Response assessment by combined PET–CT scan versus CT scan alone using RECIST in patients with locally advanced head and neck cancer treated with chemoradiotherapy

PurposeRECIST have limitations when applied to potentially curable locally advanced squamous cell carcinoma of the head and neck (SCCHN). [¹⁸F]fluorodeoxyglucose–positron emission tomography (PET) scan may be useful in assessing treatment response and predicting patient outcome.Patients and methodsWe studied patients with previously untreated stages III–IVb SCCHN treated with primary concurrent chemoradiotherapy on five prospective clinical trials. Response was assessed by clinical exam, computed tomography (CT), and PET portions of combined PET–CT scan ∼8 weeks after completion of chemoradiotherapy.ResultsFifty-three patients were analyzed. Complete response (CR) was demonstrated in 42 patients (79%) by clinical exam, 15 (28%) by CT, and 27 (51%) by PET. CR as assessed by PET, but not as assessed by clinical exam or CT using RECIST, correlated significantly with progression-free status (PFS) (P < 0.0001). The 2-year PFS for patients with CR and without CR by PET was 93% and 48%, respectively (P = 0.0002).ConclusionsA negative PET scan on combined PET–CT after chemoradiotherapy is a powerful predictor of outcome in patients receiving curative chemoradiotherapy for SCCHN. PET–CT is indicated for response evaluation in this setting to improve the accuracy of post-treatment assessment by CT.     

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.     

Role of 18F‐FDG‐PET/CT in the management of marginal zone B cell lymphoma

The use of PET in patients with marginal zone B cell lymphoma (MZL) is controversial because of variability of fluorodeoxyglucose (FDG) avidity. We analyzed 40 PET/CT in 25 consecutive patients to compare its performance with CT at staging and as a first‐line response assessment. Sensitivity of PET/CT and CT was 96 and 76%. Mean standard uptake value was 6.1, 6.9 and 3.4 (p = 0.3) in nodal, extranodal and splenic subtypes, respectively. Of 17 patients (extranodal: n = 9; nodal: n = 6; splenic subtype: n = 2) with both imaging tests available at diagnosis, 8 (47%) had more involved areas with PET/CT than with CT, 75% of which were extranodal lesions. PET/CT resulted in upstaging of five patients although treatment of only two of them was changed. Responses of 15 patients with post‐treatment PET/CT were the following: 9 negative and 6 positive of which 3 were isolated residual lesions. Progression was documented in two of these three patients. Response was also assessed by CT in 11 patients. Discrepancies were found in three: Two were in complete remission by CT while PET/CT detected localized residual disease; another patient was in partial remission by CT, whereas PET/CT showed only one positive lesion. Two of these three patients relapsed. Patients with negative post‐treatment PET/CT did not relapse. With a median follow‐up of 50 months (10–152 months), 3‐year overall survival was 100 and 80% for patients with negative and positive post‐treatment PET/CT (p = 0.2). Three‐year disease‐free survival was 86%; the negative predictive value (NPV) was 100%, and the positive predictive value (PPV) was 83.3%. Although a larger number of patients will be required to further confirm these data, we can conclude that PET/CT is a useful imaging tool for both staging and response assessment in patients with nodal and extranodal MZL as a result of its high sensitivity, NPV and PPV. Copyright © 2014 John Wiley & Sons, Ltd.     

Prognostic value of 18F‐fluoroazomycin arabinoside PET/CT in patients with advanced non‐small‐cell lung cancer

This study evaluated the prognostic value of positron emission tomography/computed tomography (PET/CT) using ¹⁸F‐fluoroazomycin arabinoside (FAZA) in patients with advanced non‐small‐cell lung cancer (NSCLC) compared with ¹⁸F‐fluorodeoxyglucose (FDG). Thirty‐eight patients with advanced NSCLC (stage III, 23 patients; stage IV, 15 patients) underwent FAZA and FDG PET/CT before treatment. The PET parameters (tumor‐to‐muscle ratio [T/M] at 1 and 2 h for FAZA, maximum standardized uptake value for FDG) in the primary lesion and lymph node (LN) metastasis and clinical parameters were compared concerning their effects on progression‐free survival (PFS) and overall survival (OS). In our univariate analysis of all patients, clinical stage and FAZA T/M in LNs at 1 and 2 h were predictive of PFS (P = 0.021, 0.028, and 0.002, respectively). Multivariate analysis also indicated that clinical stage and FAZA T/M in LNs at 1 and 2 h were independent predictors of PFS. Subgroup analysis of chemoradiotherapy‐treated stage III patients revealed that only FAZA T/M in LNs at 2 h was predictive of PFS (P = 0.025). The FDG PET/CT parameters were not predictive of PFS. No parameter was a significant predictor of OS. In patients with advanced NSCLC, FAZA uptake in LNs, but not in primary lesions, was predictive of treatment outcome. These results suggest the importance of characterization of LN metastases in advanced NSCLC patients.     

Detection rate of fluorine‐18‐fluorodeoxyglucose positron emission tomography in patients with marginal zone lymphoma of MALT type: a meta‐analysis

The aim of this article is to meta‐analyse published data about the detection rate (DR) of fluorine‐18‐fluorodeoxyglucose (¹⁸F‐FDG) positron emission tomography (PET) and PET/computed tomography (CT) in the evaluation of patients with marginal zone lymphoma of the mucosa‐associated lymphoid tissue (MALT). A comprehensive literature search of studies published through February 2014 was performed. Pooled DR of ¹⁸F‐FDG PET or PET/CT including 95% confidence intervals (95% CI) was calculated on a per‐patient‐based analysis. Twenty studies including 376 patients with MALT lymphoma were selected. The pooled DR of ¹⁸F‐FDG PET or PET/CT was 71% (95% CI: 61–80%). A significant difference between the DR of PET/CT (69%; 95% CI: 61–80%) and that of PET alone (73%; 95% CI: 60–84%) was not demonstrated. A better DR of ¹⁸F‐FDG PET or PET/CT in bronchial (94%; 95% CI: 85–99%) and head‐and‐neck (90%; 95% CI: 78–98%) MALT lymphomas compared with gastric (62%; 95% CI: 46–77%) and ocular (49%; 95% CI: 36–63%) MALT lymphomas was found. This meta‐analysis demonstrates that MALT lymphoma is an ¹⁸F‐FDG‐avid tumour in most of the cases, suggesting a potential clinical role of ¹⁸F‐FDG PET or PET/CT in the initial evaluation of these patients. In particular, the DR of ¹⁸F‐FDG PET or PET/CT is related to the primary site of the MALT lymphoma. Copyright © 2014 John Wiley & Sons, Ltd.     

Heterogeneity of 18F‐FDG PET combined with expression of EGFR may improve the prognostic stratification of advanced oropharyngeal carcinoma

The Ang's risk profile (based on p16, smoking and cancer stage) is a well‐known prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC). Whether heterogeneity in ¹⁸F‐fluorodeoxyglucose (FDG) positron emission tomographic (PET) images and epidermal growth factor receptor (EGFR) expression could provide additional information on clinical outcomes in advanced‐stage OPSCC was investigated. Patients with stage III–IV OPSCC who completed primary therapy were eligible. Zone‐size nonuniformity (ZSNU) extracted from pretreatment FDG PET scans was used as an index of image heterogeneity. EGFR and p16 expression were examined by immunohistochemistry. Disease‐specific survival (DSS) and overall survival (OS) served as outcome measures. Kaplan–Meier estimates and Cox proportional hazards regression models were used for survival analysis. A bootstrap resampling technique was applied to investigate the stability of outcomes. Finally, a recursive partitioning analysis (RPA)‐based model was constructed. A total of 113 patients were included, of which 28 were p16‐positive. Multivariate analysis identified the Ang's profile, EGFR and ZSNU as independent predictors of both DSS and OS. Using RPA, the three risk factors were used to devise a prognostic scoring system that successfully predicted DSS in both p16‐positive and ‐negative cases. The c‐statistic of the prognostic index for DSS was 0.81, a value which was significantly superior to both AJCC stage (0.60) and the Ang's risk profile (0.68). In patients showing an Ang's high‐risk profile (N = 77), the use of our scoring system clearly identified three distinct prognostic subgroups. It was concluded that a novel index may improve the prognostic stratification of patients with advanced‐stage OPSCC.     

18F‐FDG uptake and its clinical relevance in primary gastric lymphoma

We studied the clinical relevance of ¹⁸F‐fluorodeoxyglucose (¹⁸F‐FDG) uptake in patients with primary gastric lymphoma underwent positron emission tomography (PET)/ computed tomography (CT) scan. Forty‐two patients with primary gastric lymphoma were analysed: 32 diffuse large B‐cell lymphomas (DLBCL) and 10 extranodal marginal zone B‐cell lymphomas of mucosa‐associated lymphoid tissue (MALT lymphomas). The PET/CT scans were compared with clinical and pathologic features, and the results of CT and endoscopy. Nine patients were up‐staged based on the results of their PET/CT scan compared to CT (seven DLBCLs, two MALT lymphomas) while six patients were down‐staged by the PET/CT scan. The standard uptake value (SUV) was used as an indicator of a lesion with a high metabolic rate. The high SUVmax group, defined as an SUVmax ≥ median value, was significantly associated with an advanced Lugano stage (p < 0.001). Three patients with DLBCL, who showed an initially high SUVmax, died of disease progression. Among 24 patients for whom follow‐up PET/CT scan with endoscopy was performed, 11 patients with ulcerative or mucosal lesions showed residual ¹⁸F‐FDG uptake. All of these gastric lesions were grossly and pathologically benign lesions without evidence of lymphoma cells. In conclusion, PET/CT scan can be used in staging patients with primary gastric lymphoma; however, the residual ¹⁸F‐FDG uptake observed during follow‐up should be interpreted cautiously and should be combined with endoscopy and multiple biopsies of the stomach. Copyright © 2009 John Wiley & Sons, Ltd.     

Intensity‐modulated radiotherapy outcomes for oropharyngeal squamous cell carcinoma patients stratified by p16 status

BACKGROUND:

Patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with intensity‐modulated radiotherapy (IMRT) were stratified by p16 status, neck dissection, and chemotherapy to correlate these factors with outcomes.

METHODS:

A total of 112 patients with OPSCC treated with IMRT from 2002 to 2008 were retrospectively analyzed. All patients received RT to 66‐70 Gray. Forty‐five of the tumors were p16 positive (p16+), 27 were p16 negative (p16?), and 41 had unknown p16 status. Sixty‐two patients had postradiation neck dissections. Nine patients with p16? tumors and 28 patients with p16+ tumors received chemotherapy. The distribution of T, N, and stage grouping among the p16+ and p16? patients was not significantly different, and 87.5% patients had stage III/IV disease.

RESULTS:

The median follow‐up was 26.3 months. For patients with p16+ tumors, p16? tumors, and the overall cohort, the actuarial 3‐year locoregional progression‐free survival rate was 97.8%,73.5%, and 90.5% respectively (P = .006) and the disease‐free survival rate was 88.2%, 61.4%, and 81.7%, respectively (P = .004). Patients with p16+ tumors had an 89.5% and 87.5% pathologic complete response (CR) on neck dissection with and without chemotherapy, respectively. In contrast, patients with p16? tumors had a 66.7% and 25.0% pathologic CR on neck dissection with and without chemotherapy, respectively.

CONCLUSIONS:

In this series, p16 status was found to be a significant predictive biomarker and patients with p16+ tumors had much better outcomes than patients with p16? tumors. Further investigation is warranted to determine whether less intense therapy is appropriate for selected patients with p16+ OPSCC, whereas more aggressive strategies are needed to improve outcomes in patients with p16? disease. Cancer 2010. © 2010 American Cancer Society.     

18F‐FDG PET/CT vs. human papillomavirus,p16 and Epstein–Barr virus detection in cervical metastatic lymph nodes for identifying primary tumors

Squamous cell carcinoma of unknown primary of the head and neck (SCCUP) is a heterogeneous disease entity that requires careful examination to locate the occult primary. We examined the diagnostic value of expression of biomarkers, such as human papillomavirus (HPV), p16 and Epstein–Barr virus (EBV), in metastatic lymph nodes vs. ¹⁸F‐fluorodeoxyglucose (¹⁸F‐FDG) positron emission tomography/computed tomography (PET/CT). We prospectively enrolled 54 consecutive SCCUP patients who received HPV, p16 and EBV analyses of lymph node fine‐needle aspirates and ¹⁸F‐FDG PET/CT scans and subsequently underwent examinations and biopsies under general anesthesia to detect primary tumors. The diagnostic performance of the biomarkers and ¹⁸F‐FDG PET/CT were compared by using receiver operating characteristics (ROC) curve analyses with histopathological results for identification of primary tumors. Primary tumors were identified in 28 (51.9%) of 54 patients: the palatine tonsil in 24, base of the tongue in 1, nasopharynx in 2, and hypopharynx in 1. The sensitivity of p16 (85.7%) and accuracy of HPV (85.2%) were higher than those (42.9% and 68.5%) of ¹⁸F‐FDG PET/CT (p < 0.05). The area under the ROC curve of HPV was higher than that of ¹⁸F‐FDG PET/CT (0.857 vs. 0.666, p = 0.007). The disease‐free survival rates were higher in the patients with primary tumor detection or p16 nodal immunopositivity than in the other patients (p < 0.05). The results showed that HPV and p16 detection in metastatic lymph nodes can help locate hidden primary tumors, guide definitive treatment and predict patient survival.     

Initial evaluation of PET/CT with 18F‐FSU‐880 targeting prostate‐specific membrane antigen in prostate cancer patients

This first‐in‐man study was carried out to evaluate the safety, whole‐body distribution, dose estimation, and lesion accumulation of ¹⁸F‐FSU‐880, a newly developed probe targeting prostate‐specific membrane antigen. Six prostate cancer patients with known metastatic lesions underwent serial whole‐body PET/computed tomography (CT) with ¹⁸F‐FSU‐880. Blood and urine were analyzed before and after PET/CT. Accumulation of ¹⁸F‐FSU‐880 in organs and metastatic lesions in serial PET images were evaluated by measuring the standardized uptake values. From the biodistribution data, the organ doses and whole‐body effective dose were calculated using OLINDA/EXM software was developed by Dr. Michael Stabin of Vanderbilt University, Nashville, Tennessee, USA. ¹⁸F‐FSU‐880 PET/CT could be carried out without significant adverse effects. High physiological uptake was observed in the salivary/lachrymal glands and kidneys. The effective dose was calculated to be 0.921 × 10^?2 mSv/MBq. Known metastatic lesions were clearly visualized with high image contrast that increased with time, except in 1 patient, whose bone metastases were well‐controlled and inactive. The PET/CT with ¹⁸F‐FSU‐880 could be carried out safely and could clearly visualize active metastatic lesions. The present results warrant further clinical studies with a larger number of cases to verify the clinical utility of ¹⁸F‐FSU‐880 PET/CT in the management of prostate cancer patients.     

Evaluation of thoracic tumors with 18F‐FMT and 18F‐FDG PET‐CT: A clinicopathological study

L‐[3‐¹⁸F]‐α‐methyltyrosine (¹⁸F‐FMT) is an aminoacid tracer for positron emission tomography (PET). The aim of this study was to determine whether PET‐CT with ¹⁸F‐FMT provides additional information for the preoperative diagnostic workup as compared with ¹⁸F‐FDG PET. PET‐CT studies with ¹⁸F‐FMT and ¹⁸F‐FDG were performed as a part of the preoperative workup in 36 patients with histologically confirmed bronchial carcinoma, 6 patients with benign lesions and a patient with atypical carcinoid. Expression of L‐type amino acid transporter 1 (LAT1), CD98, Ki‐67 labeling index, VEGF, CD31 and CD34 of the resected tumors were analyzed by immunohistochemical staining, and correlated with the uptake of PET tracers. For the detection of pulmonary malignant tumors, ¹⁸F‐FMT PET exhibited a sensitivity of 84% whereas the sensitivity for ¹⁸F‐FDG PET was 89% (p = 0.736). ¹⁸F‐FMT PET‐CT and ¹⁸F‐FDG PET‐CT agreed with pathological staging in 85 and 68%, respectively (p = 0.151). ¹⁸F‐FMT uptake was closely correlated with LAT1, CD98, cell proliferation and angiogenesis. The specificity of ¹⁸F‐FMT PET for diagnosing thoracic tumors was higher than that of ¹⁸F‐FDG PET. Our results suggest that coexpression of LAT1 and CD98 in addition to cell proliferation and angiogenesis is relavant for the progression and metastasis of lung cancer. © 2008 Wiley‐Liss, Inc.     

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.     

P16INK4A immunostaining is a strong indicator for high‐risk‐HPV‐associated oropharyngeal carcinomas and dysplasias,but is unreliable to predict low‐risk‐HPV‐infection in head and neck papillomas and laryngeal dysplasias

Human papillomavirus (HPV) is a risk factor for the development of benign and malignant mucosal head and neck lesions. P16^INK4A is often used as a surrogate marker for HPV‐infection, although there is still controversy with respect its reliability. Our aim was to determine if p16^INK4A overexpression can accurately predict both high‐risk and low‐risk‐HPV‐presence in (pre)malignant and benign head and neck lesions. P16^INK4A immunohistochemistry was performed on paraffin‐embedded tissue sections of 162 oropharyngeal squamous cell carcinomas (OPSCC), 14 tonsillar and 23 laryngeal dysplasias, and 20 tonsillar and 27 laryngeal papillomas. PCR, enzyme‐immunoassay and FISH analysis were used to assess HPV‐presence and type. Of the 162 OPSCC and 14 tonsillar dysplasias, 51 (31%) and 10 (71%) were HPV16‐positive, respectively. All tonsillar papillomas were HPV‐negative and four laryngeal dysplasias and 26 laryngeal papillomas were positive for HPV6 or ?11. P16^INK4A immunohistochemistry revealed a strong nuclear and cytoplasmic staining in 50 out of 51 HPV16‐positive and 5 out of 111 HPV‐negative OPSCC (p < 0.0001) and in all HPV16‐positive tonsillar dysplasias, whereas highly variable staining patterns were detected in the papillomas and laryngeal dysplasias, irrespective of the HPV‐status. In addition, the latter lesions generally showed a higher nuclear than cytoplasmic p16^INK4A immunostaining intensity. In conclusion, our data show that strong nuclear and cytoplasmic p16^INK4A overexpression is a reliable surrogate indicator for HPV16 in OPSCC and (adjacent) dysplasias. For HPV6 or ?11‐positive and HPV‐negative benign and premalignant lesions of the tonsil and larynx, however, p16^INK4A immunostaining is highly variable and cannot be recommended to predict HPV‐presence.     

Diagnostic value of fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography for the detection of metastases in non–small‐cell lung cancer patients

In the recent years, fluorine 18 fluorodeoxyglucose (¹⁸F‐FDG) positron emission tomography (PET)/computed tomography (CT) has emerged as a new modality for staging non–small‐cell lung cancer (NSCLC) patients. The aim of this meta‐analysis was to assess the diagnostic value of ¹⁸F‐FDG PET/CT in detecting metastatic lesions in NSCLC patients. Meta‐analysis methods were used to pool sensitivity, specificity, positive and negative likehood ratios, diagnostic odd ratios and to construct a summary receiver‐operating characteristic curve. Data from included studies were pooled to compare the diagnostic accuracy between PET/CT and PET or CT alone in nodal staging. Totally, 56 studies involving 8,699 patients met the inclusion criteria. The pooled sensitivities and specificities of ¹⁸F‐FDG PET/CT were 0.72 [95% confidence interval (CI): 0.65–0.78] and 0.91 (95% CI: 0.86–0.94) in determining mediastinal nodal staging; 0.71 (95% CI: 0.60–0.80) and 0.83 (95% CI: 0.77–0.88) in intrathoracic staging; 0.78 (95% CI: 0.64–0.87) and 0.90 (95% CI: 0.84–0.94) in intrathoracic staging on a per‐node basis. For detecting extrathoracic metastases, the pooled sensitivities and specificities of ¹⁸F‐FDG PET/CT were 0.77 (95% CI: 0.47–0.93) and 0.95 (95% CI: 0.92–0.97) for all extrathoracic metastases; 0.91 (95% CI: 0.80–0.97) and 0.98 (95% CI: 0.94–0.99) for bone metastases. ¹⁸F‐FDG PET/CT is beneficial in detecting lymph node metastases and extrathoracic metastases although PET/CT showed low sensitivity in detecting brain metastases. ¹⁸F‐FDG PET/CT confers significantly higher sensitivity and specificity than contrast‐enhanced CT (both p < 0.01) and higher sensitivity than ¹⁸F‐FDG PET in staging NSCLC (p < 0.05).     

Prevalence of non 18F‐fluorodeoxyglucose‐avid incidental findings of clinical significance on whole body positron emission tomography/computed tomography: A review of 500 consecutive cases

Introduction

The prevalence of incidental ¹⁸F‐fluorodeoxyglucose (FDG)‐avid findings on positron emission tomography–computed tomography (PET/CT) has been extensively described. Few studies, however, have assessed the prevalence and significance of non‐FDG‐avid findings; pathology that is identified on review of the low‐dose, non‐contrast CT. The aim of this study was to determine the overall prevalence of non FDG‐avid incidental findings on PET/CT and the prevalence of ‘clinically significant’ non FDG‐avid pathology.

Methods

Five hundred consecutive whole body PET/CT studies performed in 2016 at a university affiliated tertiary hospital were retrospectively reviewed by two radiologists experienced in reporting PET/CT. Findings were categorized according to potential clinical relevance, and a targeted follow‐up of clinically significant incidental findings was performed.

Results

Incidental findings were encountered in 463 of 500 (92.6%) patients. In 226 patients, these findings had been detected on previous imaging studies, with unknown incidental findings present in 237 of 500 (47.4%) patients. 113 of 500 (22.6%) patients had non‐avid incidental findings of potentially major clinical significance, and in 35 patients (7.0%) these findings were considered previously unknown. The most common non‐avid findings of potentially major significance were pulmonary nodules (6 mm or larger), moderate or large size pleural effusions, and vascular aneurysms. Unknown incidental findings of potentially major clinical significance were significantly higher in patients imaged for melanoma staging (P= 0.004).

Conclusion

The prevalence of incidental findings of clinical significance that do not accumulate FDG in PET/CT is not insignificant. Routine systematic review of the low‐dose CT is required to avoid missing potentially clinically important findings, in particular pleural effusions, vascular aneurysms and metastatic pulmonary nodules.     

Epidemiologic associations of HPV‐positive oropharyngeal cancer and (pre)cancerous cervical lesions

Human papillomavirus (HPV)‐induced oropharyngeal squamous cell carcinoma (OPSCC) remains increasing worldwide. We aimed to investigate if the HPV‐prevalence of OPSCC in the Netherlands is rising as well, also in female patients. In addition, we evaluated the association between HPV‐positive OPSCC and suspicious Pap results of the cervix in these female patients. Patients with OPSCC treated in the period 2000–2015 at the VU University Medical Center Amsterdam, were included (n = 926). The presence of an oncogenic HPV infection was determined by p16‐immunostaining, followed by a high‐risk HPV general primer 5+/6+ DNA PCR on the p16‐immunopositive cases. A review of pathology reports in all female patients (n = 305) was undertaken to identify cytological signs of HPV‐related (pre)cancer of the cervix. In total 281 of 926 (30.3%) OPSCCs were HPV‐positive. Moreover, a significant increase in the prevalence of HPV‐positive OPSCCs was observed from 14.0% in 2000 to 48.1% in 2015 (p < 0.001). Among the female patients with an HPV‐positive OPSSC (n = 70), the results of cervical smears were available in 56 of 70 patients (80.0%). Of the female patients with HPV‐positive OPSCC, 9 of 56 (16.1%) patients had a vaginal cuff Papanicolaou (Pap) test ≥3b in their medical history compared to 7 of 168 (4.2%) in the HPV‐negative group (p = 0.003). In conclusion, a continuous increase in the HPV‐attributable fraction of OPSCC was demonstrated in the period 2000–2015 in the Amsterdam region. HPV‐positive OPSCC has a significant association with a history of suspicious Pap results of the cervix in female patients.     

Comparative study of the value of dual tracer PET/CT in evaluating breast cancer

The present study was conducted to assess the relationship between tumor uptake and pathologic findings using dual‐tracer PET/computed tomography (CT) in patients with breast cancer. Seventy‐four patients with breast cancer (mean age 54 years) who underwent ¹¹C‐choline and 2‐[¹⁸F]fluoro‐2‐deoxy‐d ‐glucose (¹⁸F‐FDG) PET/CT prior to surgery on the same day were enrolled in the present study. Images were reviewed by a board‐certified radiologist and two nuclear medicine specialists who were unaware of any clinical information and a consensus was reached. Uptake patterns and measurements of dual tracers were compared with the pathologic findings of resected specimens as the reference standard. Mean (±SD) tumor size was 5.9 ± 3.2 cm. All primary tumors were identified on ¹⁸F‐FDG PET/CT and ¹¹C‐choline PET/CT. However, ¹⁸F‐FDG PET/CT demonstrated focal uptake of the primary tumor with (n = 38; 51%) or without (n = 36; 49%) diffuse background breast uptake. Of the pathologic findings, multiple logistic regression analysis revealed an independent association between fibrocystic change and diffuse background breast uptake (odds ratio [OR] 8.57; 95% confidence interval [CI] 2.86–25.66; P < 0.0001). Tumors with higher histologic grade, nuclear grade, structural grade, nuclear atypia, and mitosis had significantly higher maximum standardized uptake values (SUV_max) and tumor‐to‐background ratios (TBR) for both tracers. Multiple logistic regression analysis revealed that only the degree of mitosis was independently associated with a high SUV_max (OR 7.45; 95%CI 2.21–25.11; P = 0.001) and a high TBR (OR 5.41; 95%CI 1.13–25.96; P = 0.035) of ¹¹C‐choline PET/CT. In conclusion, ¹¹C‐choline may improve tumor delineation and reflect tumor aggressiveness on PET/CT in patients with breast cancer.     

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.     

Predicting regional control based on pretreatment nodal size in squamous cell carcinoma of the head and neck treated with chemoradiotherapy: A clinican’s guide

The aim of this study was to determine the regional control rate with concurrent chemoradiotherapy (CRT) based on pretreatment nodal size in mucosal head and neck squamous cell carcinoma (HNSCC) in patients who achieved a complete response (CR) at the primary site by 12 weeks post‐treatment. Between December 1997 and November 2003, 117 patients with node‐positive HNSCC were treated with concurrent CRT, with 108 (92%) achieving a CR at the primary site by 12 weeks. There were 93 males (86%), median age 55 (37–79) years and the most common primary site was the oropharynx (65%). Patients were divided into three subgroups: ≤3.0 cm 70 (65%), 3.1–6.0 cm 30 (28%) and ≥6.1 cm 8 (7%). All patients received concurrent platinum‐based chemotherapy and the median radiation dose was 70 Gy (60–72 Gy). The 3‐year regional control rate based on pretreatment nodal size was ≤3.0 cm 88% (95% confidence interval (CI) 78–94%), 3.1–6.0 cm 72% (95%CI 49–86%) and ≥6.1 cm 50% (95%CI 15–77%) (P = 0.001). The 3‐year regional control rate based on pre‐treatment nodal size was ≤3.0cm 88% (95%CI 78–94%), 3.1–6.0 cm 72% (95%CI 49–86%) and ≥6.1 cm 50% (95%CI 15–77%) (P = 0.001). These results provide a quantitative guide for the clinician as to the likelihood of regional control based on pretreatment nodal size following CRT in patients who achieve a CR at the primary site by 12 weeks post‐treatment.     

Rectal cancer staging: An up‐to‐date pictorial review

Colorectal cancer is the third most common malignancy worldwide, and rectal cancer (RC) accounts for 29% of all cases. Local staging of RC is crucial for the purposes of addressing patients appropriately to surgery alone or to preoperative chemoradiotherapy (pCRT) followed by total mesorectal excision (TME). Combined pCRT and TME may negatively affect rectal function, so rectum‐sparing approaches such as transanal local excision have been proposed as an alternative to TME for patients showing a major or complete clinical response on restaging after pCRT. Magnetic resonance imaging (MRI) has a fundamental role in the local staging and restaging of RC, with or without positron emission tomography (PET). PET/MRI enables a multiplanar high‐resolution morphological study of the pelvis, providing important information on cell density and metabolic activity with diffusion‐weighted imaging (DWI) and ¹⁸F fluorodeoxyglucose uptake respectively. This article offers a pictorial review of the MRI anatomy of the ano‐rectal region and an update on local RC staging with a hybrid ¹⁸F‐FDG PET/MRI scan.