The relationship between ethnicity,social deprivation and late presentation of colorectal cancer

IntroductionTumour staging at time of presentation is an important factor in determining survival in colorectal cancer. The aim of this paper is to investigate the relationship between ethnicity and deprivation in late (Stage IV) presentation of colorectal cancer.MethodsData from the Thames Cancer Registry comprising 77,057 colorectal cancer patients between the years 2000 and 2012 were analysed.ResultsA total of 17,348 patients were identified with complete data, of which 53.9% were male. Patients from a Black Afro/Caribbean background were diagnosed with CRC at a much younger age than the White British group (median age 67 compared with 72, p < 0.001). In multiple regression, ethnicity, deprivation and age were positive predictors of presenting with advanced tumour stage at time of diagnosis. Black patients were more likely to present with Stage IV tumours than white patients (OR 1.37, 95% CI 1.18–1.59, p < 0.001). Social deprivation was also a predictor of Stage IV cancer presentation, with the most deprived group (Quintile 5) 1.26 times more likely to be diagnosed with Stage IV cancer compared with the most affluent group (CI 1.13–1.40, p < 0.001). Sub-group analyses demonstrated that Black & Affluent patients were still at greater risk of Stage IV CRC than their White & Affluent counterparts (OR 1.24, 95% CI 1.11–1.45, p = 0.023). Patients with rectal cancer were less likely to present with Stage IV CRC (OR 0.66, 95% CI 0.61–0.71, p < 0.001).ConclusionRacial and age related disparities exist in tumour presentation in the United Kingdom. Patients from black and socially deprived backgrounds as well as the elderly are more likely to present with advanced tumours at time of diagnosis.     

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.     

Regional trends of minimally invasive radical hysterectomy for cervical cancer and exploration of perioperative outcomes

IntroductionRadical hysterectomy (RH) with bilateral pelvic lymph node dissection is the standard treatment for early stage cervical cancer which can be performed either by an abdominal or a minimally invasive (MIS) approach. In 2018, Ramirez et al. presented their randomized-controlled trial data which demonstrated that patients who were treated with minimally invasive surgical (MIS) radical hysterectomy (RH) had higher rates of locoregional disease recurrence and lower rates of overall survival when compared to patients treated with an abdominal approach. The objective of this study is to examine the trends in management of patients diagnosed with cervical cancer in New York State (NYS) and to analyze their perioperative outcomes.MethodsUsing the Statewide Planning and Research Cooperative System (SPARCS) Database, patients undergoing RH for early stage cervical cancer in NYS between the years of 2007–2015 were identified and categorized based on surgical approach. Demographic information was collected and multivariable regression was conducted to assess the impact of hysterectomy approach on perioperative outcomes.ResultsIn NYS, 5575 patients were treated with RH for early stage cervical cancer with 3257 (58.4%) treated by abdominal RH and 2318 (41.6%) treated with MIS RH. Between the years of 2007 and 2015, patients diagnosed with cervical cancer treated with MIS RH increased from 25.7% to 48.3% respectively. Surgeons performing MIS RH were more likely to be younger (average age 47.1 vs 49.2, p < 0.001) and have less time elapsed from their fellowship graduation (20.37 vs 22.64 years, p < 0.001). Patients who saw high volume doctors (OR 1.95, CI 1.65–2.31) and were seen in high volume facilities (OR 1.40, CI 1.18–1.65) were more likely to undergo MIS RH compared to abdominal RH. Patients who underwent MIS RH were more likely to be discharged home as opposed to acute rehab or nursing facility, when compared to patients treated with abdominal RH (98.5 vs 94.2% p < 0.001). When analyzing perioperativce outcomes, patient undergoing MIS RH had a 85% decrease in length of hospital stay compared to abdominal RH, a 40% reduction in 30-day readmission rates, and a 10% reduction in hospital costs respectively.DiscussionIn our study period, between the years of 2007 and 2015, the number of cervical cancer cases treated with MIS RH increased from 25.7% to 48.3%. MIS techniques led to a reduction in length of hospital stay, patient readmission rates, and hospital costs. Based on recent data from Ramirez et al., preliminary data demonstrated decrease in MIS RH for treatment of cervical cancer after presentation of the LACC trial and our data confirmed these reported trends in NYS. With this change in surgical practice, there will be associated changes in perioperative outcomes. Moreover, for patients diagnosed with cervical cancer with microscopic disease or previous treatment with an excisions procedure, MIS approach should be considered for improvement in perioperative outcomes as long as oncologic outcomes are not compromised.     

miRNA-148a and miRNA-30c expressions as potential biomarkers in breast cancer patients

BackgroundBreast cancer is an extensively identified malignant tumor and is a prime cause of cancer mortalities in females. It has been shown that alteration of miRNAs expression (up or down regulation) can affect the initiation and progression of many malignancies. We aimed to evaluate the role of circulating miRNA-148a and miRNA-30c in female patients with breast cancer and estimate their usage as potential biomarkers in the diagnosis, prognosis and survival of breast cancer.MethodsThis study included 75 breast cancer female patients.They were compared with 55 apparently healthy female subjects. miRNAs expression analysis was assessed via real-time PCR.ResultsTo discriminate breast cancer patients from controls, miR-30c showed the best performance at a cut off value of ≤20.6 (AUC = 0.998, 97.33% sensitivity, 96.36% specificity, p < 0.001), followed by miR-148a (AUC = 0.995, 94.67% sensitivity, 90.91% specificity, p < 0.001 at a cut off value of ≤0.1), CA 15-3 (AUC = 0.930, 88.0% sensitivity, 81.82% specificity, p < 0.001 at a cut off value of >21.3), and finally CEA (AUC = 0.751, 70.67% sensitivity, 63.64% specificity, p < 0.001 at a cut off value of >2.5).ConclusionmiRNA-148a and miRNA-30c expressions were down regulated in female patients with breast cancer and might be considered as potential blood biomarkers. Both also might have rule in disease treatment and selection of therapeutic targets. Future studies are needed to improve their role in predicting response to treatment and prognosis.     

Trend breaks in incidence of non-cardia gastric cancer in the Netherlands

IntroductionThe incidence of gastric cancer declined over the past decades. Recently, unfavorable trend breaks (i.e. rise in incidence) were seen for non-cardia cancer in younger age groups in the US. It is unclear whether these also occur in other Western countries. We aimed to analyze the gastric cancer incidence trends by age, sex, subsite and stage in the Netherlands.MethodsData on all patients with gastric adenocarcinoma diagnosed from 1973 to 2011 (n = 9093) were obtained from the population-based Eindhoven cancer registry. Incidence time trends (European standardized rates per 100,000) were separately analyzed by sex, age group (<60, 60–74, and >75 years), subsite, and pathological stage. Joinpoint analyses were performed to discern trend breaks, age–period–cohort analyses to examine the influence of longitudinal and cross-sectional changes.ResultsThe incidence of non-cardia cancer declined annually by 3.5% (95% CI −3.8; −3.3). However, in males <60 years, the incidence flattened since 2006, and tended to rise in those >74 years. This pertained to corpus cancers. The incidence of cardia cancer peaked in 1985 and decreased subsequently by 2.4% (95% CI −3.2; −1.5) yearly. The absolute incidence of stage IV disease at first diagnosis initially decreased, but then remained stable over the past 15–20 years.ConclusionsThe incidence of non-cardia cancer declined over the past four decades in the Netherlands, but now seems to be stabilizing particularly in males. Unfavorable trend breaks are seen for corpus cancer in younger and older males. The trend breaks in the Netherlands are however not similar to those observed in the US.     

The effect of age on the opportunity to receive cancer treatment

IntroductionOlder adults with cancer may not receive the same opportunities for treatment as younger patients. In this retrospective population-based cohort study, we explored whether age was an independent predictor of receiving specialist consultation and treatment.MethodsPatients age 45–99 were identified from the Ontario Cancer Registry having a primary solid tumor diagnosed between 01/Jan/2010 and 31/Dec/2019. We used logistic regression adjusted sociodemographic and clinical characteristics to compare the likelihood of consultation or receipt of treatment using linear splines at critical ages of 65, 80, and 90 years.ResultsA total 168,232 (42%), 165,205 (41%), 57,360 (14%), and 7810 (2%) patients were diagnosed age 45–64, 65–79, 80–89, and 90–99, respectively. The likelihood of surgical consultation decreased as patients reached 65 years [adjusted odds ratio (aOR) 0.86 (0.84–0.89)], which decreased further among octogenarians [aOR 0.63 (0.59–0.67)]. Similar results were observed for consultation with a medical oncologist and radiation oncologist. Receipt of surgery also decreased with age. Three-month post-operative mortality was higher among older patients [aRR 1.38 (1.26–1.50) per 10 years, p < 0.0001], an effect that remained similar as patients reached age 65 + years of age (p = 0.09 for change). For stage I patients, 3-month post-operative survival was high across all age groups, ranging from 99.8% in 45–64 year-olds, 99.4% in 65–79 year-olds, and 98.1% among octogenarians and nonagenarians (lung, colorectal, breast, cervical cancer patients).ConclusionOlder patients were less likely to have specialist consultations. More comprehensive data collection on clinical factors and referral patterns is needed to improve care for elderly cancer patients.     

Peri-operative blood transfusion for resected colon cancer: Practice patterns and outcomes in a population-based study

Background & objectivesLiterature suggests that peri-operative blood transfusion among patients with resected colon cancer may be associated with inferior long-term survival. The study objective was to characterize this association in our population.MethodsThis is a retrospective cohort study using the population-based Ontario Cancer Registry (2002–2008). Pathology reports were obtained for a 25% random sample of all cases and constituted the study population. Log binomial regression was used to identify factors associated with transfusion. Cox proportional hazards model explored the association between transfusion and cancer specific survival (CSS) and overall survival (OS).ResultsThe study population included 7198 patients: 18% stage I, 36% stage II, 40% stage III, and 6% stage IV. Twenty-eight percent of patients were transfused. Factors independently associated with transfusion included advanced age (p < 0.001), female sex (p < 0.001), greater comorbidity (p < 0.001), more advanced disease (p < 0.001) and open surgical resection (p < 0.001). Transfusion was associated with inferior CSS (HR 1.51, 95% CI 1.38–1.65) and OS (HR 1.52, 95% CI 1.41–1.63), after adjusting for important confounders.ConclusionsPeri-operative transfusion rates among patients with colon cancer have decreased over time. Transfusion is associated with inferior long-term CSS and OS.     

Meta-analysis of the clinicopathological characteristics and peri-operative outcomes of colorectal cancer in obese patients

BackgroundThe effect of obesity on the clinicopathological characteristics of colorectal cancer (CRC) has not been clearly characterized. This meta-analysis assesses the pathological and perioperative outcomes of obese patients undergoing surgical resection for CRC.MethodsMeta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases were searched for studies reporting outcomes for obese and non-obese patients undergoing primary CRC resection, based on body-mass index measurement. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI).ResultsA total of 2183 citations were reviewed; 29 studies comprising 56,293 patients were ultimately included in the analysis, with an obesity rate of 19.3%. Obese patients with colorectal cancer were more often female (OR 1.2, 95% CI 1.1–1.2, p < 0.001) but there was no difference in the proportion of rectal cancers, T4 tumours, tumour differentiation or margin positivity. Obese patients were significantly more likely to have lymph node metastases (OR 1.2, 95% CI 1.1–1.2, p < 0.001), have a lower nodal yield, were associated with a longer duration of surgery, more blood loss and conversions to open surgery (OR 2.6, 95% CI 1.6–4.0, p < 0.001) but with no difference in length of stay or post-operative mortality.ConclusionThis meta-analysis demonstrates that obese patients undergoing resection for CRC are more likely to have node positive disease, longer surgery and higher failure rates of minimally invasive approaches. The challenges of colorectal cancer resection in obese patients are emphasized.     

Increasing incidence and survival of corpus uteri cancer in Estonia over the past two decades

BackgroundCorpus uteri cancer has become the fourth most common female cancer in Europe. In Estonia, the prevalence of obesity is increasing, and corpus uteri cancer survival has been relatively low. The aim of the study was to evaluate incidence, mortality and survival trends of corpus uteri cancer in Estonia by age, stage and histological subtypes with an emphasis on surgical treatment.MethodsEstonian Cancer Registry data on incident cases of corpus uteri cancer were used to examine incidence trends (1995–2016) and calculate relative survival ratios (RSR) (1996–2016). Cases were classified by morphology and FIGO stage. Causes of Death Registry data were used to analyse corrected mortality (1995–2017).ResultsA total of 4281 cases were diagnosed in 1996–2016. A significant increase was seen in age-standardized incidence from 2009, while mortality remained stable throughout the study period. Significant increases were observed for type I cancers and age groups ≥65 years. Overall age-standardized 5-year RSR improved from 70% in 1996–2002 to 78% in 2010–2016. Survival increased for type I cancers, all age groups and all stages (significantly for stage IV). The proportion of surgically treated cases increased significantly from 85% to 89%, with the largest increases seen in older age groups and later stages.DiscussionThe rising corpus uteri cancer incidence in Estonia is driven by the type I cancer trend. Survival gain for later stages and older age groups likely reflected more frequent surgical treatment. To reduce mortality, further efforts are necessary to ensure appropriate care for all patients.     

A study of oxidative stress in cervical cancer- an institutional study

Cervical cancer is the second most common cause of cancer-related death among women worldwide, especially in developing countries. Oxidative stress has been associated with cervical cancer. Many studies demonstrated that the low level of antioxidants induces the production of free radicals that cause lipid peroxidation, DNA, and protein damage leading to mutations that favors malignant transformation. This is a case-control institutional study conducted to evaluate the level of oxidative stress in cervical cancer patients and the age-matched healthy controls. We measured level of TBARS expressed as MDA, activity of SOD and GSH level by the spectrophotometric method, and level of 8-OHdG was estimated using a competitive sandwich ELISA assay. Our results showed a significant increase in the level of lipid peroxidation in group IV when compared to the control, group II and group III (p < 0.001). The activity of SOD was also significantly higher in group IV when compared to the control group (p < 0.001), group II (p < 0.001), and group III (p < 0.001). The level of GSH was also significantly lower in group IV when compared to the control group (p < 0.01), group II (p < 0.01), and group III (p < 0.01). The level of 8-OHdG was significantly higher in group IV than in the other groups (p < 0.01). The results suggest that oxidative stress is involved in the pathogenesis of cervical cancer, which is demonstrated by an increased level of lipid peroxidation and higher levels of 8-OHdG and an altered antioxidant defense system.     

Clinicopathological characteristics of androgen receptor splicing variant 7 (AR-V7) expression in patients with castration resistant prostate cancer: A systematic review and meta‐analysis

Background Studies have shown that AR-V7 may be correlated with the poor prognosis of castration resistant prostate cancer (CRPC), however, clinicopathological characteristics of AR-V7 have not been fully elucidated.ObjectiveThis study aimed at evaluating the clinicopathological features of AR-V7 in CRPC patients.Materials and methodsTo evaluate the clinicopathological features of AR-V7 in CRPC patients. A search of PubMed, Embase, and Web of Science was performed using the keywords prostate cancer, prostate tumor, prostate neoplasm, prostate carcinoma, AR-V7, AR3, androgen receptor splicing variant-7, or androgen receptor-3. Twenty-four trials published by February 2020 were included in this study.ResultsThe proportion of Gleason score ≥ 8 was found to be significantly higher in AR-V7-positive CRPC (69.5%) than negative (54.9%) (OR 1.68, 95% CI 1.25–2.25, p < 0.001), while the rates of T3/T4 stage (OR 1.16, 95% CI 0.60–2.24, p = 0.65) and N1 stage (OR 0.99, 95% CI 0.65–1.51, p = 0.96) were not statistically correlated with AR-V7 status. The AR-V7-positive patients exhibited a significantly higher proportion of any site metastasis (61.3% versus 35.0%; OR 2.19, 95% CI 1.57–3.05, p < 0.001) and bone metastasis (81.7% versus 69.0%; OR 1.97, 95% CI 1.44–2.69, p < 0.001), and a trend close to significance was expected in visceral metastasis (28.8% versus 22.1%; OR 1.29, 95% CI 0.96–1.74, p = 0.09). Incidences of pain in AR-V7-positive CRPC (54.6%) were significantly higher than in negative CRPC (28.1%; OR 4.23, 95% CI 2.52–7.10, p < 0.001), line with worse ECOG performance status (56.7% versus 35.0%, OR 2.18, 95% CI 1.51–3.16, P < 0.001). Limitations of the study include differences in sample sizes and designs, AR-V7 detection assays, as well as disease characteristics of the included studies.ConclusionsAR-V7 positivity is associated with a higher Gleason score, bone or any site metastasis, pain and worse ECOG performance scores in CRPC. However, it is not correlated with tumor stage or lymph node metastasis. More studies are needed to confirm these findings.     

Global changes in bladder cancer mortality in the elderly

BackgroundBladder cancer is the 14th most common cause of cancer deaths worldwide and has a mean age of diagnosis of 73 years. Elderly people have fewer curative treatment options for muscle invasive bladder cancer. The aim of this study is to investigate how bladder cancer mortality has changed over the past forty years in different world regions to assess discrepancies between elderly and younger patients with bladder cancer.MethodsBladder cancer mortality data were extracted from the World Health Organisation’s GLOBOCAN database. Age-standardised mortality rates (ASMR) for bladder cancer were computed by year, sex, region and Human Development Index (HDI) using the world standard population.ResultsOverall ASMR in all available countries with data between 1986 and 2014 for men aged ≥ 75 has decreased from 101.2 to 89.9 per 100,000 (−11.2%). The decrease in ASMR for men < 75 has been 0.3–2.0 per 100,000 (−39.4%). In women aged ≥ 75 ASMR has decreased from 26.9 to 22.5 per 100,000 (−16.4%) and in women < 75 the ASMR has decreased from 0.76 to 0.56 per 100,000 (−26.4%).Correlation analysis showed a positive linear relationship between Human Development Index (HDI) and improvement in age-standardised mortality rate in all ages. Pearson’s coefficient showed that correlation was strongest in the 60–74 age group (r = −0.61, p < 0.001) and weakest in those aged ≥ 75 (r = −0.39, p = 0.01).ConclusionBladder cancer mortality is not improving in the elderly at the same rate as the rest of the population. Particular focus should be applied in future research to enhance and expand treatment options for bladder cancer that are appropriate for elderly patients.     

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.     

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.     

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.     

Personalized automation of treatment planning in head-neck cancer: A step forward for quality in radiation therapy?

PurposeTo perform a comprehensive dosimetric and clinical evaluation of the new Pinnacle Personalized automated planning system for complex head-and-neck treatments.MethodsFifteen consecutive head-neck patients were enrolled. Radiotherapy was prescribed using VMAT with simultaneous integrated boost strategy. Personalized planning integrates the Feasibility engine able to supply an “a priori” DVH prediction of the achievability of planning goals. Comparison between clinically accepted manually-generated (MP) and automated (AP) plans was performed using dose-volume histograms and a blinded clinical evaluation by two radiation oncologists. Planning time between MP and AP was compared. Dose accuracy was validated using the PTW Octavius-4D phantom together with the 1500 2D-array.ResultsFor similar targets coverage, AP plans reported less irradiation of healthy tissue, with significant dose reduction for spinal cord, brainstem and parotids. On average, the mean dose to parotids and maximal doses to spinal cord and brainstem were reduced by 13–15% (p < 0.001), 9% (p < 0.001) and 16% (p < 0.001), respectively. The integral dose was reduced by 16% (p < 0.001). The dose conformity for the three PTVs was significantly higher with AP plans (p < 0.001). The two oncologists chose AP plans in more than 80% of cases. Overall planning times were reduced to <30 min for automated optimization. All AP plans passed the 3%/2 mm γ-analysis by more than 95%.ConclusionComplex head-neck plans created using Personalized automated engine provided an overall increase of plan quality, in terms of dose conformity and sparing of normal tissues. The Feasibility module allowed OARs dose sparing well beyond the clinical objectives.     

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.     

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.     

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.