Diagnostic performance of Fluorine-18-Fluorodeoxyglucose positron emission tomography in the assessment of pleural abnormalities in cancer patients: A systematic review and a meta-analysis

Objective

To systematically review and meta-analyze published data about the diagnostic performance of Fluorine-18-Fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in the assessment of pleural abnormalities in cancer patients.

Methods

A comprehensive literature search of studies published through June 2013 regarding the role of ¹⁸F-FDG-PET and PET/CT in evaluating pleural abnormalities in cancer patients was performed. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR−) and diagnostic odd ratio (DOR) of ¹⁸F-FDG-PET or PET/CT on a per patient-based analysis were calculated. The area under the summary ROC curve (AUC) was calculated to measure the accuracy of these methods in the assessment of pleural abnormalities. Sub-analyses considering ¹⁸F-FDG-PET/CT and patients with lung cancer only were carried out.

Results

Eight studies comprising 360 cancer patients (323 with lung cancer) were included. The meta-analysis of these selected studies provided the following results: sensitivity 86% [95% confidence interval (95%CI): 80–91%], specificity 80% [95%CI: 73–85%], LR+ 3.7 [95%CI: 2.8–4.9], LR− 0.18 [95%CI: 0.09–0.34], DOR 27 [95%CI: 13–56]. The AUC was 0.907. No significant improvement considering PET/CT studies only and patients with lung cancer was found.

Conclusions

¹⁸F-FDG-PET and PET/CT demonstrated to be useful diagnostic imaging methods in the assessment of pleural abnormalities in cancer patients, nevertheless possible sources of false-negative and false-positive results should be kept in mind. The literature focusing on the use of ¹⁸F-FDG-PET and PET/CT in this setting remains still limited and prospective studies are needed.     

18F-脱氧葡萄糖正电子发射计算机断层显像对淋巴瘤分期和预后评估的作用

 【摘要】　目的　探讨18F-脱氧葡萄糖正电子发射计算机断层显像（FDG-PET）对淋巴瘤患者分期及预后评估的作用。 方法 对初诊的41例淋巴瘤患者,化疗前和化疗4个疗程后行FDG-PET,中位随访30个月,比较化疗前FDG-PET分期和化疗4个疗程后FDG-PET结果对预后的影响。 结果 41例患者治疗前结内、外病灶的最大标准摄取值（SUVmax）分别为9.7±6.9和8.4±6.8。侵袭性非霍奇金淋巴瘤（NHL）和惰性NHL比较,结内、外病灶的SUVmax值差异有统计学意义（侵袭性NHL分别为10.3±7.5和9.1±6.5,惰性NHL分别为4.7±2.1和2.4±0.6,均P<0.05）。NHL和霍奇金淋巴瘤（HL）、B细胞和T细胞NHL、活化B与生发中心来源弥漫大B细胞淋巴瘤治疗前FDG-PET的SUVmax差异无统计学意义（P>0.05）。化疗前 22例（54 ％）患者FDG-PET检出结外器官病变;6例（15 ％）因FDG-PET发现CT等其他检查未显示的淋巴结或结外病变而提高临床分期。治疗前经FDG-PET分期为Ⅰ、Ⅱ期的患者15例（37 ％）,Ⅲ、Ⅳ期的患者26例（63 ％）。随访期间,FDG-PET分期Ⅰ、Ⅱ期的患者中1例（7 ％）因疾病进展死亡,Ⅲ、Ⅳ期的患者中6例（23 ％）因疾病进展死亡。41例患者化疗4个疗程后行FDG-PET检查,FDG-PET阴性的患者17例（41 ％）中,随访期间1例（6 ％）因疾病复发死亡,FDG-PET阳性的患者24例（59 ％）中,随访期间6例（25 ％）因疾病进展死亡。 结论　化疗前FDG-PET检查有助于对淋巴瘤患者进行准确的临床分期,化疗4个疗程后FDG-PET检查有助于评估淋巴瘤患者的预后,指导进一步治疗。     

18F‐Fluorodeoxyglucose positron emission tomography/computed tomography for the detection of recurrent bone and soft tissue sarcoma

BACKGROUND:

The clinical utility of modern hybrid imaging modalities for detecting recurrent bone or soft tissue sarcoma remains to be determined. In this report, the authors present a clinical study on the diagnostic accuracy and incremental value of integrated ¹⁸F‐fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F‐FDG PET/CT) in patients with a history of sarcoma who have clinically suspected disease recurrence.

METHODS:

Forty‐three patients who had a history of bone or soft tissue sarcoma and had documented complete remission underwent ¹⁸F‐FDG PET/CT. Image analysis was performed independently for ¹⁸F‐FDG PET (n = 43) and for contrast‐enhanced spiral CT (CE‐CT) (n = 30) by 2 separate readers, whereas combined ¹⁸F‐FDG PET/CT (n = 43) images were analyzed in consensus by both readers. Imaging findings were rated on a 5‐point scale and finally were reported as malignant, benign, or equivocal. Imaging findings were validated either by histopathology (n = 24) or by clinical follow‐up (n = 19).

RESULTS:

¹⁸F‐FDG PET/CT had greater sensitivity and specificity compared with CE‐CT alone (94% and 92% vs 78% and 67%, respectively), resulting in significantly greater accuracy (93% vs 73%; P = .03). ¹⁸F‐FDG PET/CT was particularly superior regarding detection of local recurrence or soft tissue lesions (sensitivity and specificity: 83% and 100% vs 50% and 100%, respectively) or bone metastases (100% and 100% vs 85% and 88%, respectively).

CONCLUSIONS:

¹⁸F‐FDG PET/CT had greater diagnostic accuracy in the detection of recurrent bone or soft tissue sarcoma compared with CE‐CT alone. The detection of local recurrence was the most evident advantage of ¹⁸F‐FDG PET/CT over CE‐CT. Cancer 2013. © 2012 American Cancer Society.     

[18F]FDG and [18F]FES positron emission tomography for disease monitoring and assessment of anti-hormonal treatment eligibility in granulosa cell tumors of the ovary

Purpose: Adult granulosa cell tumors (AGCTs) of the ovary represent a rare malignancy in which timing and choice of treatment is a clinical challenge. This study investigates the value of FDG-PET/CT and FES-PET/CT in monitoring recurrent AGCTs and assessing eligibility for anti-hormonal treatment.Materials and Methods: We evaluated 22 PET/CTs from recurrent AGCT patients to determine tumor FDG (n = 16) and FES (n = 6) uptake by qualitative and quantitative analysis. We included all consecutive patients from two tertiary hospitals between 2003-2020. Expression of ERα and ERβ and mitoses per 2 mm² were determined by immunohistochemistry and compared to FES and FDG uptake, respectively.Results: Qualitative assessment showed low-to-moderate FDG uptake in most patients (14/16), and intense uptake in 2/16. One patient with intense tumor FDG uptake had a high mitotic rate (18 per 2 mm²) Two out of six patients showed FES uptake on PET/CT at qualitative analysis. Lesion-based quantitative assessment showed a mean SUV_max of 2.4 (± 0.9) on FDG-PET/CT and mean SUV_max of 1.7 (± 0.5) on FES-PET/CT. Within patients, expression of ERα and ERβ varied and did not seem to correspond with FES uptake. In one FES positive patient, tumor locations with FES uptake remained stable or decreased in size during anti-hormonal treatment, while all FES negative locations progressed.Conclusions: This study shows that in AGCTs, FDG uptake is limited and therefore FDG-PET/CT is not advised. FES-PET/CT may be useful to non-invasively capture the estrogen receptor expression of separate tumor lesions and thus assess the potential eligibility for hormone treatment in AGCT patients.     

Comparison between whole-body MRI and Fluorine-18-Fluorodeoxyglucose PET or PET/CT in oncology: a systematic review

Background

The aim of the article is to systematically review published data about the comparison between positron emission tomography (PET) or PET/computed tomography (PET/CT) using Fluorine-18-Fluorodeoxyglucose (FDG) and whole-body magnetic resonance imaging (WB-MRI) in patients with different tumours.

Methods

A comprehensive literature search of studies published in PubMed/MEDLINE, Scopus and Embase databases through April 2012 and regarding the comparison between FDG-PET or PET/CT and WB-MRI in patients with various tumours was carried out.

Results

Forty-four articles comprising 2287 patients were retrieved in full-text version, included and discussed in this systematic review. Several articles evaluated mixed tumours with both diagnostic methods. Concerning the specific tumour types, more evidence exists for lymphomas, bone tumours, head and neck tumours and lung tumours, whereas there is less evidence for other tumour types.

Conclusions

Overall, based on the literature findings, WB-MRI seems to be a valid alternative method compared to PET/CT in oncology. Further larger prospective studies and in particular cost-effectiveness analysis comparing these two whole-body imaging techniques are needed to better assess the role of WB-MRI compared to FDG-PET or PET/CT in specific tumour types.     

Utility of 18F-fluorodeoxyglucose positron emission tomography in the preoperative staging of squamous cell carcinoma of the oropharynx.

BACKGROUND: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been reported to be superior to computed tomography (CT)/magnetic resonance imaging (MRI) in the evaluation of head and neck cancers, but little is known about its usefulness in oropharyngeal squamous cell carcinoma (SCC). We therefore compared FDG PET and CT/MRI in the preoperative staging of previously untreated oropharyngeal SCC. METHODS: Thirty-two consecutive patients with oropharyngeal SCC underwent FDG PET and CT/MRI before surgery. Each method was interpreted separately to assess primary tumor and cervical node status. Their sensitivity and specificity were compared relative to histopathologic analysis. RESULTS: Histopathology revealed metastases in 29 of 39 dissected neck sides and in 47 of 163 dissected cervical levels. FDG PET had higher sensitivities than CT/MRI for primary tumor detection (25/32 vs. 30/32, P=0.063) and for identification of cervical metastases on neck side (22/29 vs. 28/29, P<0.05) and level-by-level (37/47 vs. 45/47, P<0.05) bases. In contrast, the specificity of the two methods did not differ significantly (P>0.5). FDG PET correctly interpreted the false-negative results of CT/MRI in 6 of 7 primary tumors and 8 of 10 cervical levels. CONCLUSIONS: The improved preoperative staging of FDG PET may help in planning treatment, but its accuracy is insufficient to replace pathologic staging based on neck dissection.     

2-Fluorine-18-fluoro-2-deoxy-D glucose positron emission tomography in the pretreatment staging of Hodgkin's disease: Influence on patient management in a single institution

Purpose:Optimum therapy for patients with Hodgkin's disease (HD)is determined by a number of prognostic factors, one of which is an accuratedefinition of extent of disease (stage). Computerised tomography is widelyused in staging but cannot reliably evaluate normal sized lymph nodes and someextranodal sites, e.g., liver, spleen and bone marrow.2-Fluorine-18-fluoro-2-deoxy-D glucose (FDG) has been shown to concentratepreferentially in lymphoma sites (whether in nodal or extranodal tissue) andtherefore may have a useful role in staging patients with HD. This studycompares concurrent computerized tomography (CT) and FDG positron emissiontomography (PET) in the staging of Hodgkin's disease and assesses thefrequency of stage migration and possible changes in therapy related to theuse of PET scanning. Patients and methods:This was a single centre retrospective studyof 44 patients with Hodgkin's disease who underwent both staging CT and PETprior to treatment between September 1993 and August 1998 at St. Thomas'Hospital. The number and sites of disease were assessed for each patient,documenting any stage and therapy modification prompted by PET findings. Results:One hundred fifty-nine sites of disease were demonstratedin forty-four patients by FDG–PET compared with eighty-four by CT. Asa result, 18 (40.9%) patients were upstaged, nine of these byFDG-uptake in splenic or extranodal sites not visualised on CT. Only threepatients were downstaged by PET results. Eleven patients (25%) hadtreatment modified by PET scan findings. Conclusions:Significantly more sites of disease were identifiedby PET than CT resulting in stage changes and a modification of therapy in25% of patients. This has important implications not only for currentpatient management but also for the design of future clinical trials.     

[F‐18]‐fluorodeoxy‐D‐glucose–positron emission tomography response is associated with outcome for extremity osteosarcoma in children and young adults

BACKGROUND:

Response to neoadjuvant chemotherapy is 1 of the most powerful prognostic factors for extremity osteosarcoma. [F‐18]‐fluorodeoxy‐D‐glucose–positron emission tomography (FDG‐PET) is a noninvasive imaging modality that is used to predict histopathologic response. To determine the prognostic value of FDG‐PET response for progression‐free survival (PFS) in osteosarcoma, the authors of this report reviewed the University of Washington Medical Center experience.

METHODS:

Forty patients with extremity osteosarcoma were evaluated by FDG‐PET. All patients received neoadjuvant and adjuvant chemotherapy. FDG‐PET standard uptake values (SUVs) before neoadjuvant chemotherapy (SUV1) and after neoadjuvant chemotherapy (SUV2) were analyzed and correlated with histopathologic response.

RESULTS:

The median SUV1 was 6.8 (range, 3.0‐24.1), the median SUV2 was 2.3 (range, 1.2‐12.8), and the median SUV2 to SUV1 ratio (SUV2:1), was 0.36 (range, 0.12‐1.10). A good FDG‐PET response was defined as anSUV2 <2.5 or an SUV2:1 ≤0.5. FDG‐PET responses according to SUV2 and SUV2:1 were concordant with histologic response in 58% and 68% of patients, respectively. SUV2 was associated with outcome (4‐year PFS, 73% for SUV2 <2.5 vs 39% for SUV2 ≥2.5; P = .021). Both the initial disease stage and the histologic response were associated with outcome.

CONCLUSIONS:

FDG‐PET imaging of extremity osteosarcoma was correlated only partially with a histologic response to neoadjuvant chemotherapy. An SUV2 <2.5 was associated with improved PFS. Future prospective studies are warranted to determine whether FDG‐PET imaging may be used as a predictor of outcome independent of initial disease stage. Cancer 2009. © 2009 American Cancer Society.     

Fluorine-18-labeled fluoromisonidazole positron emission and computed tomography-guided intensity-modulated radiotherapy for head and neck cancer: a feasibility study

PURPOSE: Hypoxia renders tumor cells radioresistant, limiting locoregional control from radiotherapy (RT). Intensity-modulated RT (IMRT) allows for targeting of the gross tumor volume (GTV) and can potentially deliver a greater dose to hypoxic subvolumes (GTV(h)) while sparing normal tissues. A Monte Carlo model has shown that boosting the GTV(h) increases the tumor control probability. This study examined the feasibility of fluorine-18-labeled fluoromisonidazole positron emission tomography/computed tomography ((18)F-FMISO PET/CT)-guided IMRT with the goal of maximally escalating the dose to radioresistant hypoxic zones in a cohort of head and neck cancer (HNC) patients. METHODS AND MATERIALS: (18)F-FMISO was administered intravenously for PET imaging. The CT simulation, fluorodeoxyglucose PET/CT, and (18)F-FMISO PET/CT scans were co-registered using the same immobilization methods. The tumor boundaries were defined by clinical examination and available imaging studies, including fluorodeoxyglucose PET/CT. Regions of elevated (18)F-FMISO uptake within the fluorodeoxyglucose PET/CT GTV were targeted for an IMRT boost. Additional targets and/or normal structures were contoured or transferred to treatment planning to generate (18)F-FMISO PET/CT-guided IMRT plans. RESULTS: The heterogeneous distribution of (18)F-FMISO within the GTV demonstrated variable levels of hypoxia within the tumor. Plans directed at performing (18)F-FMISO PET/CT-guided IMRT for 10 HNC patients achieved 84 Gy to the GTV(h) and 70 Gy to the GTV, without exceeding the normal tissue tolerance. We also attempted to deliver 105 Gy to the GTV(h) for 2 patients and were successful in 1, with normal tissue sparing. CONCLUSION: It was feasible to dose escalate the GTV(h) to 84 Gy in all 10 patients and in 1 patient to 105 Gy without exceeding the normal tissue tolerance. This information has provided important data for subsequent hypoxia-guided IMRT trials with the goal of further improving locoregional control in HNC patients.     

Detection of occult bone metastases of lung cancer with Fluorine‐18 fluorodeoxyglucose positron emission tomography

Accurate staging of cancer has a critical role in optimal patient management. Fluorine‐18 fluorodeoxyglucose positron emission tomography (FDG PET) is superior to CT in the detection of local and distant metastases in patients with non‐small cell lung cancer. Although Tc‐99 m methylene diphosphonate (MDP) bone scanning is well established in the evaluation of bone metastases, there are conflicting reports on the use of FDG PET in the evaluation of skeletal metastases. We report on a patient with locally advanced lung carcinoma in whom FDG PET accurately identified previously unsuspected widespread asymptomatic bone metastases (bone scan and X‐rays negative, confirmed on MRI). Assessment of glucose metabolism with FDG PET might represent a more powerful tool to detect bone metastases in lung cancer compared with conventional bone scans.     

Early restaging positron emission tomography with ( 18)F-fluorodeoxyglucose predicts outcome in patients with aggressive non-Hodgkin's lymphoma.

BACKGROUND: Less than half of all patients with aggressive non-Hodgkin's lymphoma (NHL) are cured with standard chemotherapy. Therefore, it is important to distinguish between responders to standard treatment and non-responders who may benefit from an early change to a more effective therapy. This study was intended to assess the value of a midtreatment fluorine-18 fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) scan to predict clinical outcome in patients with aggressive NHL. PATIENTS AND METHODS: Seventy newly diagnosed patients with aggressive NHL, who were treated with doxorubicin-containing chemotherapy, underwent a [(18)F]FDG-PET scan at midtreatment. Presence or absence of abnormal [(18)F]FDG uptake was related to progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier survival analysis. Multivariate analysis was performed to evaluate the effect of the International Prognostic Index (IPI) and early [(18)F]FDG-PET findings on PFS and OS. RESULTS: At midtreatment, 33 patients showed persistent abnormal [(18)F]FDG uptake and none of these patients achieved a durable complete remission (CR), whereas 37 patients showed a negative scan; 31/37 remained in CR, with a median follow-up of 1107 days. Only 6/37 patients either achieved a partial response or relapsed. Comparison between groups indicated a statistically significant association between [(18)F]FDG-PET findings and PFS (P <1 x 10(-5)) and OS (P <1 x 10(-5)). In multivariate analysis, [(18)F]FDG-PET at midtreatment was a stronger prognostic factor for PFS (P <1 x 10(-7)) and OS (P <9 x 10(-6)) than the IPI (P <0.11 and P <0.03, respectively). CONCLUSIONS: Early restaging [(18)F]FDG-PET may be used to tailor induction chemotherapy in patients with aggressive NHL.     

The clinical application of 18F‐fluorodeoxyglucose positron emission tomography to predict survival in patients with operable esophageal cancer

BACKGROUND:

Metabolic tumor activity using ¹⁸F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) was believed to have a predictive value for patient outcome in malignancies. The objective of the current study was to assess the prognostic effectiveness of the highest standardized uptake value (SUV) in the primary or regional area (peak SUV) and the number of PET‐positive lymph nodes in esophageal cancer.

METHODS:

The authors retrospectively reviewed their experience with 184 consecutive esophageal cancer patients imaged preoperatively using FDG‐PET scanning.

RESULTS:

The median peak SUV was 4.5 (range, 1.4‐21.9). The survival curve was analyzed using the median peak SUV as the cutoff value. Comparison of each group and clinicopathologic characteristics revealed significant associations between peak SUV and each of the following factors: tumor status (P < .001), lymph node status (P < .001), metastatic status (P < .05), stage of disease (P < .001), number of PET‐positive lymph nodes (P < .001), and the number of histologically positive lymph nodes (P < .001). The 5‐year overall survival (OS) rate for patients having FDG uptake with a peak SUV ≥4.5 was 47% and that for patients with a peak SUV <4.5 was 76% (P < .0001). On multivariate survival analysis using the Cox proportional hazards model, peak SUV and the number of PET‐positive lymph nodes were found to be independent predictive factors for OS. The number of PET‐positive lymph nodes was a single prognostic factor predicting both disease‐free survival and OS.

CONCLUSIONS:

Pretreatment PET cannot only potentially diagnose the extent of disease, but also may be predictive of patient survival after esophageal cancer resection. Cancer 2009. © 2009 American Cancer Society.     

Imaging tumour hypoxia with positron emission tomography

Hypoxia, a hallmark of most solid tumours, is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. Given its prominent role in oncology, accurate detection of hypoxia is important, as it impacts on prognosis and could influence treatment planning. A variety of approaches have been explored over the years for detecting and monitoring changes in hypoxia in tumours, including biological markers and noninvasive imaging techniques. Positron emission tomography (PET) is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels. This review provides an overview of imaging hypoxia with PET, with an emphasis on the advantages and limitations of the currently available hypoxia radiotracers.     

Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography imaging in patients with carcinoma of the nasopharynx: diagnostic accuracy and impact on clinical management

PURPOSE: To assess the value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with nasopharyngeal carcinoma as compared with PET and conventional imaging (CI) alone, and to assess the impact of PET/CT on further clinical management. METHODS AND MATERIALS: Thirty-three patients with nasopharyngeal carcinoma had 45 PET/CT examinations. The study was a retrospective analysis. Changes in patient care resulting from the PET/CT studies were recorded. RESULTS: Positron emission tomography/computed tomography had sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 92%, 90%, 90%, 90%, and 91%, respectively, as compared with 92%, 65%, 76%, 86%, and 80% for PET and 92%, 15%, 60%, 60%, and 60% for CI. Imaging with PET/CT altered further management of 19 patients (57%). Imaging with PET/CT eliminated the need for previously planned diagnostic procedures in 11 patients, induced a change in the planned therapeutic approach in 5 patients, and guided biopsy to a specific metabolically active area inside an edematous region in 3 patients, thus decreasing the chances for tissue sampling errors and avoiding damage to nonmalignant tissue. CONCLUSIONS: In cancer of the nasopharynx, the diagnostic performance of PET/CT is better than that of stand-alone PET or CI. Positron emission tomography/computed tomography had a major impact on further clinical management in 57% of patients.     

18F-FDG PET/CT 在无症状肿瘤标志物升高患者中的应用价值研究*

目的:旨在评估18F-FDGPET/CT在无症状肿瘤标志物升高患者中的应用价值。方法:选取2008年6 月至2015年7 月间至少有一项肿瘤标志物升高后于天津医科大学肿瘤医院行18F-FDGPET/CT 检查的受检者183 例,并对所有受检者进行随访,分析肿瘤标志物升高与18F-FDGPET/CT 诊断结果之间的关系,研究18F-FDGPET/CT 在无症状肿瘤标志物升高患者中的应用价值。结果:统计分析显示18F-FDGPET/CT 诊断阳性患者43例,其中真阳性患者34例,最常见的阳性部位为肺部,其次为肠道。18F-FDGPET/CT在CEA ,CA199 和（或）CA242 升高患者中具有较好的阳性诊断准确率,其中单项CEA 升高的18F-FDG PET/CT阳性诊断准确率为13.0% 、灵敏度为79.0% ;CEA 或CA242 单项高水平异常时,18F-FDGPET/CT 阳性诊断准确率与其升高水平相关。多项肿瘤标志物升高时,如果包含CA242 或CA724,则18F-FDGPET/CT 阳性诊断准确率与升高肿瘤标志物的个数相关。结论:CEA或CA242 单项高水平异常时,推荐进行18F-FDGPET/CT 检查;当多项肿瘤标志物升高时,若其中包含CA242 或CA724,倾向于推荐18F-FDGPET/CT应用;而对于CA199 和CA724 单项升高的人群,不推荐首选18F-FDGPET/CT检查。