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1.
J Med Case Rep ; 13(1): 57, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-30853030

RESUMO

BACKGROUND: Nuclear protein in testis midline carcinoma is a rare, highly metastatic undifferentiated carcinoma that typically arises in midline structures and is characterized by having a fusion involving the nuclear protein in testis, NUT, gene. Nuclear protein in testis midline carcinoma has been identified in patients of all ages and is often initially misdiagnosed due to the rapid timeline of symptom onset. CASE PRESENTATION: Here we report the case of a 47-year-old Caucasian woman with a nuclear protein in testis midline carcinoma that was initially mistaken for a sinus infection. After symptom progression while on an aggressive antibiotic regimen, the source of her symptoms was correctly identified as a sella mass. Comprehensive analysis of the tumor was performed, and standard cytogenetic analysis identified a translocation of 15q and 19p. Further testing identified a NUT-BRD4 fusion and confirmed the diagnosis of nuclear protein in testis midline carcinoma. Despite definitive diagnosis and surgical, radiation, and, ultimately, systemic therapy, she progressed rapidly, developing widespread metastases, and ultimately died from the disease 5 months after diagnosis. CONCLUSIONS: Based on this and other previous reports, aggressive therapy should be initiated once nuclear protein in testis midline carcinoma is diagnosed and close surveillance employed in an attempt to prevent and/or recognize metastases as early as possible. Aggressive therapy has shown little efficacy such that the average overall survival for patients with nuclear protein in testis midline carcinoma is very short, often less than 6 months. Thus, early enrollment into clinical trials testing novel therapies for the treatment of nuclear protein in testis midline carcinoma should be considered. Finally, additional reports of nuclear protein in testis midline carcinoma are needed to fully characterize this rare and highly aggressive cancer.


Assuntos
Carcinoma/diagnóstico , Neoplasias de Cabeça e Pescoço/diagnóstico , Proteínas Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Oncogênicas/genética , Biomarcadores Tumorais/genética , Carcinoma/genética , Carcinoma/terapia , Quimiorradioterapia , Diagnóstico Diferencial , Evolução Fatal , Feminino , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Pessoa de Meia-Idade , Mutação/genética , Sinusite
2.
J Thorac Oncol ; 14(3): 475-481, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30503890

RESUMO

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is commonly used to treat nonsurgical patients with early-stage NSCLC. There are no prospective data on the role of adjuvant chemotherapy in this setting. METHODS: Patients (≥18 years) diagnosed with clinical stages I-II NSCLC from 2004 to 2013 were identified using the National Cancer Database (n = 11,836). The Kaplan-Meier method was used to estimate overall survival (OS) distributions and the log-rank test was used to compare distributions by treatment strategy. Clinical stages I and II were subdivided according to the TNM staging and log-rank tests was used to compare survival distributions by treatment strategy within each subgroup. RESULTS: In patients with T2bN0, median OS in the SBRT alone and SBRT plus adjuvant chemotherapy groups were 16.5 months versus 24.2 months, respectively (95% confidence interval [CI]: 14.1-20.1 months and 18.8-33.3 months, respectively; p < .001); whereas for T3N0, median OS times were 13 months and 20.1 months, respectively (95% CI: 11.7-14.5 mohths and 17.7-21.9 months, respectively; p < .001). For tumors 4 cm or larger and node-negative disease, median OS was 15.9 months in the SBRT-alone group, and 19 months in the SBRT-plus-chemotherapy group (95% CI: 15.1-16.8 months and 17.9-20.8 months, respectively; p < .001). For patients with tumors less than 4 cm and node-negative disease, the median OS was 28.5 months in the SBRT-alone group and 24.3 months in the SBRT-plus-chemotherapy group (95% CI: 27.4-29.4 months and 22.8-26.1 months, respectively; p < .001). CONCLUSIONS: SBRT followed by adjuvant chemotherapy was associated with improved OS in comparison with SBRT alone in patients with T greater than or equal to 4 cm, similar to that seen after surgery.

3.
J Cancer Res Ther ; 14(4): 799-806, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29970656

RESUMO

Aims: We have previously demonstrated that brain metastases were more common among patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma. However, the association of EGFR mutation and extracranial metastases (ECM) remains inconclusive. In this study, we explored the potential association between EGFR mutation and the risk of ECM. Patients and Methods: Between March 2007 and December 2014, 234 patients were analyzed for the potential association between EGFR mutation and ECM. Statistical Analysis Used: Multivariate Cox regression analysis. Results: There were no associations between the EGFR mutation and metastases in different organs, except for bone. The frequency of EGFR mutation was statistically higher for patients with bone metastases (BMs) at the initial diagnosis (P = 0.039) and at the last follow-up (P = 0.018) as compared to those with wild-type EGFR. In multivariate logistic regression analysis, EGFR mutation significantly increased the risk of BM at the initial diagnosis (P = 0.036). Among those patients without BM at initial diagnosis, 1- and 2-year accumulative rates of subsequent BM were significantly higher in patients with EGFR-mutant disease (P = 0.026). EGFR mutation was an independent risk factor for subsequent BM (P < 0.05). In addition, patients with finial BM and EGFR-mutant disease had longer median survival as compared to those with wild-type disease (P = 0.020). Conclusions: Only BM in patients with ECM was significantly correlated with EGFR mutation during their disease course. EGFR mutation was an independent predictive and prognostic factor for developing BM, which was also a positive predictive factor for overall survival of patients who developed BM.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Adenocarcinoma de Pulmão , Adulto , Idoso , Biomarcadores Tumorais , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Fatores de Risco
4.
J Natl Compr Canc Netw ; 16(5): 479-490, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29752322

RESUMO

The NCCN Guidelines for Head and Neck (H&N) Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the H&N, and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding evaluation and treatment of nasopharyngeal carcinoma.


Assuntos
Neoplasias de Cabeça e Pescoço , Guias como Assunto , História do Século XXI , Humanos
5.
Anticancer Res ; 38(3): 1651-1657, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29491098

RESUMO

BACKGROUND: The standard of care for T1N0 nasopharyngeal cancer (NPC) is definitive radiation therapy (RT). However, practice patterns in the elderly may not necessarily follow national guidelines. Herein, we investigated national practice patterns for T1N0 NPC. MATERIALS AND METHODS: The National Cancer Data Base (NCDB) was queried for clinical T1N0 primary NPC cases (2004-2013) in patients ≥70 years old. Patient, tumor, and treatment parameters were extracted. Kaplan-Meier analysis was used to compare overall survival (OS) between patients receiving RT versus those under observation. Logistic regression was used to examine variables associated with receipt of RT. Cox proportional hazards modeling determined variables associated with OS. Landmark analysis of patients surviving 1 year or more was performed to assess survival differences between groups. RESULTS: In total, data of 147 patients were analyzed. RT was delivered to 89 patients (61%), whereas 58 (39%) patients underwent observation. On multivariable analysis, older patients were less likely to receive RT (p=0.003), but there were no differences between groups in terms of Charlson-Deyo comorbidity index. Median and 5-year OS in patients receiving RT versus those under observation were 71 and 33 months, and 59% and 48% (p=0.011), respectively. For patients surviving 1 year or more (n=96), there was a strong trend showing that receipt of RT was associated with better median and 5-year OS. CONCLUSION: This National Data Base analysis shows that observation is relatively common for T1N0 NPC in the elderly, but is associated with poorer survival.


Assuntos
Bases de Dados Factuais/estatística & dados numéricos , Neoplasias Nasofaríngeas/radioterapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Análise Multivariada , Neoplasias Nasofaríngeas/patologia , Modelos de Riscos Proporcionais , Estados Unidos
6.
Int J Radiat Oncol Biol Phys ; 100(2): 427-435, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29174131

RESUMO

PURPOSE: To assess the safety of the superoxide dismutase mimetic GC4419 in combination with radiation and concurrent cisplatin for patients with oral cavity or oropharyngeal cancer (OCC) and to assess the potential of GC4419 to reduce severe oral mucositis (OM). PATIENTS AND METHODS: Patients with locally advanced OCC treated with definitive or postoperative intensity modulated radiation therapy (IMRT) plus cisplatin received GC4419 by 60-minute intravenous infusion, ending <60 minutes before IMRT, Monday through Friday for 3 to 7 weeks, in a dose and duration escalation study. Oral mucositis was assessed twice weekly during and weekly after IMRT. RESULTS: A total of 46 patients received GC4419 in 11 separate dosing and duration cohorts: dose escalation occurred in 5 cohorts receiving 15 to 112 mg/d over 3 weeks (n=20), duration escalation in 3 cohorts receiving 112 mg/d over 4 to 6 weeks (n=12), and then 3 additional cohorts receiving 30 or 90 mg/d over 6 to 7 weeks (n=14). A maximum tolerated dose was not reached. One dose-limiting toxicity (grade 3 gastroenteritis and vomiting with hyponatremia) occurred in each of 2 separate cohorts at 112 mg. Nausea/vomiting and facial paresthesia during infusion seemed to be GC4419 dose-related. Severe OM occurred through 60 Gy in 4 of 14 patients (29%) dosed for 6 to 7 weeks, with median duration of only 2.5 days. CONCLUSIONS: The safety of GC4419 concurrently with chemoradiation for OCC was acceptable. Toxicities included nausea/vomiting and paresthesia. Doses of 30 and 90 mg/d administered for 7 weeks were selected for further study. In an exploratory analysis, severe OM seemed less frequent and briefer than expected.


Assuntos
Quimiorradioterapia/efeitos adversos , Neoplasias Bucais/terapia , Neoplasias Orofaríngeas/terapia , Radioterapia de Intensidade Modulada/efeitos adversos , Estomatite/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estomatite/etiologia , Superóxido Dismutase/uso terapêutico
7.
Oral Oncol ; 73: 105-110, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28939061

RESUMO

INTRODUCTION: Current standard of care for locally advanced squamous cell carcinoma of the oropharynx (LA-OPC) consists of concurrent chemoradiotherapy. Due to toxicities associated with this treatment, a significant portion of patients are unable to complete the systemic therapy portion of their treatment course. The impact of incomplete systemic therapy on patient outcomes remains unclear. METHODS: Demographic, treatment, and outcome data were retrospectively collected for patients with LA-OPC treated definitively with concurrent chemoradiotherapy between 2007 and 2014. Overall and disease-free survivals were estimated via the Kaplan Meier method. Log rank test was used to compare distributions of survival amongst groups. Cox regression was utilized for all multivariate analyses. P values of <0.05 were considered statistically significant. RESULTS: In total, 73 patients with LA-OPC were identified with a median follow-up of 3.4years. Concurrent systemic therapy regimens consisted of bolus cisplatin every 3weeks (76.7%), weekly cetuximab (20.5%) and weekly cisplatin (2.7%). Forty-three patients (58.9%) were able to complete the prescribed concurrent systemic regimens. Upon multivariate analyses, patients who did not complete systemic therapy were noted to have a non-significant trend towards increased distant failure (20.0% vs 7.0%, p=0.12). Additionally, patients who did not complete systemic therapy were noted to have a near significant trend towards increased risk of death (36.7% vs 17.9%, p=0.053). CONCLUSIONS: These results suggest that completing systemic therapy may affect survival in patients undergoing definitive radiotherapy with concurrent systemic therapy for LA-OPC. Further, this data demonstrates that though local recurrences are not affected when planned systemic therapy cycles are omitted, the risk of distant failure may increase. These associations require further study to clarify the effect Incomplete systemic therapy has on outcomes for LA-OPC.


Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias Orofaríngeas/terapia , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Orofaríngeas/patologia
8.
Medicine (Baltimore) ; 96(34): e7768, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28834880

RESUMO

RATIONALE: Metastasis to the small intestine from a primary lung cancer is rare, and is associated with a poor prognosis. Early diagnosis of small intestine metastasis is difficult because of the low incidence of clinically apparent symptoms. PATIENT CONCERNS: Clinical data and treatment of a 59-year-old man with small intestine metastasis from primary solid subtype lung adenocarcinoma are summarized. DIAGNOSES: A man who was previously diagnosed with stage IIIA (T3N2M0) lung adenocarcinoma (solid subtype) came to our hospital for postoperative radiotherapy. Laboratory tests indicated anemia and melena. The patient was initially believed to have digestive ulcer and was treated with omeprazole, which proved to be ineffective. We conducted an abdominal computed tomography (CT) contrast scan and discovered a mass in the small intestine mass. Further positron emission tomography-computed tomography (PET-CT) imaging indicated the small intestine mass with fluorodeoxyglucose uptake. INTERVENTIONS: The patient underwent an enterectomy and anastomosis. Pathological analysis confirmed the diagnosis of small intestinal metastasis from lung cancer with concomitant mesenteric lymph node metastasis. OUTCOMES: One month after the operation, hemoglobin levels became normal, and the patient had good quality of life. However, 3 months after the operation, the patient suffered from anemia again. An abdominal CT scan indicated a new small intestine mass. Progression continued rapidly, and the patient died of hemorrhagic shock 5.5 months after the resection of the small intestine mass. LESSONS: Although uncommon, if lung cancer patients present with anemia and melena, enteric metastasis should be part of the differential diagnosis. Abdominal CT scans and PET-CT are effective for early diagnosis. The prognosis of metastatic spread of solid subtype lung adenocarcinoma to the small intestine with mesenteric lymph node metastasis is poor. Subgroups of patients benefitting from metastasectomy and more effective systemic therapy need to be further investigated.


Assuntos
Adenocarcinoma/patologia , Anemia/etiologia , Neoplasias Intestinais/complicações , Neoplasias Intestinais/secundário , Neoplasias Pulmonares/patologia , Melena/etiologia , Adenocarcinoma de Pulmão , Humanos , Pessoa de Meia-Idade
9.
J Natl Compr Canc Netw ; 15(6): 761-770, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28596256

RESUMO

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the head and neck (H&N), and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding the increase in human papillomavirus-associated oropharyngeal cancer and the availability of immunotherapy agents for treatment of patients with recurrent or metastatic H&N cancer.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/etiologia , Humanos
10.
World J Clin Oncol ; 8(3): 300-304, 2017 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-28638802

RESUMO

Stereotactic body radiotherapy (SBRT) is a widely accepted option for the treatment of medically inoperable early-stage non-small cell lung cancer (NSCLC). Herein, we highlight the importance of interfraction image guidance during SBRT. We describe a case of early-stage NSCLC associated with segmental atelectasis that translocated 15 mm anteroinferiorly due to re-expansion of the adjacent segmental atelectasis following the first fraction. The case exemplifies the importance of cross-sectional image-guided radiotherapy that shows the intended target, as opposed to aligning based on rigid anatomy alone, especially in cases associated with potentially "volatile" anatomic areas.

11.
Radiat Oncol ; 12(1): 80, 2017 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-28476138

RESUMO

BACKGROUND: Type-C dose algorithms provide more accurate dosimetry for lung SBRT treatment planning. However, because current dosimetric protocols were developed based on conventional algorithms, its applicability for the new generation algorithms needs to be determined. Previous studies on this issue used small sample sizes and reached discordant conclusions. Our study assessed dose calculation of a Type-C algorithm with current dosimetric protocols in a large patient cohort, in order to demonstrate the dosimetric impacts and necessary treatment planning steps of switching from a Type-B to a Type-C dose algorithm for lung SBRT planning. METHODS: Fifty-two lung SBRT patients were included, each planned using coplanar VMAT arcs, normalized to D95% = prescription dose using a Type-B algorithm. These were compared against three Type-C plans: re-calculated plans (identical plan parameters), re-normalized plans (D95% = prescription dose), and re-optimized plans. Dosimetric endpoints were extracted and compared among the four plans, including RTOG dosimetric criteria: (R100%, R50%, D2cm, V105%, and lung V20), PTV Dmin, Dmax, Dmean, V% and D90%, PTV coverage (V100%), homogeneity index (HI), and Paddick conformity index (PCI). RESULTS: Re-calculated Type-C plans resulted in decreased PTV Dmin with a mean difference of 5.2% and increased Dmax with a mean difference of 3.1%, similar or improved RTOG dose compliance, but compromised PTV coverage (mean D95% and V100% reduction of 2.5 and 8.1%, respectively). Seven plans had >5% D95% reduction (maximum reduction = 16.7%), and 18 plans had >5% V100% reduction (maximum reduction = 60.0%). Re-normalized Type-C plans restored target coverage, but yielded degraded plan conformity (average PCI reduction 4.0%), and RTOG dosimetric criteria deviation worsened in 11 plans, in R50%, D2cm, and R100%. Except for one case, re-optimized Type-C plans restored RTOG compliance achieved by the original Type-B plans, resulting in similar dosimetric values but slightly higher target dose heterogeneity (mean HI increase = 13.2%). CONCLUSIONS: Type-B SBRT lung plans considerably overestimate target coverage for some patients, necessitating Type-C re-normalization or re-optimization. Current RTOG dosimetric criteria appear to remain appropriate.


Assuntos
Algoritmos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Órgãos em Risco/efeitos da radiação , Radiocirurgia , Planejamento da Radioterapia Assistida por Computador/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos
12.
Rare Tumors ; 9(1): 6955, 2017 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-28458793

RESUMO

The incidence of laryngeal sarcoma is exceedingly low with osteosarcomas of the larynx being rarer still, comprising less than 1% of all associated malignancies. To date, only 32 cases have been reported since this pathologic entity was first described in 1942. In this article, we discuss the most recent case of laryngeal osteosarcoma in a patient presenting with respiratory distress found to be due to a tumor mass arising from her cricoid cartilage. We further summarize current knowledge regarding the epidemiology, presentation, and diagnosis of this uncommon disease. Lastly, we synthesize all available information regarding treatment and outcomes of the 32 previously described cases of osteosarcoma of the larynx as well as the presently described case in an attempt to offer some insight regarding optimal treatment in future cases.

13.
Med Phys ; 44(5): 1939-1947, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28273341

RESUMO

PURPOSE: Inhomogeneity dose modeling and respiratory motion description are two critical technical challenges for lung stereotactic body radiotherapy, an important treatment modality for small size primary and secondary lung tumors. Recent studies revealed lung density-dependent target dose differences between Monte Carlo (Type-C) algorithm and earlier algorithms. Therefore, this study aimed to investigate the equivalence of the two most popular CT datasets for treatment planning, free breathing (FB) and average intensity projection (AIP) CTs, using Type-C algorithms, and comparing with two older generation algorithms (Type-A and Type-B). METHODS: Twenty patients (twenty-one lesions) were planned using a Type-A algorithm on the FB CT. Lung was contoured separately on FB and AIP CTs and compared. Dose comparison was obtained between the two CTs using four commercial dose algorithms including one Type-A (Pencil Beam Convolution - PBC), one Type-B (Analytical Anisotropic Algorithm - AAA), and two Type-C algorithms (Voxel Monte Carlo - VMC and Acuros External Beam - AXB). For each algorithm, the dosimetric parameters of the target (PTV, Dmin , Dmax , Dmean , D95, and D90) and lung (V5, V10, V20, V30, V35, and V40) were compared between the two CTs using the Wilcoxon signed rank test. Correlation between dosimetric differences and density differences for each algorithm were studied using linear regression and Spearman correlation, in which both global and local density differences were evaluated. RESULTS: Although the lung density differences on FB and AIP CTs were statistically significant (P = 0.003), the magnitude was small at 1.21 ± 1.45%. Correspondingly, for the two Type-C algorithms, target and lung dosimetric differences were small in magnitude and statistically insignificant (P > 0.05) for all but one instance, similar to the findings for the older generation algorithms. Nevertheless, a significant correlation was shown between the dosimetric and density differences for Type-C and Type-B algorithms, but not for the Type-A algorithm. CONCLUSIONS: With the capability to more accurately model inhomogeneity, Monte Carlo (Type-C) algorithms are sensitive to respiration-induced local and global tissue density changes and exhibit a strong correlation between dosimetric and density differences. However, FB and AIP CTs may still be considered equivalent for dose calculation in the Monte Carlo era, due to the small magnitude of lung density differences between these two datasets.


Assuntos
Algoritmos , Neoplasias Pulmonares/radioterapia , Método de Monte Carlo , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Humanos , Radiocirurgia , Tomografia Computadorizada por Raios X
14.
Int J Radiat Oncol Biol Phys ; 97(4): 778-785, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28244414

RESUMO

PURPOSE: To describe the impact of fractionation scheme and tumor location on toxicities in stereotactic body radiation therapy (SBRT) for ≥5-cm non-small cell lung cancer (NSCLC), as part of a multi-institutional analysis. METHODS: Patients with primary ≥5-cm N0 M0 NSCLC who underwent ≤5-fraction SBRT were examined across multiple high-volume SBRT centers. Collected data included clinical/treatment parameters; toxicities were prospectively assessed at each institution according to the Common Terminology Criteria for Adverse Events. Patients treated daily were compared with those treated every other day (QOD)/other nondaily regimens. Stratification between central and peripheral tumors was also performed. RESULTS: Ninety-two patients from 12 institutions were evaluated (2004-2016), with median follow-up of 12 months. In total there were 23 (25%) and 6 (7%) grade ≥2 and grade ≥3 toxicities, respectively. Grades 2 and 3 pulmonary toxicities occurred in 9% and 4%, respectively; 1 patient treated daily experienced grade 5 radiation pneumonitis. Of the entire cohort, 46 patients underwent daily SBRT, and 46 received QOD (n=40)/other nondaily (n=6) regimens. Clinical/treatment parameters were similar between groups; the QOD/other group was more likely to receive 3-/4-fraction schemas. Patients treated QOD/other experienced significantly fewer grade ≥2 toxicities as compared with daily treatment (7% vs 43%, P<.001). Patients treated daily also had higher rates of grade ≥2 pulmonary toxicities (P=.014). Patients with peripheral tumors (n=66) were more likely to receive 3-/4-fraction regimens than those with central tumors (n=26). No significant differences in grade ≥2 toxicities were identified according to tumor location (P>.05). CONCLUSIONS: From this multi-institutional study, toxicity of SBRT for ≥5-cm lesions is acceptable, and daily treatment was associated with a higher rate of toxicities.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Fracionamento da Dose de Radiação , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/radioterapia , Pneumonite por Radiação/mortalidade , Radiocirurgia/mortalidade , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Comorbidade , Relação Dose-Resposta à Radiação , Feminino , Humanos , Estudos Longitudinais , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prevalência , Pneumonite por Radiação/patologia , Pneumonite por Radiação/prevenção & controle , Radiocirurgia/métodos , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologia
15.
Front Oncol ; 7: 299, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29379770

RESUMO

Objectives: Concurrent chemoradiotherapy is standard of care in locally advanced oropharyngeal cancer (LA-OPC). This treatment regimen results in significant acute toxicities. This study investigates the effect of treatment-related toxicity on patient outcomes. Methods: Patient information was retrospectively collected for patients treated for LA-OPC between 2007 and 2014. Factors analyzed included age, gender, pretreatment ECOG performance status, smoking history, patient BMI prior to and following treatment, tumor histology, disease stage, disease recurrence, incidence, and timing of feeding tube placement, radiation dose received, chemotherapy regimen used and if it was completed, and patient survival. All statistical analysis was provided through the University of Nebraska Medical Center Department of Biostatistics. Results: 74 patients were identified with a median follow-up of 3.4 years and a median age of 58.5. Most patients were male (87.8%) and had squamous cell histology (98.7%). Most patients underwent chemoradiotherapy alone (98.6%) and received concurrent cisplatin (78.4%) with approximately half (53.4%) receiving all planned chemotherapy. Upon multivariate analysis, both disease-free (DFS) and overall survival (OS) rates were improved by lower pretreatment BMI, increased weight lost during treatment, and lack of percutaneous endoscopic gastrostomy (PEG) tube placement prior to treatment initiation. Neither DFS nor OS was impacted by placement of a PEG tube during active treatment. Conclusion: These data suggest that weight loss and PEG tube placement during chemoradiotherapy for LA-OPC, presumably due to treatment-associated mucositis and xerostomia, are not associated with worse outcomes.

16.
Int J Radiat Oncol Biol Phys ; 97(2): 362-371, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28011047

RESUMO

PURPOSE: For inoperable stage I (T1-T2N0) small cell lung cancer (SCLC), national guidelines recommend chemotherapy with or without conventionally fractionated radiation therapy. The present multi-institutional cohort study investigated the role of stereotactic ablative radiation therapy (SABR) for this population. METHODS AND MATERIALS: The clinical and treatment characteristics, toxicities, outcomes, and patterns of failure were assessed in patients with histologically confirmed stage T1-T2N0M0 SCLC. Kaplan-Meier analysis was used to evaluate the survival outcomes. Univariate and multivariate analyses identified predictors of outcomes. RESULTS: From 24 institutions, 76 lesions were treated in 74 patients (median follow-up 18 months). The median age and tumor size was 72 years and 2.5 cm, respectively. Chemotherapy and prophylactic cranial irradiation were delivered in 56% and 23% of cases, respectively. The median SABR dose and fractionation was 50 Gy and 5 fractions. The 1- and 3-year local control rate was 97.4% and 96.1%, respectively. The median disease-free survival (DFS) duration was 49.7 months. The DFS rate was 58.3% and 53.2% at 1 and 3 years, respectively. The median, 1-year, and 3-year disease-specific survival was 52.3 months, 84.5%, and 64.4%, respectively. The median, 1-year, and 3-year overall survival (OS) was 17.8 months, 69.9%, and 34.0% respectively. Patients receiving chemotherapy experienced an increased median DFS (61.3 vs 9.0 months; P=.02) and OS (31.4 vs 14.3 months; P=.02). The receipt of chemotherapy independently predicted better outcomes for DFS/OS on multivariate analysis (P=.01). Toxicities were uncommon; 5.2% experienced grade ≥2 pneumonitis. Post-treatment failure was most commonly distant (45.8% of recurrence), followed by nodal (25.0%) and "elsewhere lung" (20.8%). The median time to each was 5 to 7 months. CONCLUSIONS: From the findings of the largest report of SABR for stage T1-T2N0 SCLC to date, SABR (≥50 Gy) with chemotherapy should be considered a standard option.


Assuntos
Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Carcinoma de Pequenas Células do Pulmão/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Antineoplásicos/uso terapêutico , Terapia Combinada/métodos , Irradiação Craniana/estatística & dados numéricos , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Pneumonite por Radiação/etiologia , Radiocirurgia/efeitos adversos , Dosagem Radioterapêutica , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento , Carga Tumoral
17.
Cancer ; 123(4): 688-696, 2017 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-27741355

RESUMO

BACKGROUND: Stereotactic body radiotherapy (SBRT) is the standard of care for patients with nonoperative, early-stage non-small cell lung cancer (NSCLC) measuring < 5 cm, but its use among patients with tumors measuring ≥5 cm is considerably less defined, with the existing literature limited to small, single-institution reports. The current multi-institutional study reported outcomes evaluating the largest such population reported to date. METHODS: Clinical/treatment characteristics, outcomes, toxicities, and patterns of failure were assessed in patients with primary NSCLC measuring ≥5 cm without evidence of distant/lymph node metastasis who underwent SBRT using ≤5 fractions. Statistics included Kaplan-Meier survival analyses and univariate/multivariate Cox proportional hazards models. RESULTS: A total of 92 patients treated from 2004 through 2016 were analyzed from 12 institutions. The median follow-up was 12 months (15 months in survivors). The median age and tumor size among the patients were 73 years (range, 50-95 years) and 5.4 cm (range, 5.0-7.5 cm), respectively. The median dose/fractionation was 50 Gray/5 fractions. The actuarial local control rates at 1 year and 2 years were 95.7% and 73.2%, respectively. The disease-free survival rate was 72.1% and 53.5%, respectively, at 1 year and 2 years. The 1-year and 2-year disease-specific survival rates were 95.5% and 78.6%, respectively. The median, 1-year, and 2-year overall survival rates were 21.4 months, 76.2%, and 46.4%, respectively. On multivariate analysis, lung cancer history and pre-SBRT positron emission tomography maximum standardized uptake value were found to be associated with overall survival. Posttreatment failures were most commonly distant (33% of all disease recurrences), followed by local (26%) and those occurring elsewhere in the lung (23%). Three patients had isolated local failures. Grade 3 to 4 toxicities included 1 case (1%) and 4 cases (4%) of grade 3 dermatitis and radiation pneumonitis, respectively (toxicities were graded according to the Common Terminology Criteria for Adverse Events [version 4.0]). Grades 2 to 5 radiation pneumonitis occurred in 11% of patients. One patient with a tumor measuring 7.5 cm and a smoking history of 150 pack-years died of radiation pneumonitis. CONCLUSIONS: The results of the current study, which is the largest study of patients with NSCLC measuring ≥5 cm reported to date, indicate that SBRT is a safe and efficacious option. Cancer 2017;123:688-696. © 2016 American Cancer Society.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Recidiva Local de Neoplasia/radioterapia , Radiocirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Resultado do Tratamento
18.
Phys Med Biol ; 61(23): 8157-8179, 2016 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-27804926

RESUMO

In the delivery of non-gated radiotherapy (RT), owing to intra-fraction organ motion, a certain degree of RT dose uncertainty is present. Herein, we propose a novel mathematical algorithm to estimate the mean and variance of RT dose that is delivered without gating. These parameters are specific to individual internal organ motion, dependent on individual treatment plans, and relevant to the RT delivery process. This algorithm uses images from a patient's 4D simulation study to model the actual patient internal organ motion during RT delivery. All necessary dose rate calculations are performed in fixed patient internal organ motion states. The analytical and deterministic formulae of mean and variance in dose from non-gated RT were derived directly via statistical averaging of the calculated dose rate over possible random internal organ motion initial phases, and did not require constructing relevant histograms. All results are expressed in dose rate Fourier transform coefficients for computational efficiency. Exact solutions are provided to simplified, yet still clinically relevant, cases. Results from a volumetric-modulated arc therapy (VMAT) patient case are also presented. The results obtained from our mathematical algorithm can aid clinical decisions by providing information regarding both mean and variance of radiation dose to non-gated patients prior to RT delivery.


Assuntos
Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/radioterapia , Movimento/fisiologia , Planejamento da Radioterapia Assistida por Computador/métodos , Erros de Configuração em Radioterapia/prevenção & controle , Radioterapia de Intensidade Modulada/métodos , Algoritmos , Humanos , Dosagem Radioterapêutica , Mecânica Respiratória
19.
Oncotarget ; 7(35): 56998-57010, 2016 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-27486770

RESUMO

Lung adenocarcinomas are more commonly associated with brain metastases (BM). Epidermal growth factor receptor (EGFR) mutations have been demonstrated to be both predictive and prognostic for patients with lung adenocarcinoma. We aimed to explore the potential association between EGFR mutation and the risk of BM in pulmonary adenocarcinoma patients. Data of 234 patients from 2007 to 2014 were retrospectively reviewed. A total of 108 patients had EGFR mutations in the entire cohort. Among them, 76 patients developed BM during their disease course. The incidence of BM was statistically higher in patients with EGFR mutations both at initial diagnosis (P=0.014) and at last follow-up (P<0.001). Multivariate logistic regression analysis revealed that EGFR mutation significantly increased the risk of BM at initial diagnosis (OR=2.515, P=0.022). In patients without BM at initial diagnosis, the accumulative rate of subsequent BM was significantly higher with EGFR mutations (P=0.001). Multivariate Cox regression analysis identified EGFR mutation as the only independent risk factor for subsequent BM (HR=3.036, P=0.001). Patients with EGFR mutations demonstrated longer overall survival (OS) after BM diagnosis than patients with wild-type EGFR (P=0.028). Our data suggest that EGFR mutation is an independent predictive and prognostic risk factor for BM and a positive predictive factor for OS in patients with BM.


Assuntos
Adenocarcinoma/metabolismo , Neoplasias Encefálicas/metabolismo , Receptores ErbB/genética , Neoplasias Pulmonares/metabolismo , Mutação , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/secundário , Análise Mutacional de DNA , Receptores ErbB/metabolismo , Éxons , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
20.
Pract Radiat Oncol ; 6(6): e283-e290, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27523439

RESUMO

PURPOSE: Modern experiences in stereotactic radiosurgery (SRS) report noninvasive frameless techniques as an effective alternative to frame-based SRS. Frameless techniques potentially increase positional uncertainty and planning target volume margins are frequently used. Here, we compare rates of local control and radiation necrosis in frameless versus frame-based SRS. METHODS AND MATERIALS: Ninety-eight patients (170 lesions) with radiologic and clinical follow-up were analyzed. Group 1 contained 34 patients (61 lesions) immobilized with an invasive stereotactic frame. Group 2 had 64 patients (109 lesions) immobilized with a frameless SRS mask. Patient, tumor, and treatment characteristics were recorded, as were intervals to local recurrence and radiation necrosis (asymptomatic and symptomatic). RESULTS: Median patient age was 59 years (range, 25-89), and Karnofsky performance scale was 80 (range, 50-100). Median radiologic and clinical follow-up was 6.5 months (range, 0.7-44.3) and 7 months (range, 0.7-45.7). A median of 2 tumors were treated per course (range, 1-5) with a median dose of 18 Gy (range, 13-24 Gy). The median time to local failure was not reached, and Kaplan-Meier estimates of local failure were not statistically significant between groups (P = .303). Actuarial 6-month local failure rates were 7.2% in group 1 and 12.6% in group 2 (P = .295), with 12-month local failure rates of 14.5% and 26.8% (P = .185), respectively. There was no statistically significant difference in symptomatic (P = .391) or asymptomatic (P = .149) radiation necrosis. Six-month radiation necrosis was 0% in group 1 and 1.6% in group 2 (P = .311) with 12-month rates of 20.2% and 3.8%, respectively (P = .059). Median time to necrosis was not reached in group 1, but was 44 months in group 2. CONCLUSIONS: Frameless SRS demonstrates clinical outcomes comparable to frame-based techniques with respect to local failure and radiation necrosis.


Assuntos
Neoplasias Encefálicas/radioterapia , Imobilização/instrumentação , Posicionamento do Paciente/instrumentação , Lesões por Radiação/epidemiologia , Radiocirurgia/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/patologia , Neoplasias Encefálicas/secundário , Feminino , Humanos , Imobilização/métodos , Masculino , Máscaras , Pessoa de Meia-Idade , Necrose/etiologia , Posicionamento do Paciente/métodos , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Resultado do Tratamento
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