RESUMEN
Radiotherapy (RT) continues to play a key role in the management of head and neck cancer (HNC). Xerostomia remains a principal detriment to the quality of life (QoL) for 80 % of surviving patients receiving head and neck radiation. Radiation-induced injury to the salivary glands is dose-dependent, and thus efforts have been focused on decreasing radiation to the salivary glands. Decreased saliva production reduces both short-term and long-term quality of life in head and neck survivors by impacting on taste and contributing to dysphagia. Several radioprotective agents to the salivary gland have been investigated. Although not widely practiced, surgical transfer of the submandibular gland prior to RT is the mainstay of surgical options in preventing xerostomia. This review focuses on the strategies to improve xerostomia following radiation therapy in head and neck cancers.
Asunto(s)
Neoplasias de Cabeza y Cuello , Xerostomía , Humanos , Xerostomía/etiología , Xerostomía/prevención & control , Calidad de Vida , Glándulas Salivales , Neoplasias de Cabeza y Cuello/complicaciones , Neoplasias de Cabeza y Cuello/radioterapia , Glándula SubmandibularRESUMEN
OBJECTIVES: The aim of the study was to investigate the association of surgical margin conditions, including positive specimen margins revised to negative relative to local recurrence, disease-free survival, and overall survival (OS) within a cohort of HPV-mediated oropharyngeal squamous cell carcinoma (OPSCC) who underwent en bloc resection via transoral robotic surgery (TORS). MATERIALS AND METHODS: Retrospective cohort of patients with untreated HPV-mediated OPSCC cT1 or T2 undergoing TORS resection between October 2014 and March 2020. The methodologic description of our interdisciplinary institutional approach, number of cut-through margins (CTMs) during intraoperative consultation, percentage of final positive margin cases, and disease-free survival and OS stratified by margin status and margin tumor-free distance is identified. RESULTS: 135 patients with primary cT1/T2 HPV-mediated OPSCC met inclusion criteria. Twenty-eight of 135 (20.7%) specimens revealed CTM and were revised during the same operative setting. Three of 135 (2.2%) surgical cases had positive final margin status. Local control rate was 97%. On univariate analysis, margin distance did not impact OS. CTM and final positive margins had lower OS than initially negative margins (p = 0.044). Pathologic N-stage significantly impacted OS (p < 0.001). CONCLUSIONS: High local control rate and low final positive margin status confound the study of specimen margin-based techniques in HPV-mediated OPSCC resected en bloc with TORS. Pathologic N-stage may impact OS more than margin status. Larger numbers are needed to confirm differences.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Procedimientos Quirúrgicos Robotizados , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Márgenes de Escisión , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/patología , Neoplasias Orofaríngeas/cirugía , Neoplasias Orofaríngeas/patología , Procedimientos Quirúrgicos Robotizados/métodos , Estudios Retrospectivos , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/cirugíaRESUMEN
OBJECTIVES: The eighth edition American Joint Committee on Cancer (AJCC) Staging incorporates significant changes to the seventh edition in the staging of oropharyngeal squamous cell carcinomas (OPSCC). An important change was the inclusion of OPSCC associated with the human papilloma virus (HPV). Our goal is to compare the performance of both staging systems for patients with HPV-selected and unselected clinical characteristics for OPSCC. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, 2004-2016, we identified patients with likely HPV-associated OPSCC based on surrogate markers (white males aged <65 years old with squamous cell carcinomas of the tonsil and base of tongue), excluding those who underwent surgery. We re-classified these patients using seventh and eighth edition staging for HPV-selected OPSCC and compared the prediction performance of both staging editions for overall survival (OS) and disease-specific survival (DSS). We performed the same analysis for clinically unselected patients with OPSCC. RESULTS: Our analysis included 9554 patients with a median follow-up of 67 months. Comparing the eighth versus seventh edition for our HPV-selected cohort, clinical staging changed for 92.3% of patients and 10-year OS was 62.2%, 61.2%, 35.3%, and 15.5% for Stage I, II, III, and IV, versus 52.9%, 59.2%, 61.6%, 55.1%, 38.3%, and 15.5% for stage I, II, III, IVA, IVB, and IVC, respectively. A similar pattern was observed for 10-year DSS. The concordance statistics for our HPV-selected cohort were improved for both AJCC 7 (0.6260) and AJCC 8 (0.6846) compared with the unselected cohort, 0.5860 and 0.6457 for AJCC 7 and 8, respectively. CONCLUSION: The overall performance of discrimination improved from AJCC 7 to AJCC 8 for both clinically selected and unselected patients, but more notably for our HPV-selected cohort. Despite the lack of statistically significant differentiation between Stages I and II in AJCC 8 in either groups, markedly improved discrimination was observed between Stages I/II, III, and IV in the HPV-selected cohort.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Anciano , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Estadificación de Neoplasias , Neoplasias Orofaríngeas/patología , Papillomaviridae , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/patología , Pronóstico , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/patologíaRESUMEN
PURPOSE: Quality assurance computed tomography (QACT) is the current clinical practice in proton therapy to evaluate the needs for replan. QACT could falsely indicate replan because of setup issues that would be solved on the treatment machine. Deforming the treatment planning CT (TPCT) to the pretreatment CBCT may eliminate this issue. We investigated the performance of replan evaluation based on deformed TPCT (TPCTdir) for proton head and neck (H&N) therapy. METHODS AND MATERIALS: Twenty-eight H&N datasets along with pretreatment CBCT and QACT were used to validate the method. The changes in body volume were analyzed between the no-replan and replan groups. The dose on the TPCTdir, the deformed QACT (QACTdir), and the QACT were calculated by applying the clinical plans to these image sets. Dosimetric parameters' changes, including ΔD95, ΔDmean, and ΔD1 for the clinical target volumes (CTVs) were calculated. Receiver operating characteristic curves for replan evaluation based on ΔD95 on QACT and TPCTdir were calculated, using ΔD95 on QACTdir as the reference. A threshold for replan based on ΔD95 on TPCTdir is proposed. The specificities for the proposed method were calculated. RESULTS: The changes in the body contour were 95.8 ± 83.8 cc versus 305.0 ± 235.0 cc (p < 0.01) for the no-replan and replan groups, respectively. The ΔD95, ΔDmean, and ΔD1 are all comparable for all the evaluations. The differences between TPCTdir and QACTdir evaluations were 0.30% ± 0.86%, 0.00 ± 0.22 Gy, and -0.17 ± 0.61 Gy for CTV ΔD95, ΔDmean, and ΔD1, respectively. The corresponding differences between the QACT and QACTdir were 0.12% ± 1.1%, 0.02 ± 0.32 Gy, and -0.01 ± 0.71 Gy. CTV ΔD95 > 2.6% in TPCTdir was chosen as the threshold to trigger QACT/replan. The corresponding specificity was 94% and 98% for the clinical practice and the proposed method, respectively. CONCLUSIONS: The replan evaluation based on TPCTdir provides better specificity than that based on the QACT.
Asunto(s)
Neoplasias de Cabeza y Cuello , Terapia de Protones , Radioterapia de Intensidad Modulada , Tomografía Computarizada de Haz Cónico/métodos , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodosRESUMEN
BACKGROUND: The authors measured epigenetic age acceleration (EAA) during and after cancer treatment and its association with inflammation and fatigue, which is a debilitating symptom in patients with cancer. METHODS: Patients who had head and neck cancer without distant metastases were assessed before, immediately after, and at 6 months and 12 months postradiotherapy. Blood DNA methylation was assessed using a proprietary bead chip (the Illumina MethylationEPIC BeadChip). EAA was calculated using the Levine epigenetic clock (DNAmPhenoAge), adjusted for chronological age. Fatigue was assessed using the Multidimensional Fatigue Inventory-20. Inflammatory markers were measured using standard techniques. RESULTS: Most patients (N = 133) were men, White, had advanced disease, and received concurrent chemoradiation. EAA changes over time were significant, with the largest increase (4.9 years) observed immediately after radiotherapy (P < .001). Increased EAA was associated with elevated fatigue (P = .003) over time, and patients who had severe fatigue experienced 3.1 years higher EAA than those who had low fatigue (P < .001), which was more prominent (5.6 years; P = .018) for patients who had human papillomavirus-unrelated disease at 12 months posttreatment. EAA was also positively associated with inflammatory markers, including C-reactive protein (CRP) and interleukin-6 (IL-6), over time (P < .001), and patients who had high CRP and IL-6 levels exhibited increases of 4.6 and 5.9 years, respectively, in EAA compared with those who had low CRP and IL-6 levels (P < .001). CRP and IL-6 mediated the association between EAA and fatigue (CRP: 95% CI, 0.060-0.279; IL-6: 95% CI, 0.024-0.220). CONCLUSIONS: Patients with head and neck cancer experienced increased EAA, especially immediately after treatment completion. EAA was associated with greater fatigue and inflammation, including 1 year after treatment. Inflammation may be a target to reduce the impact of age acceleration on poor functional outcomes.
Asunto(s)
Epigénesis Genética , Neoplasias de Cabeza y Cuello , Aceleración , Fatiga/genética , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Inflamación/genética , Inflamación/metabolismo , Estudios Longitudinales , MasculinoRESUMEN
PURPOSE: Recent evidence supports a key role of gut microbiome in brain health. We conducted a pilot study to assess associations of gut microbiome with cancer-related fatigue and explore the associations with DNA methylation changes. METHODS: Self-reported Multidimensional Fatigue Inventory and stool samples were collected at pre-radiotherapy and one-month post-radiotherapy in patients with head and neck cancer. Gut microbiome data were obtained by sequencing the 16S ribosomal ribonucleic acid gene. DNA methylation changes in the blood were assessed using Illumina Methylation EPIC BeadChip. RESULTS: We observed significantly different gut microbiota patterns among patients with high vs. low fatigue across time. This pattern was characterized by low relative abundance in short-chain fatty acid-producing taxa (family Ruminococcaceae, genera Subdoligranulum and Faecalibacterium; all p < 0.05), with high abundance in taxa associated with inflammation (genera Family XIII AD3011 and Erysipelatoclostridium; all p < 0.05) for high-fatigue group. We identified nine KEGG Orthology pathways significantly different between high- vs. low-fatigue groups over time (all p < 0.001), including pathways related to fatty acid synthesis and oxidation, inflammation, and brain function. Gene set enrichment analysis (GSEA) was performed on the top differentially methylated CpG sites that were associated with the taxa and fatigue. All biological processes from the GSEA were related to immune responses and inflammation (FDR < 0.05). CONCLUSIONS: Our results suggest different patterns of the gut microbiota in cancer patients with high vs. low fatigue. Results from functional pathways and DNA methylation analyses indicate that inflammation is likely to be the major driver in the gut-brain axis for cancer-related fatigue.
Asunto(s)
Epigénesis Genética/genética , Fatiga/etiología , Microbioma Gastrointestinal/fisiología , Neoplasias/complicaciones , Fatiga/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/genética , Proyectos PilotoRESUMEN
BACKGROUND: Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma have high survival when treated with radiotherapy plus cisplatin. Whether replacement of cisplatin with cetuximab-an antibody against the epidermal growth factor receptor-can preserve high survival and reduce treatment toxicity is unknown. We investigated whether cetuximab would maintain a high proportion of patient survival and reduce acute and late toxicity. METHODS: RTOG 1016 was a randomised, multicentre, non-inferiority trial at 182 health-care centres in the USA and Canada. Eligibility criteria included histologically confirmed HPV-positive oropharyngeal carcinoma; American Joint Committee on Cancer 7th edition clinical categories T1-T2, N2a-N3 M0 or T3-T4, N0-N3 M0; Zubrod performance status 0 or 1; age at least 18 years; and adequate bone marrow, hepatic, and renal function. We randomly assigned patients (1:1) to receive either radiotherapy plus cetuximab or radiotherapy plus cisplatin. Randomisation was balanced by using randomly permuted blocks, and patients were stratified by T category (T1-T2 vs T3-T4), N category (N0-N2a vs N2b-N3), Zubrod performance status (0 vs 1), and tobacco smoking history (≤10 pack-years vs >10 pack-years). Patients were assigned to receive either intravenous cetuximab at a loading dose of 400 mg/m2 5-7 days before radiotherapy initiation, followed by cetuximab 250 mg/m2 weekly for seven doses (total 2150 mg/m2), or cisplatin 100 mg/m2 on days 1 and 22 of radiotherapy (total 200 mg/m2). All patients received accelerated intensity-modulated radiotherapy delivered at 70 Gy in 35 fractions over 6 weeks at six fractions per week (with two fractions given on one day, at least 6 h apart). The primary endpoint was overall survival, defined as time from randomisation to death from any cause, with non-inferiority margin 1·45. Primary analysis was based on the modified intention-to-treat approach, whereby all patients meeting eligibility criteria are included. This study is registered with ClinicalTrials.gov, number NCT01302834. FINDINGS: Between June 9, 2011, and July 31, 2014, 987 patients were enrolled, of whom 849 were randomly assigned to receive radiotherapy plus cetuximab (n=425) or radiotherapy plus cisplatin (n=424). 399 patients assigned to receive cetuximab and 406 patients assigned to receive cisplatin were subsequently eligible. After median follow-up duration of 4·5 years, radiotherapy plus cetuximab did not meet the non-inferiority criteria for overall survival (hazard ratio [HR] 1·45, one-sided 95% upper CI 1·94; p=0·5056 for non-inferiority; one-sided log-rank p=0·0163). Estimated 5-year overall survival was 77·9% (95% CI 73·4-82·5) in the cetuximab group versus 84·6% (80·6-88·6) in the cisplatin group. Progression-free survival was significantly lower in the cetuximab group compared with the cisplatin group (HR 1·72, 95% CI 1·29-2·29; p=0·0002; 5-year progression-free survival 67·3%, 95% CI 62·4-72·2 vs 78·4%, 73·8-83·0), and locoregional failure was significantly higher in the cetuximab group compared with the cisplatin group (HR 2·05, 95% CI 1·35-3·10; 5-year proportions 17·3%, 95% CI 13·7-21·4 vs 9·9%, 6·9-13·6). Proportions of acute moderate to severe toxicity (77·4%, 95% CI 73·0-81·5 vs 81·7%, 77·5-85·3; p=0·1586) and late moderate to severe toxicity (16·5%, 95% CI 12·9-20·7 vs 20·4%, 16·4-24·8; p=0·1904) were similar between the cetuximab and cisplatin groups. INTERPRETATION: For patients with HPV-positive oropharyngeal carcinoma, radiotherapy plus cetuximab showed inferior overall survival and progression-free survival compared with radiotherapy plus cisplatin. Radiotherapy plus cisplatin is the standard of care for eligible patients with HPV-positive oropharyngeal carcinoma. FUNDING: National Cancer Institute USA, Eli Lilly, and The Oral Cancer Foundation.
Asunto(s)
Antineoplásicos/uso terapéutico , Cetuximab/uso terapéutico , Cisplatino/uso terapéutico , Neoplasias Orofaríngeas/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Cetuximab/administración & dosificación , Cetuximab/efectos adversos , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Esquema de Medicación , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/virología , Infecciones por Papillomavirus/complicaciones , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Resultado del TratamientoRESUMEN
OBJECTIVE: Fatigued cancer patients often have high peripheral inflammation; however, the biological mechanisms of this association remain unclear. We examined whether decreased sensitivity of immune cells to the anti-inflammatory effects of glucocorticoids may contribute to inflammation and fatigue in head and neck cancer (HNC) patients during treatment. METHODS: HNC patients without distant metastasis and with curative intent (n = 77) were studied 1 week before intensity-modulated radiotherapy (IMRT) and 1 month after IMRT. At each time point, fatigue was measured by the Multidimensional Fatigue Inventory-20 along with plasma inflammation markers and glucocorticoid receptor (GR) sensitivity as determined by in vitro dexamethasone suppression of lipopolysaccharide-induced interleukin 6. Linear regression models were used. RESULTS: In contrast to our hypothesis, GR sensitivity increased during treatment; however, increased fatigue was associated with a lesser increase in GR sensitivity from baseline to 1 month after IMRT (unstandardized estimate = 4.07, p = .02). This effect was more prominent in human papillomavirus-unrelated HNCs (unstandardized estimate = 8.22, p = .002). Lower increases in GR sensitivity were also associated with increased inflammation at 1 month after IMRT as represented by C-reactive protein, interleukin 6, and tumor necrosis factor α. Addition of inflammation markers to models of GR sensitivity predicting fatigue indicated that these inflammation markers were stronger predictors of fatigue than GR sensitivity. CONCLUSIONS: Lower increases in GR sensitivity during HNC treatment were significantly predictive of increased fatigue and inflammation markers. Inflammation markers in turn predicted fatigue above and beyond levels of GR sensitivity. Our findings indicate that HNC patients with cancer-related fatigue may exhibit a decreased capacity for glucocorticoids to regulate inflammatory processes, as evidenced by a lower increase in GR sensitivity. Larger studies are necessary to verify the findings.
Asunto(s)
Fatiga/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Inflamación/metabolismo , Receptores de Glucocorticoides/metabolismo , Adulto , Anciano , Proteína C-Reactiva/metabolismo , Carcinoma de Células Escamosas/metabolismo , Dexametasona/farmacología , Femenino , Glucocorticoides/metabolismo , Humanos , Interleucina-6/metabolismo , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/metabolismo , Estudios Prospectivos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
This pilot study examined whether a combined aerobic resistance exercise program reduced fatigue and the potential inflammatory and epigenetic mechanisms in patients with head and neck cancer (HNC) receiving intensity-modulated radiotherapy. The exercise group (N = 12) received a 3-month supervised aerobic resistance exercise intervention that was initiated before a 6-week radiotherapy regimen; the control group (N = 14) received standard care. Fatigue was measured using Multidimensional Fatigue Inventory-20; physical function measures included a 6-minute walk distance (6MWD), chair stands, bicep curls, and hand grip strength. Inflammatory markers and DNA methylation data were acquired using standardized protocol. Patients were mostly white (93%) and male (81%) with a mean age of 57 years. At the end of the intervention, the exercise group had a marginal decrease in fatigue compared with the control (-5.0 vs. 4.9; P = 0.10). The exercise group had a significantly greater improvement in 6MWD (29.8 vs. -55.5 m; P = 0.04), and a marginally smaller decline in hand grip (-0.3 vs. -5.8 lbs; P = 0.05) at the end of the intervention than the control. No significant difference in inflammatory markers was observed between groups. Lower plasma interleukin (IL) 6, IL1 receptor antagonist, tumor necrosis factor α (TNFα), soluble TNF receptor II and C-reactive protein were significantly associated with increased 6MWD, chair stand, and bicep curl at the end of the intervention (p < 0.05). Among the 1152 differentially methylated sites (DMS) after intervention (p < 0.001), 163 DMS were located in gene promoter regions. Enrichment analysis suggested that the top 10 upstream regulators were associated with tumor (HNF4A, RPP38, HOXA9, SAHM1, CDK7, NDN, RPS15) and inflammation (IRF7, CRKL, ONECUT1). The top 5 diseases or functions annotations of the 62 hypermethylated DMS indicated anti-tumor and anti-inflammatory effects that might be linked to exercise. These findings suggest that exercise may improve physical performance and reduce fatigue, which could be further linked to decreased inflammation, during active radiotherapy for HNC patients. Larger studies are warranted.
Asunto(s)
Neoplasias de Cabeza y Cuello , Entrenamiento de Fuerza , Epigénesis Genética , Fatiga , Fuerza de la Mano , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Calidad de VidaRESUMEN
BACKGROUND: With an expectation of excellent locoregional control, ongoing efforts to de-intensify therapy for patients with human papillomavirus-associated squamous cell oropharyngeal cancer necessitate a better understanding of the metastatic risk for patients with this disease. The objective of this study was to determine what factors affect the risk of metastases in patients with squamous cell cancers of the oropharynx. METHODS: Under a shared use agreement, 547 patients from Radiation Therapy Oncology Group 0129 and 0522 with nonmetastatic oropharyngeal squamous cell cancers who had a known p16 status and smoking status were analyzed to assess the association of clinical features with the development of distant metastases. The analyzed factors included the p16 status, sex, T stage, N stage, age, and smoking history. RESULTS: A multivariate analysis of 547 patients with a median follow-up of 4.8 years revealed that an age ≥ 50 years (hazard ratio [HR], 3.28; P = .003), smoking for more than 0 pack-years (HR, 3.09; P < .001), N3 disease (HR, 2.64; P < .001), T4 disease (HR, 1.63; P = .030), and a negative p16 status (HR, 1.60; P = .044) were all factors associated with an increased risk of distant disease. CONCLUSIONS: Age, smoking, N3 disease, T4 disease, and a negative p16 status were associated with the development of distant metastases in patients with squamous cell cancers of the oropharynx treated definitively with concurrent chemoradiation.
Asunto(s)
Carcinoma de Células Escamosas/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Neoplasias Orofaríngeas/patología , Infecciones por Papillomavirus/complicaciones , Fumar Tabaco/epidemiología , Adulto , Factores de Edad , Anciano , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias Orofaríngeas/metabolismo , Neoplasias Orofaríngeas/virología , Infecciones por Papillomavirus/patología , Estudios Prospectivos , Medición de RiesgoRESUMEN
BACKGROUND: The prognostic relevance of human papillomavirus (HPV) status in patients with nonoropharyngeal (OPX) squamous cell cancer (SCC) of the head and neck is controversial. In the current study, the authors evaluated the impact of high-risk HPV status on overall survival (OS) in patients with non-OPX SCC using a large database approach. METHODS: The National Cancer Data Base was queried to identify patients diagnosed from 2004 through 2014 with SCC of the OPX, hypopharynx (HPX), larynx, and oral cavity (OC) with known HPV status. Survival was estimated using Kaplan-Meier methods; distributions were compared using log-rank tests. Propensity score-matching and inverse probability of treatment weighing (IPTW) methods were used; cohorts were matched based on age, sex, Charlson-Deyo score, clinical American Joint Committee on Cancer (AJCC) group stage, treatments received, and anatomic subsite. Propensity analyses were stratified by group stage of disease. RESULTS: A total of 24,740 patients diagnosed from 2010 through 2013 were analyzed: 1085 patients with HPX, 4804 with laryngeal, 4,018 with OC, and 14,833 with OPX SCC. The percentages of HPV-positive cases by disease site were 17.7% for HPX, 11% for larynx, 10.6% for OC, and 62.9% for OPX. HPV status was found to be prognostic in multiple unadjusted and propensity-adjusted non-OPX populations. HPV positivity was associated with superior OS in patients with HPX SCC with a hazard ratio (HR) of 0.61 (P < .001 by IPTW), in patients with AJCC stage III to IVB laryngeal SCC (HR, 0.79; P = .019 by IPTW), and in patients with AJCC stage III to IVB OC SCC (HR, 0.78; P = .03 by IPTW). CONCLUSIONS: Positive high-risk HPV status appears to be associated with longer OS in multiple populations of patients with non-OPX head and neck disease (HPX, locally advanced larynx, and OC). If prospectively validated, these findings have implications for risk stratification.
Asunto(s)
Neoplasias Orofaríngeas/mortalidad , Neoplasias Orofaríngeas/virología , Infecciones por Papillomavirus/complicaciones , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Bases de Datos Factuales , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Neoplasias Orofaríngeas/patología , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Small cell carcinomas of the head and neck (SmCCHNs) are rare neoplasms with an unfavorable prognosis. Population-based data describing survival and prognostic factors for SmCCHN are limited. METHODS: Data were obtained from the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database for 1973-2013. Patient and tumor-related characteristics for SmCCHN were compared with those for squamous cell carcinoma of the head and neck (SCCHN). Survival was compared by constructing Kaplan-Meier curves and Cox proportional hazard models with and without propensity score matching. RESULTS: The data set included 609 SmCCHN and 227,943 SCCHN cases. Both histological subtypes were more common in men than women and more common in white patients. SmCCHN was most likely to originate in the larynx, glottis and hypopharynx, or salivary glands and to present with more advanced stage and grade. SCCHN was most likely to originate in the oral cavity and was found infrequently in the salivary glands. Overall 5- and 10-year survival estimates were 27% and 18% for SmCCHN and 46% and 31% for SCCHN, respectively. In multivariable survival analyses adjusting for age, sex, race, marital status, year of diagnosis, stage, grade, and receipt of radiation, the hazard ratio (HR) comparing SmCCHN with SCCHN was 1.53 with a 95% confidence interval (CI) from 1.39 to 1.68. Average 5-year survival varied widely between the histologic types when comparing tumor sites: 14.5% for SmCCHN versus 48.9% for SCCHN in the oropharynx. In propensity score matched analyses, the corresponding HR was 1.27 (95% CI, 1.15-1.40). CONCLUSION: Compared with SCCHN, SmCCHN carries a worse survival and is more likely to present with more advanced stage. IMPLICATIONS FOR PRACTICE: Small cell carcinoma of the head and neck (SmCCHN) is a rare subtype of head and neck cancer. In this Surveillance, Epidemiology, and End Results (SEER) data analysis, the characteristics and survival of SmCCHN are compared with those of the common squamous cell carcinoma of the head and neck. Results show that SmCCHN carries a worse prognosis and tends to present at a more advanced stage; SmCCHN also is ten times more likely to originate from the salivary glands. These findings may have implications for clinical practice, as location of the tumor may strongly associate with the pathologic diagnosis. If a SmCCHN is diagnosed, a disseminated disease is likely; hence vigilance in staging procedures is indicated.
Asunto(s)
Carcinoma de Células Pequeñas/epidemiología , Carcinoma de Células Escamosas/epidemiología , Neoplasias de Cabeza y Cuello/epidemiología , Adolescente , Adulto , Carcinoma de Células Pequeñas/mortalidad , Carcinoma de Células Escamosas/mortalidad , Niño , Preescolar , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Programa de VERF , Análisis de Supervivencia , Adulto JovenRESUMEN
A wide variety of tumors, both benign and malignant, occur in the parapharyngeal space. Depending on histology and extent, treatment may include surgery and/or radiotherapy (RT). Herein we discuss the role of RT in the management of some of the more commonly encountered neoplasms, including salivary gland tumors, paragangliomas, schwannomas, and soft-tissue sarcomas.
Asunto(s)
Neurilemoma/radioterapia , Paraganglioma/radioterapia , Neoplasias Faríngeas/radioterapia , Neoplasias de las Glándulas Salivales/radioterapia , Sarcoma/radioterapia , Terapia Combinada , Humanos , Procedimientos Quirúrgicos Otorrinolaringológicos , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/métodosRESUMEN
PURPOSE: Dual-energy computed tomography (DECT) using TwinBeam CT (TBCT) is a new option for radiation oncology simulators. TBCT scanning provides virtual monoenergetic images which are attractive in treatment planning since lower energies offer better contrast for soft tissues, and higher energies reduce noise. A protocol is needed to achieve optimal performance of this feature. In this study, we investigated the TBCT scan schema with the head-and-neck radiotherapy workflow at our clinic and selected the optimal energy with best contrast-noise-ratio (CNR) in organs-at-risks (OARs) delineation for head-and-neck treatment planning. METHODS AND MATERIALS: We synthesized monochromatic images from 40 keV to 190 keV at 5 keV increments from data acquired by TBCT. We collected the Hounsfield unit (HU) numbers of OARs (brainstem, mandible, spinal cord, and parotid glands), the HU numbers of marginal regions outside OARs, and the noise levels for each monochromatic image. We then calculated the CNR for the different OARs at each energy level to generate a serial of spectral curves for each OAR. Based on these spectral curves of CNR, the mono-energy corresponding to the max CNR was identified for each OAR of each patient. RESULTS: Computed tomography scans of ten patients by TBCT were used to test the optimal monoenergetic image for the CNR of OAR. Based on the maximized CNR, the optimal energy values were 78.5 ± 5.3 keV for the brainstem, 78.0 ± 4.2 keV for the mandible, 78.5 ± 5.7 keV for the parotid glands, and 78.5 ± 5.3 keV for the spinal cord. Overall, the optimal energy for the maximum CNR of these OARs in head-and-neck cancer patients was 80 keV. CONCLUSION: We have proposed a clinically feasible protocol that selects the optimal energy level of the virtual monoenergetic image in TBCT for OAR delineation based on the CNR in head-and-neck OAR. This protocol can be applied in TBCT simulation.
Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeza y Cuello/radioterapia , Órganos en Riesgo/efectos de la radiación , Interpretación de Imagen Radiográfica Asistida por Computador/normas , Imagen Radiográfica por Emisión de Doble Fotón/normas , Planificación de la Radioterapia Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/diagnóstico por imagen , Femenino , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Órganos en Riesgo/diagnóstico por imagen , Pronóstico , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Imagen Radiográfica por Emisión de Doble Fotón/métodos , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/métodos , Estudios Retrospectivos , Relación Señal-RuidoRESUMEN
BACKGROUND: Human papillomavirus (HPV) infection has contributed to an increased incidence of squamous cell carcinoma of the head and neck (SCCHN). Fatigue is a major side effect of SCCHN and its treatment. However, to the authors' knowledge, the association between HPV and fatigue has not been examined to date, nor is it known whether HPV influences biological mechanisms of fatigue, including inflammation. METHODS: Patients with SCCHN who were without distant metastasis were assessed at baseline (pre-radiotherapy) and 1 month and 3 months postradiotherapy. Fatigue was measured using the Multidimensional Fatigue Inventory. Peripheral inflammation was assessed by plasma C-reactive protein (CRP), interleukin 1 receptor antagonist (IL-1ra), soluble tumor necrosis factor receptor 2 (sTNFR2), and IL-6. Mixed effect models were used to examine associations. RESULTS: A total of 94 patients who were newly diagnosed were enrolled; 53% had HPV-related tumors. Patients with HPV-unrelated tumors had higher fatigue and higher plasma CRP, sTNFR2, and IL-6 over time, especially at baseline and 3 months after intensity-modulated radiotherapy compared with those with HPV-related tumors (all P < .05). However, fatigue and plasma sTNFR2 increased more significantly from baseline to 1 month after radiotherapy in the HPV-related group compared with the HPV-unrelated group (both P < .01). Controlling for significant covariates, HPV status and inflammation were found to be independent predictors of fatigue over time. CONCLUSIONS: HPV status is an important marker of vulnerability to the behavioral and immune consequences of SCCHN and its treatment, providing support for different symptom management strategies. Special emphasis should be placed on addressing marked persistent fatigue in patients with HPV-unrelated tumors, whereas attention should be paid to the large increases in fatigue during treatment among patients with HPV-related tumors. Cancer 2018. © 2018 American Cancer Society.
Asunto(s)
Fatiga/epidemiología , Inflamación/epidemiología , Infecciones por Papillomavirus/epidemiología , Carcinoma de Células Escamosas de Cabeza y Cuello/epidemiología , Anciano , Proteína C-Reactiva/metabolismo , Fatiga/sangre , Fatiga/complicaciones , Fatiga/virología , Femenino , Humanos , Inflamación/sangre , Inflamación/complicaciones , Inflamación/virología , Proteína Antagonista del Receptor de Interleucina 1/sangre , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/sangre , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Receptores Tipo II del Factor de Necrosis Tumoral/sangre , Carcinoma de Células Escamosas de Cabeza y Cuello/sangre , Carcinoma de Células Escamosas de Cabeza y Cuello/complicaciones , Carcinoma de Células Escamosas de Cabeza y Cuello/virologíaRESUMEN
PURPOSE: To review the current aspects of knowledge related to the risk of cerebrovascular events in patients receiving head and neck radiotherapy. METHODS: A literature search was performed in PubMed. Papers meeting selection criteria were reviewed. RESULTS: We provide an update on the problem by identifying key studies that have contributed to our current understanding of the epidemiology, radiologic features, pathogenesis, and treatment of the disease. The incidence of carotid artery stenosis ranged from 18 to 38% in patients who underwent radiotherapy for head and neck cancer versus from 0 to 9.2% among the nonirradiated patients. Neck irradiation increases the intima-media thickness of the carotid artery wall. These changes are the earliest visible alteration in the carotid wall and are also detected with color Doppler ultrasonography. Endovascular treatment with a carotid angioplasty and stenting is the first-line treatment for most symptomatic patients. CONCLUSIONS: Radiation-induced atherosclerosis is a different and accelerated form of atherosclerosis, which implies a more aggressive disease with a different biologic behavior. The disease is characterized by a high rate of carotid artery stenosis compared to those observed in nonirradiated control group patients. To prevent the risk of stroke, surveillance and imaging with ultrasonography should enable detection of severe stenosis. Endovascular treatment with a carotid angioplasty and stenting has been proposed as an attractive and minimally invasive alternative for some radiation-induced stenoses.
Asunto(s)
Arterias Carótidas/efectos de la radiación , Estenosis Carotídea/etiología , Neoplasias de Oído, Nariz y Garganta/radioterapia , Traumatismos por Radiación/etiología , Angioplastia de Balón , Arterias Carótidas/patología , Grosor Intima-Media Carotídeo , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/epidemiología , Estenosis Carotídea/terapia , Estudios Transversales , Humanos , Traumatismos por Radiación/diagnóstico por imagen , Traumatismos por Radiación/epidemiología , Traumatismos por Radiación/terapia , Stents , Ultrasonografía Doppler en ColorRESUMEN
Previous studies have linked plasma inflammatory markers to elevated fatigue in patients with head and neck cancer (HNC). To identify the molecular mechanisms underlying this association, we conducted promoter-based bioinformatics analyses to determine the relationship between fatigue and specific gene expression profiles associated with inflammation in human papillomavirus (HPV)-related and -unrelated HNC patients undergoing treatment. Patients with newly diagnosed HNC without distant metastasis were assessed at baseline (pre-radiotherapy) and one-month post-radiotherapy. Fatigue was measured by the Multidimensional Fatigue Inventory. Genome-wide gene expression profiles were collected from peripheral blood mononuclear cells (PBMC). Promoter-based bioinformatics analyses were employed to identify transcription control pathways underlying transcriptomic correlates of fatigue in the sample as a whole and in HPV-related and HPV-unrelated HNC patients separately. In transcriptome profiling analyses of PBMC from 44 patients, TELiS bioinformatics analyses linked fatigue to increased nuclear factor-kappa B (NF-kB) transcriptional activity and decreased interferon regulatory factor family (IRF) transcription factor activity. Patients with HPV-related HNC showed lower levels of fatigue-related gene expression profile compared to HPV-unrelated HNC. Fatigue in HNC patients undergoing treatment is associated with gene expression profiles consistent with the conserved transcriptional response to adversity (CTRA) characterized by increased proinflammatory and decreased anti-antiviral transcriptional activity. Interestingly, this CTRA response was mitigated in patients with HPV-related HNC and may explain the lower level of fatigue they experience relative to HPV-unrelated HNC.
Asunto(s)
Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Factores Reguladores del Interferón/genética , FN-kappa B/genética , Anciano , Biología Computacional/métodos , Fatiga/etiología , Fatiga/genética , Femenino , Perfilación de la Expresión Génica/métodos , Neoplasias de Cabeza y Cuello/complicaciones , Humanos , Factores Reguladores del Interferón/metabolismo , Estudios Longitudinales , Masculino , Persona de Mediana Edad , FN-kappa B/metabolismo , TranscriptomaRESUMEN
BACKGROUND: Radiographic concern for lymphatic extranodal extension (ENE) impacts upfront management decisions for patients with human papilloma virus (HPV) oropharyngeal squamous cell carcinoma (OPSCC). Therefore, we set out to evaluate the accuracy of preoperative contrast-enhanced computed tomography (CECT) to predict major ENE (> 2 mm). METHODS: Twenty-seven consecutive patients with HPV-associated OPSCC who presented at our institutional multidisciplinary tumor board were staged radiographically with positron emission tomography (PET/CT) and CECT, and underwent primary transoral robotic resection and neck dissection. CECT imaging results were correlated with pathologic ENE (pENE). RESULTS: CECT specificity for all pENE was 69 and 75% for radiologist 1 and 2, respectively. For pENE > 2 mm, the sensitivities were 88 and 100%, but specificities were 52.6 and 63.2%. Positive predictive values (PPV) were 43.8 and 53.3%; negative predictive values were 90.9 and 100%. On logistic regression analysis, only size ≥3 cm (OR 4.7-5.4, p < 0.02, 95% CI 1.3-44.0) demonstrated significant correlation with major ENE > 2 mm. CONCLUSIONS: Preoperative imaging for HPV-associated OPSCC had a PPV for pENE > 2 mm of 44-55%, based on any interruption in the capsule or invasion into the perinodal fat. The PPV is low and equipoise in treatment decision making for patients with HPV-associated OPSCC may require other imaging characteristics.
Asunto(s)
Carcinoma de Células Escamosas/diagnóstico por imagen , Invasividad Neoplásica/diagnóstico por imagen , Neoplasias Orofaríngeas/diagnóstico por imagen , Infecciones por Papillomavirus/complicaciones , Tomografía Computarizada por Rayos X , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Medios de Contraste , Humanos , Metástasis Linfática/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/virología , Papillomaviridae , Tomografía Computarizada por Tomografía de Emisión de Positrones , Cuidados Preoperatorios , Pronóstico , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Patients with resectable esophageal cancer (rEC) are managed with either concurrent chemoradiotherapy followed by surgery (CRSx) or concurrent chemoradiotherapy alone (cCR). To the authors' knowledge, there is insufficient evidence comparing the overall survival of patients treated with these 2 options. METHODS: The National Cancer Data Base was queried for rEC cases diagnosed from 2003 through 2011. Patients with previous cancers, cervical rEC, clinical stage T1N0 disease, or metastasis were excluded. cCR was defined as radiotherapy administered within 30 days of chemotherapy. CRSx was defined as cCR followed by esophagectomy within 90 days. Overall survival was compared using Kaplan-Meier methods, propensity score matching, and extended Cox proportional hazards models. RESULTS: Of the 11,122 eligible patients, 8091 (72.7%) received cCR and 3031 (27.3%) received CRSx. The odds of receiving CRSx were higher among patients with American Joint Committee on Cancer stage II disease (vs stage III), adenocarcinoma (vs squamous cell carcinoma), lesions of the lower one-third of the esophagus, private insurance, and those living >25 miles from the treating facility or in areas with a higher median income or a greater percentage of high school-educated residents. Patients aged >70 years, female patients, African-American patients, those with ≥2 comorbidities, or those treated at community programs were more likely to receive cCR. After propensity score matching, the median and 10-year survival rates were found to be significantly better with CRSx (32.5 months [95% confidence interval (95% CI), 29.6-34.8 months] and 23.8% months [95% CI, 20.0-27.9 months], respectively) compared with cCR (14.2 months [95% CI, 13.4-15.5 months] and 6.1% months [95% CI, 3.9-9.0 months], respectively). CONCLUSIONS: Data from the National Cancer Data Base support the inclusion of surgery after concurrent chemoradiotherapy for patients with locally advanced rEC. Cancer 2017;123:3476-85. © 2017 American Cancer Society.
Asunto(s)
Carcinoma de Células Escamosas/terapia , Quimioradioterapia/métodos , Neoplasias Esofágicas/terapia , Esofagectomía/métodos , Sistema de Registros , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Quimioradioterapia/mortalidad , Estudios de Cohortes , Supervivencia sin Enfermedad , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Esofagectomía/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVES: Esophageal adenosquamous carcinoma (ASC) is a rare tumor with characteristics of adenocarcinoma (AC) and squamous cell carcinoma (SCC), the two most common esophageal cancers. Its behavior is aggressive but poorly understood. Using the National Cancer Database (NCDB), the clinical features and overall survival of ASC were compared with AC and SCC. METHODS: The NCDB was queried for patients with esophageal ASC, AC, and SCC. Univariate association of histology with patient characteristics and overall survival were analyzed and socioeconomic characteristics were balanced. RESULTS: Clinical M stage was 0 in a significantly lower proportion of ASC (69.0%) than in AC (70.9%) or SCC (75.6%) (p < 0.001). Median survival was lower in patients with ASC (9.6 months) than with AC (13.5) or SCC (9.7) and 2-year OS was lower in patients with ASC (23.8%) than with AC (34.6%) or SCC (26.5%) (p < 0.001). The OS hazard ratio for ASC was 1.14 when compared to AC (95% CI = 1.016-1.267, p = 0.025) and 1.10 when compared to SCC, but the latter was not significant (95% CI = 0.980-1.222, p = 0.111). CONCLUSION: ASC is a rare tumor among esophageal carcinomas with a greater burden of metastatic disease than AC or SCC and worse OS than AC.