EBV DNA and 57.0％ (53/93) of patient with detectable EBV DNA during posttreatment follow-up experienced tumor recurrence. Compared with other cut-off values, the cut-off value of 0 copy/mL for EBV DNA during posttreatment follow-up had the highest area under the ROC curve (AUC) value (0.804, 95％ confidence interval 0.741–0.868) for predicting tumor recurrence (sensi-tivity, specificity, and accuracy: 73.6％, 87.2％, and 84.7％, respectively).Conclusion: Plasma EBV DNA level during posttreatment follow-up is a good marker for predicting distant metasta-sis but not locoregional recurrence in the patients with NPC irrespective of the pretreatment EBV DNA levels.     

Plasma Epstein–Barr viral DNA load at midpoint of radiotherapy course predicts outcome in advanced-stage nasopharyngeal carcinoma

BackgroundTo test the hypothesis that prognostication of treatment outcome is feasible by biomarker response at midcourse of chemoradiotherapy (CRT)/radiotherapy (RT), with respect to the plasma load of Epstein–Barr viral (EBV) DNA in nasopharyngeal carcinoma (NPC).Patients and methodsOne hundred seven patients with stage IIB–IV NPC were prospectively studied. Plasma EBV DNA load was measured by quantitative PCR before therapy (pre-DNA), at completion of 4 weeks of CRT/RT (mid-DNA), and within 3 months of completion of therapy (post-DNA). The end points are post-DNA load, a recognized surrogate of survival, and clinical outcome.ResultsNinety-three percent of patients had detectable EBV DNA before therapy (median load = 972 copies/ml). EBV DNA became undetectable in 55 (51%) patients at the end of week 4 of therapy. Detectable mid-DNA was associated with worse clinical outcome (median follow-up time, 6.2 years), for distant failure [hazard ratio (HR) 12.02, 95% confidence interval (CI) 2.78–51.93; P < 0.0001], progression-free survival (PFS; HR 4.05, 95% CI 1.89–8.67, P < 0.0001), and overall survival (OS; HR 3.29, 95% CI 1.37–7.90, P = 0.0077). Seventy-four percent of all failures were associated with detectable mid-DNA, whereas 34% of all failures were associated with detectable post-DNA. Stratification by tumor stage (IIB, III, IV) has no significant prognostic effect.ConclusionsUnfavorable EBV DNA response at midcourse of RT/CRT is an adverse prognosticator for treatment outcome, is linked to majority of all failures, and discriminates outcome better than tumor stage. The data could provide a basis for trial design that addresses alteration of therapy intensity during the latter phase of CRT, and adjuvant therapy. Validation studies are awaited.     

Phase Ⅱ study of induction chemotherapy followed by concurrent chemoradiotherapy with raltitrexed and cisplatin in locally advanced nasopharyngeal carcinoma

Objective: For locally advanced nasopharyngeal carcinoma(LA-NPC) patients, high incidences of distant metastases and severe treatment related toxicities are the main obstacles needed to be overcome. Raltitrexed, a specific thymidylate synthase inhibitor with a convenient administration schedule, has an acceptable and manageable toxicity, and possesses radio-sensitizing properties. To investigate the efficacy and safety of raltitrexed and cisplatin induction chemotherapy and concurrent chemoradio...     

Imaging of integrin αvβ3 expression in patients with malignant glioma by [18F] Galacto-RGD positron emission tomography

Inhibitors targeting the integrin α_vβ₃ are promising new agents currently tested in clinical trials for supplemental therapy of glioblastoma multiforme (GBM). The aim of our study was to evaluate ¹⁸F-labeled glycosylated Arg-Gly-Asp peptide ([¹⁸F]Galacto-RGD) PET for noninvasive imaging of α_vβ₃ expression in patients with GBM, suggesting eligibility for this kind of additional treatment. Patients with suspected or recurrent GBM were examined with [¹⁸F]Galacto-RGD PET. Standardized uptake values (SUVs) of tumor hotspots, galea, and blood pool were derived by region-of-interest analysis. [¹⁸F]Galacto-RGD PET images were fused with cranial MR images for image-guided surgery. Tumor samples taken from areas with intense tracer accumulation in the [¹⁸F]Galacto-RGD PET images and were analyzed histologically and immunohistochemically for α_vβ₃ integrin expression. While normal brain tissue did not show significant tracer accumulation (mean SUV, 0.09 ± 0.04), GBMs demonstrated significant but heterogeneous tracer uptake, with a maximum in the highly proliferating and infiltrating areas of tumors (mean SUV, 1.6 ± 0.5). Immunohistochemical staining was prominent in tumor microvessels as well as glial tumor cells. In areas of highly proliferating glial tumor cells, tracer uptake (SUVs) in the [¹⁸F]Galacto-RGD PET images correlated with immunohistochemical α_vβ₃ integrin expression of corresponding tumor samples. These data suggest that [¹⁸F] Galacto-RGD PET successfully identifies α_vβ₃ expression in patients with GBM and might be a promising tool for planning and monitoring individualized cancer therapies targeting this integrin.     

Quantifying initial cellular events of mouse radiation lymphomagenesis and its tumor prevention in?vivo by positron emission tomography and magnetic resonance imaging

Radiation‐induced thymic lymphoma (RITL) in mice is induced by fractionated whole‐body X‐irradiation (FX) and has served as a useful model for studying radiation carcinogenesis. In this model, the initial postirradiation cellular events in the thymus and bone marrow (BM) are critically important for tumorigenesis, and BM transplantation (BMT) prevents RITL. However, direct assessment of these events is so far restricted by the lack of noninvasive monitoring techniques. Here, we have developed positron emission tomography (PET) and magnetic resonance imaging (MRI) methods to quantify the events critical for RITL development and the effects of BMT in living animals. Apparent diffusion coefficients (ADCs) were calculated from diffusion‐weighted MRI to evaluate the changes in the BM of mice receiving FX. ADC values dramatically changed in the irradiated BM, corresponding to pathological findings of the irradiated BM, returning to normal levels following BMT sooner than with spontaneous recovery. PET with 4ʹ‐[methyl‐11C]thiothymidine, a novel tracer for cell proliferation, revealed that the irradiated thymus showed significantly higher tracer uptake than the unirradiated thymus 1 week after FX. Interestingly, its increased uptake was completely abolished by BMT, even with very few donor‐derived cells in the thymus. Thereafter, the thymus receiving BMT had significantly increased tracer uptake. These findings suggest that BMT first suppresses FX‐induced aberrant thymocyte proliferation and then accelerates thymic regeneration. This study demonstrates the feasibility of using PET and MRI for noninvasive monitoring of tumorigenic cellular processes in an animal model of radiation‐induced cancer.     

Relationship of circulating tumor cells and Epstein–Barr virus DNA to progression-free survival and overall survival in metastatic nasopharyngeal carcinoma patients

We analyzed the number of circulating tumor cells (CTCs) and Epstein–Barr virus DNA (EBV DNA) for diagnosis, monitoring and prognosis of patients with metastatic nasopharyngeal carcinoma (mNPC). The levels of CTCs and EBV DNA were measured at baseline and after first-line chemotherapy in 148 mNPC patients prospectively enrolled between December 2014 and August 2016. We also collected 122 non-mNPC cases within the same time frame for examining CTCs and EBV DNA at baseline. In 270 NPC patients, we observed improved specificity (86.0% vs. 41.0%) and inferior sensitivity (42.3% vs. 81.3%) of CTCs as compared to EBV DNA for diagnosis of distant metastasis. mNPC patients were stratified into unfavorable and favorable prognostic groups, respectively, based on CTC of 12 at baseline and 1 after first-line chemotherapy and EBV DNA of 10,000 at baseline and 4,000 after first-line chemotherapy. Conversion of baseline unfavorable CTCs and EBV DNA to favorable after first-line chemotherapy was associated with significantly longer progression-free survival (PFS) and overall survival (OS) compared to patients with unfavorable CTCs and EBV DNA at both time points. Among patients with a complete/partial response as per imaging evaluation, favorable CTCs and EBV DNA levels after first-line chemotherapy were associated with significantly longer PFS and OS. In conclusion, our data demonstrated the number of CTCs and EBV DNA before, after and during first-line chemotherapy were strong predictive markers for mNPC patients. When utilized in conjunction with imaging studies, CTCs and EBV DNA could provide additional prognostic information.     

Experimental study on the therapeutic effect of positron emission tomography agent [¹⁸F]-labeled 2-deoxy-2-fluoro-d-glucose in a colon cancer mouse model

The purpose of this study was to assess the therapeutic effect of positron emission tomography agent [1?F]-labeled 2-deoxy-2-fluoro-d-glucose (1?F-FDG) in a colorectal cancer mouse model. Three (3) tumor-bearing mice groups were treated with different doses of 1?F-FDG. Mice were imaged by positron emission tomography with 1?F-FDG before and after treatment weekly and the tumor growth rate was calculated. Tumor, brain, heart, and kidney of mice were analyzed for expression of glucose transporters and vascular endothelial growth factor (VEGF) by immunofluorescent staining, and the presence of apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) method. All 3 treated groups showed significant 1?F-FDG reduction compared with the control group (p?相似文献   

A randomized trial of induction docetaxel–cisplatin–5FU followed by concomitant cisplatin-RT versus concomitant cisplatin-RT in nasopharyngeal carcinoma (GORTEC 2006-02)

BackgroundConcomitant chemotherapy (CT)–radiotherapy (RT) is a standard of care in locally advanced nasopharyngeal carcinoma (NPC) and a role for induction CT is not established.MethodsPatients with locally advanced NPC, WHO type 2 or 3, were randomized to induction TPF plus concomitant cisplatin-RT or concomitant cisplatin-RT alone. The TPF regimen consisted of three cycles of Docetaxel 75 mg/m² day 1; cisplatin 75 mg/m² day 1; 5FU 750 mg/m²/day days 1–5. RT consisted of 70 Gy in 7 weeks plus concomitant cisplatin 40 mg/m² weekly.ResultsA total of 83 patients were included in the study. Demographics and tumour characteristics were well balanced between both arms. Most of the patients (95%) in the TPF arm received three cycles of induction CT. The rate of grade 3–4 toxicity and the compliance (NCI-CTCAE v3) during cisplatin-RT were not different between both arms. With a median follow-up of 43.1 months, the 3-year PFS rate was 73.9% in the TPF arm versus 57.2% in the reference arm [hazard ratio (HR) = 0.44; 95% confidence interval (CI): 0.20–0.97, P = 0.042]. Similarly the 3 years overall survival rate was 86.3% in the TPF arm versus 68.9% in the reference arm (HR = 0.40; 95% CI: 0.15–1.04, P = 0.05).ConclusionIn conclusion, several important aspects can be emphasized: the compliance to induction TPF was good and TPF did not compromise the tolerance of the concomitant RT-cisplatin phase. The improved PFS and overall survival rates needs to be confirmed by further trials.     

Spontaneous remission of residual post-therapy plasma Epstein–Barr virus DNA and its prognostic implication in nasopharyngeal carcinoma: A large-scale,big-data intelligence platform-based analysis

Detectable post-therapy plasma Epstein–Barr virus (EBV) DNA predicts poor survival in non-metastatic nasopharyngeal carcinoma (NPC). However, some patients subsequently experience spontaneous remission of residual EBV DNA during follow-up and it was unclear whether these patients were still at high risk of disease failure. Using the NPC database from an established big-data intelligence platform, 3269 NPC patients who had the plasma EBV DNA load measured at the end of therapy (± 1 week) were identified. In total, 93.0% (3031/3269) and 7.0% (238/3269) of patients had undetectable and detectable (> 0 copy/ml) plasma EBV DNA at the end of therapy (EBV DNA_end), respectively. Detectable EBV DNA_end was a prognostic factor for poorer 3-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS), and loco-regional recurrence-free survival (LRRFS) in both univariate and multivariate analyses. Of 238 patients with residual EBV DNA_end, 192 underwent EBV DNA assay 3 months after and s pontaneous remission occurred in 72.4% (139/192). However, these patients still had poorer 3-year DFS (55.1% vs. 89.8%), OS (79.1% vs. 96.2%), DMFS (68.4% vs. 94.1%) and LRRFS (84.5% vs. 95.0%) than patients with undetectable EBV DNA_end (all p < 0.001). And patients with persistent detectable post-therapy EBV DNA had the worst outcomes. These results were confirmed in multivariate analysis. In conclusion, residual EBV DNA post therapy was a robust biomarker for NPC prognosis. Although residual post-therapy EBV DNA could spontaneous remit during follow-up, these patients were still at high risk of disease failure and such patients may benefit from adjuvant therapy.     

Prognostic values of the integrated model incorporating the volume of metastatic regional cervical lymph node and pretreatment serum Epstein–Barr virus DNA copy number in predicting distant metastasis in patients with N1 nasopharyngeal carcinoma

Background: According to the 7th edition of the American Joint Committee on Cancer (AJCC) staging system, over 50% of patients with nasopharyngeal carcinoma (NPC) have N1 disease at initial diagnosis. However, patients with N1 NPC are relatively under-researched, and the metastasis risk of this group is not well-stratified. This study aimed to evaluate the prognostic values of gross tumor volume of metastatic regional lymph node (GTVnd) and pretreatment serum copy number of Epstein–Barr virus (EBV) DNA in predicting distant metastasis of patients with N1 NPC, and to develop an integrated prognostic model that incorporates GTVnd and EBV DNA copy number for this group of patients. Methods: The medical records of 787 newly diagnosed patients with nonmetastatic, histologically proven N1 NPC who were treated at Sun Yat-sen University Cancer Center between November 2009 and February 2012 were ana-lyzed. Computed tomography-derived GTVnd was measured using the summation-of-area technique. Blood sam-ples were collected before treatment to quantify plasma EBV DNA. The receiver operating characteristic (ROC) curve analysis was used to evaluate the cut-off point for GTVnd, and the area under the ROC curve was used to assess the predicted validity of GTVnd. The survival rates were assessed by Kaplan–Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model. Results: The 5-year distant metastasis-free survival (DMFS) rates for patients with GTVnd > 18.9 vs. ≤ 18.9 mL were 82.2% vs. 93.2% (P < 0.001), and for patients with EBV DNA copy number > 4000 vs. ≤ 4000 copies/mL were 83.5% vs. 93.9% (P < 0.001). After adjusting for GTVnd, EBV DNA copy number, and T category in the Cox regression model, both GTVnd > 18.9 mL and EBV DNA copy number > 4000 copies/mL were significantly associated with poor prognosis(both P < 0.05). According to combination of GTVnd and EBV DNA copy number, all patients were divided into low-, moderate-, and high-risk groups, with the 5-year DMFS rates of 96.1, 87.4, and 73.8%, respectively (P < 0.001). Multi-variate analysis confirmed the prognostic value of this model for distant metastatic risk stratification (hazard ratio [HR], 4.17; 95% confidence interval [CI] 2.34–7.59; P < 0.001). Conclusions: GTVnd and serum EBV DNA copy number are independent prognostic factors for predicting distant metastasis in NPC patients with N1 disease. The prognostic model incorporating GTVnd and EBV DNA copy number may improve metastatic risk stratification for this group of patients.