Imaging in head and neck oncology

Evaluation of head and neck cancer with imaging is a topic that is far more extensive than can be covered in this article. The main reason for head and neck imaging is to evaluate the true extent of disease to best determine surgical and therapeutic options. This process includes evaluation of the size, location, and extent of tumor infiltration into surrounding vascular and visceral structures. Important anatomic variants must be pointed out so the surgeon can avoid potential intraoperative complications. These variant scan be evaluated with the appropriate multiplanar and three-dimensional images to provide as much information as possible to the surgeon preoperatively. Second, nodal staging should be assessed in an effort to increase the number of abnormal nodes detected by physical examination and, more important, to precisely define their location by a standard classification system that can be understood and consistently applied by the radiologist, surgeon, radiation oncologist, and pathologist. Although secondary to the previously described tasks, imaging frequently enables a limitation of the diagnostic and histologic possibilities based on lesion location and signal-attenuation characteristics, which may lead the clinical investigation along a different path. saving the patient unnecessary risk and shortening the time to diagnosis and ultimate treatment.This article has attempted to detail the current state of the controversy between CT, MRI, and other modalities, and has emphasized the constant evolution of this controversy because of the evolving imaging technology.Although CT and MRI are both well suited to evaluation of the deep spaces and submucosal spaces of the head and neck, each has some limitations.MRI has the advantages of higher soft tissue contrast resolution, the lack of iodine-based contrast agents, and high sensitivity for perineural and intracranial disease. The disadvantages of MRI include lower patient tolerance, contraindications in pacemakers and certain other implanted metallic devices, and artifacts related to multiple causes, not the least of which is motion. CT is fast, well tolerated, and readily available but has lower contrast resolution and requires iodinated contrast and ionizing radiation. The current authors' practice is heavily centered on CT for initial evaluation, preoperative planning, biopsy targeting, and postoperative follow-up. They reserve MRI for tumors that are suspicious for perineural,cartilaginous, or bony invasion on CT, or for tumors such as adenoid cystic carcinoma that are highly likely to spread by way of these routes. For patients who have head and neck cancer, a radiologist who is educated in the treatment options, patterns of tumor growth, and important surgical landmarks, and who has a well-established pattern of communication with the head and neck clinical services, including surgery, radiation oncology,and pathology, is key in providing accurate and useful image interpretation.     

Can post-RT neck dissection be omitted for patients with head-and-neck cancer who have a negative PET scan after definitive radiation therapy?

PURPOSE: A prospective, single institution study was conducted to evaluate the role of positron emission tomography with fluoro-deoxyglucose (FDG) before and after definitive radiation therapy for patients with head-and-neck cancer. Correlation with CT or MRI imaging and pathologic findings at the time of planned neck dissection was made. METHODS AND MATERIALS: Twelve patients with AJCC Stages III-IV cancer of the head and neck received CT or MRI and PET imaging before treatment with definitive radiation therapy. One month after completion of treatment, repeat CT or MRI and PET imaging was obtained. All images were reviewed independently by radiologists who were blind to the results of the other modality. Patients then underwent planned neck dissection. Pathologic correlation with posttreatment scans allowed calculation of the sensitivity, specificity, negative predictive value, and the positive predictive value for both CT/MRI and PET. RESULTS: Comparison of CT/MRI to PET obtained before definitive RT revealed both primary tumor and nodal disease were detected by both modalities in all cases where primary tumor was known. After RT, comparison of CT/MRI imaging to findings of neck dissection revealed a sensitivity of 90%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 50%. Comparison of PET imaging with pathologic findings demonstrated sensitivity of 45%, specificity of 100%, positive predictive value of 100%, and a negative predictive value of 14%. CONCLUSIONS: In this small series of patients, the presence of a positive PET 1 month after RT accurately indicated the presence of residual disease in all cases; however, a negative PET indicated absence of disease in only 14%. Further investigation is warranted before FDG-PET should be used to determine whether post-RT neck dissection should be omitted.     

New directions in head and neck imaging

Computerized tomography (CT) and magnetic resonance imaging (MRI), positron emission tomography (PET) and the hybrid modality of PET/CT are sensitive and reliable tools for detection and staging of head and neck cancers. This article describes the role of PET/CT in initial staging of head and neck squamous cell carcinoma, the utility of CT/MR perfusion imaging in qualitative analysis of tumor tissue, and the usefulness of diffusion weighted MR and dynamic contrast-enhanced MR imaging in head and neck oncological imaging.     

Advances in imaging in the postoperative patient with a rising prostate-specific antigen level

Imaging prostate cancer continues to represent a clinical challenge for both primary and recurrent disease. In the evaluation of the persistent/recurrent/metastatic prostate cancer, knowledge of cancer location (local v distant), size, and extent are essential in order to design a treatment, tailored to each patient's needs. There are evidence-based guidelines for the use of imaging in assessing the presence of distant spread of prostate cancer. Radionuclide bone scans and computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET) supplement clinical and biochemical evaluations (prostate-specific antigen [PSA]) for suspected metastatic disease to bones and lymph nodes. There is no consensus about the use of imaging in the evaluation of local tumor recurrence. The use of ultrasound has been limited to biopsy guidance of the prostatic bed, or percutaneous biopsy of enlarged lymph nodes detected on CT or MRI. The use of MRI is evolving. Recent studies indicate that the use of MRI provides valuable information in the evaluation of local tumor recurrence, and nodal and bony metastases. In a patient post-radiation therapy, the method of combining MRI anatomic information with MR spectroscopic metabolic information is evolving. Another modality offering information about anatomy and metabolism of the local disease is PET/CT. The value of PET/CT at present is controversial, but new studies exploring the role of PET/CT in aggressive prostate cancer are promising.     

Aktueller Stellenwert von MRT, CT und PET in der Diagnostik des Zervixkarzinoms

MRI is estabished as a modality available for use in the diagnosis of cervical cancer. The soft tissue contrast it supplies is far better than that of any other method, making it the modality of choice for direct visualization of the carcinoma and thus also for tumor staging. Pelvic MRI performed as part of the pretreatment evaluation has been shown to be cost effective, and it is recommended for use in macroscopic cervical cancer in the guidelines of professional societies for gynecologists and oncologists. It has proved to be a reliable method for the early detection of recurrent tumors. It remains unsurpassed for accurate visualization of local tumor extent and involvement of adjacent pelvic organs in recurrent cervical cancer. It is also the method of choice for use in the planning of brachytherapy. With the increasing use of PET and PET/CT for investigations in oncology patients a second method has emerged. This seems to have advantages particularly in the detection of lymph node metastases by whole-body examination. Encouraging results on detection of recurrent cervical cancer during follow-up treatment by PET/CT have also been published, but a definitive assessment of the value of PET in tumor aftertreatment cannot be reached without more comparative studies against MRI. Moreover, there have so far been no studies evaluating the cost effectiveness of PET. In the near future it will be necessary to reconsider the new diagnostic modalities with reference to their accuracy in staging, since therapy is oriented increasingly to disease stage and increasingly specific treatment methods are applied.     

ACR appropriateness criteria® adjuvant therapy for resected squamous cell carcinoma of the head and neck

Locoregional recurrence following surgical resection alone for stage III/IV head and neck cancer is common. Adjuvant radiotherapy has been shown to improve post-operative locoregional control when compared to pre-operative radiotherapy for head and neck cancers. Following surgical resection, adverse pathological features determine the need for adjuvant therapy. High-risk pathologic features include extranodal tumor spread and involved surgical margins. Other adverse pathologic features include T 3-4 tumors, perineural invasion, lymphovascular space invasion, low neck adenopathy, and multiple tumor involved cervical lymph nodes. The standard adjuvant therapies are post-operative radiation therapy or post-operative chemoradiotherapy. Post-operative chemoradiotherapy yields superior locoregional control, progression-free survival, and in some studies, overall survival compared to post-operative radiotherapy for high-risk patients in multiple randomized studies. Pooled analyses of randomized data demonstrate that post-operative concurrent chemoradiotherapy is associated with overall survival benefits for patients with involved surgical margins as well as those with extranodal tumor spread. Post-operative radiotherapy concurrent with cisplatin at 100 mg/m(2) every 21 days is the current standard chemoradiotherapy platform adjuvant head and neck cancer treatment. Post-operative radiotherapy and post-operative chemoradiotherapy radiation treatment volumes are not standardized and should be designed based on the risk of recurrence and clinically occult involvement of head and neck subsites and nodal regions. Evidence supports a post-operative radiotherapy and chemoradiotherapy radiation dose of at least 63 Gy for high-risk patients and at least 57 Gy for low risk patients.     

The role of FDG PET in the clinical management of head and neck cancer

Positron emission tomography (PET) with fluorodeoxyglucose (FDG) allows the visualization of metabolic tissue activity. Use of FDG in in-vivo cancer imaging is based on enhanced glycolysis in tumor cells. In vivo experiments have demonstrated the potential use of FDG PET in squamous-cell head and neck tumors and the detection of tumor involvement in lymph nodes. Since its introduction in this area, several papers have appeared on the use of this imaging modality. Indications for the use of FDG PET in patients with head and neck cancer are discussed.     

Utility of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography and positron emission tomography/computed tomography imaging in the preoperative staging of head and neck squamous cell carcinoma

The combination of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) has been reported to be more accurate than CT or PET alone in a preoperative setting. We compared the diagnostic utility of preoperative PET/CT, PET and CT/MRI in 167 patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), of whom 104 underwent FDG PET and 63 underwent combined PET/CT with all receiving CT/MRI. These preoperative PET, PET/CT, and CT/MRI results were reviewed and their accuracies were compared in patients in whom diagnosis was confirmed histopathologically. Age, sex, primary sites and stage, and nodal involvement were comparable between two groups. The accuracy of PET and PET/CT for detecting primary tumors and cervical metastases was comparable, but significantly higher than that of CT/MRI (98%-97% vs. 86-88% for primary; 92%-93% vs. 85%-86% for neck on a level-by-level basis; P<.05). PET and PET/CT gave false negative results: in 2 (2%) and 2 (3%) patients for primary tumors; in 6 (6%) and 3 (5%) patients for neck metastases, respectively. PET and PET/CT also gave false-positive results for cervical metastases in 5 (5%) and 4 (6%) patients, respectively. Compared with PET alone, preoperative FDG PET/CT may not yield significantly improved diagnostic accuracy in patients with HNSCC. Moreover, despite their high accuracy, PET and PET/CT may not abrogate the need for conventional imaging and pathologic staging based on primary resection and neck dissection.     

Role of preoperative local and distant staging in rectal cancer

Preoperative imaging in rectal cancer is very important, as accurate staging determines optimal treatment strategy. In this review, imaging modalities for locoregional and distant staging in rectal cancer are discussed. For local staging, superficial tumors are best staged using endorectal US (EUS), as EUS is the most accurate modality for assessment of tumor ingrowth into the rectal wall layers. The more advanced tumors are best imaged using MRI, because MRI accurately predicts the distance from tumor to mesorectal fascia, and thus the circumferential resection margin (CRM), as well as possible invasion into surrounding organs. For the prediction of the nodal status none of the three imaging modalities - EUS, MRI and CT - can be reliably used for clinical decision-making. Only MRI using lymph node specific contrast (such as ultrasmall paramagnetic iron oxide-enhanced MRI) seems promising for the detection of nodal disease. For the detection of distant metastases transabdominal ultrasound and chest X-ray are used as a primary screening tool. However, for the high prevalence group (stage III) both methods are insufficiently sensitive, and CT of the chest plus abdomen is preferred.     

Detection of cervical lymph node metastasis in head and neck cancer patients with clinically N0 neck-a meta-analysis comparing different imaging modalities

ABSTRACT: BACKGROUND: How to properly manage clinically negative neck of head and neck cancer patients is a controversial topic. Research is now directed toward finding a method sensitive enough to bring the risk of occult metastases below 20%. The aim of this review was to compare the diagnostic accuracy of different imaging modalities, including CT, MRI, PET and US, in clinically N0 head and neck cancer patients. METHODS: For this systematic review and meta-analysis, PubMed and the Cochrane Database were searched for relevant original articles published up to May 2011. Inclusion criteria were as follows: articles were reported in English; CT, MRI, PET or US were performed to identify cervical metastases in clinically N0 head and neck squamous cell carcinoma; and data were sufficient for the calculation of true-positive or false-negative values. A bivariate random effect model was used to obtain pooled sensitivity and specificity. The positive and negative test probability of neck metastasis was generated based on Bayesian theory and collected data for different pre-test possibilities. RESULTS: Of the 168 identified relevant articles, 7 studies fulfilled all inclusion criteria for CT, 6 studies for MRI, 11 studies for PET and 8 studies for US. There was no difference in sensitivity and specificity among these imaging modalities, except CT was superior to US in specificity. The pooled estimates for sensitivity were 52% (95% confidence interval [CI], 39% ~ 65%), 65% (34 ~ 87%) 66% (47 ~ 80%), and 66% (45 ~ 77%), on a per-neck basis for CT, MRI, PET and US, respectively. The pooled estimates for specificity were 93% (87% ~ 97%), 81% (64 ~ 91%), 87% (77 ~ 93%), and 78% (71 ~ 83%) for CT, MRI, PET and US, respectively. With pre-examination nodal metastasis probabilities set at 10%, 20% and 30%, the post-exam probabilities of positive nodal metastasis rates were 47%, 66% and 77% for CT; 27%, 46% and 59% for MRI; 36%, 56% and 69% for PET; and 25%, 42% and 56% for US, respectively. Negative nodal metastasis probabilities were 95%, 89% and 82% for CT; 95%, 90% and 84% for MRI; 96%, 91% and 86% for PET; and 95%, 90% and 84% for US, respectively. CONCLUSIONS: Modern imaging modalities offer similar diagnostic accuracy to define and diagnose clinically N0 neck. Minimizing morbidity and avoiding elective neck dissection is acceptable in some select cases.     

Technology insight: PET and PET/CT in head and neck tumor staging and radiation therapy planning

The evolving utilization of functional imaging, mainly 2-[18F]fluoro-2-deoxyglucose (18FDG) imaging, with positron emission tomography (PET) and PET/CT, is profoundly altering head and neck tumor staging approaches, radiation treatment planning, and follow-up management. Tumor-node-metastasis staging with PET/CT has improved the characterization of patient disease versus CT, MRI, or PET alone, thereby affecting patient disease management. Therefore, the utilization of PET/CT is appropriate for head and neck cancer staging in the initial presentation and in the recurrent setting. In the setting of radiation therapy treatment planning, PET-directed tumor volume contouring is not ready for clinical practice without further technological improvements in imaging specificity/sensitivity and resolution. Patient or organ motion might interfere with the accuracy of anatomical co-alignment, and variability in defining the threshold of imaging signals on PET images can affect the contour of the biological tumor volume. The use of PET/CT for staging and detecting both primary and recurrent head and neck cancer is valuable; however, its application in radiation treatment planning should be viewed as investigational.     

Current applications and future developments of positron emission tomography in head and neck cancer]

Positron emission tomography (PET-scan) is a well-established imaging modality in oncology. Using FDG, PET has also a wide range of applications in head and neck tumors for diagnosis, staging, monitoring of response to therapy, and detection of relapse. After a short technical introduction, the current indications of PET-FDG in head and neck tumors are reviewed. Present and future developments of PET are twofold: the use of new tracers for protein synthesis, cellular proliferation or detection of hypoxia etc., and the introduction of metabolic imaging as a adjunct to CT and MRI to determine target-volumes in radiation treatment planning. However, it has to be emphasized that a thorough clinical validation of the methods used is mandatory before their implementation in routine practice.     

Comparison of five segmentation tools for 18F-fluoro-deoxy-glucose-positron emission tomography-based target volume definition in head and neck cancer

PURPOSE: Target-volume delineation for radiation treatment to the head and neck area traditionally is based on physical examination, computed tomography (CT), and magnetic resonance imaging. Additional molecular imaging with (18)F-fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) may improve definition of the gross tumor volume (GTV). In this study, five methods for tumor delineation on FDG-PET are compared with CT-based delineation. METHODS AND MATERIALS: Seventy-eight patients with Stages II-IV squamous cell carcinoma of the head and neck area underwent coregistered CT and FDG-PET. The primary tumor was delineated on CT, and five PET-based GTVs were obtained: visual interpretation, applying an isocontour of a standardized uptake value of 2.5, using a fixed threshold of 40% and 50% of the maximum signal intensity, and applying an adaptive threshold based on the signal-to-background ratio. Absolute GTV volumes were compared, and overlap analyses were performed. RESULTS: The GTV method of applying an isocontour of a standardized uptake value of 2.5 failed to provide successful delineation in 45% of cases. For the other PET delineation methods, volume and shape of the GTV were influenced heavily by the choice of segmentation tool. On average, all threshold-based PET-GTVs were smaller than on CT. Nevertheless, PET frequently detected significant tumor extension outside the GTV delineated on CT (15-34% of PET volume). CONCLUSIONS: The choice of segmentation tool for target-volume definition of head and neck cancer based on FDG-PET images is not trivial because it influences both volume and shape of the resulting GTV. With adequate delineation, PET may add significantly to CT- and physical examination-based GTV definition.     

Bildgebung des Prostatakarzinoms

Prostatic carcinoma (PCa) is the most common life-threatening cancer in the Western world. In Germany about 40,609 new cases are expected per year. Mortality is 10%. The major goals of pretherapeutic imaging are determination of local intraprostatic tumor extent, presence of extracapsular extension (ECE), seminal vesicle invasion (SVI), invasion into neurovascular bundles and if so into surrounding tissues and organs. In addition, determination of presence and extent of nodal spread as well as distant metastases is required. Exact pretherapeutic staging is mandatory, because the choice of optimal tumor treatment is initiated in strict dependence on tumor stage and risk profile. Anatomic as well as functional molecular imaging of PCa has made significant progress in recent years. Transrectal ultrasonography (TRUS) is primarily used as the basic imaging test in PCa and to guide prostate biopsies. When prostate biopsies are negative but suspicion of PCa persists, MRI/MRS and C-11-/F-18-choline PET/CT may be helpful for localization of PCa, determining intraprostatic tumour extent – and if so – ECE, SVI, invasion into neurovascular bundles and to guide targeted biopsies. Lymphotrophic contrast agents are highly promising for accurate nodal staging of PCa, but are not yet available for clinical use. Thus, nodal staging with commonly available imaging modalities remains insufficiently sensitive and inadequately specific. Localization of local relapse of PCa with contrast-enhanced MRI and C-11-choline PET/CT has made significant progress and allows imaging of local recurrence of PCa in the majority of patients with a PSA >1 ng/ml.     

Diagnostic accuracy of <Superscript>18</Superscript>F–FDG PET/CT and MR imaging in patients with adenoid cystic carcinoma

Background

The aim of this study was to evaluate the value of 18F–FDG PET/CT (PET/CT) and MRI for local and/or whole-body restaging of adenoid cystic carcinoma of the head and neck (ACC).

Methods

Thirty-six patients with ACC underwent conventional MRI of the head and neck and a whole-body PET/CT and were analysed with regards to detection of a local tumor recurrence, lymph node or distant metastases. A consensus interpretation of all available imaging data was used as reference standard. Sensitivity, specificity, diagnostic accuracy, positive and negative predictive values were calculated for MRI and PET/CT.

Results

The sensitivity of PET/CT and MRI was 96% (89%), specificity 89% (89%), PPV 96% (96%), NPV 89% (73%) and accuracy 94% (89%) for detection of local tumors. Additionally, PET/CT revealed lymph node metastases in one patient and distant metastases in 9/36 patients. In three patients secondary primaries were found.

Conclusions

Whole-body PET/CT in addition to MRI of the head and neck improves detection of local tumour and metastastic spread in ACC.

     

Functional imaging in head and neck cancer

Functional imaging has become an increasingly important diagnostic tool for head and neck cancer, and as its availability increases so will its utilization. Positron emission tomography (PET) with the radiotracer 18-fluorodeoxyglucose (¹⁸FDG) is the most commonly used functional imaging technology, and it has the potential to improve the staging and detection of head and neck tumors compared with conventional cross-sectional imaging techniques such as CT or magnetic resonance imaging. Specifically, PET contributes valuable information for localizing a primary tumor in patients with an unknown primary and neck metastasis, in the staging of untreated head and neck cancer, in the detection of residual disease after definitive radiotherapy or chemoradiotherapy, and in the detection of recurrent disease. New technologies have been introduced using the combination of CT and PET, which allows exact anatomic correlation with areas of increased tracer uptake. In addition, new tracers may allow quantification of important cellular processes related to tumor proliferation or identification of tumors that may respond to certain targeted therapies. This strategy will eventually enable physicians to tailor therapy to molecular characteristics and therefore improve outcomes for patients with head and neck cancer.     

Bildgebung in der Diagnostik des CUP-Syndroms

Diagnostic imaging in patients with CUP (cancer of unknown primary) is aimed at identification of well treatable subgroups, staging (local versus disseminated disease), and early detection of complications in addition to the search for a primary tumor. The basic diagnostic imaging modality is contrast-enhanced whole-body computer tomography (neck to pelvis). Additional PET/CT is recommended as the next step in cases with negative or solitary findings and the possibility for a radical therapy. Mammography, breast sonography and in negative cases breast MRI are recommended for female patients with axillary CUP. In cervical CUP with negative CT or MRI of the neck and thorax, there is strong evidence for PET/CT. Special imaging of the somatostatin receptors is indicated in neuroendocrine metastases with unknown primary.     

Correlation of positron emission tomography standard uptake value and pathologic specimen size in cancer of the head and neck

PURPOSE: To correlate positron emission tomography (PET) standard uptake value (SUV) with pathologic specimen size in patients with head-and-neck cancers. METHODS AND MATERIALS: Eighteen patients with Stage II-IVB head-and-neck cancer with 27 tumors who underwent PET and computed tomography (CT) imaging of the head and neck followed by surgical resection were selected for this study. Various SUV thresholds were examined, including the software default (SUV(def)), narrowing the window by 1 standard deviation (SD) of the maximum (SUV-1SD), and SUV cutoff values of 2.5 or greater (SUV2.5) and 40% or greater maximum (SUV40). Volumetric pathologic data were available for 12 patients. Tumor volumes based on pathologic examination (gold standard), CT, SUV(def), SUV-1SD, SUV2.5, and SUV40 were analyzed. RESULTS: PET identified five tumors not seen on CT. The sensitivity of PET for identifying primary tumors was 94% (17 of 18). The Sensitivity of PET for staging the neck was 90% (9 of 10), whereas the specificity was 78% (7 of 9). The SUV2.5 method was most likely to overestimate tumor volume, whereas SUV(def) and SUV-1SD were most likely to underestimate tumor volume. CONCLUSIONS: The PET scan provides more accurate staging of primary tumors and nodal metastases for patients with advanced head-and-neck cancer than CT alone. Compared with the gold standard, significant variability exists in volumes obtained by using various SUV thresholds. A combination of clinical, CT, and PET data should continue to be used for optimal treatment planning. The SUV40 method appears to offer the best compromise between accuracy and reducing the risk of underestimating tumor extent.     

Utility of combined (18)F-fluorodeoxyglucose-positron emission tomography and computed tomography in patients with cervical metastases from unknown primary tumors

(18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) has been reported to identify primary tumors in patients with cervical metastases from cancer of unknown primary (CUP). However, few reports have assessed the use of combined FDG-PET/computed tomography (CT) in this setting. We therefore examined the utility of combined FDG-PET/CT in the detection of primary tumors and unrecognized metastases in these patients. Patients with previously untreated CUPs underwent head and neck CT and whole-body FDG-PET/CT before panendoscopy and guided biopsy. The diagnostic accuracy of CT and FDG-PET/CT in detecting primary tumors and cervical metastases was compared with that of histopathology. The ability of FDG-PET/CT to detect distant metastases was also tested. Of the 44 eligible patients, 16 had occult primary tumors in the head and neck. FDG-PET/CT was significantly more sensitive than CT for detecting primary tumors (87.5% vs. 43.7%, P=.016), but their specificity did not differ (82.1% vs. 89.3%, P=.500). Thirty-four of 44 patients underwent neck dissection; 67 of 182 dissected cervical levels had metastatic nodal diseases. On a level-by-level basis, FDG-PET/CT was significantly more sensitive than CT (94.0% vs. 71.6%, P<.001), but the two methods were equally specific (94.8% vs. 96.5%). FDG-PET/CT correctly detected distant metastases in 6 of 6 patients. Combined FDG-PET/CT is a useful screening method for primary tumor detection, accurate nodal staging, and distant metastases in patients with CUPs.     

Perineural invasion and spread in head and neck cancer

Perineural involvement is a well-recognized clinicopathologic entity found in head and neck (H&N) cancers, including mucosal epithelial carcinomas and salivary gland malignancies. Perineural disease remains a diagnostic, prognostic and therapeutic challenge for the multidisciplinary H&N oncology team. Nerves are important routes of tumor spread in H&N malignancies, yet the biology and prognostic implications of perineural tumor growth are not fully understood. On balance, the available evidence suggests that it is associated with an increased risk of locoregional recurrence but the impact on survival remains uncertain. Perineural involvement has implications for locoregional disease diagnosis and management. MRI is the best imaging modality to detect tumor extent. Advanced radiotherapy technologies such as intensity-modulated radiation therapy and image-guided radiation therapy have the potential for more accurate targeting and treatment of anatomically complex patterns of disease spread. This review is limited to nondermatologic H&N cancers.