Risk of subsequent cancers in renal cell carcinoma survivors with a family history

BackgroundThis study aimed at elucidating the effect of family history on the development of subsequent cancers in renal cell carcinoma (RCC) survivors and aimed at assessing whether the interactions between risks of subsequent cancers in RCC survivors and familial risk of subsequent cancer are additive or multiplicative interactions.MethodsA population-based cohort (Swedish Family-Cancer Database) of 14,267 RCC patients diagnosed in 1990–2010 was followed for cancer incidence. Standardised incidence ratios (SIRs) were calculated for subsequent cancers in RCC survivors and in RCC survivors with a family history of subsequent cancer. Familial risk of subsequent cancer was calculated for individuals with family history of specific cancer, compared to those without.ResultsFor subsequent hemangioblastoma (HB) in RCC survivors, drastically elevated risk was observed for the effect of family history of HB [SIR = 777 (95% confidence interval (CI): 160–2270)] and of family history of RCC [378 (46–1367)]. Colorectal, lung, prostate and RCCs favoured additive interactions between risk of subsequent cancers in RCC survivors and familial risk, while endocrine glands, nervous system and urinary bladder cancers favoured multiplicative interactions.ConclusionsRisks of subsequent HB in RCC survivors were tremendously modified by family history of RCC or HB, which may resemble characteristics of von Hippel–Lindau syndrome and show the power of present approach to detect heritable cancer clusters. Additive or multiplicative interactions found for colorectal, lung, prostate, endocrine glands, nervous system, urinary bladder and RCCs might raise awareness among clinicians and RCC survivors with a family history of seven cancers about elevated risks of subsequent those cancers.     

Quality of life among long-term (⩾5 years) colorectal cancer survivors – Systematic review

BackgroundDue to the growing number of long-term (?5 years) colorectal cancer survivors, investigation of their quality of life (QoL) is important for an evaluation of chronic or late effects of the disease and treatment and to adjust treatment strategies to patients’ needs.MethodTo summarise current research results, multiple databases including PubMed, EMBASE and CINAHL were used to identify articles about long-term QoL of colorectal cancer survivors. The content of 10 included studies was independently extracted by two reviewers.ResultsColorectal cancer survivors indicated a good overall QoL, but may have slightly lower physical QoL than the general population. Furthermore, survivors had worse depression scores and reported to suffer from long-term symptoms such as bowel problems and distress regarding cancer. Apart from stoma and recurrence of the disease, mainly general and health-related factors such as age, social network size, income, education, BMI and number of comorbidities were associated with QoL. Studies were mainly conducted in the United States (US) (n = 7) and were heterogeneous with respect to the QoL instrument used and the adjustment to covariates. QoL assessment was cross-sectional in all studies.ConclusionDespite an overall good QoL, colorectal cancer survivors have specific physical and psychological problems. The reported determinants of QoL may serve to identify survivors with special needs. But further studies are needed that focus on problems like distress, depression and bowel problems of long-term colorectal cancer survivors.     

Interval from diagnosis to treatment onset for six major cancers in Catalonia,Spain

Background: Targets set by health care organizations on time intervals between cancer diagnosis and treatment often go unmet. The objective of the study was to analyse the interval from diagnosis to treatment onset, and related factors, in the six most incident cancers in Catalonia (Spain), a developed European region with universal free access to health care. Methods: Twenty-two hospitals contributed 1023 incident cancer patients (198 lung, 253 colorectal, 95 prostate, 109 urinary bladder, 266 breast, 102 endometrial). Information was gathered from hospital medical records. The dependent variable was the length of the diagnosis to treatment interval (DTI). Independent variables were age, sex, disease stage, hospital level, mode of admission to hospital, and type of physician seen before admission. Multivariate-adjusted odds ratios were calculated by unconditional logistic regression for each cancer site. Results: The median DTI (in days) was 39 for lung cancer, 25 for colorectal, 108 for prostate, 69 for bladder, 35 for breast and 40 for endometrial cancer. In prostate and bladder cancers, over 78% of patients showed a DTI >30 days, while in colorectal the figure was 42%. Disseminated stage (distant metastases) was associated with a lower DTI in all sites. Patients admitted to third-level hospitals and with an elective admission were more likely to have a DTI >30 days. Conclusions: In Catalonia, a substantial proportion of cancer patients experience treatment delays that may impact negatively on psychological well-being, quality of life, and probably survival as well.     

Interval from diagnosis to treatment onset for six major cancers in Catalonia, Spain

Background: Targets set by health care organizations on time intervals between cancer diagnosis and treatment often go unmet. The objective of the study was to analyse the interval from diagnosis to treatment onset, and related factors, in the six most incident cancers in Catalonia (Spain), a developed European region with universal free access to health care. Methods: Twenty-two hospitals contributed 1023 incident cancer patients (198 lung, 253 colorectal, 95 prostate, 109 urinary bladder, 266 breast, 102 endometrial). Information was gathered from hospital medical records. The dependent variable was the length of the diagnosis to treatment interval (DTI). Independent variables were age, sex, disease stage, hospital level, mode of admission to hospital, and type of physician seen before admission. Multivariate-adjusted odds ratios were calculated by unconditional logistic regression for each cancer site. Results: The median DTI (in days) was 39 for lung cancer, 25 for colorectal, 108 for prostate, 69 for bladder, 35 for breast and 40 for endometrial cancer. In prostate and bladder cancers, over 78% of patients showed a DTI >30 days, while in colorectal the figure was 42%. Disseminated stage (distant metastases) was associated with a lower DTI in all sites. Patients admitted to third-level hospitals and with an elective admission were more likely to have a DTI >30 days. Conclusions: In Catalonia, a substantial proportion of cancer patients experience treatment delays that may impact negatively on psychological well-being, quality of life, and probably survival as well.     

Recruiting long-term survivors of European Organisation for Research and Treatment of Cancer phase III clinical trials into quality of life studies: Challenges and opportunities

ObjectivesIn this pilot study we evaluated the feasibility of and methods for assessing the quality of life of long term survivors of European Organisation for Research and Treatment of Cancer (EORTC) phase III clinical trials. Here we report the results pertaining to the feasibility of conducting such research.MethodsIn this cross-sectional study, we recruited long-term, disease-free survivors from two mature EORTC clinical trials in testicular and prostate cancer from centres in Northern and Southern Europe, and the United Kingdom (UK).ResultsA number of challenges were encountered in recruiting participating centres, obtaining medical ethical approval and in recruiting survivors and collecting the health-related quality of life (HRQoL) data in a timely manner. The efficiency with which the study could be conducted varied widely across centres and countries. Time to obtain medical ethical approval for the study ranged from 1.5 to 25 months. We encountered most problems with ethical approval in the UK, Italy and Belgium. In most cases, data collection was completed within 3 months (range 10 weeks–1 year). Completed questionnaires were obtained from 68% and 56%, respectively, of the testicular and prostate cancer survivors who were approached.ConclusionsHRQoL research among long-term survivors of EORTC phase III clinical trials is possible, but the process of ethical approval and data collection is a lengthy one. To minimise many of the logistical problems, long-term follow-up of patients should be an integral part of future clinical trials. Moreover, regulations governing medical ethical approval for clinical research within the EU should be carefully evaluated to facilitate long-term follow-up of cancer survivors in Europe.     

An examination of the relationship between patient satisfaction with healthcare and quality of life in a geriatric population with cancer in the Southeastern United States

BackgroundUnderstanding factors that impact patient satisfaction with cancer care within the growing population of older adults living with cancer will contribute to tailoring programs that address patient needs and expectations. Further, patient satisfaction is a determinant of healthcare organizations' institutional performance. The purpose of this study was to investigate the relationship between patient satisfaction with care and health-related quality of life (HRQoL) among Medicare recipients with common cancers types (breast, prostate, or lung cancer).MethodsCross-sectional analysis of survey data from 637 Medicare beneficiaries (≥65 years) with breast (n = 304), lung (n = 158), or prostate cancer (n = 175) in twelve hospitals in the Southeastern United States. Participants responded eighteen satisfaction questions across five domains. HRQoL was measured with the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores of the SF-12.v2 instrument.ResultsSF-12 scores were positively associated with satisfaction domain scores. The magnitude of these associations was small with covariate-adjusted effect sizes r ranging from 0.05 to 0.12. Satisfaction scores were highest within the Quality of Care domain and lowest within the Patient Engagement domain.ConclusionsPatient satisfaction domains had only modest association with HRQoL, indicating that these constructs should not be assumed to correlate. Satisfaction domains, including how patients access care, coordinate care, and engage within the healthcare system, were identified as potential areas for improvement. Patient satisfaction assessment across age groups may inform oncology care providers on ways in which their patients perceive the quality of care received, which ultimately affect healthcare organizations' accreditation, ranking, and reimbursement.     

The association between patient experience and healthcare outcomes using SEER-CAHPS patient experience and outcomes among cancer survivors

ObjectiveTo understand the relationship between patient experience, as measured by scores on the Consumer Assessment of Healthcare Providers and Systems (CAHPS®) survey, and clinical and financial outcomes among older cancer survivors.Materials and MethodsWe analyzed the records of all Fee-for-Service (FFS) Medicare beneficiaries 66 years and older who completed one CAHPS survey from 2001 to 2004 or 2007–2013 with one of the five following cancer types: breast, bladder, colorectal, lung, or prostate; and completed a CAHPS survey within 5 years of cancer diagnosis date. We conducted a multivariate analysis, controlling for clinical and demographic variables, to evaluate the association between excellent CAHPS scores and the following clinical and financial outcomes: mortality, emergency department visits, and total healthcare expenditures.ResultsA total of 7395 individuals were present in our cohort, with 57% being male and 85.7% non-Hispanic White. Breakdown of the cohort by cancer site is as follows: prostate (40.4%), breast (28.6%), colorectal (14.0%), lung (9.4%), and bladder (7.6%). When looking at the relationship between CAHPS scores and clinical outcomes, there was no significant difference between excellent and non-excellent CAHPS score respondents in all three of the clinical outcomes studied. Furthermore, there was no association between ED utilization and patient experience scores when stratifying by cancer site and race/ethnicity among this cohort.ConclusionIn this cohort, a highly rated patient experience, as measured by responses on the CAHPS survey, is not associated with improved clinical outcomes among older cancer survivors.     

Familial transmission of prostate,breast and colorectal cancer in adoptees is related to cancer in biological but not in adoptive parents: A nationwide family study

AimFamilial clustering of prostate, breast and colorectal cancer is well established, but the familial risk of these cancers has not been determined among adoptees. The aim was to disentangle the contributions of genetic and environmental factors to the familial transmission of prostate, breast and colorectal cancer.MethodsThe Swedish Multi-Generation Register was used to follow all adoptees born between 1932 and 1969 (n = 70,965) for prostate, breast and colorectal cancer from January 1958 up to December 2010. The risk of prostate, breast and colorectal cancer was estimated in adoptees with at least one biological parent with the same cancer type compared with adoptees without a biological parent with the same cancer type. The risk of cancer was also determined in adoptees with at least one adoptive parent with cancer compared with adoptees with an adoptive parent without cancer.ResultsAdoptees with at least one biological parent with prostate, breast or colorectal cancer were more likely to have cancer of the same type than adoptees with biological parents not affected by these respective cancer types (standardised incidence ratio = SIR: 1.8 [95% confidence interval 1.2–2.7], 2.0 [1.6–2.5] and 1.9 [1.2–2.9], respectively). In contrast, adoptees with at least one adoptive parent with prostate, breast or colorectal cancer were not at an increased risk of these respective cancer types (SIR = 1.2 [0.94–1.6], 0.97 [0.71–1.3], and 1.1 [0.71–1.5], respectively).ConclusionsThe findings of the study support the importance of genetic/biological factors in the familial transmission of prostate, breast and colorectal cancer.     

Cancer in the oldest old in the United States: Current statistics and projections

ObjectivesThe oldest old population in the US, defined as aged ≥ 85 years, is projected to double from 4.3 million in 2000 to 9.6 million in 2030. The purpose of this study was to assess the current and projected cancer burden in the oldest old.Materials and MethodsThis was a retrospective cohort study using the national Surveillance, Epidemiology, and End Results (SEER) tumor registry. Historical trends were assessed and projections were created for the top 10 cancers by incidence, and also by proportion of cancer deaths for those aged ≥ 85 years.ResultsCurrently, the oldest old experiences about 7% of annual new cancer cases and 14% of cancer deaths. The most common cancers by incidence per 100,000 people are colorectal (336), lung (297), breast (254), and prostate (165), while the leading causes of cancer deaths are lung (19%), colorectal (13%), prostate (9%), and breast (7%). The incidences of non-Hodgkin lymphoma, melanoma, bladder, lung, and pancreatic cancers have been increasing, while those of other cancers are stable or decreasing. A substantial proportion of the oldest old (24%) had prior primary cancers. If historical trends continue to 2030, we project that 9% of newly diagnosed cancer cases and 23% of cancer deaths annually will occur in the oldest old.ConclusionThe oldest old may have unique cancer incidence and mortality. To manage a projected major increase in the burden of cancer care, substantial investments in geriatric oncology research, education, and practice are needed.     

Perceptions of care coordination among older adult cancer survivors: A SEER-CAHPS study

ObjectiveCare coordination reflects deliberate efforts to harmonize patient care. This study examined variables associated with patient-reported care coordination scores among Medicare beneficiaries with a history of cancer.MethodsWe utilized Surveillance, Epidemiology, and End Results-Consumer Assessment of Healthcare Providers and Systems (SEER-CAHPS) linked data, which includes cancer registry data, patient experience surveys, and Medicare claims. We identified Medicare beneficiaries with a CAHPS survey ≤10 years after cancer diagnosis who reported seeing a personal doctor within six months. Multivariable regression models examined associations between cancer survivor characteristics and patient-reported care coordination, with higher scores indicating better coordination.ResultsCancer site distribution of the 14,646 survey respondents was 33.7% prostate, 22.1% breast, 11.1% colorectal, 7.2% lung, and 25.9% other. Rural residence at diagnosis (versus urban, 1.1-point difference; p = 0.04) and reporting >4 visits with a personal doctor (versus 1–2 visits, 3.0-point difference; p < 0.001) were significantly associated with higher care coordination. Older age (p < 0.001) and seeing more specialists (p = 0.006) were associated with significantly lower care coordination. Patients with melanoma (women: 5.2-point difference, p < 0.001; men: 2.7 points, p = 0.01) or breast cancer (women: 2.4 points; p < 0.001) reported significantly lower care coordination scores than did men with prostate cancer (reference group). Time from diagnosis to survey, cancer stage, number of cancers, and comorbidities were not significantly associated with care coordination scores.DiscussionCancer site, rural residence, and number of physician interactions are associated with patient-reported care coordination scores. Future research should address multilevel influences that lead to worse care coordination for older adult cancer survivors.     

Age-related health deficits and five-year mortality among older,long-term cancer survivors

IntroductionGeriatric assessment evaluates multiple domains of health that, together, are superior to using chronologic age for predicting outcomes, such as hospitalization and mortality among patients with cancer. Most studies have not included comparison groups of individuals without cancer and assessed domains around the time of initial cancer diagnosis. Further, the potential for brief, self-reported measures to capture deficits that similarly predict mortality has not been well examined. This study compared age-related health deficit prevalence between older, long-term cancer survivors and individuals without a cancer history, and estimated associations between deficits and mortality risk among survivors.Materials and methodsAnalyses included participants in the Cancer Prevention Study (CPS)-II Nutrition Cohort who were cancer-free at enrollment in 1992/1993 and completed the Patient Reported Outcome Measurement Information System® (PROMIS®) global health questionnaire in 2011. Age-related deficits in five domains (comorbidities, functional status, mental health, malnutrition/weight loss, and social support) were self-reported. Cancer information was self-reported and confirmed via medical records or state cancer registries. Vital status through 2016 and cause of death was ascertained by linkage with the National Death Index.ResultsAnalyses included 9979 participants (median age = 80) diagnosed with invasive cancer 5–20 years prior to completing the 2011 survey and 63,578 participants without a cancer history (median age = 79). Overall deficits in the five domains were similar among long-term cancer survivors and controls. However, survivors of specific cancer types — non-Hodgkin lymphoma (NHL), lung, and kidney cancer – were more likely to report deficits in mental health and functional status than the control group. Among all survivors, each domain was independently associated with all-cause mortality, particularly functional status (hazard ratio [HR] = 2.02; 95% confidence interval [CI]: 1.80–2.27) and mental health (HR = 1.84; 95% CI: 1.65–2.04). Mortality risk increased with the number of deficits.DiscussionThese results suggest that, several years after treatment, NHL, lung, and kidney cancer survivors are still more likely to experience age-related deficits compared to other similarly-aged individuals. Furthermore, results show that shorter, self-reported physical and mental health assessments, such as the PROMIS® global health questions, are predictive of mortality among older, long-term cancer survivors and, therefore, may be useful in clinical and research settings.     

Thoracotomy and VATS Surgery in Local Non–Small-Cell Lung Cancer: Differences in Long-Term Health-Related Quality Of Life

BackgroundAs a result of routine low-dose computed tomographic screening, lung cancer is more frequently diagnosed at earlier, operable stages of disease. In treating local non–small-cell lung cancer, video-assisted thoracoscopic surgery (VATS), a minimally invasive surgical approach, has replaced thoracotomy as the standard of care. While short-term quality-of-life outcomes favor the use of VATS, the impact of VATS on long-term health-related quality of life (HRQoL) is unknown.Patients and MethodsWe studied patients who underwent lobectomy for the treatment of non–small-cell lung cancer from January 2006 to January 2013 at a single institution (n = 456). Patients who underwent segmentectomy (n = 27), who received neoadjuvant therapy (n = 13), or who were found to have clinical stage > T2 or > N0 disease (n = 45) were excluded from analysis. At time of HRQoL assessment, 199 patients were eligible for study and were mailed the generic HRQoL instrument 15D.ResultsA total of 180 patients (90.5%) replied; 92 respondents underwent VATS while 88 underwent open thoracotomy. The VATS group more often had adenocarcinoma (P = .006), and lymph node stations were sampled to a lesser extent (P = .004); additionally, hospital length of stay was shorter among patients undergoing VATS (P = .001). No other clinical or pathologic differences were observed between the 2 groups. Surprisingly, patients who underwent VATS scored significantly lower on HRQoL on the dimensions of breathing, speaking, usual activities, mental function, and vitality, and they reported a lower total 15D score, which reflects overall quality of life (P < .05).ConclusionIn contrast to earlier short-term reports, long-term quality-of-life measures are worse among patients who underwent VATS compared to thoracotomy.     

Incidence and prognostic impact of other cancers in a population of long-term survivors of chronic lymphocytic leukemia

BackgroundInformation on the impact of other cancers (OCs) in long-term survivors (LTSs) of chronic lymphocytic leukemia (CLL) is limited.Patients and methodsPatients with CLL who survived >10 years were defined as LTSs of CLL. We calculated standardized incidence ratios (SIRs) to compare the incidence of OC in LTS of CLL versus the general population. A multivariable model was used to identify independent predictors of OC. Overall survival was analyzed as a function of the presence of OC.ResultsAmong 797 LTSs of CLL, the cumulative frequency of OC was 36%, similar between 570 patients (72%) who required treatment for CLL (TRT) and 227 (28%) who remained untreated (UT). The most common OC in both groups was non-melanoma skin cancer, followed by prostate cancer, breast cancer, melanoma, lung cancer, and leukemia in TRT patients, and by prostate cancer, breast cancer, melanoma, lung cancer, and gastrointestinal tumors in the UT group. The SIR for all OC was 1.2 (P = 0.034). It was higher in males (SIR 1.31; P = 0.013) and patients <60 years (SIR 1.27; P = 0.027). A higher SIR was shown for secondary leukemia, melanoma, and head-and-neck cancers, whereas a lower SIR was found for gastrointestinal and bladder cancers. Independent predictors of OC development were advanced age, male gender, and lower platelets. The survival of patients with OC was 16.2 months and that of patients without OC 22.9 years.ConclusionsLTSs of CLL have an increased incidence of OC compared with the general population. CLL therapy is not a risk factor for OC in LTSs of CLL. The presence of an OC in these patients may be associated with shorter survival.     

Impact of the SARS-CoV-2 pandemic on female breast,colorectal and non-small cell lung cancer incidence,stage and healthcare pathway to diagnosis during 2020 in Wales,UK, using a national cancer clinical record system

Background COVID-19 pandemic responses impacted behaviour and health services. We estimated the impact on incidence, stage and healthcare pathway to diagnosis for female breast, colorectal and non-small cell lung cancers at population level in Wales.Methods Cancer e-record and hospital admission data linkage identified adult cases, stage and healthcare pathway to diagnosis (population ~2.5 million). Using multivariate Poisson regressions, we compared 2019 and 2020 counts and estimated incidence rate ratios (IRR).Results Cases decreased 15.2% (n = −1011) overall. Female breast annual IRR was 0.81 (95% CI: 0.76–0.86, p < 0.001), colorectal 0.80 (95% CI: 0.79–0.81, p < 0.001) and non-small cell lung 0.91 (95% CI: 0.90–0.92, p < 0.001). Decreases were largest in 50–69 year olds for female breast and 80+ year olds for all cancers. Stage I female breast cancer declined 41.6%, but unknown stage increased 55.8%. Colorectal stages I–IV declined (range 26.6–29.9%), while unknown stage increased 803.6%. Colorectal Q2-2020 GP-urgent suspected cancer diagnoses decreased 50.0%, and 53.9% for non-small cell lung cancer. Annual screen-detected female breast and colorectal cancers fell 47.8% and 13.3%, respectively. Non-smal -cell lung cancer emergency presentation diagnoses increased 9.5% (Q2-2020) and 16.3% (Q3-2020).Conclusion Significantly fewer cases of three common cancers were diagnosed in 2020. Detrimental impacts on outcomes varied between cancers. Ongoing surveillance with health service optimisation will be needed to mitigate impacts.Subject terms: Cancer epidemiology, Cancer epidemiology     

Informed decision making does not affect health-related quality of life in lung cancer screening (NELSON trial)

BackgroundIt is believed that making an informed decision about (screening) participation is associated with better health-related quality of life (HRQoL) outcomes. This is the first study in cancer screening to explore this association in subjects participating in a lung cancer computed tomography (CT) screening trial.MethodsParticipants that made either an informed decision to participate (n = 155) or not (n = 133) were selected for this study. Differences in HRQoL, measured as generic HRQoL (Short Form 12 [SF-12] and EuroQol questionnaire [EQ-5D]), anxiety/distress (State-Trait Anxiety Inventory [STAI-6], Impact of Event Scale [IES] and Consequences of Screening-Lung Cancer [COS-LC]), were tested with Mann–Whitney U tests and ANOVA at three assessment points (when deciding about participation, before trial randomisation and 2 months after receiving the CT result).ResultsSubjects who made an informed decision to participate had no better scores than those who did not make an informed decision for 23 out of 24 HRQoL comparisons, except for a better mean score for mental health (Mental Component Summary (MCS) = 53.9 ± 9.2 versus 51.0 ± 10.1, p = 0.003) before randomisation. For subjects with an indeterminate CT result (n = 64), no significant differences were found between subjects with (n = 35) or without (n = 29) an informed decision.ConclusionSubjects who did not make an informed decision to participate in lung cancer CT screening trial did not experience worse HRQoL during screening than subjects who did make an informed decision, either in general or after receiving an indeterminate result.     

Three-Year Safety,Tolerability, and Health-Related Quality of Life Outcomes of Adjuvant Osimertinib in Patients With Resected Stage IB to IIIA EGFR-Mutated NSCLC: Updated Analysis From the Phase 3 ADAURA Trial

IntroductionIn ADAURA, adjuvant osimertinib significantly improved disease-free survival versus placebo in resected stage IB to IIIA EGFR-mutated NSCLC. We report in-depth analyses of three-year safety, tolerability, and health-related quality of life (HRQoL) from ADAURA.MethodsPatients were randomized 1:1 to osimertinib 80 mg or placebo once daily for up to 3 years. Safety assessments were performed at baseline, week 2, week 4, week 12, and every 12 weeks until treatment completion or discontinuation, and 28 days after treatment was stopped. The SF-36 survey measured HRQoL at baseline, week 12, week 24, and every 24 weeks until recurrence, treatment completion or discontinuation. Data cutoff: April 11, 2022.ResultsSafety and HRQoL analysis sets: osimertinib, n = 337 and n = 339; placebo, n = 343 each. Median (range) total exposure duration was longer with osimertinib versus placebo: 35.8 (0–38) versus 25.1 (0–39) months. Most adverse events (AEs) were first reported within 12 months of starting treatment (osimertinib 97%, placebo 86%). AEs leading to dose reduction, interruption or discontinuation were reported in 12%, 27% and 13% respectively of patients with osimertinib; 1%, 13% and 3% with placebo. Stomatitis and diarrhea were the most common AEs leading to osimertinib dose reduction or interruption; interstitial lung disease was the most common leading to osimertinib discontinuation (per protocol). There were no differences in time to deterioration for SF-36 physical, mental component summaries between osimertinib and placebo.ConclusionsNo new safety signals were reported and HRQoL was maintained with 3 years of adjuvant osimertinib treatment. Combined with significant efficacy benefit, these data further support adjuvant osimertinib in stage IB to IIIA EGFR-mutated NSCLC.     

High RNA-binding motif protein 3 expression is an independent prognostic marker in operated prostate cancer and tightly linked to ERG activation and PTEN deletions

BackgroundThe RNA-binding motif protein 3 (RBM3) has recently been suspected as a prognostic biomarker in several cancers.MethodsRBM3 expression was analysed by immunohistochemistry on a tissue microarray containing 11,152 prostate cancers.ResultsRBM3 expression was more often detectable in malignant compared to benign prostate. RBM3 immunostaining was found in 64% of the interpretable prostate cancers and was considered strong in 25.6%. High RBM3 expression was linked to advanced tumour stage, high Gleason score, positive nodal involvement and positive surgical margin status (p < 0.0001 each). There was a remarkable accumulation of strong RBM3 expression in v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) positive prostate cancers and tumours harbouring PTEN deletions (p < 0.0001 each). Moreover, RBM3 staining was tightly related to early biochemical recurrence if all tumours or subgroups of ERG negative and ERG positive cancers were analysed (p < 0.0001 each). In multivariate analysis, including RBM3 staining, Gleason grade, pT stage, prostate-specific antigen (PSA), surgical margin status, and nodal status, the prognostic impact of RBM3 staining retained statistically significance (p = 0.0084).ConclusionOur observations indicate that high RBM3 expression is an independent prognostic marker in prostate cancer. The tight link to ERG activation and PTEN deletions suggest interaction with key molecular pathways in prostate cancer.     

Long-term survival among Hodgkin's lymphoma patients with gastrointestinal cancer: a population-based study

BackgroundThe increased risk of gastrointestinal (GI) cancers after Hodgkin's lymphoma (HL) is well established. However, no large population-based study has described the actuarial survival after subsequent GI cancers in HL survivors (HL-GI).Patients and methodsFor 209 patients with HL-GI cancers (105 colon, 35 stomach, 30 pancreas, 21 rectum, and 18 esophagus) and 484 165 patients with first primary GI cancers (GI-1), actuarial survival was compared, accounting for age, gender, race, GI cancer stage, radiation for HL, and other variables.ResultsThough survival of HL patients who developed localized stage colon cancer was similar to that of the GI-1 group, overall survival (OS) of HL patients with regional or distant stage colon cancer was reduced [hazard ratio, (HR) = 1.46, P = 0.01]. The HL survivors with regional or distant stage colon cancer in the transverse segment had an especially high risk of mortality (HR: 2.7, P = 0.001 for OS). For localized stomach cancer, OS was inferior among HL survivors (HR = 3.46, P = 0.006).ConclusionsThe HL patients who develop GI cancer experience significantly reduced survival compared with patients with a first primary GI cancer. Further research is needed to explain the inferior survival of HL patients and to define selection criteria for cancer screening in HL survivors.     

Body mass index and 20 specific cancers: re-analyses of dose–response meta-analyses of observational studies

BackgroundObjectives were to provide an overview and understand the strength of evidence and extent of potential biases and validity of claimed associations between body mass index (BMI) and risk of developing cancer.MethodsWe carried out an umbrella review and comprehensively re-analyzed the data of dose–response meta-analyses on associations between BMI and risk of 20 specific cancers (bladder, brain, breast, colonic, rectal, endometrial, gallbladder, gastric, leukemia, liver, lung, melanoma, multiple myeloma, non-Hodgkins lymphoma, esophagus, ovarian, pancreatic, prostate, renal, thyroid) by adding big data or missed individual studies. Convincing evidence for an association was defined as a strong statistical significance in fixed-effects and random-effects meta-analyses at P < 0.001, 95% prediction interval (PI) excluded null, there was no large between-study heterogeneity and no small study effects. Suggestive evidence was defined as meeting the significance threshold for the random summary effects of P < 0.05, but 95% PI included the null. Weak evidence was defined as meeting the significance threshold for the random summary effects at a P < 0.05, but 95% PI included the null and there was large between-study heterogeneity or there were small study effects.ResultsConvincing evidence for an association with BMI was detectable for six cancers (leukemia, multiple myeloma, pancreatic, endometrial, rectal, and renal cell carcinoma). Suggestive evidence was detectable for malignant melanoma, non-Hodgkins lymphoma, and esophageal adenocarcinoma. Weak evidence was detectable for brain and central nervous system tumors, breast, colon, gall bladder, lung, liver, ovarian, and thyroid cancer. No evidence was detectable for bladder, gastric, and prostate cancer.ConclusionsThe association of increased BMI and cancer is heterogeneous across cancer types. Leukemia, multiple myeloma, pancreatic, endometrial, rectal, and renal cell carcinoma are convincingly associated with an increased BMI by dose–response meta-analyses.