Consensus on Screening, Diagnosis, and Staging Tools for Prostate Cancer in Developing Countries: A Report From the First Prostate Cancer Consensus Conference for Developing Countries (PCCCDC).

PURPOSE: To generate and present the survey results on critical issues relevant to screening, diagnosis, and staging tools for prostate cancer (PCa) focused on developing countries. METHODS: A total of 36 of 300 questions concern the main areas of interest of this paper: (1) screening, (2) diagnosis, and (3) staging for various risk levels of PCa in developing countries. A panel of 99 international multidisciplinary cancer experts voted on these questions to create recommendations for screening, diagnosing, and staging tools for PCa in areas of limited resources discussed in this manuscript. RESULTS: The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion not a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations consider cost-effectiveness and the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. The results were tabulated in real time. CONCLUSION: The voting results and recommendations presented in this document can be used by physicians to support the screening, diagnosis, and staging of PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for screening, diagnosis, and staging of PCa in developing countries have not been developed, this document will serve as a point of reference when confronted with this disease.

Impact of COVID-19 pandemic on a daily-based outpatient treatment routine: experience of a radiotherapy department of a tertiary public/university hospital in Brazil.

OBJECTIVES: To report the impact of the COVID-19 pandemic on patient attendance at a radiotherapy department two months after the implementation of specific policies regarding the pandemic. METHODS: The proposed treatment schemes, favoring hypofractionated schedules, and COVID-19 management strategies regarding irradiation are presented. Attendance after two months of implementation of these policies was measured and compared with that during the same period in 2019. RESULTS: A 10% reduction in the number of treated patients and a 26% reduction in the number of sessions was observed. The main impact was a decrease in the treatment of benign diseases and gastrointestinal tumors, with a general increase in breast cancer treatments. Eighteen (1.7%) patients were confirmed as having COVID-19 during radiotherapy in April and May 2020, three of whom were hospitalized, and one patient died because of COVID-19. Among the 18 patients, 12 had their treatments interrupted for at least 15 days from symptom appearance. CONCLUSION: There was a decrease in the number of treated patients in our radiotherapy department, with a greater decrease in the total number of sessions. This indicated, overall, a smaller number of fractions/patients treated, despite our efforts to maintain the treatment routine. We had several patients who were infected with COVID-19 and one related death during treatment in the first few months of the pandemic in São Paulo Brazil.

Impact of COVID-19 pandemic on a daily-based outpatient treatment routine: experience of a radiotherapy department of a tertiary public/university hospital in Brazil

OBJECTIVES: To report the impact of the COVID-19 pandemic on patient attendance at a radiotherapy department two months after the implementation of specific policies regarding the pandemic. METHODS: The proposed treatment schemes, favoring hypofractionated schedules, and COVID-19 management strategies regarding irradiation are presented. Attendance after two months of implementation of these policies was measured and compared with that during the same period in 2019. RESULTS: A 10% reduction in the number of treated patients and a 26% reduction in the number of sessions was observed. The main impact was a decrease in the treatment of benign diseases and gastrointestinal tumors, with a general increase in breast cancer treatments. Eighteen (1.7%) patients were confirmed as having COVID-19 during radiotherapy in April and May 2020, three of whom were hospitalized, and one patient died because of COVID-19. Among the 18 patients, 12 had their treatments interrupted for at least 15 days from symptom appearance. CONCLUSION: There was a decrease in the number of treated patients in our radiotherapy department, with a greater decrease in the total number of sessions. This indicated, overall, a smaller number of fractions/patients treated, despite our efforts to maintain the treatment routine. We had several patients who were infected with COVID-19 and one related death during treatment in the first few months of the pandemic in São Paulo Brazil.

Dentin-pulp complex reactions in conventional and radiation-related caries: A comparative study.

BACKGROUND: Radiation-related caries (RRC) is one of the most significant oral toxicities of head and neck radiotherapy (HNRT); however, the potential of radiation to directly cause harmful dentin and pulpal effects and impair response to caries progression is controversial. MATERIAL AND METHODS: Therefore, the aim of this study was to characterize the reactions of the dentin-pulp complex in teeth affected by RRC. Patients and methods: Twenty-two carious teeth extracted from 22 head and neck cancer (HNC) patients were divided into control (conventional caries; n=11) and irradiated (RRC; n=11) groups and paired matched by dental homology, clinical patterns of caries progression following the Post-Radiation Dental Index (PRDI) and microscopic depth of carious invasion. Histopathological characteristics based on morphological hierarchy, cell populations of dental pulp, blood vessels, neural elements, extracellular matrix components, inflammation, patterns of carious invasion and reactionary dentin presence were evaluated by optical light microscopy and histomorphometry. RESULTS: Mean PRDI scores were 3.2 for the control group and 3.8 for the irradiated group. Dentin demineralization patterns were also similar between the groups and the mean depths of demineralization were 1,158.58µm and 1,056.89µm for the control and irradiated groups, respectively. CONCLUSIONS: Pulp histopathological changes and dentin reaction patterns were similar between groups and varied according to the PRDI scores and carious lesions depth. Dentin and pulp reactions are highly preserved in RRC teeth. Key words:Cancer, radiotherapy, radiation-related caries, teeth, pulp.

Evolution of gamma knife capsulotomy for intractable obsessive-compulsive disorder.

For more than half a century, stereotactic neurosurgical procedures have been available to treat patients with severe, debilitating symptoms of obsessive-compulsive disorder (OCD) that have proven refractory to extensive, appropriate pharmacological, and psychological treatment. Although reliable predictors of outcome remain elusive, the establishment of narrower selection criteria for neurosurgical candidacy, together with a better understanding of the functional neuroanatomy implicated in OCD, has resulted in improved clinical efficacy for an array of ablative and non-ablative intervention techniques targeting the cingulum, internal capsule, and other limbic regions. It was against this backdrop that gamma knife capsulotomy (GKC) for OCD was developed. In this paper, we review the history of this stereotactic radiosurgical procedure, from its inception to recent advances. We perform a systematic review of the existing literature and also provide a narrative account of the evolution of the procedure, detailing how the procedure has changed over time, and has been shaped by forces of evidence and innovation. As the procedure has evolved and adverse events have decreased considerably, favorable response rates have remained attainable for approximately one-half to two-thirds of individuals treated at experienced centers. A reduction in obsessive-compulsive symptom severity may result not only from direct modulation of OCD neural pathways but also from enhanced efficacy of pharmacological and psychological therapies working in a synergistic fashion with GKC. Possible complications include frontal lobe edema and even the rare formation of delayed radionecrotic cysts. These adverse events have become much less common with new radiation dose and targeting strategies. Detailed neuropsychological assessments from recent studies suggest that cognitive function is not impaired, and in some domains may even improve following treatment. We conclude this review with discussions covering topics essential for further progress of this therapy, including suggestions for future trial design given the unique features of GKC therapy, considerations for optimizing stereotactic targeting and dose planning using biophysical models, and the use of advanced imaging techniques to understand circuitry and predict response. GKC, and in particular its modern variant, gamma ventral capsulotomy, continues to be a reliable treatment option for selected cases of otherwise highly refractory OCD.

Cracked tooth syndrome in irradiated patients with head and neck cancer.

OBJECTIVES: The aim of this study was to assess the presence of enamel craze lines (ECLs), part of the spectrum of the so-called cracked tooth syndrome, on the surface of teeth irradiated in vivo. STUDY DESIGN: Forty teeth extracted from patients with head and neck cancer were paired, matched, and equally divided into 4 groups: noncarious irradiated (G1); noncarious control (G2); radiation-related caries (RRC) (G3), and carious control (G4). Samples were examined for ECL detection with a fiberoptic transillumination device and photographed, and ECL mean size, number, and patterns of topographic distribution in tooth crown were determined. Groups were compared accordingly: G1 versus G2; G3 versus G4. RESULTS: We analyzed 538 ECLs, of which 30.1% were found in noncarious irradiated teeth, 19.3% in noncarious controls, 27.6% in RRC, and 23% in carious controls. Non-carious irradiated teeth presented higher quantities of ECL than non-carious control (P < 0.05). Higher incidences of ECLs were identified in specific enamel topographies of anterior G1 and G3 samples (P <.05). There was no correlation between ECL size/numbers and radiation isodose delivery to teeth. CONCLUSIONS: Increased incidence of ECLs may indicate weakened enamel structure in irradiated teeth, and this may play a role in the onset and progression of RRC.

Locally advanced oral squamous cell carcinoma patients treated with photobiomodulation for prevention of oral mucositis: retrospective outcomes and safety analyses.

PURPOSE: The well-established clinical efficacy of photobiomodulation (PBM) therapy in management of oral mucositis (OM) is leading to increasing use in oncology care. This protection and enhanced repair of damage to mucosal tissue have led to the question of the potential effects of PBM therapy on pre-malignant and malignant cells. The purpose of this study was to examine the outcome of cancer therapy and incidence of tumor recurrence in locally advanced oral squamous cell carcinoma (OSCC) patients treated with PBM therapy for OM. METHODS: A retrospective clinical analysis of 152 advanced OSCC patients treated with prophylactic PBM therapy for radiotherapy-induced OM from January 2009 to December 2014 was conducted. RESULTS: Of the 152 OSCC patients treated with PBM therapy in this study, 19 (12.5%) had stage III and 133 (87.5%) had stage IV tumors. Of these, 52 (34.2%) received initial treatment with surgery followed by adjuvant radiotherapy, 94 (61.8%) with exclusive chemoradiation, and 6 (4%) with induction chemotherapy followed by surgery and radiotherapy. After a mean follow-up of 40.84 (± 11.71) months, the overall survival and disease-free survival rates were 46.7 and 51.8%, respectively. Forty-five (29.6%) patients developed local-regional recurrence, 10 (6.57%) patients developed distant relapse, and 19 (12.5%) developed new (second) primary tumors. CONCLUSIONS: Clinicopathological features and survival outcomes in the PBM-treated patients were similar to previously published data for conventional treatments in patients with advanced OSCC. In this study, prophylactic use of PBM therapy did not impact treatment outcomes of the primary cancer, recurrence or new primary tumors, or survival in advanced OSCC patients.

Radiation-related caries assessment through the International Caries Detection and Assessment System and the Post-Radiation Dental Index.

OBJECTIVE: Although radiation-related caries (RRC) are a well-known toxicity of head and neck radiotherapy, a clinical classification system for RRC has not yet been clinically validated. Therefore, the aim of this study was to assess whether the International Caries Detection and Assessment System (ICDAS) and the Post-Radiation Dental Index (PRDI) were viable methods for the assessment of RRC. STUDY DESIGN: Clinicopathologic data and intraoral digital photographs of 60 patients (833 teeth) affected by RRC were assessed and classified according to the ICDAS and PRDI criteria. RESULTS: A total of 814 (97.7%) teeth presented RRC lesions ranging from early stage to complete tooth destruction. Mean scores for the whole sample were 5 for ICDAS and 3 for PRDI, indicating that RRC were diagnosed predominately in late stages. ICDAS and PRDI criteria underestimate the clinical expressivity of RRC by not including the whole qualitative clinical spectrum of RRC, such as enamel cracks, delamination, dental crown amputation, surface color alterations, and atypical lesions topography (incisal/cuspal caries). CONCLUSIONS: ICDAS and PRDI may not be considered viable for the assessment of RRC. The development of a specific clinical classification system is urgently needed to help clinicians recognize the peculiar patterns of RRC, particularly in incipient cases.

Head and neck radiotherapy does not increase gelatinase (metalloproteinase-2 and -9) expression or activity in teeth irradiated in vivo.

OBJECTIVE: Recent studies suggested that head and neck radiotherapy increases active forms of matrix metalloproteinases (MMPs) in the dentin-enamel junction (DEJ), leading to enamel delamination and radiation-related caries. This study aimed to assess the expression and activity of the gelatinases MMP-2 and MMP-9 in the DEJ and dentin-pulp complex tissues of teeth irradiated in vivo. STUDY DESIGN: Thirty-six teeth were studied, including 19 irradiated and 17 non-irradiated controls. In situ zymography was used to investigate the gelatinolytic activity in the micromorphologic components of enamel, DEJ, dentin-pulp complex, and caries. Immunohistochemical analysis was conducted on the demineralized samples to assess MMP-2 and MMP-9 expression levels in the DEJ, dentin-pulp complex components, and caries. RESULTS: No statistically significant differences were detected between groups in gelatinolytic activity or in MMP-2 expression levels (P > .05). Odontoblast MMP-9 expression was reduced in the irradiated group (P = .02). CONCLUSIONS: The study rejected the hypothesis that MMP-2 and MMP-9 would be overexpressed or more activated in the DEJ and dentin-pulp complex of irradiated teeth. Direct effects of radiation should not be regarded as an independent factor for explaining radiation-related caries onset and progression.

A review of the epidemiology and treatment of Merkel cell carcinoma.

Merkel cell carcinoma is a very rare and aggressive neoplasm. Due to its rarity, therapeutic guidelines are not well established, especially for regionally advanced disease. Articles in English, French, Italian, Portuguese, and Spanish from the last 20 years were identified in MEDLINE and reviewed. The key word "Merkel" was used for the search, relevant articles were selected, and their references were examined. The most important articles related to epidemiology, genesis and treatment were reviewed. The incidence of Merkel cell carcinoma is increasing due to the advancing age of the population, higher rates of sun exposure and an increasing number of immunocompromised individuals. With regard to etiology, the recently described Merkel Cell polyomavirus is thought to play a role. Either local or regional surgical intervention remains the standard of care, but adjuvant radiotherapy or radiotherapy as a primary treatment have been discussed as reasonable therapeutic options. An update on this rare neoplasia is essential because of its increasing incidence and changing treatment options.

Impacto da nutrição enteral na toxicidade aguda e na continuidade do tratamento dos pacientes com tumores de cabeça e pescoço submetidos a radioterapia com intensidade modulada / Impact of enteral nutrition on acute toxicity and treatment continuity in head and neck cancer patients submitted to intensity-modulated radiotherapy

OBJETIVO: Analisar o impacto da terapia nutricional enteral na manutenção do peso corpóreo e na necessidade de replanejamento e/ou interrupção da radioterapia em pacientes com câncer de cabeça e pescoço submetidos a radioterapia de intensidade modulada (IMRT). MATERIAIS E MÉTODOS: Foram analisados, retrospectivamente, os pacientes submetidos a IMRT entre janeiro de 2005 e outubro de 2008, com a inclusão de 83 casos. RESULTADOS: A idade mediana foi de 58,6 anos. Em apenas em cinco pacientes (6 por cento) houve interrupção do tratamento, que variou de 4 a 18 dias, e em 19 casos (23 por cento) houve necessidade de replanejamento. A terapia nutricional enteral foi instituída antes do início da radioterapia em 16 pacientes (19 por cento). Perda de peso > 5 por cento ocorreu em 58 casos (70 por cento), sendo mais prevalente no grupo de pacientes em que a terapia nutricional enteral não foi instituída pré-radioterapia. Na comparação entre os grupos não houve diferença significativa na realização de replanejamento (25 por cento versus 21 por cento; p = 0,741) ou na ocorrência e duração da interrupção da radioterapia. CONCLUSÃO: A terapia nutricional enteral tem um claro ganho na manutenção do peso corporal, porém, não houve um benefício na realização da gastrostomia percutânea endoscópica ou da sonda nasoenteral em relação à interrupção e ao replanejamento da radioterapia.

OBJECTIVE: The present study was aimed at analyzing the impact of enteral nutrition on the maintenance of body weight and on the necessity of replanning and/or interruption of treatment of head and neck cancer patients undergoing intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Cases of patients submitted to IMRT in the period from January 2005 to October 2008 were retrospectively reviewed, and 83 of them were included in the study. RESULTS: Median patients' age was 58.6 years. Only five patients (6 percent) had their treatment interrupted for a period ranging from 4 to 18 days, and in 19 cases (23 percent) required replanning. Enteral nutrition was initiated before the radiotherapy in 16 patients (19 percent). Weight loss of > 5 percent was observed in 58 patients (70 percent), with a higher prevalence in the group of patients who had not received pre-radiotherapy enteral nutrition. No significant difference was observed between the groups regarding the necessity of radiotherapy replanning (25 percent versus 21 percent; p = 0.741) and necessity and duration of treatment interruption. CONCLUSION: Enteral nutrition is of a great value in the body weight maintenance, but no benefit was observed with the performance of endoscopic percutaneous gastrostomy as compared with radiotherapy interruption/replanning.

A review of the epidemiology and treatment of Merkel cell carcinoma

Merkel cell carcinoma is a very rare and aggressive neoplasm. Due to its rarity, therapeutic guidelines are not well established, especially for regionally advanced disease. Articles in English, French, Italian, Portuguese, and Spanish from the last 20 years were identified in MEDLINE and reviewed. The key word "Merkel" was used for the search, relevant articles were selected, and their references were examined. The most important articles related to epidemiology, genesis and treatment were reviewed. The incidence of Merkel cell carcinoma is increasing due to the advancing age of the population, higher rates of sun exposure and an increasing number of immunocompromised individuals. With regard to etiology, the recently described Merkel Cell polyomavirus is thought to play a role. Either local or regional surgical intervention remains the standard of care, but adjuvant radiotherapy or radiotherapy as a primary treatment have been discussed as reasonable therapeutic options. An update on this rare neoplasia is essential because of its increasing incidence and changing treatment options.

Treatment of resistant obsessive-compulsive disorder with ventral capsular/ventral striatal gamma capsulotomy: a pilot prospective study.

A subgroup of obsessive-compulsive disorder (OCD) patients remains refractory to conventional treatments. For them, a new stereotactic radiosurgery has been recently developed: the ventral capsular/ventral striatal (VC/VS) gamma capsulotomy. The authors aim to report efficacy and adverse events of VC/VS gamma capsulotomy. Five refractory OCD patients were selected. The authors assessed OCD, anxiety and depressive symptoms, and side effects pre- and postoperatively. Three patients (60%) met response criteria 48 months after surgery. Adverse effects were episodic and transient. Ventral capsular/ventral striatal gamma capsulotomy holds therapeutic promise, with few adverse effects.

Neoadjuvant chemoradiation therapy for soft tissue sarcomas of the extremities.

INTRODUCTION AND OBJECTIVE: Neoadjuvant and adjuvant therapies for soft tissue sarcomas of the extremities are still controversial. The aim of this study was to analyze the results of a protocol of neoadjuvant chemoradiation therapy for extremity sarcomas. METHODS: A retrospective analysis was carried out in a consecutive series of 49 adult patients with advanced extremity soft tissue sarcomas that could not be resected with adequate margins during the primary resection. All patients were treated with a protocol of preoperative radiation therapy at a total dose of 30 Gy, concomitant with doxorubicin (60 mg/m(2)) chemotherapy. The main endpoints assessed were local recurrence-free survival, metastasis-free survival and overall survival. The median follow-up time was 32.1 months. RESULTS: The five-year local recurrence-free survival, metastasis-free survival and overall survival rates were 81.5%, 46.7% and 58.3%, respectively. For high-grade tumors, the five-year metastasis-free and overall survival rates were only 36.3% and 41.2%, respectively. Severe wound complications were observed in 41.8% of the patients who underwent surgery. These complications precluded adjuvant chemotherapy in 73.7% (14/19) of the patients eligible to receive it. CONCLUSIONS: In this study, neoadjuvant chemoradiation therapy was associated with a good local control rate, but the distant relapse-free rate and overall survival rate were still poor. The high rate of wound complications modified the planning of adjuvant treatment in most patients.

Neoadjuvant chemoradiation therapy for soft tissue sarcomas of the extremities

INTRODUCTION AND OBJECTIVE: Neoadjuvant and adjuvant therapies for soft tissue sarcomas of the extremities are still controversial. The aim of this study was to analyze the results of a protocol of neoadjuvant chemoradiation therapy for extremity sarcomas. METHODS: A retrospective analysis was carried out in a consecutive series of 49 adult patients with advanced extremity soft tissue sarcomas that could not be resected with adequate margins during the primary resection. All patients were treated with a protocol of preoperative radiation therapy at a total dose of 30 Gy, concomitant with doxorubicin (60 mg/m²) chemotherapy. The main endpoints assessed were local recurrence-free survival, metastasis-free survival and overall survival. The median follow-up time was 32.1 months. RESULTS: The five-year local recurrence-free survival, metastasis-free survival and overall survival rates were 81.5 percent, 46.7 percent and 58.3 percent, respectively. For high-grade tumors, the five-year metastasis-free and overall survival rates were only 36.3 percent and 41.2 percent, respectively. Severe wound complications were observed in 41.8 percent of the patients who underwent surgery. These complications precluded adjuvant chemotherapy in 73.7 percent (14/19) of the patients eligible to receive it. CONCLUSIONS: In this study, neoadjuvant chemoradiation therapy was associated with a good local control rate, but the distant relapse-free rate and overall survival rate were still poor. The high rate of wound complications modified the planning of adjuvant treatment in most patients.