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The incidence of human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) is increasing among elderly (≥70 years) patients and the optimal treatment approach is not known. In this study, we aimed to determine disease and toxicity outcomes in an elderly HPV-OPSCC population primarily treated with a chemoradiation (CRT) approach. We identified 70 elderly HPV-OPSCC patients who were treated with either surgery, radiotherapy, or CRT between 2011 and 2021. Time-to-event analysis for overall survival (OS), progression-free survival (PFS), and local control (LC) were conducted using the Kaplan-Meier method. Univariate and multivariable cox regression models were used to estimate the hazard ratio associated with covariates. The median follow-up for our cohort was 43.9 months. Of the 70 elderly patients, 55 (78.6%) receive CRT and 15 (22.4%) received RT alone. Two patients underwent TORS resection. Of the 55 patients treated with CRT, the most common systemic agents were weekly carboplatin/taxol (n = 18), cetuximab (n = 17), and weekly cisplatin (n = 11). The 5-year OS, PFS, and LC were 57%, 52%, and 91%, respectively. On univariate analysis, Eastern Cooperative Oncology Group performance status and Charlson Comorbidity Index (CCI) were significant predictors of OS, while on multivariate analysis only CCI was a significant predictor of OS (p = 0.006). The rate of late peg tube dependency, osteoradionecrosis, and aspiration was 10%, 4%, and 4%, respectively. Definitive local therapy in elderly HPV-OPSCC patients is associated with excellent LC and a low rate of late toxicities. Prospective studies are needed to further stratify subgroups of elderly patients who may benefit from aggressive definitive local therapy.
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Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Humanos , Anciano , Virus del Papiloma Humano , Infecciones por Papillomavirus/complicaciones , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/patología , Carcinoma de Células Escamosas de Cabeza y Cuello , Estudios RetrospectivosRESUMEN
BACKGROUND: Immune checkpoint inhibitors (ICI) treatment in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) offers new therapeutic venues. We have previously developed a predictive survival model in this patient population based on clinical parameters, and the purpose of this study was to expand the study cohort and internally validate the model. METHODS: A single institutional retrospective analysis of R/M HNSCC patients treated with ICI. Clinical parameters collected included p-16 status, hemoglobin (Hb), albumin (Alb), lactate dehydrogenase (LDH), neutrophil, lymphocyte and platelet counts. Cox proportional hazard regression was used to assess the impact of patient characteristics and clinical variables on survival. A nomogram was created using the rms package to generate individualized survival prediction. RESULTS: 201 patients were included, 47 females (23%), 154 males (77%). Median age was 61 years (IQR: 55-68). P-16 negative (66%). Median OS was 12 months (95% CI: 9.4, 14.9). Updated OS model included age, sex, absolute neutrophil count, absolute lymphocyte count, albumin, hemoglobin, LDH, and p-16 status. We stratified patients into three risk groups based on this model at the 0.33 and 0.66 quantiles. Median OS in the optimal risk group reached 23.7 months (CI: 18.5, NR), 13.8 months (CI: 11.1, 20.3) in the average risk group, and 2.3 months (CI: 1.7, 4.4) in the high-risk group. Following internal validation, the discriminatory power of the model reached a c-index of 0.72 and calibration slope of 0.79. CONCLUSIONS: Our updated nomogram could assist in the precise selection of patients for which ICI could be beneficial and cost-effective.
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Neoplasias de Cabeza y Cuello , Inhibidores de Puntos de Control Inmunológico , Albúminas/uso terapéutico , Femenino , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Hemoglobinas , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológicoRESUMEN
Purpose/Objective(s): Microbiome has been shown to affect tumorigenesis by promoting inflammation. However, the association between the upper aerodigestive microbiome and head and neck squamous cell carcinoma (HNSCC) is not well established. Hypoxia is a modifiable factor associated with poor radiation response. Our study analyzed the HNSCC tumor samples from The Cancer Genome Atlas (TCGA) to investigate the relationship between different HNSCC tumor subsites, hypoxia, and local tumor microbiome composition. Results: A total of 357 patients were included [Oral cavity (OC) = 226, Oropharynx (OPx) = 53, and Larynx/Hypopharynx (LHPx) = 78], of which 12.8%, 71.7%, and 10.3%, respectively, were HPV positive. The mean (SD) hypoxia scores were 30.18 (11.10), 24.31 (14.13), and 29.53 (12.61) in OC, OPx, and LHPx tumors, respectively, with higher values indicating greater hypoxia. The hypoxia score was significantly higher for OC tumors compared to OPx (p = 0.044) and LHPx (p = 0.002). There was no significant correlation between hypoxia and HPV status. Pseudomonas sp. in OC, Actinomyces sp. and Sulfurimonas sp. in OPx, and Filifactor, Pseudomonas and Actinomyces sp. in LHPx had the strongest association with the hypoxia score. Materials/Methods: Tumor RNAseq samples from TCGA were processed, and the R package "tmesig" was used to calculate gene expression signature, including the Buffa hypoxia (BH) score, a validated hypoxia signature using 52 hypoxia-regulated genes. Microbe relative abundances were modeled with primary tumor location and a high vs. low tertile BH score applying a gamma-distributed generalized linear regression using the "stats" package in R, with adjusted p-value < 0.05 considered significant. Conclusions: In our study, oral cavity tumors were found to be more hypoxic compared to other head and neck subsites, which could potentially contribute to their radiation resistance. For each subsite, distinct microbial populations were over-represented in hypoxic tumors in a subsite-specific manner. Further studies focusing on an association between microbiome, hypoxia, and patient outcomes are warranted.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Microbiota , Neoplasias de la Boca , Infecciones por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/complicaciones , Carcinoma de Células Escamosas/patología , Infecciones por Papillomavirus/complicaciones , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/complicaciones , Hipoxia/complicacionesRESUMEN
BACKGROUND: The COVID-19 pandemic has required triage and delays in surgical care throughout the world. The impact of these surgical delays on survival for patients with head and neck squamous cell carcinoma (HNSCC) remains unknown. METHODS: A retrospective cohort study of 37 730 patients in the National Cancer Database with HNSCC who underwent primary surgical management from 2004 to 2016 was performed. Uni- and multivariate analyses were used to identify predictors of overall survival. Bootstrapping methods were used to identify optimal time-to-surgery (TTS) thresholds at which overall survival differences were greatest. Cox proportional hazard models with or without restricted cubic splines were used to determine the association between TTS and survival. RESULTS: The study identified TTS as an independent predictor of overall survival (OS). Bootstrapping the data to dichotomize the cohort identified the largest rise in hazard ratio (HR) at day 67, which was used as the optimal TTS cut-point in survival analysis. The patients who underwent surgical treatment longer than 67 days after diagnosis had a significantly increased risk of death (HR, 1.189; 95% confidence interval [CI], 1.122-1.261; P < 0.0001). For every 30-day delay in TTS, the hazard of death increased by 4.6%. Subsite analysis showed that the oropharynx subsite was most affected by surgical delays, followed by the oral cavity. CONCLUSIONS: Increasing TTS is an independent predictor of survival for patients with HNSCC and should be performed within 67 days after diagnosis to achieve optimal survival outcomes.
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Neoplasias Hipofaríngeas/cirugía , Neoplasias Laríngeas/cirugía , Neoplasias de la Boca/cirugía , Neoplasias Orofaríngeas/cirugía , Procedimientos Quirúrgicos Otorrinolaringológicos/estadística & datos numéricos , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Tiempo de Tratamiento/estadística & datos numéricos , Anciano , COVID-19 , Estudios de Cohortes , Atención a la Salud , Femenino , Humanos , Neoplasias Hipofaríngeas/mortalidad , Neoplasias Laríngeas/mortalidad , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/mortalidad , Neoplasias Orofaríngeas/mortalidad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , SARS-CoV-2 , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Oncología QuirúrgicaRESUMEN
For patients ineligible for cisplatin with definitive radiotherapy (CP-CRT) for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), concurrent cetuximab (C225-RT) is a popular substitute. Carboplatin-based chemoradiation (CB-CRT) is another option; however, relative efficacies of CP-CRT, CB-CRT and C225-RT are unclear, particularly in the human papillomavirus (HPV)-unrelated population. We identified 316 patients with stage III-IVB cancers of the oropharynx (24.7%), larynx (58.2%) and hypopharynx (17.1%) undergoing definitive C225-RT (N = 61), CB-CRT (N = 74) or CP-CRT (N = 181). Kaplan-Meier and cumulative incidence functions were generated to estimate overall survival (OS), locoregional failure (LRF) and distant metastasis (DM). Cox proportional hazards were used to determine the association of survival endpoints with clinical characteristics. Respectively, 3-year cumulative incidences for CP-CRT, CB-CRT and C225-RT were: LRF (0.19, 0.18 and 0.48, p ≤ 0.001), DM (0.17, 0.12 and 0.25, p = 0.32). Kaplan-Meier estimates for 3 year OS were: CP-CRT: 71%; CB-CRT: 59% and C225-RT: 54%; p = 0.0094. CP-CRT (hazard ratio [HR] 0.336; 95% confidence interval [CI] 0.203-0.557, p < 0.01) and CB-CRT (HR 0.279; 95% CI 0.141-0.551, p < 0.01) were associated with reduced hazard for LRF on multivariable analysis. CP-CRT (HR 0.548; 95% CI 0.355-0.845, p < 0.01) and CB-CRT (HR 0.549; 95% CI 0.334-0.904, p = 0.02) were associated with a reduced hazard for death on multivariable analysis. Propensity matching confirmed reduced hazards with a combined CP/CB-CRT group compared to C225-RT for LRF: HR 0.384 (p = 0.018) and OS: HR 0.557 (p = 0.045) and CB-CRT group compared to C225-RT for LRF: HR 0.427 (p = 0.023). In conclusion, CB-CRT is an effective alternative to CP-CRT in HPV-unrelated LA-HNSCC with superior locoregional control and OS compared to C225-RT.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cetuximab/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/radioterapia , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Carboplatino/administración & dosificación , Quimioradioterapia , Cisplatino/administración & dosificación , Femenino , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/virología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Papillomaviridae , Infecciones por Papillomavirus/patología , Ensayos Clínicos Controlados Aleatorios como Asunto , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Tasa de SupervivenciaAsunto(s)
Quimioradioterapia , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Humanos , Neoplasias Orofaríngeas/virología , Neoplasias Orofaríngeas/terapia , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Quimioradioterapia/efectos adversos , Pronóstico , Anciano , Radioterapia/efectos adversos , Anciano de 80 o más Años , Papillomaviridae/aislamiento & purificaciónRESUMEN
Cancer-related inflammation is considered the "seventh hallmark of cancer"; numerous studies demonstrate that tumors develop and progress within inflammatory diseases. Central to the development of cancer are genetic changes that endow these cancer cells with many of the hallmarks of cancer, such as self-sufficient growth and resistance to anti-growth and pro-death signals. However, while the genetic changes that occur within cancer cells themselves, such as activated oncogenes or dysfunctional tumor suppressors, are responsible for many aspects of cancer development, they are not sufficient. Tumor promotion and progression are dependent on ancillary processes involving cells of the tumor environment that are not necessarily cancerous themselves. Infiltration of immune cells facilitates tumor development through the production of factors that promote carcinogenesis and by enabling tumors to evade the host immune response. Small molecules including cytokines, chemokines, and growth factors play key roles in both inflammation and cancer by promoting proliferation, angiogenesis, and carcinogenesis and by recruiting immune cells. The extracellular matrix is altered in inflammation and provides structural support to developing tumors. Hypoxia is a common state in cancers and inflamed tissues which causes DNA damage and induces tumorigenic factors. Finally, tissue vasculature is a vital part of its microenvironment, supplying oxygen, nutrients, and growth factors to rapidly dividing cells and providing a mechanism for metastatic spread. This review will discuss the reflexive relationship between cancer and inflammation with particular focus on how by considering the role of inflammation in physiologic processes such as the maintenance of tissue homeostasis and repair may provide a logical framework for understanding the connection between the inflammatory response and cancer. The cells and molecules outlined here represent potential targets for the treatment of head and neck cancer.
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Carcinoma de Células Escamosas/etiología , Neoplasias de Cabeza y Cuello/etiología , Inflamación/complicaciones , Animales , Carcinoma de Células Escamosas/irrigación sanguínea , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/irrigación sanguínea , Neoplasias de Cabeza y Cuello/patología , Humanos , Mediadores de Inflamación/fisiología , Metástasis de la Neoplasia , Neovascularización Patológica/genética , Neovascularización Patológica/inmunología , Transducción de Señal/fisiología , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
Cisplatin, one of the most ototoxic anti-neoplastic agents, causes permanent hearing loss in up to 90% of patients. We assessed ototoxicity rates and prospectively collected audiologic outcomes of patients receiving low-dose or high-dose cisplatin with concurrent cochlear-sparing intensity-modulated radiation therapy (IMRT). Patients with head and neck squamous cell carcinoma (HNSCC) receiving definitive or adjuvant cisplatin-based chemoradiotherapy (CRT) were analyzed. Cisplatin was administered either in low doses weekly (40 mg/m2) for up to seven doses or in high doses triweekly (100 mg/m2) for up to three doses. Cochlear-sparing IMRT was delivered in all cases. Audiologic data were prospectively collected before, during, and after treatment completion. The primary endpoint was a hearing change grade of ≥3 after CRT completion. Of the 96 HNSCC patients evaluated, 69 received weekly cisplatin and 58 received definitive CRT. Of patients receiving weekly cisplatin, 13% developed ≥G3 ototoxicity vs. 56% of patients who received triweekly cisplatin (p < 0.001). In multivariable modeling, the cisplatin dose schedule remained significant (OR: 8.4, 95%CI: 2.8-27.8, p < 0.001) for risk of severe irreversible ototoxicity. Triweekly cisplatin CRT significantly increased the ≥G3 severe irreversible ototoxicity risk compared to low-dose weekly cisplatin, irrespective of the cumulative cisplatin dose, even with the use of cochlear-sparing IMRT. No significant difference in oncologic outcomes was observed between the two schedules.
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OBJECTIVE: To comprehensively analyze reported cases of nasolacrimal squamous cell carcinoma (NLSCC), focusing on risk factors, treatment modalities, and outcomes. Additionally, investigate the impact of human Papillomavirus (HPV) status and histopathological subtypes' impact on prognosis. DATA SOURCES: Pubmed, Embase. REVIEW METHODS: We conducted a systematic literature review to identify relevant studies reporting cases of NLSCC. The review methods adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The final update was performed on May 31, 2023. RESULTS: The 72 studies included a total of 313 participants (mean age: 55; 60% male). Longer symptom duration (44.1 ± 59.2 months) correlated with recurrence (p = 0.004), and males exhibited higher mortality rates (19.6% vs. 2.4% in females, p = 0.01). The overall survival (OS) rate among all patients was 87.1%. Basaloid NLSCC had a worse death outcome (p ≤ 0.001). HPV-positive cases showed comparable OS, recurrence, and metastasis rates to the general population (p = 0.917, 0.851, 0.07, respectively). Comparing treatment approaches (surgery, surgery with adjuvant radiation, chemoradiotherapy [CRT] followed by surgery), no significant differences in 5 and 10-year OS rates or recurrence were observed (p = 0.4, 0.24, respectively), but 5-year metastasis events were significant (p = 0.024). Eye exenteration rates were 31.1%, 20%, and 0% for the respective treatments (p = 0.089). Induction chemotherapy saved four cases from potential exenteration with favorable prognosis. CONCLUSION: Early detection and diagnosis are of utmost importance in the management of NLSCC. Regardless of the treatment approach, HPV-related NLSCC demonstrated similar outcomes to the general population. Basaloid histology represents the worst subtype in terms of prognosis. Limited adjuvant CRT cases showed improved outcomes and induction chemotherapy's importance was emphasized in recent literature and our shared experience. Laryngoscope, 134:3892-3902, 2024.
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Neoplasias del Ojo , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias del Ojo/terapia , Neoplasias del Ojo/mortalidad , Neoplasias del Ojo/patología , Neoplasias del Ojo/tratamiento farmacológico , Conducto Nasolagrimal/patología , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/virología , Infecciones por Papillomavirus/complicaciones , Quimioterapia de Inducción , Pronóstico , Recurrencia Local de NeoplasiaRESUMEN
OBJECTIVES: Patients with recurrent and metastatic head and neck cancer (HNC) have limited treatment options. 'QuadShot' (QS), a hypofractionated palliative radiotherapy regimen, can provide symptomatic relief and local control and may potentiate the effects of immune checkpoint inhibitors (ICIs). We compared outcomes of QS ± concurrent ICIs in the palliative treatment of HNC. MATERIALS AND METHODS: We identified patients who received ≥three cycles of QS from 2017 to 2022 and excluded patients without post-treatment clinical evaluation or imaging. Outcomes for patients who received QS alone were compared to those treated with ICI concurrent with QS, defined as receipt of ICI within 4 weeks of QS. RESULTS: Seventy patients were included, of whom 57% received concurrent ICI. Median age was 65.5 years (interquartile range [IQR]: 57.9-77.8), and 50% patients had received prior radiation to a median dose of 66 Gy (IQR: 60-70). Median follow-up was 8.8 months. Local control was significantly higher with concurrent ICIs (12-month: 85% vs. 63%, p = 0.038). Distant control (12-month: 56% vs. 63%, p = 0.629) and median overall survival (9.0 vs. 10.0 months, p = 0.850) were similar between the two groups. On multivariable analysis, concurrent ICI was a significant predictor of local control (HR for local failure: 0.238; 95% CI: 0.073-0.778; p = 0.018). Overall, 23% patients experienced grade 3 toxicities, which was similar between the two groups. CONCLUSIONS: The combination of QS with concurrent ICIs was well tolerated and significantly improved local control compared to QS alone. The median OS of 9.4 months compares favorably to historical controls for patients with HNC treated with QS. This approach represents a promising treatment option for patients with HNC unsuited for curative-intent treatment and warrants prospective evaluation.
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Head and Neck Squamous Cell Carcinoma (HNSCC) comprises a diverse group of tumors with variable treatment response and prognosis. The tumor microenvironment (TME), which includes microbiome and immune cells, can impact outcomes. Here, we sought to relate the presence of specific microbes, gene expression, and tumor immune infiltration using tumor transcriptomics from The Cancer Genome Atlas (TCGA) and associate these with overall survival (OS). RNA sequencing (RNAseq) from HNSCC tumors in TCGA was processed through the exogenous sequences in tumors and immune cells (exotic) pipeline to identify and quantify low-abundance microbes. The detection of the Papillomaviridae family of viruses assessed HPV status. All statistical analyses were performed using R. A total of 499 RNAseq samples from TCGA were analyzed. HPV was detected in 111 samples (22%), most commonly Alphapapillomavirus 9 (90.1%). The presence of Alphapapillomavirus 9 was associated with improved OS [HR = 0.60 (95%CI: 0.40-0.89, p = .01)]. Among other microbes, Yersinia pseudotuberculosis was associated with the worst survival (HR = 3.88; p = .008), while Pseudomonas viridiflava had the best survival (HR = 0.05; p = .036). Microbial species found more abundant in HPV- tumors included several gram-negative anaerobes. HPV- tumors had a significantly higher abundance of M0 (p < .001) and M2 macrophages (p = .035), while HPV+ tumors had more T regulatory cells (p < .001) and CD8+ T-cells (p < .001). We identified microbes in HNSCC tumor samples significantly associated with survival. A greater abundance of certain anaerobic microbes was seen in HPV tumors and pro-tumorigenic macrophages. These findings suggest that TME can be used to predict patient outcomes and may help identify mechanisms of resistance to systemic therapies.
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Neoplasias de Cabeza y Cuello , Microbiota , Infecciones por Papillomavirus , Carcinoma de Células Escamosas de Cabeza y Cuello , Microambiente Tumoral , Humanos , Neoplasias de Cabeza y Cuello/virología , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/microbiología , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/genética , Femenino , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/inmunología , Infecciones por Papillomavirus/complicaciones , Masculino , Microbiota/genética , Microambiente Tumoral/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Carcinoma de Células Escamosas de Cabeza y Cuello/microbiología , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Pronóstico , Persona de Mediana Edad , Papillomaviridae/genética , AncianoRESUMEN
BACKGROUND AND PURPOSE: A bolus is required when treating scalp lesions with photon radiation therapy. Traditional bolus materials face several issues, including air gaps and setup difficulty due to irregular, convex scalp geometry. A 3D-milled bolus is custom-formed to match individual patient anatomy, allowing improved dose coverage and homogeneity. Here, we describe the creation process of a 3D-milled bolus and report the outcomes for patients with scalp malignancies treated with Volumetric Modulated Arc Therapy (VMAT) utilizing a 3D-milled bolus. MATERIALS AND METHODS: Twenty-two patients treated from 2016 to 2022 using a 3D-milled bolus and VMAT were included. Histologies included squamous cell carcinoma (n = 14, 64%) and angiosarcoma (n = 8, 36%). A total of 7 (32%) patients were treated in the intact and 15 (68%) in the postoperative setting. The median prescription dose was 66.0 Gy (range: 60.0-69.96). RESULTS: The target included the entire scalp for 8 (36%) patients; in the remaining 14 (64%), the median ratio of planning target volume to scalp volume was 35% (range: 25-90%). The median dose homogeneity index was 1.07 (range: 1.03-1.15). Six (27%) patients experienced acute grade 3 dermatitis and one (5%) patient experienced late grade 3 skin ulceration. With a median follow-up of 21.4 months (range: 4.0-75.4), the 18-month rates of locoregional control and overall survival were 75% and 79%, respectively. CONCLUSIONS: To our knowledge, this is the first study to report the clinical outcomes for patients with scalp malignancies treated with the combination of VMAT and a 3D-milled bolus. This technique resulted in favorable clinical outcomes and an acceptable toxicity profile in comparison with historic controls and warrants further investigation in a larger prospective study.
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BACKGROUND: Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland neoplasm. They can present with distinct immunoprofiles, such as androgen receptor (AR) and HER-2/Neu-positivity. To date, no consensus exists on how to best manage this entity. METHODS: All patients diagnosed with nonmetastatic AR+ SDC of the parotid from 2013 to 2019 treated with curative intent were included. Immunologic tumor profiling was conducted using 24 distinct markers. Kaplan-Meier analyses were used to estimate locoregional recurrence (LRR), distant control, and overall survival (OS). RESULTS: Fifteen patients were included. Nine (60%) patients presented with T4 disease and eight (53%) had positive ipsilateral cervical lymphadenopathy. Ten (67%) patients underwent trimodality therapy, including surgery followed by adjuvant radiation and concurrent systemic therapy. The median follow-up was 5.5 years (interquartile range, 4.8-6.1). The estimated 5-year rates of LRR, distant progression, and OS were 6%, 13%, and 87%, respectively. CONCLUSION: Despite only including AR+ SDC of the parotid, immunoprofiles, such as expression of HER-2, were highly variable, highlighting the potential to tailor systemic regimens based on individual histologic profiles in the future. Studies with larger patient numbers using tumor-specific molecular profiling and tumor heterogeneity analyses are justified to better understand the biology of these tumors. Molecularly informed treatment approaches, including the potential use of AR- and HER-2/Neu-directed therapies upfront in the definitive setting, may hold future promise to further improve outcomes for these patients.
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PURPOSE: The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiation therapy is considered the standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older patients with HNSCC. METHODS AND MATERIALS: The SENIOR study is an international multicenter cohort study including older patients (≥65 years) with HNSCC treated with definitive radiation therapy at 13 academic centers in the United States and Europe. Patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) via Kaplan-Meier analyses. Fine-Gray competing risk regressions were performed regarding the incidence of locoregional failures and distant metastases. RESULTS: Six hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n = 310; 44%), followed by cisplatin plus 5-fluorouracil (n = 137; 20%), carboplatin (n = 73; 10%), and mitomycin C plus 5-fluorouracil (n = 64; 9%). Carboplatin-based regimens were associated with diminished PFS (hazard ratio [HR], 1.39 [1.03-1.89]; P < .05) and a higher incidence of locoregional failures (subdistribution HR, 1.54 [1.00-2.38]; P = .05) compared with single-agent cisplatin, whereas OS (HR, 1.15 [0.80-1.65]; P = .46) was comparable. There were no oncological differences between single-agent and multiagent cisplatin regimens (all P > .05). The median cumulative dose of cisplatin was 180 mg/m2 (IQR, 120-200 mg/m2). Cumulative cisplatin doses ≥200 mg/m2 were associated with increased OS (HR, 0.71 [0.53-0.95]; P = .02), increased PFS (HR, 0.66 [0.51-0.87]; P = .003), and lower incidence of locoregional failures (subdistribution HR, 0.50 [0.31-0.80]; P = .004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR, 0.996 [0.993-0.999]; P = .009). CONCLUSIONS: Single-agent cisplatin can be considered in the standard chemotherapy regimen for older patients with HNSCC who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant in older patients with HNSCC.
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Cisplatino , Neoplasias de Cabeza y Cuello , Humanos , Anciano , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carboplatino , Neoplasias de Cabeza y Cuello/radioterapia , Estudios de Cohortes , Resultado del Tratamiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/métodos , FluorouraciloRESUMEN
BACKGROUND: Sinonasal malignancy (SNM) is a heterogeneous group of diseases for which induction chemotherapy (IC) may reduce tumor burden. The purpose of this study was to characterize the response to IC in SNM as a prognostic factor through its effect on survival. METHODS: Retrospective cohort of patients undergoing IC for SNM between 2010 and 2019 at our quaternary referral center. RESULTS: Forty-two patients with advanced SNM were included in the analysis. Patients with a favorable response to IC had higher survival rates than those who had an unfavorable response (5-year OS: 66.8% vs. 9.7%; p < 0.001; PFS: 56.8% vs. 0%; p < 0.001). CONCLUSIONS: Response to IC in our patient cohort was a prognostic indicator of overall response to treatment. Further elucidation of predictors of response is needed for appropriate patient selection.
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Quimioterapia de Inducción , Neoplasias , Humanos , Estudios Retrospectivos , PronósticoRESUMEN
PURPOSE: No Food and Drug Administration-approved intervention exists for oral mucositis (OM) from chemoradiotherapy (CRT) used to treat head and neck cancers. RRx-001 is a hypoxia-activated, cysteine-directed molecule that affects key pathways involved in OM pathogenesis. This phase 2a, multi-institutional trial was designed to assess the safety and feasibility of 3 schedules of a fixed concentration of RRx-001; a standard-of-care arm was included to identify potential signals of efficacy for further study. METHODS AND MATERIALS: This study enrolled patients with oral cavity and oropharynx squamous cell carcinoma receiving definitive or postoperative cisplatin-based CRT. Patients were randomized into 4 cohorts. In arms 1 to 3, RRx-001 was coinfused with patients' blood at differing intervals. Arm 4 was a control cohort of patients treated with CRT alone. Trained evaluators assessed OM using a standardized data collection instrument twice weekly during treatment and then until resolution. OM severity was scored centrally using World Health Organization criteria. Safety outcomes were assessed using National Cancer Institute - Common Terminology Criteriav4 benchmarks. Long-term tumor response was defined by Response evaluation criteria in solid tumors v1.1 criteria. RESULTS: Fifty-three patients were enrolled, with 46 and 45 individuals contributing safety and efficacy data, respectively. There were no severe adverse events attributed to the study drug. Across all 3 active arms, the study drug was infused fully per protocol in 86% of patients. All 3 RRx-001 treatment cohorts appeared to demonstrate a similar or lower OM duration relative to control; arm 1 had the lowest median duration of severe oral mucositis (SOM), 8.5 days versus 24 days in controls among patients who developed at least 1 day of SOM. There were no locoregional failures in any patient. CONCLUSIONS: Our results support the safety and feasibility of RRx-001 as an intervention to mitigate SOM. Additional studies are planned to confirm its efficacy.
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Azetidinas , Neoplasias de Cabeza y Cuello , Estomatitis , Humanos , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Quimioradioterapia/efectos adversos , Azetidinas/uso terapéutico , Estomatitis/terapia , Estomatitis/tratamiento farmacológicoRESUMEN
PURPOSE: To identify the proportion of Emergency Department (ED) visits in cancer patients associated with a mental and substance use disorder (MSUD) and the subsequent healthcare costs. METHODS: Nationally representative data on ED visits from 2009 to 2018 was obtained from the Nationwide Emergency Department Sample (NEDS). We identified cancer-related visits with or without a MSUD using the Clinical Classifications Software diagnoses documented during the ED visit. Survey-adjusted frequencies and proportions of ED visits among adult cancer patients with or without a MSUD was evaluated. Survey-adjusted multivariable logistic regression models were used to examine demographic and clinical predictors of the presence of an MSUD and the likelihood of hospital admission for patients with a primary MSUD. RESULTS: Among 54,004,462 ED visits with a cancer diagnosis between 2009 and 2018, 11,803,966 (22%) were associated with a MSUD. Compared to a primary diagnosis of cancer, patients who presented to the ED with a chief complaint of MSUD were more likely to be female (54% vs. 49%), younger (median: 58 vs. 66), more likely to have Medicaid insurance, and more likely to be discharged home. The three most common MSUD diagnoses among cancer patients were alcohol-related disorders, anxiety disorders, and depressive disorders. The total costs associated with a primary MSUD from 2009 to 2018 was $3,133,432,103, of which alcohol-related disorders claimed the largest majority. Younger age (OR per 10-year increase: 0.86, 95% CI: 0.85, 0.86) and female sex (OR: 1.34, 95% CI: 1.33-1.35) were associated with higher odds of having an MSUD. CONCLUSIONS: Our findings demonstrate a high burden of psychiatric and substance use illness in the cancer population and provide the rationale for early psychosocial intervention to support these patients.
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Trastornos Relacionados con Alcohol , Neoplasias , Trastornos Relacionados con Sustancias , Adulto , Estados Unidos/epidemiología , Humanos , Femenino , Masculino , Estrés Financiero , Trastornos Relacionados con Sustancias/epidemiología , Hospitalización , Servicio de Urgencia en Hospital , Neoplasias/epidemiología , Estudios RetrospectivosRESUMEN
PURPOSE: Tumoral programmed cell death ligand-1 (PD-L1) expression is common in human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC). We assessed whether a DNA vaccine targeting HPV-16/18 E6/E7 with IL12 adjuvant (MEDI0457) combined with the PD-L1 inhibitor durvalumab could enhance HPV-specific T-cell response and improve outcomes in recurrent/metastatic HPV-16/18-associated HNSCC. PATIENTS AND METHODS: In this phase Ib/IIa study, immunotherapy-naïve patients with ≥1 previous platinum-containing regimen (neoadjuvant/adjuvant therapy or for recurrent/metastatic disease) received MEDI0457 7 mg intramuscularly with electroporation on weeks 1, 3, 7, and 12, then every 8 weeks, plus durvalumab 1,500 mg intravenously on weeks 4, 8, and 12, then every 4 weeks, until confirmed progression and/or unacceptable toxicity. Coprimary objectives were safety and objective response rate (ORR; H0: ORR ≤ 15%); secondary objectives included 16-week disease control rate (DCR-16), overall survival (OS), and progression-free survival (PFS). RESULTS: Of 35 treated patients, 29 were response evaluable (confirmed HPV-associated disease; received both agents). ORR was 27.6% [95% confidence interval (CI), 12.7-47.2; four complete responses, four partial responses]; responses were independent of PD-L1 tumor-cell expression (≥25% vs. <25%). DCR-16 was 44.8% (95% CI, 26.5-64.3). Median PFS was 3.5 months (95% CI, 1.9-9.0); median OS was 29.2 months (15.2-not calculable). Twenty-eight (80.0%) patients had treatment-related adverse events [grade 3: 5 (14.3%); no grade 4/5], resulting in discontinuation in 2 (5.7%) patients. HPV-16/18-specific T cells increased on treatment; 4 of 8 evaluable patients had a >2-fold increase in tumor-infiltrating CD8+ T cells. CONCLUSIONS: MEDI0457 plus durvalumab was well tolerated. While the primary efficacy endpoint was not reached, clinical benefit was encouraging.
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Neoplasias de Cabeza y Cuello , Infecciones por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Virus del Papiloma Humano , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Infecciones por Papillomavirus/complicaciones , Papillomavirus Humano 16/genética , Antígeno B7-H1/genética , Papillomavirus Humano 18RESUMEN
BACKGROUND: Data about patient-reported outcomes (PROs) among patients with head and neck squamous cell carcinoma (HNSCC) treated with immune checkpoint inhibitors are sparse. Our exploratory study evaluated PROs in patients with HNSCC starting treatment with immune checkpoint inhibitor monotherapy or combination therapy with cetuximab. METHODS: Patients were recruited prior to receipt of their first checkpoint inhibitor therapy infusion. Participants completed measures of checkpoint inhibitor toxicities and quality of life (QOL) at on-treatment clinic visits. RESULTS: Among patients treated with checkpoint inhibitor monotherapy (n = 48) or combination therapy (n = 38) toxicity increased over time (p < 0.05), while overall QOL improved from baseline to 12 weeks, with stable or declining QOL thereafter (p < 0.05). There were no group differences in change in toxicity index or QOL. Toxicity index scores were significantly higher in the combination group at 18-20 weeks and 6 months post-initiation of immune checkpoint inhibitor (p < 0.05). There were no significant group differences at baseline, the 6-8 week (p = 0.13) or 3-month (p = 0.09) evaluations. The combination group reported better emotional well-being at baseline than the monotherapy group (p = 0.04), There were no other group differences QOL at baseline or later timepoints. CONCLUSIONS: Despite increasing patient-reported toxicity, checkpoint inhibitor monotherapy and combination therapy were associated with similar transient improvements, then worsening, of QOL in patients with HNSCC.
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Neoplasias de Cabeza y Cuello , Calidad de Vida , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/etiología , Inhibidores de Puntos de Control Inmunológico , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/etiología , Inmunoterapia/efectos adversos , Medición de Resultados Informados por el PacienteRESUMEN
BACKGROUND: The potential role of postoperative radiation therapy (PORT) for patients who have completely resected, stage III nonsmall cell lung cancer (NSCLC) with N2 disease remains controversial. By using population-based data, the authors of this report compared the survival of a concurrent cohort of elderly patients who had N2 disease treated with and without PORT. METHODS: By using the Surveillance, Epidemiology, and End Results (SEER) registry linked to Medicare records, 1307 patients were identified who had stage III NSCLC with N2 lymph node involvement diagnosed between 1992 and 2005. Propensity scoring methods and instrumental variable analysis were used to compare the survival of patients who did and did not receive PORT after controlling for selection bias. RESULTS: Overall, 710 patients (54%) received PORT. Propensity score analysis indicated that PORT was not associated with improved survival in patients with N2 disease (hazard ratio [HR], 1.11; 95% confidence interval [CI], 0.97-1.27). Analyses that were limited to patients who did or did not receive chemotherapy, who received intermediate-complexity or high-complexity radiotherapy planning, or adjusted for time trends produced similar results. The instrumental variable estimator for the absolute improvement in 1-year and 3-year survival with PORT was -0.04 (95% CI, -0.15 to 0.08) and -0.08 (95% CI, -0.24 to 0.15), respectively. CONCLUSIONS: The current data suggested that PORT is not associated with improved survival for elderly patients with N2 disease. These findings have important clinical implications, because SEER data indicate that a large percentage of elderly patients currently receive PORT despite the lack of definitive evidence about its effectiveness. The potential effectiveness of PORT should be evaluated further in randomized controlled trials.