Dedifferentiation of a Chondrosarcoma of the Larynx: A Case Report

ABSTRACT Background Chondrosarcomas of the larynx, relatively rare tumors with low grade pathology in approximately 95% of cases, can most often be managed with conservation laryngeal procedures. Dedifferentiated chondrosarcomas are much more rare and aggressive requiring more aggressive surgical extirpation. Methods A patient underwent three debulking procedures for a laryngeal chondrosarcoma Grade I/II histologically over a 2.5 year period of time during which slow growth was closely monitored. He then presented with relatively rapid onset of hoarseness and shortness of breath. Fiberoptic laryngoscopy demonstrated new bilateral vocal fold fixation with near occlusion of his subglottis by soft tissue mass. Results A total laryngectomy was performed that pathologically demonstrated a Grade III dedifferentiated chondrosarcoma. Shortly thereafter, the patient developed regional metastases, then distant metastases and then succumbed to the disease. Conclusion This first case of a Grade III dedifferentiating chondrosarcoma arising from closely monitored and multiple debulked previously Grade I/II tumor demonstrates the potential change in aggressiveness in low‐grade chondrosarcomas of the larynx. Sudden increase in growth along with a soft tissue component to the tumor based on exam and/or imaging should heighten suspicion for dedifferentiation of the tumor and necessitates a more aggressive surgical resection. However, the chance of cure once dedifferentiation occurs is drastically reduced.

Decompression Obturator Prostheses in the Treatment of Cystic Odontogenic Lesions: A Case Series and Review of the Literature

ABSTRACT Background To spare important anatomical structures from damage during treatment of cystic odontogenic lesions, decompression has become a conservative alternative to enucleation. Marsupialization, in combination with the use of a custom‐made decompression prosthesis, is an effective method of inducing reduction and bony infill of cystic lesions of the jaw. Methods In this case series and review of the literature, we describe three patients with odontogenic cysts of the mandible who were treated with custom‐made decompression obturator prostheses (DOP) at the Memorial Sloan Kettering Cancer Center Dental Service. Results At the conclusion of treatment, all patients demonstrated complete resolution of their respective bony defects. Conclusion DOP provide effective means of keeping the cyst opening patent following marsupialization, which allows for adequate, if not complete, resolution of defects, often without need for subsequent enucleation.

Geriatric Nutritional Risk Index and Postoperative Outcomes Following Head and Neck Cancer Surgery

ABSTRACT Background The geriatric nutritional risk index (GNRI) is a tool to assess preoperative nutritional status that can be calculated simply based on height, weight, and serum albumin. This study assesses the utility of GNRI in predicting postoperative complications in patients undergoing major head and neck cancer (HNC) surgery. Methods Retrospective review of the 2016–2020 National Surgical Quality Improvement Program database. Patients were categorized into GNRI > 98 (normal nutritional status), GNRI 92–98 (moderate malnutrition status), and GNRI < 92 (severe malnutrition status). Univariable and multivariable binary logistic regression analyses were performed. Results Sixteen thousand seven hundred eight‐nine patients undergoing HNC resection were included. On multivariable analysis, moderate and severe malnourishment based on GNRI remained significantly associated with any surgical complication, any medical complication, any complication, Clavien‐Dindo grade IV complications, and 30‐day mortality. Conclusions GNRI may have utility as a potentially modifiable preoperative prognostic factor that can be optimized to improve complications and mortality following HNC resection. Level of Evidence Level 4.

Laryngeal Squamous Cell Carcinoma Incidence and Survival Trends in the United States: A Population‐Based Analysis of Two Decades

ABSTRACT 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.

Paranasal Sinus and Nasal Cavity Cancers: Systematic Review and Executive Summary of the American Radium Society Appropriate Use Criteria

ABSTRACT Tumors of the paranasal sinus and nasal cavity (PNS/NC) are rare and exhibit diverse histology, anatomic subsite, and malignant potential. Early‐stage disease is typically managed with surgery, and locally advanced disease is treated with a combination of surgery, radiotherapy, and chemotherapy. Clinical decision‐making is commonly guided by limited retrospective evidence. To address this limitation, we performed a systematic review to inform evidence‐based consensus for the management of common clinical scenarios, including the potential roles of radiation and systemic therapy to promote structural preservation, elective neck management, and radiation technique considerations. A librarian‐mediated literature search identified 39 studies of adult patients with PNS/NC tumors treated with curative intent that met the study inclusion criteria. Search results were reported using the preferred reporting items for systematic reviews and meta‐analyses (PRISMA) methodology. A modified‐Delphi process was used to guide consensus for the appropriate use of various management strategies. Strong consensus existed for the appropriateness of primary surgery for early‐stage disease, approaches to locally advanced disease with minimal periorbital fat invasion, and the use of induction chemotherapy with response‐directed local therapy. Consensus regarding nodal treatment and the use of proton therapy in the adjuvant setting was less robust. The rarity and diversity of PNS/NC tumors limit randomized phase III trials to guide management. As such, this systematic review and appropriate‐use consensus statements provide clinical guidance for the management of this challenging disease spectrum.

Outcomes of Reduced Elective Nodal Radiation Dose and Volume for Laryngeal, Hypopharyngeal, and p16‐Negative Oropharyngeal Cancers

ABSTRACT Background Reducing elective nodal irradiation dose can decrease treatment toxicity and improve quality of life for head and neck cancer patients. Methods We determined the effectiveness of reducing elective radiotherapy doses to 40 Gy for a consecutive cohort of laryngeal, hypopharyngeal, and p16‐negative oropharyngeal or unknown primary squamous cell carcinomas treated with concurrent chemoradiation. The primary outcome measure was solitary elective nodal recurrence. Results The cohort included 73 consecutive patients with a median follow up of 23.3 months. There were no cases of solitary elective nodal recurrence. Six patients had locoregional recurrence, eight had distant recurrence, and two had simultaneous locoregional and distant recurrence. All locoregional recurrences occured in the 70 Gy target volume (three in the primary tumor target, three in the involved node target, and two in both). Conclusions Reduction in elective nodal radiation dose did not lead to solitary elective nodal recurrences for laryngeal, hypopharyngeal, and p16‐negative oropharyngeal cancers.

Swallowing and Communication Outcomes Post Chemoradiotherapy for Low‐Risk Human Papillomavirus ( HPV )‐Associated Oropharyngeal Squamous Cell Carcinoma: A Substudy of TROG 12.01

ABSTRACT Background This substudy aimed to assess swallow and communication outcomes in patients undergoing treatment for low‐risk human papillomavirus‐associated oropharyngeal squamous cell carcinoma. Methods Videofluoroscopy swallowing studies (VFSS) were conducted pre‐treatment, 12 and 24 months post treatment, alongside quality of life and symptom severity measures for patients receiving 70Gy radiotherapy with either weekly cisplatin or cetuximab. Results Of 126 patients who underwent VFSS, there were no differences in swallowing outcomes between cisplatin and cetuximab arms. VFSS outcomes were worst at 12 months and improved by 24 months, with low aspiration rates and high swallow function at all timepoints. Older age, higher T‐stage, and base of tongue tumors (versus tonsil) were associated with poorer swallowing. Clinician‐and patient‐reported speech and voice problems were minimal. Conclusions Swallowing was safe and efficient, and communication highly intelligible at 24 months post treatment. Both 'objective' and patient‐reported measures are important to understand the impact of new treatment approaches on swallowing‐related outcomes.

The CD123 antibody–drug conjugate pivekimab sunirine exerts profound activity in preclinical models of pediatric acute lymphoblastic leukemia

Abstract Antibody–drug conjugates (ADCs) combining monoclonal antibodies with cytotoxic payloads are a rapidly emerging class of immune‐based therapeutics with the potential to improve the treatment of cancer, including children with relapse/refractory acute lymphoblastic leukemia (ALL). CD123, the α subunit of the interleukin‐3 receptor, is overexpressed in ALL and is a potential therapeutic target. Here, we show that pivekimab sunirine (PVEK), a recently developed ADC comprising the CD123‐targeting antibody, G4723A, and the cytotoxic payload, DGN549, was highly effective in vivo against a large panel of pediatric ALL patient‐derived xenograft (PDX) models ( n  = 39). PVEK administered once weekly for 3 weeks resulted in a median event‐free survival (EFS) of 57.2 days across all PDXs. CD123 mRNA and protein expression was significantly higher in B‐lineage ( n  = 65) compared with T‐lineage ( n  = 25) ALL PDXs ( p  < 0.0001), and mice engrafted with B‐lineage PDXs achieved significantly longer EFS than those engrafted with T‐lineage PDXs ( p  < 0.0001). PVEK treatment also resulted in significant clearance of human leukemia cells in hematolymphoid organs in mice engrafted with B‐ALL PDXs. Notably, our results showed no direct correlation between CD123 expression and mouse EFS, indicating that CD123 is necessary but not sufficient for in vivo PVEK activity. Importantly, a PDX with very high CD123 cell surface expression but resistant to in vivo PVEK treatment, failed to internalize the G4723A antibody while remaining sensitive to the PVEK payload, DGN549, suggesting a novel mechanism of resistance. In conclusion, PVEK was highly effective against a large panel of B‐ALL PDXs supporting its clinical translation for B‐lineage pediatric ALL.

Efficacy of anti‐PD1 therapy in extranodal NK/T cell lymphoma: A matched cohort analysis from the LYSA

Outcomes of patients with relapsed or refractory primary mediastinal B‐cell lymphoma treated with anti‐CD19 CAR‐T cells: CARTHYM, a study from the French national DESCAR‐T registry

ABSTRACT Primary mediastinal B‐cell lymphoma (PMBL) is often cured with dose‐dense anthracycline‐based regimens but the prognosis at relapse or progression remains poor. While anti‐CD19 CAR‐T cell therapy has dramatically improved outcomes in relapsed or refractory large B‐cell lymphoma, far less is known about their efficacy in PMBL. Using the systematic record of all patients treated with CAR‐T cells prospectively included in the DESCAR‐T registry in France, along with centrally reviewed positon‐emission tomography (PET) imaging, we describe the outcomes and key determinants of treatment success in PMBL patients treated over a 6‐year period. Among 82 patients infused in the registry we observed a best complete response (CR) rate, 2‐year progression‐free survival (PFS), and 2‐year overall survival (OS) of 68.1%, 57.4%, and 73.8%, respectively. Outcomes were even better for the 62 patients infused with axicabtagene ciloleucel, with best CR rate, 2‐year PFS, and 2‐year OS reaching 74.5%, 70.4%, and 86.9%, respectively. Achieving a Deauville score of 1–4 or a ΔSUVmax reduction of more than 24% at the 1‐month evaluation was associated with excellent outcomes, whereas increased total metabolic tumor volume baseline PET increased the risk of treatment failure. Surprisingly, neither the response to bridging therapy nor the type of bridging therapy (chemotherapy versus immune checkpoint inhibitors) were associated with long‐term outcomes. In conclusion, this study confirms that anti‐CD19 CAR‐T cells is a valid standard‐of‐care for relapsed and refractory PMBL and highlights key determinants of treatment success.