Characteristics of advantages of positron emission tomography over computed tomography for N-staging in lung cancer patients

OBJECTIVE: We analyzed the characteristics of advantages of positron emission tomography (PET) over computed tomography (CT) for N-staging in lung cancer patients. METHODS: Preoperative PET and CT scans were performed for 2057 lymph node stations in 205 patients with peripheral-type lung cancer. The advantages of PET over CT for N-staging were analyzed among lymph node locations and histological subtypes. RESULTS: The pathological N-stages were N0 in 143 patients, N1 in 31, N2 in 24 and N3 in 7. PET was able to diagnose N0, N2 and N3 diseases more accurately than CT (P=0.03, 0.01 and 0.02, respectively), but there was no significant difference between the two modalities for N1 disease. In the upper mediastinal lymph node stations, both false-negative and false-positive were significantly less frequent with PET than with CT (P=0.001). In the lower mediastinal and supra clavicle lymph nodes, PET showed a lower frequency of false-negative than CT (P=0.04 and 0.003, respectively), but there was no significant difference in the frequency of false-positive between the two modalities. Among histological types, PET could stage adenocarcinoma with less frequent false-negative and squamous cell carcinoma with less frequent false-positive than CT (P=0.02 and 0.005, respectively). CONCLUSION: For N-staging, PET was superior to CT for the following: (1) more accurate for N0, N2 and N3 diseases but not for N1; (2) lower frequency of false-positive in the upper mediastinal nodes; and (3) lower frequencies of false-negative in adenocarcinoma and false-positive in squamous cell carcinoma. Recognizing these advantages of PET could make the N-staging of lung cancer more accurate.     

Positron emission tomography imaging in nonsmall-cell lung cancer

Positron emission tomography (PET) using 18F-2-deoxy-D-glucose, a D-glucose analog labeled with fluorine-18, complements conventional radiologic assessment in the evaluation of patients with nonsmall-cell lung cancer (NSCLC). PET is being routinely used to improve the detection of nodal and extrathoracic metastases. PET is also currently being evaluated in the assessment of prognosis and therapeutic response and by potentially allowing an earlier assessment of response may prove invaluable in the oncologic management of patients. The article discusses the diagnosis, staging, and assessment of treatment response and prognosis with an emphasis on the appropriate clinical use of PET in management.     

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.     

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.     

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.     

Laparoscopic extraperitoneal para-aortic lymphadenectomy in locally advanced cervical cancer: a prospective correlation of surgical findings with positron emission tomography/computed tomography findings

BACKGROUND:

Failure to detect metastasis to para‐aortic nodes in patients with locally advanced cervical cancer leads to suboptimal treatment. No previous studies have prospectively compared positron emission tomography (PET)/computed tomography (CT) with laparoscopic extraperitoneal staging in the evaluation of para‐aortic lymph nodes.

METHODS:

Sixty‐five patients were enrolled; 60 were available for analysis. Patients with stage IB2‐IVA cervical cancer without evidence of para‐aortic lymphadenopathy on preoperative CT or magnetic resonance imaging (MRI) were prospectively enrolled. All patients underwent preoperative PET/CT. Laparoscopic extraperitoneal lymphadenectomy was performed from the common iliac vessels to the left renal vein.

RESULTS:

The median age at diagnosis was 48 years (range, 23‐84). The median operative time was 140 minutes (range, 89‐252). The median blood loss was 22.5 mL (range, 5‐150). The median length of hospital stay was 1 day (range, 0‐4). The median number of lymph nodes retrieved was 11 (range, 1‐39). Fourteen (23%) patients had histopathologically positive para‐aortic nodes. Of the 26 patients with negative pelvic and para‐aortic nodes on PET/CT, 3 (12%) had histopathologically positive para‐aortic nodes. Of the 27 patients with positive pelvic but negative para‐aortic nodes on PET/CT, 6 (22%) had histopathologically positive para‐aortic nodes. The sensitivity and specificity of PET/CT in detecting positive para‐aortic nodes when nodes were negative on CT or MRI were 36% and 96%, respectively. Eleven (18.3%) patients had a treatment modification based on surgical findings.

CONCLUSIONS:

Laparoscopic extraperitoneal para‐aortic lymphadenectomy is safe and feasible. Surgical staging of patients with locally advanced cervical cancer should be considered before planned radiation and chemotherapy. Cancer 2011. © 2010 American Cancer Society.     

PET在肺癌诊断和分期中的应用

本文介绍正电子发射断层显像(PET)在肺癌诊断和分期中的应用概况，肯定了其临床应用价值。并简要叙述我国PET目前现状及今后展望。PET系大型医疗设备，我国未纳入医疗保险，其发展要根据社会经济发展和病人承受能力，合理布局，有限量地增加。作者指出，加强核医学科人员培训与临床各科医师(包括放射科，肿瘤科，胸外科，放射治疗等)的合作是提高PET临床应用和研究水平的关键因素。     

Ability of integrated positron emission and computed tomography to detect significant colonic pathology

BACKGROUND:

The ability of integrated positron emission tomography and computed axial tomography (PET‐CT) to detect colonic pathology is not fully defined. The purpose of this study was to assess the ability of PET‐CT to detect colonic pathology and to determine the significance of (¹⁸F)2‐fluoro‐2‐deoxyglucose (¹⁸F‐FDG) activity noted incidentally in the colon on PET‐CT.

METHODS:

Records for all patients who underwent PET‐CT and colonoscopy at our institution were reviewed. Patients with history of colonic malignancy or colon surgery were excluded.

RESULTS:

Fifty‐eight patients had incidental colonic ¹⁸F‐FDG activity on PET (Group A) and 272 had none (Group B). In Group A, 65% of patients had pathologic findings detected on colonoscopy that corresponded to the site of PET activity. Standardized uptake value (SUV) readings were not helpful in distinguishing true‐positives from false‐positives. In Group B, 11.8% of patients were found to have significant colonic findings. Lesions not detected by PET‐CT included 4 colon cancers, 7 advanced adenomas, and 10 patients with colonic lymphoma. Overall, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET‐CT for detecting significant pathology were 53%, 93%, 65%, 89%, and 85%, respectively. For detecting colon cancer and adenomas 10 mm or more, the sensitivity, specificity, PPV, NPV, and accuracy of PET‐CT were 72%, 90%, 45%, 96%, and 88%, respectively.

CONCLUSIONS:

Incidental colonic activity detected by PET‐CT warrants further evaluation with colonoscopy. However, negative PET‐CT does not rule out significant colonic pathology including colon cancer, advanced adenomas, or lymphoma. Cancer 2010. © 2010 American Cancer Society.     

The role of positron emission tomography in management of small cell lung cancer

Accurate radiological staging of small-cell lung cancer (SCLC) is of paramount importance in selection of individual patients with limited stage disease for potentially curative treatment while avoiding toxic treatment in those with distant metastatic disease. [¹⁸F] flurodeoxy-d-glucose (FDG) positron emission tomography (PET) is an attractive tool for this purpose but there is limited evidence to support its use in the routine staging of SCLC. Whether therapeutic decisions based on FDG-PET imaging should be made remains uncertain. There is only preliminary evidence for use of FDG-PET as a prognostic biomarker, in the assessment of response to treatment and delineation of disease in conformal radiation planning.     

Localised disease in cancer of unknown primary (CUP): The value of positron emission tomography (PET) for individual therapeutic management

Background:Two to four percent of cancer patients presentwith CUP syndrome. Median survival for localised disease is 20 and fordisseminated disease, seven months. For localised disease, curativetreatment is more likely and individual therapeutic strategies becomemore important. After conservative diagnostic procedures including MRI,the primary is detected in less than 25%. The diagnostic value ofPET and its influence on therapeutic strategies was evaluated. Patients and methods:Forty-two patients with localised CUPwere investigated from 5 of 98 to 10 of 2000. The presenting site waslymph node metastasis in 34 and visceral metastasis in 8 patients. Aftera median of 7 (3–11) diagnostic procedures without detection ofthe primary, but evidence of localised disease, PET was performed withfluorine-18-fluorodeoxyglucose. Results:In 26 of 42patients (62%), a primary was suggested by PET and confirmed in18 (43%). In 5 of 18 patients beyond localised disease,additional dissemination, not detected by previous diagnostic measures,was diagnosed by PET. Overall, dissemination was only detected only byPET in 16 of 42 patients (38%). In 29 of 42 patients(69%), the PET result influenced selection of the definitivetreatment. Conclusion:In CUP patients, PET has acertain impact on detection of the primary as well as of thedisseminated disease, and may also have a certain impact on therapeuticmanagement.     

Detectors in positron emission tomography

Positron emission tomography is a highly sensitive molecular imaging modality, based on the coincident detection of annihilation photons after positron decay. The most used detector is based on dense, fast, and luminous scintillators read out by light sensors. This review covers the various detector concepts for clinical and preclinical systems.     

Impact of positron emission tomography/computed tomography surveillance at 12 and 24 months for detecting head and neck cancer recurrence

BACKGROUND:

In head and neck cancer (HNC), 3‐month post‐treatment positron emission tomography (PET)/computed tomography (CT) reliably identifies persistent/recurrent disease. However, further PET/CT surveillance has unclear benefit. The impact of post‐treatment PET/CT surveillance on outcomes is assessed at 12 and 24 months.

METHODS:

A 10‐year retrospective analysis of HNC patients was carried out with long‐term serial imaging. Imaging at 3 months included either PET/CT or magnetic resonance imaging, with all subsequent imaging comprised of PET/CT. PET/CT scans at 12 and 24 months were evaluated only if preceding interval scans were negative. Of 1114 identified patients, 284 had 3‐month scans, 175 had 3‐ and 12‐month scans, and 77 had 3‐, 12‐, and 24‐month scans.

RESULTS:

PET/CT detection rates in clinically occult patients were 9% (15 of 175) at 12 months, and 4% (3 of 77) at 24 months. No difference in outcomes was identified between PET/CT‐detected and clinically detected recurrences, with similar 3‐year disease‐free survival (41% vs 46%, P = .91) and 3‐year overall survival (60% vs 54%, P = .70) rates. Compared with 3‐month PET/CT, 12‐month PET/CT demonstrated fewer equivocal reads (26% vs 10%, P < .001). Of scans deemed equivocal, 6% (5 of 89) were ultimately found to be positive.

CONCLUSIONS:

HNC patients with negative 3‐month imaging appear to derive limited benefit from subsequent PET/CT surveillance. No survival differences were observed between PET/CT‐detected and clinically detected recurrences, although larger prospective studies are needed for further investigation. Cancer 2013. © 2012 American Cancer Society.     

Influence of 18F‐fluorodeoxyglucose‐positron emission tomography on computed tomography‐based radiation treatment planning for oesophageal cancer

The addition of positron emission tomography (PET) information to CT‐based radiotherapy treatment planning has the potential to improve target volume definition through more accurate localization of the primary tumour and involved regional lymph nodes. This case report describes the first patient enrolled to a prospective study evaluating the effects of coregistered positron emission tomography/CT images on radiotherapy treatment planning for oesophageal cancer. The results show that if combined positron emission tomography/CT is used for radiotherapy treatment planning, there may be alterations to the delineation of tumour volumes when compared to CT alone. For this patient, a geographic miss of tumour would have occurred if CT data alone were used for radiotherapy planning.     

Coregistered whole body magnetic resonance imaging‐positron emission tomography (MRI‐PET) versus PET‐computed tomography plus brain MRI in staging resectable lung cancer

BACKGROUND:

The objective of this study was to assess whether coregistered whole brain (WB) magnetic resonance imaging‐positron emission tomography (MRI‐PET) would increase the number of correctly upstaged patients compared with WB PET‐computed tomography (PET‐CT) plus dedicated brain MRI in patients with nonsmall cell lung cancer (NSCLC).

METHODS:

From January 2010 through November 2011, patients with NSCLC who had resectable disease based on conventional staging were assigned randomly either to coregistered MRI‐PET or WB PET‐CT plus brain MRI (ClinicalTrials.gov trial NCT01065415). The primary endpoint was correct upstaging (the identification of lesions with higher tumor, lymph node, or metastasis classification, verified with biopsy or other diagnostic test) to have the advantage of avoiding unnecessary thoracotomy, to determine appropriate treatment, and to accurately predict patient prognosis. The secondary endpoints were over staging and under staging compared with pathologic staging.

RESULTS:

Lung cancer was correctly upstaged in 37 of 143 patients (25.9%) in the MRI‐PET group and in 26 of 120 patients (21.7%) in the PET‐CT plus brain MRI group (4.2% difference; 95% confidence interval, ?6.1% to 14.5%; P = .426). Lung cancer was over staged in 26 of 143 patients (18.2%) in the MRI‐PET group and in 7 of 120 patients (5.8%) in the PET‐CT plus brain MRI group (12.4% difference; 95% confidence interval, 4.8%‐20%; P = .003), whereas lung cancer was under staged in 18 of 143 patients (12.6%) and in 28 of 120 patients (23.3%), respectively (?10.7% difference; 95% confidence interval, ?20.1% to ?1.4%; P = .022).

CONCLUSIONS:

Although both staging tools allowed greater than 20% correct upstaging compared with conventional staging methods, coregistered MRI‐PET did not appear to help identify significantly more correctly upstaged patients than PET‐CT plus brain MRI in patients with NSCLC. Cancer 2013. © 2013 American Cancer Society.     

Cancer Research UK procedures in manufacture and toxicology of radiotracers intended for pre-phase I positron emission tomography studies in cancer patients

Radiolabelled compounds formulated for injection (radiopharmaceuticals), are increasingly being employed in drug development studies. These can be used in tracer amounts for either pharmacokinetic or pharmacodynamic studies. Such radiotracer studies can also be carried out early in man, even prior to conventional Phase I clinical testing. The aim of this document is to describe procedures for production and safety testing of oncology radiotracers developed for imaging by positron emission tomography in cancer patients. We propose strategies for overcoming the inability to produce compounds in sufficient quantities via the radiosynthetic routes for full chemical characterisation and toxicology testing including (i) independent confirmation as far as possible that the stable compound associated with the radiopharmaceutical is identical to the non-labelled compound, (ii) animal toxicity studies with > or = 10 times (typically 100 times) the intended tracer dose in humans scaled by body surface area, and (iii) patient monitoring during the radiotracer positron emission tomography clinical trial.     

F-18]Fluorodeoxyglucose positron emission tomography can predict pathological tumor stage and proliferative activity determined by Ki-67 in clinical stage IA lung adenocarcinomas

OBJECTIVE: To predict a malignant grade of lung cancer by fluorodeoxyglucose positron emission tomography (FDG-PET) scanning, we investigated the correlation between FDG uptake and pathological tumor stage, proliferative activities determined by Ki-67 and cyclin D1, and an alteration of p53, in clinical stage (c-stage) IA lung adenocarcinomas. METHODS: FDG-PET was performed for 71 patients with c-stage IA lung adenocarcinomas. FDG uptake was measured by a contrast ratio (CR) between the tumor and contralateral lung. Ki-67, cyclin D1 and p53 staining scores were examined by immunohistochemistry. RESULTS: The lesions with ground-glass opacity were found in 26 patients, and solid lesions in 45 by computed tomography. The pathological tumor stages (p-stage) were stage IA in 59 and more advanced stages in 12. The latter had significantly higher CR value than the former (P < 0.001). Patients with CR > or = 0.55 could be predicted to be at advanced tumor stages, with a sensitivity of 0.83 and a specificity of 0.82. The CR and staining scores of Ki-67 were significantly correlated with each other (P < 0.0001), and both the values were significantly higher in advanced tumor stages than in p-stage IA, and were also significantly higher in tumors with intratumoral lymphatic, vascular and pleural involvements than in those without such features (P < 0.05-0.0001). CONCLUSIONS: In c-stage IA lung adenocarcinomas, the FDG uptake can predict p-stage and tumor proliferative activity determined by Ki-67. For c-stage IA lung adenocarcinomas showing CR > or = 0.55, mediastinoscopy or neoadjuvant chemotherapy is indicated.