Health of children born to childhood cancer survivors: Participant characteristics and methods of the Multicenter Offspring Study

IntroductionResearch on childhood cancer survivor offspring has been limited to genetic disease occurrence, malformations or non-hereditary cancers. However, previous surveys indicated that survivors harbor fears about their (prospective) children's overall health. Our Multicenter Offspring Study examined extensive health aspects in children born to survivors and their siblings providing comprehensive information to be used in patient counseling to elucidate and alleviate existing concerns.MethodsUsing a specifically designed questionnaire, childhood cancer survivors and their siblings were surveyed on their offspring’s health (Supplementary material). Recruitment strategies depended on local infrastructures and standards of participating centers, including registry-based and direct approaches. Group differences were tested non-parametrically and effect sizes were calculated.ResultsIn total, 1126 survivors reported on 1780 offspring and 271 siblings reported on 441 offspring. Response rates ranged from 32.1% (Czech Republic) to 85.0% (Austria). Respondents were more likely to be female (p = .007), older at time of survey (p < .001), diagnosed 1980–1999 (p < .001) and treated with chemotherapy (p < .001). Compared to siblings, survivors were younger at time of survey (35 years vs. 39 years, p < .001) and at first birth (29 years vs. 30 years, p < .001). Survivor and sibling offspring only differed in terms of age at survey (6.3 years vs. 8.9 years, p < .001).ConclusionThe Multicenter Offspring Study investigates a wide variety of health aspects in offspring born to survivors and their siblings in five European countries. Our study cohorts form a solid basis for future analyses; yet, certain limitations, due to differences in approach among participating centers, must be considered when interpreting findings.     

Late effects of childhood cancer treatment in long-term survivors diagnosed before the age of 3 years – A multicenter,nationwide study

BackgroundThe effect of age on the incidence of late sequelae that occur after anticancer treatment in childhood is still not fully elucidated. In this multicenter study of long-term survivors diagnosed before age of three, we investigated the prevalence of late effects many years after treatment.MethodsThe study group (n = 561) was selected from the Polish National Childhood Cancer Survivors Registry (n = 1761) created in 2007. A survivor was defined as an individual who has survived at least 5 years after completion of anticancer treatment. All children were diagnosed between 1991 and 2016, mean age at diagnosis was 1.82 years (range 0.03–2.99) and median follow up time - 9.85 years (range 5.0–23.6). They were treated in accordance with international protocols approved by the Polish Pediatric Leukemia and Lymphoma Group and Polish Solid Tumor Group. Chemotherapy alone was used in 192 (34.2%), chemotherapy and radiotherapy – 56 (10%), chemotherapy and surgery – 176 (31.4%), chemotherapy, radiotherapy, and surgery – 79 (14.1%), and surgery alone in 58 patients (10.3%).ResultsOf all patients enrolled to the study, only 94 (16.8%) had normal function of all organs. Seventy-six (13.5%) children developed dysfunction in one organ, another 83 (14.8%) had symptoms or complaints suggestive of dysfunction in two organs or systems, 88 (15.7%) had abnormalities in three organs, and 220 (39.2%) had at least four or more dysfunctions. In the entire study group, dysfunctions most frequently (> 20% of cases) involved the following organs/systems: circulatory – 21.8%, urinary – 30.8%, gastrointestinal – 20.8%, immune – 23.5%, vision – 20.7%, hearing – 21.8%, and oral and masticatory dysfunction – 26.9%. We did not find any significant differences in organ dysfunction between children diagnosed under the age of 1 and those diagnosed at the age of 1–3, except for a lower incidence of thyroid abnormalities (p = 0.007) and the higher prevalence of liver dysfunction in youngest patients. In the subset with longer follow-up period (> 10 years) more frequent thyroid abnormalities (p = 0.019), male (p = 0.002) and female (p = 0.026) gonads dysfunction, as well as musculoskeletal problems (p < 0.001) were observed. Among subjects who received radiotherapy compared to those who did not, short stature (p = 0.001), and dysfunction of the following systems/organs – circulatory (p = 0.049), urinary (p = 0.012), thyroid gland (p < 0.0001), nervous (p = 0.007), immunological (p = 0.002), liver (p = 0.03), dental or chewing difficulties (p = 0.001), hearing (p = 0.001) and musculoskeletal (p = 0.026) were more frequently reported. When multimodal therapy was applied (chemotherapy, radiotherapy, and surgery) a higher incidence of short stature (p = 0.007), urinary system disorders (p < 0.0001), thyroid dysfunction (p < 0.0001), hearing loss (p < 0.0001), and skin problems (p = 0.031) were observed.ConclusionThis study confirms that radiotherapy and some specific toxicity of cytostatics are the most important factors affecting organ function. Apart from a higher incidence of liver dysfunction in the youngest patients, there were no significant differences in organ and system toxicities between children diagnosed under the age of 1 and those diagnosed at the age of 1–3. We have shown that this group requires systematic, careful and long-term follow-up.     

Long-term survival of patients with prostate cancer in Martinique: Results of a population-based study

BackgroundMartinique has one of the highest incidences of prostate cancer (PCa) worldwide. We analysed overall survival (OS) among patients with PCa in Martinique, using data from a population-based cancer registry between 2005 and 2014.MethodsThe log-rank test was used to assess the statistical differences between survival curves according to age at diagnosis, risk of disease progression including Gleason score, stage at diagnosis and Prostate Specific Antigen (PSA). A multivariable Cox model was constructed to identify independent prognostic factors for OS.ResultsA total of 5045 patients were included with a mean age at diagnosis of 68.1±9.0 years [36.0 – 98.0 years]. Clinical stage was analysed in 4999 (99.1% of overall), 19.5% were at low risk, 34.7% intermediate and 36.9% at high risk. In our study, 8.9% of patients with available stage at diagnosis, were regional/metastatic cancers. Median PSA level at diagnosis was 10.4 ng/mL. High-risk PCa was more frequent in patients aged 65-74 and ≥75 years as compared to those aged <65 years (36.6% and 48.8% versus 28.7% respectively; p<0.0001). One-year OS was 96.3%, 5-year OS was 83.4 and 10-year OS was 65.0%. Median survival was not reached in the whole cohort. High-risk PCa (HR=2.32; p<0.0001), regional/metastatic stage (HR= 9.51; p<0.0001) and older age (65-74 and ≥75 years - respectively HR=1.70; and HR=3.38), were independent prognostic factors for OS (p<0.0001).ConclusionThis study provides long term data that may be useful in making cancer management decisions for patients with PCa in Martinique.     

Regional variations in age at diagnosis and overall survival among patients with chronic myeloid leukemia from low and middle income countries

IntroductionThe epidemiology of chronic myeloid leukemia (CML) in low and middle income countries is limited. As a result, we analyzed a contemporary cohort of patients from low and middle income countries treated with Imatinib through The Glivec^® International Patient Assistance Program (GIPAP).MethodsGeneralized estimating equations (GEE) and Kaplan–Meier estimation were utilized to test for regional variations in age at diagnosis and overall survival among 33,985 patients from 94 countries.ResultsPatients participated from Asia (79.2%), Africa (9.4%), Latin America (8.7%) and Southern/Eastern Europe (2.5%). Sixty-one (61.2%) percent were male. Mean age at diagnosis was 38.5 years (9.4% <20 years and only 4.7% ≥65 years). Using GEE, Asians were youngest (38.3 years), followed by Africans (39.5 years), Southern/Eastern Europeans (41.1 years) and Latin Americans (41.3 years; p < 0.0001). Diagnoses were predominately in chronic stage (78.3%). In 2002, 85.2% of patients had a delay in treatment >1 year; decreasing to 15.5% in 2010 (p < 0.0001). The 3-year overall survival probability was 89.4% (95% CI, 88.9–89.9). In multivariate analysis, risk of death increased among patients 65 years or older at diagnosis (p < 0.0001), time from diagnosis to treatment >1-year (p < 0.0001), diagnoses in the accelerated or blast crisis (p < 0.0001), initial dose of Imatinib >400 mg (p < 0.0001) and among Latin Americans and Africans (p < 0.0001).ConclusionThe GIPAP cohort is the largest series of patients with CML described from low and middle income countries. Differences in age at diagnosis and overall survival exist within and between regions. Additional epidemiological studies should be conducted to assess for possible environmental factors associated with the earlier age at onset.     

The impact of health insurance affiliation and socioeconomic status on cervical cancer survival in Bucaramanga,Colombia

Cervical cancer is still an important cause of death in countries like Colombia. We aimed to determine whether socioeconomic status of residential address (SES) and type of health insurance affiliation (HIA) might be associated with cervical cancer survival among women in Bucaramanga, Colombia. All patients residing in the Bucaramanga Metropolitan Area diagnosed with invasive cervical cancer (ICD-0–3 codes C53.X) between 2008 and 2016 (n = 725) were identified through the population-based cancer registry, with 700 women having follow-up data for >5 years (date of study closure: Dec 31, 2021), yielding an overall 5-year survival estimate (95 % CI) of 56.4 % (52.7 – 60.0 %). KM estimates of 5-year overall survival were obtained to assess differences in cervical cancer survival by SES and HIA. Multivariable Cox-proportional hazards modeling was also conducted, including interaction effects between SES and HIA. Five-year overall survival was lower when comparing low vs. high SES (41.9 % vs 57.9 %, p < 0.0001) and subsidized vs. contributive HIA (45.1 % vs 63.0 %, p < 0.0001). Multivariable Cox modeling showed increased hazard ratios (HR) of death for low vs. high SES (HR = 1.78; 95 % CI = 1.18–2.70) and subsidized vs. contributive HIA (HR = 1.44; 95 % CI = 1.13–1.83). The greatest disparity in HR was among women of low SES affiliated to subsidized HIA (vs. contributive HIA and high SES) (HR=2.53; 95 % CI = 1.62–3.97). Despite Colombia’s universal healthcare system, important disparities in cervical cancer survival by health insurance affiliation and socioeconomic status remain.     

Evaluation of disparities in maintaining healthy lifestyle behaviors among female cancer survivors by race/ethnicity and US nativity

BackgroundThere are well-known racial/ethnic disparities in maintaining healthy lifestyle behaviors throughout cancer survivorship among US-born women. Less is known about these associations among women born outside the US, as these women may experience disparities in survivorship care due to the lack of access to culturally appropriate health services. We evaluated disparities in the associations between race/ethnicity and US nativity and the likelihood of meeting recommendations for maintaining a healthy lifestyle during cancer survivorship.Methods2044 female cancer survivors contributed data from the National Health and Nutrition Examination Survey (NHANES) (1999–2018). Adjusted odds ratios (aORs) and 95 % confidence intervals (CIs) were calculated with multivariable logistic regression models to measure the association between independent variables (race/ethnicity, US nativity, length of time in the US) and outcomes (obesity, meeting weekly physical activity (PA) recommendations, smoking history, alcoholic drinks/day) overall and by comorbidity.ResultsMost survivors were breast cancer survivors (27.6 %), non-Hispanic white (64.2 %), and US native (84.5 %). Compared to US native survivors, foreign-born survivors were less likely (aOR, 0.30, 95 % CI, 0.10–0.87) to not meet PA recommendations, while foreign-born survivors living in the US ≥ 15 years were 2.30 times more likely (95 % CI, 1.12–4.73) to not meet PA recommendations. Having at least one comorbidity modified (p-interaction< 0.05) the relationships between US nativity and length of time in the US.ConclusionOur findings provide new evidence for disparities in maintaining healthy lifestyle behaviors among female cancer survivors and can help inform lifestyle interventions for female cancer survivors from different racial/ethnic backgrounds.     

Características basales de los pacientes nonagenarios ingresados por fracaso renal agudo en comparación con otros grupos etarios

BackgroundThe increase in life expectancy leads to higher hospitalisation rates in elderly patients. The aim of this work is to study the characteristics of the population over 90 years of age that are admitted due to acute kidney injury (AKI).Material and methodsA cross-sectional study was conducted that included all patients admitted to hospital with AKI in the years 2013 and 2014. Epidemiological characteristics, comorbidity, medication and baseline analytical data were collected, and a comparison was made between patients with age over 90 years-old and the others.ResultsA total of 1733 patients were included, of whom 264 (15%) were over 90 years-old. A significantly higher proportion of these patients were women. The most frequent cause of AKI in patients older than 90 years was functional (81%) (p < 0.001 compared to other age groups). The main cause of hospital admission was infection. In the group of over 90 years of age, a higher prevalence was found for arterial hypertension (p = 0.005), chronic kidney disease (p = 0.014), congestive heart failure (p = 0.006), and cognitive impairment (p < 0.0001). The baseline glomerular filtration rate by CKD-EPI was lower in the group of patients older than 90 years (p < 0.0001). Patients under 90 years admitted to hospital due to AKI, had a higher prevalence of diabetes mellitus (p < 0.001), dyslipidaemia (p < 0.001), history of neoplasia (p < 0.001), and a higher Barthel index (p < 0.0001).ConclusionsNonagenarians admitted due to AKI have functional aetiology as the most common factor. These patients have a higher prevalence of hypertension, heart failure, chronic kidney disease, low functional status, and more cognitive impairment.     

Association between cardiovascular disease and a history of cancer in patients with chest pain on the fast track outpatient clinic

Background

The purpose of this study is to investigate the prevalence of a history of malignancy in patients with chest pain who were referred for computed tomography angiography as well as the long-term survival and cardiovascular outcomes, including coronary artery disease (CAD) and coronary artery calcium (CAC) percentiles of cancer survivors. These data are relevant since it is unknown how cancer survivors, who underwent cardio-toxic therapies, should be monitored.

Methods

We analysed all patients with chest pain, who came to the outpatient clinic and underwent computed tomography angiography. The primary study endpoint was long-term survival. The secondary endpoints included CAD on computed tomography angiogram (CTA), CAC percentiles, suspected and confirmed malignancy on CTA, and other accidental findings on CTA.

Results

Of all 1,892 patients included in the analyses, 133 (7%) had a history of malignancy and 1,759 (93%) did not. Mortality rates were higher for the cancer survivors (6.5% vs 20.9% after ten years, p < 0.001). The multivariable Cox regression model also showed higher mortality for cancer survivors after ten years (adjusted hazard ratio 2.48 [95% confidence interval: 1.58–3.90]). CAD did not differ between both groups. CAC percentiles were higher in cancer survivors (p = 0.037). Cancer survivors had more suspected malignancies (3.8% vs 0.5%; p = 0.001) and also more confirmed malignancies on CTA (3.0% vs 0.1%; p < 0.001).

Conclusions

Cancer survivors have higher mortality rates, no difference in CAD on CTA, higher CAC percentiles and more often malignancy on CTA compared with patients without a cancer history.

     

Time dependent decline of neutralizing antibody titers in COVID-19 patients from Pune,India and evidence of reinfection

PurposeTo assess modulation of neutralizing antibody titers in COVID-19 patients and understand association of variables such as age, presence of comorbidity, BMI and gender with antibody titers.MethodsPatients (n = 100) diagnosed from 20th March 2020 to 17th August 2020 and treated at two large hospitals from Pune, India were included and followed up (clinical and serologic) for varied periods. IgG-anti-SARS-CoV-2 (Spike protein-based ELISA) and neutralizing antibody titers (NAb, PRNT) were determined in all the samples.ResultsOf the 100 patients enrolled initially (median 60 days of diagnosis), follow up samples were collected from 70 patients (median 106 days of diagnosis). Overall, NAb titers reduced significantly (p < 0.001) and as early as 3–4 months. During two visits, 20% and 7.1% patients reported some symptoms. At the first visit, NAb titers were higher in patients with severe disease (p < 0.001), comorbidities (p < 0.005), age <50 years (p < 0.05) and male gender (p < 0.05). Multivariate analysis identified older age (p < 0.001), duration post-diagnosis and female gender as independent variables influencing NAb titers (negative correlation, p < 0.05). During the follow-up, reduction in NAb titers was recorded in patients with comorbidity (p < 0.05), mild disease (p < 0.05), age <50 years (p < 0.05), higher BMI (p < 0.05) and male gender (p < 0.001). Serology identified six cases of asymptomatic reinfections.ConclusionsDecline of NAb titers was associated with age <50 years, mild disease, comorbidities, higher BMI and male gender. At the time of follow up, 8/70 (11.4%) patients lacked neutralizing antibodies. Evidence of 6 probable asymptomatic reinfections suggests waning of immunity, but, probable protection from clinical disease needing hospitalization.     

Temporal trends and factors associated with the cancer diagnosed at stage IV in patients included in the integrated hospital-based cancer registry system in Brazil in two decades

BackgroundIn several countries, such as Brazil, the oncological diagnosis usually occurs at an advanced stage of the disease. Thus, the aim of this study was to investigate temporal trends and factors associated with the cancer diagnosed at stage IV in Brazil in two decades.MethodsSecondary-based study, with time series analysis for trend assessment and cross-sectional of factors associated with diagnosis of female breast, prostate, cervix uteri, colorectal, lung, stomach, lip and oral cavity, thyroid, esophagus or corpus uteri at stage IV.Results1,218,322 cases were evaluated. The types of cancer with the highest proportion of stage IV at diagnosis in men and women, respectively, were: lung (53.7% and 57.4%), stomach (48.4% and 45.0%) and lip/oral cavity (53.5% and 43.4%). Most showed an increasing trend of annual percent change of cancer diagnosed at stage IV, being more pronounced in corpus uteri cancer (2013–2019: +7.4%, p < 0.001). The odds of cancer diagnosed at stage IV were associated with different factors, according to primary tumor site, but marked by the inverse association with female sex [odds ratio (OR) ranging from 0.42 to 0.91, p < 0.001] and direct association in cases with < 7 years of study (OR ranging from 1.08 to 1.81, p < 0.001), living without a partner (OR ranging from 1.06, p < 0.050 to1.27, p < 0.001), living in the South and Southeast regions (OR ranging from 1.04 to 1.13, p < 0.001), with more than one tumor (OR ranging from 1.19, p < 0.050 to 1.54, p < 0.001) and treated in Centers of High Complexity in Oncology (OR ranging from 1.03, p < 0.050 to1.24, p < 0.001).ConclusionThere was a high frequency of cancer diagnosed at stage IV and an increasing trend in different cancer types, which were associated with distinct sociodemographic, lifestyle, and clinical factors.     

Predictors of treatment initiation and mapping the cancer diagnostic pathway: A retrospective observational cohort study of patients with metastatic non-small cell lung cancer

BackgroundHealth-care providers in the US revealed that a substantial proportion of mNSCLC patients do not receive any first-line therapy and the biggest gaps in care are time inefficiencies in the diagnostic process. The goal of this study was to determine whether such gaps are found in Israel where healthcare is universal and participation in a medical insurance plan is free and compulsory.MethodsWe conducted a retrospective, observational cohort study using the computerized data of Maccabi Healthcare Services, a 2.5 million-member state-mandated health-service. Patients with mNSCLC diagnosed between 2017 and 2018 were followed until December 2019.ResultsAmong 434 patients (62% male, mean age 68 y, 74% adenocarcinoma), 345 (79%) initiated first-line treatment. Compared to treated, untreated patients (n = 89) were more likely to be older (mean [SD]=71 years [10] vs. 67 [10], p < 0.001), have a higher co-morbidity index (5.6 ([4.4] vs. 4.0 [3.4], p < 0.001), smokers (84% vs. 66%, p = 0.001), and require hospitalization in the year prior to diagnosis (80% vs 61%, p = 0.002). There was no difference in socioeconomic status. Time from first symptom to imaging was longer for untreated than treated patients (6.51 months [4.24, 7.33] vs 3.48 months [2.76, 4.34] respectively, p = 0.22). Predictors of treatment initiation included age< 70 years, non-smokers, EGFR testing performed, ECOG performance status 0–1 and shorter wait from first symptom to imaging. Median time from first symptom to initiation of 1 L, was 7.76 months (6.51–8.75).ConclusionThe proportion of untreated mNSCLC patients are comparable to those reported in the US; we did not find health disparities between socioeconomic levels. Our data suggest that the main barrier to effective diagnostic process is the wait between symptom complaint and imaging.     

Dysregulation of exosomal miR-192 and miR-194 expression in lung adenocarcinoma patients

Non-small cell lung cancer (NSCLC) is the main reason of cancer linked mortality and around 80% of cases diagnosed in advanced stage. Therefore current study designed to evaluate the deregulation of miRNA-194 and miRNA-192 in different body fluid of Non small cell lung cancer participants. Present study recruited newly diagnosed histopathologically confirmed. It was observed that the 40% NSCLC participants showed elevated miR-194 expression and 60% NSCLC participants showed reduced miR-194 expression in serum sample while in Bronchial wash, only 20% NSCLC participants showed elevated miR-194 expression while 80% showed reduced miR-194 expression (p = 0.003). It was found that the 54% NSCLC participants showed elevated miR-192 expression and 55% NSCLC participants showed reduced miR-192 expression in serum sample while In Bronchial wash sample, only 25% NSCLC participants showed high miR-192 expression while 75% showed low miR-192 expression (P = 0.0004). Expression of miR-194 was significantly associated with TNM stages (p < 0.0001, p < 0.0001), distant organ metastases (p < 0.0001, p < 0.0001), pathological grade (p = 0.0009, p = 0.0005) among serum sample and bronchial wash sample. Same observation was found with expression of miR-192 and it was significantly associated with TNM stages (p < 0.0001, p < 0.0001), distant organ metastases (p < 0.0001, p < 0.0001), pathological grade (p = 0.006, p = 0.001) among serum sample and bronchial wash sample. It was observed that the NSCLC participants who had high serum based miR-194 expression showed 22 months of overall median survival while low expression of serum based miR-194 expression showed 18 months of overall median survival. Present study suggests that decreased expression of miR-194 and miR-192 was significantly associated with different clinical features of NSCLC cases. However, significantly higher number of NSCLC cases showed low expression of miR-194 and miR-192 in bronchial lavage sample. Decreased poor overall survival was found to be associated with bronchial wash sample with respect to low miR-194 and miR-192 expression while NSCLC participants showed better overall survival with high miR-194 and miR-192 expression. This suggested decreased expression of miR-192 and miR-194 expression could be the potential prognostic marker among NSCLC participants.     

Safety and efficacy of cryoballoon versus radiofrequency ablation for atrial fibrillation in elderly patients: A real-world evidence

BackgroundThere are limited data describing the experience of radiofrequency (RF) vs. cryoballoon (CB) ablation for atrial fibrillation (AF) among elderly patients in the United States.MethodsWe conducted a retrospective analysis of patients ≥75 years of age undergoing index RF vs. CB ablation between January 2014 and May 2020 at our center. The choice of ablation technique was left to the operator's discretion. Major complications and efficacy, defined as freedom from any atrial tachyarrhythmia (ATA) lasting ≥30 s after one year of follow-up, were assessed in patients with index RF vs. CB ablation.ResultsIn our cohort of 186 patients, the median age was 78 (76–81) years, 54.8% were men, and 39.2% had persistent AF. The median CHA₂DS₂-VASc score was 4 (3–4), while the median duration of AF was 3 (1–7) years. The majority (n = 112, 60.2%) underwent RF ablation. The median procedure time was significantly lower in CB group (197 vs 226.5 min, p=<0.01). The incidence of complications was similar in the two sub-groups (RF: 1.8% vs. CB: 2.7%, p = 0.67). Similarly, arrhythmia-free survival rate on antiarrhythmic drugs at 1-year follow-up remained statistically comparable (63.4% vs. 68.9%, p = 0.33) between patients receiving RF vs. CB ablation.ConclusionThe safety and efficacy of RF vs. CB ablation for AF remained comparable in our cohort of patients older than 75 years. CB ablation was associated with a shorter procedure time.     

Safety and Efficacy of Apixaban versus warfarin in patients with atrial fibrillation or Venous Thromboembolism and End-Stage renal disease on hemodialysis: A systematic review and meta-analysis

BackgroundWarfarin is traditionally the drug of choice for stroke prophylaxis or treatment of venous thromboembolism in patients with end-stage renal disease (ESRD) on hemodialysis as data on apixaban use is scarce. We aimed to assess the safety and efficacy of Apixaban in patients with ESRD on hemodialysis when compared with warfarin.MethodsA comprehensive literature search in PubMed, Google Scholar, and Cochrane databases from inception until Nov 25, 2019, was performed. Studies reporting clinical outcomes comparing Apixaban (2.5 mg BID or 5 mg BID) versus Warfarin in ESRD patients on hemodialysis were included. Mantel-Haenszel risk ratio (RR) random-effects model was used to summarize data.ResultsFour studies (three retrospective and one randomized) with a total of 9862 patients (apixaban = 2,547, warfarin = 7315) met inclusion criteria. The overall mean age was 66.6 ± 3.9 years and mean CHA2DS2-VASc score 4.56 ± 0.58. Apixaban was associated with lower rates of major bleeding (RR 0.53, 95% CI 0.45–0.64, p < 0.0001], gastrointestinal (GI) bleed (RR 0.65, 95% CI 0.55–0.76, p < 0.0001), intracranial bleed (RR 0.56, 95% CI 0.36–0.89, p = 0.01), and stroke/systemic embolism [RR 0.65, 95% CI 0.52–0.83, p = 0.0004] compared with warfarin in patients with ESRD on hemodialysis. There was no significant increased risk of all-cause mortality with the apixaban vs. warfarin (RR 0.90, 95% CI 0.41–1.96, p = 0.78).ConclusionApixaban had an overall favorable risk-benefit profile, with significant reductions in ischemic stroke, major bleeding, and intracranial bleeding compared to Warfarin in ESRD patients on hemodialysis with non-valvular AF and/or venous thromboembolism.     

Epidemiology of laryngeal cancer in Brazil: Historical data from 2000 to 2019

IntroductionTo determine the incidence, morbidity, and mortality rate of laryngeal cancer in two decades and its epidemiological, clinical, and histological characteristics by sex in Brazil.MethodsThis ecological study used three reliable sources of secondary data: population- and hospital-based cancer registries and the national mortality database. All data available from 2000 to 2019 were considered.ResultsThe incidence of male laryngeal cancer decreased from 9.20 to 4.95 per 100,000 from 2000 to 2018, while mortality slightly decreased from 3.37 to 3.30 per 100,000 from 2000 to 2019. In the same period, the female incidence decreased from 1.26 to 0.48 per 100,000; however, mortality slightly increased from 0.34 to 0.36 per 100,000. Of 221,566 individuals with head and neck cancer, 27 % presented laryngeal cancer. The median age was 61 years (54−69), and most individuals were male (86.6 %), smokers (66.2 %), diagnosed with locally advanced cancer (66.7 %), and squamous cell carcinoma as the main histological type (93.2 %). Male tended to be older (p < 0.001), white (p < 0.001), smokers (p < 0.001), and present late treatment initiation (p < 0.001) and early death (p < 0.001) compared with female.ConclusionThe male laryngeal cancer affected mainly at productive age but with a decreased incidence, probably due to a reduction in smoking habit. However, mortality did not change, which may be explained by the late diagnosis and lack of access to radiotherapy.     

Effect of radiation exposure on survival after first solid cancer diagnosis in A-bomb survivors

BackgroundComparison of the estimated effect of atomic bomb radiation exposure on solid cancer incidence and solid cancer mortality in the RERF Life Span Study (LSS) reveals a difference in the magnitude and shape of the excess relative risk dose response. A possible contributing factor to this difference is pre-diagnosis radiation effect on post-diagnosis survival. Pre-diagnosis radiation exposure theoretically could influence post-diagnosis survival by affecting the genetic makeup and possibly aggressiveness of cancer, or by compromising tolerance for aggressive treatment for cancer.MethodsWe analyze the radiation effect on post-diagnosis survival in 20,463 LSS subjects diagnosed with first-primary solid cancer between 1958 and 2009 with particular attention to whether death was caused by the first-primary cancer, other cancer, or non-cancer diseases.ResultsFrom multivariable Cox regression analysis of cause-specific survival, the excess hazard at 1 Gy (EH_1Gy) for death from the first primary cancer was not significantly different from zero – p = 0.23, EH_1Gy = 0.038 (95 % CI: −0.023, 0.104). Death from other cancer and death from non-cancer diseases both were significantly associated with radiation dose: other cancer EH_1Gy = 0.38 (95 % CI: 0.24, 0.53); non-cancer EH_1Gy = 0.24 (95 % CI: 0.13, 0.36), both p < 0.001.ConclusionThere is no detectable large effect of pre-diagnosis radiation exposure on post-diagnosis death from the first primary cancer in A-bomb survivors.ImpactA direct effect of pre-diagnosis radiation exposure on cancer prognosis is ruled out as an explanation for the difference in incidence and mortality dose response in A-bomb survivors.     

Predictive value of vascular calcification identified in 4D planning CT of lung cancer patients treated with stereotactic body radiation therapy

PurposeThe aim was to identify vascular calcification in 4DCT scan of lung cancer patients and establish the association between overall survival (OS) and vascular calcification, as surrogate for vascular health.MethodsVascular calcification within the thoracic cavity were segmented in 334 lung cancer patients treated with stereotactic body radiation therapy (SBRT). This has been done automatically on 4D planning CT and average reconstruction scans. Correlation between cardiac comorbidity and calcification volumes was evaluated for patients with recorded Adult Co-Morbidity Evaluation (n = 303). Associations between the identified calcifications and OS were further investigated.ResultsThe volume of calcification from the average scan was significantly lower than from each phase (p < 0.001). The highest level of correlations between cardiac comorbidity and volume of the calcifications were found for one phase representing inhale and two phases representing exhale with the least motion blurring due to respiration (p < 0.005). The volume of the calcifications was subsequently averaged over these three phases. The average of calcification volumes over the three phases (denoted by inhale-exhale) showed the highest likelihood in univariate analysis and was chosen as vascular calcification measure. Cox-model suggested that tumor volume (Hazard Ratio [HR] = 1.46, p < 0.01) and inhale-exhale volume (HR = 1.05, p < 0.05) are independent factors predicting OS after adjusting for age, sex, and performance status.ConclusionIt was feasible to use. It 4DCT scan for identifying thoracic calcifications in lung cancer patients treated with SBRT. Calcification volumes from inhale-exhale phases had the highest correlation with overall cardiac comorbidity and the average of the calcification volume obtained from these phases was an independent predictive factor for OS.     

Comparison among four immobilization devices for whole breast irradiation with Helical Tomotherapy

PurposeTo evaluate the repositioning accuracy of 4 immobilization devices (ID) used for whole breast Helical Tomotherapy treatments: arm float with VacFix® (Par Scientific, Denmark), all-in-one® (AIO®) system (Orfit, Belgium), MacroCast thermoplastic mask (Macromedics, The Netherlands) and BlueBag® system with Arm-Shuttle (Elekta, Sweden).Materials and methodsTwenty four women with breast cancer with PTV including the breast/chest wall and lymph nodes were involved in this study (6 women per group). Pretreatment registration results were first collected using automatic bone registration + manual adjustment on the vertebra followed by independent registrations on different ROIs representing each treated area (axillary, mammary chain, clavicular, breast/chest wall). The differences in translations and rotations between reference registration and the above mentionned ROIs were calculated. A total of 120 MVCT images were analyzed.ResultsSignificant differences were found between IDs (p < 0.0001), ROIs (p = 0.0002) and the session number (p < 0.0001) on the observed shifts, when examining 3D translation vectors. 3D-vectors were significantly lower for the BlueBag® than for the VacFix® or for the AIO® (p < 0.0001), but differences were not significant compared to the mask (p = 0.674). Finally, setup margins were overall smaller for the BlueBag® than for other IDs, with values ranging from 1.53 to 1.91 mm on the mammary chain area, 4.52–6.07 mm on the clavicular area, 2.71–4.62 mm on the axillary area, and 3.39–5.10 mm on the breast.ConclusionWe demonstrated in this study that the BlueBag® combined with arm shuttle is a robust solution for breast and nodes immobilization during HT treatments.     

Real-world effectiveness and safety of multiple myeloma treatments based on thalidomide and bortezomib: A retrospective cohort study from 2009 to 2020 in a Brazilian metropolis

BackgroundMultiple myeloma (MM) is an incurable cancer of plasma cells; the survival of which has improved over the years with the emergence of new treatments. In Brazil, the availability of treatment-regimens is different from developed countries. Real-world evidence with Brazilian patients is lacking.ObjectivesOur aim was to evaluate the effectiveness and the safety of MM treatments in a Brazilian metropolis.MethodsThis was a retrospective cohort study with MM patients, beginning MM treatment from 2009 to 2020 (i.e., before bortezomib became available in public health services). Patients’ medical records were revised to obtain clinical variables. The primary outcomes were Overall Survival (OS) and Progression Free Survival (PFS, measured as time to next treatment), and the secondary outcomes were Adverse Events (AE). Kaplan-Meier curves were obtained and the Cox proportional hazards model was performed for univariate and multivariate analyses. The incidence of AE was estimated and the chi-squared test was performed to evaluate the association between AE and MM regimens.ResultsIn total, 278 patients participated in the study with median age of 64 years; 50.4 % were females, 55.8 % attended a private clinic, 34.9 % received autologous stem cell transplantation (ASCT) and 32.4 % were on polypharmacy. Most patients from public services used thalidomide-based regimens (40.3 %) and at private clinics used bortezomib-based regimens (38.1 %) as first-line treatment. Patients had a median OS of 99 months. Patients had median PFS of 28 months in first-line treatment, which was significantly different for age (p = 0.0055), polypharmacy (p = 0.0094) and ASCT (p < 0.0001). PFS was independently associated to polypharmacy and ASCT. The incidence of peripheral neuropathy (39.6 %) was high. In contrast, the incidence of severe AE was low. We found significant difference between first-line T + B-based regimens and leukopenia (p = 0.012).ConclusionOur study showed that patients on polypharmacy and who did not receive ASCT had worse PFS. Similar to other Latin countries, most patients used thalidomide- and bortezomib-based regimens as first-line treatments having similar OS and PFS. Treatments were considered relatively safe, especially regarding serious AE.