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Purpose: When treating esophageal cancer with radiation therapy, it is critical to limit the dose to surrounding structures, such as the lung and/or heart, as much as possible. Proton radiation therapy allows a reduced radiation dose to both the heart and lungs, potentially reducing the risk of cardiopulmonary toxicity. Here, we report disease control, survival, and toxicity outcomes among patients with esophageal cancer treated with proton radiation therapy and concurrent chemotherapy (chemoradiation therapy; CRT) with or without surgery. Materials and Methods: We enrolled 17 patients with thoracic esophageal carcinoma on a prospective registry between 2010 and 2021. Patients received proton therapy to a median dose of 50.4-GyRBE (range, 50.4-64.8) in 1.8-Gy fractions.Acute and late toxicities were graded per the Common Terminology Criteria for Adverse Events, version 4.0 (US National Cancer Institute, Bethesda, Maryland). In addition, disease control, patterns of failure, and survival outcomes were collected. Results: Nine patients received preoperative CRT, and 8 received definitive CRT. Overall, 88% of patients had adenocarcinoma, and 12% had squamous cell carcinoma. With a median follow-up of 2.1 years (range, 0.5-9.4), the 3-year local progression-free, disease-free, and overall survival rates were 85%, 66%, and 55%, respectively. Two patients (1 with adenocarcinoma and 1 with squamous cell carcinoma) recurred at the primary site after refusing surgery after a complete clinical response to CRT. The most common acute nonhematologic and hematologic toxicities, respectively, were grades 1 to 3 esophagitis and grades 1 to 4 leukopenia, both affecting 82% of patients. No acute cardiopulmonary toxicities were observed in the absence of surgical resection. Reagarding surgical complications, 3 postoperative cardiopulmonary complications occurred as follows: 1 grade 1 pleural effusion, 1 grade 3 pleural effusion, and 1 grade 2 anastomotic leak. Two severe late CRT toxicities occurred: 1 grade 5 tracheoesophageal fistula and 1 grade 3 esophageal stenosis requiring a feeding tube. Conclusion: Proton radiation therapy is a safe, effective treatment for esophageal cancer with increasing evidence supporting its role in reducing cardiopulmonary toxicity.
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OBJECTIVES: The incidence and predictors of pneumonitis for patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) in the era of consolidation durvalumab have yet to be fully elucidated. In this large single institution analysis, we report the incidence of and factors associated with grade 2 + pneumonitis in NSCLC patients treated with the PACIFIC regimen. MATERIALS AND METHODS: We identified all patients treated at our institution with definitive CRT followed by durvalumab from 2018 to 2021. Clinical documentation and imaging studies were reviewed to determine grade 2 + pneumonitis events, which required the following: 1) pulmonary symptoms warranting prolonged steroid taper, oxygen dependence, and/or hospital admission and 2) radiographic findings consistent with pneumonitis. RESULTS: One-hundred ninety patients were included. The majority received 60 Gray (Gy) in 30 fractions with concurrent carboplatin and paclitaxel. Median number of durvalumab cycles received was 12 (IQR: 4-22). At a median follow-up of 14.8 months, 50 (26.3%) patients experienced grade 2 + pneumonitis with a 1-year cumulative incidence of 27.8% (95% CI: 21.9-35.4). Seventeen (8.9%) patients experienced grade 3 + pneumonitis and 4 grade 5 (2.1%). Dosimetric predictors of pneumonitis included ipsilateral and total lung volume receiving 5 Gy or greater (V5Gy), V10Gy, V20Gy, V40Gy, and mean dose and contralateral V40Gy. Heart V5Gy, V10Gy, and mean dose were also significant variables. Overall survival estimates at 1 and 3 years were 87.4% (95% CI: 82.4-92.8) and 60.3% (95% CI: 47.9-74.4), respectively. CONCLUSION: We report a risk of pneumonitis higher than that seen on RTOG 0617 and comparable to the PACIFIC study. Multiple lung and heart dosimetric factors were predictive of pneumonitis.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumonia , Pneumonite por Radiação , Anticorpos Monoclonais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimiorradioterapia/efeitos adversos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Pneumonia/complicações , Pneumonia/etiologia , Pneumonite por Radiação/diagnóstico , Pneumonite por Radiação/epidemiologia , Pneumonite por Radiação/etiologia , Dosagem RadioterapêuticaRESUMO
PURPOSE: Radiation therapy (RT) plays an important role in locoregional tumor control for anaplastic thyroid cancer (ATC). Due to its rarity, RT guidelines for ATC are lacking. We describe ATC patterns of nodal disease at presentation and progression and propose corresponding RT target volumes. METHODS AND MATERIALS: We identified all patients with ATC treated at our institution with definitive or adjuvant intensity modulated radiation therapy and concomitant chemotherapy from 2006 to 2020. We identified in-field, marginal, and out-of-field sites of locoregional recurrence and progression (LRR). RESULTS: Forty-seven patients met inclusion. Median follow-up was 6.6 months (interquartile range, 1.9-19.6). Nodal levels involved at presentation included: IB (2.1%), II (23.4%), III (21.3%), IV (21.3%), V (12.8%), VI (34%), and mediastinal (6.4%). All patients received elective nodal RT to levels II-IV and VI. RT volumes also included: IA (23.4%), IB (44.7%), V (87.2%), retropharyngeal/retrostyloid (RP/RS) (27.7%), and mediastinal 1 to 6 (53.2%). Cumulative incidence of LRR at 3- and 12-months was 26.1% (95% confidence interval, 15.9-42.8) and 35.7% (23.9-53.4). Isolated LRR risk at 3- and 12-months was 6.5% (2.2-19.8) and 8.9% (3.4-22.9). Fourteen (29.8%) patients experienced in-field LRR in the thyroid gland or postoperative tumor bed, II-IV, VI, and mediastinal 1 and 3A. Four (8.5%) patients had marginal LRRs, 3 of whom progressed in the mediastinum at 2, 3P, 4, and 6. Two (4.3%) patients experienced out-of-field LRRs. Throughout the pretreatment and follow-up period, no patients had disease at IA, and 1 (2.1%) patient each had disease at IB and RP/RS. No baseline or treatment characteristics, including RT dose (stratified by < or ≥66 Gy), were significant predictors of LRR on univariate analysis. CONCLUSIONS: Isolated LRR risk in patients with ATC treated with comprehensive RT and chemotherapy is low. Aggressive multimodality therapy should be reserved for willing, fit patients with no or limited distant disease burden. When treating comprehensively, complete inclusion of mediastinal levels 1 to 6 may be warranted to avoid marginal disease progression. Omission of levels I and RP/RS can be considered.
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Radioterapia de Intensidade Modulada , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Quimiorradioterapia , Humanos , Recidiva Local de Neoplasia/patologia , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Carcinoma Anaplásico da Tireoide/terapia , Neoplasias da Glândula Tireoide/terapiaRESUMO
Localized hepatocellular carcinoma (HCC) that is unresectable and non-transplantable can be treated by several liver-directed therapies. External beam radiation therapy (EBRT) is an increasingly accepted and widely utilized treatment modality in this setting. Accelerated charged particles such as proton beam therapy (PBT) and carbon ion radiation therapy (CIRT) offer technological advancements over conventional photon radiotherapy. In this review, we summarize the distinct advantages of CIRT use for HCC treatment, focusing on physical and biological attributes, and outline dosimetric and treatment planning caveats. Based on these considerations, we posit that HCC may be among the best indications for use of CIRT, as it allows for maximizing tumoricidal doses to the target volume while minimizing the dose to the organs at risk.
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AIM: report primary results from the first multicentre randomised trial evaluating induction chemotherapy prior to trimodality therapy in patients with oesophageal or gastro-oesophageal junction adenocarcinoma. Notably, recent data from a single-institution randomised trial reported that induction chemotherapy prolonged overall survival (OS) in patients with well/moderately differentiated tumours. METHODS: In this phase 2 trial (28 centres in the U.S. NCI-sponsored North Central Cancer Treatment Group [Alliance]), trimodality-eligible patients (T3-4N0, TanyN+) were randomised to receive induction (docetaxel, oxaliplatin, capecitabine; Arm A) or no induction chemotherapy (Arm B) followed by oxaliplatin/5-fluorouracil/radiation and subsequent surgery. The primary endpoint was the rate of pathologic complete response (pathCR). Secondary/exploratory endpoints were OS and disease-free survival (DFS). RESULTS: Of 55 patients evaluable for the primary endpoint, the pathCR rate was 28.6% (8/28) in A versus 40.7% (11/27) in B (P = .34). Given interim results indicating futility, accrual was terminated, but patients were followed. After a median follow-up of 60.4 months, a longer median OS in Arm A versus B was unexpectedly observed (3-year rates 57.1% versus 41.7%, respectively) driven by longer DFS after margin-free surgery. In posthoc analysis, induction (versus no induction) chemotherapy was associated with significantly longer OS and DFS among patients with well/moderately differentiated tumours, but not among patients with poorly/undifferentiated tumours (Pinteraction = 0.037). CONCLUSIONS: Adding induction chemotherapy prior to trimodality therapy did not improve the primary endpoint, pathCR. However, induction chemotherapy was associated with longer median OS, particularly among patients with well/moderately differentiated tumours. These findings may inform further development of curative-intent trials in this disease.
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Adenocarcinoma/terapia , Quimiorradioterapia Adjuvante , Neoplasias Esofágicas/terapia , Esofagectomia , Quimioterapia de Indução , Terapia Neoadjuvante , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/mortalidade , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Esofagectomia/efeitos adversos , Esofagectomia/mortalidade , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/mortalidade , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Fatores de Tempo , Estados UnidosRESUMO
The Gamma Knife Icon (Elekta AB, Stockholm) is a cobalt-based stereotactic radiosurgery (SRS) unit to support the use of a thermoplastic mask in lieu of a rigid frame, using an onboard cone-beam CT (CBCT) and an intrafraction motion management system (IFMM). We retrospectively reviewed 124 patients treated with Gamma Knife SRS from January 2018 to December 2019 at our institution using a mask-based immobilization system. Patient and treatment characteristics were collected and summarized as well as interfraction shifts and treatment-related outcomes. This dataset includes 124 patients with an associated 358 intracranial tumors. Twenty-four patients presented with primary brain tumors, which included 14 meningiomas and 10 other histologies, with 100 patients having brain metastases. Sixty tumors were post-operative, while 298 were intact. The median dose for primary tumors was 25 Gy in 5 fractions. Median doses to metastases were 20 Gy in 1 fraction, 27 Gy in 3 fractions, and 25 Gy in 5 fractions. Median interfraction CBCT shifts were submillimeter. Median patient follow-up was 6.28 months. 91% of patients with metastases maintained local control. Our early clinical experience has demonstrated limited toxicity profiles and high patient tolerance, which suggests that mask-based Gamma Knife SRS provides a safe alternative option for frameless SRS. Patients with large target volumes where fractionation is preferred or with small target volumes in non-eloquent areas can be considered for this approach. Response rates are encouraging, and continued follow-up is necessary to investigate long-term control and survival.
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Neoplasias Encefálicas/cirurgia , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomografia Computadorizada de Feixe Cônico , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Pessoa de Meia-Idade , Movimento (Física) , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Pathogenic AXIN2 variants cause absence of permanent teeth (hypodontia), sparse hair and eye brows (ectodermal dysplasia), and gastrointestinal polyps and cancer. Inheritance is autosomal dominant with variable penetrance. Only twenty- five patients have been reported from five families. A Mayo Clinic pilot program tested 3009 newly diagnosed cancer patients for pathogenic germline variants in 83 hereditary cancer genes, including AXIN2. We found only one patient with a pathogenic AXIN2 variant. CASE PRESENTATION: The proband was a 49 year-old female who came to Otolaryngology clinic complaining of right-sided nasal obstruction. Biopsy of identified nasal polyp revealed olfactory neuroblastoma (esthesioneuroblastoma). Surgical resection with gross, total tumor resection was followed by radiation therapy. The patient enrolled in a clinical pilot of genetic testing and a pathogenic variant in AXIN2, c.1822del (p.Leu608Phefs*81) (NM_004655.3) was found. She was seen in Medical Genetics clinic and found to have a personal history of hypodontia. Her eyebrows, hair, and nails were all normal. She underwent upper endoscopy and colonoscopy. A four mm gastric adenoma was found and removed. CONCLUSIONS: This is the first case reported on a patient with a pathogenic, germline AXIN2 variant and an olfactory neuroblastoma or a gastric adenoma. We propose that these could be features of the AXIN2 phenotype. The known association between gastric adenomas and familial adenomatous polyposis, the other Wnt/beta-catenin disorder, supports the hypothesis that pathogenic AXIN2 variants increase risk as well. As the odds of a chance co-occurrence of a pathogenic AXIN2 variant and an olfactory neuroblastoma are so rare, it is worth exploring potential causation. We are building a clinical registry to expand understanding of the AXIN2 phenotype and request any clinicians caring for patients with pathogenic AXIN2 variants to contact us.
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Adenoma/genética , Proteína Axina/genética , Estesioneuroblastoma Olfatório/genética , Células Germinativas/metabolismo , Neoplasias Gástricas/genética , Estesioneuroblastoma Olfatório/diagnóstico por imagem , Estesioneuroblastoma Olfatório/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Radiografia Panorâmica , Neoplasias Gástricas/diagnóstico por imagemRESUMO
BACKGROUND: Low dose computerized tomography (LDCT) has been shown to reduce lung cancer specific mortality by 20 %. Despite U.S. Preventive Services Task Force (USPSTF) endorsement, screening of appropriate patients in the U.S. remains low, at 1.9 %. The goal of this study was to assess the number and type of patients that would qualify for lung cancer screening based upon recommendations by various guidelines. METHODS: We prospectively collected a patient reported questionnaire, including smoking history, family history, exposure history, and demographics, from April-October 2017 from new consults in the Department of Radiation Oncology and Otolaryngology (ORL). Patients smoking status and patient factors were collected and reported. Patients qualifying for screening by USPSTF, the National Comprehensive Cancer Network (NCCN), and Tammemagi scoring criteria were identified. Multivariate analysis assessed the factors associated with positive criteria for screening and the sensitivity of each criterion was calculated. RESULTS: There were 546 new consults during the study period and 528 successfully completed the questionnaire. A total of 104/528 (20 %) patients who completed questionnaires qualified for screening based on any guideline. After exclusion of active lung cancer (nâ¯=â¯19), poor prognosis (nâ¯=â¯24), and CT as part of surveillance (nâ¯=â¯16), 45 (8.5 %) patients would require LDCT. Of the entire population, 10 %, 11 % and 18 % of patients qualified based on USPSTF, NCCN, and Tammemagi, which was reduced to 4.9 %, 5.3 %, and 7.8 %, respectively after exclusions. Patients with head and neck cancer (40 %), skin cancer (27 %), and prostate cancer (11 %) accounted for the majority of patients eligible for screening after exclusions. The sensitivity of the USPSTF, NCCN, and Tammemagi criteria in patients with a diagnosis of lung cancer (nâ¯=â¯26) was 38.5 % (CI95 20.2 %-59.4 %), 46.2 % (CI95 26.6 %-66.6 %), and 61.5 % (CI95 40.6 %-79.8 %), respectively. CONCLUSIONS: We successfully identified 9 % of an oncology population at consultation who could benefit from lung cancer screening in survivorship. Distribution of a written or electronic questionnaire at consultation is a simple, low cost, effective method of identifying patients who would benefit from LDCT.
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Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Masculino , Programas de Rastreamento , Fumar , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: To investigate the frequency, magnitude and possible causes of frame-shifts that may occur between treatment planning and treatment delivery when performing Gamma Knife radiosurgery with rigid frame-based immobilization. METHODS: Differences between computed tomography (CT) framed fiducial stereotactic coordinate reference and cone beam computed tomography stereotactic coordinates after image registration were recorded for 49 frame-based GK radiosurgery cases performed using the Gamma Knife Icon. Parameters recorded include rotational shifts, translational shifts, and the GK-computed Maximum Shot Displacement (MSD) between the two stereotactic coordinate spaces. Other patient-specific parameters were collected and linear regression analysis was performed to evaluate predictors of increased displacement. RESULTS: The median values of rotational shifts were: pitch 0.14°, yaw 0.17°, and roll 0.13°. The median absolute values of translational shifts were: left-right 0.39 mm, anteroposterior 0.14 mm, and superior-inferior 0. 22 mm. The median value of MSD was 0.71 mm. Twelve cases (24.5%) had a MSD of greater than 1.0 mm. Male gender was associated with increased MSD (p = 0.013) and translational shifts (root-mean-squared value, p = 0.017). Cases with large differences between right and left sided pin lengths were also associated with increased MSD (p = 0.011). CONCLUSIONS: The use of CBCT image guidance in frame-based GK radiosurgery allows unintended frame shifts to be identified and corrected. A significant fraction (24.5%) of patients had large enough shifts to result in a MSD of greater than 1.0 mm. Male gender and eccentrically placed frames were associated with increased MSD, and particular care should be taken in these cases.
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Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Tomografia Computadorizada de Feixe Cônico/métodos , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Artefatos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery have become widely used in both palliative and curative treatments for variety of primary and secondary malignancies. Although the indications and use of stereotactic techniques have increased substantially in the past decades, there been no studies to date analyzing public interest in these techniques. Using Google Trends (Google LLC, Mountain View, CA), four search terms ("SBRT," "stereotactic radiosurgery," "Gamma Knife" and "Cyberknife") were analyzed in the U.S. from January 2004 to June 2019. Each term was assigned a relative interest score based on frequency of searches. "SBRT" is becoming an increasingly popular search term, reaching peak interest in October 2018. Conversely, "stereotactic radiosurgery" and "Gamma Knife" radiosurgery initially had high interest, before declining over the past decade. "Cyberknife" was most popular in the mid-2000s but decreased steadily since that time. These trends were subsequently compared against PubMed publication data over the same time.
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BACKGROUND AND PURPOSE: To analyze outcomes of non-small cell lung cancer (NSCLC) patients with brain metastases harboring EGFR or ALK mutations and examine for differences between tyrosine kinase inhibitors (TKIs) alone, radiotherapy (RT) alone (either whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS)), or combined TKIs and RT. MATERIALS AND METHODS: Thirty studies were identified. PATIENTS: with brain metastases from NSCLC. INTERVENTION: initial TKIs alone with optional salvage RT, RT alone, or TKIs and RT. CONTROL: wild-type NSCLC and TKIs alone for mutational and treatment analysis, respectively. OUTCOMES: overall survival (OS) and intracranial progression-free survival (PFS). SETTING: studies with mutation information. RESULTS: A total of 2649 patients were included. Patients with ALK and EGFR mutations had significantly higher median OS (48.5 months, p < 0.0001; and 20.9 months; p = 0.0006, respectively) compared to wild-type patients (9.9 months). Similar median OS was noted between TKIs and RT (28.3 months), RT alone (32.2 months; p = 0.22), or TKIs alone (23.9 months; p = 0.2). Patients treated with TKIs and RT had higher median PFS (18.6 months; p = 0.06) compared to TKIs alone (13.6 months) with no difference between TKIs and RT vs. RT alone (16.9 months; p = 0.72). No PFS difference was found between WBRT and TKI (23.2 months; p = 0.72) vs. WBRT alone (24 months) or SRS and TKI (16.7 months; p = 0.56) vs. SRS alone (13.6 months). CONCLUSION: NSCLC patients with brain metastases harboring EGFR or ALK mutations have superior OS compared to wild-type patients. No PFS or OS benefit was found with the addition of TKIs to RT.
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Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias Encefálicas/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Estudos RetrospectivosRESUMO
INTRODUCTION: Vestibular schwannomas are benign tumors of the 8th cranial nerve. Initial treatment options include active surveillance, surgery, and/or radiation therapy. We analyzed the United States National Cancer Database (NCDB) for patients with vestibular schwannomas and evaluated the initial management trends after diagnosis. METHODS: We queried the NCDB for patients with vestibular schwannomas, excluding patients who did not have schwannomas of the vestibulocochlear nerve. Categorical and continuous variables were analyzed, and multivariate Cox regression analyses were performed to investigate for predictors of initial local therapy at diagnosis. All statistical analyses were performed using commercially available software (SPSS, Version 22; SPSS Inc., Chicago, IL). RESULTS: A total of 28,446 patients met the inclusion criteria. In this cohort, 7351 (25.8%) underwent observation, 12,362 (43.5%) underwent surgical resection, 7785 (27.4%) underwent SRS, 824 (2.9%) underwent EBRT, and 124 (0.4%) underwent RT NOS. On multivariate analysis, younger age, increased distance to treating facility, Charlson/Deyo score of 1, primary payer insurance, facility location and facility type (academic or cancer center) (pâ¯<â¯0.001) were all factors that predicted patients undergoing initial definitive treatment. CONCLUSION: Age, distance to treating facility, Charlson/Deyo score, primary payer, facility location, and facility type are factors that influence initial treatment for patients with vestibular schwannoma. Clinical stratification systems are needed to identify which patients would benefit most from initial local therapy versus active surveillance.
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Neuroma Acústico/terapia , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/tendências , Adolescente , Adulto , Idoso , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Procedimentos Neurocirúrgicos/tendências , Radiocirurgia/estatística & dados numéricos , Radiocirurgia/tendências , Estados Unidos , Conduta Expectante/estatística & dados numéricos , Conduta Expectante/tendências , Adulto JovemRESUMO
Importance: Oral mucositis causes substantial morbidity during head and neck radiotherapy. In a randomized study, doxepin mouthwash was shown to reduce oral mucositis-related pain. A common mouthwash comprising diphenhydramine-lidocaine-antacid is also widely used. Objective: To evaluate the effect of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash for the treatment of oral mucositis-related pain. Design, Setting, and Participants: A phase 3 randomized trial was conducted from November 1, 2014, to May 16, 2016, at 30 US institutions and included 275 patients who underwent definitive head and neck radiotherapy, had an oral mucositis pain score of 4 points or greater (scale, 0-10), and were followed up for a maximum of 28 days. Interventions: Ninety-two patients were randomized to doxepin mouthwash (25 mg/5 mL water); 91 patients to diphenhydramine-lidocaine-antacid; and 92 patients to placebo. Main Outcome and Measures: The primary end point was total oral mucositis pain reduction (defined by the area under the curve and adjusted for baseline pain score) during the 4 hours after a single dose of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash compared with a single dose of placebo. The minimal clinically important difference was a 3.5-point change. The secondary end points included drowsiness, unpleasant taste, and stinging or burning. All scales ranged from 0 (best) to 10 (worst). Results: Among the 275 patients randomized (median age, 61 years; 58 [21%] women), 227 (83%) completed treatment per protocol. Mucositis pain during the first 4 hours decreased by 11.6 points in the doxepin mouthwash group, by 11.7 points in the diphenhydramine-lidocaine-antacid mouthwash group, and by 8.7 points in the placebo group. The between-group difference was 2.9 points (95% CI, 0.2-6.0; P = .02) for doxepin mouthwash vs placebo and 3.0 points (95% CI, 0.1-5.9; P = .004) for diphenhydramine-lidocaine-antacid mouthwash vs placebo. More drowsiness was reported with doxepin mouthwash vs placebo (by 1.5 points [95% CI, 0-4.0]; P = .03), unpleasant taste (by 1.5 points [95% CI, 0-3.0]; P = .002), and stinging or burning (by 4.0 points [95% CI, 2.5-5.0]; P < .001). Maximum grade 3 adverse events for the doxepin mouthwash occurred in 3 patients (4%); diphenhydramine-lidocaine-antacid mouthwash, 3 (4%); and placebo, 2 (2%). Fatigue was reported by 5 patients (6%) in the doxepin mouthwash group and no patients in the diphenhydramine-lidocaine-antacid mouthwash group. Conclusions and Relevance: Among patients undergoing head and neck radiotherapy, the use of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash vs placebo significantly reduced oral mucositis pain during the first 4 hours after administration; however, the effect size was less than the minimal clinically important difference. Further research is needed to assess longer-term efficacy and safety for both mouthwashes. Trial Registration: ClinicalTrials.gov Identifier: NCT02229539.
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Antiácidos/uso terapêutico , Difenidramina/uso terapêutico , Doxepina/uso terapêutico , Neoplasias de Cabeça e Pescoço/radioterapia , Lidocaína/uso terapêutico , Antissépticos Bucais , Lesões por Radiação/tratamento farmacológico , Estomatite/tratamento farmacológico , Administração Tópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Difenidramina/efeitos adversos , Método Duplo-Cego , Doxepina/efeitos adversos , Fadiga/induzido quimicamente , Feminino , Humanos , Lidocaína/efeitos adversos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Estomatite/etiologiaRESUMO
BACKGROUND: The country of Georgia launched the world's first Hepatitis C Virus (HCV) Elimination Program in 2015 and set a 90% prevalence reduction goal for 2020. We conducted a nationally representative HCV seroprevalence survey to establish baseline prevalence to measure progress toward elimination over time. METHODS: A cross-sectional seroprevalence survey was conducted in 2015 among adults aged ≥18 years using a stratified, multi-stage cluster design (n = 7000). Questionnaire variables included demographic, medical, and behavioral risk characteristics and HCV-related knowledge. Blood specimens were tested for antibodies to HCV (anti-HCV) and HCV RNA. Frequencies were computed for HCV prevalence, risk factors, and HCV-related knowledge. Associations between anti-HCV status and potential risk factors were calculated using logistic regression. RESULTS: National anti-HCV seroprevalence in Georgia was 7.7% (95% confidence interval (CI) = 6.7, 8.9); HCV RNA prevalence was 5.4% (95% CI = 4.6, 6.4). Testing anti-HCV+ was significantly associated with male sex, unemployment, urban residence, history of injection drug use (IDU), incarceration, blood transfusion, tattoos, frequent dental cleanings, medical injections, dialysis, and multiple lifetime sexual partners. History of IDU (adjusted odds ratio (AOR) = 21.4, 95% CI = 12.3, 37.4) and blood transfusion (AOR = 4.5, 95% CI = 2.8, 7.2) were independently, significantly associated with testing anti-HCV+ after controlling for sex, age, urban vs. rural residence, and history of incarceration. Among anti-HCV+ participants, 64.0% were unaware of their HCV status, and 46.7% did not report IDU or blood transfusion as a risk factor. CONCLUSIONS: Georgia has a high HCV burden, and a majority of infected persons are unaware of their status. Ensuring a safe blood supply, implementing innovative screening strategies beyond a risk-based approach, and intensifying prevention efforts among persons who inject drugs are necessary steps to reach Georgia's HCV elimination goal.
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Erradicação de Doenças/estatística & dados numéricos , Hepacivirus , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Programas de Rastreamento/estatística & dados numéricos , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , República da Geórgia/epidemiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Estudos SoroepidemiológicosRESUMO
OBJECTIVES: The natural history of squamous cell carcinoma (SCC) of the oral cavity (OC) in young adults is unknown. We sought to provide an updated report on treatment outcomes of patients with OC SCC who were 40â¯years or younger. MATERIALS AND METHODS: We performed a retrospective analysis of 124 consecutive patients with primary OC SCC treated at Mayo Clinic (1980-2014). Patient and tumor characteristics and treatment approach were abstracted from patient charts. RESULTS: Median patient age was 35â¯years (range, 19-40â¯years). The most common primary site was oral tongue (107 patients; 86.3%). Most patients (101; 81.5%) underwent wide local excision. Surgery alone was curative in 77 patients (62.1%); 47 (37.9%) received radiotherapy, and 26 (21%) received chemotherapy. Five-year overall survival (OS) was 78.1%; 10-year OS was 76.9%. Five-year disease-free survival (DFS) was 66.6%; 5-year local control was 87.6%; and 5-year locoregional control was 78.5%. On multivariable analysis, factors associated with worse OS and DFS were higher pathologic T stage (Pâ¯=â¯.008), lymph node positivity (Pâ¯<â¯.001), and disease recurrence (Pâ¯<â¯.001). CONCLUSION: Young adults with primary OC SCC may be treated with a similar treatment approach as older adults.
Assuntos
Metástase Linfática/patologia , Neoplasias Bucais/terapia , Recidiva Local de Neoplasia/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto , Fatores Etários , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Boca/cirurgia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Adulto JovemRESUMO
OBJECTIVE: To examine disease control and survival after stereotactic body radiotherapy (SBRT) for medically inoperable, early-stage non-small cell lung cancer (NSCLC) and determine associations of pretreatment 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) maximum standardized uptake values (SUVmax), biologically effective dose, and mediastinal staging with disease control and survival outcomes. PATIENTS AND METHODS: We retrospectively reviewed the cases of consecutive patients with FDG-PET-staged, medically inoperable NSCLC treated with SBRT at our institution between January 1, 2008, and August 4, 2014. Cumulative incidences of recurrence were estimated, accounting for the competing risk of death. Associations of SUVmax, biologically effective dose, and mediastinal staging with outcomes were evaluated using Cox proportional hazards regression models. RESULTS: Among 282 patients, 2-year cumulative incidences of recurrence were 4.9% (95% CI, 2.6%-8.3%) for local, 9.8% (95% CI, 6.3%-14.2%) for nodal, 10.8% (95% CI, 7.0%-15.5%) for ipsilateral lung, 6.0% (3.3%-9.8%) for contralateral lung, 9.7% (95% CI, 6.3%-14.0%) for distant recurrence, and 26.1% (95% CI, 20.4%-32.0%) for any recurrence. The 2-year overall survival was 70.4% (95% CI, 64.5%-76.8%), and the 2-year disease-free survival was 51.2% (95% CI, 44.9%-58.5%). Risk of any recurrence was significantly higher for patients with higher SUVmax (hazard ratio [per each doubling], 1.29 [95% CI, 1.05-1.59]; P=.02). A similar association with SUVmax was observed when considering the composite outcome of any recurrence or death (hazard ratio, 1.23 [95% CI, 1.05-1.44]; P=.01). The SUVmax was not significantly associated with other outcomes (P≥0.69). Two-year cumulative incidences of local recurrence for patients receiving 48 Gy in 4 fractions, 54 Gy in 3 fractions, or 50 Gy in 5 fractions were 1.7% (95% CI, 0.3%-5.6%), 3.7% (95% CI, 0.7%-11.4%), and 15.3% (95% CI, 5.9%-28.9%), respectively (P=.02); this difference was independent of lesion size (P=.02). CONCLUSION: Disease control was excellent for patients who received SBRT for early-stage NSCLC, and this series represents the largest single-institution experience from the United States on SBRT for early-stage inoperable NSCLC. Higher pretreatment FDG-PET SUVmax was associated with increased risk of any recurrence, and the 50 Gy in 5 fractions dose prescription was associated with increased risk of local recurrence.
RESUMO
BACKGROUND: Treatment of non-small-cell lung cancer (NSCLC) has been rapidly advancing over the last decade. Academic centers are considered equipped with better expertise. NSCLC outcome trends in novel therapeutic era and impact of initial treatment at academic centers have not been reported. METHODS: The National Cancer Database (NCDB) was used to identify NSCLC incident cases from 2004 to 2013. Overall survival (OS) was plotted by year of diagnosis and type of initial treatment center, accounting for several factors available in NCDB. RESULTS: A total of 1 150 722 NSCLC patients were included and separated by initial treatment center type (academic: 31.5%; nonacademic: 68.5%). Median follow-up and OS for all patients were 11.8 months (range: 0-133.6 months) and 13.1 months (95% CI: 13.08-13.17), respectively. Median OS improved significantly for those diagnosed in 2010-2013 (14.8 months [95% CI: 14.7-14.9]) as compared to 2004-2009 (12.4 months [95% CI: 12.3-12.5]) (P < 0.001). Treatment at academic centers was associated with improved OS (multivariate HR for OS = 0.929 [95% CI: 0.92-0.94], P < 0.0010). Four-year OS for academic and nonacademic cohorts was 28.5%% and 22.1%, respectively (P < 0.001), and the difference was more pronounced in stage I to III NSCLC. CONCLUSION: In this largest analysis, thus far, NSCLC survival has improved over time, and type of initial treatment center significantly influences survival. Identifying and removing barriers to obtaining initial treatment of NSCLC at academic medical centers could improve OS.
Assuntos
Centros Médicos Acadêmicos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Centros Médicos Acadêmicos/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Bases de Dados Factuais , Feminino , Humanos , Incidência , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida , Tempo para o TratamentoRESUMO
Glioblastoma multiforme (GBM) is a primary brain neoplasm accounting for approximately 75% of all high grade gliomas. It is diffusely infiltrative and exhibits rapid proliferation with a poor overall prognosis. Maximum surgical resection and postoperative radiotherapy, accompanied by concurrent and adjuvant temozolomide chemotherapy, remain the standard of care without major therapeutic advances over the past 10â¯years. Herein, we present the case of a 64-year-old Caucasian male with a GBM who subsequently developed a left frontal dural metastasis, subsequently treated with stereotactic radiosurgery (20â¯Gy in 1 fraction). With six month follow-up, the patient showed near complete resolution of his dural metastases and no overall change in neurological symptoms or side effects following radiosurgery. Due to the paucity of clinical literature regarding dural metastases from GBM, its optimal treatment remains unknown. While the role of SRS has yet to be defined in this setting, here we provide evidence suggesting its overall efficacy in the treatment of select dural GBM metastases.