ACR Appropriateness Criteria® Staging and Post-Therapy Assessment of Head and Neck Cancer.

Imaging of head and neck cancer at initial staging and as part of post-treatment surveillance is a key component of patient care as it guides treatment strategy and aids determination of prognosis. Head and neck cancer includes a heterogenous group of malignancies encompassing several anatomic sites and histologies, with squamous cell carcinoma the most common. Together this comprises the seventh most common cancer worldwide. At initial staging comprehensive imaging delineating the anatomic extent of the primary site, while also assessing the nodal involvement of the neck is necessary. The treatment of head and neck cancer often includes a combination of surgery, radiation, and chemotherapy. Post-treatment imaging is tailored for the evaluation of treatment response and early detection of local, locoregional, and distant recurrent tumor. Cross-sectional imaging with CT or MRI is recommended for the detailed anatomic delineation of the primary site. PET/CT provides complementary metabolic information and can map systemic involvement. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Neuroendocrine Neoplasms: Epidemiology, Diagnosis, and Management.

Neuroendocrine tumors have variety of biological and clinical characteristics. The classification of neuroendocrine neoplasm has evolved, and the newest 2019 World Health Organization classification outlines a well-differentiated high-grade G3 subtype, recognizing its differences from the poorly differentiated neuroendocrine carcinoma. 68Ga-DOTAT PET has largely replaced somatostatin scintigraphy as the diagnostic workup choice for NENs. NETest, a multi-analyte liquid biopsy, is a promising recent development in the biochemical diagnosis. Management includes wait and watch approach, surgical resection, somatostatin analogs, 177Lu DOTATATE therapy, chemotherapy, radiotherapy or immunotherapy combinations. Further clinical trials are necessary for determining the appropriate sequencing.

Impact of Neck PET/CT Positivity on Survival Outcomes-Visual and Quantitative Assessment: Results From ACRIN 6685.

INTRODUCTION: FDG PET/CT was prospectively studied in 287 cN0 head and neck cancer patients in ACRIN 6685, and additional analysis of neck FDG uptake upon recurrence-free survival (RFS) and overall survival (OS) was performed. PATIENTS AND METHODS: Two hundred eight had analyzable data. Survival analysis was performed to compare RFS and OS based on neck FDG visual assessment (VA) and SUV max . For SUV max , the optimal thresholds were calculated using conditional inference trees on a randomly selected 70% training data set and validated using the remaining 30% of data. Kaplan-Meier curves with log-rank tests were generated for the patient groups based on VA and optimal SUV max thresholds, and the hazards ratios (HRs) and 95% confidence intervals (CIs) were also calculated. Hypothesis testing was set at a significance level of 0.05. RESULTS: A total of 73.9% of bilateral cN0 and 50.0% of unilateral cN0 were alive at the end of the study with the remaining being dead or lost to follow-up. Overall survival median follow-up time was 24.0 months (interquartile range, 15.8-25.3; range, 0-37.0). A total of 63.3% of bilateral cN0 and 42.5% of unilateral cN0 patients remained disease free during the study. Recurrence-free survival median follow-up time was 23.9 months (interquartile range, 12.4-25.2; range, 0-35.6). Visual assessment of necks by our panel of radiologists was significantly associated with RFS (HR [95% CI], 2.30 [1.10-4.79]; P = 0.02), but not with OS (HR [95% CI], 1.64 [0.86-3.14]; P = 0.13). The optimal SUV max thresholds were 2.5 for RFS and 5.0 for OS. For SUV max assessment, applying the optimal thresholds to the 30% test data yielded HRs (95% CIs) of 2.09 (0.61-7.14; P = 0.23) for RFS and 3.42 (1.03-11.41; P = 0.03) for OS. The SUV max threshold of 5.0 was significantly associated with RFS (HR [95% CI], 5.92 [1.79-19.57]; P < 0.001). CONCLUSIONS: Neck FDG uptake by VA is significant for RFS. An SUV max threshold of 5.0 is significantly associated with OS and RFS.

2-Deoxy-2-[18F] Fluoro-d-Glucose PET/Computed Tomography: Therapy Response Assessment in Head and Neck Cancer.

18F-FDG-PET/CT (2-deoxy-2-[18F] fluoro-d-glucose PET/computed tomography) is a reliable modality for accurate assessment of treatment response, early detection of recurrence, or second primary tumors in head and neck squamous cell carcinoma (HNSCC), if performed at the appropriate time after therapy. This review focuses on the utility of posttreatment 18F-FDG-PET/CT in HNSCC, reviews the expected imaging findings and pitfalls after treatments, summarizes common 18F-FDG-based quantitative and qualitative response assessment methods, and discusses the value of imaging surveillance in HNSCC. We also provide an overview of recently approved immune checkpoint inhibitors in HNSCC and current recommendations on immunotherapy-response monitoring.

The Value of FDG PET/CT in Treatment Response Assessment, Follow-Up, and Surveillance of Lung Cancer.

OBJECTIVE: The purpose of this article is to summarize the evidence regarding the role of FDG PET/CT in treatment response assessment and surveillance of lung cancer and to provide suggested best practices. CONCLUSION: FDG PET/CT is a valuable imaging tool for assessing treatment response for patients with lung cancer, though evidence for its comparative effectiveness with chest CT is still evolving. FDG PET/CT is most useful when there is clinical suspicion or other evidence for disease recurrence or metastases. The sequencing, cost analysis, and comparative effectiveness of FDG PET/CT and conventional imaging modalities in the follow-up setting need to be investigated.

Molecular Imaging and Precision Medicine: PET/Computed Tomography and Therapy Response Assessment in Oncology.

A variety of methods have been developed to assess tumor response to therapy. Standardized qualitative criteria based on 18F-fluoro-deoxyglucose PET/computed tomography have been proposed to evaluate the treatment effectiveness in specific cancers and these allow more accurate therapy response assessment and survival prognostication. Multiple studies have addressed the utility of the volumetric PET biomarkers as prognostic indicators but there is no consensus about the preferred segmentation methodology for these metrics. Heterogeneous intratumoral uptake was proposed as a novel PET metric for therapy response assessment. PET imaging techniques will be used to study the biological behavior of cancers during therapy.

Therapy Response Assessment and Patient Outcomes in Head and Neck Squamous Cell Carcinoma: FDG PET Hopkins Criteria Versus Residual Neck Node Size and Morphologic Features.

OBJECTIVE: This study investigates the prognostic value of (18)F-FDG PET/CT qualitative therapy assessment (Hopkins criteria) in patients with head and neck squamous cell carcinomas (HNSCCs) with residual neck nodes after definitive chemoradiation therapy and compares the Hopkins criteria with anatomic nodal size and morphologic features for prediction of survival outcomes. MATERIALS AND METHODS: A total of 72 patients with HNSCC, with negative primary tumor and positive residual neck nodes (CT criteria > 1 cm short-axis diameter) after the completion of definitive chemoradiation therapy, were included. PET/CT was performed 6-24 weeks after completion of treatment. FDG uptake in residual nodes on PET/CT was interpreted using a structured qualitative 5-point scale (Hopkins criteria). The 5-point scale was dichotomized to negative (scores 1, 2, and 3) or positive (scores 4 and 5) results. Cystic or necrotic nodes were defined as those with central low attenuation with a relatively hyperdense capsule. Kaplan-Meier curve and Cox regression analysis were performed. RESULTS: On the basis of the Hopkins criteria, 10 (13.9%) patients had positive findings and 62 (86.1%) had negative findings for residual nodal disease. According to CT interpretation, 25 patients (34.7%) had residual cervical lymph nodes greater than or equal to 1.5 cm in diameter, and 41 (56.9%) patients had cystic or necrotic nodes. Patients were followed for a median of 27 months after posttherapy PET/CT. There was a statistically significant difference in overall survival (OS) (hazard ratio, 7.06; p < 0.001) and progression-free survival (PFS) (hazard ratio, 6.18; p < 0.001) between patients with negative versus positive residual FDG nodal uptake. There was no statistically significant difference in OS and PFS in patients categorized on the basis of nodal size or morphologic features. CONCLUSION: PET-based structured qualitative therapy assessment (Hopkins criteria) can predict survival outcomes of patients with HNSCC with residual neck nodes after definitive chemoradiotherapy.

18F-FDG PET/CT: Therapy Response Assessment Interpretation (Hopkins Criteria) and Survival Outcomes in Lung Cancer Patients.

UNLABELLED: The purpose of this study was to evaluate the value of an (18)F-FDG PET/CT-based interpretation system (Hopkins criteria) to assess the therapy response and survival in lung cancer. METHODS: This is an Institutional Review Board-approved, retrospective study. A total of 201 patients with biopsy-proven lung cancer, who underwent therapy assessment (18)F-FDG PET/CT within 6 mo (mean, 7.5 wk) of completion of treatment, were included. Patients were primarily treated with surgical resection, chemotherapy, radiation therapy, or a combination of these treatments. PET/CT studies were interpreted by 2 nuclear medicine physicians, and discrepancies were resolved by a third interpreter. The studies were scored using a qualitative 5-point scale for the primary tumor, mediastinum, distant metastatic site, if present, and overall assessment. Scores 1, 2, and 3 were considered negative and scores 4 and 5 were considered positive for residual disease. Patients were followed for a median of 12 mo (up to 128 mo). Kaplan-Meier plots with a Mantel-Cox log-rank test were performed considering death as the endpoint. RESULTS: Overall, the PET/CT studies were positive in 144 (71.6%) and negative in 57 (28.4%) patients. There was substantial agreement between 2 interpreters (R1, R2), with a κ of 0.78 (P < 0.001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the Hopkins scoring system were 89%, 80%, 92.8%, 71.4%, and 86.7%, respectively. Overall, PET/CT resulted in starting a new treatment plan in 70.8% of patients with positive residual disease on therapy assessment PET/CT. There was a significant difference in overall survival (OS) between patients who were categorized as positive in comparison to those who were categorized as negative (hazard ratio [HR] = 2.12; 95% confidence interval = 1.44-3.12), which remained significant after adjustment for disease stage, prior clinical suspicion, and primary treatment. Subgroup analysis according to the tumor histology showed that positive Hopkins scoring could significantly predict the OS in both small cell lung cancer (HR = 2.88; log-rank, P = 0.02) and non-small cell lung cancer (HR = 2.01; log-rank, P = 0.001). Similarly, there was a significant difference in OS between patients with positive and negative Hopkins score both in those who had surgical resection as part of the primary treatment (HR = 6.09; log-rank, P < 0.001) and in those who were treated with chemotherapy with or without radiation (HR = 1.60; log-rank, P = 0.02). CONCLUSION: The 5-point qualitative therapy response interpretation for lung cancer has substantial interinterpreter agreement and high accuracy and could significantly predict survival in lung cancer, irrespective of tumor histology and treatment modality.

Follow-up FDG PET/CT in Patients With Non-Hodgkin Lymphoma: Value to Clinical Assessment and Patient Management.

OBJECTIVE: The aim of this study was to evaluate the value of each follow-up PET/CT in the clinical assessment of recurrence as well as determining its impact on management in patients with non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: All patients diagnosed with NHL who had at least 1 follow-up PET/CT study, 6 months after primary treatment completion, were included. There were 204 eligible NHL patients with 560 follow-up PET/CT scans. The change in management was recorded after each follow-up PET/CT scan in comparison to the management plan before the study. RESULTS: Among the 560 scans, 388 scans (69.3%) were done without clinical suspicion and 172 scans (30.7%) were done with prior clinical suspicion of recurrence. Follow-up scan results suggested disease in 12.4% of the scans performed without clinical suspicion and ruled out disease in 16.3% scans performed with prior clinical suspicion. The management of NHL patients was changed after 37.8% of follow-up scans with prior clinical suspicion of recurrence and after 8.3% of scans in patients without prior clinical suspicion of recurrence. The management of NHL patients was not changed after 50.6% scans with prior clinical suspicion of recurrence of which 23.3% had no treatment before and after the scan and 27.3% had the same treatment continued before and after the scan. CONCLUSIONS: Follow-up FDG PET/CT performed with prior clinical suspicion of recurrence added value to patients with NHL for clinical assessment in 16.3% of the scan times and influenced the management in 37.8% of scan times. The management change was only 8.3% in patients without prior clinical suspicion of recurrence, and hence, surveillance FDG PET/CT in NHL should be avoided.

18F-FDG-PET/CT therapy assessment of locally advanced pancreatic adenocarcinoma: impact on management and utilization of quantitative parameters for patient survival prediction.

OBJECTIVES: This study aims to evaluate the impact of therapy assessment PET/computed tomography (CT) scan on the management of locally advanced pancreatic adenocarcinoma (LAPC), and the value of qualitative versus quantitative PET/CT interpretation for patient outcome prediction. MATERIALS AND METHODS: Forty-two LAPC patients were retrospectively included. PET/CT was performed at a median of 4.6 weeks after completion of chemo ± radiotherapy to assess the primary treatment response. PET was interpreted visually using a qualitative five-point scale (Hopkins criteria for therapy assessment). Quantitative PET parameters including maximum and peak standardized uptake value (SUV max and SUV peak), total lesion glycolysis, and metabolic tumor volume (MTV) were also measured using the gradient segmentation method. Kaplan-Meier and Cox regression analyses were performed. RESULTS: Thirty-five patients were followed up until death. Therapy assessment PET/CT led to a change in the overall management of 22 (52.4%) patients, prompting surgical resection (eight patients), adding radiation therapy (eight patients), or starting palliative chemotherapy (six patients). The median survival in patients with a negative or a positive PET scan, according to the Hopkins criteria, was 14.6 and 8.7 months, respectively (P=0.06). The median quantitative thresholds of SUV peak 2.64 [hazard ratio (HR)=2.67, P=0.03], total lesion glycolysis 44.0 g (HR=2.64, P=0.005), and MTV 24.7 ml (HR=2.57, P=0.008) were significant predictors of overall survival. Using combined quantitative scoring, patients with high SUV peak and high MTV (>median cut point) had a 5.45-fold (95% confidence interval: 1.76-16.87) increased risk for death compared with those with both low SUV peak and MTV (the reference group). CONCLUSION: PET-based volumetric parameters can predict survival outcomes of patients with LAPC. A combined quantitative PET/CT scoring system provides significantly improved prognostication.

(18)F-FDG PET/CT and Melanoma: Staging, Immune Modulation and Mutation-Targeted Therapy Assessment, and Prognosis.

OBJECTIVE: Monoclonal antibodies that target the programmed cell death 1 (PD-1) immune checkpoint protein and its associated ligands, PD-L1 and PD-L2, and targeted inhibitors of mutated signal transduction molecules such as BRAF inhibitors show immense promise in treating patients with melanoma. We discuss the use of (18)F-FDG PET/CT for assessing therapy effectiveness, staging advanced disease, and determining prognosis of patients with melanoma. CONCLUSION: FDG PET/CT is useful in staging disease, assessing therapy, and determining prognosis in patients with melanoma.

Repeatability of 18F-FDG PET/CT in Advanced Non-Small Cell Lung Cancer: Prospective Assessment in 2 Multicenter Trials.

UNLABELLED: PET/CT with the glucose analog (18)F-FDG has several potential applications for monitoring tumor response to therapy in patients with non-small cell lung cancer (NSCLC). A prerequisite for many of these applications is detailed knowledge of the repeatability of quantitative parameters derived from (18)F-FDG PET/CT studies. METHODS: The repeatability of the (18)F-FDG signal was evaluated in 2 prospective multicenter trials. Patients with advanced NSCLC (tumor stage III-IV) underwent two (18)F-FDG PET/CT studies while not receiving therapy. Tumor (18)F-FDG uptake was quantified by measurement of the maximum standardized uptake value within a lesion (SUVmax) and the average SUV within a small volume of interest around the site of maximum uptake (SUVpeak). Analysis was performed for the lesion in the chest with the highest (18)F-FDG uptake and a size of at least 2 cm (target lesion) as well as for up to 6 additional lesions per patient. Repeatability was assessed by Bland-Altman plots and calculation of 95% repeatability coefficients (RCs) of the log-transformed SUV differences. RESULTS: Test-retest repeatability was assessed in 74 patients (34 from the ACRIN 6678 trial and 40 from the Merck MK-0646-008 trial). SUVpeak was 11.57 ± 7.89 g/mL for the ACRIN trial and 6.89 ± 3.02 for the Merck trial. The lower and upper RCs were -28% (95% confidence interval [CI], -35% to -23%) and +39% (95% CI, 31% to 54%) in the ACRIN trial, indicating that a decrease of SUVpeak by more than 28% or an increase by more than 39% has a probability of less than 2.5%. The corresponding RCs from the Merck trial were -35% (95% CI, -42% to -29%) and +53% (95% CI, 41% to 72%). Repeatability was similar for SUVmax of the target lesion, averaged SUVmax, and averaged SUVpeak of up to 6 lesions per patient. CONCLUSION: The variability of repeated measurements of tumor (18)F-FDG uptake in patients with NSCLC is somewhat larger than previously reported in smaller single-center studies but comparable to that of gastrointestinal malignancies in a previous multicenter trial. The variability of measurements supports the definitions of tumor response according to PET Response Criteria in Solid Tumors.

18F-FDG PET/CT and lung cancer: value of fourth and subsequent posttherapy follow-up scans for patient management.

UNLABELLED: The Centers for Medicare and Medicaid Services recently ruled that only 3 posttherapy follow-up (18)F-FDG PET/CT scans are funded for a tumor type per patient and any additional follow-up PET/CT scans will be funded at the discretion of the local Medicare administrator. The purpose of this study was to evaluate the added value of 4 or more follow-up PET/CT scans to clinical assessment and impact on patient management. METHODS: This was an institutional review board-approved, retrospective study. A total of 1,171 patients with biopsy-proven lung cancer who had undergone (18)F-FDG PET/CT at a single tertiary center from 2001 to 2013 were identified. Among these, 85 patients (7.3%) had undergone 4 or more follow-up PET/CT scans, for a total of 285 fourth and subsequent follow-up PET/CT scans. Median follow-up from the fourth follow-up PET/CT scan was 31.4 mo (range, 0-155.2 mo). The follow-up PET/CT scan results were correlated with clinical assessment and treatment changes. RESULTS: Of the 285 fourth and subsequent follow-up PET/CT scans, 149 (52.28%) were interpreted as positive and 136 (47.7%) as negative for recurrence or metastasis. A total of 47 patients (55.3%) died during the study period. PET/CT identified recurrence or metastasis in 44.3% of scans performed without prior clinical suspicion and ruled out recurrence or metastasis in 24.2% of scans performed with prior clinical suspicion. The PET/CT scan resulted in a treatment change in 28.1% (80/285) of the patients. New treatment was initiated for 20.4% (58/285) of the scans, treatment was changed in 5.6% (16/285), and ongoing treatment was stopped in 2.1% (6/285). CONCLUSION: The fourth and subsequent (18)F-FDG PET/CT scans performed during follow-up after completion of primary treatment added value to clinical assessment and changed management 28.1% of the time.

Head and neck squamous cell cancer (stages III and IV) induction chemotherapy assessment: value of FDG volumetric imaging parameters.

INTRODUCTION: To evaluate whether the change in the metabolic tumour volume (MTV) or total lesion glycolysis (TLG) of the primary tumour, before and after induction chemotherapy, predicts outcome for patients with advanced head and neck squamous cell cancer (SCC). METHODS: Twenty-eight patients with advanced (American Joint Committee on Cancer stage III and IV) head and neck SCC who underwent positron emission tomography (PET)/CT were included in this retrospective study. Primary tumour MTV and TLG were measured using gradient and fixed percentage threshold segmentations. Outcome endpoint was disease progression or mortality. Pearson correlation, Bland-Altman and receiver operator characteristic analysis were performed. RESULTS: The Pearson's correlation coefficients between percentage changes (pre- and post-induction chemotherapy) from gradient MTV (MTVG) and the 38% SUVmax threshold MTV (MTV38) was 0.96 and between MTVG and the 50% threshold MTV (MTV50) was 0.95 (P < 0.0001). The corresponding Pearson r between TLGG and TLG38 was 0.94 and between TLGG and TLG50 was 0.96 (P < 0.0001). The least bias was 1.89% (standard deviation = 25.30%) between the percentage changes of MTVG and MTV50. The areas under the curve for predicting progression or mortality were 0.76 (P = 0.03) for MTVG and 0.82 for TLGG (P = 0.009). Optimum cut points of a 42% reduction in MTVG and a 55% reduction in the TLGG predict event-free survival with a sensitivity of 62.5% and a specificity of 90% and a hazards ratio of 6.25. CONCLUSION: A reduction in primary tumour MTV of at least 42% or in TLG of at least 55% after induction chemotherapy may predict event-free survival in patients with advanced head and neck SCC.

Addition of 18F-FDG PET/CT to clinical assessment predicts overall survival in HNSCC: a retrospective analysis with follow-up for 12 years.

UNLABELLED: (18)F-FDG PET/CT is used in the follow-up of patients with head and neck squamous cell cancer (HNSCC). However, its impact on clinical decision making and patient outcome is not fully established. The objective of this study was to determine the prognostic value of (18)F-FDG PET/CT for overall survival (OS) of HNSCC patients when performed in addition to clinical assessment between 4 and 24 mo after treatment. METHODS: This was a retrospective study at a single tertiary center. The institutional review board approved this study, and the requirement to obtain informed consent was waived. The study included 134 biopsy-proven HNSCC patients with 227 follow-up PET/CT scans. The primary outcome measure was OS. Median follow-up was 40 mo (range, 7-145 mo). Survival is presented as Kaplan-Meier plots with Mantel-Cox log-rank test. The multivariate Cox model included clinical covariates. RESULTS: Of the 227 PET/CT scans, 41 (18%) were positive for tumor and 186 (82%) were negative for tumor. PET/CT identified recurrence in 5% (9/194) of scans performed without prior clinical concern and ruled out tumor in 51.5% (17/33) of scans performed to evaluate clinical suspicion or uncertainty of recurrence. The median survival of PET-positive and -negative groups from the date of the scan was 20 and 30.5 mo, respectively (P < 0.0001). There was a significant difference in OS from the scan date between patients who had a positive PET/CT result for tumor and those who had a negative result (log-rank, P < 0.0001), with a hazard ratio of 29.74. Human papillomavirus status (P = 0.001) and PET/CT result (P = 0.04) were the only factors significantly associated with OS, adjusted for all other covariates. CONCLUSION: (18)F-FDG PET/CT performed between 4 and 24 mo after treatment adds value to clinical assessment at the time of the study, especially when there is clinical suspicion or uncertainty, and can serve as a prognostic marker of OS in HNSCC.

PET/CT of cancer patients: part 1, pancreatic neoplasms.

OBJECTIVE: Pancreatic cancer continues to have a poor prognosis despite impressive improvements in the outcomes of many other types of cancer, often because most pancreatic neoplasms are found to be unresectable at diagnosis. The purpose of this review is to provide an overview of pancreatic cancer and the role of modern imaging in its diagnosis and management with an emphasis on (18)F-FDG PET/CT fusion imaging. CONCLUSION: Multimodality imaging is critical in the diagnosis and management of pancreatic cancer. PET/CT is increasingly viewed as a useful, accurate, and cost-effective modality in diagnosing and managing pancreatic cancer, but further studies are warranted. Early data suggest that contrast-enhanced PET/CT performed with modern PET/CT scanners yields high-resolution anatomic information for surgical and radiotherapeutic planning and functional information for whole-body staging in the care of patients with this disease.