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Salivary gland cancers are a rare, histologically diverse group of tumors. They range from indolent to aggressive and can cause significant morbidity and mortality. Surgical resection remains the mainstay of treatment, but radiation and systemic therapy are also critical parts of the care paradigm. Given the rarity and heterogeneity of these cancers, they are best managed in a multidisciplinary program. In this review, the authors highlight standards of care as well as exciting new research for salivary gland cancers that will strive for better patient outcomes.
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Neoplasias das Glândulas Salivares , Humanos , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/terapiaRESUMO
Transparent and precise endpoint definitions are a crucial aspect of clinical trial conduct and reporting, and are used to communicate the benefit of an intervention. Previous studies have identified inconsistencies in endpoint definitions across oncological clinical trials. Here, the Head and Neck Cancer International Group assessed endpoint definitions from phase 3 trials or trials considered practice-changing for patients with recurrent or metastatic mucosal head and neck squamous cell carcinoma, published between 2008 and 2021. We identify considerable and global heterogeneity in endpoint definitions, which undermines the interpretation of results and development of future studies. We show how fundamental components of even incontrovertible endpoints such as overall survival vary widely, highlighting an urgent need for increased rigour in reporting and harmonisation of endpoints.
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Consenso , Determinação de Ponto Final , Neoplasias de Cabeça e Pescoço , Recidiva Local de Neoplasia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundário , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Recidiva Local de Neoplasia/patologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Determinação de Ponto Final/normas , Ensaios Clínicos Fase III como Assunto , Metástase NeoplásicaRESUMO
Robust time-to-event endpoint definitions are crucial for the assessment of treatment effect and the clinical value of trial interventions. Here, the Head and Neck Cancer International Group investigated endpoint use in phase 3 trials and trials considered potentially practice-changing published between 2008 and 2021 in the curative-intent setting for patients with mucosal head and neck squamous cell carcinoma. Of the 92 trials reviewed, we show that all core components of endpoint reporting were heterogeneous, including definitions of common terms, such as overall survival and progression-free survival. Our report highlights the urgent need for harmonisation of fundamental components of clinical trial endpoints and the engagement of all stakeholders to ensure the transparent reporting of endpoint details.
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Consenso , Determinação de Ponto Final , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/mortalidade , Determinação de Ponto Final/normas , Ensaios Clínicos Fase III como Assunto , Intervalo Livre de ProgressãoRESUMO
OPINION STATEMENT: Patients with HPV-associated oropharyngeal squamous cell carcinoma have improved prognosis relatively to those with tumors not driven by HPV. Both definitive radiotherapy (typically with concurrent chemotherapy) and transoral robotic surgery (with adjuvant therapies based on pathologic risk factors) are both acceptable treatment options for patients. The decision on which treatment is optimal depends on individual patient factors and should be made in a multi-disciplinary setting with input from a radiation oncologist, head and neck surgeon, and medical oncologist. Where appropriate, patients in this setting should be considered for enrollment on clinical studies evaluating de-escalation of treatment intensity given the very favorable outcomes and high toxicity profile associated with conventional therapies. However, caution is needed given negative data for de-escalation in the definitive chemotherapy and radiation setting. It remains unclear what the prognostic significance of HPV status is in patients with squamous cell carcinomas of the head and neck outside of the oropharynx.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapiaRESUMO
BACKGROUND: Out-of-field neutron dissemination during double-scattered proton therapy has raised concerns of increased second malignancies, disproportionally affecting pediatric patients due to the proportion of body exposed to scatter dose and inherent radiosensitivity of developing tissue. We sought to provide empiric data on the incidence of early second tumors. METHODS: Between 2006 and 2019, 1713 consecutive children underwent double-scattered proton therapy. Median age at treatment was 9.1 years; 371 were ≤3 years old. Thirty-seven patients (2.2%) had tumor predisposition syndromes. Median prescription dose was 54 Gy (range 15-75.6). Median follow-up was 3.3 years (range 0.1-12.8), including 6587 total person-years. Five hundred forty-nine patients had ≥5 years of follow-up. A second tumor was defined as any solid neoplasm throughout the body. RESULTS: Eleven patients developed second tumors; the 5- and 10-year cumulative incidences were 0.8% (95% CI, 0.4-1.9%) and 3.1% (95% CI, 1.5-6.2%), respectively. Using age- and gender-specific data from the Surveillance, Epidemiology, and End Results (SEER) program, the standardized incidence ratio was 13.5; the absolute excess risk was 1.5/1000 person-years. All but one patient who developed second tumors were irradiated at ≤5 years old (p < .0005). There was also a statistically significant correlation between patients with tumor predisposition syndromes and second tumors (p < .0001). Excluding patients with tumor predisposition syndromes, 5- and 10-year rates were 0.6% (95% CI, 0.2-1.7%) and 1.7% (95% CI, 0.7-4.0%), respectively, with all five malignant second tumors occurring in the high-dose region. CONCLUSION: Second tumors are rare within the decade following double-scattered proton therapy, particularly among children irradiated at >5 years old and those without tumor predisposition syndrome.
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Segunda Neoplasia Primária , Neoplasias , Terapia com Prótons , Criança , Pré-Escolar , Humanos , Incidência , Neoplasias/epidemiologia , Neoplasias/radioterapia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Terapia com Prótons/efeitos adversos , SíndromeRESUMO
PURPOSE: Radiotherapy-related visual decline is a significant concern in survivors of childhood cancer; however, data establishing the dose-response relationship between dose to the optic apparatus and visual acuity decline in children are sparse. We aimed to determine this relationship in a cohort of children treated with proton therapy. MATERIAL AND METHODS: We identified 458 children with 875 eyes at risk treated with proton therapy for intracranial malignancy between December 2006 and September 2018. Eyes were considered at risk if either the ipsilateral optic nerve or optic chiasm received ≥30 GyRBE to 0.1 cm3. Kaplan-Meier and Normal Tissue Complication Probability modeling was used to establish the relationship between radiotherapy dose and risk of visual decline. RESULTS: Excluding children with tumor progression, no patient experienced complete vision loss. The actuarial 5-year rate of any visual acuity decline was 2.6% (95% confidence interval [CI]: 1.5%-4.6%). The dose to 0.1 cm3 of the ipsilateral optic nerve or optic chiasm resulting in a 1%, 5%, and 10% risk of acuity decline were 52.7 GyRBE, 56.6 GyRBE, and 58.3 GyRBE. Visual decline was only seen in children with primary tumors of the optic pathway or suprasellar region. CONCLUSIONS: Visual acuity decline following radiotherapy for intracranial malignancies in children is rare. A dose of approximately 56 GyRBE to 0.1 cm3 results in an approximately 5% risk of visual acuity decline for children with suprasellar or optic pathway tumors. A dose to 0.1 cm3 of 56 GyRBE appears to be safe for children with tumors elsewhere in the brain.
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Neoplasias Encefálicas/radioterapia , Terapia com Prótons/efeitos adversos , Acuidade Visual/efeitos da radiação , Criança , Humanos , Quiasma Óptico/efeitos da radiação , Nervo Óptico/efeitos da radiação , Órgãos em Risco , SobreviventesRESUMO
Myxopapillary ependymoma (MPE) is an exceedingly rare tumor histology. While surgery is clearly the treatment of choice, controversy exists regarding the role of adjuvant radiotherapy (RT). Using the Surveillence, epidemiology, and end results (SEER) database, we aimed to determine the epidemiology, prognostic factors, and treatment-related outcomes for MPE. A total of 773 cases were found in the SEER database. The incidence in the American population was found to be 1.00 per million person-years. On multivariate analysis, receipt of surgery (HR = 0.14, CI = 0.06-0.35, p < 0.001), receipt of RT (HR = 4.06, CI = 1.87-8.81, p < 0.001), age less than 30 (HR = 0.24, CI = 0.08-0.72, p = 0.01), and Caucasian race (HR = 0.37, CI = 0.13-0.996, p = 0.049) were statistically significant prognostic factors. The mean tumor size among those receiving RT (4.6 cm) was significantly larger than among those not receiving RT (3.2 cm, p = 0.0002). Those who lived in metropolitan areas were more likely to receive RT than those who did not. Given multiple previous studies show that RT improves PFS and the discrepancy in tumor size, selection bias is likely a significant contributor to the apparent negative impact of RT on OS. Regardless, surgery remains the most crucial aspect in the care of patients with MPE.
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Neoplasias do Sistema Nervoso Central/epidemiologia , Neoplasias do Sistema Nervoso Central/mortalidade , Ependimoma/epidemiologia , Ependimoma/mortalidade , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/terapia , Criança , Pré-Escolar , Bases de Dados Factuais/estatística & dados numéricos , Ependimoma/terapia , Feminino , Seguimentos , Inquéritos Epidemiológicos , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Adulto JovemRESUMO
Patients with brain metastasis from melanoma have poor outcomes. Radiation is used both for prognostic and symptomatic value. We aimed to further clarify the role of stereotactic radiosurgery (SRS) and whole brain radiotherapy (WBRT) as well as the prognostic implication of various sites of extracranial disease. The records of 73 consecutive patients treated at the University of Rochester Medical Center for brain-metastatic melanoma from January 2004 to October 2013 were reviewed. The median overall survival (OS) was 3.0 months. Patients treated with WBRT alone had decreased OS compared to those treated with SRS alone (HR = 0.38, p = 0.001) or WBRT and SRS (HR = 0.51, p = 0.039). The mean number of brain metastasis differed (p = 0.002) in patients in patients who received WBRT (4.0) compared to those who did not (2.0). Among patients with extracranial disease (n = 63), bone metastasis (HR = 1.86, p = 0.047, n = 15) was a negative prognostic factor; liver (HR = 1.59, p = 0.113, n = 17), lung (HR = 1.51, p = 0.23, n = 51) and adrenal metastasis (HR = 1.70, p = 0.15, n = 10) were not. In patients with concurrent brain and lung metastasis, those with disease limited to those two sites (OS = 8.7 mo, n = 13) had improved OS (HR = 0.44, p = 0.014) compared to those with additional disease (OS = 1.8 mo, n = 50). Based on this hypothesis-generating retrospective analysis, SRS may offer survival benefit compared to WBRT alone in patients with brain metastatic melanoma. Bone metastasis appears to confer a particularly poor prognosis. Those with disease confined to the lung and brain may represent a population with improved prognosis.
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Neoplasias Encefálicas , Encéfalo/patologia , Irradiação Craniana , Melanoma/patologia , Radiocirurgia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/cirurgia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Feminino , Humanos , Avaliação de Estado de Karnofsky , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are very rare in the general population and challenging to treat. A paucity of data exists regarding the incidence of MPNST across all age groups and treatment outcomes in the pediatric population. We aimed to characterize both using the Survival, Epidemiology, and End Results (SEER) database. PROCEDURE: The SEER-18 database with information on the United States population from 1973 to 2009 was queried for cases of MPNST. For incidence data, 1,182 cases were found among the general population. Of those, 165 cases were in individuals aged 0-19. After exclusions, 139 cases from the SEER-18 database met study criteria for outcomes analysis. For each patient, variables including gender, age, race, stage (localized, regional, or distant), surgical treatment, and radiotherapy were obtained. RESULTS: The overall incidence of MPNST was 1.46 per million person-years, with increased incidence among the elderly. In the pediatric population, the incidence was 0.56 per million person-years, and was higher among post-pubertal children aged 10-19. Median overall survival in the pediatric population was 30 months, with only localized disease and treatment with surgery being positive prognostic factors on multivariate analysis. CONCLUSIONS: MPNST is a rare disease and, among children, is most frequent seen in adolescents. Surgery is crucial as first-line treatment for MPNST, especially if the tumor is localized at diagnosis. In patients with non-localized MPNST, the disease remains extremely difficult to manage, and both surgery and radiotherapy are interventions that should be considered.
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Neoplasias de Bainha Neural/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Genes da Neurofibromatose 1 , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Análise Multivariada , Neoplasias de Bainha Neural/mortalidade , Neoplasias de Bainha Neural/terapia , Modelos de Riscos Proporcionais , Programa de SEERAssuntos
Cardiopatias/etiologia , Doença de Hodgkin/radioterapia , Órgãos em Risco/efeitos da radiação , Lesões por Radiação/etiologia , Adulto , Sobreviventes de Câncer , Criança , Relação Dose-Resposta à Radiação , Coração/efeitos da radiação , Cardiopatias/patologia , Humanos , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por ComputadorRESUMO
PURPOSE: Early exposure to oncology care during the preclinical years of medical school may translate to increased student interest in oncology-related fields and improved understanding of oncologic treatment modalities, including radiation oncology. Many schools incorporate problem-based learning (PBL) into the medical school curriculum; this is an opportunity to immerse students in oncologic case management. We describe the effective incorporation of one course into the medical school curriculum that may be replicated at other institutions. METHODS AND MATERIALS: A PBL case regarding pancreatic cancer was created by a radiation oncology resident and faculty member in collaboration with the gastrointestinal course director for first-year medical students at a single institution. Pancreatic cancer was chosen based on curricular needs. Learning objectives were discussed to guide the creation of the case. RESULTS: All 140 first-year medical students participated in the 1-hour small group case focused on oncologic work up, multidisciplinary care, and radiation therapy concepts. Students were provided with a case prompt and resources to review prior to the PBL session. Volunteer radiation oncology facilitators attended a 30-minute educational meeting and were provided a detailed case guide 1 week before the PBL session. During the PBL case, facilitators guided students to achieve desired learning objectives. Among the 76 (54%) medical students who completed an optional post-PBL survey, the majority reported that the case motivated them to learn more about oncology (89%) and radiation oncology (82%). There was an increase in the number of subscribers to the Oncology Interest Group (43% increase from previous year) and preclinical students shadowing in the radiation oncology department. The PBL case was continued in future years for all first-year students and extended to 2 hours to promote additional discussion in response to student and facilitator feedback. CONCLUSIONS: A cancer-specific PBL case facilitated by radiation oncology educators is an effective avenue to integrate radiation oncology into the preclinical curriculum and stimulate interest in oncology among first-year medical students.
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Neoplasias Pancreáticas , Radioterapia (Especialidade) , Estudantes de Medicina , Humanos , Aprendizagem Baseada em Problemas/métodos , CurrículoRESUMO
BACKGROUND: This practice parameter was revised collaboratively by the American College of Radiology (ACR), and the American Radium Society (ARS). Timely, accurate, and effective communications are critical to quality and safety in contemporary medical practices. Radiation oncology incorporates the science and technology of complex, integrated treatment delivery and the art of providing care to individual patients. Through written physical and/or electronic reports and direct communication, radiation oncologists convey their knowledge and evaluation regarding patient care, clinical workup, and treatment provided to others in the management of the patient. Applicable practice parameters need to be revised periodically regarding medical record documentation for professional and technical components of services delivered. METHODS: This practice parameter was developed and revised according to the process described under the heading "The Process for Developing ACR Practice Parameters and Technical Standards" on the ACR website ( https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards ) by the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the ARS. Both societies have reviewed and approved the document. RESULTS: This practice parameter addresses radiation oncology communications in general, including (a) medical record, (b) electronic, and (c) doctor-patient communications, as well as specific documentation for radiation oncology reports such as (a) consultation, (b) clinical treatment management notes (including inpatient communication), (c) treatment (completion) summary, and (d) follow-up visits. CONCLUSIONS: The radiation oncologist's participation in the multidisciplinary management of patients is reflected in timely, medically appropriate, and informative communication with patients, caregivers, referring physician, and other members of the health care team. The ACR-ARS Practice Parameter for Communication: Radiation Oncology is an educational tool designed to assist practitioners in providing appropriate communication regarding radiation oncology care for patients.
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Comunicação , Radioterapia (Especialidade) , Humanos , Radioterapia (Especialidade)/normas , Relações Médico-Paciente , Sociedades Médicas , Estados UnidosRESUMO
OBJECTIVES: The adoption of transoral robotic surgery and shifting epidemiology in oropharyngeal squamous cell cancer have stimulated debate over upfront and adjuvant treatment. Institutional variation in practice patterns can be obscured in patient-level analyses. We aimed to characterize institutional patterns of care as well as identify potential associations between patterns of care and survival. METHODS: This was a retrospective cohort study of patients identified from 2004-2015 in the National Cancer Database. We analyzed 42,803 cases of oropharyngeal squamous cell cancer Stage cT1-2N0-2bM0 (AJCC 7th edition) treated with curative intent surgery and/or radiotherapy. We defined facility-4-year periods to account for changing institutional practice patterns. The 42,803 patients were treated within 2578 facility-4-year periods. We assessed institutional practice patterns, including the ratio of upfront surgery to definitive radiotherapy, case volumes, use of adjuvant therapies (radiotherapy or chemoradiotherapy), and margin positivity rates. Survival associations with institutional practice patterns were estimated with Cox regression. RESULTS: The ratio of upfront surgery to definitive radiotherapy ranged from 80-to-1 to 1-to-23. The institution-level median rate of adjuvant radiotherapy was 69% (IQR 50%-100%), adjuvant chemoradiotherapy was 44% (IQR 0%-67%), and margin-positive resection was 33% (IQR 0%-50%). On patient-level MVA, worse overall survival was not significantly associated with institutional case volume, adjuvant radiotherapy, or adjuvant chemoradiotherapy utilization. CONCLUSIONS: High rates of multimodal therapy and positive margins underscore the importance of multidisciplinary care and highlight variable patterns of care across institutions. Further work is warranted to explore indicators of high-quality care and to optimize adjuvant therapy in the HPV era.
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Because proton beam therapy (PBT) can lower the dose of radiation to the heart, lungs, and breast, it is an established radiation modality for patients with Hodgkin lymphoma (HL). Pencil beam scanning (PBS) PBT facilitates the treatment of more extensive targets. This may be especially of value for lymphoma patients who require RT to both mediastinal and axillary targets, defined here as extended target RT (ETRT), given the target distribution and need to minimize the lung, heart, and breast dose. Using the Proton Collaborative Group registry, we identified patients with HL treated with PBT to both their mediastinum and axilla, for which DICOM-RT was available. All patients were treated with PBS. To evaluate the dosimetric impact of PBS, we compared delivered PBS plans with VMAT butterfly photon plans optimized to have the same target volume coverage, when feasible. Between 2016 and 2021, twelve patients (median 26 years) received PBS ETRT (median 30.6 Gy (RBE)). Despite the large superior/inferior (SI, median 22.2 cm) and left/right (LR, median 22.8 cm) extent of the ETRT targets, all patients were treated with one isocenter except for two patients (both with SI and LR > 30 cm). Most commonly, anterior beams, with or without posterior beams, were used. Compared to photons, PBS had greater target coverage, better conformity, and lower dose heterogeneity while achieving lower doses to the lungs and heart, but not to the breast. No acute grade 3+ toxicities were reported, including pneumonitis. Proton ETRT in this small cohort was safely delivered with PBS and was associated with an improved sparing of the heart and lungs compared to VMAT.
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Purpose: The effect of climate-driven events, such as wildfires, on health care delivery and cancer care is a growing concern. Patients with cancer undergoing radiation therapy are particularly vulnerable to treatment interruptions, which have a direct effect on survival. We report the results of a study characterizing the effect of wildfires on radiation oncology clinics and their patients. Methods and Materials: A survey of California radiation oncologists was used to evaluate emergency preparedness and the effect of wildfires on the delivery of radiation therapy services between 2017 and 2022. Descriptive statistics and Pearson's χ2 tests were performed to investigate potential relationships between provider characteristics, practice settings, and perceptions of the effect of wildfire events. California Department of Forestry and Fire Protection data were employed to map the geographic distribution of wildfires to clinic locations. Results: Response rate was 12.3% (51/415 radiation oncologists), representing 25% of clinics (43/176) in 41% (24/58) of California counties. Sixty-one percent (31/51) of respondents reported being affected by a wildfire, 2 of which are rural clinics (100%, 2/2) and 29 are (59%, 29/49) metropolitan practices. Of these, 18% (9/51) reported a clinic closure, and 29% (15/51) reported staffing shortages. Respondents reported effects on patients, including having to evacuate (55%, 28/51), cancel/reschedule treatments (53%, 27/51), and experiencing physical, mental, or financial hardship due to wildfires (45%, 23/51). Respondents described effects on clinical operations, including being forced to transfer patients (24%, 12/51), transportation interruptions (37%, 19/51), regional/community evacuations (35%, 18/51), and physical/mental health effects (27%, 14/51) on clinic personnel. Less than half of the respondents (47%, 24/51) reported their workplace had a wildfire emergency preparedness plan. Additionally, geographic analysis revealed that 100% (176/176) of clinics were located within 25 miles of a wildfire. Conclusions: This study highlights the effects of wildfires on radiation oncology clinics and patients and underscores the need for emergency preparedness planning to minimize the consequences of such disasters.
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BACKGROUND: The purpose of this study was to provide further insights into whether age and/or sex are associated with prognosis in oral tongue squamous cell carcinoma. METHODS: This was a retrospective cohort study utilizing hospital registry data from 2006 to 2016 obtained from the National Cancer Database. Identified patients were divided into various cohorts based on age, sex, and staging. A descriptive analysis was performed using chi-square tests and overall survival rates were estimated using Kaplan-Meier method. RESULTS: A total of 17 642 patients were included in the study. The 5-year overall survival rates were 82.0% (95% CI: 79.8%-84.0%) in younger patients versus 67.5% (95% CI: 66.7%-68.3%, p-value <0.0001) older patients. The median overall survival for females was 143.4 months (95% CI: 133.2-NA) versus 129.8 (95% CI: 125.4-138.7, p-value <0.0001) in males. CONCLUSIONS: Our analysis suggests that younger age and female sex are both predictors of improved survival in oral tongue squamous cell carcinoma.
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Carcinoma de Células Escamosas , Estadiamento de Neoplasias , Neoplasias da Língua , Humanos , Masculino , Feminino , Neoplasias da Língua/mortalidade , Neoplasias da Língua/patologia , Neoplasias da Língua/terapia , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Fatores Etários , Fatores Sexuais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Adulto , Taxa de Sobrevida , Prognóstico , Estudos de Coortes , Idoso de 80 Anos ou mais , Estimativa de Kaplan-Meier , Sistema de Registros , Estados Unidos/epidemiologiaRESUMO
Importance: Intensity-modulated radiation therapy (IMRT) reirradiation of nonmetastatic recurrent or second primary head and neck squamous cell carcinoma (HNSCC) results in poor progression-free survival (PFS) and overall survival (OS). Objective: To investigate the tolerability, PFS, OS, and patient-reported outcomes with nivolumab (approved standard of care for patients with HNSCC) during and after IMRT reirradiation. Design, Setting, and Participants: In this multicenter nonrandomized phase 2 single-arm trial, the treatment outcomes of patients with recurrent or second primary HNSCC who satisfied recursive partitioning analysis class 1 and 2 definitions were evaluated. Between July 11, 2018, and August 12, 2021, 62 patients were consented and screened. Data were evaluated between June and December 2023. Intervention: Sixty- to 66-Gy IMRT in 30 to 33 daily fractions over 6 to 6.5 weeks with nivolumab, 240 mg, intravenously 2 weeks prior and every 2 weeks for 5 cycles during IMRT, then nivolumab, 480 mg, intravenously every 4 weeks for a total nivolumab duration of 52 weeks. Main Outcomes and Measures: The primary end point was PFS. Secondary end points included OS, incidence, and types of toxic effects, including long-term treatment-related toxic effects, patient-reported outcomes, and correlatives of tissue and blood biomarkers. Results: A total of 62 patients were screened, and 51 were evaluable (median [range] age was 62 [56-67] years; 42 [82%] were male; 6 [12%] had p16+ disease; 38 [75%] had salvage surgery; and 36 [71%.] had neck dissection). With a median follow-up of 24.5 months (95% CI, 19.0-25.0), the estimated 1-year PFS was 61.7% (95% CI, 49.2%-77.4%), rejecting the null hypothesis of 1-year PFS rate of less than 43.8% with 1-arm log-rank test P = .002 within a 1-year timeframe. The most common treatment-related grade 3 or higher adverse event (6 [12%]) was lymphopenia with 2 patients (4%) and 1 patient each (2%) exhibiting colitis, diarrhea, myositis, nausea, mucositis, and myasthenia gravis. Functional Assessment of Cancer Therapy-General and Functional Assessment of Cancer Therapy-Head and Neck Questionnaire quality of life scores remained stable and consistent across all time points. A hypothesis-generating trend favoring worsening PFS and OS in patients with an increase in blood PD1+, KI67+, and CD4+ T cells was observed. Conclusions and Relevance: This multicenter nonrandomized phase 2 trial of IMRT reirradiation therapy and nivolumab suggested a promising improvement in PFS over historical controls. The treatment was well tolerated and deserves further evaluation. Trial Registration: ClinicalTrials.gov Identifier: NCT03521570.
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Neoplasias de Cabeça e Pescoço , Recidiva Local de Neoplasia , Nivolumabe , Radioterapia de Intensidade Modulada , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Nivolumabe/uso terapêutico , Nivolumabe/efeitos adversos , Masculino , Feminino , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Radioterapia de Intensidade Modulada/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Pessoa de Meia-Idade , Idoso , Recidiva Local de Neoplasia/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/mortalidade , Reirradiação/métodos , Reirradiação/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Segunda Neoplasia Primária , Intervalo Livre de Progressão , AdultoRESUMO
[This corrects the article DOI: 10.1016/j.tipsro.2022.09.002.].
RESUMO
OBJECTIVE: To evaluate lymphovascular invasion as an independent predictor for overall survival in patients with oral cavity squamous cell carcinoma. STUDY DESIGN: Retrospective cohort study. SETTING: Multi-center, population-based facilities reporting to the National Cancer Database registry. METHODS: The database was accessed to collect data on patients with oral cavity squamous cell carcinoma. A multivariate cox proportional hazards model was used to analyze the association between presence of lymphovascular invasion and overall survival. RESULTS: 16,992 patients met inclusion criteria. 3,457 patients had lymphovascular invasion. The mean follow-up was 32 ± 19 months. Lymphovascular invasion predicted reduced 2-year overall survival (relative hazard 1.29, 95% CI: 1.20, 1.38, p < 0.001) and 5-year overall survival (relative hazard 1.30, 95% CI: 1.23, 1.39, p < 0.001). LVI reduced overall survival in patients with squamous cell carcinoma of the oral tongue (HR: 1.27, 95% CI: 1.17, 1.39, p < 0.001), floor of mouth (HR: 1.33, 95% CI: 1.17, 1.52, p < 0.001) and buccal mucosa (HR: 1.44, 95% CI: 1.15, 1.81, p = 0.001). Patients with lymphovascular invasion treated with surgery plus post-operative radiotherapy had significantly improved survival compared to those who underwent surgery alone (relative hazard 1.79, 95% CI: 1.58, 2.03, p < 0.001), and patients treated with surgery + post-operative chemoradiotherapy had improved survival compared to those treated with surgery alone (relative hazard 2.0, 95% CI: 2.26, 1.79, p < 0.001). CONCLUSION: Lymphovascular invasion is an important independent risk factor for decreased overall survival in oral cavity squamous cell carcinoma involving the oral tongue, floor of mouth and buccal mucosa subsites.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Estadiamento de Neoplasias , Prognóstico , Invasividade Neoplásica/patologia , Análise de SobrevidaRESUMO
As the prognosis for squamous cell carcinoma of the head and neck remains unsatisfactory when compared to other malignancies, novel therapies targeting specific biomarkers are a critical emerging area of great promise. One particular class of drugs that has been developed to impede tumor angiogenesis is vascular endothelial growth factor-tyrosine kinase inhibitors. As current data is primarily limited to preclinical and phase I/II trials, this review summarizes the current and future prospects of these agents in squamous cell carcinoma of the head and neck. In particular, the combination of these agents with immunotherapy is an exciting area that may be a promising option for patients with recurrent or metastatic disease, evidenced in recent trials such as the combination immune checkpoint inhibitors with lenvatinib and cabozantinib. In addition, the use of such combination therapy preoperatively in locally advanced disease is another area of interest.