Correlation of [18F]‐2‐fluoro‐deoxy‐D‐glucose positron emission tomography standard uptake values with the cellular composition of stage I nonsmall cell lung cancer

BACKGROUND:

The aim of the current study was to determine whether the [18F]‐2‐fluoro‐deoxy‐D‐glucose (FDG) positron emission tomography (PET) standardized uptake value (SUV) in patients with a new diagnosis of stage I lung cancer correlates with a specific cellular component in the primary tumor.

METHODS:

This study was Health Insurance Portability and Accountability Act compliant and approved by our Institutional Review Board with a waiver of informed consent. Forty patients with stage I nonsmall cell lung cancer (NSCLC) who underwent FDG‐PET imaging at the time of diagnosis followed by surgical resection were retrospectively identified. Histologic sections of the primary tumor were reviewed by a pathologist without any clinical data and scored according to the percentage of each cellular component (tumor cells, normal stroma, inflammatory cells, necrosis, fibrosis, and other). Each component was compared with maximal (SUV_max) and mean (SUV_mean) SUVs using Pearson correlation coefficient analysis.

RESULTS:

The mean SUV_max and SUV_mean values for 40 stage I NSCLC tumors were 8.8 and 5.4, respectively. The mean histologic composition of tumor specimens in order of frequency was as follows: tumor cells (38.9%), fibrosis (30.8%), inflammatory cells (14.8%), normal stroma (5.2%), necrosis (5.8%), and other components (4.5%); however, there was considerable variation noted among individual tumors. There was no statistically significant correlation between SUV_max (r = .19; P = .24) or SUV_mean (r = .017; P = .29) and the proportion of tumor cells in the tumor mass or any other cellular components.

CONCLUSIONS:

The cellular composition of stage I NSCLC appears to be highly variable, with no correlation noted between a specific tumor cellular component and FDG activity. Cancer 2010. © 2010 American Cancer Society.     

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.     

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.     

18F‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography and positron emission tomography/computed tomography imaging of malignant pleural mesothelioma*

Malignant pleural mesothelioma (MPM) is the most common primary pleural tumor and its incidence is rising. Its diagnosis, staging and response assessment are challenging for imaging. Integrated positron emission tomography (PET)/CT increases the accuracy of overall staging in patients with mesothelioma and improves the selection of patients for curative surgical resection. It is particularly useful in identifying occult distant metastases. It may be used to predict prognosis and to assess the metabolic response to therapy.     

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.     

Influence of the baseline 18F‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography results on survival and pathologic response in patients with gastroesophageal cancer undergoing chemoradiation

BACKGROUND:

In patients with esophageal cancer who receive chemoradiation, tools to predict/prognosticate outcome before administering therapy are lacking. The authors evaluated initial standardized unit value (iSUV) of 18F‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography and its association with overall survival and the degree of pathologic response after surgery.

METHODS:

The authors analyzed 161 patients with esophageal adenocarcinoma who had chemoradiation followed by surgery. The log‐rank test, univariate Cox proportional hazards model, Kaplan‐Meier survival plot, and Fisher exact test were used to analyze dichotomized iSUV and its association with overall survival and pathologic response.

RESULTS:

The median age of 161 patients was 61 years (range, 26‐80 years) and the majority of patients had lower esophageal or gastroesophageal junction involvement. All patients received fluoropyrimidine and, most commonly, a taxane or platinum compound with concomitant radiation. The median radiation dose was 45 grays (Gy) (range, 45 Gy‐50.4 Gy). The median iSUV for all patients was 10.1 (range, 0‐58). Using the Fisher exact test, iSUV was not found to be associated with the location of the primary cancer. iSUV higher than the median (10.1) was associated with a better pathologic response (P = .06). Patients with primary cancer with iSUV >10.1 had a lower risk for death (hazards ratio of 0.56) compared with those with iSUV ≤10.1. Higher iSUV was nonsignificantly associated with improved survival (P = .07).

CONCLUSIONS:

Data from the current study suggest that lower iSUV is associated with poor survival and lower probability of response to chemoradiation. iSUV needs to be further evaluated because it may be used to complement other imaging or biomarker assessments to individualize therapy. Cancer 2009. © 2009 American Cancer Society.     

Quantitative F18‐fluorodeoxyglucose positron emission tomography accurately characterizes peripheral nerve sheath tumors as malignant or benign

BACKGROUND:

Correct pretreatment classification is critical for optimizing diagnosis and treatment of patients with peripheral nerve sheath tumors (PNSTs). The aim of this study was to evaluate whether F18‐fluorodeoxyglucose positron emission tomography (FDG PET) can differentiate malignant (MPNST) from benign PNSTs.

METHODS:

Thirty‐four adult patients presenting with PNST who underwent a presurgical FDG PET/computed tomography (CT) scan between February 2005 and November 2008 were included in the study. Tumors were characterized histologically, by FDG maximum standardized uptake value (SUV_max [g/mL]), and by CT size (tumor maximal diameter [cm]). The accuracy of FDG PET for differentiating MPNSTs from benign PNSTs (neurofibroma and schwannoma) was evaluated by receiver operating characteristic (ROC) curve analysis.

RESULTS:

SUV_max was measured in 34 patients with 40 tumors (MPNSTs: n = 17; neurofibromas: n = 9; schwannomas: n = 14). SUV_max was significantly higher in MPNST compared with benign PNST (12.0 ± 7.1 vs 3.4 ± 1.8; P < .001). An SUV_max cutoff point of ≥6.1 separated MPNSTs from BPSNTs with a sensitivity of 94% and a specificity of 91% (P < .001). By ROC curve analysis, SUV_max reliably differentiated between benign and malignant PNSTs (area under the ROC curve of 0.97). Interestingly, the difference between MPNSTs and schwannomas was less prominent than that between MPNSTs and neurofibromas.

CONCLUSIONS:

Quantitative FDG PET imaging distinguished between MPNSTs and neurofibromas with high accuracy. In contrast, MPNSTs and schwannomas were less reliably distinguished. Given the difficulties in clinically evaluating PNST and in distinguishing benign PNST from MPNST, FDG PET imaging should be used for diagnostic intervention planning and for optimizing treatment strategies. Cancer 2010. © 2010 American Cancer Society.     

The diagnostic and prognostic utility of positron emission tomography/computed tomography‐based follow‐up after radiotherapy for head and neck cancer

BACKGROUND:

The detection of subclinical head and neck cancer recurrence or a second primary tumor may improve survival. In the current study, the authors investigated the clinical value of a follow‐up program incorporating serial ¹⁸F?fluorodeoxyglucose?positron emission tomography integrated with computed tomography (PET/CT) in the detection of recurrent disease in patients with head and neck cancer.

METHODS:

A total of 240 PET/CT scans were reviewed in 80 patients with head and neck cancer who were treated with radiotherapy (RT) from July, 2005 through August, 2007. All patients were followed with clinical examination, PET/CT, and correlative imaging for a minimum of 11 months (median follow?up, 21 months).

RESULTS:

The sensitivity, specificity, and positive and negative predictive values of PET/CT‐based follow‐up for detecting locoregional recurrence were 92%, 82%, 42%, and 98%, respectively. Corresponding values for distant metastases or second primary tumors were 93%, 96%, 81%, and 98%, respectively. Eight patients (10%) developed disease recurrences or second primary tumors that were amenable to salvage surgery with negative surgical margins. The 2‐year progression‐free survival and 2‐year overall survival rates were significantly different between patients who had a negative and those with a positive PET/CT result within 6 months of the completion of RT (93% vs 30% [P<.001] and 100% vs 32% [P<.001], respectively).

CONCLUSIONS:

Although post‐therapy follow‐up using PET/CT is reportedly associated with a high false‐positive rate in the irradiated head and neck, PET/CT appears to be a highly sensitive technique for the detection of recurrent disease. Furthermore, negative PET/CT results within 6 months of the completion of RT offer significant prognostic value. Cancer 2009. © 2009 American Cancer Society.     

Early 18F‐2‐fluoro‐2‐deoxy‐d‐glucose positron emission tomography may identify a subset of patients with estrogen receptor‐positive breast cancer who will not respond optimally to preoperative chemotherapy

BACKGROUND:

A pathologic complete response (pCR) and minimal residual disease (pMRD) after preoperative chemotherapy (PCT) for early stage or locally advanced breast cancer (BC) correlates with a good prognosis.

METHODS:

Patients who received from 6 to 8 cycles of PCT for BC were monitored by ¹⁸F‐2‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography (¹⁸F‐FDG‐PET), and the maximal standardized uptake value (SUVmax) was calculated at baseline, after 2 cycles, after 4 cycles, and at the end of PCT. SUVmax percentage changes (Δ‐SUV) were compared with the pathologic response rate. Patients who had a pCR or pMRD in the tumor and an absence of cancer cells in ipsilateral axillary lymph nodes were defined as having obtained an optimal pathologic response (pR), whereas all the other conditions were classified as a pathologic nonresponse (pNR).

RESULTS:

Of 34 patients, 7 (21%) achieved a pR (3 patients had a pCR, and 4 patients had pMRD). After the second cycle, the Δ‐SUV threshold with optimal negative predictive value to predict a pR was 50%. Twenty‐six patients (76%) had a Δ‐SUV >50%, including all 7 patients who had a pR and 19 patients who had a pNR. Conversely, all 8 patients who had a Δ‐SUV ≤50% had a pNR. All 8 of those patients had estrogen recepetor‐positive tumors.

CONCLUSIONS:

Early evaluation of metabolic response by ¹⁸F‐FDG‐PET during PCT was able to identify 30% of patients, all with estrogen receptor‐positive tumors, who would not obtain pR after completion of chemotherapy program. Cancer 2010. © 2010 American Cancer Society.     

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.     

[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.     

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.     

Impact of 18F-fluorodeoxyglucose positron emission tomography in the staging and treatment response assessment of extra-pulmonary small-cell cancer

The aim of this study was to retrospectively evaluate the value of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in extrapulmonary small-cell cancer (EPSCC). Patients with EPSCC who underwent PET for staging or response assessment between 1996 and 2007 were identified from a database. Patient records were reviewed. PET-based, and conventional staging and restaging results were compared. The binary staging classification of limited disease (LD) versus extensive disease (ED) was used. Patients with LD had tumours that could be encompassed within a tolerable radiation therapy (RT) volume. Of 33 eligible patients, 12 had staging PET scans, 11 had restaging scans and 10 had both. All known gross disease sites were FDG-avid. PET and conventional stage groupings were concordant in 21 of 22 cases. One patient was appropriately upstaged from LD to ED by PET. PET detected additional disease sites, without causing upstaging in three further patients. Restaging PET scans identified previously unrecognised persistent or progressive disease in 4 of 21 cases. In four further cases, persistent FDG uptake after treatment was either false positive (n = 2) or of uncertain (n = 2) aetiology. PPV was 100% for staging and 82% for restaging. In 8 of 43 imaging episodes (19%), PET appropriately influenced management in five cases by changing treatment intent from radical to palliative, and in three cases by altering the RT volume. PET has incremental value compared to conventional imaging for staging EPSCC, and may also be useful for restaging after therapy. PET influenced patient management in 19% of 43 imaging episodes.     

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.     

The prevalence and clinical significance of 18F–2‐fluoro‐2‐deoxy‐D‐glucose (FDG) uptake in the thyroid gland on PET or PET‐CT in patients with lymphoma

F¹⁸–2‐fluoro‐2‐deoxy‐D‐glucose (FDG) positron emission tomography (PET) has become a well established tool in staging and assessing therapy response in lymphoma. Incidental thyroid uptake on PET is not uncommon and can pose a diagnostic and management challenge. We retrospectively evaluate the prevalence and clinical significance of incidental FDG uptake in the thyroid gland in patients with lymphoma. 1868 lymphoma patients underwent PET and PET‐CT between August 2002 and August 2008. 52 patients (2.8%) demonstrated FDG thyroid uptake (M = 17, F = 35; mean age 63 yr). Thyroid uptake was determined as focal or diffuse, maximum standardized uptake values (SUVmax) recorded as well as SUV max ratio compared to background mediastinum activity (SUVR). Corresponding CT findings on PET‐CT were evaluated independently. Results were correlated with clinical, histopathological and imaging follow‐up. 30 (1.6%) patients had focal thyroid uptake. 16 (53%) had histological confirmation either by surgery (n = 7) or FNA under USS (n = 9). The final diagnosis was benign in 12/30 patients and malignant in 9/30. The malignancy risk for focal thyroid uptake was 30%. Five patients had intercurrent thyroid cancer (four papillary, one microinvasive follicular) and four had lymphomatous involvement. There was no significant difference between the mean sizes of benign (23.7 mm, range 12–34) and malignant nodules (23.6 mm, range 8–48). The mean SUVmax of malignant and benign nodules was 4.4 (range 1.8–10.1) and 3.2 (range 1.8–6.9) respectively with no statistically significant difference. 22 (1.2%) patients had diffuse FDG uptake in thyroid and benign aetiology was found in all with adequate follow‐up (15/22). Focal FDG thyroid uptake on PET or PET‐CT in lymphoma patients warrants further investigations. The malignancy risk is 30% either due to intercurrent thyroid cancer or lymphomatous involvement. SUVmax, SUVR and CT attenuation characteristics are not helpful in distinguishing between benign and malignant aetiologies. Diffuse thyroid uptake has a benign aetiology. Copyright © 2010 John Wiley & Sons, Ltd.