SET8 Inhibition Potentiates Radiotherapy by Suppressing DNA Damage Repair in Carcinomas / 生物医学与环境科学（英文）

Objective@#SET8 is a member of the SET domain-containing family and the only known lysine methyltransferase (KMT) that monomethylates lysine 20 of histone H4 (H4K20me1). SET8 has been implicated in many essential cellular processes, including cell cycle regulation, DNA replication, DNA damage response, and carcinogenesis. There is no conclusive evidence, however, regarding the effect of SET8 on radiotherapy. In the current study we determined the efficacy of SET8 inhibition on radiotherapy of tumors and the underlying mechanism.@*Methods@#First, we explored the radiotherapy benefit of the SET8 expression signature by analyzing clinical data. Then, we measured a series of biological endpoints, including the xenograft tumor growth in mice and apoptosis, frequency of micronuclei, and foci of 53BP1 and γ-H2AX in cells to detect the SET8 effects on radiosensitivity. RNA sequencing and subsequent experiments were exploited to verify the mechanism underlying the SET8 effects on radiotherapy.@*Results@#Low expression of SET8 predicted a better benefit to radiotherapy in lung adenocarcinoma (LUAD) and invasive breast carcinoma (BRCA) patients. Furthermore, genetic deletion of SET8 significantly enhanced radiation treatment efficacy in a murine tumor model, and A549 and MCF7 cells; SET8 overexpression decreased the radiosensitivity. SET8 inhibition induced more apoptosis, the frequency of micronuclei, and blocked the kinetics process of DNA damage repair as 53BP1 and γ-H2AX foci remained in cells. Moreover, RNF8 was positively correlated with the SET8 impact on DNA damage repair.@*Conclusion@#Our results demonstrated that SET8 inhibition enhanced radiosensitivity by suppressing DNA damage repair, thus suggesting that SET8 potentiated radiotherapy of carcinomas. As new inhibitors of SET8 are synthesized and tested in preclinical and clinical settings, combining SET8 inhibitors with radiation warrants consideration for precise radiotherapy.

Recommendations for hypofractionated whole-breast irradiation

SUMMARY This recommendation consensus for hypofractionated whole-breast radiotherapy (RT) was organized by the Brazilian Society of Radiotherapy (SBRT) considering the optimal scenario for indication and safety in the technology applied. All controversies and contraindication matters (hypofractionated RT in patients who underwent chemotherapy [CT], hypofractionated RT in lymphatic drainage, hypofractionated RT after mastectomy with or without immediate reconstruction, boost during surgery, hypofractionated RT in patients under 50 years old, hypofractionated RT in large breasts, hypofractionated RT in histology of carcinoma in situ [DCIS]) was discussed during a meeting in person, and a consensus was reached when there was an agreement of at least 75% among panel members. The grade for recommendation was also suggested according to the level of scientific evidence available, qualified as weak, medium, or strong. Thus, this consensus will aid Brazilian radiotherapy experts regarding indications and particularities of this technique as a viable and safe alternative for the national reality.

RESUMO Este consenso de recomendações para a radioterapia (RT) hipofracionada de toda a mama foi organizado pela Sociedade Brasileira de Radioterapia (SBRT) considerando o cenário ideal para indicação e segurança na tecnologia aplicada. Questões de controvérsias e contraindicações (RT hipofracionada em pacientes submetidas à quimioterapia [QT], RT hipofracionada nas drenagens linfáticas, RT hipofracionada após mastectomia com ou sem reconstrução imediata, a realização de reforço de dose em leito cirúrgico [ou boost], RT hipofracionada em pacientes com idade menor que 50 anos, RT hipofracionada em mamas volumosas, RT hipofracionada em histologia de carcinoma in situ [CDIS]) foram discutidas em encontro presencial, sendo o consenso atingido quando existisse concordância de pelo menos 75% dos panelistas. O grau de recomendação foi também sugerido de acordo com o nível de evidência científico disponível, qualificado entre fraco, médio ou forte. Assim, este consenso deverá servir para auxiliar os especialistas da radioterapia brasileira em relação às indicações e particularidades dessa técnica, como uma alternativa segura e viável para a realidade nacional.

Características humorales de los tumores de cabeza y cuello en pacientes tratados con nimotuzumab / Humoral characteristics of head and neck tumors in patients treated with nimotuzumab

Se efectuó un estudio observacional, descriptivo y retrospectivo de 36 pacientes incluidos en el ensayo clínico (fase IV) Seguridad y efectividad del nimotuzumab en tumores de cabeza y cuello, desarrollado en el Hospital Oncológico Conrado Benítez de Santiago de Cuba, desde enero de 2013 hasta diciembre de 2016, con vistas a identificar las características humorales de dichos tumores en los afectados. Se utilizó la prueba t de Student con una significación estadística de p <0,05. Predominaron el sexo masculino en mayores de 60 años de edad, los efectos adversos clínicos y el tumor de faringe; el estadio clínico III y el carcinoma epidermoide bien diferenciado fueron los más frecuentes. No existieron diferencias estadísticamente significativas entre los parámetros de laboratorio antes del tratamiento combinado con nimotuzumab y durante este. Dicho medicamento constituyó una alternativa terapéutica segura, ventajosa y factible como parte del plan terapéutico convencional en las condiciones asistenciales

An observational, descriptive and retrospective study of 36 patients included in the (phase IV) clinical trial Security and effectiveness of nimotuzumab in head and neck tumors was carried out. It was developed at Conrado Benítez Oncological Hospital in Santiago de Cuba, from January, 2013 to December, 2016, aimed at identifying the humoral characteristics of these tumors in the affected patients. The Student t test was used with a statistical significance of p <0.05. There was a prevalence of the male sex in older than 60 years, the clinical adverse effects and the pharynx tumor; the clinical stage III and the well differentiated epidermoid carcinoma were the most frequent findings. There were no statistically significant differences among the laboratory parameters before and during the combined treatment with nimotuzumab. This medication constituted a sure, advantageous and feasible therapeutic alternative as part of the conventional therapeutic plan in assistance conditions

Clinical outcomes of low and intermediate risk differentiated thyroid cancer patients treated with 30mCi for ablation or without radioactive iodine therapy

ABSTRACT Objective To retrospectively evaluate the outcomes of patients with low and intermediate risk thyroid carcinoma treated with total thyroidectomy (TT) and who did not undergo radioiodine remnant ablation (RRA) and to compare them to patients receiving low dose of iodine (30 mCi). Subjects and methods A total of 189 differentiated thyroid cancer (DTC) patients treated with TT followed by 30mCi for RRA or not, followed in two referral centers in Brazil were analyzed. Results From the 189 patients, 68.8% was ATA low-risk, 30.6% intermediate and 0.6% high risk. Eighty-seven patients underwent RRA and 102 did not. The RRA groups tended to be younger and had a higher frequency of extra-thyroidal extension (ETE). RRA did not have and impact on response to initial therapy neither in low (p = 0.24) nor in intermediate risk patients (p = 0.66). It also had no impact on final outcome and most patients had no evidence of disease (NED) at final follow-up. Recurrence/persistence of disease was found in 1.2% of RRA group and 2% in patients treated only with TT (p = 0.59). Conclusions Our study shows that in low and intermediate-risk patients, RRA with 30 mCi seems to have no major advantage over patients who did not undergo RRA regarding response to initial therapy in each risk group and also in long term outcomes.

Cytopathologic evaluation of patients submitted to radiotherapy for uterine cervix cancer / Avaliação citopatológica no seguimento de pacientes submetidas à radioterapia por câncer de colo uterino

Summary Cervical cancer is an important public health problem. Pap smear is the leading strategy of screening programs for cervical cancer worldwide. However, delayed diagnosis leads to more aggressive and less effective treatments. Patients with uterine cervix malignancies who are referred for radiotherapy have advanced-stage disease, which results in high rates of locoregional recurrence. The use of radiotherapy as a treatment for cervical cancer causes morphological changes in neoplastic and non-neoplastic epithelial cells, as well as in stromal cells, which make it difficult to diagnose the residual lesion, resulting in a dilemma in cytopathological routine. Based on the difficulties of cytopathologic evaluation for the follow-up of patients treated with radiotherapy for cervical cancer, our objective was to describe the actinic cytopathic effects. Our paper was based on a structured review including the period from June 2015 to April 2016, aiming at an exploratory-descriptive study. Bibliographic investigations were carried out through selection and analysis of articles, list of authors and keywords, selection of new articles focused on the analysis of bibliographic references to previously selected documents, as well as textbooks of recognized merit. The most incident actinic cytopathological alterations as described in the literature are: cellular gigantism, nuclear and cytoplasmic vacuolization, dyskeratosis, bi- and multinucleated (B/M) cells, macro and multiple nucleoli, anisokaryosis, anisonucleolosis and nuclear pyknosis. To date, a protocol has not been established that can precisely differentiate the morphological characteristics between benign cells with actinic effects from recurrent malignant cells on post-radiotherapy smears.

Resumo O câncer de colo uterino configura-se como um importante problema de saúde pública. O teste citopatológico é a principal estratégia de programas de rastreamento dessa neoplasia maligna em todo o mundo. Entretanto, a demora no diagnóstico ocasiona tratamentos mais agressivos e menos efetivos. Pacientes com neoplasia maligna de colo uterino que são encaminhadas para radioterapia apresentam doença em estádios avançados, e esse fato determina altos índices de recidiva locorregional. A utilização da radioterapia como tratamento do câncer do colo uterino provoca alterações morfológicas não só nas células epiteliais neoplásicas e não neoplásicas como também nas células estromais, o que dificulta o diagnóstico da lesão residual e resulta em um dilema na rotina citopatológica. Com base nas dificuldades da avaliação citopatológica do seguimento das pacientes pós-radioterapia, o objetivo deste trabalho foi descrever os efeitos citopáticos actínicos. O trabalho teve como base uma revisão estruturada no período de junho de 2015 a abril de 2016, visando a um estudo exploratório-descritivo. As investigações bibliográficas foram realizadas por meio de seleção e análise dos artigos, lista de autores e palavras-chave; seleção de novos artigos focada na análise de referências bibliográficas dos documentos previamente selecionados e livros-texto de relevância conceitual. As alterações citopatológicas actínicas mais incidentes descritas na literatura são: gigantismo celular, vacuolização nuclear e citoplasmática, disceratose, bi e multinucleações, macro e múltiplos nucléolos, anisocariose, anisonucleolose e picnose nuclear. Até o momento, não se conseguiu estabelecer um protocolo que possa diferenciar precisamente as características morfológicas entre células benignas com efeitos actínicos das células malignas recidivantes em esfregaços pós-radioterapia.

Radioiodine-induced oxidative stress in patients with differentiated thyroid carcinoma and effect of supplementation with vitamins C and E and selenium (antioxidants)

ABSTRACT Objective The objective of this study, in addition to confirming that therapy with 131I causes oxidative stress, was to evaluate the effect of supplementation with vitamins C and E and selenium on this phenomenon by measuring plasma 8-epi-PGF2a, a marker of lipid peroxidation. Subjects and methods Forty patients with thyroid cancer submitted to thyroidectomy, who received 3.7 GBq 131I after levothyroxine withdrawal, were selected; 20 patients did not receive (control group) and 20 patients received (intervention group) daily supplementation consisting of 2000 mg vitamin C, 1000 mg vitamin E and 400 µg selenium for 21 days before 131I. Plasma 8-epi-PGF2a was measured immediately before and 2 and 7 days after 131I. Results A significant increase in plasma 8-epi-PGF2a after 131I was observed in the two groups. The concentrations of 8-epi-PGF2α were significantly higher in the control group before and 2 and 7 days after 131I. The percentage of patients with elevated 8-epi-PGF2α was also significantly higher in the control group before and after 131I. Furthermore, the increase (percent) in 8-epi-PGF2α was significantly greater in the control group (average of 112.3% versus 56.3%). Only two patients (10%) reported side effects during supplementation. Conclusions Ablation with 131I causes oxidative stress which can be minimized by the use of antioxidants.

Difference in the rate of rectal complications following prostate brachytherapy based on the prostate-rectum distance and the prostate longitudinal length among early prostate cancer patients

PURPOSE: To investigate the difference in rectal complications rate following prostate low dose rate (LDR) brachytherapy based on prostate-rectum distance and prostate longitudinal length among early prostate cancer patients. MATERIALS AND METHODS: From March 2008 to February 2013, 245 prostate cancer patients with a Gleason score or =6 months were evaluated for radiation proctitis. Magnetic resonance imaging (MRI) was performed for a prebrachytherapy evaluation, and prostate-rectum distance and prostate longitudinal length were measured. The radiation proctitis was confirmed and graded via colonoscopy based on the radiation therapy oncology group (RTOG) toxicity criteria. RESULTS: Twenty-three patients received a colonoscopy for proctitis evaluation, and 12 were identified as grade 1 on the RTOG scale. Nine patients were diagnosed as grade 2 and 2 patients were grade 3. No patient developed grade 4 proctitis. The rectal-complication group had a mean prostate-rectum distance of 2.51+/-0.16 mm, while non-rectal-complication control group had 3.32+/-0.31 mm. The grade 1 proctitis patients had a mean prostate-rectum distance of 2.80+/-0.15 mm, which was significantly longer than 2.12+/-0.31 mm of grades 2 and 3 patient groups (p=0.045). All 11 patients of grades 2 and 3 had a prostate longitudinal length of 35.22+/-2.50 mm, which was longer than group 1, but the difference was not statistically significant (p=0.214). CONCLUSIONS: As the prostate-rectum distance increased, fewer postimplantation rectal symptoms were observed. Patients with a shorter prostate-rectum distance in MRI should receive modified implantation techniques or radical prostatectomy.

Surgical treatment of clinically early-stage endometrial carcinoma without systematic lymphadenectomy / Tratamento cirúrgico do câncer de endométrio em estágio clínico precoce sem linfadenectomia radical.

Objective: the main aim of this study was to describe the authors’ experience with the surgical treatment of endometrial cancer without systematic lymphadenectomy. Methods: a retrospective cohort study was carried out on a subset of patients suffering of clinically early-stage endometrial carcinoma who underwent hysterectomy and salpingo-oophorectomy without systematic (radical) lymph nodes dissection at our centers from June, 2002, to November, 2011. Descriptive statistics were explored as medians (interquartile range) or frequencies (percentages), as appropriated, and the Kaplan–Meier method was applied for survival estimation. Results: eighty-three patients who underwent surgical treatment with no lymph node dissection (n = 20; 24.1%) or with only a sampling procedure (n=63; 75.98%) were selected for analysis. Among these patients, 27 (32.53%) underwent surgery alone and 56 (67.46%) received some adjuvant treatment. Postoperative complications occurred in five patients (6.02%). Over a median follow-up of 27.4 months (Q25 = 13.7 – Q75 = 46.5), 15 (18.07%) patients suffered from relapses and 11 deaths occurred as result of disease recurrence. Cumulative 1, 2 and 3-year disease- free survivals were 97.32, 91.18 and 78.02%, respectively. Conclusion: on a case-by-case basis, the surgical treatment of clinically early-stage endometrial carcinoma without systematic lymphadenectomy did not seem to decrease survival outcomes and presented low rates of surgical morbidity in our experience, but was also related to a high rate use of adjuvant therapy. .

Objetivo: descrever a experiência dos autores com o tratamento cirúrgico do câncer de endométrio em estádio precoce sem linfadenectomia radical. Métodos: realizou-se estudo de coorte retrospectivo envolvendo um subgrupo de pacientes com câncer de endométrio em estágio clínico precoce tratadas com histerectomia e salpingo-ooforectomia sem linfadenectomia radical, em dois centros pernambucanos, de junho de 2002 a novembro de 2011. As variáveis foram descritas como mediana (intervalo interquartílico) ou frequências (percentuais), utilizando- se o método de Kaplan-Meier para a estimativa das taxas de sobrevivência. Resultados: oitenta e três pacientes submetidas a tratamento cirúrgico sem dissecção linfonodal (n = 20, 24,1%) ou com dissecção apenas por amostragem (n = 63; 75,98%) foram selecionadas para análise. Entre essas pacientes, 27 (32,53%) foram tratadas somente com cirurgia e 56 (67,46%) receberam tratamento adjuvante. Cinco pacientes apresentaram complicações pós-operatórias (6,02%). Durante o acompanhamento mediano de 27,4 meses (Q25 = 13,7 - Q75 = 46,5), 15 (18,07%) pacientes apresentaram recorrência, dentre as quais 11 faleceram em decorrência da recidiva neoplásica. Observou-se sobrevivência cumulativa proporcional livre de doença em um, dois e três anos de 97,32, 91,18 e 78,02%, respectivamente. Conclusão: em um contexto de indicação caso-a-caso, o tratamento cirúrgico do câncer de endométrio em estádio precoce sem linfadenectomia radical parece não ter prejudicado a sobrevivência e apresentou baixas taxas de morbidade cirúrgica em nossa experiência, mas também foi acompanhado de elevada utilização de terapia adjuvante. .

Rare renal metastases from differentiated thyroid carcinoma: early clinical detection and treatment based on radioiodine / Metástases renais raras de carcinoma diferenciado da tireoide: detecção clínica precoce e tratamento com radioiodoterapia

Objective : The aim of this study was to explore the clinical characteristics of renal metastatic cancer, the methods for its detection by radioiodine (131I), and the response to 131I treatment in fourteen patients with renal metastases from differentiated thyroid carcinoma (DTC).Subjects and methods : DTC patients (n = 2,955) that received treatment with 131I were retrospectively analyzed. Scans (131I-WBS, 31I-SPECT/CT and/or 18F-FDG-PET/CT) were performed after an oral therapeutic dose of 131I. Therapeutic efficacy was evaluated based on changes in Tg and anatomical imaging changes at renal lesions.Results : Among these 14 patients, 11 had avidity for 131I, but three patients did not accumulate 131I after 131I treatment. In the 11 131I-positive renal lesions, 10 cases were detected by 131I-SPECT/CT combined with another imaging modality and one case by 131I-WBS combined with ultrasonography (US). In the three 131I-negative renal lesions, two cases were detected by 18F-FDG-PET/CT and one case by computed tomography (CT). In 11 patients with 131I-avid renal metastases, Serum Tg levels in 81.82% (9/11) patients showed a gradual decline, and 18.18% (2/11) of the patients showed a significant elevation. There was no marked difference in serum Tg before the last 131I treatment (Z = 0.157; p = 0.875). Only one patient presented partial response, eight patients exhibited stable disease, and renal metastases progressed in two patients showing progressive disease. No patients reached complete response.Conclusion : 131I-SPECT/CT, combined with another imaging modality after 131I-WBS, can contribute to the early detection of renal metastases of DTC. 131I therapy is a feasible and effective treatment for most DTC renal metastases with avidity for 131I. Arq Bras Endocrinol Metab. 2014;58(3):260-9.

Objetivo : O objetivo deste estudo foi analisar as características clínicas de metástases renais, os métodos para sua detecção por radioiodo (131I) e a resposta ao tratamento com 131I em 14 pacientes com metástases renais de carcinoma diferenciado da tireoide (DTC).Sujeitos e métodos Pacientes com DTC (n = 2.955) que receberam tratamento com 131I foram analisados retrospectivamente. 131I-PCI, 31I-SPECT/CT e/ou 18F-FDG-PET/CT foram feitos após uma dose terapêutica oral de 131I. A eficácia terapêutica foi baseada nas alterações da Tg e nas imagens anatômicas das lesões renais.Resultados : Dos 14 pacientes, 11 apresentaram lesões ávidas por 131I, mas três pacientes não acumularam 131I depois do tratamento com 131I. Nas 11 lesões renais positivas para 131I, 10 casos foram detectados por 131I-SPECT/CT combinado com outra modalidade de exame de imagem e um caso por 131I-WBS combinado com US. Nas três lesões renais negativas para 131I, dois casos foram detectados por 18F-FDG-PET/CT e um caso por tomografia computadorizada (TC). Em 11 pacientes com metástases renais ávidas por 131I, os níveis séricos de Tg em 81,82% (9/11) dos pacientes mostraram um declínio gradual e 18,18% (2/11) apresentaram uma elevação significativa. Não houve diferenças marcadas na Tg sérica antes do último tratamento com 131I (Z = 0,157; p = 0,875). Apenas um paciente apresentou resposta parcial, oito pacientes apresentaram doença estável e as metástases renais progrediram em dois pacientes que apresentaram doença progressiva. Nenhum dos pacientes apresentou resposta completa.Conclusão : 131I-SPECT/CT, combinada com outra modalidade de diagnóstico por imagem após 131I-PCI, pode contribuir para a detecção precoce de metástases renais de DTC. O tratamento ...

Lipiodol as a Fiducial Marker for Image-Guided Radiation Therapy for Bladder Cancer

Purpose To evaluate Lipiodol as a liquid, radio-opaque fiducial marker for image-guided radiation therapy (IGRT) for bladder cancer.Materials and Methods Between 2011 and 2012, 5 clinical T2a-T3b N0 M0 stage II-III bladder cancer patients were treated with maximal transurethral resection of a bladder tumor (TURBT) and image-guided radiation therapy (IGRT) to 64.8 Gy in 36 fractions ± concurrent weekly cisplatin-based or gemcitabine chemotherapy. Ten to 15mL Lipiodol, using 0.5mL per injection, was injected into bladder submucosa circumferentially around the entire periphery of the tumor bed immediately following maximal TURBT. The authors looked at inter-observer variability regarding the size and location of the tumor bed (CTVboost) on computed tomography scans with versus without Lipiodol.Results Median follow-up was 18 months. Lipiodol was visible on every orthogonal two-dimensional kV portal image throughout the entire, 7-week course of IGRT. There was a trend towards improved inter-observer agreement on the CTVboost with Lipiodol (p = 0.06). In 2 of 5 patients, the tumor bed based upon Lipiodol extended outside a planning target volume that would have been treated with a radiation boost based upon a cystoscopy report and an enhanced computed tomography (CT) scan for staging. There was no toxicity attributable to Lipiodol.Conclusions Lipiodol constitutes a safe and effective fiducial marker that an urologist can use to demarcate a tumor bed immediately following maximal TURBT. Lipiodol decreases inter-observer variability in the definition of the extent and location of a tumor bed on a treatment planning CT scan for a radiation boost.

Normalization of lymphocyte count after high ablative dose of I-131 in a patient with chronic lymphoid leukemia and secondary papillary carcinoma of the thyroid. Case report / Normalização da contagem de linfócitos após dose ablativa de I-131 em um paciente com leucemia linfóide crônica e carcinoma papilífero da tireóide. Relato de caso

The authors report the case of a 70-year-old male patient with chronic lymphoid leukemia who presented subsequently a papillary carcinoma of the thyroid with metastases to regional lymph nodes. The patient was treated with surgical thyroidectomy with regional and cervical lymph node excision and radioiodine therapy (I-131). The protocolar control scintigraphy 4 days after the radioactive dose showed I-131 uptake in both axillae and even in the inguinal regions. PET/CT showed faint FDG-F-18 uptake in one lymph node of the left axilla. An ultrasound guided fine needle biopsy of this lymph node identified by I-131 SPECT/CT and FDG-F-18 PET/CT revealed lymphoma cells and was negative for thyroid tissue and thyroglobulin content. The sequential blood counts done routinely after radiation treatment showed a marked fall until return to normal values of leucocytes and lymphocytes (absolute and relative), which were still normal in the last control 19 months after the radioiodine administration. Chest computed tomography showed a decrease in size of axillary and para-aortic lymph nodes. By immunohistochemistry, cells of the lymphoid B lineage decreased from 52% before radioiodine therapy to 5% after the procedure. The authors speculate about a possible sodium iodide symporter expression by the cells of this lymphoma, similar to some other non-thyroid tumors, such as breast cancer cells.

Os autores relatam o caso de um paciente de 70 anos com leucemia linfóide crônica que apresentou subsequentemente um carcinoma papilífero da tireóide com metástases para linfonodos regionais. O paciente foi tratado com tireoidectomia total cirúrgica com exérese de linfonodos regionais e cervicais e radioiodoterapia (I-131). A pesquisa de corpo inteiro protocolar de controle 4 dias após a dose radioativa mostrou captação de I-131 em ambas as axilas e mesmo nas regiões inguinais. PET/CT mostrou discreta captação de FDG-F-18 em um linfonodo da axila esquerda. A biópsia por agulha fina guiada por ultrassom deste linfonodo identificado por SPECT/CT com I-131 e PET/CT com FDG-F-18 revelou células linfomatosas e foi negativa para tecido tireoidiano e conteúdo de tireoglobulina. Os hemogramas sequenciais feitos rotineiramente após tratamento com radiações mostraram uma acentuada queda até retorno aos valores normais de leucócitos e de linfócitos (absolutos e relativos), que continuavam normais no último controle 19 meses após a administração do radioiodo. Tomografia computadorizada de tórax mostrou uma redução em tamanho de linfonodos axilares e para-aorticos. Por imunohistoquímica, as células da linhagem linfoide B decresceram de 52% antes da radioiodoterapia para 5% depois do procedimento. Os autores conjeturam sobre uma possível expressão de symporter de iodeto de sódio pelas células deste linfoma, à semelhança de outros tumores não tireoidianos, tais como células de câncer da mama.

The efficacy of hemostatic radiotherapy for bladder cancer-related hematuria in patients unfit for surgery

Objective The aim of our study was to assess short and mid-term clinical efficacy of external beam radiation therapy to achieve hemostasis in patients with bladder-cancer related gross hematuria who were unfit for surgery. We also assessed hypofractionation as a possible alternative option for more severe patients. Patients and Methods Thirty-two patients were included for hemostatic radiation therapy, with two schedules based on Eastern Cooperative Oncology Group performance status. The standard treatment was 30 Gy in 10 fractions over 2 weeks. More severe patients underwent a hypofractionated regimen, with 20 Gy in 5 fractions over a one week period. Clinical evaluation was performed at 2 weeks and 6 months. Results At 2 weeks, 69% of patients were hematuria-free. Subgroup analysis showed that 79% of patients undergoing hypofractionated regimen were hematuria-free. A total of 54% were hematuria-free with the standard regimen. Based on tumor stage, hematuria was controlled at 2 weeks for 57% of non-muscle invasive tumors and 72% of muscle-invasive tumors. After 6 months, 69% of patients had relapsed, regardless of tumor stage or therapy schedules. Conclusions Hemostatic radiotherapy is an effective option for palliative-care hematuria related to bladder cancer in patients unfit for surgery. Although it appears to be rapidly effective, its effect is of limited duration. Hypofractionation also seems to be an effective option; however larger cohorts and prospective trials are needed to evaluate its efficacy compared to standard schedules. .

The role of radiotherapy in urinary bladder cancer: current status

The role of radiotherapy (RT) in the treatment of urinary bladder cancer has undergone several modifications along the last decades. In the beginning, definitive RT was used as treatment in an attempt to preserve the urinary bladder; however, the results were poor compared to those of radical surgery. Recently, many protocols have been developed supporting the use of multi-modality therapy, and the concept of organ preservation began to be reconsidered. Although phase III randomized clinical studies comparing radical cystectomy with bladder preservation therapies do not exist, the conservative treatment may present low toxicity and high indexes of complete response for selected patients. The aim of this study was to review the literature on the subject in order to situate RT in the current treatment of urinary bladder cancer.

Avaliação da abertura bucal em pacientessubmetidos à radioterapia de cabeça e pescoço / Evaluation of mouth opening in patients undergoing head and neck radiotherapy

A radioterapia de cabeça e pescoço quando direcionada à articulaçãotemporomandibular e músculos da mastigação, pode provocar sequelas como redução daamplitude de abertura bucal e trismo, que, muitas vezes, pode ser irreversível.Objetivo: comparar a amplitude de abertura bucal, antes e após a radioterapia da regiãode cabeça e pescoço.Metodologia: foram selecionados 30 pacientes com diagnóstico de tumores malignos decabeça e pescoço para serem submetidos à mensuração da abertura bucal 30 dias antes daradioterapia, e 90 dias após. Também foram observadas as características gerais comotipo histológico do tumor e dose de radioterapia.Resultados: a idade média da amostra foi de 58 anos, sendo que 80,76% eram do sexomasculino e 19,24% do feminino. Na primeira avaliação encontrou‐se limitação deabertura bucal (35,08±8,74), e 90 dias após a radioterapia houve aumento da limitação deabertura bucal (31,5±10,42), porém, sem mostrar significância estatística (p≤0,061).Conclusão: não houve agravamento da limitação de abertura bucal após três meses deradioterapia...

When temporomandibular joint and muscles of mastication are in the fieldof radiation, trismus and restriction of mouth opening are common and often irreversiblesequelae.Aim: compare mouth opening before and after head and neck radiotherapy.Methodology: thirty patients with head and neck malignant tumors were chosen to havetheir mouth opening measured 30 days before and 90 days after radiotherapy. Generalcharacteristics as histological type of the tumor and radiotherapy dose were alsoevaluated.Results: the mean age of the sample was 58 years, 21 subjects (80.76%) were male, and 5(19.24%) were female. At the first evaluation, we found mouth opening restriction(35.08±8.74) and ninety days after radiotherapy the mouth opening increased (31.5±10.42),but without statistical significance (p≤0.061).Conclusion: the mouth opening did not worse after 3 months of radiotherapy...

Radioiodine concentration by the thymus in differentiated thyroid carcinoma: report of five cases / Captação do radioiodo pelo timo no carcinoma diferenciado de tireoide: relato de cinco casos

The radioactive iodine has been used with great value as a diagnostic and therapeutic method in patients with differentiated thyroid carcinoma previously submitted to total thyroidectomy. False-positive whole-body scans may occur due to misinterpretation of the physiologic distribution of the radioisotope or lack of knowledge on the existence of other pathologies that could eventually present radioiodine uptake. Thymic uptake is an uncommon cause of false-positive whole-body scan, and the mechanism through which it occurs is not completely understood. The present paper reports five cases of patients with differentiated thyroid cancer who presented a mediastinum uptake of radioiodine in a whole-body scan during follow-up. The patients had either histological or radiological confirmation of the presence of residual thymus gland. It is very important to know about the possibility of iodine uptake by the thymus in order to avoid unnecessary treatment, such as surgery or radioiodine therapy.

O iodo radioativo tem sido utilizado com grande valia como método diagnóstico e terapêutico em pacientes com carcinoma diferenciado de tireoide previamente submetidos à tireoidectomia total. Resultados falso-positivos na pesquisa de corpo inteiro (PCI) podem ocorrer por má interpretação da distribuição fisiológica do radioisótopo ou por não conhecimento da existência de outras patologias que podem eventualmente captar o radioiodo. Captação pelo timo é uma causa incomum de resultado falso-positivo e o mecanismo pelo qual ocorre não é totalmente esclarecido. O presente trabalho relata cinco casos que apresentaram PCI positiva em mediastino durante o seguimento, com comprovação histológica ou tomográfica sugestiva de timo. Ressalta-se a importância do conhecimento dessa possível causa de falso-positivo a fim de se evitar tratamentos desnecessários.

Avaliação dos fatores clínicos e do tratamento em pacientes com carcinoma indiferenciado da nasofaringe / Assessment of clinical and therapeutic factors in patients with nasopharyngeal undifferentiated carcinoma

O carcinoma de nasofaringe é neoplasia rara, com incidência maior em países do Sudeste Asiático. OBJETIVO: Avaliar dados demográficos, clínicos, terapêuticos e prognósticos do carcinoma indiferenciado de nasofaringe em um serviço de referência. CASUÍSTICA E MÉTODO: Estudo retrospectivo de 46 pacientes, de janeiro de 1978 a agosto de 2000. Nenhum paciente foi previamente tratado e não apresentava tumor sincrônico e metástase à distância. RESULTADOS: A idade variou de 14 a 78 anos (média, 46), sendo 35 (76 por cento) pacientes masculinos. Todos eram de etnia caucasiana ou afro-brasileira. O tempo de história variou de 1 a 48 meses (média, 7), sendo 47 por cento tabagistas e 33 por cento etilistas. O sintoma mais relatado foi a presença de nódulo no pescoço (34 pacientes). Quanto ao estadiamento clínico, 22 foram estadiados como T1/T2 e 24 como T3/T4, enquanto 24 foram classificados como N2 e 16, N3. O tratamento instituído com finalidade curativa foi a radioterapia, associada à quimioterapia concomitante nos estádios III e IV. Dos 27 pacientes com seguimento após o tratamento inicial, 52 por cento apresentavam-se vivos e livres de doença há três anos. CONCLUSÃO: Os pacientes eram de estádio clínico avançado, com sobrevida livre de doença em três anos de 52 por cento.

The nasopharyngeal carcinoma (NPC) is a rare cancer with a high incidence in Southern Asia. AIM: to study the demographic, clinical, therapeutic, and prognostic factors of nasopharyngeal undifferentiated carcinoma in a reference service. MATERIALS AND METHODS: A retrospective study was made of 46 patients from January 1998 to August 2000. The patients had no previous treatment and did not present any evidence of synchronous tumors or distance metastases. RESULTS: The age ranged from 14 to 78 years (mean = 46 years); 35 (76 percent) patients were male. All patients were Caucasian or African-Brazilian. The onset of initial symptoms ranged from 1 to 48 months (mean = 7 months); 47 percent of the subjects smoked tobacco and 33 percent consumed alcoholic beverages. A lump in the neck was the most frequent symptom (34 patients). Twenty-two patients were clinically staged as T1/T2 and 24 patients as T3/T4; 24 patients were classified as N2, and 16 patients were staged as N3. Curative treatment consisted of radiotherapy and simultaneous chemotherapy in clinical stages III and IV. Of 27 patients that were monitored, 52 percent were alive with no evidence of disease after three years. CONCLUSION: All patients were in advanced clinical stages of the disease. The three-year disease-free survival rate was 52 percent.

Laringectomía parcial en cáncer laríngeo precoz: 25 años de experiencia / Partial laryngectomy for early laryngeal cancer: a 25-year experience

Introducción: La laringectomía parcial y la radioterapia son alternativas eficaces en el tratamiento de pacientes con cáncer laríngeo precoz, comparables tanto en tasas de sobrevida como en conservación laríngea. Objetivo: Se describe la experiencia del primer autor en los últimos 25 años. Material y método: Estudio retrospectivo de pacientes con cáncer laríngeo precoz tratados entre los años 1980 y 2005. Se analiza los antecedentes de los pacientes, tipo de tratamiento, histología del tumor, complicaciones y tasas de sobrevida. Resultados: Se incluye un total de 96 pacientes, con una edad promedio de 58 años. El tipo histológico más frecuente fue el carcinoma epidermoide (92%). El 53% se sometió a cirugía laríngea parcial y 47% a radioterapia. La intervención más habitual fue la laringectomía frontolateral (68%). Las complicaciones más frecuentes fueron la presencia de granulomas (16%) y falta de cierre del traqueostoma (16%). Se constató recidiva en 4 pacientes tratados con radioterapia y 1 sometido a cirugía. La sobrevida actual es de 91% para quienes recibieron radioterapia y 100 por ciento en quienes se practicó laringectomía parcial. Se presenta los resultados del tratamiento con o sin compromiso de la comisura anterior. Discusión y conclusiones: La experiencia con ambas modalidades son comparables a la literatura, con complicaciones y secuelas esperables. La aparición de nuevas técnicas debe compararse en su realidad local con las terapias establecidas y la decisión terapéutica sigue correspondiendo a un acuerdo informado entre el tratante y su paciente.

Introduction. Partial laryngectomy and radiotherapy are good alternatives for early laryngeal cancer, as they are similar in both survival rate and laryngeal preservation. Aim. The first author's 25-year experience on this subject is described. Material and method. Retrospective review of early laryngeal cancer patients treated between 1980 and 2005. History type of treatment, tumor histology complications and survival rates are analyzed. Results. A total of 96 patients is included, with an average age of 58 years. The most frequent histological type was epidermoid carcinoma (92%). 53% of patients had partial laryngectomy, and 47% had radiotherapy. Most patients had a fronto-lateral laryngectomy (68%), and the most frequent complications were granulomas (16%) and failure of tracheostoma closure (16%). Four radiotherapy patients and one that underwent surgery had recurrences. Present survival rate is 91% for radiotherapy and 100% for partial laryngectomy. Treatment results with and without anterior comissure involvement are presented. Discussion and conclusions. Our experience with both treatment alternatives is comparable to that reponed in the literature, with similar complications. New techniques must be compared with those currently used, taking into account local reality and the therapeutic decision is still an informed agreement between the treating physician and the patient.

Hidrocefalia aguda como forma de presentación de carcinomatosis meníngea: Reporte de 2 casos y revisión de la bibliografía / Onset of meningeal carcinomatosis as acute hydrocefalus

Objective: To present two cases of leptomeningeal carcinomatosis, their management, and a bibliographical revision. Description: case 1: patient of 48 years, who enters by sensory abnormalities, with CT that demotrated tetraventricular hydrocephalus. The CSF was positive for neoplasic cells. Primary tumor was found in bladder. Case 2: patient of 55 years, who entered by progressive cuadriparesia. He presented sensory abnormalities by acute hydrocephalus. The autopsy informed meningeal affectation by gastric carcinoma. Discussion: Although patognomonic signs do not exist, the more frequent clinical manifestations are affectation of cranial nerves, headache and alterations of the mental functions. The RNM with gadolinium is the best method, with a sensitivity of 70. In the infrequent cases of acute hydrocephalus, the CT is the first study to perform. Conclusion: Before the unspecific signs, the diagnosis of certainty of meningeal carcinomatosis is based on the help of radiological investigations and the findings of the LCR, on an oncologic context.