Pediatric Papillary Thyroid Carcinoma: Outcomes After Surgery Without Adjuvant Radioactive Iodine.

CONTEXT: Pediatric papillary thyroid carcinoma (PTC) is usually treated with total thyroidectomy followed by radioactive iodine (RAI). Recently, RAI is being used more selectively based on surgical pathology and postoperative dynamic risk stratification (DRS). OBJECTIVE: To describe patients with pediatric PTC not initially treated with RAI and their disease outcomes. METHODS: This was an ambispective study at a tertiary cancer center of patients < 19 years diagnosed from 1/1/1990 to 12/31/2021 with stage I PTC who intentionally were not treated with RAI within a year of diagnosis. We assessed clinical characteristics, management, and disease outcomes using DRS. RESULTS: Of 490 PTC patients, we identified 93 eligible patients (median age at diagnosis 16y; 87% female), including 46 (49%) with cervical lymph node metastases. Initial management included: total thyroidectomy ± neck dissection (n=69, 75%), lobectomy ± neck dissection (n=20, 21%), or a Sistrunk procedure for ectopic PTC (n=4, 4%). After a median follow-up of 5.5 years (range 1-26), most patients (85/93; 91%) remained disease-free with no further therapy. Persistent (n=5) or recurrent (n=3) disease was found in 9% of the entire cohort. Four patients ultimately received RAI, of which only one clearly benefited, and additional surgery was performed or planned in four patients, two of whom had an excellent response at last follow-up. CONCLUSIONS: Selected pediatric PTC patients, even those with lymph node metastases, may not require therapeutic 131I and can avoid the unnecessary risks of RAI while still benefitting from the excellent long-term outcomes that are well-described for this disease.

Potentially functional variants of CHMP4A and PANX1 in the pyroptosis-related pathway predict survival of patients with non-oropharyngeal head and neck squamous cell carcinoma.

BACKGROUND: Pyroptosis has been implicated in the advancement of various cancers. Triggering pyroptosis within tumors amplifies the immune response, thereby fostering an antitumor immune environment. Nonetheless, few published studies have evaluated associations between functional variants in the pyroptosis-related genes and clinical outcomes of patients with non-oropharyngeal head and neck squamous cell carcinoma (NON-ORO HNSCC). METHODS: We conducted an association study of 985 NON-ORO HNSCC patients who were randomly divided into two groups: the discovery group of 492 patients and the replication group of 493 patients. We used Cox proportional hazards regression analysis to examine associations between genetic variants of the pyroptosis-related genes and survival of patients with NON-ORO HNSCC. Bayesian false discovery probability (BFDP) was used for multiple testing correction. Functional annotation was applied to the identified survival-associated genetic variants. RESULTS: There are 8254 single-nucleotide polymorphisms (SNPs) located in 82 pyroptosis-related genes, of which 202 SNPs passed multiple testing correction with BFDP < 0.8 in the discovery and six SNPs retained statistically significant in the replication. In subsequent stepwise multivariable Cox regression analysis, two independent SNPs (CHMP4A rs1997996 G > A and PANX1 rs56175344 C > G) remained significant with an adjusted hazard ratios (HR) of 1.31 (95% confidence interval [CI] = 1.09-1.57, p = 0.004) and 0.65 (95% CI = 0.51-0.83, p = 0.0005) for overall survival (OS), respectively. Further analysis of the combined genotypes revealed progressively worse OS associated with the number of unfavorable genotypes (ptrend < 0.0001 and 0.021 for OS and disease-specific survival, respectively). Moreover, both PANX1 rs56175344G and CHMP4A rs1997996A alleles were correlated with reduced mRNA expression levels. CONCLUSIONS: Genetic variants in the pyroptosis pathway genes may predict the survival of NON-ORO HNSCC patients, likely by reducing the gene expression, but our findings need to be replicated by larger studies.

Outcomes for Patients With Head and Neck Sarcoma Treated Curatively With Radiation Therapy and Surgery.

PURPOSE: Soft tissue sarcomas (STSs) of the head and neck (H&N) are rare malignancies that are challenging to manage. We sought to describe the outcomes of patients treated with curative intent using combined surgery and radiation therapy (RT) for H&N STS. METHODS AND MATERIALS: We performed a single-institution retrospective review of patients with nonmetastatic STS of the H&N who were treated from 1968 to 2020. The Kaplan-Meier method was used to estimate disease-specific survival (DSS) and local control (LC). Multivariable analyses (MVAs) were conducted using Cox proportional hazards model. RESULTS: One hundred ninety-two patients had a median follow-up of 82 months. Tumors arose in the neck (n = 50, 26%), paranasal sinuses (n = 36, 19%), or face (n = 23, 12%). Most patients were treated with postoperative RT (n = 134, 70%). Postoperative RT doses were higher (median, 60 Gy; preoperative dose, 50 Gy; P < .001). Treatment sequence was not associated with LC (preoperative RT, 78% [63%-88%]; postoperative RT, 75% [66%-82%]; P = .48). On MVA, positive/uncertain margin was the only variable associated with LC (hazard ratio [HR], 2.54; 95% CI, 1.34-4.82; P = .004). LC was significant on MVA (HR, 4.48; 95% CI, 2.62-7.67; P < .001) for DSS. Patients who received postoperative RT were less likely to experience a major wound complication (7.5% vs 22.4%; HR, 0.28; 95% CI, 0.11-0.68; P = .005). There was no difference in the rate of late toxicities between patients who received preoperative or postoperative RT. CONCLUSIONS: H&N STS continues to have relatively poorer LC than STS of the trunk or extremities. We found LC to be associated with DSS. Timing of RT did not impact oncologic or long-term toxicity outcomes; however, preoperative RT did increase the chance of developing a major wound complication.

Cocaine use and head and neck cancer risk: A pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

BACKGROUND: Cocaine is an illegal recreational drug used worldwide, yet little is known about whether cocaine inhalation (smoking/snorting) increases the risk of head and neck cancer (HNC). METHODS: The analyses were conducted by pooling data from three case-control studies with 1639 cases and 2506 controls from the International Head and Neck Cancer Epidemiology Consortium. Epidemiologic data, including cocaine use histories, were obtained in face-to-face interviews. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using hierarchical logistic regression models. RESULTS: Controlling for cumulative tobacco and alcohol use, we observed a weak positive association between cocaine use and HNC (ORever vs. never = 1.35, 95% CI: 0.96, 1.90). In stratified analysis, while we did not detect associations among never tobacco or alcohol users due to the limited sample size, the association with cocaine use was observed among tobacco users and alcohol drinkers. ORs for ever and high cumulative use (>18 times) versus never use were 1.40 (95% CI: 0.98, 2.00) and 1.66 (95% CI: 1.03, 2.69) among tobacco users, and 1.34 (95% CI: 0.93, 1.92) and 1.59 (95% CI: 1.00, 2.51) among alcohol drinkers, respectively. CONCLUSION: In this pooled analysis, we observed a weak positive association between cocaine inhalation and HNC risk. Our findings provide preliminary evidence of the potential carcinogenic effect of cocaine on HNC. Because of study limitations, including limited number of cocaine users, confounding, and heterogeneity across studies, future investigations will require larger studies with more detailed information on cocaine use history.

Outcomes of Head and Neck Microvascular Free Tissue Transfer for Advanced Cutaneous Squamous Cell Carcinoma: A Comparison of Solid Organ Transplant Recipients to Nontransplant Patients.

BACKGROUND: Patients with solid organ transplant (SOT) are at increased risk of developing aggressive cutaneous malignancies due to their immunosuppression, particularly cutaneous squamous cell carcinoma (cSCC). PURPOSE: There is limited data regarding SOT patients with locally advanced cSCC requiring radical surgery and microvascular free tissue transfer (MVFTT). Our objectives were to characterize outcomes in SOT patients and compare them with a non-SOT cohort. STUDY DESIGN: This is a retrospective cohort study of patients undergoing MVFTT for advanced cSCC of the head and neck between January 2016 and May 2020 at a tertiary referral center. Patients who underwent MVFTT as part of curative intent surgery for advanced cSCC during the study were considered for inclusion. Exclusion criteria included distant metastasis, palliative intent treatment, age less than 18 years, and lip primaries. PREDICTOR: The predictor variable was SOT status. A cohort of non-SOT patients was matched to the SOT cohort based on age, smoking status, tumor stage, and defect size. MAIN OUTCOME VARIABLES: The primary reconstructive outcome was the major surgical complications and secondary outcome measures included major medical complications and minor surgical complications. The primary oncologic outcome was overall survival and the secondary outcome was disease-specific survival. The primary predictor was transplant status. COVARIATES: Covariates included patient comorbidities, prior treatment, tumor stage, type of reconstruction, pathologic findings, and adjuvant therapy. ANALYSIS: Continuous and categorical variables were compared using Student's T test and Fisher's exact test. Survival was calculated using the Kaplan-Meier method and differences in survival between groups were calculated using the log-rank test. Statistical significance was set a priori at P ≤ .05. RESULTS: Fourteen SOT and 14 matched non-SOT patients met inclusion criteria. There was not a statistically significant difference in the rate of major surgical complications (7 vs 7%, P = .74) between the SOT and non-SOT cohorts. Rates of minor (21 vs 43%, P = .26) wound complications and medical complications (0 vs 14%, P = .24) were also similar between the SOT and non-SOT cohorts. Locoregional recurrences and distant metastasis were more common for SOT patients, though this was not statistically significant. Overall survival was significantly worse for SOT patients (21.7 vs 31.0 months, P = .04), though there was not a significant difference in disease-free survival (9.8 vs 31.0 months, P = .17). CONCLUSIONS AND RELEVANCE: MVFTT in the management of SOT patients with locally advanced head and neck cSCC demonstrates similar complication rates with non-SOT patients. While survival and oncologic outcomes are worse in the SOT cohort, aggressive surgical intervention with MVFTT can be performed with comparable complication rates to patients without a history of SOT.