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1.
Clin Otolaryngol ; 49(4): 506-511, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38572684

RESUMO

OBJECTIVE: The purpose of this study was to investigate whether patient, tumour and radiation therapy factors are associated with development of middle ear effusion (MEE) in nasopharyngeal carcinoma (NPC) patients. DEIGN, SETTINGS, AND PARTICIPANTS: A retrospective review of NPC patients treated between January 2000 and June 2018 at Rabin Medical Center. Patient factors, tumour factors, radiation doses, and radiation fields were collected and outlined if needed (middle ear, eustachian tube [ET], tensor veli palatini [TVP], and levator palatini [LVP] muscles), then analysed and compared between patients with MEE and those without and between sides in patients with unilateral MEE. MAIN OUTCOME MEASURES AND RESULTS: Seventy-three patients were enrolled. Most were males (71.2%) with advanced-stage diseases (78%). At the time of diagnosis 14 patients (19.2%) presented with MEE. Following radiation, 18 patients, with no evidence of MEE at presentation, developed MEE. Tumour stage, histology, and laterality were not associated with development of MEE. Comparison of mean radiation field dosages including-gross target volume, clinical target volume, and patient target volume showed no association with post-radiation MEE. In addition, no difference was found in the radiation doses to the middle ear, ET or the LVP nor the TVP between ears with and without MEE. CONCLUSIONS: Post-irradiation MEE remains a common adverse effect in NPC patients. Surprisingly, tumour stage, tumour laterality, and histology were not associated with MEE. Similar findings were observed for total radiation doses and specific doses to the middle ear, ET, and ET muscles.


Assuntos
Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Otite Média com Derrame , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/complicações , Otite Média com Derrame/etiologia , Adulto , Idoso , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/complicações , Carcinoma Nasofaríngeo/patologia , Fatores de Risco , Estadiamento de Neoplasias
2.
Dermatol Ther ; 35(10): e15747, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36190005

RESUMO

Melanoma is widely treated with programmed cell death-1 (PD-1) inhibitors. As part of their anti-tumor immunity effect, they increase the susceptibility to cutaneous immune-related adverse events (cIRAE) among other autoimmune effects. To characterize the manifestations of cIRAE in melanoma patients treated with PD-1 inhibitors, and evaluate the correlation with tumor response. A retrospective study of 95 metastatic malignant melanoma patients treated with PD-1 inhibitors at the Hadassah Medical Center during 2013-2016. The most common cIRAE was pruritus reported by 39 (41%) patients. All other cIRAE were noted in 34 patients (35.8%), of which the most common cutaneous manifestation was vitiligo, demonstrated in 17 patients (17.9%) followed by various rashes (7.4%, including erythema multiforme, oral lichen planus, photosensitive rash, insect bite-like reaction, and urticaria), psoriasiform rash (3.2%), bullous pemphigoid (3.2%), and eczema (1%). Interestingly, higher response rates to immunotherapy were demonstrated in patients who developed pruritus (85%) and cIRAE (88%), with lower mortality rates in the cIRAE group (38.2%) versus the non-cIRAE group (70.5%, p = 0.002). cIRAE are common among malignant melanoma patients treated with PD-1 inhibitors and may be a marker for favorable prognosis.


Assuntos
Exantema , Melanoma , Segunda Neoplasia Primária , Apoptose , Humanos , Inibidores de Checkpoint Imunológico , Prognóstico , Receptor de Morte Celular Programada 1 , Prurido , Estudos Retrospectivos
3.
Mol Cell Proteomics ; 19(8): 1360-1374, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32451349

RESUMO

Personalized cancer immunotherapy targeting patient-specific cancer/testis antigens (CTA) and neoantigens may benefit from large-scale tumor human leukocyte antigen (HLA) peptidome (immunopeptidome) analysis, which aims to accurately identify antigens presented by tumor cells. Although significant efforts have been invested in analyzing the HLA peptidomes of fresh tumors, it is often impossible to obtain sufficient volumes of tumor tissues for comprehensive HLA peptidome characterization. This work attempted to overcome some of these obstacles by using patient-derived xenograft tumors (PDX) in mice as the tissue sources for HLA peptidome analysis. PDX tumors provide a proxy for the expansion of the patient tumor by re-grafting them through several passages to immune-compromised mice. The HLA peptidomes of human biopsies were compared with those derived from PDX tumors. Larger HLA peptidomes were obtained from the significantly larger PDX tumors as compared with the patient biopsies. The HLA peptidomes of different PDX tumors derived from the same source tumor biopsy were very reproducible, even following subsequent passages to new naïve mice. Many CTA-derived HLA peptides were discovered, as well as several potential neoantigens/variant sequences. Taken together, the use of PDX tumors for HLA peptidome analysis serves as a highly expandable and stable source of reproducible and authentic peptidomes, opening up new opportunities for defining large HLA peptidomes when only small tumor biopsies are available. This approach provides a large source for tumor antigens identification, potentially useful for personalized immunotherapy.


Assuntos
Antígenos de Neoplasias/metabolismo , Antígenos HLA/metabolismo , Peptídeos/metabolismo , Proteoma/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Biópsia , Análise por Conglomerados , Feminino , Humanos , Masculino , Camundongos , Mutação/genética
4.
Isr Med Assoc J ; 24(8): 491-496, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35971997

RESUMO

BACKGROUND: Recent studies show a high risk of developing malignancy in patients with Fanconi anemia. The most common solid tumor in this condition is head and neck squamous cell carcinoma (HNSCC) and there is often uncertainty and about disease behavior as well as chemotherapy and radiation response. OBJECTIVES: To describe and characterize HNSCC among Fanconi anemia patients on the Israeli Fanconi Registry. METHODS: Our study population included patients in Israel's inherited bone marrow failure registry who were diagnosed with Fanconi anemia between1980 and 2016. Demographic, clinical, and laboratory data were collected from patient charts. RESULTS: From the collected data, HNSCC was confirmed in 6/111 (5.4%) Fanconi anemia patients; 1 (17%) had classic HNSCC risk factors of tobacco abuse and 4 (56%) had undergone primary surgery. The 3 (50%) receiving concurrent chemoradiotherapy had mild side effects, while half developed metachronous primary malignancy, and all developed > 2 primary malignancies. The overall median survival of the patients in our study was 14 (0.5-57) months. CONCLUSIONS: Fanconi anemia patients have a very high risk of developing HNSCC. Proactive screening for malignancies is needed for the head and neck regions. We also found that chemoradiotherapy can be used safely in high-stage cancers.


Assuntos
Anemia de Fanconi , Neoplasias de Cabeça e Pescoço , Anemia de Fanconi/complicações , Anemia de Fanconi/epidemiologia , Anemia de Fanconi/terapia , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Israel/epidemiologia , Sistema de Registros , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia
5.
Oncology ; 99(7): 464-470, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33789303

RESUMO

INTRODUCTION: Immune-checkpoint inhibitors have demonstrated a significant survival benefit in metastatic and non-resectable head and neck squamous cell carcinoma (HNSCC). Patients with a combined positivity score (CPS) of 20 and higher benefit the most from therapy. Inaccurate definition of the CPS category might lead to the incorrect stratification of patients to immunotherapy. This study's main aim was to investigate programmed death-ligand 1 (PD-L1) antigen expression in HNSCC in diverse clinical situations and histological settings. MATERIALS AND METHODS: This is a prospective cohort study conducted in a tertiary referral medical center. Tissues were investigated for PD-L1 expression using the FDA-approved 22C3 immunohistochemistry assay (Dako). We analyzed potential associations between the CPS category and meaningful demographic, clinical, and outcome metrics. Furthermore, we investigated morphologically separate sites for CPS scores in whole surgical tissue specimens and matched preoperative biopsies. RESULTS: We analyzed 36 patients, of whom 26 had oral cavity SCC and 10 had laryngeal SCC. The overall, disease-specific, and progression-free survival of the HNSCC group of patients were not associated with the CPS category (p = 0.45, p = 0.31, and p = 0.88, respectively). There was a significant (18%, 95% CI 0.65-0.9) inconsistency between the CPS category determined in biopsies versus whole carcinoma analyses. We also found an uneven distribution of whole-tumor CPS attributed to spatial carcinoma invasiveness, tumor differentiation, and inflammatory cell infiltration heterogeneity. DISCUSSION AND CONCLUSIONS: Our data suggest that careful selection of tumor area for CPS analysis is important. PD-L1 antigen expression, clinically represented by CPS, may be up- or down-categorized in different clinical and pathological circumstances. The high whole-tissue CPS category scatter may clinically result in potential treatment modifications. We argue that CPS analysis requires not only adequacy (at least 100 viable tumor cells), but also correct representation of the tumor microenvironment.


Assuntos
Antígeno B7-H1/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Biópsia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Microambiente Tumoral
6.
Dermatology ; 237(6): 988-994, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33378750

RESUMO

BACKGROUND: The incidence of epidermal growth factor receptor inhibitor (EGFRI)-induced papulopustular rash is 60-85%. OBJECTIVE: To investigate prophylactic topical treatment for EGFRI-induced rash. METHODS: A single-center, randomized, double-blind, placebo-controlled trial. Adult cancer patients initiating treatment with EGFRIs were randomized to receive facial topical treatment with chloramphenicol 3% + prednisolone 0.5% (CHL-PRED) ointment, chloramphenicol 3% (CHL) ointment, or aqua cream (AQUA). The primary end points were the incidence of ≥grade 3 rash using the Common Terminology Criteria for Adverse Events (CTCAE), on days 14 and 30. A subanalysis was conducted for incidence of a protocol-specified significant rash, defined as ≥10 facial papulopustular lesions. RESULTS: The per-protocol analysis on day 14 included 69 patients, who received CHL-PRED (21), CHL (23), or AQUA (25). The incidence of CTCAE ≥grade 3 rash was not statistically significant between arms; however, the incidence of the protocol-specified significant rash was: CHL-PRED 14%, CHL 39%, and AQUA 48% (p = 0.03, CHL-PRED vs. AQUA). At 30 days, the CTCAE ≥grade 3 incidence was similar, but the incidences of protocol-specified significant rash were 6%, 16%, and 43% (p = 0.03, CHL-PRED vs. AQUA). No significant differences were found between CHL and CHL-PRED and between CHL and AQUA. CONCLUSIONS: Prophylactic topical CHL-PRED was efficacious when compared to AQUA, in the treatment of EGFRI-induced facial papulopustular rash.


Assuntos
Antibacterianos/uso terapêutico , Cloranfenicol/uso terapêutico , Receptores ErbB/efeitos adversos , Receptores ErbB/antagonistas & inibidores , Exantema/prevenção & controle , Inibidores de Proteínas Quinases/efeitos adversos , Administração Tópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/uso terapêutico , Método Duplo-Cego , Exantema/induzido quimicamente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Prednisolona/uso terapêutico
7.
Isr Med Assoc J ; 23(12): 759-765, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34954913

RESUMO

BACKGROUND: The increased susceptibility of cancer patients to coronavirus disease-2019 (COVID-19) infections and complications calls for special precautions while treating cancer patients during COVID-19 pandemics. Thus, oncology departments have had to implement a wide array of prevention measures. OBJECTIVES: To address issues associated with cancer care during the COVID-19 pandemic and to assess the implementation of measures aimed at containment of COVID-19 diffusion while allowing continuation of quality cancer care. METHODS: A national survey among oncology departments in Israel was conducted between 12 April 2020 and 14 April 2020. Eighteen heads of hospital-based oncology departments completed a self-report questionnaire regarding their institute's preparedness for treatment of cancer patients during the COVID-19 pandemic. RESULTS: In this national survey, prevention measures against COVID-19 spread were taken prior to patients' arrival and at arrival or while staying in the departments. Most participants (78-89%) reported using a quick triage of patients and caregivers prior to their entrance to the oncology units, limiting the entrance of caregivers, and reducing unnecessary visits to the clinic. Switching to oral therapies rather than intravenous ones when possible was considered by 82% and shortage in personal protective equipment was reported by five (28%) heads of oncology departments. Some differences between large and small/medium sized medical centers were observed regarding issues related to COVID-19 containment measures and changes in treatment. CONCLUSIONS: Oncology departments in Israel were able to prepare and adapt their services to guidelines and requirements related to the COVID-19 pandemic with little harm to their treatment capacity.


Assuntos
COVID-19/prevenção & controle , Hospitais/estatística & dados numéricos , Neoplasias/terapia , Equipamento de Proteção Individual/provisão & distribuição , Pesquisas sobre Atenção à Saúde , Humanos , Israel , Triagem/métodos
8.
Medicina (Kaunas) ; 57(5)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064551

RESUMO

Background and Objectives: Determine the contribution of coexisting factors to the risk to develop Osteoradionecrosis (ORN) of the jaws among patients who have received radiotherapy by intensity modulated radiation therapy (IMRT) for head and neck cancer (HNC) between 2013 and 2016, in a single medical center. Materials and Methods: The records of all patients treated with IMRT for HNC between 2013 and 2016 in The Davidoff Center for the treatment and Research of Cancer in Rabin Medical Center-Beilinson hospital, Petah-Tikva, Israel were screened. Patients who have received a minimum mean dose of 40 Gy to the oral cavity entered the research and their medical records were retrospectively reviewed. Collected background data included: age, gender, smoking, diabetes mellitus (DM), ASA score, mean and maximal radiation doses (Gy), and diseases characteristics including histological diagnosis, primary tumor site, and disease stage. Results: A total of 1232 patients were surveyed. Out of all screened patients, 93 received a minimum mean dose of 40 Gy to the oral cavity. Out of the 93 patients, 7 (7.52%) developed ORN (ORN+) and 86 did not develop ORN (ORN-). Tumor type in all seven patients in the ORN+ group was Squamous Cell Carcinoma (SCC). In three out of those seven patients (42.9%), the tumor was located in the mandible. Conclusions: within the limits of the relatively small cohort in the current study, we suggest that the development of ORN due to Radiation therapy (RT) with IMRT is related significantly only to the location of a tumor in the mandible. Other co-factors do not significantly increase the risk to develop ORN when RT is delivered via IMRT.


Assuntos
Neoplasias de Cabeça e Pescoço , Osteorradionecrose , Radioterapia de Intensidade Modulada , Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Israel , Osteorradionecrose/epidemiologia , Osteorradionecrose/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Fatores de Risco
9.
Am J Otolaryngol ; 41(1): 102293, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31732301

RESUMO

PURPOSE: To assess the clinical value of ultrasound (US) and fine needle aspiration (FNA) of salivary gland lesions prior to surgery, for preoperative decision-making and long-term follow-up/outcome. MATERIALS & METHODS: We retrospectively analyzed the medical charts of 98 consecutive patients with major salivary gland lesions who were treated in a single medical from 2008 to 2017. Preoperative US and FNA was performed in all patients. Cytology results were compared with histopathological diagnoses. The correlation between preoperative US findings, cytology and histopathological diagnoses was assessed. RESULTS: Twenty-three specimens were histopathologically malignant, and 75 were diagnosed as benign. Three false-positive results diagnosed as malignant in cytology had a final histology of sialadenitis, pleomorphic adenoma and Warthin's tumor, respectively. In six cases, cytology yielded false-negative results. The overall accuracy of FNA in distinguishing benign from malignant lesions was 91%. Sensitivity was 70% and specificity 93%. There was no significant correlation between US features and final pathology, but larger size had some correlation with malignancy (p = 0.306). No complications were observed during or after performing FNA. CONCLUSION: FNA from salivary gland lesions is safe and in many cases can help in preoperative decision making or surgical planning. Hence, the results of FNA cytology should have an integral role in clinical decision-making and management of major salivary gland lesions. False-negative results do occur and therefore should be used only as an adjunctive measure.


Assuntos
Biópsia por Agulha Fina , Doenças das Glândulas Salivares/diagnóstico , Ultrassonografia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisões , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade
10.
Int J Cancer ; 145(3): 748-762, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30694565

RESUMO

An understanding of the mechanisms underlying acquired resistance to cetuximab is urgently needed to improve cetuximab efficacy in patients with head and neck squamous cell carcinoma (HNSCC). Here, we present a clinical observation that MET pathway activation constitutes the mechanism of acquired resistance to cetuximab in a patient with HNSCC. Specifically, RNA sequencing and mass spectrometry analysis of cetuximab-sensitive (CetuxSen ) and cetuximab-resistant (CetuxRes ) tumors indicated MET amplification and overexpression in the CetuxRes tumor compared to the CetuxSen lesion. Stimulation of MET in HNSCC cell lines was sufficient to reactivate the MAPK pathway and to confer resistance to cetuximab in vitro and in vivo. In addition to the direct role of MET in reactivation of the MAPK pathway, MET stimulation abrogates the well-known cetuximab-induced compensatory feedback loop of HER2/HER3 expression. Mechanistically, we showed that the overexpression of HER2 and HER3 following cetuximab treatment is mediated by the ETS homologous transcription factor (EHF), and is suppressed by MET/MAPK pathway activation. Collectively, our findings indicate that evaluation of MET and HER2/HER3 in response to cetuximab in HNSCC patients can provide the rationale of successive line of treatment.


Assuntos
Cetuximab/farmacologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Proteínas Proto-Oncogênicas c-met/metabolismo , Receptor ErbB-2/metabolismo , Receptor ErbB-3/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Cetuximab/farmacocinética , Resistencia a Medicamentos Antineoplásicos , Ativação Enzimática , Expressão Gênica , Neoplasias de Cabeça e Pescoço/enzimologia , Neoplasias de Cabeça e Pescoço/genética , Humanos , Indóis/farmacologia , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Distribuição Aleatória , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/biossíntese , Receptor ErbB-2/genética , Receptor ErbB-3/antagonistas & inibidores , Receptor ErbB-3/biossíntese , Receptor ErbB-3/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/enzimologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Sulfonas/farmacologia , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Lancet ; 402(10412): 1521, 2023 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-37844591

Assuntos
Prisioneiros , Humanos , Israel
12.
Am J Otolaryngol ; 38(3): 316-320, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28169008

RESUMO

OBJECTIVE: To determine if the clinical behavior of T1 glottic squamous cell carcinoma varies by its location on the medial free edge or upper aspect of the vocal cords. STUDY DESIGN: Retrospective cohort. SETTING: Single tertiary university-affiliated medical center. SUBJECTS AND METHODS: Clinical, treatment, and outcome data were collected for 104 patients with T1N0M0 glottic squamous cell carcinoma who were treated and followed at our center in 1995-2013. Findings were compared between those with a tumor on the medial (n=60, 57.7%) or superior (n=44, 42.3%) aspect of the cords. RESULTS: Mean follow-up time was 4.15years. No between-group differences were found in demographic or risk factors. There was a significant association of anterior commissure involvement with disease recurrence (P=0.0012) and of superior (vs medial) location with higher rates of anterior commissure involvement (P<0.001) and recurrence (P=0.01) and shorter time to recurrence (P<0.001). CONCLUSIONS: T1 squamous cell carcinomas on the superior aspect of the vocal cords have a poorer prognosis than medial tumors and should be closely monitored for recurrence.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Laríngeas/patologia , Laringoscopia/métodos , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Estroboscopia/métodos , Prega Vocal , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Incidência , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências
14.
Reprod Biomed Online ; 33(1): 102-10, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27184186

RESUMO

Epidermal growth factor receptor (EGFR) has proliferative properties in the testis. Cetuximab, an anti-EGFR, is administered together with chemotherapy to patients with various types of cancer. This studies aim was to investigate the effect of cetuximab on testicular function. Adult male mice were injected with cetuximab (10 mg/kg), cisplatin (8 mg/kg) or a combination of both, and killed one week or one month later. The doses were chosen by human equivalent dose calculation. Testicular function was evaluated by epididymal-spermatozoa total motile count and sperm motility, weights of testes and epididymides, and the level of anti-Müllerian hormone (AMH) in the serum. Immunohistochemistry was performed to examine germ cell proliferation (Ki-67), apoptosis (Terminal transferase-mediated deoxyuridine 5-triphosphate nick-end labelling), reserve (DAZL-Deleted in azoospermia-like, Promyelocytic leukaemia zinc-finger), blood vessels (CD34) and Sertoli cells (GATA-4). Administration of cetuximab alone increased testicular apoptosis and decreased epididymal-spermatozoa total motile count over time. When added to cisplatin, cetuximab exacerbated most of the recorded testicular parameters, compared with the effect of cisplatin alone, including testis and epididymis weights, epididymal-spermatozoa total motile count, AMH concentration, meiosis and apoptosis. In conclusion, cetuximab has only a mild effect on testicular reserve, but when added to cisplatin, it exacerbates cisplatin-induced testicular toxicity.


Assuntos
Cetuximab/toxicidade , Cisplatino/toxicidade , Testículo/efeitos dos fármacos , Animais , Hormônio Antimülleriano/metabolismo , Antígenos CD34/metabolismo , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Apoptose , Biomarcadores/metabolismo , Cetuximab/administração & dosagem , Cisplatino/administração & dosagem , Epididimo/efeitos dos fármacos , Epididimo/metabolismo , Receptores ErbB/metabolismo , Fator de Transcrição GATA4/metabolismo , Marcação In Situ das Extremidades Cortadas , Antígeno Ki-67/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Testículo/patologia , Testes de Toxicidade
15.
J Surg Oncol ; 114(6): 714-718, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27468730

RESUMO

BACKGROUND: Recurrent pleomorphic adenoma (PA) of the parotid gland is a challenging surgical issue with controversy regarding management and long term outcome. METHODS: All patients who were operated for recurrent PA of the parotid gland between the years 1991 and 2013 were reviewed. Patient demographics, clinicopathologic variables, and operative details were collected retrospectively. RESULTS: A total of 22 patients were operated for recurrent PA of the parotid gland. Mean interval between recurrences was 7 and 6 years for first recurrence and second recurrence, accordingly. Second recurrence was significantly influenced by younger age at initial treatment (P = 0.009). Only two patients (9%) with a recurrence developed facial nerve paralysis following surgery. Adjuvant radiotherapy was given to nine patients with no evidence of disease progression or recurrence. There were no cases of malignant transformation. CONCLUSIONS: Recurrent PA of the parotid gland tends to occur in long intervals in a multifocal pattern. Adjuvant radiotherapy could be suggested as an alternative for surgery. J. Surg. Oncol. 2016;114:714-718. © 2016 Wiley Periodicals, Inc.


Assuntos
Adenoma Pleomorfo/radioterapia , Recidiva Local de Neoplasia/radioterapia , Glândula Parótida/cirurgia , Neoplasias Parotídeas/radioterapia , Adenoma Pleomorfo/patologia , Adenoma Pleomorfo/cirurgia , Adolescente , Adulto , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/cirurgia , Radioterapia Adjuvante , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
16.
Ann Otol Rhinol Laryngol ; 125(3): 242-6, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26443720

RESUMO

BACKGROUND: Radiation exposure is a well-known risk factor for well-differentiated thyroid cancer (WDTC). However, gender disparity in disease characteristics is not completely understood. The purpose of this study was to determine the behavior of radiation-induced thyroid cancer according to gender. METHODS: Charts of all patients diagnosed with WDTC after radiation exposure between the years 1985 and 2013 in a tertiary referral center were retrieved. RESULTS: Forty-three patients were reviewed, 29 females and 14 males. Mean age of exposure for women and men were 17.1 ± 19.5 and 15.5 ± 12.5 years, respectively (P = .78). Age at diagnosis were 47.5 ± 15.5 and 41.5 ± 15 years for women and men, respectively (P = .18). Mean disease-specific survival was 44.1 and 43.7 years for women and men, respectively (P = .50). CONCLUSIONS: Similar disease characteristics, tumor pathology, disease-free survival, and overall survival in both genders. In sporadic well-differentiated thyroid carcinoma, female gender is associated with better tumor behavior and prognosis. However, our results suggest that women are more affected by radiation than men and therefore have the same prognosis as men.


Assuntos
Neoplasias Induzidas por Radiação/mortalidade , Neoplasias da Glândula Tireoide/mortalidade , Adenocarcinoma Folicular/mortalidade , Adenocarcinoma Folicular/cirurgia , Adolescente , Adulto , Idoso , Carcinoma Papilar/mortalidade , Carcinoma Papilar/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/cirurgia , Fatores de Risco , Fatores Sexuais , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adulto Jovem
17.
Isr Med Assoc J ; 18(2): 90-4, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26979000

RESUMO

BACKGROUND: Radiation exposure is a well-known risk factor for well-differentiated thyroid cancer (WDTC). However, disease characteristics, optimal treatment, time from exposure to disease appearance, and the effect of age at initial exposure on the outcome have yet to be determined. OBJECTIVES: To identify the characteristics of radiation-induced thyroid carcinoma. METHODS: We retrieved the charts of all patients previously exposed to radiation who were diagnosed with WDTC between the years 1985 and 2013 in a tertiary referral center. RESULTS: Forty-four patients were reviewed. Median time from radiation exposure to diagnosis was 23 years. These patients had higher rates of aerodigestive symptoms and distant metastases on presentation than seen in non-radiated patients. Patients who were exposed to radiation before age 15 years tended to develop the disease at a younger age but had a longer latency period (34.7 ± 15.3 vs. 16.3 ± 10 years, P < 0.001) and none had significantly higher rates of vocal cord palsy, hoarseness on presentation, or aggressive variants on histology compared to patients exposed to radiation at an older age. Disease-specific survival (DSS) was the same for both groups and were similar to that seen in the general population (95% 20 year DSS). CONCLUSIONS: Radiation-induced thyroid cancer has a more aggressive presentation and the age at exposure affects the presentation of disease. Nonetheless, appropriate treatment leads to a favorable prognosis.


Assuntos
Neoplasias Induzidas por Radiação/patologia , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Induzidas por Radiação/epidemiologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/epidemiologia , Fatores de Tempo , Adulto Jovem
18.
Radiol Oncol ; 48(3): 323-30, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25177248

RESUMO

BACKGROUND: Magnetic resonance imaging (MRI) has been found to be better than computed tomography for defining the extent of primary gross tumor volume (GTV) in advanced nasopharyngeal cancer. It is routinely applied for target delineation in planning radiotherapy. However, the specific MRI sequences/planes that should be used are unknown. METHODS: Twelve patients with nasopharyngeal cancer underwent primary GTV evaluation with gadolinium-enhanced axial T1 weighted image (T1) and T2 weighted image (T2), coronal T1, and sagittal T1 sequences. Each sequence was registered with the planning computed tomography scans. Planning target volumes (PTVs) were derived by uniform expansions of the GTVs. The volumes encompassed by the various sequences/planes, and the volumes common to all sequences/planes, were compared quantitatively and anatomically to the volume delineated by the commonly used axial T1-based dataset. RESULTS: Addition of the axial T2 sequence increased the axial T1-based GTV by 12% on average (p = 0.004), and composite evaluations that included the coronal T1 and sagittal T1 planes increased the axial T1-based GTVs by 30% on average (p = 0.003). The axial T1-based PTVs were increased by 20% by the additional sequences (p = 0.04). Each sequence/plane added unique volume extensions. The GTVs common to all the T1 planes accounted for 38% of the total volumes of all the T1 planes. Anatomically, addition of the coronal and sagittal-based GTVs extended the axial T1-based GTV caudally and cranially, notably to the base of the skull. CONCLUSIONS: Adding MRI planes and sequences to the traditional axial T1 sequence yields significant quantitative and anatomically important extensions of the GTVs and PTVs. For accurate target delineation in nasopharyngeal cancer, we recommend that GTVs be outlined in all MRI sequences/planes and registered with the planning computed tomography scans.

19.
J Laryngol Otol ; 138(4): 443-447, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36776099

RESUMO

BACKGROUND: Treatment selection for squamous cell carcinoma patients aged over 84 years is controversial. This retrospective chart review examined and compared characteristics of laryngeal squamous cell carcinoma in very elderly (over 84 years) and younger patients (approximately 65 years). The secondary objective was to further evaluate the outcome of radiotherapy as a treatment modality in this patient population. METHODS: Of all 23 very elderly patients with laryngeal squamous cell carcinoma treated with radiotherapy, with or without surgery, in the Davidoff Cancer Center, from 1992 to 2012, 19 had sufficient data for analysis, and comprised the study group. RESULTS: Median age at diagnosis was 86 years. Disease stage at diagnosis was I, II, III and IVA in 53 per cent, 21 per cent, 21 per cent and 5 per cent, respectively. Median radiotherapy dose was 60 Gy given in 25 fractions. Three patients had recurrence. No patient discontinued treatment because of toxicity. Median overall survival was 3.6 years (range, 0-10 years). CONCLUSION: Very elderly laryngeal squamous cell carcinoma patients may derive a similar survival advantage as younger counterparts. Modern radiotherapy is effective and safe for treating laryngeal squamous cell carcinoma in this study population. Further, large-scale studies are needed.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , Humanos , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias Laríngeas/cirurgia , Estudos Retrospectivos , Glote/patologia , Neoplasias de Cabeça e Pescoço/patologia , Resultado do Tratamento , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/patologia
20.
J Clin Neurosci ; 121: 89-96, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38377883

RESUMO

BACKGROUND: This retrospective study aims to assess the efficacy of stereotactic radiosurgery (SRS) in the treatment of brain metastases (BM) originating from gynecological cancers. It focuses on local control (LC), distant tumor control (DTC), and overall survival (OS). METHODS: The analysis comprised 18 individuals with gynecological-origin BM treated with SRS at the Hadassah Medical Center from 2004 to 2021. Statistical analyses evaluate factors impacting LC, DTC, and OS. RESULTS: A total of 36 BM of gynecological origin underwent SRS. The median age at the first SRS treatment was 60 years, with a median time of 24.5 months from the primary malignancy diagnosis to BM detection. The 12-month LC rate per patient was 84.6 %, and 5.6 % per BM. Only two instances of local recurrence were observed. The DTC at 12 months was 75 %, with a 29 % overall. Non-significant trends indicating a correlation with distant brain failure with increased cumulative volume and the occurrence of craniotomy before SRS. The median OS of the cohort was 16.5 months from SRS treatment. The 6, 12, 18, and 24-month survival rates were 77.8 %, 66.7 %, 50 %, and 22.2 % respectively. Higher number of BM was associated with lower OS (p = 0.046). On multivariate analysis, age was a significant factor for OS (p = 0.03), demonstrating that older age was associated with a more favorable prognosis. CONCLUSION: This study supports SRS effectiveness for treating BM from gynecological cancers and suggests similar outcomes to more common malignancies.


Assuntos
Neoplasias Encefálicas , Neoplasias dos Genitais Femininos , Radiocirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias dos Genitais Femininos/radioterapia , Resultado do Tratamento , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia
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