Late endocrine diseases in survivors of adolescent and young adult cancer in California: a population-based study.

BACKGROUND: Cancer survivors have increased risk of endocrine complications, but there is a lack of information on the occurrence of specific endocrinopathies at the population-level. METHODS: We used data from the California Cancer Registry (2006-2018) linked to statewide hospitalisation, emergency department, and ambulatory surgery databases. We estimated the cumulative incidence of and factors associated with endocrinopathies among adolescents and young adults (AYA, 15-39 years) who survived ≥2 years after diagnosis. RESULTS: Among 59,343 AYAs, 10-year cumulative incidence was highest for diabetes (4.7%), hypothyroidism (4.6%), other thyroid (2.2%) and parathyroid disorders (1.6%). Hypothyroidism was most common in Hodgkin lymphoma, leukaemia, breast, and cervical cancer survivors, while diabetes was highest among survivors of leukaemias, non-Hodgkin lymphoma, colorectal, cervical, and breast cancer. In multivariable models, factors associated with increased hazard of endocrinopathies were treatment, advanced stage, public insurance, residence in low/middle socioeconomic neighbourhoods, older age, and non-Hispanic Black or Hispanic race/ethnicity. Haematopoietic cell transplant was associated with most endocrinopathies, while chemotherapy was associated with a higher hazard of ovarian dysfunction and hypothyroidism. CONCLUSIONS: We observed a high burden of endocrinopathies among AYA cancer survivors, which varied by treatment and social factors. Evidence-based survivorship guidelines are needed for surveillance of these diseases.

Molecular Alterations and Comprehensive Clinical Management of Oncocytic Thyroid Carcinoma: A Review and Multidisciplinary 2023 Update.

Importance: Oncocytic (Hürthle cell) thyroid carcinoma is a follicular cell-derived neoplasm that accounts for approximately 5% of all thyroid cancers. Until recently, it was categorized as a follicular thyroid carcinoma, and its management was standardized with that of other differentiated thyroid carcinomas. In 2022, given an improved understanding of the unique molecular profile and clinical behavior of oncocytic thyroid carcinoma, the World Health Organization reclassified oncocytic thyroid carcinoma as distinct from follicular thyroid carcinoma. The International Thyroid Oncology Group and the American Head and Neck Society then collaborated to review the existing evidence on oncocytic thyroid carcinoma, from diagnosis through clinical management and follow-up surveillance. Observations: Given that oncocytic thyroid carcinoma was previously classified as a subtype of follicular thyroid carcinoma, it was clinically studied in that context. However, due to its low prevalence and previous classification schema, there are few studies that have specifically evaluated oncocytic thyroid carcinoma. Recent data indicate that oncocytic thyroid carcinoma is a distinct class of malignant thyroid tumor with a group of distinct genetic alterations and clinicopathologic features. Oncocytic thyroid carcinoma displays higher rates of somatic gene variants and genomic chromosomal loss of heterozygosity than do other thyroid cancers, and it harbors unique mitochondrial DNA variations. Clinically, oncocytic thyroid carcinoma is more likely to have locoregional (lymph node) metastases than is follicular thyroid carcinoma-with which it was formerly classified-and it develops distant metastases more frequently than papillary thyroid carcinoma. In addition, oncocytic thyroid carcinoma rarely absorbs radioiodine. Conclusions and Relevance: The findings of this review suggest that the distinct clinical presentation of oncocytic thyroid carcinoma, including its metastatic behavior and its reduced avidity to radioiodine therapy, warrants a tailored disease management approach. The reclassification of oncocytic thyroid carcinoma by the World Health Organization is an important milestone toward developing a specific and comprehensive clinical management for oncocytic thyroid carcinoma that considers its distinct characteristics.

Clinician feedback using a shared decision-making tool for the evaluation of patients with thyroid nodules-an observational study.

BACKGROUND: We pilot-tested an encounter conversation aid to support shared decision making (SDM) between patients with thyroid nodules and their clinicians. OBJECTIVE: Characterize the clinician feedback after providing care to patients with thyroid nodules using a tool to promote SDM conversations during the clinical encounter, and evaluate how clinicians used the tool during the visit. METHODS: Mixed method study in two academic centers in the U.S., including adult patients presenting for evaluation of thyroid nodules and their clinicians. We thematically analyzed interviews with clinicians after they used the SDM tool in at least three visits to characterize their feedback. Additionally, investigators evaluated visits recordings to determine the extent to which clinicians engaged patients in the decision-making process (OPTION score, scale 0 to 100, higher levels indicating higher involvement), the tool's components used (fidelity), and encounter duration. Using a post-visit survey, we evaluated the extent to which clinicians felt the tool was easy to use, helpful, and supportive of the patient-clinician collaboration. RESULTS: Thirteen clinicians participated in the study and used the SDM tool in the care of 53 patients. Clinicians thought the tool was well-organized and beneficial to patients and clinicians. Clinicians noticed a change in their routine with the use of the conversation aid and suggested it needed to be more flexible to better support varying conversations. The median OPTION score was 34, the fidelity of use 75%, and the median visit duration 17 min. In most encounters, clinicians agreed or strongly agreed the tool was easy to use (86%), helpful (65%), and supported collaboration (62%). CONCLUSION: Clinicians were able to use a SDM tool in the care of patients with thyroid nodules. Although they wished it were more flexible, they found on the whole that its use in the clinical encounter was beneficial to patients and clinicians.

Clinical Outcomes of Radioactive Iodine Redifferentiation Therapy in Previously Iodine Refractory Differentiated Thyroid Cancers.

Objective: Redifferentiation therapy (RDT) can restore radioactive iodine (RAI) uptake in differentiated thyroid cancer (DTC) cells to enable salvage 131I therapy for previously RAI refractory (RAIR) disease. This study evaluated the clinical outcomes of patients who underwent RDT and identified clinicopathologic characteristics predictive of RAI restoration following RDT. Methods: This is a retrospective case series of 33 patients with response evaluation criteria in solid tumors (RECIST)-progressive metastatic RAIR-DTC who underwent RDT between 2017 and 2022 at the Mayo Clinic (Rochester, MN). All patients underwent genomic profiling and received MEK, RET or ALK inhibitors alone, or combination BRAF-MEK inhibitors for 4 weeks. At week 3, those with increased RAI avidity in metastatic foci received high-dose 131I therapy. Baseline and clinicopathologic outcomes were comprehensively reviewed. Results: Of the 33 patients, 57.6% had restored RAI uptake following RDT (Redifferentiated subgroup). 42.1% (8/19) with papillary thyroid cancers (PTC), 100% (4/4) with invasive encapsulated follicular variant PTCs (IEFV-PTCs), and 100% (7/7) with follicular thyroid cancers (FTC) redifferentiated. All (11/11) RAS mutant tumors redifferentiated compared with 38.9% (7/18) with BRAF mutant disease (6 PTC and 1 IEFV-PTC). 76.5% (13/17) of redifferentiated and 66.7% (8/12) of non-redifferentiated patients achieved a best overall RECIST response of stable disease (SD) or non-complete response/non-progressive disease. Both subgroups had a median 12% tumor shrinkage at 3 weeks on drug(s) alone. The redifferentiated subgroup, following high-dose 131I therapy, achieved an additional median 20% tumor reduction at 6 months after RDT. There were no statistically significant differences between both groups in progression free survival (PFS), time to initiation of systemic therapy, and time to any additional therapy. Of the entire cohort, 6.1% (2/33) experienced histologic transformation to anaplastic thyroid cancer, 15.1% (5/33) died, and all had redifferentiated following RDT and received 131I therapy. Conclusion: RDT has the potential to restore RAI avidity and induce RECIST responses following 131I therapy in select patients with RAIR-DTC, particularly those with RAS-driven "follicular" phenotypes. In patients with PTC, none of the evaluated clinical outcomes differed statistically between the redifferentiated and non-redifferentiated subgroups. Further studies are needed to better characterize the long-term survival and/or safety outcomes of high-dose RAI following RDT, particularly whether it could be associated with histologic anaplastic transformation.

Genomic and Transcriptomic Characteristics of Metastatic Thyroid Cancers with Exceptional Responses to Radioactive Iodine Therapy.

PURPOSE: The determinants of response or resistance to radioiodine (RAI) are unknown. We aimed to identify genomic and transcriptomic factors associated with structural responses to RAI treatment of metastatic thyroid cancer, which occur infrequently, and to test whether high MAPK pathway output was associated with RAI refractoriness. EXPERIMENTAL DESIGN: Exceptional response to RAI was defined as reduction of tumor volume based on RECIST v1.1. We performed a retrospective case-control study of genomic and transcriptomic characteristics of exceptional responders (ER; n = 8) versus nonresponders (NR; n = 16) matched by histologic type and stage at presentation on a 1:2 ratio. RESULTS: ER are enriched for mutations that activate MAPK through RAF dimerization (RAS, class 2 BRAF, RTK fusions), whereas NR are associated with BRAFV600E, which signals as a monomer and is unresponsive to negative feedback. ER have a lower MAPK transcriptional output and a higher thyroid differentiation score (TDS) than NR (P < 0.05). NR are enriched for 1q-gain (P < 0.05) and mutations of genes regulating mRNA splicing and the PI3K pathway. BRAFV600E tumors with 1q-gain have a lower TDS than BRAFV600E/1q-quiet tumors and transcriptomic signatures associated with metastatic propensity. CONCLUSIONS: ER tumors have a lower MAPK output and higher TDS than NR, whereas NR have a high frequency of BRAFV600E and 1q-gain. Molecular profiling of thyroid cancers and further functional validation of the key findings discriminating ER from NR may help predict response to RAI therapy.

Patient feedback receiving care using a shared decision making tool for thyroid nodule evaluation-an observational study.

PURPOSE: To characterize the feedback of patients with thyroid nodules receiving care using a shared decision making (SDM) tool designed to improve conversations with their clinicians related to diagnostic options (e.g. thyroid biopsy, ultrasound surveillance). METHODS: Investigators qualitatively analyzed post-encounter interviews with patients to characterize their feedback of a SDM tool used during their clinical visits. Additionally, investigators counted instances of diagnostic choice awareness and of patients' expression of a diagnostic management preference in recordings of clinical encounters of adult patients presenting for evaluation of thyroid nodules in which the SDM tool was used. RESULTS: In total, 53 patients (42 (79%) women); median age 62 years were enrolled and had consultations supported by the SDM tool. Patients were favorable about the design of the SDM tool and its ability to convey information about options and support patient-clinician interactions. Patients identified opportunities to improve the tool through adding more content and improve its use in practice through training of clinicians in its use. There was evidence of diagnostic choice awareness in 52 (98%) of these visits and patients expressed a diagnostic management preference in 40 (76%). CONCLUSION: User centered design including feedback from patients and real life observation supports the use of the SDM tool to facilitate collaboration between patients and clinicians.

Circulating immunophenotypes are potentially prognostic in follicular cell-derived thyroid cancer.

Background: Exploring the immune interface of follicular cell-derived thyroid cancer has prognostic and therapeutic potential. The available literature is lacking for comprehensive immunophenotyping in relation to clinical outcomes. In this study, we identify circulating immunophenotypes associated with thyroid cancer prognosis. Methods: We conducted a pilot observational study of adults with follicular cell-derived thyroid cancer who underwent surgery at our tertiary care referral center and had consented for flow cytometry on peripheral blood collected at the time of thyroidectomy. Results: Of the 32 included subjects, 20 (62%) had well differentiated, 5 (16%) had poorly differentiated, and 7 (22%) had anaplastic thyroid cancer. The most frequent AJCC stage was 4 (59%) and the ATA risk of recurrence category was high (56%). Patients with AJCC stage 3/4 demonstrated fewer circulating mononuclear cells (CD45+), more monocytes (CD14+), fewer total lymphocytes (CD14-), fewer T cells (CD3+), fewer CD4+ T cells, fewer gamma-delta T cells, fewer natural killer (NK) T-like cells, more myeloid-derived suppressor cells (MDSCs; Lin-CD33+HLADR-), and more effector memory T cells but similar CD8+ T cells compared to stage1/2. Immunophenotype comparisons by ATA risk stratification and course of thyroid cancer were comparable to those observed for stage, except for significant differences in memory T cell subtypes. The median follow-up was 58 months. Conclusions: Aggressive follicular cell-derived thyroid cancer either at presentation or during follow-up is associated with down-regulation of the T cell populations specifically CD4+ T cells, gamma-delta T cells, and NK T-like cells but up-regulation of MDSCs and altered memory T cells. These immunophenotypes are potential prognostic biomarkers supporting future investigation for developing targeted immunotherapies against advanced thyroid cancer.

Added value of mass characteristic frequency to 2-D shear wave elastography for differentiation of benign and malignant thyroid nodules.

Mass characteristic frequency (fmass) is a novel shear wave (SW) parameter that represents the ratio of the averaged minimum SW speed within the regions of interest to the largest dimension of the mass. Our study objective was to evaluate if the addition of fmass to conventional 2-D shear wave elastography (SWE) parameters would improve the differentiation of benign from malignant thyroid nodules. Our cohort comprised 107 patients with 113 thyroid nodules, of which 67 (59%) were malignant. Two-dimensional SWE data were obtained using the Supersonic Imagine Aixplorer ultrasound system equipped with a 44- to 15-MHz15-MHz linear array transducer. A receiver operating characteristic curve was generated based on a multivariable logistic regression analysis to evaluate the ability of SWE parameters with/without fmass and with/without clinical factors to discriminate benign from malignant thyroid nodules. The addition of fmass to conventional SW elasticity parameters increased the area under the curve from 0.808 to 0.871 (p = 0.02). The combination of SW elasticity parameters plus fmass plus clinical factors provided the strongest thyroid nodule malignancy probability estimate, with a sensitivity of 93.4% and specificity of 91.1% at the optimal threshold. In summary, fmass can be a valuable addition to conventional 2-D SWE parameters.

Management of Immunotherapy-Related Toxicities, Version 1.2022, NCCN Clinical Practice Guidelines in Oncology.

The aim of the NCCN Guidelines for Management of Immunotherapy-Related Toxicities is to provide guidance on the management of immune-related adverse events resulting from cancer immunotherapy. The NCCN Management of Immunotherapy-Related Toxicities Panel is an interdisciplinary group of representatives from NCCN Member Institutions, consisting of medical and hematologic oncologists with expertise across a wide range of disease sites, and experts from the areas of dermatology, gastroenterology, endocrinology, neurooncology, nephrology, cardio-oncology, ophthalmology, pulmonary medicine, and oncology nursing. The content featured in this issue is an excerpt of the recommendations for managing toxicities related to CAR T-cell therapies and a review of existing evidence. For the full version of the NCCN Guidelines, including recommendations for managing toxicities related to immune checkpoint inhibitors, visit NCCN.org.

Lenvatinib as a Therapeutic Option in Unresectable Metastatic Pheochromocytoma and Paragangliomas.

Context: Metastatic pheochromocytomas and paragangliomas (mPPGL) are rare vascular neuroendocrine tumors that highly express vascular growth factors. Systemic treatment options in cases of unresectable multisite disease are limited. Multikinase inhibitors that inhibit angiogenesis, such as lenvatinib, have proven effective in several other malignancies, and may be a viable option for mPPGL. Objective: We aimed to evaluate the efficacy of lenvatinib as salvage therapy in mPPGLs. Methods: This was a retrospective analysis of mPPGL patients ≥ 18 years of age who received lenvatinib from 2015 to 2020 at a tertiary referral center. Patients were started on lenvatinib 20 mg daily and dose was adjusted according to tolerance or disease progression. Results: Eleven patients were included. Median treatment duration was 14.7 months (95% CI, 2.3-NE). Treatment was discontinued due to disease progression, adverse events, or death. Overall survival at 12 months was 80.8% (95% CI, 42.3-94.9%) but its median was not reached. Median progression-free survival was 14.7 months (95% CI, 1.7-NE). Among the 8 patients with measurable disease, overall response rate was 63%, as 5/8 experienced a partial response and 3/8 had stable disease. Worsening hypertension and anemia were the most common adverse events. Conclusion: Lenvatinib may be a viable treatment option for mPPGL, although at the potential risk of worsening hypertension. Larger, multicenter studies are needed to better characterize treatment efficacy.

American Head and Neck Society Endocrine Surgery Section and International Thyroid Oncology Group consensus statement on mutational testing in thyroid cancer: Defining advanced thyroid cancer and its targeted treatment.

BACKGROUND: The development of systemic treatment options leveraging the molecular landscape of advanced thyroid cancer is a burgeoning field. This is a multidisciplinary evidence-based statement on the definition of advanced thyroid cancer and its targeted systemic treatment. METHODS: An expert panel was assembled, a literature review was conducted, and best practice statements were developed. The modified Delphi method was applied to assess the degree of consensus for the statements developed by the author panel. RESULTS: A review of the current understanding of thyroid oncogenesis at a molecular level is presented and characteristics of advanced thyroid cancer are defined. Twenty statements in topics including the multidisciplinary management, molecular evaluation, and targeted systemic treatment of advanced thyroid cancer are provided. CONCLUSIONS: With the growth in targeted treatment options for thyroid cancer, a consensus definition of advanced disease and statements regarding the utility of molecular testing and available targeted systemic therapy is warranted.

Outcomes and Patterns of Recurrence for Anaplastic Thyroid Cancer Treated With Comprehensive Chemoradiotherapy.

PURPOSE: Radiation therapy (RT) plays an important role in locoregional tumor control for anaplastic thyroid cancer (ATC). Due to its rarity, RT guidelines for ATC are lacking. We describe ATC patterns of nodal disease at presentation and progression and propose corresponding RT target volumes. METHODS AND MATERIALS: We identified all patients with ATC treated at our institution with definitive or adjuvant intensity modulated radiation therapy and concomitant chemotherapy from 2006 to 2020. We identified in-field, marginal, and out-of-field sites of locoregional recurrence and progression (LRR). RESULTS: Forty-seven patients met inclusion. Median follow-up was 6.6 months (interquartile range, 1.9-19.6). Nodal levels involved at presentation included: IB (2.1%), II (23.4%), III (21.3%), IV (21.3%), V (12.8%), VI (34%), and mediastinal (6.4%). All patients received elective nodal RT to levels II-IV and VI. RT volumes also included: IA (23.4%), IB (44.7%), V (87.2%), retropharyngeal/retrostyloid (RP/RS) (27.7%), and mediastinal 1 to 6 (53.2%). Cumulative incidence of LRR at 3- and 12-months was 26.1% (95% confidence interval, 15.9-42.8) and 35.7% (23.9-53.4). Isolated LRR risk at 3- and 12-months was 6.5% (2.2-19.8) and 8.9% (3.4-22.9). Fourteen (29.8%) patients experienced in-field LRR in the thyroid gland or postoperative tumor bed, II-IV, VI, and mediastinal 1 and 3A. Four (8.5%) patients had marginal LRRs, 3 of whom progressed in the mediastinum at 2, 3P, 4, and 6. Two (4.3%) patients experienced out-of-field LRRs. Throughout the pretreatment and follow-up period, no patients had disease at IA, and 1 (2.1%) patient each had disease at IB and RP/RS. No baseline or treatment characteristics, including RT dose (stratified by < or ≥66 Gy), were significant predictors of LRR on univariate analysis. CONCLUSIONS: Isolated LRR risk in patients with ATC treated with comprehensive RT and chemotherapy is low. Aggressive multimodality therapy should be reserved for willing, fit patients with no or limited distant disease burden. When treating comprehensively, complete inclusion of mediastinal levels 1 to 6 may be warranted to avoid marginal disease progression. Omission of levels I and RP/RS can be considered.

Immune checkpoint inhibitor-induced hypophysitis: lessons learnt from a large cancer cohort.

Immune checkpoint inhibitors (ICIs) can cause pituitary dysfunction due to hypophysitis. We aimed to characterize ICI-induced hypophysitis and examine its association with overall survival in this single-center retrospective cohort study of adult patients with cancer who received an ICI from January 1, 2012 through December 31, 2016. A total of 896 patients were identified who received ipilimumab alone (n=120); ipilimumab and nivolumab (n=50); ipilimumab before or after pembrolizumab (n=70); pembrolizumab alone (n=406); and nivolumab alone (n=250). Twenty-six patients (2.9%) developed hypophysitis after a median of 2.3 months. Median age at the start of ICI was 57.9 years and 54% were men. Hypophysitis occurred in 7.9% of patients receiving ipilimumab alone or in combination or sequence with a programmed cell death protein 1 inhibitor; 1.7% after pembrolizumab alone, never after nivolumab alone. Secondary adrenal insufficiency occurred in all hypophysitis cases. Use of ipilimumab alone or in combination was associated with pituitary enlargement on imaging and mass effects more frequently than pembrolizumab alone. Occurrence of hypophysitis was associated with improved overall survival by univariate analysis (median 50.7 vs 16.5 months; p=0.015) but this association was not observed in multivariable landmark survival analysis (HR for mortality 0.75; 95% CI 0.38 to 1.30; p=0.34) after adjusting for age, sex and malignancy type. To conclude, hypophysitis occurred most frequently after ipilimumab and manifested as anterior hypopituitarism affecting the corticotrophs more commonly than thyrotrophs and gonadotrophs. Mass effects and pituitary enlargement occurred more frequently in ipilimumab-induced hypophysitis. The association of hypophysitis with overall survival needs further investigation.

Survival benefit of endocrine dysfunction following immune checkpoint inhibitors for nonthyroidal cancers.

PURPOSE OF REVIEW: Our goal is to review pertinent data evaluating the association between immune checkpoint inhibitor (ICI)-induced endocrine dysfunction and survival in cancer patients as well as to understand the potential molecular links between these. RECENT FINDINGS: ICIs have revolutionized cancer therapy but have also led to multiple immune-related adverse events (irAEs). Studies have demonstrated a link between the development of irAEs and improved survival, suggesting that ICI-induced antitumor immunity and autoimmunity are coupled. Thyroid irAEs are most frequently and strongly associated with improved survival, particularly in the context of overt thyroid dysfunction. Other endocrine irAEs, such as hypophysitis and diabetes are quite rare wherein the treatment approach or the disease process itself may mitigate improvement in survival. Preclinical and translational data indicate a role for CD4+ T cells, regulatory T cells and/or cytokines mediating irAEs, including thyroiditis. SUMMARY: The development of irAEs is associated with improved tumor responses and survival in cancer patients. Thyroid irAEs, alone or in combination with other irAEs, are most strongly associated with improved outcomes. Biomarkers of response to ICIs are lacking, despite well-characterized pathologic and genomic susceptibilities predicting ICI efficacy. Early detection of thyroid irAEs may identify patients most likely to have durable antitumor response to ICIs. Although irAEs and antitumor immunity appear 'coupled', translational studies indicate the potential for their 'uncoupling', which could enable antitumor efficacy with greater safety margins.

Blocking the Thyrotropin Receptor with K1-70 in a Patient with Follicular Thyroid Cancer, Graves' Disease, and Graves' Ophthalmopathy.

Background: We report the therapeutic use of K1-70™, a thyrotropin receptor (TSHR) antagonist monoclonal antibody, in a patient with follicular thyroid cancer (FTC), Graves' disease (GD), and Graves' ophthalmopathy (GO). Methods: A 51-year-old female patient, who smoked, presented in October 2014 with FTC complicated by GD, high levels of TSHR autoantibodies with high thyroid stimulating antibody (TSAb) activity, and severe GO. K1-70 was administered at 3 weekly intervals with the dose adjusted to block TSAb activity. Her cancer was managed with lenvatinib and radioiodine therapy. Results: Following initiation of K1-70 therapy, TSAb activity measured in serum decreased and GO (proptosis and inflammation) improved. On K1-70 monotherapy during the pause in lenvatinib, several metastatic lesions stabilized while others showed progression attenuation compared with that before lenvatinib therapy. Conclusions: These observations suggest that blocking TSHR stimulation with K1-70 can be an effective treatment for GO and may also benefit select patients with FTC and GD.

Categorisation of patients based on immune profiles: a new approach to identifying candidates for response to checkpoint inhibitors.

OBJECTIVES: Inhibitors to the checkpoint proteins cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are becoming widely used in cancer treatment. However, a lack of understanding of the patient response to treatment limits accurate identification of potential responders to immunotherapy. METHODS: In this study, we assessed the expression of PD-1 and CTLA-4 on 19 leucocyte populations in the peripheral blood of 74 cancer patients. A reference data set for PD-1 and CTLA-4 was established for 40 healthy volunteers to determine the normal expression patterns for these checkpoint proteins. RESULTS: Unsupervised hierarchical clustering found four immune profiles shared across the solid tumor types, while chronic lymphocytic leukaemia patients had an immune profile largely unique to them. Furthermore, we measured these leucocyte populations on an additional cohort of 16 cancer patients receiving the PD-1 inhibitor pembrolizumab in order to identify differences between responders and non-responders, as well as compared to healthy volunteers (n = 20). We observed that cancer patients had pre-treatment PD-1 and CTLA-4 expression on their leucocyte populations at different levels compared to healthy volunteers and identified two leucocyte populations positive for CTLA-4 that had not been previously described. We found higher levels of PD-1+ CD3+ CD4- CD8- cells in patients with progressive disease and have identified it as a potential biomarker of response, as well as identifying other significant differences in phenotypes between responders and non-responders. CONCLUSION: These results are suggestive that categorisation of patients based on immune profiles may differentiate responders from non-responders to immunotherapy for solid tumors.

The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Management of Metastatic and/or Unresectable Pheochromocytoma and Paraganglioma.

ABSTRACT: This manuscript is the result of the North American Neuroendocrine Tumor Society consensus conference on the medical management and surveillance of metastatic and unresectable pheochromocytoma and paraganglioma held on October 2 and 3, 2019. The panelists consisted of endocrinologists, medical oncologists, surgeons, radiologists/nuclear medicine physicians, nephrologists, pathologists, and radiation oncologists. The panelists performed a literature review on a series of questions regarding the medical management of metastatic and unresectable pheochromocytoma and paraganglioma as well as questions regarding surveillance after resection. The panelists voted on controversial topics, and final recommendations were sent to all panel members for final approval.

Prognostic Factors in Patients with Differentiated Thyroid Cancers Metastatic to the Cervical Spine.

OBJECTIVES: The spine is the most common site of bone metastases in differentiated thyroid cancer (DTC). The role of surgery in the management of cervical spine (C-spine) metastases (CSpM) has not been adequately explored. METHODS: This is a retrospective cohort study at a tertiary referral center from 2002 to 2018. Inclusion criteria were pathologic diagnosis of DTC and imaging/pathologic diagnosis of CSpM. Statistical analysis utilized t tests for continuous variables and χ2 tests for categorical variables. Survival analysis was conducted using Kaplan-Meier curves with univariate and multivariate Cox regressions. RESULTS: Fifty patients with DTC and CSpM were identified. Of those, 16 underwent surgical resection of the C-spine, whereas 34 did not. The most common presenting symptom was neck pain (N = 37, 74%). Patients in the surgery group were more likely to report a subjective improvement of symptoms (P < .01) and to have local (P < .01) and systemic (P = .04) disease control. Five-year overall survival was 44.7% for the surgery group (95% confidence interval [CI]: 17.1-69.3) and 11.1% (95% CI: 2.1-28.8) for the nonsurgery group (P = .01). The strongest risk factor for improved overall survival after C-spine metastasis was local disease control at the C-spine (multivariate hazard ratio [HR] = 0.32, 95% CI: 0.12-0.85, P = .02). Surgical intervention was significantly associated with improved survival on both univariate (HR = 0. 35, 95% CI: 0.15-0.82, P = .02) and multivariate (HR = 0.37, 95% CI: 0.14-0.98, P = .04) analysis. CONCLUSION: Surgical management of CSpM in differentiated thyroid cancers is associated with significantly improved local disease control and overall survival. Referral to spine surgeons should be considered after diagnosis. LEVEL OF EVIDENCE: IV. Laryngoscope, 131:E1741-E1747, 2021.

123I Scan With Whole-Body Retention Measurement at 48 Hours for Simplified Dosimetry Before 131I Treatment of Metastatic Thyroid Cancer.

ABSTRACT: A previously published model (Atkins) allows for calculation of 131I maximum tolerated activity on the basis of 48-hour whole-body retention of 131I on a pretherapy diagnostic scan. Our practice uses iodine 123I for diagnostic imaging of metastatic thyroid cancer for staging before 131I therapy, with images typically acquired 24 hours after administration of the radiopharmaceutical. We explored the feasibility of an additional 123I whole-body scan and retention measurement at 48 hours, with application of the model to estimate maximum tolerated activity of radioiodine before 131I treatment of metastatic thyroid cancer.