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Head and neck cancer (HNC) patients suffer from a range of health-related quality of life (HRQoL) issues, but little is known about their long-term HRQoL. This study explored associations between treatment group and HRQoL at least 5 years' post-diagnosis in HNC survivors. In an international cross-sectional study, HNC survivors completed the European Organization for Research and Treatment of Cancer (EORTC) quality of life core questionnaire (EORTC-QLQ-C30) and its HNC module (EORTC-QLQ-H&N35). Meaningful HRQoL differences were examined between five treatment groups: (a) surgery, (b) radiotherapy, (c) chemo-radiotherapy, (d) radiotherapy ± chemotherapy and neck dissection and (e) any other surgery (meaning any tumour surgery that is not a neck dissection) and radiotherapy ± chemotherapy. Twenty-six sites in 11 countries enrolled 1105 survivors. They had a median time since diagnosis of 8 years, a mean age of 66 years and 71% were male. After adjusting for age, sex, tumour site and UICC stage, there was evidence for meaningful differences (10 points or more) in HRQoL between treatment groups in seven domains (Fatigue, Mouth Pain, Swallowing, Senses, Opening Mouth, Dry Mouth and Sticky Saliva). Survivors who had single-modality treatment had better or equal HRQoL in every domain compared to survivors with multimodal treatment, with the largest differences for Dry Mouth and Sticky Saliva. For Global Quality of Life, Physical and Social Functioning, Constipation, Dyspnoea and Financial Difficulties, at least some treatment groups had better outcomes compared to a general population. Our data suggest that multimodal treatment is associated with worse HRQoL in the long-term compared to single modality.
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Neoplasias de Cabeza y Cuello , Xerostomía , Humanos , Masculino , Anciano , Femenino , Calidad de Vida , Estudios Transversales , Sobrevivientes , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Lung cancer in never-smoker (LCINS) patients accounts for 20% of lung cancer cases, and its biology remains poorly understood, particularly in genetically admixed populations. We elucidated the molecular profile of driver genes in Brazilian LCINS. METHODS: The mutational and gene fusion status of 119 lung adenocarcinomas from self-reported never-smoker patients, was assessed using targeted sequencing (NGS), nCounter, and immunohistochemistry. A panel of 46 ancestry-informative markers determined patients' genetic ancestry. RESULTS: The most frequently mutated gene was EGFR (49.6%), followed by TP53 (39.5%), ALK (12.6%), ERBB2 (7.6%), KRAS (5.9%), PIK3CA (1.7%), and less than 1% alterations in RET, NTRK1, MET∆ex14, PDGFRA, and BRAF. Except for TP53 and PIK3CA, all other alterations were mutually exclusive. Genetic ancestry analysis revealed a predominance of European (71.1%), and a higher African ancestry was associated with TP53 mutations. CONCLUSION: Brazilian LCINS exhibited a similar molecular profile to other populations, except the increased ALK and TP53 alterations. Importantly, 73% of these patients have actionable alterations that are suitable for targeted treatments.
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INTRODUCTION: TP53 is the most frequently mutated gene in lung tumors, but its prognostic role in admixed populations, such as Brazilians, remains unclear. In this study, we aimed to evaluate the frequency and clinicopathological impact of TP53 mutations in non-small cell lung cancer (NSCLC) patients in Brazil. METHODS: We analyzed 446 NSCLC patients from Barretos Cancer Hospital. TP53 mutational status was evaluated through targeted next-generation sequencing (NGS) and the variants were biologically classified as disruptive/nondisruptive and as truncating/nontruncating. We also assessed genetic ancestry using 46 ancestry-informative markers. Analysis of lung adenocarcinomas from the cBioportal dataset was performed. We further examined associations of TP53 mutations with patients' clinicopathological features. RESULTS: TP53 mutations were detected in 64.3% (n = 287/446) of NSCLC cases, with a prevalence of 60.4% (n = 221/366) in lung adenocarcinomas. TP53 mutations were associated with brain metastasis at diagnosis, tobacco consumption, and higher African ancestry. Disruptive and truncating mutations were associated with a younger age at diagnosis. Additionally, cBioportal dataset revealed that TP53 mutations were associated with younger age and Black skin color. Patients harboring disruptive/truncating TP53 mutations had worse overall survival than nondisruptive/nontruncating and wild-type patients. CONCLUSION: TP53 mutations are common in Brazilian lung adenocarcinomas, and their biological characterization as disruptive and truncating mutations is associated with African ancestry and shorter overall survival.
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Adenocarcinoma del Pulmón , Población Negra , Neoplasias Pulmonares , Proteína p53 Supresora de Tumor , Humanos , Adenocarcinoma del Pulmón/etnología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/mortalidad , Adenocarcinoma del Pulmón/patología , Población Negra/genética , Brasil/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/etnología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/etnología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Mutación , Prevalencia , Pronóstico , Proteína p53 Supresora de Tumor/genéticaRESUMEN
BACKGROUND: This study aims to evaluate whether hypofractionated radiotherapy (HYPOFRT) is a cost-effective strategy than conventional fractionated radiotherapy (CFRT) for early-stage glottic cancer (ESGC) in the Brazilian public and private health systems. METHODS: Adopting the perspective of the Brazilian public and private health system as the payer, a Markov model with a lifetime horizon was built to delineate the health states for a cohort of 65-year-old men after with ESGC treated with either HYPOFRT or CFRT. Probabilities of controlled disease, local failure, distant metastasis, and death and utilities scores were extracted from randomized clinical trials. Costs were based on the public and private health system reimbursement values. RESULTS: In the base case scenario, for both the public and private health systems, HYPOFRT dominated CFRT, being more effective and less costly, with a negative ICER of R$264.32 per quality-adjusted life-year (QALY) (public health system) and a negative ICER of R$2870.69/ QALY (private health system). The ICER was most sensitive to the probability of local failure, controlled disease, and salvage treatment costs. For the probabilistic sensitivity analysis, the cost-effectiveness acceptability curve indicates that there is a probability of 99.99% of HYPOFRT being cost-effective considering a willingness-to-pay threshold of R$2,000 ($905.39) per QALY (public sector) and willingness-to-pay threshold of R$16,000 ($7243.10) per QALY (private sector). The results were robust in deterministic and probabilistic sensitivity analyses. CONCLUSIONS: Considering a threshold of R$ 40,000 per QALY, HYPOFRT was cost-effective compared to CFRT for ESGC in the Brazilian public health system. The Net Monetary Benefit (NMB) is approximately 2,4 times (public health system) and 5,2 (private health system) higher for HYPOFRT than CFRT, which could open the opportunity of incorporating new technologies.
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Neoplasias Laríngeas , Masculino , Humanos , Anciano , Análisis Costo-Beneficio , Brasil/epidemiología , Neoplasias Laríngeas/radioterapia , Fraccionamiento de la Dosis de Radiación , Años de Vida Ajustados por Calidad de VidaRESUMEN
BACKGROUND: Targeted and immunotherapies are currently moving toward early-stage settings for patients with non-small cell lung cancer (NSCLC). Predictive biomarkers data are scarce in this scenario. We aimed to describe the frequency of EGFR mutations and PD-L1 expression levels in early-stage non-squamous patients with NSCLC from a large, single Brazilian oncology center. METHODS: We retrospectively evaluated patients with NSCLC diagnosed at an early-stage (IB to IIIA-AJCC seventh edition) at Barretos Cancer Hospital (n = 302). EGFR mutational status was assessed in FFPE tumor tissues using distinct methodologies (NGS, Cobas, or Sanger sequencing). PD-L1 expression was evaluated by immunohistochemistry (clone 22C3) and reported as Tumor Proportion Score (TPS), categorized as <1%, 1-49%, and ≥50%. We evaluated the association between EGFR mutational status and PD-L1 expression with sociodemographic and clinicopathological parameters by Fisher's test, qui-square test, and logistic regression. Survival analysis was assessed by the Kaplan-Meier method and Cox regression model. RESULTS: EGFR mutations were detected in 17.3% (n = 48) of cases and were associated with female sex, never smokers, and longer overall and event-free survival. PD-L1 positivity was observed in 36.7% (n = 69) of cases [TPS 1-49% n = 44(23.4%); TPS ≥50% n = 25(13.3%)]. PD-L1 positivity was associated with smoking, weight loss, and higher disease stages (IIB/IIIA). CONCLUSION: The frequencies of EGFR mutations and PD-L1 positivity were described for early-stage non-squamous patients with NSCLC. These results will be essential for guiding treatment strategies with the recent approvals of osimertinib and immunotherapy in the adjuvant setting.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Femenino , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Brasil/epidemiología , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Mutación , Receptores ErbB/genéticaRESUMEN
BACKGROUND: The evolution of radiotherapy over recent decades has reintroduced the hypofractionation for many tumor sites with similar outcomes to those of conventional fractionated radiotherapy. The use of hypofractionation in locally advanced head and neck cancer (LAHNC) has been already used, however, its use has been restricted to only a few countries. The aim of this trial was to evaluate the safety and feasibility of moderate hypofractionated radiotherapy (HYP-RT) with concomitant cisplatin (CDDP). METHODS: This single-arm trial was designed to evaluate the safety and feasibility of HYP-RT with concomitant CDDP in LAHNC. Stage III and IV patients withnonmetastatic disease were enrolled. Patients were submitted to intensity modulatedradiation therapy, which comprised 55 Gy/20 fractions to the gross tumor and44-48 Gy/20 fractions to the areas of subclinical disease. Concomitant CDDPconsisted of 4 weekly cycles of 35 mg/m2. The primary endpoints were the treatment completion rate and acute toxicity. RESULTS: Twenty patients were enrolled from January 2015 to September 2016, and 12 (60%) were classified as unresectable. All patients completed the total dose of radiotherapy, and 19 patients (95%) received at least 3 of 4 cycles of chemotherapy. The median overall treatment time was 29 days (27-34). Grade 4 toxicity was reported twice (1 fatigue and 1 lymphopenia). The rates of grade 3 dermatitis and mucositis were 30% and 40%, respectively, with spontaneous resolution. Nasogastric tubes were offered to 15 patients (75%) during treatment; 4 patients (20%) needed feeding tubes after 2 months, and only 1 patient needed a feeding tube after 12 months. CONCLUSION: HYP-RT with concomitant CDDP was considered feasible for LAHNC, and the rate of acute toxicity was comparable to that of standard concomitant chemoradiation. A feeding tube was necessary for most patients during treatment. Further investigation of this strategy is warranted. TRIAL REGISTRATION: ClinicalTrials, NCT03194061 . Registered 21 Jun 2017 - Retrospectively registered.
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Carcinoma de Células Escamosas , Quimioradioterapia/efectos adversos , Cisplatino , Neoplasias de Cabeza y Cuello , Anciano , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Femenino , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Hipofraccionamiento de la Dosis de RadiaciónRESUMEN
BACKGROUND: In 2012, the Brazilian government launched a radiotherapy (RT) expansion plan (PER-SUS) to install 100 linear accelerators. This study assesses the development of this program after eight years. METHODS: Official reports from the Ministry of Health (MoH) were reviewed. RT centres projects status, timeframes, and cost data (all converted to US dollars) were extracted. The time analysis was divided into seven phases, and for cost evaluation, there were five stages. The initial predicted project time (IPPT) and costs (estimated by the MoH) for each phase were compared between the 18 operational RT centres (able to treat patients) and 30 non-operational RT centres using t-tests, ANOVA, and the Mann-Whitney U. A p-value < 0.05 indicates statistical significance. RESULTS: A significant delay was observed when comparing the IPPT with the overall time to conclude each 48 RT centres project (p < 0.001), with considerable delays in the first five phases (p < 0.001 for all). Moreover, the median time to conclude the first 18 operational RT centres (77.4 months) was shorter compared with the 30 non-operational RT centres (94.0 months), p < 0.001. The total cost of 48 RT services was USD 82,84 millions (mi) with a significant difference in the per project median total cost between 18 operational RT centres, USD1,34 mi and 30 non-operational RT centres USD2,11 mi, p < 0.001. All phases had a higher cost when comparing 30 non-operational RT centres to 18 operational RT centres, p < 0.001. The median total cost for expanding existing RT centres was USD1,30 mi versus USD2,18 mi for new RT services, p < 0.0001. CONCLUSION: After eight years, the PER-SUS programs showed a substantial delay in most projects and their phases, with increased costs over time. POLICY SUMMARY: Our findings indicate a need to act to increase the success of this plan. This study may provide a benchmark for other developing countries trying to expand RT capacity.
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Gobierno , Humanos , Estudios Longitudinales , BrasilRESUMEN
Head and neck squamous cell carcinoma (HNSCC) is well known as a serious health problem worldwide, especially in low-income countries or those with limited resources, such as most countries in Latin America. International guidelines cannot always be applied to a population from a large region with specific conditions. This study established a Latin American guideline for care of patients with head and neck cancer and presented evidence of HNSCC management considering availability and oncologic benefit. A panel composed of 41 head and neck cancer experts systematically worked according to a modified Delphi process on (1) document compilation of evidence-based answers to different questions contextualized by resource availability and oncologic benefit regarding Latin America (region of limited resources and/or without access to all necessary health care system infrastructure), (2) revision of the answers and the classification of levels of evidence and degrees of recommendations of all recommendations, (3) validation of the consensus through two rounds of online surveys, and (4) manuscript composition. The consensus consists of 12 sections: Head and neck cancer staging, Histopathologic evaluation of head and neck cancer, Head and neck surgery-oral cavity, Clinical oncology-oral cavity, Head and neck surgery-oropharynx, Clinical oncology-oropharynx, Head and neck surgery-larynx, Head and neck surgery-larynx/hypopharynx, Clinical oncology-larynx/hypopharynx, Clinical oncology-recurrent and metastatic head and neck cancer, Head and neck surgery-reconstruction and rehabilitation, and Radiation therapy. The present consensus established 48 recommendations on HNSCC patient care considering the availability of resources and focusing on oncologic benefit. These recommendations could also be used to formulate strategies in other regions like Latin America countries.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , América Latina/epidemiología , Consenso , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/terapiaRESUMEN
NTRK1, 2, and 3 fusions are important therapeutic targets for NSCLC patients, but their prevalence in South American admixed populations needs to be better explored. NTRK fusion detection in small biopsies is a challenge, and distinct methodologies are used, such as RNA-based next-generation sequencing (NGS), immunohistochemistry, and RNA-based nCounter. This study aimed to evaluate the frequency and concordance of positive samples for NTRK fusions using a custom nCounter assay in a real-world scenario of a single institution in Brazil. Out of 147 NSCLC patients, 12 (8.2%) cases depicted pan-NTRK positivity by IHC. Due to the absence of biological material, RNA-based NGS and/or nCounter could be performed in six of the 12 IHC-positive cases (50%). We found one case exhibiting an NTRK1 fusion and another an NTRK3 gene fusion by both RNA-based NGS and nCounter techniques. Both NTRK fusions were detected in patients diagnosed with lung adenocarcinoma, with no history of tobacco consumption. Moreover, no concomitant EGFR, KRAS, and ALK gene alterations were detected in NTRK-positive patients. The concordance rate between IHC and RNA-based NGS was 33.4%, and between immunohistochemistry and nCounter was 40%. Our findings indicate that NTRK fusions in Brazilian NSCLC patients are relatively rare (1.3%), and RNA-based nCounter methodology is a suitable approach for NRTK fusion identification in small biopsies.
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Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptor trkA/genética , ARN , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Proteínas de Fusión Oncogénica/genéticaRESUMEN
The long-term problems of head and neck cancer survivors (HNCS) are not well known. In a cross-sectional international study aimed at exploring the long-term quality of life in this population, 1114 HNCS were asked to state their two most serious long-term effects. A clinician recorded the responses during face-to-face appointments. A list of 15 example problems was provided, but a free text field was also available. A total of 1033 survivors responded to the question. The most frequent problems were 'dry mouth' (DM) (n = 476; 46%), 'difficulty swallowing/eating' (DSE) (n = 408; 40%), 'hoarseness/difficulty speaking' (HDS) (n = 169; 16%), and 'pain in the head and neck' (PHN) (n = 142; 14%). A total of 5% reported no problems. Logistic regression adjusted for age, gender, treatment, and tumor stage and site showed increased odds of reporting DM and DSE for chemo-radiotherapy (CRT) alone compared to surgery alone (odds ratio (OR): 4.7, 95% confidence interval (CI): 2.5-9.0; OR: 2.1, CI: 1.1-3.9), but decreased odds for HDS and PHN (OR: 0.3, CI: 0.1-0.6; OR: 0.2, CI: 0.1-0.5). Survivors with UICC stage IV at diagnosis compared to stage I had increased odds of reporting HDS (OR: 1.9, CI: 1.2-3.0). Laryngeal cancer survivors had reduced odds compared to oropharynx cancer survivors of reporting DM (OR: 0.4, CI: 0.3-0.6) but increased odds of HDS (OR: 7.2, CI: 4.3-12.3). This study provides evidence of the serious long-term problems among HNCS.
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OBJECTIVES: Assess Once daily (OD) chemoradiation effectiveness for LS-SCLC compared with twice daily (BID) chemoradiation. METHODS AND MATERIALS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, eligible randomized clinical trials (RCT) comparing OD and BID were identified on electronic databases. A meta-analysis was performed to compare overall survival (OS), progression-free survival (PFS), and toxicity. A metaregression analysis was conducted to explore the influence of fractionation, biological effective dose (BED), the proportion of patients treated with prophylactic cranial irradiation (PCI), elective nodal irradiation (ENI), and the start of radiotherapy (week 1 or week 4). RESULTS: Five RCTs with a total of 1941 patients (OD vs. BID) were included. The relative risk (RR) for OS and PFS was 0.97 (CI95% 0.8-1.1, p = 0.731) and 0.90 (CI95% 0.7-1.1, p = 0.20) at 3-years. In the metaregression analysis, hypofractionated radiotherapy schedules were associated with an improvement in overall survival (p = 0.03). The start of radiotherapy (W1 or W4), BED, and ENI had no significant effect on OS and PFS. The complete response rate partial response and overall response rate for BID vs OD were 40% vs. 33% (p = 0.97), 50% vs. 57% (p = 0.94), and 89% vs. 93% (p = 0.99). The rate of completed planned RT 96% vs. 94% (p = 0.66), and the % of ≥4 chemotherapy cycles received 74% vs. 74% (p = 0.99), did not differ between OD and BID. The local and distant failure rates were not significantly different between OD and BID 40% vs. 33% (p = 0.88) and 36% vs. 36% (p = 0.99). No difference in grade 2 or grade 3 pneumonitis and esophagitis was observed among the groups (p = NS). CONCLUSION: For LS-SCLC, OD conventional chemoradiation results in similar outcomes to BID chemoradiation. In contrast, hypofractionated radiotherapy was associated with a better OS and PFS than BID. Additional randomized phase III trials exploring hypofractionation with systemic therapy are warranted to validate our findings.
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Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/efectos adversos , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/radioterapiaRESUMEN
Background: The Brazilian public health system does not pay for the use of Stereotactic body radiotherapy (SBRT) due to its costs and the absence of cost-effectiveness analysis showing its benefit. The present study aims to evaluate whether the SBRT is a more cost-effective strategy than the conventional fractionated radiotherapy (CFRT) for surgically ineligible stage I non-small cell lung cancer (NSCLC) in the Brazilian public health system. Methods: Adopting the perspective of the Brazilian Unified Healthcare System (SUS) as the payer, a Markov model with a lifetime horizon was built to delineate the health states for a cohort of 75-years-old men with medically inoperable NSCLC after treatment with SBRT or CFRT. Transition probabilities and health states utilities were adapted from the literature. Costs were based on the public health system reimbursement values and simulated in the private sector. Findings: The SBRT strategy results in more quality-adjusted life-year (QALYs) and costs with an incremental cost-effectiveness ratio (ICER) of R$ 164.86 (U$ 65.16) per QALY and R$ 105 (U$ 41.50) per life-year gained (LYG). This strategy was cost-effective, considering a willingness-to-pay of R$ 25,000 (U$ 9,881.42) per QALY. The net monetary benefit (NMB) was approximately twice higher. The outcomes were confirmed with 92% of accuracy in the probabilistic sensitivity analysis. Interpretation: Using a threshold of R$25,000 per QALY, SBRT was more cost-effective than CFRT for NSCLC in a public health system of an upper-middle-income country. SBRT generates higher NMB than CFRT, which could open the opportunity to incorporate new technologies. Funding: Varian Medical Systems.
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ERBB2 exon 20 insertions may impact the clinical management of lung cancer patients. However, the frequency of ERBB2 exon 20 insertions in lung cancer patients in Brazil is scarce. Here, we analyzed 722 Brazilian non-small cell lung cancer (NSCLC) patients from Barretos Cancer Hospital that were indicated to require routine lung cancer molecular testing. ERBB2 exon 20 insertions were evaluated by a targeted panel using next-generation sequencing (NGS). Clinicopathological and molecular data were collected from patient medical records. Among the 722 NSCLC patients, 85.2% had lung adenocarcinomas, 53.9% were male, 66.8% were quitter or current smokers, and 63.2% were diagnosed at an advanced stage of the disease. We identified 0.8% (6/722) of patients who harbored the insertion p.(Tyr772_Ala775dup) at exon 20 of the ERBB2 gene. All ERBB2 mutated patients were diagnosed with lung adenocarcinoma, were never smokers, and wild-type for EGFR, KRAS, and ALK hotspot alterations. Less than 1% of Brazilian NSCLC patients harbor ERBB2 exon 20 insertions, yet they could benefit in future from the new drugs in development.
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Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Masculino , Femenino , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Brasil , Mutación , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Exones , Receptor ErbB-2/genéticaRESUMEN
OBJECTIVES: To provide an overview of the achievements and future research with stereotactic body radiotherapy (SBRT) in prostate cancer. METHODS: SBRT publications for prostate cancer were retrieved from the Web of Science and Dimension database. Bibliometric analyses were performed using VOSviewer and Prism graph. Analysis of variance test was used to compare the publication, citation, and the mean citation between specialty journals. Network maps were produced to identify authors' and countries' collaboration clusters. RESULTS: Between 2006 and 2020, 574 publications fulfilling the inclusion criteria were identified, and a significant growth trend in publication (P<0.0001) and citation (P=0.001) number was recognized over the period. The United States was the most productive country with 253 (44.2%) articles. The RED Journal had the highest number of publications (14%) and citations (19%). Urology journals published (P=0.01) and cited significantly less than radiation oncology journals (P=0.01). All open access and non-open access number of publications increased over time, with a significant difference between non-open access and open access journals (P<0.0001). Two author clusters were identified, in the United States with the collaboration of Canadian and British authors, and in Italy with the participation of European authors. CONCLUSION: The number of publications and citations on SBRT for prostate cancer has grown linearly in the last decades. The United States is the leading country in this research field, and the use of SBRT in oligometastatic disease, reirradiation, and salvage seems to be hot topics in this research field.
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Bibliometría , Neoplasias de la Próstata/radioterapia , Radiocirugia , Humanos , MasculinoRESUMEN
Schistosoma mansoni ATP diphosphohydrolase isoforms and potato apyrase share conserved epitopes. By enzyme-linked immunosorbent assays, elevated levels of IgM, IgG2a and IgG1 antibody reactivity against potato apyrase were observed in S. mansoni-infected BALB/c mice during the acute phase of infection, while only IgM and IgG1 antibody reactivity levels maintained elevated during the chronic phase of infection. Antibody reactivity against potato apyrase was monitored over an 11-month period in chronically-infected mice treated with oxamniquine. Eleven months later, the level of seropositive IgM decreased significantly (approximately 30%) compared to the level found in untreated, infected mice. The level of seropositive IgG1 decreased significantly four months after treatment (MAT) (61%) and remained at this level even after 11 months. The IgG2a reactivity against potato apyrase, although unchanged during chronic phase to 11 MAT, appeared elevated again in re-infected mice suggesting a response similar to that found during the acute phase. BALB/c mouse polyclonal anti-potato apyrase IgG reacted with soluble egg antigens probably due to the recognition of parasite ATP diphosphohydrolase. This study, for the first time, showed that the IgG2a antibody from S. mansoni-infected BALB mice cross-reacts with potato apyrase and the level of IgG2a in infected mice differentiates disease phases. The results also suggest that different conserved-epitopes contribute to the immune response in schistosomiasis.
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Anticuerpos Antihelmínticos/inmunología , Antígenos Helmínticos/inmunología , Apirasa/inmunología , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/inmunología , Solanum tuberosum/enzimología , Enfermedad Aguda , Animales , Antihelmínticos/uso terapéutico , Enfermedad Crónica , Reacciones Cruzadas , Ensayo de Inmunoadsorción Enzimática , Femenino , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Ratones , Ratones Endogámicos BALB C , Oxamniquina/uso terapéutico , Esquistosomiasis mansoni/tratamiento farmacológicoRESUMEN
The effects of the alkylaminoalkanethiosulfuric acids (AAATs), new schistosomicidal drugs, on Schistosoma mansoni ATP diphosphohydrolase isoforms, members of the NTPDase family, were analyzed. Pre-incubation of worm adult tegument with AAATs derivatives, with small apolar alkyl groups and an apolar alkane portion of 6 or 8 carbon atoms linked to the amino group, inhibited ATPase activity with a Ki 100-1000 microM. Little inhibition (20%) was observed when ADP was the substrate. The 2-[(tert-butyl)amino]-1-ethanethiosulfuric acid (100 microM) which has a less lipophilic structure, inhibited 28% ATPase and 12% ADPase activities, suggesting that the lipophilicity, although important, is not the only requisite for enzyme activity inhibition. The N-(sec-butyl)-2-bromo-1-octanaminium bromide, which contains a bromide atom instead of thiosulphate, inhibited <10% of the enzyme activity, suggesting the involvement of cysteine residue(s) from S. mansoni ATP diphosphohydrolase isoforms in a mixed disulfide formation. Treatment of parasite tegument with 5 mM iodoacetamide or 1 mM dithiothreitol protected ATPase and ADPase activities against inhibition by AAATs, corroborating the participation of disulfide interchange in the AAATs mechanism. Since S. mansoni ATP diphosphohydrolase isoforms and potato apyrase share structural similarities, the latter enzyme was also tested. ADPase activity from potato apyrase was inhibited by 55%, showing a higher sensitivity to 1 mM AAATs than that shown by ADPase activity from the tegument, while the ATPase activities from both samples showed similar inhibition levels. Furthermore, sulfhydryl reagents protected potato apyrase activity. Therefore, it is possible that both soluble S. mansoni ATP diphosphohydrolase and membrane-associated isoforms are targets for the AAATs.
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Apirasa/antagonistas & inhibidores , Schistosoma mansoni/efectos de los fármacos , Esquistosomicidas/farmacología , Ésteres del Ácido Sulfúrico/farmacología , Adenosina Trifosfatasas/metabolismo , Animales , Apirasa/metabolismo , Ditiotreitol/farmacología , Glutatión/farmacología , Yodoacetamida/farmacología , Masculino , Ratones , Schistosoma mansoni/enzimología , Solanum tuberosum/enzimología , Reactivos de Sulfhidrilo/farmacologíaRESUMEN
Introduction: The challenge of modern radiotherapy (RT) in breast cancer is to maintain its satisfactory oncological results, adapting to oncoplastic surgery and avoiding possible cosmetic damage. Considering that the breast prosthesis is not a target volume in RT planning, this study sought to analyze the effect of this volume on the coverage of the clinical target volume (CTV) of the breast. Methods: We performed a retrospective analysis of plans in 48 patients who submitted to RT in the first half of 2014. Two volumes were measured, such as breast CTV (breast tissue with the prosthesis) and real CTV (breast tissue excluding the prosthesis). The D95% values (dose that covers 95% of the volume) for each of them were verified and related to the volume of each one as well as the volume of breast prosthesis. Results: The analysis of the CTVs showed a significant difference between the mean volumes for the real CTV and breast CTV. While performing the CTV coverage, including the prosthesis, there is a perception that the dose covered 95% of the volume. Nevertheless, the analysis of the same plan after prosthesis volume exclusion revealed a difficulty in covering 95% of the breast tissue volume, indicating the interference of the prosthesis in therapy planning. Considering the dosimetric aspects, there were patients with real CTV values below the ideal dose of 47.5 Gy, after exclusion of implant volume. Conclusions: Our data reflected the volume of the prosthesis as an important variable that should be considered when planning adjuvant RT.
RESUMEN
BACKGROUND: The purpose of this phase II trial was to evaluate the tolerability, safety, and efficacy of a non-5-fluorouracil (5-FU)-based induction chemotherapy followed by chemoradiotherapy (CRT) for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). METHODS: Sixty patients with stage III to IV HNSCC were treated with induction paclitaxel and cisplatin (TP; paclitaxel 175 mg/m(2) and cisplatin 80 mg/m(2) , 3 cycles) followed by CRT (cisplatin 100 mg/m(2) ; D1, 22, and 43 of radiotherapy). RESULTS: Fifty-six patients (93.3%) completed 3 cycles of induction TP (no treatment-related deaths), 52 (86.7%) completed definitive CRT per protocol (adverse event [AE] grade ≥2 in 53.3%). The overall response rate after induction TP was 82.5% for patients with resectable disease and 55.5% for unresectable disease (p = .023), and complete response (CR) rate after CRT was 70.0% for patients with resectable disease and 30.0% for unresectable disease (p = .005). CONCLUSION: Induction TP followed by cisplatin based-CRT was well-tolerated, safe, and had high overall response rate in selected patients with locally advanced HNSCC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E970-E980, 2016.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Cisplatino/uso terapéutico , Neoplasias de Cabeza y Cuello/terapia , Paclitaxel/uso terapéutico , Adulto , Anciano , Femenino , Fluorouracilo , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
AIMS: The nuclear factor κ B (NF-κB) family comprises transcription factors that promote the development and progression of cancer. The NF-κB pathway is induced by radiation therapy and may be related to tumour radioresistance. The aim of this study was to evaluate the expression of NF-κB as a predictor of the response to radiotherapy and its value as a prognostic marker. METHODS: A retrospective analysis was performed in a series of 32 individuals with stage IB2 and IIB cervical cancer who underwent radiotherapy, followed by radical hysterectomy, from January 1992 to June 2001. NF-κB-p65 and NF-κB-p50 expression was examined by immunohistochemistry in biopsies from all patients before radiotherapy and in 12 patients with residual tumours after radiotherapy. RESULTS: 16 (50%) patients had residual disease after radical hysterectomy. The median follow-up time was 73.5 months, and the 5-year overall survival was 66.5%. Before radiotherapy, cytoplasmic expression of NF-κB-p65 and NF-κB-p50 was noted in 91% and 97% of cases, respectively, versus 59% of cases with nuclear expression of these subunits. Cytoplasmic expression of NF-κB-p65 and NF-κB-p50 in the residual tumours after radiotherapy was observed in 50% of cases; 75% of cases with residual tumours had nuclear expression of NF-κB-p50 versus none with NF-κB-p65. NF-κB-p65 and NF-κB-p50 did not correlate with the risk of residual tumours after radiotherapy or recurrence or death. CONCLUSIONS: These data suggest that NF-κB does not predict the response to radiotherapy and does not correlate with poor outcomes in advanced cervical cancer.
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Biomarcadores de Tumor/metabolismo , Histerectomía , FN-kappa B/metabolismo , Radioterapia , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Cuello del Útero/metabolismo , Cuello del Útero/patología , Terapia Combinada , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias del Cuello Uterino/patologíaRESUMEN
PURPOSE: To report the outcomes and toxicity of high dose rate brachytherapy as a boost for localized prostate cancer. MATERIALS AND METHODS: Between 1997 and 2000, the medical records of 131 patients with prostate adenocarcinoma who were treated with external beam radiation therapy and high dose rate brachytherapy, were retrospectively analyzed. Furthermore, 55% of the patients received neoadjuvant/concurrent or adjuvant androgen deprivation therapy. Patients were stratified into 2 groups. Group 1 included 65 patients with Gleason score 7, pretreatment prostate specific antigen (PSA) between 10 and 20 ng/mL, and clinical stage T2b. Group 2 included 66 patients with Gleason score between 8 and 10, PSA greater than 20 ng/mL, and clinical stage greater than T2b. RESULTS: At a median follow-up of 62.8 months, the 5-year biochemical control (BC) rate, as defined by the American Society for Therapeutic Radiology and Oncology Phoenix Consensus panel statement, was 81% and overall survival was 91%. BC in Groups 1 and 2 were 87% and 71%, respectively. On univariate analysis risk group, pretreatment PSA and age were significant predictors of BC. However, on multivariate analysis only pretreatment PSA was significant. Using the Radiation therapist oncology group criteria, there were 2 (1.5%) cases of grade 3 acute urinary toxicity. Regarding late side effects (n = 5), 4% of patients had grade 3 genitourinary toxicity and no grade 4 complication was observed. CONCLUSIONS: External beam radiation therapy and high dose rate brachytherapy for prostate cancer resulted in excellent BC, and overall survival with minimal severe, acute, or late complications.