Incidence Of Other Cancers Research Articles

A maternal germline mutator phenotype in a family affected by heritable colorectal cancer.

Variation in DNA repair genes can increase cancer risk by elevating the rate of oncogenic mutation. Defects in one such gene, MUTYH, are known to elevate the incidence of colorectal cancer in a recessive Mendelian manner. Recent evidence has also linked MUTYH to a mutator phenotype affecting normal somatic cells as well as the female germline. Here, we use whole genome sequencing to measure germline de novo mutation rates in a large extended family containing both mothers and fathers who are affected by pathogenic MUTYH variation. By developing novel methodology that uses siblings as "surrogate parents" to identify de novo mutations, we were able to include mutation data from several children whose parents were unavailable for sequencing. In the children of mothers affected by the pathogenic MUTYH genotype p.Y179C/V234M, we identify an elevation of the C>A mutation rate that is weaker than mutator effects previously reported to be caused by other pathogenic MUTYH genotypes, suggesting that mutation rates in normal tissues may be useful for classifying cancer-associated variation along a continuum of severity. Surprisingly, we detect no significant elevation of the C>A mutation rate in children born to a father with the same MUTYH genotype, and we similarly find that the mutator effect of the mouse homolog Mutyh appears to be localized to embryonic development, not the spermatocytes. Our results suggest that maternal MUTYH variants can cause germline mutations by attenuating the repair of oxidative DNA damage in the early embryo.

POT1 tumour predisposition: a broader spectrum of associated malignancies and proposal for additional screening program

Protection of Telomeres Protein 1 (POT1) protein is an essential subunit of the shelterin telomere binding complex, regulating telomere length. Some POT1 gene pathogenic variants (PV) lead to telomere elongation, genomic instability and higher risk of cancer. POT1 tumour predisposition syndrome (POT1-TPD) has autosomal dominant inheritance and unknown penetrance. It is associated with increased risk of cutaneous melanoma, chronic lymphocytic leukaemia, angiosarcoma and gliomas. In this work, we aim to describe a broader cancer phenotype related to POT1-TPD, in three families (two with a four generation pedigree, one with a five generation pedigree). The three index cases were referred to our oncogenetic centre for genetic counselling due to their personal history of cancer. Two underwent clinical exome sequencing of 4,867 genes associated with Mendelian genetic diseases, and another underwent gene panel sequencing including POT1, which identified three different POT1 PV: NC_000007.14(NM_015450.2):c.349C>T; NC_000007.14(NM_015450.2):c.233T>C and NC_000007.14(NM_015450.2):c.818G>A; already described in the literature. Referenced relatives, did a target genetic test (according to the POT1 PV identified in the family). In total, 37 individuals were tested (51.4% females), median age of 46 (22–81) years, with POT1 PV detected in 22. POT1-TPD was observed, but also a higher incidence of other cancers (other sarcomas, papillary thyroid cancer, early onset prostate cancer and leukaemia). These findings contribute to an increase in our knowledge about POT1 PV, and it can play a role in the definition of future POT1 PV screening criteria, POT1 carrier surveillance protocols (possibly considering screening for all types of sarcomas) and in genetic counselling.

Malignancy risk and mortality after lung transplantation: A single-institution experience over 31 years

BackgroundMalignancy is a long-term complication of lung transplantation (LTx); however, contemporary Australian data and detailed evaluation of non-reportable cancers are lacking. MethodsRetrospective review of LTx recipients’ medical records and registry data linkage were performed to identify histologically proven malignancies. Baseline clinico-demographic variables were collected, and cancer incidence was compared with reported data for the general Australian population. ResultsThere were 1,715 LTx in 1,631 patients between 1989-2021, with a follow-up of 9,696 person-years. 893 (54.8%) patients were male, and the median age at first LTx was 54.7 years. There were 886 deaths with a median overall survival of 7.5 years (95% CI 6.8-8.3 years). 1,774 separate invasive cancer events occurred across 407 patients, of which, 1,588 (89.5%) were non-melanoma skin cancers (NMSCs). This translated to a 9-fold increased incidence of NMSCs, and a 4-fold increased incidence of other cancers compared with the general population. Cancer mortality reached parity with chronic lung allograft dysfunction ten years post-first transplant, and was independently associated with age (HR per year increase in age 1.02 [95% CI 1.01-1.03], p=0.001), EBV primary mismatch (HR 3.24 [95% CI 1.68-6.25], versus non-mismatch, p=0.002) and cancer count (HR per cancer event 1.19 [95% CI 1.13-1.24], p<0.0001), but was not associated with a pre-transplant malignancy history. ConclusionsOur 31-year single-center experience demonstrates that malignancies are a significant mortality burden to long-term LTx survivors, dominated by NMSCs that are poorly reported in cancer datasets. A history of pre-transplant malignancy was associated with shorter time to post-transplant malignancy, but was not associated with cancer death.

Risk of Breast Cancer After Diabetes in Pregnancy: A Population-based Cohort Study

ObjectivesDiabetes is associated with an increased risk of several cancers, including postmenopausal breast cancer. The evidence for higher breast cancer risk after diabetes in pregnancy is conflicting. We compared the incidence of breast and other cancers between pregnant women with and without diabetes. MethodsThis work was a propensity-matched, retrospective cohort study using population-based health-care databases from Ontario, Canada. Those deliveries with gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (pregestational DM) were identified and matched to deliveries without diabetes mellitus (non-DM). Deliveries from each diabetes cohort were matched 1:2 on age, parity, year of delivery, and propensity score to non-DM deliveries. Matched subjects were followed from delivery for incidence of breast cancer as a primary outcome, and other site-specific cancers as secondary outcomes. We performed Cox proportional hazards regression to compare rates of breast cancer between matched groups. ResultsOver a median of 8 (interquartile range 4 to 13) years of follow-up, compared with non-DM deliveries, the incidence of breast cancer was significantly lower for GDM but similar for pregestational DM deliveries (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.82 to 0.98; and HR 0.92, 95% CI 0.80 to 1.07, respectively). GDM was associated with a significantly higher incidence of pancreatic and hepatocellular cancer, and pregestational DM was associated with a higher incidence of thyroid, hepatocellular, and endometrial cancers. ConclusionsDiabetes in pregnancy does not have a higher short-term risk of subsequent breast cancer, but there may be a higher incidence of other cancers.

Ibrutinib Plus Venetoclax with MRD-Directed Duration of Treatment Is Superior to FCR and Is a New Standard of Care for Previously Untreated CLL: Report of the Phase III UK NCRI FLAIR Study

Ibrutinib Plus Venetoclax with MRD-Directed Duration of Treatment Is Superior to FCR and Is a New Standard of Care for Previously Untreated CLL: Report of the Phase III UK NCRI FLAIR Study

Cancer incidence in the US military: An updated analysis.

Military and general populations differ in factors related to cancer occurrence and diagnosis. This study compared incidence of colorectal, lung, prostate, testicular, breast, and cervical cancers between the US military and general US populations. Data from the US Department of Defense's Automated Central Tumor Registry (ACTUR) and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program were analyzed. Persons in ACTUR were active-duty members 20-59 years old during 1990-013. The same criteria applied to persons in SEER. Age-adjusted incidence rates, incidence rate ratios, and 95% confidence intervals were calculated by sex, race, age, and cancer stage. Temporal trends were analyzed. ACTUR had higher rates of prostate and breast cancers, particularly in 40- to 59-year-olds. Further analyses by tumor stage showed this was primarily confined to localized stage. Incidence rates of colorectal, lung, testicular, and cervical cancers were significantly lower in ACTUR than in SEER, primarily for regional and distant tumors in men. Temporal incidence trends were generally similar overall and by stage between the populations, although distant colorectal cancer incidence tended to decrease starting in 2006 in ACTUR whereas it increased during the same period in SEER. Higher rates of breast and prostate cancers in servicemembers 40-59 years of age than in the general population may result from greater cancer screening utilization or cumulative military exposures. Lower incidence of other cancers in servicemembers may be associated with better health status.

Variation in Post-Transplant Cancer Incidence among Italian Kidney Transplant Recipients over a 25-Year Period

This cohort study examined 25-year variations in cancer incidence among 11,418 Italian recipients of kidney transplantation (KT) from 17 Italian centers. Cancer incidence was examined over three periods (1997-2004; 2005-2012; and 2013-2021) by internal (Incidence rate ratio-IRR) and external (standardized incidence ratios-SIR) comparisons. Poisson regression was used to assess trends. Overall, 1646 post-transplant cancers were diagnosed, with incidence rates/1000 person-years ranging from 15.5 in 1997-2004 to 21.0 in 2013-2021. Adjusted IRRs showed a significant reduction in incidence rates across periods for all cancers combined after exclusion of nonmelanoma skin cancers (IRR = 0.90, 95% confidence interval-CI: 0.76-1.07 in 2005-2012; IRR = 0.72, 95% CI: 0.60-0.87 in 2013-2021 vs. 1997-2004; Ptrend < 0.01). In site-specific analyses, however, significant changes in incidence rates were observed only for Kaposi's sarcoma (KS; IRR = 0.37, 95% CI: 0.24-0.57 in 2005-2012; IRR = 0.09, 95% CI: 0.04-0.18 in 2013-2021; Ptrend < 0.01). As compared to the general population, the overall post-transplant cancer risk in KT recipients was elevated, with a decreasing magnitude over time (SIR = 2.54, 95% CI: 2.26-2.85 in 1997-2004; SIR = 1.99, 95% CI: 1.83-2.16 in 2013-2021; Ptrend < 0.01). A decline in SIRs was observed specifically for non-Hodgkin lymphoma and KS, though only the KS trend retained statistical significance after adjustment. In conclusion, apart from KS, no changes in the incidence of other cancers over time were observed among Italian KT recipients.

Evolution of the Incidence of Oral Cavity Cancers in the Elderly from 1990 to 2018.

To describe the evolution of the incidence of oral cavity cancers (OCC) among elderly patients in France between 1990 and 2018 and to compare it to the incidence of other cancers sharing the same main risk factors. The incidence of cancers in mainland France from 1990 to 2018 was estimated from incidence data observed in every cancer registry of the Francim network. Incidence was modeled by a 2-dimensional penalized spline of age and year of diagnosis, associated with a random effect corresponding to the registry. The elderly population was divided into two groups: 70-79 years old and ≥80 years old. There was a 72% increase in the number of OCC cases in women over 70 years of age between the periods 1990-1999 and 2010-2018. As for men, there was a stabilization in the number of cases (+2%). Over the same period, for laryngeal and hypopharyngeal cancers, there was a decrease in incidence in elderly men and an increase in elderly women, although less marked than for OCC. Since the 1990s, the incidence of OCC has been increasing in elderly subjects in France, particularly in women. Population aging and growth or alcohol and tobacco consumption alone do not seem to explain this increase, which is not observed in the same proportions for other upper aerodigestive tract cancer subsites sharing the same main risk factors.

Abstract P057: Application of multi-cancer early detection to lung and breast cancer screening populations

Abstract The Center for Global Early Detection at MD Anderson has initiated two longitudinal early detection studies: LEAP (Lung Cancer Early Detection and Prevention, 2013-2019) for lung cancer screening and MERIT (Mammography Early Detection Risk Assessment and Imaging Technologies, 2017-ongoing) for breast cancer screening. Both cohorts enrolled subjects based on US standard-of-care guidelines at the time of enrollment for low-dose CT screening and mammography, respectively. The cohorts collected detailed health data from questionnaires, imaging data, and blood specimens at the time of screening. In addition to information on the screened-detected cancers, follow-up information was collected on any other types of cancers that are diagnosed after enrollment. Here, we evaluate the incidence of other cancers without available screening to assess the potential impact of multi-cancer early detection studies for these two types of screening populations. The two studies enrolled approximately 9,300 subjects (N = 2853 for LEAP; N = 6,400 for MERIT) with median follow up times of 2.99 years (IQR: 1.09-4.08) for LEAP and 2.05 years (IQR: 0.09-3.01) for MERIT. Currently, there are more than 800,000 aliquots of banked biospecimens from both cohorts. The incidence of lung cancer for the LEAP cohort undergoing low-dose CT screening was 0.91% per year. Cancers other than lung cancer were also diagnosed after enrollment including prostate, breast, bladder, head, and neck, colorectal, lymphoma, endocrine, gynecologic, and kidney cancers. Overall, the incidence of other cancers in LEAP was high for those cancers without available screening - 0.49% per year excluding breast, prostate, and colorectal cancers. The incidence of breast cancer for women in LEAP was lower than expected, 0.17% per year, likely a result of underscreening by mammography. For the MERIT cohort, the incidence of breast cancer was 0.89% per year. Cancers other than breast were diagnosed in MERIT after enrollment including gynecologic, melanoma, lung, colorectal, endocrine, bladder, and gastrointestinal cancers. The incidence of other cancers in MERIT was 0.55% per year, excluding colorectal cancer. We conclude that the incidence of cancers without a current screening modality in LEAP and MERIT is sufficiently high (0.49-0.55% per year) to justify the application of multi-cancer screening. Even for cancers with standard-of-care screening, a multi-cancer blood-based biomarker test could be useful given the possibility of underscreening, as we observed for breast cancer in the LEAP cohort. Citation Format: Jennifer Dennison, Ehsan Irajizad, Edwin Ostrin, Myrna Godoy, Olena Weaver, Jessica Leung, Samir Hanash. Application of multi-cancer early detection to lung and breast cancer screening populations. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P057.

Use of Multiple Correspondence Analysis and K-means to Explore Associations Between Risk Factors and Likelihood of Colorectal Cancer: Cross-sectional Study.

BackgroundPrevious works have shown that risk factors are associated with an increased likelihood of colorectal cancer.ObjectiveThe purpose of this study was to detect these associations in the region of Lleida (Catalonia) by using multiple correspondence analysis (MCA) and k-means.MethodsThis cross-sectional study was made up of 1083 colorectal cancer episodes between 2012 and 2015, extracted from the population-based cancer registry for the province of Lleida (Spain), the Primary Care Centers database, and the Catalan Health Service Register. The data set included risk factors such as smoking and BMI as well as sociodemographic information and tumor details. The relations between the risk factors and patient characteristics were identified using MCA and k-means.ResultsThe combination of these techniques helps to detect clusters of patients with similar risk factors. Risk of death is associated with being elderly and obesity or being overweight. Stage III cancer is associated with people aged ≥65 years and rural/semiurban populations, while younger people were associated with stage 0.ConclusionsMCA and k-means were significantly useful for detecting associations between risk factors and patient characteristics. These techniques have proven to be effective tools for analyzing the incidence of some factors in colorectal cancer. The outcomes obtained help corroborate suspected trends and stimulate the use of these techniques for finding the association of risk factors with the incidence of other cancers.

Incidence of other cancer diagnoses in women with breast cancer: a retrospective cohort study with 42,248 women.

The aim of the present study was to determine whether women diagnosed with breast cancer (BC) have an increased incidence of other cancers, e.g., gastric cancer, lung cancer, skin cancer, and so on, compared to healthy women without a breast cancer diagnosis. This retrospective cohort study was based on data from the Disease Analyzer database (IQVIA) and included adult women with an initial diagnosis of BC documented in one of 1,274 general practices in Germany between January 2000 and December 2018. Women with BC were matched to women without cancer by age, index year, yearly consultation frequency, and co-diagnoses. Univariate Cox regression models were used to study the association between BC and the incidence of other cancer diagnoses. 21,124 women with BC and 21,124 women (mean age: 63years) without cancer were included. Within 10years of the index date, 14.3% of women with BC and 10.0% of women without cancer were diagnosed with cancer (p < 0.001). BC was significantly associated with the incidence of other cancer diagnoses (HR: 1.42, p < 0.001). The strongest association was observed for respiratory organ cancer (HR = 1.69, p < 0.001), followed by female genital organ cancer (HR = 1.61, p < 0.001) and cancer of lymphoid and hematopoietic tissue (HR: 1.59, p < 0.001). The results of this study show that women with BC have an increased incidence of another cancer compared to women without cancer. Therefore, it is important to pay particular attention to the development of other malignancies during follow-up in patients with BC. This should be considered especially in patients with a proven genetic mutation.

Cancer during Pregnancy: A Review of Preclinical and Clinical Transplacental Transfer of Anticancer Agents.

Simple SummaryThe use of anti-cancer treatments in pregnant women is an increasingly common situation given the increasing age at first pregnancy. The aim of this study is to review data concerning the transplacental transfer of drugs that can be used in the management of the most common pregnancy-associated cancers. This work is intended to guide clinicians in the choice of the treatments that offer the best benefit–risk ratio for the mother and the fetus and to deliver balanced information to pregnant patients.The occurrence of cancer during pregnancy is observed in 1 in 1000 pregnancies and is expected to increase given the trend of delaying childbearing. While breast cancer is the most common, the incidence of other cancers, such as cervical, ovarian, and lung cancers as well as hemopathies and melanomas, is also increasing. Thus, cancer occurrence in pregnant women raises questions of management during pregnancy and, especially, assessment of the treatment benefit–risk ratio to ensure optimal management for the mother while ensuring the safety of the fetus. Chemotherapy remains a cornerstone of cancer management. If the use of anticancer agents appears possible during pregnancy, while avoiding the first trimester, the extent of placental transfer of different anticancer agents varies considerably thereafter. Furthermore, the significant physiological pharmacokinetic variations observed in pregnant women may have an impact on the placental transfer of anticancer agents. Given the complexity of predicting placental transfer of anticancer agents, preclinical studies are therefore mandatory. The aim of this review was to provide updated data on in vivo and ex vivo transplacental transfer of anticancer agents used in the management of the most common pregnancy-associated cancers to better manage these highly complex cases.

Adherence to Dietary Approaches to Stop Hypertension (DASH)-Style Diet and the Risk of Cancer: A Systematic Review and Meta-Analysis of Cohort Studies

Objective: Several investigators have proposed a protective association between dietary approaches to stop hypertension (DASH) style diet and risk of cancers; however, they have had inconsistent results. The present study aimed to systematically review the prospective cohort studies and if possible quantify the overall effect using meta-analysis.Methods: PubMed, Scopus, and Google Scholar were searched for cohort studies published up to July 2018. Relative risks (RRs) that were reported for fully adjusted models and their confidence intervals were extracted for meta-analysis. The random effects model was used to combine the RRs.Results: Seventeen studies were eligible to be included in the systematic review, from which nine reports assessed the association between the DASH diet and risk of mortality from all cancer types, four assessed incidence of colorectal cancer, and two studies assessed the risk of colon and rectal cancer separately. Four studies examined the association with the incidence of other cancers (breast, hepatic, endometrial, and lung cancer). Meta-analysis showed that high adherence to DASH is associated with a decreased mortality from all cancer types (RR = 0.84, 95% confidence interval [95%CI]: 0.81–0.86). Participants with the highest adherence to the DASH diet had a lower risk of developing colorectal (RR = 0.79, 95%CI: 0.75–0.83), colon (RR = 0.80, 95%CI: 0.74–0.87), and rectal (RR = 0.84, 95%CI: 0.74–0.96) cancers compared to those with the lowest adherence.Conclusion: DASH-style diet should be suggested as a healthy approach associated with decreased risk of cancer in the community. Prospective studies exploring the association for other cancer types and from regions other than the United States are highly recommended.

Loss of BRCA1 Spontaneously Induces the Tumorigenesis in Lacrimal Gland.

Environmental and genetic factors exert important influences on lifespan and neoplastic transformation. We have previously shown that spontaneous tumors form frequently in mice homozygous for a full-length Brca1 deletion. In general, mutations of BRCA1 are closely associated with induction of breast and ovarian cancers but are also known to contribute to the incidence of other cancers at a low frequency. Female Brca1-mutant mice (Brca1co/coMMTV-cre) were generated by crossing Brca1 conditional knockout mice and MMTV-cre mice, and the occurrence of lacrimal gland abnormalities and tumors was followed until mice reached 18 months of age. Lacrimal gland tumors, which occur at a very low frequency in the human population (1 per 1,000,000 per year), were detected in 7 cases of Brca1co/coMMTV-cre mice (2.75%) older than 9 months of age. None of seven mice exhibited any abnormality in the mammary gland including neoplasia, suggesting lacrimal gland tumor is spontaneously and independently formed. These tumors, which were detected in seven mutant mice that displayed exophthalmoses, were malignant, originated from epithelial cells, and were identified as acinic cell carcinoma by pathological analysis. Further analysis revealed that tumorigenesis was accompanied by the accumulation of cyclin D1 and decreased expression of the cellular oncogenes, c-Myc, c-Jun, and c-Raf. Tumors also exhibited rearrangement of cytoskeletal proteins, including β-catenin, keratin 5, and vimentin, depending on tumor progression. These results suggest that BRCA1 is involved in genetic stability of the lacrimal gland, providing new insight into genomic instability in organism maintenance and tumorigenesis of the lacrimal gland.

Common breast cancer risk alleles and risk assessment: a study on 35 441 individuals from the Danish general population

We hypothesized that common breast cancer risk alleles are associated with incidences of breast cancer and other cancers in the general population, and identify low risk women among those invited for screening mammography. About 35 441 individuals from the Danish general population were followed in Danish health registries for up to 21 years after blood sampling. After genotyping 72 breast cancer risk loci, each with 0–2 alleles, the sum for each individual was calculated. We used the simple allele sum instead of the conventional polygenic risk score, as it is likely more sensitive in detecting associations with risks of other endpoints than breast cancer. Breast cancer incidence in the 19 010 women was increased across allele sum quintiles (log-rank trend test; P = 1×10 − 12), but not incidence of other cancers (P = 0.41). Age- and study-adjusted hazard ratio for the fifth versus the first allele sum quintile was 1.82 (95% confidence interval; 1.53–2.18). Corresponding hazard ratios per allele were 1.04 (1.03–1.05) and 1.05 (1.02–1.08) for breast cancer incidence and mortality, similar across risk factors. In 50-year-old women, the starting age for screening mammography in Denmark, the average 5-year breast cancer risk was 1.5%, overall and 1.1%, 1.4%, 1.6%, 1.7%, 2.1%, for the first through fifth quintile, respectively. Based on age, nulliparity, familial history, and allele sum, 25% of women aged 50–69 years, and 94% of women aged 40–49 years, had absolute 5-year breast cancer risks ≤ 1.5%. Using polygenic risk score led to similar results. Common breast cancer risk alleles are associated with incidence and mortality of breast cancer in the general population, but not with other cancers. After including breast cancer allele sum in risk assessment, 25% of women currently being offered screening mammography had an absolute 5-year risk below the cutoff of average risk for a 50-year-old woman.

Agent Orange Exposure Does Not Predict for Shorter Overall Survival in Patients with Chronic Lymphocytic Leukemia: A National Veteran Affairs Tumor Registry Study

BACKGROUNDAgent Orange (AO), a 1:1 mixture of herbicides + TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), was used during the Vietnam War to destroy dense jungle and enemy crops. In 2002 the Department of Veteran Affairs (VA) determined that chronic lymphocytic leukemia (CLL) was associated with AO exposure. Case-control studies suggest an increased risk of death from CLL in areas where herbicide use was highest. There is also an increased incidence of other cancers (prostate, melanoma) in AO-exposed veterans. Limited data exists as to the specific impact of AO exposure on CLL disease presentation and outcome. METHODSPatients (pts) diagnosed with CLL from 2009-2013 were identified in the National VAMC Tumor Registry. Baseline demographic and laboratory parameters were obtained, including Rai stage, marrow cytogenetics (when available), and lymphocyte doubling time (LDT). AO exposure was identified according to the medical record. The VA Benefits and Compensation officers determine AO exposure based on whether a person served on land and in the brown waters in Vietnam during the appropriate timeframe. Timing and types of CLL therapies were identified to determine if AO exposure influenced CLL treatment. RESULTS2052 CLL pts were identified, of which 418 had AO exposure. AO-exposed pts presented at a younger age (63.2 versus [vs] 70.5 years (yrs), p <0.0001), had a higher hemoglobin (14.3 vs 13.8 g/dl, p<0.001) and lower lactate dehydrogenase (LDH) (203 vs 227 IU/L, p = 0.01) compared to those without AO exposure. There were no differences in white cell, platelet, or absolute lymphocyte counts, Rai stage or LDT among the groups. Cytogenetic data was available for 1167 pts. There was no difference in the incidence of 17p-, 11q-, or 13q- between the two groups. Median overall survival (OS) was significantly better in patients with AO exposure, even when adjusted for age and Rai stage (median not reached vs 91.2 months, p <0.0001. OS benefit was primarily seen in pts age 60-69 yrs (p = 0.002), and those with 11q- (p = 0.001). No OS differences were found in pts with 17p- or 13q-. Among all pts, regardless of AO exposure status, OS decreased with higher Rai stage. There was a trend towards AO-exposed pts to be more likely to receive CLL-directed therapies (37% vs 32%, p = 0.07). AO exposed pts were more likely, than unexposed pts, to receive therapies as follows: fludarabine, chlorambucil, rituximab (FCR) first-line (38% vs 21%) and second-line (11.6 vs 5%); bendamustine + rituximab (BR) first-line (25% vs 18%), second-line (35 vs 26%), and third-line (31 vs 23%). Pts with no AO exposure were more likely to receive single agent chlorambucil or cyclophosphamide as first-line therapy (17 vs 10%). CONCLUSIONPts with AO exposure, compared to unexposed pts, had an OS benefit independent of age and Rai stage, with this benefit seen primarily in younger pts (age 60-69 yrs) and in those with 11q-. AO-exposed pts were also more likely to receive disease-specific therapy. This unexpected OS finding will require further analyses for confounding variables, but could potentially be related to earlier treatment with regimens as FCR or BR. DisclosuresMorrison:Celgene: Speakers Bureau; Genentech: Speakers Bureau; Gilead: Speakers Bureau; Pharmacyclics: Speakers Bureau; Celgene: Other: Data Monitoring Committee; Merck: Other: Adjudication Committee.

Skuteczność lenalidomidu u chorego na szpiczaka plazmocytowego współistniejącego z zespołem mielodysplastycznym związanym z izolowaną delecją chromosomu 5q–

Ze względu na znaczne wydłużenie przeżycia chorych na szpiczaka plazmocytowego (PCM) coraz częściej obserwuje się u nich występowanie innych nowotworów. Klasycznym przykładem jest rozwój wtórnych do zastosowanej wcześniej chemioterapii zespołów mielodysplastycznych (MDS). W niniejszej pracy opisano rzadki przypadek chorego, u którego stwierdzono współistnienie PCM oraz MDS związanym z izolowaną del 5q– (MDS 5q–). Zastosowanie lenalidomidu pozwoliło na uzyskanie częściowej remisji cytogenetycznej MDS oraz częściowej remisji PCM.

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

Information on the impact of other cancers (OCs) in long-term survivors (LTSs) of chronic lymphocytic leukemia (CLL) is limited. Patients 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. Among 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. LTSs 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.

Immunosuppression with mammalian target of rapamycin inhibitor and incidence of post-transplant cancer in kidney transplant recipients.

Evidence is limited regarding the effect of de novo therapy with mammalian target of rapamycin (mTOR) inhibitors on cancer risk after kidney transplantation. Collaborative Transplant Study data from 78 146 adult recipients of first deceased-donor kidney transplants (1999-2013) were analysed (4279 mTOR inhibitor, 73 867 no mTOR inhibitor) using standard methods. Propensity score matching was performed for analysis of basal cell and squamous cell skin cancer. Standardized incidence ratios (SIR) versus a matched non-transplant population showed reduced tumour incidence in recipients with de novo mTOR inhibitor therapy compared with no mTOR inhibitor for non-melanoma skin cancer (NMSC) (SIR 5.1 versus 6.1; P =0.019) but not non-NMSC cancers (SIR 1.6 versus 1.7; P =0.35). Within propensity score-matched groups (n = 4265), multivariable Cox regression analysis showed a trend to reduced NMSC with mTOR inhibition [hazard ratio (HR) 0.77; P =0.063] but not for all non-NMSC tumours (HR 0.94; P= 0.59). A significant effect for mTOR inhibition was observed for basal cell carcinoma of the skin (HR 0.56; P= 0.004) but not squamous cell carcinoma (HR 0.87; P= 0.54). De novo mTOR inhibition was associated with a substantially and significantly reduced risk of basal cell carcinoma of the skin after kidney transplantation. A significant reduction of the incidence of other cancers was not found.

Tea consumption and the incidence of cancer: a systematic review and meta-analysis of prospective observational studies.

The aim of this study was to summarize the current evidence on the strength of associations between tea consumption and the incidence of cancer at different sites. We searched PubMed, Embase and the Cochrane Library for relevant articles published before October 2013. Prospective studies that reported effect estimates of cancer incidence, with 95% confidence intervals (CIs), for more than two categories of tea consumption were included. We analysed 87 datasets (57 articles), which included a total of 49,812 incident cases. Overall, high tea consumption had no significant effect on the risk of gastric, rectal, colon, lung, pancreatic, liver, breast, prostate, ovarian, bladder cancers or gliomas. However, high tea consumption was associated with a reduced risk of oral cancer (risk ratio 0.72; 95% CI 0.54-0.95; P=0.021). A dose-response meta-analysis suggested that an increase in tea consumption by one cup per day was associated with a reduced risk of oral cancer (risk ratio 0.89; 95% CI 0.80-0.98; P=0.022), but had little effect on the incidence of other cancers. Subgroup analysis indicated that an increase in the consumption of black tea by one cup per day was associated with an increased risk of breast cancer. Moreover, in western countries, we found that an increase in the consumption of tea by one cup per day was associated with a reduced risk of bladder cancer. Increased tea consumption has no significant effect on the risk of common malignancies. For some cancer types, associations differ according to sex, ethnicity and tea type.