Radiotherapy and immune response: the systemic effects of a local treatment

Technological developments have allowed improvements in radiotherapy delivery, with higher precision and better sparing of normal tissue. For many years, it has been well known that ionizing radiation has not only local action but also systemic effects by triggering many molecular signaling pathways. There is still a lack of knowledge of this issue. This review focuses on the current literature about the effects of ionizing radiation on the immune system, either suppressing or stimulating the host reactions against the tumor, and the factors that interact with these responses, such as the radiation dose and dose / fraction effects in the tumor microenvironment and vasculature. In addition, some implications of these effects in cancer treatment, mainly in combined strategies, are addressed from the perspective of their interactions with the more advanced technology currently available, such as heavy ion therapy and nanotechnolog

High dose-rate endobronchial brachytherapy: a dosimetric study

OBJETIVO: Avaliar a distribuição de dose em diferentes situações de braquiterapia endobrônquica de alta taxa de dose, com foco principalmente nos volumes de altas doses, e tentar definir situações de melhor ou pior distribuição de dose que possam servir de guia na prática clínica. MATERIAIS E MÉTODOS: Estudo teórico, simulando braquiterapia endobrônquica de alta taxa de dose utilizando dois cateteres, com variação da extensão de carregamento, angulação entre os cateteres, profundidade de cálculo e o intervalo entre as paradas da fonte. Com prescrição de 7,5 Gy, foram calculados os volumes englobados pelas isodoses correspondentes a 100%, 150% e 200% da dose prescrita (V100, V150 e V200, respectivamente) e as razões V150/V100 e V200/V100. RESULTADOS: Os volumes aumentaram com o aumento da extensão de carregamento dos cateteres, profundidade de cálculo e angulação, com tendência a um aumento proporcionalmente menor para angulações maiores. As relações V150/V100 e V200/V100 foram, em geral, homogêneas, ao redor de 0,50 e 0,30, respectivamente. CONCLUSÃO: A distribuição de dose na situação considerada padrão é em geral adequada. Nenhum parâmetro específico que pudesse ser relacionado à maior toxicidade foi identificado. Recomendamos uma avaliação rápida da qualidade do implante por meio da análise das relações V150/V100 e V200/V100.OBJECTIVE: To evaluate the dose distribution in different situations of high dose-rate endobronchial brachytherapy, focusing especially on high-dose volumes, and try to identify better or worse situations in terms of dose distribution to aid as guidance in the clinical practice. MATERIALS AND METHODS: Theoretical study simulating high dose-rate endobronchial brachytherapy utilizing two catheters, varying the loading extent, angle between the catheters, prescription depth, and source step. With a prescription dose of 7.5 Gy, the volumes involved by the 100%, 150% and 200% isodoses (V100, V150 and V200, respectively) and V150/V100 and V200/V100 ratios were calculated. RESULTS: There was a volume enhancement with larger loaded lengths, increase in prescription depth and angles, with a tendency towards a proportionally smaller increase with larger angulations. In general, the V150/V100 and V200/V100 ratios were homogeneous, respectively around 0.50 and 0.30. CONCLUSION: Overall, the dose distribution in the standard situation was appropriate. No specific parameter that could be related to a higher toxicity was identified. The authors recommend a swift evaluation of the treatment quality through the analysis of the V150/V100 and V200/V100 ratios

Metástase em polegar de carcinoma de pequenas células de pulmão tratada com radioterapia

A rare case of thumb metastasis from small cell lung cancer is presented. The patient underwent local radiotherapy with complete palliation of symptoms. She died 4 months later with disseminated disease. Considerations about incidence, treatment, and physiopathology of this kind of dissemination are made. Conservative treatment of finger metastasis with radiation may be considered due to the poor outcome of these patients.Apresentamos um caso raro de metástase em polegar de carcinoma de pequenas células de pulmão. A paciente foi submetida a radioterapia local com alívio completo dos sintomas. Quatro meses após o término do tratamento evoluiu a óbito com doença disseminada. São feitas considerações sobre incidência, tratamento e fisiopatologia desse tipo de disseminação. O tratamento conservador com radioterapia de metástases em dedos deve ser considerado, principalmente devido ao prognóstico reservado desses pacientes

Braquiterapia de alta taxa de dose como opção terapêutica nos tumores primários da traquéia

PURPOSE: To present experience with high dose-rate endobronchial brachytherapy in the treatment of primary tracheal tumors. PATIENTS AND METHODS: Four patients with nonresected primary tracheal tumors are presented: 2 cases of squamous cell carcinoma of the trachea, 1 of recurrent adenoid cystic carcinoma, and 1 with recurrent plasmacytoma. All received brachytherapy, alone or as a boost for primary irradiation, in 3 or 4 fractions of 7.5 Gy, calculated at a depth of 1 cm. Follow-up was considered to start from the end of brachytherapy. RESULTS: Local control was achieved in all cases at the time of first bronchoscopic evaluation. Two patients with squamous cell carcinoma died at 6th and 33rd months after brachytherapy, respectively. The first had no evidence of disease, and the latter had local recurrence. The other 2 patients were alive after 64 and 110 months of follow-up, respectively, both with no evidence of disease. Tracheal stenosis developed in these 2 cases, 22 and 69 months after brachytherapy. Tracheal stent placement was needed only for the patient with an adenoid cystic carcinoma. CONCLUSIONS: Endobronchial high dose-rate brachytherapy may be used for tracheal tumors, even as a boost for external beam irradiation, or in recurrences. Local control in 3 out of 4 patients indicates that individual cases may benefit from the treatment. Long-term survival may also be expected, mainly for tumors with adenoid cystic histology.OBJETIVO: Apresentar a experiência do tratamento de 4 pacientes com tumores primários de traquéia, não operados, submetidos à braquiterapia endobrônquica de alta taxa de dose. PACIENTES E MÉTODOS: Dois casos de carcinoma espinocelular, uma recidiva de carcinoma adenóide cístico e uma recidiva de plasmocitoma primário da traquéia. Todos receberam braquiterapia endobrônquica, exclusiva ou como reforço de dose da radioterapia externa. Foram administradas 3 ou 4 frações de 7,5 Gy cada, calculados a 1 cm de profundidade. O seguimento foi considerado a partir do término da braquiterapia. RESULTADOS: Em todos os casos houve resposta completa. Dois pacientes com carcinoma espinocelular evoluíram a óbito em 6 e 33 meses após a braquiterapia, o primeiro, sem evidência de doença e o outro por recidiva local, respectivamente. As outras 2 pacientes encontravam-se vivas após 64 e 110 meses de seguimento, sem evidência de doença. Esses 2 casos apresentaram estenose traqueal em 22 e 69 meses após a braquiterapia, sendo necessária a colocação de prótese traqueal apenas na paciente com carcinoma adenóide cístico. CONCLUSÕES: A braquiterapia endobrônquica de alta taxa de dose pode ser utilizada tanto como reforço de dose da irradiação externa quanto em recidivas. O controle local obtido em 3 de 4 pacientes indica que casos individuais podem se beneficiar desse procedimento. Sobrevida a longo prazo pode ser observada, principalmente nos casos de histologia adenóide cística

Dosimetric evaluation of a combination of brachytherapy applicators for uterine cervix cancer with involvement of the distal vagina

OBJETIVO: Avaliar uma alternativa de braquiterapia para tumores do colo uterino acometendo a porção distal da vagina, sem aumentar os riscos de toxicidade. MATERIAIS E MÉTODOS: Estudo teórico comparando três diferentes aplicadores de braquiterapia intracavitária de alta taxa de dose: sonda intrauterina e cilindro vaginal (SC); sonda e anel associado ao cilindro vaginal (SA+C) e um aplicador virtual com sonda, anel e cilindro vaginal em um único conjunto (SAC). Foram prescritas doses de 7 Gy no ponto A e 5 Gy na superfície ou a 5 mm de profundidade na mucosa vaginal, mantendo as doses nos pontos de reto, bexiga e sigmoide abaixo dos limites de tolerância. Foram comparados os volumes englobados pelas isodoses de 50% (V50), 100% (V100), 150% (V150) e 200% (V200), respectivamente. RESULTADOS: Tanto SA+C quanto SAC apresentaram melhor distribuição de dose quando comparados ao aplicador SC. A distribuição de dose obtida com SA+C foi semelhante à do aplicador SAC, sendo V150 e V200 cerca de 50% maiores para SA+C, todavia, dentro do cilindro. CONCLUSÃO: A utilização de SA+C em uma única aplicação em dois tempos pode ser uma alternativa de tratamento para pacientes que apresentam tumores de colo uterino com acometimento distal da vagina.OBJECTIVE: To evaluate an alternative brachytherapy technique for uterine cervix cancer involving the distal vagina, without increasing the risk of toxicity. MATERIALS AND METHODS: Theoretical study comparing three different high-dose rate intracavitary brachytherapy applicators: intrauterine tandem and vaginal cylinder (TC); tandem/ring applicator combined with vaginal cylinder (TR+C); and a virtual applicator combining both the tandem/ring and vaginal cylinder in a single device (TRC). Prescribed doses were 7 Gy at point A, and 5 Gy on the surface or at a 5 mm depth of the vaginal mucosa. Doses delivered to the rectum, bladder and sigmoid colon were kept below the tolerance limits. Volumes covered by the isodoses, respectively, 50% (V50), 100% (V100), 150% (V150) and 200% (V200) were compared. RESULTS: Both the combined TR+C and TRC presented a better dose distribution as compared with the TC applicator. The TR+C dose distribution was similar to the TRC dose, with V150 and V200 being about 50% higher for TR+C (within the cylinder). CONCLUSION: Combined TR+C in a two-time single application may represent an alternative therapy technique for patients affected by uterine cervix cancer involving the distal vagina

Comparison between irradiated lung volumes with two-dimensional and three-dimensional conformal radiotherapy techniques for locally advanced lung cancer

OBJETIVO: Comparar e quantificar os volumes pulmonares irradiados utilizando planejamentos bidimensional (2D) e tridimensional (3D) conformado na radioterapia de tumores de pulmão. MATERIAIS E MÉTODOS: Em 27 pacientes portadores de câncer de pulmão foi feito planejamento 3D e outro correspondente em 2D. As doses prescritas variaram de 45 a 66 Gy. Foram avaliadas as doses no volume alvo planejado (PTV), volume tumoral macroscópico (GTV) e pulmões (volume de pulmão que recebe 20 Gy ou 30 Gy - V20 e V30, respectivamente, e dose média). Os órgãos de risco adjacentes (medula espinhal, esôfago e coração) receberam doses abaixo dos limites de tolerância. RESULTADOS: O GTV variou de 10,5 a 1.290,0 cm³ (média de 189,65 cm³). Nos planejamentos 2D foi utilizado, em média, um total de 59,33 campos, e nos planejamentos 3D, 75,65 campos. Em todas as situações analisadas houve significante (p < 0,05) preservação dos volumes pulmonares com o planejamento 3D, com diminuição de cerca de 15% dos volumes irradiados. O pulmão sem tumor foi mais beneficiado. CONCLUSÃO: A radioterapia 3D permitiu maior preservação dos pulmões, tanto para tumores iniciais quanto avançados. A radioterapia 3D deve ser utilizada nos pacientes com tumores de pulmão, mesmo que volumosos.OBJECTIVE: To compare and quantify irradiated lung volumes using two-dimensional (2D) and three-dimensional (3D) conformal planning for radiotherapy in the treatment of lung cancer. MATERIALS AND METHODS: 2D and 3D conformal radiotherapy plannings were performed for 27 patients with lung cancer. Prescribed doses ranged from 45 to 66 Gy. The analysis covered the doses to planning target volume (PTV), gross tumor volume (GTV) and lungs (lung volume receiving 20 Gy or 30 Gy - V20 and V30, respectively, and mean dose). The doses to adjacent organs at risk (spinal cord, esophagus and heart) were maintained below the tolerance limits. RESULTS: GTV ranged from 10.5 to 1,290.0 cm³ (mean, 189.65 cm³). On average, a total of 59.33 fields were utilized in the 2D planning and 75.65 fields in the 3D planning. Lung volumes were significantly preserved (P < 0.05) with the 3D conformal planning in all the evaluated cases, with about 15% decrease in the irradiated lung volumes. Lungs without tumor were most benefited from this technique. CONCLUSION: 3D radiotherapy allowed a better sparing of the lungs, both in cases of early and advanced tumors. 3D radiotherapy should be used in the treatment of patients with lung cancer, even in cases of large tumors

Spine radiosurgery for the local treatment of spine metastases: Intensity-modulated radiotherapy, image guidance, clinical aspects and future directions

Many cancer patients will develop spinal metastases. Local control is important for preventing neurologic compromise and to relieve pain. Stereotactic body radiotherapy or spinal radiosurgery is a new radiation therapy technique for spinal metastasis that can deliver a high dose of radiation to a tumor while minimizing the radiation delivered to healthy, neighboring tissues. This treatment is based on intensity-modulated radiotherapy, image guidance and rigid immobilization. Spinal radiosurgery is an increasingly utilized treatment method that improves local control and pain relief after delivering ablative doses of radiation. Here, we present a review highlighting the use of spinal radiosurgery for the treatment of metastatic tumors of the spine. The data used in the review were collected from both published studies and ongoing trials. We found that spinal radiosurgery is safe and provides excellent tumor control (up to 94% local control) and pain relief (up to 96%), independent of histology. Extensive data regarding clinical outcomes are available; however, this information has primarily been generated from retrospective and nonrandomized prospective series. Currently, two randomized trials are enrolling patients to study clinical applications of fractionation schedules spinal Radiosurgery. Additionally, a phase I clinical trial is being conducted to assess the safety of concurrent stereotactic body radiotherapy and ipilimumab for spinal metastases. Clinical trials to refine clinical indications and dose fractionation are ongoing. The concomitant use of targeted agents may produce better outcomes in the future

Importance of amylases for physiological quality in maize seeds

Seed quality is the result of the sum of genetic, physical, physiological and sanitary attributes that affect seed ability to perform vital functions related to germination, vigor, and longevity. The expression of genes associated with physiological quality can be assessed by means of germination and vigor analyses, as well as by transcript and protein analyses. The objective in this work was to review the relevance of amylase group enzymes to the physiological quality of maize seeds. Within this group, α-amylase (1,4-α-D-glucan glucanohydrolase E.C 3.2.1.1) plays an important role in starch hydrolysis, and is responsible for 90% of the amylolytic activity in maize seeds. It is responsible for starch conversion into sugars (e.g., destrin), which is used for embryo growth. β-amylase (1,4-α-D-glucan maltohydrolase E.C 3.2.1.2) catalyzes the release of maltose and dextrins from the non-reducing ends of starch. Research has shown that amylase enzymes are directly linked to physiological quality of maize seeds. Alpha- and beta-amylases are mainly involved in the germination process and seed heterosis, and can also be used as molecular markers associated with seed tolerance for drying

Fanconi anemia and vaginal squamous cell carcinoma

Fanconi Anemia (FA) is an autosomal recessive disease characterized by chromosome instability, cellular hypersensitivity to DNA cross-linking agents, and increased predisposition to malignancies. We describe here a 28 year-old female with FA and vaginal squamous cell carcinoma treated by radiation therapy alone. The patient developed arm phlebitis, pulmonary fungal infection, and severe rectal bleeding, followed by hypocalcaemia, hypokalemia, vaginal bacterial and fungal infection, with subsequent leg and arm phlebitis, perineal abscess, and sepsis. The patient died 12 weeks later

Urinary infection or radiation cystitis? A prospective evaluation of urinary symptoms in patients submitted to pelvic radiotherapy

OBJECTIVES: The purpose of this study was to evaluate the incidence of urinary tract infection (UTI) in patients with cystitis symptoms who underwent pelvic radiation therapy and identify correlated predictive factors. METHODS: A prospective cohort study was conducted of patients who met the following: primary pelvic cancer treated with curative intent, older than 18 years old, and good performance status. The exclusion criteria were patients being treated for a UTI, using a urinary catheter, in dialysis or with cystostomy or nephrostomy, and using antibiotics during treatment. Urinalysis and urine culture were collected before the beginning of radiation therapy. Weekly evaluations of urinary symptoms were subsequently performed. In cases of new or worsening symptoms, a questionnaire was applied, and new urine exams were collected. The UTI diagnosis was defined by uroculture as bacterial growth greater than 104 CFU/mL. RESULTS: From September 2014 to November 2015, 112 patients were sequentially recruited, and 72 (64%) fulfilled the inclusion criteria. During follow-up, 24 (33%) patients had new urinary symptoms or worse preexisting symptoms. A UTI was confirmed in the second urinary culture in only one (1.4%) patient. CONCLUSIONS: The incidence of UTI was much lower than expected, suggesting that asymptomatic bacteriuria develops symptoms due to radiotherapy. Due to the low rate of UTI, no predictive factor was identified