Publications by authors named "Allen S Ho"

70 Publications

Nodal staging convergence for HPV- and HPV+ oropharyngeal carcinoma.

Cancer 2021 Feb 17. Epub 2021 Feb 17.

Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.

Background: Modern disease staging systems have restructured human papillomavirus (HPV)-negative (HPV-) and HPV-positive (HPV+) oropharyngeal carcinoma (OPC) into distinct pathologic nodal systems. Given that quantitative lymph node (LN) burden is the dominant prognostic factor in most head and neck cancers, we investigated whether HPV- and HPV+ OPC warrant divergent pathologic nodal classification.

Methods: Multivariable Cox regression models of OPC surgical patients identified via U.S. cancer registry data were constructed to determine associations between survival and nodal characteristics. Nonlinear associations between metastatic LN number and survival were modeled with restricted cubic splines. Recursive partitioning analysis (RPA) was used to derive unbiased nodal schema.

Results: Mortality risk escalated continuously with each successive positive LN in both OPC subtypes, with analogous slope. Survival hazard increased by 18.5% (hazard ratio [HR], 1.19 [95% CI, 1.16-1.21]; P < .001) and 19.1% (HR, 1.19 [95% CI, 1.17-1.21]; P < .001), with each added positive LN for HPV- and HPV+ OPC, respectively, up to identical change points of 5 positive LNs. Extranodal extension (ENE) was an independent predictor of HPV- OPC (HR, 1.55 [95% CI, 1.20-1.99]; P < .001) and HPV+ OPC (HR 1.73 [95% CI, 1.36-2.20]; P < .001) mortality. In RPA for both diseases, metastatic LN was the principal nodal covariate driving survival, with ENE as a secondary determinant. Given the similarities across analyses, we propose a concise, unifying HPV-/HPV+ OPC pathologic nodal classification schema: N1, 1-5 LN+/ENE-; N2, 1-5 LN+/ENE+; N3, >5 LN+.

Conclusion: HPV- and HPV+ OPC exhibit parallel relationships between nodal characteristics and relative mortality. In both diseases, metastatic LN number represents the principal nodal covariate governing survival, with ENE being an influential secondary element. A consolidated OPC pathologic nodal staging system that is based on these covariates may best convey prognosis.

Lay Summary: The current nodal staging system for oropharyngeal carcinoma (OPC) has divided human papillomavirus (HPV)-negative (HPV-) and HPV-positive (HPV+) OPC into distinct systems that rely upon criteria that establish them as separate entities, a complexity that may undermine the core objective of staging schema to clearly communicate prognosis. Our large-scale analysis revealed that HPV- and HPV+ pathologic nodal staging systems in fact mirror each other. Multiple analyses produced conspicuously similar nodal staging systems, with metastatic lymph node number and extranodal extension delineating the highest risk groups that shape prognosis. We propose unifying HPV- and HPV+ nodal systems to best streamline prognostication and maximize staging accuracy.
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http://dx.doi.org/10.1002/cncr.33414DOI Listing
February 2021

A Clinical Decision Analysis for Use of Antibiotic Prophylaxis for Nonabsorbable Nasal Packing.

Otolaryngol Head Neck Surg 2021 Feb 16:194599820988740. Epub 2021 Feb 16.

Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Objective: Nonabsorbable nasal packing is often placed for the treatment of epistaxis or after sinonasal or skull base surgery. Antibiotics are often prescribed to prevent toxic shock syndrome (TSS), a rare, potentially fatal occurrence. However, the risk of TSS must be balanced against the major risk of antibiotic use, specifically colitis (CDC). The purpose of this study is to evaluate in terms of cost-effectiveness whether antibiotics should be prescribed when nasal packing is placed.

Study Design: A clinical decision analysis was performed using a Markov model to evaluate whether antibiotics should be given.

Setting: Patients with nonabsorbable nasal packing placed.

Methods: Utility scores, probabilities, and costs were obtained from the literature. We assess the cost-effectiveness of antibiotic use when the risk of community-acquired CDC is balanced against the risk of TSS from nasal packing. Sensitivity analysis was performed for assumptions used in the model.

Results: The incremental cost-effectiveness ratio for antibiotic use was 334,493 US dollars (USD)/quality-adjusted life year (QALY). Probabilistic sensitivity analysis showed that not prescribing antibiotics was cost-effective in 98.0% of iterations at a willingness to pay of 50,000 USD/QALY. Sensitivity analysis showed that when the risk of CDC from antibiotics was greater than 910/100,000 or when the incidence of TSS after nasal packing was less than 49/100,000 cases, the decision to withhold antibiotics was cost-effective.

Conclusions: Routine antibiotic prophylaxis in the setting of nasal packing is not cost-effective and should be reconsidered. Even if antibiotics are assumed to prevent TSS, the risk of complications from antibiotic use is of greater consequence.

Level Of Evidence: 3a.
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http://dx.doi.org/10.1177/0194599820988740DOI Listing
February 2021

Incidental parathyroidectomy in thyroidectomy and central neck dissection.

Surgery 2021 Jan 11. Epub 2021 Jan 11.

Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA. Electronic address:

Background: Although higher thyroidectomy volume has been linked with lower complication rates, its association with incidental parathyroidectomy remains less studied. The volume relationship is even less clear for central neck dissection, where individual parathyroid glands are at greater risk.

Methods: Patients undergoing thyroidectomy with or without central neck dissection were evaluated for incidental parathyroidectomy, hypoparathyroidism, and hypocalcemia. Univariate and multivariable analyses were performed using binary logistic regression.

Results: Overall, 1,114 thyroidectomies and 396 concurrent central neck dissections were performed across 7 surgeons. Incidental parathyroidectomy occurred in 22.4% of surgeries (range, 16.9%-43.6%), affecting 7.1% of parathyroids at risk (range, 5.8%-14.5%). When stratified by surgeon, lower incidental parathyroidectomy rates were associated with higher thyroidectomy volumes (R = 0.77, P = .008) and higher central neck dissection volumes (R = 0.93, P < .001). On multivariable analysis, low-volume surgeon (odds ratio 2.94, 95% confidence interval 2.06-4.19, P < .001), extrathyroidal extension (odds ratio 3.13, 95% confidence interval 1.24-7.87, P = .016), prophylactic central neck dissection (odds ratio 2.68, 95% confidence interval 1.65-4.35, P <.001), and therapeutic central neck dissection (odds ratio 4.44, 95% confidence interval 1.98-9.96, P < .001) were the most significant factors associated with incidental parathyroidectomy. In addition, incidental parathyroidectomy was associated with a higher likelihood of temporary hypoparathyroidism (odds ratio 2.79, 95% confidence interval 1.45-5.38, P = .002) and permanent hypoparathyroidism (odds ratio 4.62, 95% confidence interval 1.41-5.96, P = .025), but not permanent hypocalcemia (odds ratio 1.27, 95% confidence interval 0.48-3.35, P = .63). Higher lymph node yield in central neck dissection was not associated with higher incidental parathyroidectomy rates (odds ratio 1.13, 95% confidence interval 0.85-8.81, P = .82).

Conclusion: Higher surgical volume conferred a lower rate of incidental parathyroidectomy. Nonetheless, greater lymph node yield in central neck dissections did not result in greater parathyroid-related morbidity. Such findings support the value of leveraging surgical volume to both optimize oncologic resection and minimize complication rates.
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http://dx.doi.org/10.1016/j.surg.2020.11.023DOI Listing
January 2021

Enlarged hemorrhagic lingual thyroid managed with transoral robotic surgery.

Endocrine 2021 Jan 9. Epub 2021 Jan 9.

Division of Otolaryngology-Head & Neck Surgery, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Purpose: Lingual thyroid glands are rare embryologic variants of undescended tissue centered in the base of the tongue. Despite notable size, many lingual thyroids can be asymptomatic, though intervention is warranted for progressive or emergent symptoms. We report a rare manifestation of a hemorrhagic lingual thyroid addressed with both interventional radiology and robotic techniques.

Methods: A previously asymptomatic 41-year old female presented to the emergency department with massive hematemesis after significant binge drinking and vomiting. Emergent intubation was performed and gastroenterology workup ruled out Mallory-Weiss tears or ruptured esophageal varices. Fiberoptic laryngoscopy and imaging revealed a bleeding tongue base mass concerning for malignancy.

Results: Aberrant feeding vessels with identifiable blush were embolized by Neurointerventional Radiology and the patient underwent tracheostomy for airway protection. Lingual thyroid was confirmed by biopsy and the mass was definitively resected via transoral robotic surgery. The patient had no further bleeding events and was decannulated uneventfully.

Conclusions: Lingual thyroid glands can present with life-threatening hematemesis and obstruction that may masquerade as entities of vascular or neoplastic origin. Management encompasses multidisciplinary diagnostic confirmation, airway protection, and minimally invasive resection that minimizes functional morbidity.
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http://dx.doi.org/10.1007/s12020-020-02586-wDOI Listing
January 2021

Variations in the association of grade with survival across the head and neck cancer landscape.

Head Neck 2021 Apr 10;43(4):1105-1115. Epub 2020 Dec 10.

Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Background: Although pathologic tumor grade is a well-established prognostic risk factor that impacts staging and treatment decisions across multiple cancer types, its role in head and neck squamous cell carcinoma (HNSCC) is less certain.

Methods: HNSCC patients diagnosed from 2010 to 2015 and undergoing primary surgery in the National Cancer Data Base were identified. Propensity score matching and multivariable Cox regression were performed.

Results: Among 27 041 HNSCC patients, 13 941 had oral cavity cancers (OCC). Intermediate-grade (hazard ratio [HR] 1.16, 95% CI 1.07-1.26, P < .001) and high-grade (HR 1.38, 95% CI 1.26-1.52, P < .001) tumors had worse survival than low-grade tumors. This magnitude was comparable to other well-established prognostic factors, including margin positivity, extranodal extension, and lymphovascular invasion. By contrast, there was no association between grade and survival in larynx/hypopharynx or HPV(-) oropharynx cancer.

Conclusions: The prognostic impact of pathologic grade is highly variable across head and neck subsites and is the strongest among OCC patients.
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http://dx.doi.org/10.1002/hed.26566DOI Listing
April 2021

Virtual Surgical Planning for Bisphosphonate-Related Osteonecrosis of the Jaw: A Valuable Application in Advanced Cases.

Cureus 2020 Aug 12;12(8):e9696. Epub 2020 Aug 12.

Otolaryngology - Head and Neck Surgery, Cedars-Sinai Medical Center, Los Angeles, USA.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare but potentially devastating complication of extended use of bisphosphonates. fibula free flaps (FFFs) are the gold standard of mandibular reconstruction. Virtual surgical planning (VSP) is a technique that utilizes high-definition three-dimensional reconstructions that enable the production of highly accurate intra-operative surgical guides and templates that help guide osteotomies and fibula contouring.  The aim of this report is to highlight the value of VSP in the surgical management of advanced BRONJ. We report a case study of a woman with advanced BRONJ that required an angle-to-angle mandibular resection with subsequent reconstruction with an FFF. VSP was used to improve the accuracy of the reconstruction and minimize ischemia time. We present the first reported case of the successful implementation of VSP for the planning of FFF reconstruction for a woman with advanced symptomatic BRONJ that had failed conservative measures.
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http://dx.doi.org/10.7759/cureus.9696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486086PMC
August 2020

ASO Author Reflections: Revisiting the Prognostic Significance of Grade in Papillary Thyroid Carcinoma.

Ann Surg Oncol 2020 Dec 30;27(Suppl 3):852-853. Epub 2020 Aug 30.

Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

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http://dx.doi.org/10.1245/s10434-020-09055-8DOI Listing
December 2020

Management of FDG avid Benign Sinonasal Schneiderian Papilloma: A Case Report and Review of the Literature.

Ann Otol Rhinol Laryngol 2021 Apr 27;130(4):424-428. Epub 2020 Aug 27.

Cedars-Sinai Division of Otolaryngology-Head and Neck Surgery, Los Angeles, CA, USA.

Background: The inverted and oncocytic subtypes of sinonasal Schneiderian papillomas are benign tumors with possible rare malignant transformation and are typically managed with complete surgical resection and close follow-up. While computed tomography (CT) and magnetic resonance imaging (MRI) are mainstays in preoperative evaluation of bony invasion and soft tissue extension of the lesion, their imaging characteristics by 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is less well characterized.

Objective: To describe the clinical presentation and management of a PET positive sinonasal lesion. To conduct a literature review of FDG uptake in benign sinonasal papillomas.

Methods: Case report (n = 1) and literature review of similar cases (n = 32).

Results: We report the case of a 69-year-old man presenting with an isolated left maxillary sinus mass with avid FDG uptake, discovered on PET/CT imaging. An endoscopic left maxillary mega-antrostomy provided successful definitive treatment for final pathologic diagnosis of oncocytic papilloma. Literature review of cases of sinonasal papillomas with avid FDG uptake found that oncocytic papillomas, on average, exhibit greater uptake than inverted papillomas and both may be mistaken as malignancies on PET.

Conclusion: While PET imaging demonstrating avid FDG uptake is associated with an increased risk of malignancy, it does not rule out the possibility of a benign sinonasal papilloma nor other benign inflammatory lesions. Particularly, oncocytic papillomas may have very high FDG uptake and mimic malignant lesions.
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http://dx.doi.org/10.1177/0003489420952478DOI Listing
April 2021

Comparison of Survival After Transoral Robotic Surgery vs Nonrobotic Surgery in Patients With Early-Stage Oropharyngeal Squamous Cell Carcinoma.

JAMA Oncol 2020 10;6(10):1555-1562

Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California.

Importance: Transoral robotic surgery has been widely adopted since approval by the US Food and Drug Administration in December 2009, despite limited comparative data.

Objective: To compare the long-term outcomes of transoral robotic surgery with those of nonrobotic surgery for patients with early-stage oropharyngeal cancer.

Design, Setting, And Participants: A retrospective cohort comparative effectiveness analysis was performed of patients in the National Cancer Database with clinical T1 and T2 oropharyngeal squamous cell carcinoma diagnosed between January 1, 2010, and December 31, 2015, who underwent definitive robotic and nonrobotic surgery. Multivariable Cox proportional hazards regression analysis and propensity score matching were performed in patients with known human papillomavirus status to adjust for patient- and disease-related covariates. Survival after robotic and nonrobotic surgery was also compared in 3 unrelated cancers: prostate, endometrial, and cervical cancer. Statistical analysis was performed from April 10, 2019, to May 21, 2020.

Main Outcomes And Measures: Overall survival.

Results: Of 9745 patients (7652 men [78.5%]; mean [SD] age, 58.8 [9.6] years) who met inclusion criteria, 2694 (27.6%) underwent transoral robotic surgery. There was a significant increase in the use of robotic surgery from 18.3% (240 of 1309) to 35.5% (654 of 1841) of all surgical procedures for T1 and T2 oropharyngeal cancers from 2010 to 2015 (P = .003). Robotic surgery was associated with lower rates of positive surgical margins (12.5% [218 of 1746] vs 20.3% [471 of 2325]; P < .001) and lower use of adjuvant chemoradiotherapy (28.6% [500 of 1746] vs 35.7% [831 of 2325]; P < .001). Among 4071 patients with known human papillomavirus status, robotic surgery was associated with improved overall survival compared with nonrobotic surgery in multivariable Cox proportional hazards regression (hazard ratio [HR], 0.74; 95 CI, 0.61-0.90; P = .002). Similar results were seen when analyzing only the subset of facilities offering both robotic and nonrobotic surgery. The 5-year overall survival was 84.8% vs 80.3% among patients undergoing robotic vs nonrobotic surgery in propensity score-matched cohorts (P = .001). By contrast, there was no evidence that robotic surgery was associated with improved survival in other cancers, such as prostate cancer (HR, 0.92; 95% CI, 0.79-1.07; P = .26), endometrial cancer (HR, 0.97; 95% CI, 0.90-1.04; P = .36), and cervical cancer (HR, 1.27; 95% CI, 0.96-1.69; P = .10).

Conclusions And Relevance: This study suggests that transoral robotic surgery was associated with improved surgical outcomes and survival compared with nonrobotic surgery in patients with early-stage oropharyngeal cancer. Evaluation in comparative randomized trials is warranted.
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http://dx.doi.org/10.1001/jamaoncol.2020.3172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441465PMC
October 2020

Prognostic Impact of Histologic Grade for Papillary Thyroid Carcinoma.

Ann Surg Oncol 2021 Mar 17;28(3):1731-1739. Epub 2020 Aug 17.

Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Background: While numerous factors affect prognosis in papillary thyroid carcinoma (PTC), the comparative impact of histologic grade has not been well described. Moreover, indications for external beam radiation therapy (EBRT) remain imprecise. We evaluate clinicopathologic characteristics and outcomes for PTC stratified by grade.

Methods: We profiled histologic grade for PTC (well differentiated, moderately differentiated, poorly differentiated) via hospital (National Cancer Database) and population-based (Surveillance, Epidemiology, and End Results) registries. Cox regression was used to adjust for clinicopathologic covariates. Statistical interactions between subtypes and the effect of EBRT on survival were assessed.

Results: Collectively, worsening clinicopathologic factors (age, tumor size, extrathyroidal extension, nodal spread, M1 disease) and outcomes (disease-free survival, overall survival) correlated with less differentiated state, across all histologic grades (p < 0.001). Multivariable analysis showed escalating hazard with loss of differentiation relative to well-differentiated PTC (moderately differentiated hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.04-1.41, p = 0.02; poorly differentiated HR 2.62, 95% CI 2.23-3.08, p < 0.001). Correspondingly, greater survival benefit was associated with EBRT for poorly differentiated cases (HR 0.36, 95% CI 0.18-0.72, p = 0.004). This finding was upheld after landmark analysis to address potential immortal time bias (HR 0.37, 95% CI 0.17-0.80, p = 0.01).

Conclusions: Worsening histologic grade in PTC is independently associated with parallel escalation in mortality risk, on a scale approximating or surpassing established thyroid cancer risk factors. On preliminary analysis, EBRT was associated with improved survival in the most aggressive or least differentiated subvariants. Further investigation is warranted to examine the efficacy of EBRT for select poorly differentiated thyroid carcinomas.
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http://dx.doi.org/10.1245/s10434-020-09023-2DOI Listing
March 2021

The role of concomitant chemoradiotherapy in AJCC 7 edition T1-2N1 oropharyngeal carcinoma in the human papillomavirus era.

Oral Oncol 2020 11 7;110:104882. Epub 2020 Jul 7.

Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States. Electronic address:

Background: Radiotherapy (RT) without chemotherapy is considered a standard of care for the management of American Joint Committee on Cancer (AJCC) 7th edition (7E) T1-2N1 oropharyngeal squamous cell carcinoma (OPSCC). Recent data suggests concurrent chemoradiation (CCRT) may benefit these patients but did not include human papillomavirus (HPV) status. Given the radiosensitivity differences between HPV-positive versus HPV-negative OPSCC, the effect of chemotherapy may differ in these patients.

Methods: We analyzed patients in the National Cancer Database diagnosed between 2010 and 2015 with AJCC 7E stage cT1-2N1M0 OPSCC and known HPV status undergoing definitive RT or CCRT.

Results: Overall, 1964 patients were included, including 1297 (66%) HPV-positive and 667 (34%) HPV-negative patients. 66% received CCRT and 34% received RT alone. In multivariate analysis, CCRT was associated with improved survival compared with RT alone (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.57-0.87; P = 0.001). In propensity score-matched cohorts, 4-year overall survival was 87.4% vs 78.4% in HPV-positive patients receiving CCRT and RT alone, respectively (P = 0.002), and 65.5% vs 58.9% in HPV-negative patients, respectively (P = 0.2). There was no evidence that HPV-positivity diminished the association between CCRT and longer survival (HR, 0.57; 95% CI, 0.42-0.81) versus what was observed in HPV-negative patients (HR, 0.86; 95% CI, 0.64-1.16) (interaction P = 0.06).

Conclusions: CCRT is associated with improved survival in AJCC 7E T1-2N1 OPSCC. Despite the radiosensitivity of HPV-positive OPSCC, the association of CCRT with improved survival for T1-2N1 HPV-positive OPSCC was at least as strong, if not stronger, than what was observed in HPV-negative patients.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104882DOI Listing
November 2020

Cost-effectiveness of fiberoptic laryngoscopy prior to total thyroidectomy for low-risk thyroid cancer patients.

Head Neck 2020 09 8;42(9):2593-2601. Epub 2020 Jun 8.

Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Background: Flexible fiberoptic laryngoscopy is performed prior to thyroid surgery to evaluate the function of the recurrent laryngeal nerve. We assess the cost-effectiveness of preoperative laryngoscopy prior to total thyroidectomy for a low-risk thyroid cancer patient without dysphonia.

Methods: A decision tree analysis was performed from a third-party payer perspective. We assessed the cost-effectiveness of fiberoptic laryngoscopy prior to total thyroidectomy for T2N0M0 papillary thyroid carcinoma, such that an ipsilateral vocal fold paralysis alters the surgical plan to hemi-thyroidectomy, when permissible, to avoid the risk of bilateral vocal fold paralysis.

Results: Performing preoperative laryngoscopy to assess vocal fold function has an incremental cost-effectiveness ratio (ICER) of 45 193 USD/QALY compared to no laryngoscopy. At a willingness-to-pay of 100 K/QALY, the intervention is cost-effective if the incidence of vocal fold paralysis is at least 0.57%, or when the permissible rate of hemithyroidectomy in cases of incidental paralysis is at least 41%. Probabilistic sensitivity analysis shows that laryngoscopy is cost-effective in 90.9% of cases.

Conclusions: Fiberoptic laryngoscopy is a cost-effective prior to total thyroidectomy in asymptomatic, low-risk thyroid cancer patients.
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http://dx.doi.org/10.1002/hed.26312DOI Listing
September 2020

Improved survival in women versus men with merkel cell carcinoma.

J Am Acad Dermatol 2021 Feb 15;84(2):321-329. Epub 2020 May 15.

Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:

Background: Studies have observed that women have better outcomes than men in melanoma, but less is known about the influence of sex differences on outcomes for other aggressive cutaneous malignancies.

Objective: To investigate whether women and men have disparate outcomes in Merkel cell carcinoma (MCC).

Methods: Patients with nonmetastatic MCC undergoing surgery and lymph node evaluation were identified from the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier analysis and Cox proportional hazards regression models were used for overall survival, and competing-risks analysis and Fine-Gray models were used for cause-specific and other-cause mortality.

Results: The NCDB cohort (n = 4178) included 1516 (36%) women. Women had a consistent survival advantage compared with men in propensity score-matched analysis (66.0% vs 56.8% at 5 years, P < .001) and multivariable Cox regression (hazard ratio, 0.68; 95% confidence interval, 0.61-0.75; P < .001). Similarly, women had a survival advantage in the SEER validation cohort (n = 1202) with 457 (38.0%) women, which was entirely due to differences in MCC-specific mortality (5-year cumulative incidence: 16.4% vs 26.7%, P = .002), with no difference in other-cause mortality (16.8% vs 17.8%, P = .43) observed in propensity score-matched patients.

Limitations: Potential selection bias from a retrospective data set.

Conclusion: In MCC, women have improved survival compared with men, driven by MCC-related mortality.
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http://dx.doi.org/10.1016/j.jaad.2020.02.034DOI Listing
February 2021

The association between facility volume and overall survival in patients with Merkel cell carcinoma.

J Surg Oncol 2020 Aug 15;122(2):254-262. Epub 2020 Apr 15.

Department of Radiation Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.

Background: Merkel cell carcinoma is an uncommon malignancy often requiring multidisciplinary management. The purpose of this study was to determine whether high-volume facilities have improved outcomes in patients with Merkel cell carcinoma relative to lower-volume facilities.

Methods: A total of 5304 patients from the National Cancer Database with stage I-III Merkel cell carcinoma undergoing surgery were analyzed. High-volume facilities were the top 1% by case volume. Multivariable Cox regression and propensity score-matching were performed to account for imbalances between groups.

Results: Treatment at high-volume facilities (hazard ratio: 0.74; 95% confidence interval: 0.65-0.84, P < .001) was independently associated with improved overall survival (OS) in multivariable analyses. In propensity score-matched cohorts, 5-year OS was 62.3% at high-volume facilities vs 56.8% at lower-volume facilities (P < .001). Median OS was 111 months at high-volume facilities vs 79 months at lower-volume facilities.

Conclusion: Treatment at high-volume facilities is associated with improved OS in Merkel cell carcinoma. Given the impracticality of referring all elderly patients with Merkel cell carcinoma to a small number of facilities, methods to mitigate this disparity should be explored.
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http://dx.doi.org/10.1002/jso.25931DOI Listing
August 2020

Incidence and Mortality Risk Spectrum Across Aggressive Variants of Papillary Thyroid Carcinoma.

JAMA Oncol 2020 05;6(5):706-713

Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.

Importance: While well-differentiated papillary thyroid carcinoma (WDPTC) outcomes have been well characterized, the prognostic implications of more aggressive variants are far less defined. The rarity of these subtypes has led to their consolidation as intermediate risk for what are in fact likely heterogeneous diseases.

Objective: To analyze incidence, clinicopathologic characteristics, and outcomes for aggressive variants of papillary thyroid carcinoma (PTC).

Design, Setting, And Participants: This cohort study used data from 2000 to 2016 from hospital-based and population-based US cancer registries to analyze aggressive PTC variants, including diffuse sclerosing (DSV), tall-cell (TCV), insular, and poorly differentiated (PDTC) subtypes. These variants were compared against WDPTC and anaplastic cases. Data analysis was conducted from January 2019 to October 2019.

Main Outcomes And Measures: Age-adjusted incidence was calculated via annual percentage change (APC) using the weighted least-squares method. Overall survival and disease-specific survival were analyzed via Cox regression. Propensity-score matching was used to adjust survival analyses for clinical and demographic covariates.

Results: Collectively, 5447 aggressive PTC variants were identified (including 415 DSV, 3339 TCV, 362 insular, and 1331 PDTC cases), as well as 35 812 WDPTC and 2249 anaplastic cases. Over the study period, a substantial increase in aggressive variant incidence was observed (APC, 9.1 [95% CI, 7.33-10.89]; P < .001), surpassing the relative increases observed in WDPTC (APC, 5.1 [95% CI, 3.98-6.12]; P < .001) and anaplastic cases (APC, 1.9 [95% CI, 0.75-3.05]; P = .003; parallelism P < .007). Survival varied markedly based on histologic subtype, with a wide spectrum of mortality risk noted; 10-year overall survival was 85.4% (95% CI, 84.6%-86.3%) in WDPTC, 79.2% (95% CI, 73.6%-85.3%) in DSV, 71.9% (95% CI, 68.4%-75.6%) in TCV, 45.1% (95% CI, 40.2%-50.6%) in PDTC, 27.9% (95% CI, 20.0%-38.9%) in the insular variant, and 8.9% (95% CI, 7.5%-10.6%) in anaplastic cases (P < .001). These differences largely persisted even after adjusting for inherent differences in baseline characteristics by multivariable Cox regression and propensity-score matching.

Conclusions And Relevance: An upsurge in aggressive PTC incidence was observed at a rate beyond that seen in WDPTC or anaplastic thyroid carcinoma. Moreover, long-term survival outcomes for aggressive PTC subgroups exhibit heterogeneous clinical behavior and a wide range of mortality risk, suggesting that treatment should be tailored to specific histologic subtypes. Given increasing prevalence and disparate outcomes, further investigation to identify optimal therapeutic strategies is needed in these diverse, understudied populations.
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http://dx.doi.org/10.1001/jamaoncol.2019.6851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059113PMC
May 2020

Quantitative metastatic lymph node burden and survival in Merkel cell carcinoma.

J Am Acad Dermatol 2021 Feb 16;84(2):312-320. Epub 2020 Jan 16.

Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:

Background: Current lymph node (LN) staging for Merkel cell carcinoma (MCC) does not account for the number of metastatic LNs, which is a primary driver of survival in multiple cancers.

Objective: To determine the impact of the number of metastatic LNs on survival in MCC.

Methods: Patients with MCC undergoing surgery were identified from the National Cancer Database (NCDB). The association between metastatic LN number and survival was modeled with restricted cubic splines. A novel nodal classification system was derived by using recursive partitioning analysis. MCC patients undergoing surgery in the Surveillance, Epidemiology, and End Results (SEER) Program were used as validation cohort.

Results: Among 3670 patients in the NCDB, increasing metastatic LN number was associated with decreased survival (P < .001). Mortality risk increased continuously with each additional positive LN when using multivariable, nonlinear modeling. According to a novel staging system derived via recursive partitioning analysis, the hazard ratio for death in multivariable regression compared with patients without LN involvement was 1.24 (P = .049), 2.08 (P < .001), 3.24 (P < .001), and 6.13 (P < .001) for the proposed N1a (1-3 metastatic LNs with microscopic detection), N1b (1-3 metastatic LNs with macroscopic detection), N2 (4-8 metastatic LNs), and N3 (≥9 metastatic LNs), respectively. This system was validated in the SEER cohort and showed improved concordance compared with the American Joint Committee on Cancer, Eighth Edition.

Limitations: Retrospective design.

Conclusions: Number of metastatic LNs is the dominant nodal factor driving survival in patients with MCC.
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http://dx.doi.org/10.1016/j.jaad.2019.12.072DOI Listing
February 2021

Survival outcomes with concomitant chemoradiotherapy in older adults with oropharyngeal carcinoma in an era of increasing human papillomavirus (HPV) prevalence.

Oral Oncol 2019 12 5;99:104472. Epub 2019 Nov 5.

Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, United States; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States. Electronic address:

Background: Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has dramatically increased in incidence and prevalence among patients aged 70 and older. There are virtually no data regarding outcomes in this population, and thus optimal therapy, including the role of chemotherapy for those undergoing radiotherapy (RT), remains unclear.

Methods: The National Cancer Database was queried for older adults (defined as age 70 years and older) with locally advanced OPSCC (cT1-2N1-3, cT3-4N0-3) diagnosed from 2010 to 2014 with known HPV-status undergoing definitive RT alone or chemoradiation (CRT).

Results: Overall, 1,965 older adults with locally advanced OPSCC met inclusion criteria, including 1,141 HPV-positive (58%) and 824 HPV-negative (42%) patients. 1,211 patients (62%) received CRT. In multivariable analysis, CRT was associated with improved survival in older patients when compared to RT alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI] 0.64-0.86, P < 0.001). CRT was associated with improved survival in both HPV-positive (HR = 0.80, 95% CI: 0.64-1.00, P = 0.05) and HPV-negative (HR = 0.69, 95% CI: 0.56-0.85, P < 0.001) subgroups. There was no significant interaction between HPV status and the impact of CRT on survival (P interaction = 0.57).

Conclusions: Despite the radiosensitivity of HPV-positive OPSCC and the challenges in delivering CRT to older adults, CRT was associated with improved survival in older patients with HPV-positive OPSCC, similar in magnitude to the benefit in HPV-negative patients. As the incidence of HPV-positive OPSCC in older patients continues to increase, further studies are needed to investigate optimal therapeutic strategies in this population.
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http://dx.doi.org/10.1016/j.oraloncology.2019.104472DOI Listing
December 2019

Impact of insurance on survival in patients < 65 with head & neck cancer treated with radiotherapy.

Clin Otolaryngol 2020 01 13;45(1):63-72. Epub 2019 Nov 13.

Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Objectives: The United States has a heterogenous health insurance landscape for patients <65 years. We sought to characterise the impact of primary payer on overall survival (OS) in insured patients younger than 65 with head and neck squamous cell carcinoma (HNSCC) treated with definitive radiotherapy.

Design/study/participants: The National Cancer Database was queried for patients <65 years old diagnosed from 2004 to 2014 undergoing definitive radiotherapy ± chemotherapy for cancers of the nasopharynx, oropharynx, hypopharynx and larynx. Uninsured patients and oropharyngeal cancers without known HPV status were excluded.

Main Outcome: Overall survival.

Results: Overall, 27 292 insured patients were identified, including 17 060 (62.5%) with private insurance. Median follow-up was 52.1 months. In multivariable models, patients receiving Medicaid (HR = 1.66, 95% CI 1.57-1.75, P < .001), Medicare (HR = 1.64, 95% CI 1.55-1.73, P < .001) and other government insurance (HR = 1.44, 95% CI 1.29-1., P < .001) had independently increased mortality in comparison to those with private insurance. In propensity score-matched cohorts, 5-year OS was 65.5% vs 50.6% for privately vs government-insured patients, respectively (P < .001). In multivariable subgroup analysis, private insurance was associated with improved survival in all subgroups. However, the magnitude of this effect was most pronounced in patients with HPV-positive oropharyngeal cancer vs non-HPV-related cancer (interaction P < .001), younger patients (interaction P = .001), and those without comorbidity (interaction P < .001).

Conclusions: Patients <65 with HNSCC undergoing definitive radiation with private health insurance have markedly longer survival relative to patients with government-sponsored insurance. This illustrates that increasing access to care may be necessary, but is not sufficient, to mitigate the significant disparities in the US healthcare system.
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http://dx.doi.org/10.1111/coa.13467DOI Listing
January 2020

Papillary thyroid microcarcinoma: optimal management versus overtreatment.

Curr Opin Oncol 2020 01;32(1):1-6

Department of Surgery, Division of Otolaryngology - Head and Neck Surgery.

Purpose Of Review: The treatment of small, low-risk papillary thyroid carcinoma has undergone a paradigm shift, with many tumors now initially treated with active surveillance rather than upfront surgery. Further studies on patients enrolled in active surveillance have refined our knowledge of the clinical behavior of papillary thyroid microcarcinomas.

Recent Findings: This article summarizes the major conclusions of landmark trials that launched active surveillance as a viable treatment option for selected patients. We discuss patient factors such as age and tumor size, the assessment of candidates for active surveillance, barriers to acceptance of active surveillance, quality of life issues, and economic considerations.

Summary: Active Surveillance is a viable first-line treatment option for select papillary microcarcinomas.
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http://dx.doi.org/10.1097/CCO.0000000000000595DOI Listing
January 2020

Stage I HPV-positive oropharyngeal cancer: Should all patients receive similar treatments?

Cancer 2020 01 19;126(1):58-66. Epub 2019 Sep 19.

Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.

Background: Patients with clinical stage I human papillomavirus (HPV)-positive oropharyngeal squamous cell cancer (OPSCC) according to the American Joint Committee on Cancer (AJCC) eighth edition classification comprise a heterogeneous group formerly classified as stage I to stage IVA according to the seventh edition of the AJCC classification. These patients historically were treated with disparate treatment regimens, particularly with respect to the use of concurrent chemotherapy.

Methods: The National Cancer Data Base was queried for patients with AJCC eighth edition clinical stage I HPV-positive OPSCC (AJCC seventh edition stage T1-2N0-2bM0) who were diagnosed from 2010 to 2014 and underwent definitive radiotherapy. Concurrent chemotherapy with definitive radiotherapy was defined as chemotherapy administered within 7 days of the initiation of radiotherapy.

Results: The current analysis included 4473 patients with HPV-positive stage I OPSCC with a median follow-up of 36.3 months. A total of 3127 patients (69.9%) received concurrent chemotherapy. Concurrent chemotherapy was found to be associated with improved overall survival on multivariable analyses (hazard ratio [HR], 0.782; 95% CI, 0.645-0.948 [P = .012]). The effect of chemotherapy on survival varied based on lymph node involvement (P for interaction = .001). Specifically, chemotherapy was associated with improved survival for patients with lymph node-positive stage I disease (stage III-IVA according to the AJCC seventh edition: HR, 0.682; 95% CI, 0.557-0.835 [P < .001]), but not for patients with N0 disease (stage I-II according to the AJCC seventh edition: HR, 1.646; 95% CI, 1.011-2.681 [P = .05]). Similar results were noted among propensity score-matched cohorts.

Conclusions: Treatment with concurrent chemotherapy was associated with improved overall survival for patients with lymph node-positive, but not lymph node-negative, AJCC eighth edition stage I HPV-positive OPSCC undergoing definitive radiotherapy, thereby supporting different treatment paradigms for these patients.
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http://dx.doi.org/10.1002/cncr.32501DOI Listing
January 2020

Genetic hallmarks of recurrent/metastatic adenoid cystic carcinoma.

J Clin Invest 2019 10;129(10):4276-4289

Head and Neck Service, Department of Surgery, and.

BACKGROUNDAdenoid cystic carcinoma (ACC) is a rare malignancy arising in salivary glands and other sites, characterized by high rates of relapse and distant spread. Recurrent/metastatic (R/M) ACCs are generally incurable, due to a lack of active systemic therapies. To improve outcomes, deeper understanding of genetic alterations and vulnerabilities in R/M tumors is needed.METHODSAn integrated genomic analysis of 1,045 ACCs (177 primary, 868 R/M) was performed to identify alterations associated with advanced and metastatic tumors. Intratumoral genetic heterogeneity, germline mutations, and therapeutic actionability were assessed.RESULTSCompared with primary tumors, R/M tumors were enriched for alterations in key Notch (NOTCH1, 26.3% vs. 8.5%; NOTCH2, 4.6% vs. 2.3%; NOTCH3, 5.7% vs. 2.3%; NOTCH4, 3.6% vs. 0.6%) and chromatin-remodeling (KDM6A, 15.2% vs. 3.4%; KMT2C/MLL3, 14.3% vs. 4.0%; ARID1B, 14.1% vs. 4.0%) genes. TERT promoter mutations (13.1% of R/M cases) were mutually exclusive with both NOTCH1 mutations (q = 3.3 × 10-4) and MYB/MYBL1 fusions (q = 5.6 × 10-3), suggesting discrete, alternative mechanisms of tumorigenesis. This network of alterations defined 4 distinct ACC subgroups: MYB+NOTCH1+, MYB+/other, MYBWTNOTCH1+, and MYBWTTERT+. Despite low mutational load, we identified numerous samples with marked intratumoral genetic heterogeneity, including branching evolution across multiregion sequencing.CONCLUSIONThese observations collectively redefine the molecular underpinnings of ACC progression and identify further targets for precision therapies.FUNDINGAdenoid Cystic Carcinoma Research Foundation, Pershing Square Sohn Cancer Research grant, the PaineWebber Chair, Stand Up 2 Cancer, NIH R01 CA205426, the STARR Cancer Consortium, NCI R35 CA232097, the Frederick Adler Chair, Cycle for Survival, the Jayme Flowers Fund, The Sebastian Nativo Fund, NIH K08 DE024774 and R01 DE027738, and MSKCC through NIH/NCI Cancer Center Support Grant (P30 CA008748).
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http://dx.doi.org/10.1172/JCI128227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763222PMC
October 2019

Unusual Presentation of Primary Syphilis as Pharyngeal Chancre: A Case Report.

OTO Open 2019 Apr-Jun;3(2):2473974X19841867. Epub 2019 Apr 23.

Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.

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http://dx.doi.org/10.1177/2473974X19841867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684139PMC
April 2019

Mortality Risk of Nonoperative Papillary Thyroid Carcinoma: A Corollary for Active Surveillance.

Thyroid 2019 10 24;29(10):1409-1417. Epub 2019 Sep 24.

Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.

Active surveillance is established as an alternative to surgery for papillary thyroid microcarcinomas, but inclusion criteria and mortality risk for pursuing a nonsurgical approach have not been clearly defined. To gauge the feasibility of expanding active surveillance thresholds, we investigated the effects of increasing size and age on disease-specific survival (DSS) in a large nonoperative thyroid cancer cohort, compared against a matched group of surgical patients. Papillary thyroid carcinoma patients staged T1-4N0M0 were identified in the Surveillance, Epidemiology, and End Results (SEER) database between 1975 and 2015, stratified by nonsurgical and surgical management. Propensity score matching was performed to adjust for imbalances in covariates. Multivariable models were constructed using restricted cubic splines to model nonlinear relationships of age and tumor size with DSS. Overall, 1453 nonoperative patients and 54,718 surgical patients met the inclusion criteria. Collectively, increasing age and size after certain thresholds independently led to greater differences in DSS between nonsurgical and surgical patients. For younger ages (14-55 years), surgical approach compared with nonsurgical approach was not associated with any difference in the 10-year DSS among 0-4 cm cancers (99.8% vs. 100%,  = 0.470), 4.1-6 cm cancers (98.8% vs. 100%,  = 0.599), or >6 cm cancers (97.3% vs. 100%,  = 0.718). Older patients with larger tumors (>75 years, >6 cm) demonstrated the greatest difference in DSS (48.1% vs. 91.3%,  < 0.001). Similar results were found when applying propensity score matching. For age, restricted cubic spline plots showed minimal relative survival hazard in nonoperative cases beginning after age 60 years, with a change point illustrating acceleration in relative hazard beyond age 72 years. For size, relative survival hazard was observed after 2.0 cm and increased slowly with nodule growth up to an inflection point of 4.5 cm. Beyond this, mortality risk escalated with each additional year without plateau. Increasing age and size lead to progressively greater mortality risk without surgery, but only beyond certain thresholds. We define escalating gradients at which a nonsurgical approach may be deemed appropriate, and beyond which survival benefits from surgery become apparent. Such findings reconcile controversial observations regarding age and size in active surveillance and further reshape evolving treatment paradigms in thyroid cancer.
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http://dx.doi.org/10.1089/thy.2019.0060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476400PMC
October 2019

American Joint Committee on Cancer 8 edition staging-an improvement in prognostication in HPV-associated oropharyngeal cancer?

Ann Transl Med 2019 Mar;7(Suppl 1):S10

Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.

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http://dx.doi.org/10.21037/atm.2019.01.30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462603PMC
March 2019

Survival Impact of Adjuvant Therapy in Salivary Gland Cancers following Resection and Neck Dissection.

Otolaryngol Head Neck Surg 2019 06 5;160(6):1048-1057. Epub 2019 Feb 5.

2 Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Objective: To evaluate the impact of postoperative radiotherapy (PORT) and chemotherapy on survival in salivary gland cancer (SGC) treated with curative-intent local resection and neck dissection.

Study Design: Retrospective population-based cohort study.

Setting: National Cancer Database.

Subjects And Methods: Patients with SGC who were undergoing surgery were identified from the National Cancer Database between 2004 and 2013. Neck dissection removing a minimum of 10 lymph nodes was required. Because PORT violated the proportional hazards assumption, this variable was treated as a time-dependent covariate.

Results: Overall, 4145 cases met inclusion criteria (median follow-up, 54 months). PORT was associated with improved overall survival in multivariable analysis, both ≤9 months from diagnosis (hazard ratio [HR], 0.26; 95% CI, 0.20-0.34; P < .001) and >9 months (HR, 0.75; 95% CI, 0.66-0.86; P < .001). In propensity score-matched cohorts, 5-year overall survival was 67.1% and 60.6% with PORT and observation, respectively ( P < .001). Similar results were observed in landmark analysis of patients surviving at least 6 months following diagnosis. Adjuvant chemotherapy was not associated with improved survival (HR, 1.15; 95% CI, 0.99-1.34; P = .06).

Conclusion: PORT, but not chemotherapy, is associated with improved survival among patients with SGC for whom neck dissection was deemed necessary. These results are not applicable to low-risk SGCs not requiring neck dissection.
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http://dx.doi.org/10.1177/0194599819827851DOI Listing
June 2019

Parallels Between Low-Risk Prostate Cancer and Thyroid Cancer: A Review.

JAMA Oncol 2019 Apr;5(4):556-564

Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.

Importance: Across many countries, a rapid escalation of the incidence of thyroid cancer has been observed, a surge that nonetheless underestimates the true extent of the disease. Most thyroid cancers now diagnosed comprise small, low-risk cancers that are incidentally found and are unlikely to cause harm. In many ways, prostate cancer similarly harbors a well-behaved subclinical reservoir, a long natural history, and superlative outcomes that have made active surveillance the de facto guideline recommendation for low-risk disease. This review highlights the parallels and differences between prostate cancer and thyroid cancer regarding screening, diagnosis, risk stratification, and considerations for active surveillance.

Observations: Prostate cancer and thyroid cancer have undergone recalibrated, de-escalatory shifts to counter changing epidemiologic landscapes. The US Preventive Services Task Force has issued cautionary recommendations on screening via prostate-specific antigen testing or neck ultrasonography, while the thresholds to performing biopsy have increased. Comparable changes to cancer terminology and staging have also helped alleviate patient anxiety and minimize pressure for overtreatment. Long-term, randomized prospective clinical trials for prostate cancer have established active surveillance as a first-line treatment approach for properly stratified low-risk patients, while observational trials for thyroid cancer have also made strides in defining risk and eligibility for surgery. Caveats requiring deeper investigation include aggressive disease in older patients, underestimation of the extent of the disease, and patient-physician bias in shared decision making. For prostate cancer, survival may not improve and function will likely worsen after intervention; for thyroid cancer, patients are younger, surgery is safer, and the bar for surveillance will likely be higher.

Conclusions And Relevance: Despite similarities in biological indolence between low-risk prostate and thyroid malignant neoplasms, key distinctions in life expectancy and treatment sequelae may ultimately confer somewhat disparate management paradigms for the 2 diseases. Nevertheless, the experience forged by prostate cancer trials serves as a model for thyroid cancer management, potentially reshaping the perception of active surveillance into a credible, valuable treatment modality.
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http://dx.doi.org/10.1001/jamaoncol.2018.5321DOI Listing
April 2019

Interinstitutional variation in predictive value of the ThyroSeq v2 genomic classifier for cytologically indeterminate thyroid nodules.

Surgery 2019 01 22;165(1):17-24. Epub 2018 Oct 22.

Department of Surgery (Head and Neck Service), Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address:

Background: The ThyroSeq v2 next-generation sequencing assay estimates the probability of malignancy in indeterminate thyroid nodules. Its diagnostic accuracy in different practice settings and patient populations is not well understood.

Methods: We analyzed 273 Bethesda III/IV indeterminate thyroid nodules evaluated with ThyroSeq at 4 institutions: 2 comprehensive cancer centers (n = 98 and 102), a multicenter health care system (n = 60), and an academic medical center (n = 13). The positive and negative predictive values of ThyroSeq and distribution of final pathologic diagnoses were analyzed and compared with values predicted by Bayes theorem.

Results: Across 4 institutions, the positive predictive value was 35% (22%-43%) and negative predictive value was 93% (88%-100%). Predictive values correlated closely with Bayes theorem estimates (r = 0.84), although positive predictive values were lower than expected. RAS mutations were the most common molecular alteration. Among 84 RAS-mutated nodules, malignancy risk was variable (25%, range 10%-37%) and distribution of benign diagnoses differed across institutions (adenoma/hyperplasia 12%-85%, noninvasive follicular thyroid neoplasm with papillary-like nuclear features 5%-46%).

Conclusion: In a multi-institutional analysis, ThyroSeq positive predictive values were variable and lower than expected. This is attributable to differences in the prevalence of malignancy and variability in pathologist interpretations of noninvasive tumors. It is important that clinicians understand ThyroSeq performance in their practice setting when evaluating these results.
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http://dx.doi.org/10.1016/j.surg.2018.04.062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289715PMC
January 2019

Human papillomavirus-associated oropharyngeal cancer among patients aged 70 and older: Dramatically increased prevalence and clinical implications.

Eur J Cancer 2018 11 27;103:195-204. Epub 2018 Sep 27.

Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address:

Background: Oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence among older adults. However, the role of human papillomavirus (HPV) in driving this trend and its prognostic significance in this population have not been established.

Methods: The National Cancer Database was queried for patients with OPSCC diagnosed from 2010 to 2015 undergoing either surgery or radiotherapy (RT) with known HPV status. Older adults were defined as those aged 70 years or older.

Results: Among 43,427 OPSCC patients, the proportion of HPV-positive OPSCC increased from 45.1% to 63.3% in older adults (P < 0.001). In 19,358 patients meeting the inclusion criteria for survival analyses, HPV positivity was associated with improved survival for older adults undergoing either definitive RT (hazard ratio [HR] = 0.63, 95% confidence interval [CI] 0.55-0.72, P < 0.001) or surgery (HR = 0.37, 95% CI 0.25-0.53, P < 0.001) in multivariable analysis. In propensity score-matched cohorts, 3-year overall survival was 69.1% versus 55.5% (P < 0.001) in older adults with HPV-positive and HPV-negative OPSCC undergoing definitive RT, respectively, and 88.5% versus 69.1% (P = 0.001) for older adults undergoing surgery. Although HPV positivity was associated with improved survival among all age groups receiving RT, the magnitude of the effect diminished with increasing age (interaction P < 0.001). No interaction between age and the impact of HPV status on survival was seen for surgical patients (interaction P = 0.72).

Conclusions: The epidemiologic landscape of HPV-positive OPSCC is evolving, with a dramatic increase in the proportion of HPV-associated OPSCC among patients 70 years or older. HPV remains a powerful predictor of improved survival in elderly patients, but with less pronounced effect on older adults undergoing definitive RT.
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http://dx.doi.org/10.1016/j.ejca.2018.08.015DOI Listing
November 2018

Reply to: Selective history of radioactive iodine in medicine: Inexactitudes no longer.

Eur J Surg Oncol 2019 04 7;45(4):713-714. Epub 2018 Sep 7.

Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.ejso.2018.08.025DOI Listing
April 2019

Evolving management considerations in active surveillance for micropapillary thyroid carcinoma.

Curr Opin Endocrinol Diabetes Obes 2018 10;25(5):353-359

Samuel Oschin Comprehensive Cancer Institute.

Purpose Of Review: To summarize developments on active surveillance for micropapillary thyroid cancers, with a focus on strategies for optimal risk stratification and caveats that currently limit adoption.

Recent Findings: Observational trials encompassing thousands of active surveillance patients worldwide have increasingly demonstrated the viability of active surveillance for small, low-risk thyroid cancers. Collectively, these data have established that with proper patient selection and strict monitoring, more than 85% of such cases remain indolent no meaningful clinical growth over at least 10 years. Moreover, to date no cases of symptomatic progression or distant metastasis have been reported, and that delayed treatment when needed has not led to unresectable disease or higher risk of complications. Deeper investigation to better predict clinical progression is necessary to improve patient selection, given concerns regarding patient anxiety, age eligibility, and underestimation of true disease extent.

Summary: Compelling data from ongoing trials support active surveillance as a first-line management option for micropapillary thyroid carcinomas. Proper risk stratification and strict monitoring protocols will be necessary to sustain the excellent results achieved to date. Broad adoption of active surveillance will require further education, collaboration, and equipoise between physicians and patients to optimize such individualized treatment plans.
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http://dx.doi.org/10.1097/MED.0000000000000438DOI Listing
October 2018