Dual time point imaging in locally advanced head and neck cancer to assess residual nodal disease after chemoradiotherapy.

BACKGROUND: FDG-PET/CT has a high negative predictive value to detect residual nodal disease in patients with locally advanced squamous cell head and neck cancer after completing concurrent chemoradiotherapy (CCRT). However, the positive predictive value remains suboptimal due to inflammation after radiotherapy, generating unnecessary further investigations and possibly even surgery. We report the results of a preplanned secondary end point of the ECLYPS study regarding the potential advantages of dual time point FDG-PET/CT imaging (DTPI) in this setting. Standardized dedicated head and neck FDG-PET/CT images were obtained 12 weeks after CCRT at 60 and 120 min after tracer administration. We performed a semiquantitative assessment of lymph nodes, and the retention index (RI) was explored to optimize diagnostic performance. The reference standard was histology, negative FDG-PET/CT at 1 year, or > 2 years of clinical follow-up. The time-dependent area under the receiver operator characteristics (AUROC) curves was calculated. RESULTS: In total, 102 subjects were eligible for analysis. SUV values increased in malignant nodes (median SUV1 = 2.6 vs. SUV2 = 2.7; P = 0.04) but not in benign nodes (median SUV1 = 1.8 vs. SUV2 = 1.7; P = 0.28). In benign nodes, RI was negative although highly variable (median RI = - 2.6; IQR 21.2), while in malignant nodes RI was positive (median RI = 12.3; IQR 37.2) and significantly higher (P = 0.018) compared to benign nodes. A combined threshold (SUV1 ≥ 2.2 + RI ≥ 3%) significantly reduced the amount of false-positive cases by 53% (P = 0.02) resulting in an increased specificity (90.8% vs. 80.5%) and PPV (52.9% vs. 37.0%), while sensitivity (60.0% vs. 66.7%) and NPV remained comparably high (92.9% vs. 93.3%). However, AUROC, as overall measure of benefit in diagnostic accuracy, did not significantly improve (P = 0.62). In HPV-related disease (n = 32), there was no significant difference between SUV1, SUV2, and RI in malignant and benign nodes, yet this subgroup was small. CONCLUSIONS: DTPI did not improve the overall diagnostic accuracy of FDG-PET/CT to detect residual disease 12 weeks after chemoradiation. Due to differences in tracer kinetics between malignant and benign nodes, DTPI improved the specificity, but at the expense of a loss in sensitivity, albeit minimal. Since false negatives at the 12 weeks PET/CT are mainly due to minimal residual disease, DTPI is not able to significantly improve sensitivity, but repeat scanning at a later time (e.g. after 12 months) could possibly solve this problem. Further study is required in HPV-associated disease.

Tumor and tumorlike conditions of the pleura and juxtapleural region: review of imaging findings.

Pleural lesions form a diagnostic challenge for the radiologist. Whereas lesions can be initially detected on chest radiographs, CT and MRI imaging are the imaging modalities of choice for further characterization. In a number of cases, imaging findings can be relatively specific. In general unfortunately, imaging findings are rather aspecific. Evolution and extrathoracic imaging findings are important clues toward the diagnosis.

Quality Assessment in FDG-PET/CT Imaging of Head-and-Neck Cancer: One Home Run Is Better Than Two Doubles.

2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) is indicated in head-and-neck cancer for the initial workup when clinically indicated (e. g., large tumors, clinically positive neck, cervical adenopathy from an unknown primary, etc.), for the assessment of treatment response 12 weeks after completion of (chemo)radiotherapy, and during follow-up when there is suspicion of relapse. The successful implementation of FDG-PET/CT in routine clinical practice requires an in-depth understanding of the recent advances in physics and engineering that have significantly improved the imaging capabilities of PET/CT scanners (e.g., digital silicon photomultipliers, point-spread function modeling, and time-of-flight, and Bayesian penalized likelihood reconstruction). Moreover, a coordinated harmonization effort from professional societies (e.g., EANM) and international bodies (e.g., IAEA) has resulted in the creation of quality assurance frameworks (e.g., QUANUM, EARL, GMP) and guidelines that collectively cover the entire spectrum from tracer production, hardware calibration, patient preparation, and scan acquisition, to image interpretation (e.g., PERCIST, Hopkins criteria). The ultimate goal is to standardize the PET/CT technique and to guarantee accurate and reproducible imaging results for every patient. This review summarizes the recent technical breakthroughs in PET/CT scan design and describes the existing quality assessment frameworks with a focus on applications in head-and-neck cancer. Strict adherence to these harmonization efforts will enable leveraging the full potential of PET/CT and translate the proven benefits of this technique into tangible improvements in outcome for patients with head-and-neck cancer in routine clinical care.

Quantification of 18F-fluorodeoxyglucose uptake to detect residual nodal disease in locally advanced head and neck squamous cell carcinoma after chemoradiotherapy: results from the ECLYPS study.

BACKGROUND: The Hopkins criteria were introduced for nodal response evaluation after therapy in head and neck cancer, but its superiority over quantification is not yet confirmed. METHODS: SUVbody weight thresholds and lesion-to-background ratios were explored in a prospective multicenter study of standardized FDG-PET/CT 12 weeks after CRT in newly diagnosed locally advanced head and neck squamous cell carcinoma (LAHNSCC) patients (ECLYPS). Reference standard was histology, negative FDG-PET/CT at 12 months after treatment or ≥ 2 years of negative follow-up. Area under the receiver operator characteristics curves (AUROC) were estimated and obtained thresholds were validated in an independent cohort of HNSCC patients (n = 127). RESULTS: In ECLYPS, 124 patients were available for quantification. With a median follow-up of 20.4 months, 23 (18.5%) nodal neck recurrences were observed. A SUV70 threshold of 2.2 (AUROC = 0.89; sensitivity = 79.7%; specificity = 80.8%) was identified as optimal metric to identify nodal recurrence within 1 year after therapy. For lesion-to-background ratios, an SUV50/SUVliver threshold of 0.96 (AUROC = 0.89; sensitivity = 79.7%; specificity = 82.8%) had the best performance. Compared with Hopkins criteria (AUROC = 0.81), SUV70 and SUV50/SUVliver provided a borderline significant (p = 0.040 and p = 0.094, respectively) improvement. Validation of thresholds yielded similar AUROC values (SUV70 = 0.93, SUV50/SUVliver = 0.95), and were comparable to the Hopkins score (AUROC = 0.91; not statistically significant). CONCLUSION: FDG quantification detects nodal relapse in LAHNSCC patients. When using EARL standardized PET acquisitions and reconstruction, absolute SUV metrics (SUV70 threshold 2.2) prove robust, yet ratios (SUV50/SUVliver, threshold 0.96) may be more useful in routine clinical care. In this setting, the diagnostic value of quantification is comparable to the Hopkins criteria. TRIAL REGISTRATION: US National Library for Medicine, NCT01179360. Registered 11 August 2010, https://clinicaltrials.gov/ct2/show/NCT01179360.

Diagnostic and clinical features of lung cancer associated with cystic airspaces.

"Lung cancer associated with cystic airspaces" is an uncommon manifestation, in which lung cancer presents on imaging studies with a cystic area with associated consolidation and/or ground glass. With the widespread use of computed tomography (CT), both in clinical practice and for lung cancer screening, these tumors are being more frequently recognized. An association of this entity with smoking has been established with the majority of cases reported being in former and current smokers. The true pathogenesis of the cystic airspace is not yet fully understood. Different causes of this cystic airspace have been described, including a check-valve mechanism obstructing the small airways, lepidic growth of adenocarcinoma on emphysematous lung parenchyma, cyst formation of tumor and tumor growth along the wall of a pre-existing bulla. Adenocarcinoma is the commonest histological type, followed by squamous cell carcinoma. Two classification systems have been described, based on morphological features of the lesion, taking into account both the cystic airspace as well as the morphology of the surrounding consolidation or ground glass. The cystic component may mislead radiologists to a benign etiology and the many different faces on imaging can make early diagnosis challenging. Special attention should be made to focal or diffuse wall thickening and consolidation or ground glass abutting or interspersed with cystic airspaces. Despite their atypical morphology, staging and management currently are still similar to that of other lung cancer types. Although the rarity of this entity will hamper larger studies, numerous aspects regarding this particular lung cancer type still need to be unraveled. This manuscript reviews the CT-imaging findings and gives an overview of available data in the English literature on pathogenesis, histopathology and clinical findings. Differential diagnosis and pitfalls are discussed as well as future directions regarding staging and management.

Bloodpool SPECT as part of bone SPECT/CT in painful total knee arthroplasty (TKA): validation and potential biomarker of prosthesis biomechanics.

PURPOSE: To compare bloodpool SPECT with planar imaging in bone SPECT/CT of painful total knee arthroplasty (TKA) with respect to inter-rater agreement, confidence, prosthesis outcome, and biomechanical functioning. METHODS: Retrospective study of bloodpool SPECT and planar control images. Four raters used the validated Bruderholz scheme and a 5-point scale to grade uptake. Inter-rater agreement and overall confidence scores were calculated. Variable cluster analysis was performed to identify patterns of uptake, and associations between patterns and prosthesis outcome and biomechanical functioning were examined. RESULTS: In all, 55 knees in 43 patients were analyzed (median follow-up 17 months; revision rate 21.8%). SPECT significantly improved inter-rater agreement in 24% of regions (all P < 0.05) and overall confidence by 20% (P < 0.001). Regional uptake cluster analysis showed improved antero-posterior separation with SPECT, and distinct patterns associated with prosthesis survival in lateral femoral (P = 0.041) and medial tibial (P < 0.001) regions. The prognostic value of SPECT outperformed planar imaging for tibial (P < 0.001), patellar (P = 0.009), and synovial (P = 0.040) assessment. Internal femoral malrotation resulted in increased uptake in posteromedial (P = 0.042) and anterolateral (P = 0.016) femoral, and lateral patellar (P = 0.011) regions. Internal tibial malrotation increased uptake in posterolateral (P = 0.026) and posteromedial tibial (P = 0.005), and medial patellar regions (P = 0.004). Bloodpool SPECT improved the prognostic value of late-phase SPECT/CT for the assessment of the medial tibial region. CONCLUSIONS: Bloodpool SPECT outperforms planar assessment of painful TKAs and the identification of distinct uptake patterns make it a potentially clinically relevant biomarker of prosthesis survival and biomechanical functioning.

The eighth TNM classification for malignant pleural mesothelioma.

In 2016, the International Association for the Study of Lung Cancer (IASLC) published a number of revisions of the seventh edition of the tumor, node and metastasis (TNM) classification for malignant pleural mesothelioma (MPM). The purpose was to establish a set of recommendations for the eighth edition of the TNM staging system. A large number of patients were included in the IASLC database and subsequently analysed to determine new definitions for the components of the TNM classification. A number of important changes were introduced for the T component. Survival analysis of the different T categories showed no significant difference in categories T1a and T1b. This has resulted in a collapse of categories T1a and T1b into one category T1. In addition, tumor thickness was also significantly associated with overall survival. The descriptors for the N components have been redefined as well for the eighth TNM classification. A major revision is the removal of category N3 in the N component. Both intrapleural and extrapleural (N1 and N2 in the seventh edition) are now combined into a single category N1. Lymph nodes that were previously categorized as N3 are now considered N2. For the M component, no redefinition has been published. However, a recommendation has been made to only consider M1 involvement as stage IV disease. This is in contrast to the seventh edition in which T4 and N3 disease were considered stage IV as well. In conclusion, a number of important revisions for the eighth TNM classification of MPM have been published as a result of this IASLC project. This type of large-scale and international joint efforts are key in establishing effective staging systems. Research into using tumor thickness as a prognostic instrument will be an important part of any future editions of the TNM classification.

FDG-PET/CT for treatment response assessment in head and neck squamous cell carcinoma: a systematic review and meta-analysis of diagnostic performance.

PURPOSE: 18-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) is increasingly used to evaluate treatment response in head and neck squamous cell carcinoma (HNSCC). This analysis assessed the diagnostic value of FDG-PET/CT in detecting nodal disease within 6 months after treatment, considering patient and disease characteristics. METHODS: A systematic review was performed using the MEDLINE and Web of Knowledge databases. The results were pooled using a bivariate random effects model of the sensitivity and specificity. RESULTS: Out of 22 identified studies, a meta-analysis of 20 studies (1293 patients) was performed. The pooled estimates of sensitivity, specificity and diagnostic odds ratio (with 95% CI) were 85% (76-91%), 93% (89-96%) and 76 (35-165), respectively. With the prevalence set at 10%, the positive and negative predictive values were 58% and 98%. There was significant heterogeneity between the trials (p < 0.001). HPV positive tumors were associated with lower sensitivity (75% vs 89%; p = 0.01) and specificity (87% vs 95%; p < 0.005). CONCLUSION: FDG-PET/CT within 6 months after (chemo)radiotherapy in HNSCC patients is a reliable method for ruling out residual/recurrent nodal disease and obviates the need for therapeutic intervention. However, FDG-PET/CT may be less reliable in HPV positive tumors and the optimal surveillance strategy remains to be determined.

Mesothelioma With a Large Prevascular Lymph Node: N1 Involvement or Something Different?

A 64-year-old man presented with a large amount of right-sided pleural fluid on imaging, together with calcified pleural plaques and an enlarged nodular structure in the prevascular mediastinum, presumably an enlarged lymph node. Pleural biopsies were obtained during video-assisted thoracoscopic surgery to exclude malignancy. Histopathology showed an epithelial malignant pleural mesothelioma. Induction chemotherapy with cisplatin and pemetrexed was administered followed by an extended pleurectomy and decortication with systematic nodal dissection. Histopathology confirmed the diagnosis of a ypT3N0M0 (stage IB) mesothelioma, and an unexpected thymoma type B2 (stage II) was discovered in the prevascular nodule. Simultaneous occurrence of a mesothelioma and thymoma is extremely rare.

Wolf in Sheep's Clothing: Primary Lung Cancer Mimicking Benign Entities.

Lung cancer is the most common cancer worldwide. On imaging, it typically presents as mass or nodule. Recognition of these typical cases is often straightforward, whereas diagnosis of uncommon manifestations of primary lung cancer is far more challenging. Lung cancer can mimic a variety of benign entities, including pneumonia, lung abscess, postinfectious scarring, atelectasis, a mediastinal mass, emphysema and granulomatous diseases. Correlation with previous history, clinical and biochemical parameters is necessary in the assessment of these cases, but often aspecific and inconclusive. Whereas 18F-fluorodeoxyglucose (18F-FDG) Positron Emission Tomography is the cornerstone in staging of lung cancer, its role in diagnosis of these uncommon manifestations is less straightforward since benign entities can present with increased 18F-FDG-uptake and, on the other hand, a number of these uncommon lung cancer manifestations do not exhibit increased uptake. Chest Computed Tomography (CT) is the imaging modality of choice for both lesion detection and characterization. In this pictorial review we present the wide imaging spectrum of CT-findings as well as radiologic-pathologic correlation of these uncommon lung cancer manifestations. Knowledge of the many faces of lung cancer is crucial for early diagnosis and subsequent treatment. A multidisciplinary approach in these cases is mandatory.

18F-FDG-PET/CT for the detection of disease in patients with head and neck cancer treated with radiotherapy.

OBJECTIVE: The aim of this study is to evaluate the diagnostic performance of FDG-PET/CT for the detection of residual disease after (chemo)radiotherapy in patients with head and neck squamous cell carcinoma (HNSCC) and to evaluate the prognostic value of the FDG-PET/CT findings. METHODS: Patients with HNSCC who underwent FDG-PET/CT after (chemo)radiotherapy were studied retrospectively. RESULTS: 104 FDG-PET/CT-scans were performed at a median of 13.2 weeks post-treatment (5.4-19.0 weeks). The diagnostic performance was time dependent with decreasing sensitivity and slightly increasing specificity over time. Sensitivity, specificity, PPV and NPV at 9 months after imaging were 91%, 87%, 77% and 95%, respectively. In a logistic regression model, the odds of a correct FDG-PET/CT increased with 33% every additional week after end of therapy (p = 0.01) and accuracy plateaued after 11 weeks (97%; p<0.001). A complete response on FDG-PET/CT was associated with an overall survival benefit (50.7 versus 10.3 months; p<0.001). Residual disease on FDG-PET/CT increased the risk of death 8-fold (p<0.001). CONCLUSION: FDG-PET/CT is able to detect residual disease after (chemo)radiotherapy, with an optimal time point for scanning between 11-12 weeks after therapy. However, a reevaluation is probably necessary 10-12 months after the FDG-PET/CT to detect late recurrences. In addition, FDG-PET/CT can guide decisions about neck dissection and identifies patients with poor prognosis.

Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography After Concurrent Chemoradiotherapy in Locally Advanced Head-and-Neck Squamous Cell Cancer: The ECLYPS Study.

Purpose To assess the standardized implementation and reporting of surveillance [18F]fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scan of the neck in locoregionally advanced head-and-neck squamous cell carcinoma (LAHNSCC) after concurrent chemoradiotherapy (CCRT). Patients and Methods We performed a prospective multicenter study of FDG-PET/CT scanning 12 weeks after CCRT in newly diagnosed patients with LAHNSCC (stage IVa/b) that used standardized reconstruction and Hopkins reporting criteria. The reference standard was histology or > 12 months of clinical follow-up. The primary outcome measure was the negative predictive value (NPV) of FDG-PET/CT scans and other supporting diagnostic test characteristics, including time dependency with increasing follow-up time. Results Of 152 patients, 125 had adequate primary tumor control after CCRT and entered follow-up (median, 20.4 months). Twenty-three (18.4%) had residual neck disease. Overall, NPV was 92.1% (95% CI, 86.9% to 95.3%; null hypothesis: NPV = 85%; P = .012) with sensitivity of 65.2% (95% CI, 44.9% to 81.2%), specificity of 91.2% (95% CI, 84.1% to 95.3%), positive predictive value of 62.5% (95% CI, 45.5% to 76.9%), and accuracy of 86.4% (95% CI, 79.3% to 91.3%). Sensitivity was time dependent and high for residual disease manifesting up to 9 months after imaging but lower (59.7%) for disease detected up to 12 months after imaging. Standardized reporting criteria reduced the number of equivocal reports (95% CI for the difference, 2.6% to 15.0%; P = .003). Test characteristics were not improved with the addition of lymph node CT morphology criteria. Conclusion FDG-PET/CT surveillance using Hopkins criteria 12 weeks after CCRT is reliable in LAHNSCC except for late manifesting residual disease, which may require an additional surveillance scan at 1 year after CCRT to be detected.

Long-term remission of locally recurrent oropharyngeal cancer after docetaxel-based chemotherapy plus cetuximab.

BACKGROUND: In recurrent head and neck squamous cell carcinoma ineligible for resection or irradiation, treatment aims primarily at symptom control and quality of life enhancement with an expected outcome of 6-12 months. METHODS: In 2005, a male patient, born in 1944, with a second local recurrence of human papillomavirus negative tonsil cancer was enrolled in the EXTREME trial, and randomized to platinum/5-fluorouracil/cetuximab arm resulting in partial remission with progression-free survival of 12 months. The second-line systemic therapy comprised 5 cycles of 3-weekly docetaxel/cisplatin/5-fluorouracil regimen plus weekly cetuximab. RESULTS: As confirmed on imaging and repeated biopsies, complete response was achieved with disease-free survival of 8 years and follow-up period of 12 years. Severe acute toxicities during the taxane-based chemotherapy plus cetuximab included grade 4 anorexia and grade 3 febrile neutropenia. CONCLUSIONS: Poor tumor differentiation, no weight loss, oropharyngeal location, white race, and particularly the induced complete response were most likely the key favorable prognostic factors in the reported patient. The possibility of a synergistic interaction between taxanes and cetuximab should be further explored.

Surgery for oligometastatic disease in non-small-cell lung cancer.

In general, patients with additional metastatic nodules or distant metastases of a non-small-cell lung cancer (NSCLC) have a poor prognosis. However, published results suggest that in carefully selected patients with synchronous or metachronous metastatic lesions, long-term survival can be obtained when a complete resection of the primary site and metastasis - mostly single brain or adrenal - is achieved. Different subgroups of patients with metastatic NSCLC exist and a distinction should be made between additional malignant nodules in the ipsilateral and contralateral lung, malignant pleural effusion and extrathoracic, single or multiple metastases. Patients with additional malignant nodules in the same lobe or ipsilateral nonprimary lobe have a better prognosis than suggested by the current tumor-node-metastasis (TNM) classification. The other subgroups have a poor prognosis. In view of recent data from a large, international database, proposals have been made for the new TNM classification that will be introduced in 2009.

The use of positron emission tomography with (18)F-fluorodeoxyglucose for the diagnosis of vascular graft infection.

Vascular graft infection is associated with a high morbidity and mortality rate. Diagnosis is difficult, as there is no single diagnostic criterion that has a 100% accuracy. A combination of physical examination, laboratory tests, and several imaging techniques is mandatory. Beside a wide range of indications in the oncological field, positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) has a well-known role in the diagnosis of bone and soft-tissue infections. Some authors have recently reported on the potential use of FDG-PET in the diagnosis of vascular graft infections. The aim of this study is to review personal experience. Five consecutive patients with a suspected prosthetic infection (1 aortobifemoral bypass, 3 femoropopliteal bypasses, and 1 femorofemoral bypass) underwent FDG-PET. All prostheses showed a moderate or intense FDG tracer uptake. All 3 patients with an intense FDG uptake proved to have a prosthetic infection (based on microbiologic examination). These preliminary results suggest that FDG-PET might be an interesting tool to confirm vascular graft infection.

Malignant pleural mesothelioma with heterologous osteoblastic elements: computed tomography, magnetic resonance, and positron emission tomography imaging characteristics of a rare tumor.

The imaging findings of a rare mixed type of malignant mesothelioma of the pleura with heterologous bone stroma in a patient without a previous history of asbestos exposure are reported. Imaging findings of this type of bone-forming pleural mesothelioma are scarcely reported in the literature, with only a few case reports describing findings on conventional radiography, computed tomography, and magnetic resonance imaging. To the best of our knowledge, no positron emission tomography imaging characteristics of this type of mesothelioma have been previously reported.