Quality of life following surgery for head and neck cancer: Evidence from ACRIN 6685.

BACKGROUND: This study examined the trajectory of health-related quality of life (HRQoL) for patients with clinical stage N0 HNSCC enrolled in ACRIN 6685 who underwent elective neck dissection(s). METHODS: HRQoL of 230 patients in the ACRIN 6685 trial was measured prospectively up to 2 years following surgery using the University of Washington Quality of Life instrument. RESULTS: General Health Within the Last 7 Days did not differ significantly from baseline at any follow-up. General Health Relative to Before Cancer fell significantly by 5.8 points following surgery (p = 0.048), and then returned to 3.0 points above baseline at 1 year (p = 0.65). For Overall Quality of Life, HRQoL fell significantly by 4.3 points following surgery (p = 0.031) and then returned to levels not significantly different from baseline. CONCLUSIONS: Patients with stage N0 HNSCC experience significant declines in HRQoL immediately following surgery, including neck dissection, which recovers to near or better than baseline within 1-2 years.

Genetic and epigenetic features of neuroendocrine prostate cancer and their emerging applications.

Prostate cancer is the second most prevalent cancer in men globally. De novo neuroendocrine prostate cancer (NEPC) is uncommon at initial diagnosis, however, (treatment-induced) t-NEPC emerges in up to 25% of prostate adenocarcinoma (PRAD) cases treated with androgen deprivation, carrying a drastically poor prognosis. The transition from PRAD to t-NEPC is underpinned by several key genetic mutations; TP53, RB1, and MYCN are the main genes implicated, bearing similarities to other neuroendocrine tumours. A broad range of epigenetic alterations, such as aberrations in DNA methylation, histone post-translational modifications, and non-coding RNAs, may drive lineage plasticity from PRAD to t-NEPC. The clinical diagnosis of NEPC is hampered by a lack of accessible biomarkers; recent advances in liquid biopsy techniques assessing circulating tumour cells and ctDNA in NEPC suggest that the advent of non-invasive means of monitoring progression to NEPC is on the horizon. Such techniques are vital for NEPC management; diagnosis of t-NEPC is crucial for implementing effective treatment, and precision medicine will be integral to providing the best outcomes for patients.

Quarter-Century PET/CT Transformation of Oncology: Lymphoma.

The clinical landscape of lymphomas has changed dramatically over the last 2 decades, including significant progress made in the understanding and utilization of imaging modalities and the available treatment options for both indolent and aggressive lymphomas. Since the introduction of hybrid PET/CT scanners in 2001, the indications of 18F-fluorodeoxyglucose (FDG) PET/CT in the management of lymphomas have grown rapidly. In today's clinical practice, FDG PET/CT is used in successful management of the vast majority patients with lymphomas.

Role of PET/Computed Tomography in Gastric and Colorectal Malignancies.

This article focuses on the role of PET/computed tomography in evaluating and managing gastric cancer and colorectal cancer. The authors start with describing the common aspects of imaging with 2-deoxy-2-18F-d-glucose, followed by tumor-specific discussions of gastric and colorectal malignancies. Finally, the authors provide a brief overview of non-FDG tracers including their potential clinical applications, and describe future directions in imaging these malignancies.

Quarter Century Positron Emission Tomography/Computed Tomography Transformation of Oncology: Head and Neck Cancer.

During the last 2 decades, f-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F FDG PET/CT) has transformed the clinical head and neck cancer imaging for patient management and predicting survival outcomes. It is now widely used for staging, radiotherapy planning, posttherapy assessment, and for detecting recurrence in head and neck cancers and is widely included in NCCN and other evidence based clinical practice guidelines. Future Directions would include evaluating the potential value of FAPI PET/CT for head and neck cancers, opportunity to use volumetric and tumor heterogeneity parameters and deploying AI in diagnostic and therapeutic assessments.

ACR-ACNM-ARS-ASTRO-SNMMI Practice Parameter for the Performance of Therapy With Radiopharmaceuticals.

OBJECTIVES: This practice parameter was revised collaboratively by the American College of Radiology (ACR), the American College of Nuclear Medicine, the American Radium Society, the American Society for Radiation Oncology, and the Society of Nuclear Medicine and Molecular Imaging. The document is intended to serve as a resource for appropriately trained and licensed physicians who perform therapeutic procedures with unsealed sources, referred to in the document using the more inclusive terminology of radiopharmaceuticals, for which a written directive is required for authorized users under NRC 10 CFR 35.300. METHODS: This practice parameter was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website ( https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards ) by the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the American Radium Society. RESULTS: This practice parameter addresses the overall role of the applicable physician-authorized user, Qualified Medical Physicist, and other specialized personnel involved in the delivery of radiopharmaceutical therapy. Therapeutic radiopharmaceuticals include those administered as elemental radioactive isotopes (radionuclides) or the radioactive element incorporated into a targeting molecule (ligand) by one or more chemical bonds. This document provides guidance regarding general principles of radionuclide therapies and indications of various alpha, beta, gamma, and mixed emission agents with references to several recent practice parameters on new and commonly performed radiopharmaceutical therapies. CONCLUSION: This document addresses clinical circumstances, elements of available agents, and the qualifications and responsibilities of various members of the radiation care team, specifications of consultation and other clinical documentation, post-therapy follow-up, radiation safety precautions, elements of quality control and improvement programs, infection control, and patient education to ensure optimal patient care and safety when utilizing radiopharmaceuticals.

Quarter Century PET/Computed Tomography Transformation of Oncology: Neuroendocrine Tumors.

Significant improvement in molecular imaging and theranostics in the management of neuroendocrine tumors (NETs) has been made in the last few decades. Somatostatin receptor-targeted PET imaging outperforms conventional, planar, and single-photon emission computed tomography imaging and is indicated in the evaluation of these patients when available, resulting in a significant impact on staging, treatment response assessment, and restaging of these patients. Radionuclide therapy can have an impact on patient outcome in metastatic disease when not many treatment options are available.

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.

Clinical practice in prostate PET imaging.

Positron emission tomography (PET) imaging in prostate cancer has advanced significantly in the past decade with prostate cancer targeted radiopharmaceuticals now playing a growing role in diagnosis, staging, and treatment. This narrative review focuses on the most commonly used PET radiopharmaceuticals in the USA: prostate-specific membrane antigen (PSMA), fluciclovine, and choline. 18F-fluorodeoxyglucose (FDG) is used in many other malignancies, but rarely in prostate cancer. Previous literature is discussed regarding each radiopharmaceutical's utility in the settings of screening/diagnosis, initial staging, biochemical recurrence, advanced disease, and evaluation prior to targeted radiopharmaceutical therapy and radiation therapy. PET imaging has demonstrated utility over traditional imaging in various scenarios; however, there are few head-to-head studies comparing PET radiopharmaceuticals. PSMA radiopharmaceuticals are the newest tracers developed and have unique properties and uses, especially at low prostate-specific antigen (PSA) levels. However, each PET radiopharmaceutical has different properties which can affect image interpretation. Choline and fluciclovine have minimal urinary activity, whereas PSMA agents can have high urinary activity which may affect locoregional disease evaluation. Of the three radiopharmaceuticals, only PSMA is approved for both diagnostic and therapeutic indications with 177Lu-PSMA. A variety of diagnostic PET radiotracers for prostate cancer allows for increased flexibility, especially in the setting of supply chain and medication shortages. For the time being, keeping a diverse group of PET radiopharmaceuticals for prostate cancer is justifiable.

Evaluation of the Diagnostic Accuracy of FAPI PET/CT in Oncologic Studies: Systematic Review and Metaanalysis.

Fibroblast-activation protein is a promising target for oncologic molecular imaging. Studies show that fibroblast activation protein inhibitor (FAPI) radiotracers are accurate diagnostics with favorable tumor-to-background ratios across various cancers. Therefore, we performed a systematic review and metaanalysis to assess the diagnostic performance of FAPI PET/CT in comparison with [18F]FDG PET/CT, the most widely used radiotracer in oncology. Methods: We conducted a systematic search in MEDLINE, Embase, Scopus, PubMed, Cochrane Central Register of Controlled Trials, relevant trial registries, and bibliographies. The search consisted of combinations of terms for 3 topics: neoplasia, PET/CT, and FAPI. Two authors independently screened retrieved articles using predefined inclusion and exclusion criteria and extracted the data. Study quality was assessed using the criteria of QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). For each study, the sensitivity, specificity, and 95% CIs were calculated to determine diagnostic accuracy for primary, nodal, and metastatic lesions. A random-effects metaanalysis was used for pooling the data, and heterogeneity was assessed (I2 index). Results: Thirty-nine studies (1,259 patients) investigating the use of FAPI PET/CT were included. On a patient-based analysis, pooled sensitivity was 0.99 (95% CI, 0.97-1.0) for the detection of primary lesions. Pooled sensitivity for nodal and distant metastases was 0.91 (95% CI, 0.81-0.96) and 0.99 (95% CI, 0.96-1.0), respectively. On a paired analysis between FAPI and [18F]FDG PET/CT, FAPI had a higher sensitivity in the detection of primary, nodal, and metastatic lesions (all P < 0.001). The differences in sensitivities between FAPI and [18F]FDG were statistically significant. In terms of heterogeneity, analyses on primary lesions were moderately affected, distant metastatic lesions were highly affected, and the nodal metastatic analyses had negligible heterogeneity. Conclusion: The diagnostic performance of FAPI PET/CT is superior to that of [18F]FDG in the detection of primary, nodal, and distant metastases. However, further studies are needed to better evaluate its utility and indication in specific cancer types and clinical settings.

Screening for extranodal extension in HPV-associated oropharyngeal carcinoma: evaluation of a CT-based deep learning algorithm in patient data from a multicentre, randomised de-escalation trial.

BACKGROUND: Pretreatment identification of pathological extranodal extension (ENE) would guide therapy de-escalation strategies for in human papillomavirus (HPV)-associated oropharyngeal carcinoma but is diagnostically challenging. ECOG-ACRIN Cancer Research Group E3311 was a multicentre trial wherein patients with HPV-associated oropharyngeal carcinoma were treated surgically and assigned to a pathological risk-based adjuvant strategy of observation, radiation, or concurrent chemoradiation. Despite protocol exclusion of patients with overt radiographic ENE, more than 30% had pathological ENE and required postoperative chemoradiation. We aimed to evaluate a CT-based deep learning algorithm for prediction of ENE in E3311, a diagnostically challenging cohort wherein algorithm use would be impactful in guiding decision-making. METHODS: For this retrospective evaluation of deep learning algorithm performance, we obtained pretreatment CTs and corresponding surgical pathology reports from the multicentre, randomised de-escalation trial E3311. All enrolled patients on E3311 required pretreatment and diagnostic head and neck imaging; patients with radiographically overt ENE were excluded per study protocol. The lymph node with largest short-axis diameter and up to two additional nodes were segmented on each scan and annotated for ENE per pathology reports. Deep learning algorithm performance for ENE prediction was compared with four board-certified head and neck radiologists. The primary endpoint was the area under the curve (AUC) of the receiver operating characteristic. FINDINGS: From 178 collected scans, 313 nodes were annotated: 71 (23%) with ENE in general, 39 (13%) with ENE larger than 1 mm ENE. The deep learning algorithm AUC for ENE classification was 0·86 (95% CI 0·82-0·90), outperforming all readers (p<0·0001 for each). Among radiologists, there was high variability in specificity (43-86%) and sensitivity (45-96%) with poor inter-reader agreement (κ 0·32). Matching the algorithm specificity to that of the reader with highest AUC (R2, false positive rate 22%) yielded improved sensitivity to 75% (+ 13%). Setting the algorithm false positive rate to 30% yielded 90% sensitivity. The algorithm showed improved performance compared with radiologists for ENE larger than 1 mm (p<0·0001) and in nodes with short-axis diameter 1 cm or larger. INTERPRETATION: The deep learning algorithm outperformed experts in predicting pathological ENE on a challenging cohort of patients with HPV-associated oropharyngeal carcinoma from a randomised clinical trial. Deep learning algorithms should be evaluated prospectively as a treatment selection tool. FUNDING: ECOG-ACRIN Cancer Research Group and the National Cancer Institute of the US National Institutes of Health.

Gastro-Enteric-Pancreatic Neuroendocrine Tumor Treatment: 177Lu-DOTATATE.

177Lu-DOTA-TATE therapy is a highly effective therapy in metastatic, well-differentiated, somatostatin receptor-positive GEP-neuroendocrine tumors (NETs) with mostly tolerable adverse effects. Guidelines generally refer to peptide receptor radionuclide therapy as a second-line therapy after SSA in gastroenteric and second- or third-line therapy in pancreatic NETs to improve survival rates and quality of life. Although we do not have sufficient data, 177Lu-DOTA-TATE therapy may also have a role in high-grade NET therapy, mostly in combination with other treatments such as chemotherapy.

Neuroendocrine Neoplasms: Genetics and Epigenetics.

Neuroendocrine neoplasms (NENs) are a group of rare, heterogeneous tumors of neuroendocrine cell origin, affecting a range of different organs. The clinical management of NENs poses significant challenges, as tumors are often diagnosed at an advanced stage where overall survival remains poor with current treatment regimens. In addition, a host of complex and often unique molecular changes underpin the pathobiology of each NEN subtype. Exploitation of the unique genetic and epigenetic signatures driving each NEN subtype provides an opportunity to enhance the diagnosis, treatment, and monitoring of NEN in an emerging era of individualized medicine.

Asian migrants navigating New Zealand primary care: a qualitative study.

Introduction Information on the responsiveness of the New Zealand (NZ) health system to Asians to enable navigation of healthcare services is currently lacking. Barriers experienced by Asian patients to enable optimal navigation of, and engagement with, healthcare services are also sparse. Aim This research aimed to: (1) document and analyse resources available on the websites of general practices that aid in optimal health care navigation for NZ Asians; and (2) explore the barriers perceived by Asian migrants to navigating the NZ Health System, particularly primary care. Methods This study involved qualitative document analysis of existing resources on general practice websites. Information on perceived barriers and experiences of navigating the health system was collected through semi-structured interviews (n = 9). Results Overall, 293 general practice websites were analysed. The themes from content analysis were: availability of basic information, linguistic accessibility, and culturally appropriate support for patients. Relevant and reliable information facilitating effective navigation of the NZ health system by Asians was lacking. Interview data supported the findings about the general practices, with participants reporting significant difficulties navigating and understanding NZ primary care services. Discussion Current navigational resources presume knowledge that Asian migrants do not often possess. Participants felt this lack of accessible information acutely, and it influenced how they perceived and engaged with healthcare services. Increased accessibility through resources in Asian languages, including an overview of how Health NZ functions in providing health care and professional interpreter services, would be critical to increase appropriate engagement with healthcare services and thus contribute to better health outcomes for Asians.

Utility of pre-treatment 18 F-fluorodeoxyglucose PET radiomic analysis in assessing nodal involvement in cervical cancer.

OBJECTIVE: Intratumor heterogeneity has prognostic value in cervical cancer, which can be depicted on 18 F-fluorodeoxyglucose ( 18 F-FDG) PET/computed tomography (PET/CT) and then quantitatively characterized by texture features. This study aimed to evaluate the discriminative performance and predictive ability of the texture features in determining lymph node involvement in cervical cancer. METHODS: A total of 101 patients with newly diagnosed cervical cancer, who underwent pre-treatment whole-body 18 F-FDG PET/CT imaging were retrospectively recruited. Patients were categorized based on their nodal status. Thirty-five radiomic features together with the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary cervical tumors were extracted. Conventional indices were used to build logistic regression model and texture features were used to build random forest model. The performances for differentiating nodal status were assessed by receiver operating characteristic analysis. RESULTS: Conventional PET indices were significantly higher in patients with nodal involvement compared to those without: SUVmax = 14.22 vs. 10.05; MTV = 57.02 vs. 28.73; TLG = 492.8 vs. 188.8 ( P < 0.05). Nineteen radiomic features describing regional heterogeneity were significantly different between nodal involvements. Area under the curves of the models with conventional indices and PET texture features for discriminating nodal status were 0.72 and 0.76, respectively. CONCLUSION: PET-derived radiomic features had moderate performance in discriminating nodal involvement in cervical cancer; and they did not outperform model based on conventional indices.

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.

Immunotherapy and Biomarker Testing in Recurrent and Metastatic Head and Neck Cancers: ASCO Guideline.

PURPOSE: To provide evidence-based recommendations for practicing physicians and other health care providers on immunotherapy and biomarker testing for head and neck cancers. METHODS: ASCO convened an Expert Panel of medical oncology, surgical oncology, radiation oncology, radiology, pathology, and patient advocacy experts to conduct a literature search, including systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 2000 through 2022. Outcomes of interest included survival, overall response, and locoregional control. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 28 relevant studies to inform the evidence base for this guideline. RECOMMENDATIONS: When possible, evidence-based recommendations were developed to address biomarker testing, first-line treatment regimens based on programmed death ligand-1 scores, immunotherapy in platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma, immunotherapy in nasopharyngeal carcinoma, and radiation therapy in combination with immunotherapy for treatment of local recurrence.Additional information is available at www.asco.org/head-neck-cancer-guidelines.

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.