Aya F Salem, Melissa M Chen, Michelle D Williams, David M Swanson, Jennifer L McQuade, Rodabe N Amaria, Ehab Y Hanna, Andrew J Bishop, Ahsan S Farooqi, B Ashleigh Guadagnolo, Shirley Y Su, Devarati Mitra
Objective: We aim to evaluate outcomes for patients with resectable SNMM treated in the immunotherapy era.
Methods: Thirty-seven patients with resectable SNM were identified using our institutional database between 2016 and 2023.
Results: Patients receiving neoadjuvant Ipi/Nivo (46%, n = 17) were more likely to have disease involving the sinuses and/or the skull base (71% vs. 35%, p = 0.05). The overall response rate to Ipi/Nivo was 24%. Two-year LRFS from the start of therapy was 63%, and from the end of local therapy was 78%. Two-year PFS was 49%. The patients who received Ipi/Nivo with evidence of response (n = 4, 24%) had better PFS (2-year PFS 100% vs. 15%, p = 0.02) and LRFS (2-year LRFS 100% vs. 31%, p = 0.08).
Conclusions: Outcomes for resectable SNMM patients continue to be poor in the immunotherapy era. In the context of selection bias, neoadjuvant Ipi/Nivo was not associated with better outcomes in all-comers. However, those with evidence of response to Ipi/Nivo had better prognosis.
{"title":"Resectable Sinonasal Mucosal Melanoma in the Immunotherapy Era: Upfront Surgery vs. Neoadjuvant Therapy.","authors":"Aya F Salem, Melissa M Chen, Michelle D Williams, David M Swanson, Jennifer L McQuade, Rodabe N Amaria, Ehab Y Hanna, Andrew J Bishop, Ahsan S Farooqi, B Ashleigh Guadagnolo, Shirley Y Su, Devarati Mitra","doi":"10.1002/hed.28098","DOIUrl":"https://doi.org/10.1002/hed.28098","url":null,"abstract":"<p><strong>Objective: </strong>We aim to evaluate outcomes for patients with resectable SNMM treated in the immunotherapy era.</p><p><strong>Methods: </strong>Thirty-seven patients with resectable SNM were identified using our institutional database between 2016 and 2023.</p><p><strong>Results: </strong>Patients receiving neoadjuvant Ipi/Nivo (46%, n = 17) were more likely to have disease involving the sinuses and/or the skull base (71% vs. 35%, p = 0.05). The overall response rate to Ipi/Nivo was 24%. Two-year LRFS from the start of therapy was 63%, and from the end of local therapy was 78%. Two-year PFS was 49%. The patients who received Ipi/Nivo with evidence of response (n = 4, 24%) had better PFS (2-year PFS 100% vs. 15%, p = 0.02) and LRFS (2-year LRFS 100% vs. 31%, p = 0.08).</p><p><strong>Conclusions: </strong>Outcomes for resectable SNMM patients continue to be poor in the immunotherapy era. In the context of selection bias, neoadjuvant Ipi/Nivo was not associated with better outcomes in all-comers. However, those with evidence of response to Ipi/Nivo had better prognosis.</p>","PeriodicalId":55072,"journal":{"name":"Head and Neck-Journal for the Sciences and Specialties of the Head and Neck","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neel R Sangal, Katherine Xu, Praneet Kaki, Steven Cannady, Robert M Brody
Importance: Laryngeal cancer has undergone a complex evolution in incidence, management, and standards of care over the past 20 years. Disease-wide demographic and survival risk factors have yet to be elucidated.
Objective: Examine incidence, management, and survival trends in laryngeal cancer from 2000 to 2019.
Design, setting, and participants: The Surveillance, Epidemiology, and End Results database was utilized to identify age-adjusted incidence rates (AAIRs) of laryngeal squamous cell carcinoma (LSCCa) from 2000 to 2019. Joinpoint regression was conducted to identify annual percentage changes (APCs). Chi-squared analysis was used to find changes in demographic, clinicopathologic, and treatment changes over the study period. Finally, univariate Kaplan-Meier and COX multivariate regressions were conducted to identify survival differences.
Results: There were 46 266 cases of LSCCa identified between 2000 and 2019 with AAIR of 2.7 per 100 000 person-years with APC of -2.6% [95% CI: -2.8% to 2.4%]. These rates have largely been down-trending among demographic substratifications. Age at initial diagnosis has been increasing (64.6 → 66.0, p < 0.001). Higher median household income was associated with lower AAIR (35 000 5.3; > $75 000 2.2) and increased annual percentage decrease (< $35 000, -1.1%*; > $75 000, -3.2%*). There were no other clinically significant differences in demographic and clinicopathologic trends although persistent demographic differences were noted. Late T-stage at diagnosis has increased over the study period (T3, 18% → 23%, p < 0.001). Treatment with primary chemoradiotherapy has increased significantly (20.0% → 27.0%, p < 0.001). On univariate analysis, there were no significant differences in survival; however, on multivariate analysis, there has been a progressive improvement in disease-specific and overall survival over 5-year bins. Late-stage disease had a progressive improvement in survival with each treatment period on both univariate and multivariate analysis.
Conclusions and relevance: There has been a progressively significant decrease in age-adjusted incidence of LSCCa with increased utilization of primary chemoradiotherapy. When adjusted for associated characteristics, there has been a continuing improvement in survival over the study period, primarily in late-stage disease.
{"title":"Laryngeal Squamous Cell Carcinoma Incidence and Survival Trends in the United States: A Population-Based Analysis of Two Decades.","authors":"Neel R Sangal, Katherine Xu, Praneet Kaki, Steven Cannady, Robert M Brody","doi":"10.1002/hed.28077","DOIUrl":"https://doi.org/10.1002/hed.28077","url":null,"abstract":"<p><strong>Importance: </strong>Laryngeal cancer has undergone a complex evolution in incidence, management, and standards of care over the past 20 years. Disease-wide demographic and survival risk factors have yet to be elucidated.</p><p><strong>Objective: </strong>Examine incidence, management, and survival trends in laryngeal cancer from 2000 to 2019.</p><p><strong>Design, setting, and participants: </strong>The Surveillance, Epidemiology, and End Results database was utilized to identify age-adjusted incidence rates (AAIRs) of laryngeal squamous cell carcinoma (LSCCa) from 2000 to 2019. Joinpoint regression was conducted to identify annual percentage changes (APCs). Chi-squared analysis was used to find changes in demographic, clinicopathologic, and treatment changes over the study period. Finally, univariate Kaplan-Meier and COX multivariate regressions were conducted to identify survival differences.</p><p><strong>Results: </strong>There were 46 266 cases of LSCCa identified between 2000 and 2019 with AAIR of 2.7 per 100 000 person-years with APC of -2.6% [95% CI: -2.8% to 2.4%]. These rates have largely been down-trending among demographic substratifications. Age at initial diagnosis has been increasing (64.6 → 66.0, p < 0.001). Higher median household income was associated with lower AAIR (35 000 5.3; > $75 000 2.2) and increased annual percentage decrease (< $35 000, -1.1%*; > $75 000, -3.2%*). There were no other clinically significant differences in demographic and clinicopathologic trends although persistent demographic differences were noted. Late T-stage at diagnosis has increased over the study period (T3, 18% → 23%, p < 0.001). Treatment with primary chemoradiotherapy has increased significantly (20.0% → 27.0%, p < 0.001). On univariate analysis, there were no significant differences in survival; however, on multivariate analysis, there has been a progressive improvement in disease-specific and overall survival over 5-year bins. Late-stage disease had a progressive improvement in survival with each treatment period on both univariate and multivariate analysis.</p><p><strong>Conclusions and relevance: </strong>There has been a progressively significant decrease in age-adjusted incidence of LSCCa with increased utilization of primary chemoradiotherapy. When adjusted for associated characteristics, there has been a continuing improvement in survival over the study period, primarily in late-stage disease.</p>","PeriodicalId":55072,"journal":{"name":"Head and Neck-Journal for the Sciences and Specialties of the Head and Neck","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katrin Håkansson, Daha Hassan Muse, Anna Bäck, Jacob H Rasmussen, Anne Marie Lindegaard, Lena Specht, Jeppe Friborg, Hedda Haugen Cange, Ivan R Vogelius
Background: A previously published failure-type specific risk model showed good performance in the original cohort.
Aim: to validate the model and separate patients with high- and low-risk loco-regional failure (LRF).
Goal: to identify patients potentially suitable for treatment intensification trials.
Methods: Validation data: 756 patients from two institutions (different countries). Predictive performance was evaluated by Brier scores and AUCs. Discriminatory performance was compared to Union for International Cancer Control (UICC) staging (versions 7 and 8).
Results: The model's 3-year AUC for LRF was 65%, significantly better than UICC7 staging, but no significant difference to UICC8. Model-based risk stratification and UICC8 both identified high-risk patient groups with 3-year LRF ≈30%. The population mean was 18%.
Conclusions: The model performed well on a group level. UICC8 staging performed equally well. Although developed for the endpoint of OS, an improvement from UICC version 7 to version 8 was evident also for the prediction of LRF.
{"title":"Risk Stratification for Trial Enrichment Considering Loco-Regional Failure in Head and Neck Cancer: UICC8 Versus Purpose-Built Failure-Type Specific Risk Prediction Model.","authors":"Katrin Håkansson, Daha Hassan Muse, Anna Bäck, Jacob H Rasmussen, Anne Marie Lindegaard, Lena Specht, Jeppe Friborg, Hedda Haugen Cange, Ivan R Vogelius","doi":"10.1002/hed.28085","DOIUrl":"https://doi.org/10.1002/hed.28085","url":null,"abstract":"<p><strong>Background: </strong>A previously published failure-type specific risk model showed good performance in the original cohort.</p><p><strong>Aim: </strong>to validate the model and separate patients with high- and low-risk loco-regional failure (LRF).</p><p><strong>Goal: </strong>to identify patients potentially suitable for treatment intensification trials.</p><p><strong>Methods: </strong>Validation data: 756 patients from two institutions (different countries). Predictive performance was evaluated by Brier scores and AUCs. Discriminatory performance was compared to Union for International Cancer Control (UICC) staging (versions 7 and 8).</p><p><strong>Results: </strong>The model's 3-year AUC for LRF was 65%, significantly better than UICC7 staging, but no significant difference to UICC8. Model-based risk stratification and UICC8 both identified high-risk patient groups with 3-year LRF ≈30%. The population mean was 18%.</p><p><strong>Conclusions: </strong>The model performed well on a group level. UICC8 staging performed equally well. Although developed for the endpoint of OS, an improvement from UICC version 7 to version 8 was evident also for the prediction of LRF.</p>","PeriodicalId":55072,"journal":{"name":"Head and Neck-Journal for the Sciences and Specialties of the Head and Neck","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The role of post-operative radiotherapy (PORT) in early-stage (T1-T2N0M0) oral tongue squamous cell carcinoma (OTSCC) with minor adverse features (MAF) including perineural invasion (PNI) and poorly differentiated carcinoma (PDC) is not well described. We aimed to study the role of PORT among these patients.
Methods: A retrospective review of patients treated for early-stage OTSCC between 2000 and 2022 in a tertiary-care referral center while comparing patients treated by surgery and PORT with patients treated by surgery alone.
Results: One hundred fifty-four patients were included and 36 (23.4%) received PORT. The PORT subgroup had a significantly higher rate of MAF. Survival rates were similar between the two sub-groups. PORT demonstrated a trend toward improved overall survival (odds ratio = 0.406, p = 0.07). Patients with PNI or PDC treated with PORT experienced improved survival rates.
Conclusion: PORT has an important role when treating early-stage OTSCC with MAF. It should be considered especially among patients with PNI or PDC.
{"title":"The Role of Adjuvant Radiotherapy for Early-Stage Oral Cavity Cancer With Minor Adverse Features; A Single Institute Experience.","authors":"Eyal Yosefof, Nofar Edri, Noga Kurman, Gideon Bachar, Thomas Shpitzer, Aviram Mizrachi, Aron Popovtzer","doi":"10.1002/hed.28093","DOIUrl":"https://doi.org/10.1002/hed.28093","url":null,"abstract":"<p><strong>Background: </strong>The role of post-operative radiotherapy (PORT) in early-stage (T1-T2N0M0) oral tongue squamous cell carcinoma (OTSCC) with minor adverse features (MAF) including perineural invasion (PNI) and poorly differentiated carcinoma (PDC) is not well described. We aimed to study the role of PORT among these patients.</p><p><strong>Methods: </strong>A retrospective review of patients treated for early-stage OTSCC between 2000 and 2022 in a tertiary-care referral center while comparing patients treated by surgery and PORT with patients treated by surgery alone.</p><p><strong>Results: </strong>One hundred fifty-four patients were included and 36 (23.4%) received PORT. The PORT subgroup had a significantly higher rate of MAF. Survival rates were similar between the two sub-groups. PORT demonstrated a trend toward improved overall survival (odds ratio = 0.406, p = 0.07). Patients with PNI or PDC treated with PORT experienced improved survival rates.</p><p><strong>Conclusion: </strong>PORT has an important role when treating early-stage OTSCC with MAF. It should be considered especially among patients with PNI or PDC.</p>","PeriodicalId":55072,"journal":{"name":"Head and Neck-Journal for the Sciences and Specialties of the Head and Neck","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The AJCC cutoff value of 2 mm for the extranodal extension (ENE) distance was determined from an analysis of patients with or without adjuvant therapy. The purpose of this study was to find out the ENE distance that reflects prognosis only in patients with head and neck squamous cell carcinoma (SCC) who received adjuvant therapy.
Methods: The ENE distance was defined for 109 patients who underwent surgery for SCC of larynx or hypopharynx as a primary tumor.
Results: To standardize patient conditions, only 26 patients who received additional postoperative treatment were analyzed. Receiver operating characteristic analysis of the ENE distance for overall survival (OS) and recurrence-free survival (RFS) yielded a cutoff value of 4250 μm. Multivariate analysis showed that the ENE distance was an independent poor prognostic factor for OS and RFS.
Conclusion: The optimal ENE distance cutoff for OS and RFS in postoperatively treated patients was 4250 μm.
{"title":"Clinicopathological Significance of Extranodal Extension in Hypopharyngeal and Laryngeal Squamous Cell Carcinoma.","authors":"Natsumi Kijima, Yui Uzawa, Yuri Hirai, Yusuke Nojima, Jun Aoyama, Hideaki Takahashi, Yasuhiro Arai, Daisuke Sano, Goshi Nishimura, Nobuhiko Oridate, Satoshi Fujii","doi":"10.1002/hed.28090","DOIUrl":"https://doi.org/10.1002/hed.28090","url":null,"abstract":"<p><strong>Background: </strong>The AJCC cutoff value of 2 mm for the extranodal extension (ENE) distance was determined from an analysis of patients with or without adjuvant therapy. The purpose of this study was to find out the ENE distance that reflects prognosis only in patients with head and neck squamous cell carcinoma (SCC) who received adjuvant therapy.</p><p><strong>Methods: </strong>The ENE distance was defined for 109 patients who underwent surgery for SCC of larynx or hypopharynx as a primary tumor.</p><p><strong>Results: </strong>To standardize patient conditions, only 26 patients who received additional postoperative treatment were analyzed. Receiver operating characteristic analysis of the ENE distance for overall survival (OS) and recurrence-free survival (RFS) yielded a cutoff value of 4250 μm. Multivariate analysis showed that the ENE distance was an independent poor prognostic factor for OS and RFS.</p><p><strong>Conclusion: </strong>The optimal ENE distance cutoff for OS and RFS in postoperatively treated patients was 4250 μm.</p>","PeriodicalId":55072,"journal":{"name":"Head and Neck-Journal for the Sciences and Specialties of the Head and Neck","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emma Charters, Jessica Boehm, Anita Macdonald D'Silva, Raymond Wu, Simon A Mueller, Tsu-Hui Hubert Low, Jonathan R Clark, James Wykes
Background: Subtotal and total glossectomies for advanced tongue cancer result in significant speech- and swallow-related morbidity, impairing quality of life. This prospective pilot study compares the safety and functional outcomes associated with using a chimeric innervated muscle and fasciocutaneous flap for soft tissue reconstruction.
Materials and methods: A prospective, non-randomized controlled pilot study evaluated a standardized technique for tongue reconstruction using a chimeric innervated vastus lateralis muscle and anterolateral thigh fasciocutaneous flap. Inclusion criteria were ≥ 50% resection of the oral tongue. Participants were followed longitudinally, with measures recorded at baseline, 6-8 weeks, 6 months, and 12 months after surgery. The primary endpoints were post-operative complications, time to radiotherapy, operative time, and locoregional failure, videofluoroscopy swallow studies (dynamic imaging grade of swallowing toxicity (DIGEST), penetration and aspiration score, performance status scale for head and neck). Secondary endpoints were patient-rated outcomes.
Results: Eighteen participants were recruited (10 intervention: 8 controls). Fourteen (78%) experienced complications, only one of which was related to the innervated flap. DIGEST scores deteriorated post-operatively across all participants but did not differ significantly between the intervention and control groups (p = 0.4) at any point post-surgery, despite more extensive resections in the intervention group. Those in the intervention group had better patient-rated intelligibility (p = 0.04). Multimodality treatment was associated with worse speech (p = 0.03) and normalcy of diet (p = 0.02). Less extensive resections were associated with better scores in eating in public (p = 0.005), tongue range of movement (p = 0.0008), intelligibility (p = 0.006), and diet (p = 0.001).
Conclusions: The innervated vastus lateralis and antero-lateral thigh free-flap technique is safe and improves speech intelligibility for patients with subtotal and total glossectomy defects. However, the technique requires refinement to optimize functional and quality-of-life outcomes.
{"title":"A Pilot Trial of Tongue Reconstruction Using the Chimeric Innervated Vastus Lateralis Muscle and Antero-Lateral Thigh Free Flap.","authors":"Emma Charters, Jessica Boehm, Anita Macdonald D'Silva, Raymond Wu, Simon A Mueller, Tsu-Hui Hubert Low, Jonathan R Clark, James Wykes","doi":"10.1002/hed.28087","DOIUrl":"https://doi.org/10.1002/hed.28087","url":null,"abstract":"<p><strong>Background: </strong>Subtotal and total glossectomies for advanced tongue cancer result in significant speech- and swallow-related morbidity, impairing quality of life. This prospective pilot study compares the safety and functional outcomes associated with using a chimeric innervated muscle and fasciocutaneous flap for soft tissue reconstruction.</p><p><strong>Materials and methods: </strong>A prospective, non-randomized controlled pilot study evaluated a standardized technique for tongue reconstruction using a chimeric innervated vastus lateralis muscle and anterolateral thigh fasciocutaneous flap. Inclusion criteria were ≥ 50% resection of the oral tongue. Participants were followed longitudinally, with measures recorded at baseline, 6-8 weeks, 6 months, and 12 months after surgery. The primary endpoints were post-operative complications, time to radiotherapy, operative time, and locoregional failure, videofluoroscopy swallow studies (dynamic imaging grade of swallowing toxicity (DIGEST), penetration and aspiration score, performance status scale for head and neck). Secondary endpoints were patient-rated outcomes.</p><p><strong>Results: </strong>Eighteen participants were recruited (10 intervention: 8 controls). Fourteen (78%) experienced complications, only one of which was related to the innervated flap. DIGEST scores deteriorated post-operatively across all participants but did not differ significantly between the intervention and control groups (p = 0.4) at any point post-surgery, despite more extensive resections in the intervention group. Those in the intervention group had better patient-rated intelligibility (p = 0.04). Multimodality treatment was associated with worse speech (p = 0.03) and normalcy of diet (p = 0.02). Less extensive resections were associated with better scores in eating in public (p = 0.005), tongue range of movement (p = 0.0008), intelligibility (p = 0.006), and diet (p = 0.001).</p><p><strong>Conclusions: </strong>The innervated vastus lateralis and antero-lateral thigh free-flap technique is safe and improves speech intelligibility for patients with subtotal and total glossectomy defects. However, the technique requires refinement to optimize functional and quality-of-life outcomes.</p>","PeriodicalId":55072,"journal":{"name":"Head and Neck-Journal for the Sciences and Specialties of the Head and Neck","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karim Botros, Khashayar Esfahani, Khalil Sultanem, Jonathan D Spicer, Alex A Mlynarek, Michael P Hier, Marco A Mascarella
Background: Airway obstruction secondary to chyle leak is an exceptionally rare phenomenon. Here, we describe this complication in a patient with anaplastic thyroid carcinoma (ATC) undergoing consolidative surgery after BRAF-targeted therapy.
Methods: A 55-year-old man presented with a rapidly enlarging neck mass. Work-up was consistent with metastatic unresectable BRAFV600E-mutant ATC. After a remarkable response to neoadjuvant dabrafenib and trametinib, he underwent curative-intent surgery with a right hemithyroidectomy and bilateral neck dissection. Within 48 h, he developed an expanding left neck mass with laryngeal obstruction due to a chyle leak.
Results: Despite surgical repair and maximal medical therapy, the leak persisted necessitating thoracoscopic ligation of the thoracic duct. Final pathology showed a completely excised residual tumor. The patient remains disease-free on long-term dabrafenib and trametinib.
Conclusions: BRAF-directed therapy has transformed the care of patients with mutated ATC. As more patients undergo consolidative surgery, increased vigilance is paramount in minimizing complications and their associated morbidity.
{"title":"\"Tension Chyle Leak\": A Life-Threatening Sequela of Thoracic Duct Injury Following Resection of BRAF-Mutated Anaplastic Thyroid Carcinoma.","authors":"Karim Botros, Khashayar Esfahani, Khalil Sultanem, Jonathan D Spicer, Alex A Mlynarek, Michael P Hier, Marco A Mascarella","doi":"10.1002/hed.28091","DOIUrl":"https://doi.org/10.1002/hed.28091","url":null,"abstract":"<p><strong>Background: </strong>Airway obstruction secondary to chyle leak is an exceptionally rare phenomenon. Here, we describe this complication in a patient with anaplastic thyroid carcinoma (ATC) undergoing consolidative surgery after BRAF-targeted therapy.</p><p><strong>Methods: </strong>A 55-year-old man presented with a rapidly enlarging neck mass. Work-up was consistent with metastatic unresectable BRAF<sup>V600E</sup>-mutant ATC. After a remarkable response to neoadjuvant dabrafenib and trametinib, he underwent curative-intent surgery with a right hemithyroidectomy and bilateral neck dissection. Within 48 h, he developed an expanding left neck mass with laryngeal obstruction due to a chyle leak.</p><p><strong>Results: </strong>Despite surgical repair and maximal medical therapy, the leak persisted necessitating thoracoscopic ligation of the thoracic duct. Final pathology showed a completely excised residual tumor. The patient remains disease-free on long-term dabrafenib and trametinib.</p><p><strong>Conclusions: </strong>BRAF-directed therapy has transformed the care of patients with mutated ATC. As more patients undergo consolidative surgery, increased vigilance is paramount in minimizing complications and their associated morbidity.</p>","PeriodicalId":55072,"journal":{"name":"Head and Neck-Journal for the Sciences and Specialties of the Head and Neck","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Erica McArdle, Mustafa Bulbul, Chantz Collins, Umamaheswar Duvvuri, Neil Gross, Meghan Turner
Background: Human papillomavirus (HPV) negative oropharyngeal squamous cell carcinoma (OPSCC) is associated with worse survival when compared to HPV-positive OPSCC. Primary surgery is one option to intensify therapy in this high-risk group of patients. Unfortunately, the only randomized trial to explore this approach (RTOG 1221) failed to accrue and the role of primary surgery in the treatment of HPV-negative OPSCC remains unanswered.
Methods: A systematic review and meta-analysis were performed to examine the outcomes of surgery in the treatment of HPV-negative OPSCC. We used the PRISMA statement for reporting and queried Pubmed, Web of Science and the Cochrane databases for studies examining the use of primary surgery in the treatment of HPV-negative OPSCC. Excluded from analysis were reviews, commentaries, case series with fewer than 10 patients, and studies that included HPV-negative head and neck cancers of mixed sites. Our primary outcomes were 2-year and 5-year overall survival (OS) and disease-free survival (DFS). OS and DFS were pooled using meta-analysis of proportions.
Results: A total of 15 studies were included in qualitative synthesis and 11 were included in the meta-analysis. There were 923 patients total included. Eight studies including 483 patients reported staging of HPV negative disease, of which 81.6% had T1/T2 tumors and 41.4% had N0 nodal disease. The average rate of positive margins was 12.6%. The average rate of patients who underwent risk-stratified adjuvant RT was 30.7% and CRT was 29.5%. The average follow-up was 32.7 months (SD = 12.47 months). Only two studies reported survival outcomes for HPV-negative disease based on overall staging: 5-year OS was improved for stage III versus stage IV and early versus late stage disease. The pooled 2- and 5-year OS were 84% (95% CI 77%-91%, I2 = 52.4%; 5 studies) and 72% (95% CI 46%-92%, I2 = 95.5%; 4 studies), respectively. The pooled 2- and 5-year DFS for the entire population were 77% (95% CI 66%-86%, I2 = 55%; 6 studies) and 59% (95% CI 50%-69%, I2 = 0%; 3 studies). Of the subgroup undergoing TOS alone, the pooled 2- and 5-year OS were 87% (95% CI 79%-93%, I2 = 46.8%; 4 studies) and 82% (95% CI 69%-92%, I2 = 74.2%; 3 studies). The pooled 2- and 5-year DFS for the subgroup of patients undergoing TOS alone were 78% (95% CI 63%-90%, I2 = 56%; 4 studies) and 59% (95% CI 47%-71%, I2 = undetermined; 2 studies).
Conclusions: The two- and five-year OS for patients with HPV-negative OPSCC treated with any surgical approach and pathology-directed adjuvant therapy is 84% and 72%, respectively. The two- and five-year OS for HPV-negative OPCSCC treated with transoral surgery and pathology-directed adjuvant therapy is 87% and 82%, respectively.
{"title":"Surgery for the Treatment of HPV-Negative Oropharyngeal Squamous Cell Carcinoma-A Systematic Review and Meta-Analysis.","authors":"Erica McArdle, Mustafa Bulbul, Chantz Collins, Umamaheswar Duvvuri, Neil Gross, Meghan Turner","doi":"10.1002/hed.28088","DOIUrl":"https://doi.org/10.1002/hed.28088","url":null,"abstract":"<p><strong>Background: </strong>Human papillomavirus (HPV) negative oropharyngeal squamous cell carcinoma (OPSCC) is associated with worse survival when compared to HPV-positive OPSCC. Primary surgery is one option to intensify therapy in this high-risk group of patients. Unfortunately, the only randomized trial to explore this approach (RTOG 1221) failed to accrue and the role of primary surgery in the treatment of HPV-negative OPSCC remains unanswered.</p><p><strong>Methods: </strong>A systematic review and meta-analysis were performed to examine the outcomes of surgery in the treatment of HPV-negative OPSCC. We used the PRISMA statement for reporting and queried Pubmed, Web of Science and the Cochrane databases for studies examining the use of primary surgery in the treatment of HPV-negative OPSCC. Excluded from analysis were reviews, commentaries, case series with fewer than 10 patients, and studies that included HPV-negative head and neck cancers of mixed sites. Our primary outcomes were 2-year and 5-year overall survival (OS) and disease-free survival (DFS). OS and DFS were pooled using meta-analysis of proportions.</p><p><strong>Results: </strong>A total of 15 studies were included in qualitative synthesis and 11 were included in the meta-analysis. There were 923 patients total included. Eight studies including 483 patients reported staging of HPV negative disease, of which 81.6% had T1/T2 tumors and 41.4% had N0 nodal disease. The average rate of positive margins was 12.6%. The average rate of patients who underwent risk-stratified adjuvant RT was 30.7% and CRT was 29.5%. The average follow-up was 32.7 months (SD = 12.47 months). Only two studies reported survival outcomes for HPV-negative disease based on overall staging: 5-year OS was improved for stage III versus stage IV and early versus late stage disease. The pooled 2- and 5-year OS were 84% (95% CI 77%-91%, I<sup>2</sup> = 52.4%; 5 studies) and 72% (95% CI 46%-92%, I<sup>2</sup> = 95.5%; 4 studies), respectively. The pooled 2- and 5-year DFS for the entire population were 77% (95% CI 66%-86%, I<sup>2</sup> = 55%; 6 studies) and 59% (95% CI 50%-69%, I<sup>2</sup> = 0%; 3 studies). Of the subgroup undergoing TOS alone, the pooled 2- and 5-year OS were 87% (95% CI 79%-93%, I<sup>2</sup> = 46.8%; 4 studies) and 82% (95% CI 69%-92%, I<sup>2</sup> = 74.2%; 3 studies). The pooled 2- and 5-year DFS for the subgroup of patients undergoing TOS alone were 78% (95% CI 63%-90%, I<sup>2</sup> = 56%; 4 studies) and 59% (95% CI 47%-71%, I<sup>2</sup> = undetermined; 2 studies).</p><p><strong>Conclusions: </strong>The two- and five-year OS for patients with HPV-negative OPSCC treated with any surgical approach and pathology-directed adjuvant therapy is 84% and 72%, respectively. The two- and five-year OS for HPV-negative OPCSCC treated with transoral surgery and pathology-directed adjuvant therapy is 87% and 82%, respectively.</p>","PeriodicalId":55072,"journal":{"name":"Head and Neck-Journal for the Sciences and Specialties of the Head and Neck","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The detection rate of oncogenic human papillomaviruses (HPVs) in sinonasal squamous cell carcinomas (SNSCCs) varies among studies. The mutational landscape of SNSCCs remains poorly investigated.
Methods: We investigated the prevalence and prognostic significance of HPV infections based on p16 protein expression, HPV-DNA detection, and E6/E7 mRNA expression using immunohistochemistry, polymerase chain reaction, and in situ hybridization, respectively. In addition, we evaluated the genetic mutations in 59 patients using next-generation sequencing.
Results: One-third of the SNSCCs were truly oncogenic HPV-driven tumors associated with a nonkeratinizing morphology (p = 0.01) and did not correlate with the prognosis. The following gene mutations were detected: TP53, PIK3CA, CDKN2A, EGFR, and FGFR3. These mutations occurred alone, in association with, or with oncogenic HPV.
Conclusion: One-third of SNSCCs were high-risk HPV driven lesions. However, gene mutations and HR-HPV infections are not mutually exclusive. Further studies are required to analyze the prognostic value of these associations.
{"title":"Oncogenic Human Papillomaviruses Drive One-Third of Sinonasal Squamous Cell Carcinoma and Are Not Mutually Exclusive for Gene Mutations.","authors":"Maxime Henrion, Valérie Costes-Martineau, Ignacio González Bravo, Nathalie Boulle, Jérôme Solassol, Julie Vendrell, Renaud Garrel, Aude Trinquet, Vanessa Lacheretz-Szablewski","doi":"10.1002/hed.28084","DOIUrl":"https://doi.org/10.1002/hed.28084","url":null,"abstract":"<p><strong>Background: </strong>The detection rate of oncogenic human papillomaviruses (HPVs) in sinonasal squamous cell carcinomas (SNSCCs) varies among studies. The mutational landscape of SNSCCs remains poorly investigated.</p><p><strong>Methods: </strong>We investigated the prevalence and prognostic significance of HPV infections based on p16 protein expression, HPV-DNA detection, and E6/E7 mRNA expression using immunohistochemistry, polymerase chain reaction, and in situ hybridization, respectively. In addition, we evaluated the genetic mutations in 59 patients using next-generation sequencing.</p><p><strong>Results: </strong>One-third of the SNSCCs were truly oncogenic HPV-driven tumors associated with a nonkeratinizing morphology (p = 0.01) and did not correlate with the prognosis. The following gene mutations were detected: TP53, PIK3CA, CDKN2A, EGFR, and FGFR3. These mutations occurred alone, in association with, or with oncogenic HPV.</p><p><strong>Conclusion: </strong>One-third of SNSCCs were high-risk HPV driven lesions. However, gene mutations and HR-HPV infections are not mutually exclusive. Further studies are required to analyze the prognostic value of these associations.</p>","PeriodicalId":55072,"journal":{"name":"Head and Neck-Journal for the Sciences and Specialties of the Head and Neck","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael Schachtel, Mitesh Gandhi, James Bowman, Mark Midwinter, Benedict Panizza
Background: Standardized surgical approaches to advanced pre-auricular cutaneous squamous cell carcinomas (cSCC) are lacking.
Methods: Fifty-four patients who underwent lateral temporal bone resection (LTBR) for pre-auricular cSCC were grouped into "Levels" of increasing disease spread. Surgical approaches to achieve negative-margin resection were designed for each Level and replicated on cadaveric specimens.
Results: Level 1 extended to the external auditory canal, requiring LTBR ± superficial parotidectomy. Level 2 involved the retromandibular space ± temporomandibular joint, necessitating partial mandibulectomy, in addition to the above. Level 3 and 4 involved the deep parotid, being situated either away from (> 5 mm) or close (≤ 5 mm) to the anterior carotid sheath (ACS), respectively. These tumors require radical parotidectomy, with incorporation of the ACS for Level 4. Level 5 involved the ACS at the skull base and should be treated non-surgically.
Conclusion: This Level-based system will hopefully lead to further prospective studies and improvements in outcomes for advanced pre-auricular cSCC.
{"title":"Surgical Approaches to Pre-Auricular Cutaneous Squamous Cell Carcinomas Extending to the Temporal Bone.","authors":"Michael Schachtel, Mitesh Gandhi, James Bowman, Mark Midwinter, Benedict Panizza","doi":"10.1002/hed.28073","DOIUrl":"https://doi.org/10.1002/hed.28073","url":null,"abstract":"<p><strong>Background: </strong>Standardized surgical approaches to advanced pre-auricular cutaneous squamous cell carcinomas (cSCC) are lacking.</p><p><strong>Methods: </strong>Fifty-four patients who underwent lateral temporal bone resection (LTBR) for pre-auricular cSCC were grouped into \"Levels\" of increasing disease spread. Surgical approaches to achieve negative-margin resection were designed for each Level and replicated on cadaveric specimens.</p><p><strong>Results: </strong>Level 1 extended to the external auditory canal, requiring LTBR ± superficial parotidectomy. Level 2 involved the retromandibular space ± temporomandibular joint, necessitating partial mandibulectomy, in addition to the above. Level 3 and 4 involved the deep parotid, being situated either away from (> 5 mm) or close (≤ 5 mm) to the anterior carotid sheath (ACS), respectively. These tumors require radical parotidectomy, with incorporation of the ACS for Level 4. Level 5 involved the ACS at the skull base and should be treated non-surgically.</p><p><strong>Conclusion: </strong>This Level-based system will hopefully lead to further prospective studies and improvements in outcomes for advanced pre-auricular cSCC.</p>","PeriodicalId":55072,"journal":{"name":"Head and Neck-Journal for the Sciences and Specialties of the Head and Neck","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}