Safety and Feasibility Analysis of a Prospective Trial on Stereotactic Body Radiotherapy for Solitary Bone Plasmacytoma.

BACKGROUND: There have been reports on the use of hypofractionated stereotactic body radiotherapy (SBRT) for bone plasmacytomas, but no prospective data are available. We present the initial analysis of an ongoing prospective protocol on SBRT addressing the feasibility and safety of this treatment for solitary bone plasmacytomas. PATIENTS AND METHODS: A prospective cohort of SBRT for solitary bone plasmacytoma was developed. Patients could receive different doses depending on the index bone, from single fraction for skull base lesions, 24 Gy in 3 fractions for spine lesions, and 30 Gy in 5 fractions for other bones. Overall survival, bone events, local control, and progression to multiple myeloma (MM) were measured and compared to our retrospective cohort of patients treated with conformal standard-dose radiotherapy. Quality of life was assessed via the EORTC QLQ-C30 questionnaire, and toxicities were assessed by the CTCAE v5.0 criteria. After 1 year or the inclusion of 5-10 patients, a feasibility and safety analysis was programmed. RESULTS: Between April 2018 and April 2019, 5 patients were included. All were male, with a median age of 53.1 years. The median follow-up was 21.8 months. No patient had local progression, bone event, or died. Two patients had progressions to MM. The mean survival free of progression to MM was 18.6 months, compared to 19 months in the retrospective cohort; median values were not reached. There were no grade 3 toxicities. CONCLUSION: SBRT for plasmacytoma is safe and feasible. More robust data are awaited.

Prospective validation of a core curriculum progress assimilation instrument for radiation oncology residentship.

OBJECTIVES: To develop a tool that could assess residents' knowledge beyond simple information gathering and evaluate its reliability. METHODS: An assessment tool of 40 objective questions and at least one essay-based question was developed to assess residents' comprehension of general radiation oncology accordingly to validated training curricula beyond level 2 in the Bloom scale. With randomized content, questions were developed such as to be classified as at least 2 in the Bloom scale, so that reasoning and not only information gathering could be assessed. Criteria validation was made using the Classical Test Theory to describe difficulty and discrimination of each item. Reliability was tested by internal consistency using the Cronbach alpha test. RESULTS: Between 2016 and 2019, 24 residents were assessed. Six different versions of the test were made with a total of 240 objective questions and 18 essay-based questions. Five of the six versions were deemed valid and reliable. Comparisons between 1st (PGY-1) and 3rd (PGY-3) year residents were made. Consistently, PGY-3 residents had scores 150% higher than PGY-1 residents. Only two different PGY-3 reached the most complex level of answers in the essay-based questions. The results demonstrated that the major part of the acquired knowledge and retention occurs in the first six months of training rather than in all the following period. CONCLUSION: The instrument can be considered valid. This developed instrument also raised the hypothesis that residents may not assess and analyze their acquired knowledge beyond the application level.

Impact of bone events on survival in solitary bone plasmacytoma.

BACKGROUND: Although much studied in multiple myeloma, bone events (BE) can also cause important morbidity in bone plasmacytoma patients. To our knowledge, the effect of BE on overall survival (OS) and progression to multiple myeloma free-survival (MPFS) also has never been studied. PATIENTS AND METHODS: Fifty-nine patients treated from 2008 to 2017 were retrospectively assessed. All patients had histological proof of disease and were treated with radical radiotherapy (RT). Available clinical information for at least 6 months follow-up or until death had to be available. BE were described as one of the following events in the index bone: fractures, osteomyelitis, chronic pain, surgery or loss of limb function after RT. RESULTS: Mean age at diagnosis was 57.3 years (18-80); most male (67.8%). Mean OS, bone event free-survival (BEFS), local progression-free survival (LPFS) and MPFS were 41, 36, 37 and 19 months, respectively. There were 15 deaths. BEFS (p = 0.008) and age>55y (p = 0.044) were associated with MPFS. Only BEFS correlated with OS (p = 0.029). BE was independently associated with both MPFS and OS in multivariate analysis. CONCLUSION: BE and survival end-points were correlated. BE should be investigated in prospective trials.

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 nanotechnology.

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 nanotechnology.

Oral mucositis prevention by low-level laser therapy in head-and-neck cancer patients undergoing concurrent chemoradiotherapy: a phase III randomized study.

PURPOSE: Oral mucositis is a major complication of concurrent chemoradiotherapy (CRT) in head-and-neck cancer patients. Low-level laser (LLL) therapy is a promising preventive therapy. We aimed to evaluate the efficacy of LLL therapy to decrease severe oral mucositis and its effect on RT interruptions. METHODS AND MATERIALS: In the present randomized, double-blind, Phase III study, patients received either gallium-aluminum-arsenide LLL therapy 2.5 J/cm(2) or placebo laser, before each radiation fraction. Eligible patients had to have been diagnosed with squamous cell carcinoma or undifferentiated carcinoma of the oral cavity, pharynx, larynx, or metastases to the neck with an unknown primary site. They were treated with adjuvant or definitive CRT, consisting of conventional RT 60-70 Gy (range, 1.8-2.0 Gy/d, 5 times/wk) and concurrent cisplatin. The primary endpoints were the oral mucositis severity in Weeks 2, 4, and 6 and the number of RT interruptions because of mucositis. The secondary endpoints included patient-reported pain scores. To detect a decrease in the incidence of Grade 3 or 4 oral mucositis from 80% to 50%, we planned to enroll 74 patients. RESULTS: A total of 75 patients were included, and 37 patients received preventive LLL therapy. The mean delivered radiation dose was greater in the patients treated with LLL (69.4 vs. 67.9 Gy, p = .03). During CRT, the number of patients diagnosed with Grade 3 or 4 oral mucositis treated with LLL vs. placebo was 4 vs. 5 (Week 2, p = 1.0), 4 vs. 12 (Week 4, p = .08), and 8 vs. 9 (Week 6, p = 1.0), respectively. More of the patients treated with placebo had RT interruptions because of mucositis (6 vs. 0, p = .02). No difference was detected between the treatment arms in the incidence of severe pain. CONCLUSIONS: LLL therapy was not effective in reducing severe oral mucositis, although a marginal benefit could not be excluded. It reduced RT interruptions in these head-and-neck cancer patients, which might translate into improved CRT efficacy.

ERCC1 protein, mRNA expression and T19007C polymorphism as prognostic markers in head and neck squamous cell carcinoma patients treated with surgery and adjuvant cisplatin-based chemoradiation.

Adjuvant cisplatin-based chemoradiation improves survival in HNSCC patients presenting with risk features. ERCC1 (excision repair cross-complementation group 1) is associated with resistance to chemo- and radiation therapy and may have a prognostic value in HNSCC patients. Here we studied ERCC1 expression and the polymorphism T19007C as prognostic markers in these patients. This is a retrospective and translational analysis, where ERCC1 protein expression was evaluated by immunohistochemistry, using an H-score, and mRNA expression was determined by RT-PCR. T19007C genotypes were detected by PCR-RFLP carried out using DNA template extracted from normal lymph nodes. A high H-score was seen in 32 patients (54%), who presented better 5-year overall survival (5-y OS: 50% vs. 18%, HR 0.43, p=0.026). Fifteen out of 45 patients (33%), with high mRNA expression, presented better 5-year overall survival (OS) (86% vs. 30%, HR 0.26, p=0.052). No OS difference was detected among T19007C genotypes. High H-score and mRNA expression remained significant as favorable prognostic factors in a multivariate analysis. Collectively, our results suggest that high ERCC1 expression seems to be associated with better OS rates in HNSCC patients submitted to adjuvant cisplatin-based chemoradiation.

Efficacy of low-level laser therapy and aluminum hydroxide in patients with chemotherapy and radiotherapy-induced oral mucositis.

This study evaluated the efficacy of low-level laser therapy (LLLT) and aluminum hydroxide (AH) in the prevention of oral mucositis (OM). A prospective, comparative and non-randomized study was conducted with 25 patients with head and neck cancer subjected to radiotherapy (RT) or radiochemotherapy (RCT). Twelve patients received LLLT (830 nm, 15 mW, 12 J/cm²) daily from the 1st day until the end of RT before each sessions during 5 consecutive days, and the other 13 patients received AH 310 mg/5 mL, 4 times/day, also throughout the duration of RT, including weekends. OM was measured using an oral toxicity scale (OTS) and pain was measured using the visual analogue scale (VAS). EORTC questionnaires were administered to the evaluate impact of OM on quality of life. The LLLT group showed lower mean OTS and VAS scores during the course of RT. A significant difference was observed in pain evaluation in the 13th RT session (p=0.036). In both groups, no interruption of RT was needed. The prophylactic use of both treatments proposed in this study seems to reduce the incidence of severe OM lesions. However, the LLLT was more effective in delaying the appearance of severe OM.

Efficacy of low-level laser therapy and aluminum hydroxide in patients with chemotherapy and radiotherapy-induced oral mucositis

This study evaluated the efficacy of low-level laser therapy (LLLT) and aluminum hydroxide (AH) in the prevention of oral mucositis (OM). A prospective, comparative and non-randomized study was conducted with 25 patients with head and neck cancer subjected to radiotherapy (RT) or radiochemotherapy (RCT). Twelve patients received LLLT (830 nm, 15 mW, 12 J/cm²) daily from the 1st day until the end of RT before each sessions during 5 consecutive days, and the other 13 patients received AH 310 mg/5 mL, 4 times/day, also throughout the duration of RT, including weekends. OM was measured using an oral toxicity scale (OTS) and pain was measured using the visual analogue scale (VAS). EORTC questionnaires were administered to the evaluate impact of OM on quality of life. The LLLT group showed lower mean OTS and VAS scores during the course of RT. A significant difference was observed in pain evaluation in the 13th RT session (p=0.036). In both groups, no interruption of RT was needed. The prophylactic use of both treatments proposed in this study seems to reduce the incidence of severe OM lesions. However, the LLLT was more effective in delaying the appearance of severe OM.

Este estudo avaliou a eficácia da terapia do laser de baixa potência (LBP) e hidróxido de alumínio (HA) na prevenção da mucosite oral (MO). Um estudo prospectivo, comparativo e não-aleatorizado foi conduzido com 25 pacientes com câncer de cabeça e pescoço submetidos a radioterapia (RT) ou radioquimioterapia (RT/QT). Doze pacientes receberam LBP (830 nm, 15 mW, 12 J/cm²) diariamente desde o primeiro dia até o final da RT antes de cada sessão durante 5 dias consecutivos, e os outros 13 pacientes receberam HA 310 mg/5 mL, 4 vezes ao dia, também por toda a duração da RT, incluindo finais de semana. MO foi mensurada usando uma escala de toxicidade oral (ETO) e dor foi mensurada usando a escala visual analógica (EVA). Questionários da EORTC foram administrados para a avaliação do impacto da MO na qualidade de vida. O grupo LBP mostrou menores médias dos escores da ETO e EVA durante o curso da RT. Uma diferença significante foi observada na avaliação da dor na 13ª sessão de RT (p=0,036). Em ambos os grupos, nenhuma interrupção da RT foi necessária. O uso profilático de ambos os tratamentos propostos neste estudo parece reduzir a incidência de lesões severas de MO. No entanto, o LBP foi mais efetivo no atraso do aparecimento da MO severa.

Linfoma de sistema nervoso central com comprometimento intra e extracraniano em paciente näo imunodeprimido: relato de caso e revisäo da literatura / Central nervous system Hodgkin's limphoma with intra and extra cranial envolvent in a non immunocompromised patient. Case report and literature review

Relatamos um caso de linfoma näo Hodgkin de grandes células B em gânglios da regiäo cervical e retroperitôneo e com sítios de comprometimento extra nodal: encéfalo, calota craniana, couro cabeludo e infiltraçäo de vértebra T4. O perfil sorológico se mostrou negativo para anticorpos anti-HIV e a paciente foi tratada com seis ciclos de quimioterapia sistêmica de terceira geraçäo para linfomas agressivos (ProMACE-CytaBOM) em doses convencionais e radioterapia em encéfalo (dose total 4.000 cGY).Encontra-se em remissäo clínica e radiológica completa dez meses após o diagnóstico de linfoma. Discutimos o tratamento do linfoma primário de sistema central em pacientes näo imunodeprimidos.