Racial/Ethnic Disparities in Survival Among Patients With Young-Onset Colorectal Cancer

Purpose Racial disparities in colorectal cancer (CRC) persist, despite overall reductions in morbidity and mortality. In addition, incidence is rising among individuals younger than 50 years of age. We compared the survival of young-onset CRC among non-Hispanic black (NHB), non-Hispanic white (NHW), and Hispanic individuals. Patients and Methods Using the National Cancer Institute’s Surveillance, Epidemiology, and End Results program data, we identified individuals between the ages of 20 and 49 years, diagnosed with CRC between 2000 and 2009. Survival rates and Cox proportional hazards models were used to compare stage-specific 5-year survival among NHBs, NHWs, and Hispanics. Results We identified 28,145 patients with young-onset CRC (19,497 NHW; 4,384 NHB; 4,264 Hispanic) during the 10-year study period. Overall survival at 5 years after CRC diagnosis was 54.9% among NHB, 68.1% among NHW, and 62.9% among Hispanic individuals (P < .001). NHB individuals had a significantly higher hazard of cancer-specific death compared with NHWs after adjusting for age, sex, race, stage, county-level poverty, and treatment history in cases of colon (hazard ratio [HR], 1.35; 95% CI 1.26 to 1.45) and rectum/rectosigmoid junction (HR, 1.51; 95% CI, 1.37 to 1.68) cancers, whereas there was no significant difference in survival between NHWs and Hispanics. The greatest racial disparities in cancer-specific survival were observed among NHB and NHW patients diagnosed with stage II cancers of the colon (HR, 1.69; 95% CI, 1.33 to 2.14) and stage III cancers of the rectum (HR, 1.98; 95% CI, 1.63 to 2.40). Conclusion Survival after CRC diagnosis at a young age is significantly worse among NHBs compared with NHWs, even among patients with early-stage disease. Further study is needed to determine whether differences in tumor biology and/or treatment are associated with racial disparities in outcomes, which would have implications for CRC treatment and prevention.

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Racial disparities in survival after young-onset colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.524 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 524-524

Author(s):

Elena Martinez Stoffel ◽

Julie Ruterbusch ◽

Laura S. Rozek ◽

Michele L. Cote

Keyword(s):

Colorectal Cancer ◽

Racial Disparities ◽

Early Stage ◽

Tumor Biology ◽

Cox Proportional Hazards ◽

Stage Ii ◽

Disease Stage ◽

Early Stage Disease ◽

Young Onset ◽

Black And White

524 Background: Despite overall reductions in morbidity and mortality from colorectal cancer (CRC), racial disparities persist. In addition, incidence among individuals age <50 is rising. Our aim was to compare survival of young onset CRC cases diagnosed in black and white individuals. Methods: Using data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program we identified individuals with CRC between the ages of 20 to 49, diagnosed in 2000-2008. Kaplan-Meier and Cox proportional hazards models were used to compare stage-specific 5 year survival between black and white individuals with young onset CRC. Results: A total of 26,236 incident young onset CRC cases (22,121 white, 4,115 black) were identified during the 9 year study period. Overall survival at 5 years following CRC diagnosis was 54.8% among blacks and 67.4% among whites (p<0.001), with blacks having a significantly higher hazard of death after adjusting for age, sex, stage, tumor site, and treatment history (HR 1.34, 95% CI 1.26-1.43). Stratifying by stage at CRC diagnosis, blacks had worse survival at every disease stage compared with whites, with the greatest racial disparities observed among stage II cancers of colon (HR 1.68 95% CI 1.38-2.04) and stage II and III cancers of the rectum (HR 1.78, 95% CI 1.51-2.09, and HR 1.86, 95% CI 1.54-2.24, respectively). Conclusions: Survival after diagnosis of CRC at young age is significantly worse among blacks compared to whites, even among individuals with early stage disease. These findings suggest that differences in tumor biology may play a role in racial disparities in CRC outcomes, which may have implications for adjuvant treatment.

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Effects of metformin and sulfonylureas on overall and colorectal cancer-specific mortality.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.2599 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 2599-2599

Author(s):

Susan Spillane ◽

Kathleen Bennett ◽

Linda Sharp ◽

Thomas Ian Barron

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Proportional Hazards ◽

Early Stage ◽

Population Based ◽

Cox Proportional Hazards ◽

Stage I ◽

Early Stage Disease ◽

All Cause Mortality ◽

Specific Mortality

2599 Background: Preclinical studies have suggested a role for metformin in the treatment of colorectal cancer (CRC). Associations between metformin versus sulfonylurea exposure and mortality (all-cause and colorectal cancer specific) are assessed in this population-based study of patients with a diagnosis of stage I-IV CRC. Methods: National Cancer Registry Ireland records were linked to prescription claims data and used to identify a cohort of patients with incident TNM stage I-IV CRC diagnosed 2001-2006. From this cohort, 2 patient groups were identified and compared for outcomes - those who received a prescription for metformin +/- a sulfonylurea (MET) or a prescription for sulfonylurea alone (SUL) in the 90 days pre CRC diagnosis. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox proportional hazards models adjusted for age, sex, stage, grade, site, comorbidities, year of diagnosis, and insulin, aspirin or statin exposure. Analyses were repeated stratifying by stage and site. Results: 5,617 patients with stage I-IV CRC were identified, of whom 369 received a prescription for metformin or a sulfonylurea in the 90 days pre diagnosis (median follow-up 1.6 years; MET: n=257; SUL: n=112). In adjusted analyses metformin exposure was associated with a 28% lower risk of all-cause mortality relative to sulfonylurea exposure (HR 0.72, 95% CI 0.53-0.98) and a non-significant 24% reduction in CRC-specific mortality (HR 0.76, 95% CI 0.52-1.13). In analyses stratified by site, in colon cancer, metformin exposure was associated with a significant one-third reduction in all-cause mortality (HR 0.66, 95% CI 0.46-0.95) and a non-significant reduction in site-specific mortality (HR 0.64, 95% CI 0.40-1.02). No mortality benefit was observed for rectal cancer. The association between metformin exposure and reduced mortality was strongest for stage I/II disease (all-cause mortality: HR 0.56, 95% CI 0.32-0.98; CRC-specific mortality: HR 0.48, 95% CI 0.21-1.11). Conclusions: Pre-diagnosis metformin exposure in CRC patients was associated with a significant reduction in mortality relative to sulfonylurea exposure. This benefit was greatest in patients with colon cancer and early stage disease.

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The Relationship Between Co-morbidity, Screen-Detection and Outcome in Patients Undergoing Resection for Colorectal Cancer

World Journal of Surgery ◽

10.1007/s00268-021-06079-3 ◽

2021 ◽

Author(s):

Mark S. Johnstone ◽

Donald C. McMillan ◽

Paul G. Horgan ◽

David Mansouri

Keyword(s):

Colorectal Cancer ◽

Cox Regression ◽

Early Stage ◽

Univariate Analysis ◽

Charlson Index ◽

Early Stage Disease ◽

Neutrophil Lymphocyte Ratio ◽

Co Morbidity ◽

Significant Difference ◽

The Relationship

Abstract Background Bowel cancer screening increases early stage disease detection and reduces cancer-specific mortality. We assessed the relationship between co-morbidity, screen-detection and survival in colorectal cancer. Methods A retrospective, observational cohort study compared screen-detected (SD) and non-screen-detected (NSD) patients undergoing potentially curative resection (April 2009–March 2011). Co-morbidity was quantified using ASA, Lee and Charlson Indices. Systemic inflammatory response was measured using the neutrophil lymphocyte ratio (NLR). Covariables were compared using crosstabulation and the χ2 test for linear trend. Survival was analysed using Cox Regression. Results Of 770 patients, 331 had SD- and 439 NSD-disease. A lower proportion of SD patients had a high ASA (≥3) compared to NSD (27.2% vs 37.3%; p = 0.007). There was no significant difference in the proportion of patients with a high (≥2) Lee Index (16.3% SD vs 21.9% NSD; p = 0.054) or high (≥3) Charlson Index (22.7% SD vs 26.9% NSD; p = 0.181). On univariate analysis, NSD (HR 2.182 (1.594–2.989;p < 0.001)), emergency presentation (HR 3.390 (2.401–4.788; p < 0.001)), advanced UICC-TNM (III or IV) (p < 0.001), high ASA (≥3) (HR 1.857 (1.362–2.532; p < 0.001)), high Charlson Index (≥3) (HR 1.800 (1.333–2.432; p < 0.001)) and high (≥3) NLR (HR 1.825 (1.363–2.442; p < 0.001)) were associated with poorer overall survival (OS). NSD predicted poorer cancer-specific survival (CSS) (HR 2.763 (1.776–4.298; p < 0.001)). On multivariate analysis, NSD retained significance as an independent predictor of poorer OS (HR 1.796 (1.224–2.635; p = 0.003)) and CSS (HR 1.924 (1.193–3.102; p = 0.007)). Conclusions Patients with SD cancers have significantly lower ASA scores. After adjusting for ASA, co-morbidity and a broad range of covariables, SD patients retain significantly better OS and CSS.

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The effects of age on treatment and outcomes in women with stage IB-IIB cervical cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.5100 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 5100-5100

Author(s):

Dario R. Roque ◽

Beth Cronin ◽

Katina Robison ◽

Vrishali Lopes ◽

Tina Rizack ◽

...

Keyword(s):

Cervical Cancer ◽

Older Women ◽

Proportional Hazards ◽

Early Stage ◽

Cox Proportional Hazards ◽

Early Stage Disease ◽

Increased Risk ◽

Significant Difference ◽

All Cause Mortality ◽

Disease Specific

5100 Background: Advanced age may affect the treatment choice and subsequent outcome in elderly patients with cervical cancer. Given the potential for cure with either surgery or chemoradiation in early stage disease, we aimed to determine whether a patient’s age influenced the treatment received and the outcome. Methods: Our retrospective cohort identified a total of 303 patients diagnosed with Stage IB1 through IIB cervical carcinoma who were treated at our institution between 2000 and 2010. The eligible patients were divided into two groups based on age at the time of diagnosis: <65 and > 65 years. Adjusted odd ratios were calculated to determine variables associated with treatment received (chemoradiation or surgery). Single and multivariate Cox proportional hazards modeling were used to estimate hazard ratios for variables associated with disease specific survival. Results: Of the patients meeting inclusion criteria, 253 were <65 years and 50 were > 65 years. The distribution of tumor histology, stage and grade was not different between the two groups. After adjusting for histology, stage and a validated comorbidity score, the odds ratio of receiving chemoradiation vs. surgery for the cohort > 65 years was 1.69 (OR 95% CI: 0.68-4.17). There was no significant difference in the type of primary treatment received between the two groups (P = 0.16). Persistent disease was seen in 46 (18%) of the younger patients and in 19 (38%) of the older patients (P = 0.02). In the elderly cohort the treatment received did not influence disease-specific or all-cause mortality. However, compared to women under 65, older women treated surgically had increased disease specific (HR 3.18, 95% CI: 0.98-10.3) and all-cause mortality (HR 6.53, 95% CI: 2.57-16.6). Conclusions: Age does not appear to be a factor influencing the treatment received by patients with Stage IB1-IIB cervical cancer. The type of treatment received does not seem to affect disease-specific mortality among older versus younger women. However, surgery was associated with a 6.5-fold increased risk of all cause mortality among older women when compared to women under 65 years.

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Efficacy of a population-based colorectal cancer screening program and analysis of outcomes in screen-detected and non-screen-detected tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.394 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 394-394

Author(s):

David Mansouri ◽

Donald C. Mcmillan ◽

David S. Morrison ◽

Emilia M. Crighton ◽

Paul G. Horgan

Keyword(s):

Colorectal Cancer ◽

Screening Program ◽

Early Stage ◽

Population Based ◽

Mortality Data ◽

Cancer Specific Survival ◽

Early Stage Disease ◽

Background Population ◽

Specific Mortality ◽

Cancer Specific Mortality

394 Background: Population based faecal occult blood test (FOBt) screening for colorectal cancer reduces cancer specific mortality through the detection of early stage disease. However, programmes are limited by uptake and the characteristics of the test itself. The aim of the present study was to compare features of screen detected (SD) and non-screen detected tumours (NSD) and assess the effect on cancer specific mortality. Methods: Prospectively maintained databases of both the prevalence round of a biennial population based FOBt screening programme and a regional cancer audit database were analysed. Mortality data was obtained from the national registry. Results: Of the 395,097 males and females aged 50 to 74yrs invited to screening, 203,886 (52%) responded, 6,085 (3%) tested positive and 4,632 (76%) attended for colonoscopy. A total of 951 patients were diagnosed with cancer within two years of screening invite: 378 (40%) SD and 573 (60%) NSD. Of the NSD patients, 376 (66%) were non-responders, 134 (23%) were FOBt negative and 63 (11%) did not attend or did not have cancer diagnosed at colonoscopy. Therefore, estimated FOBt sensitivity was 77%, and specificity was 99%. Comparing SD and NSD patients, SD patients were more likely to be male, less socioeconomically deprived, have a tumour with a lower Dukes stage, and more likely to have a left-sided tumour (all p<0.05). In addition, SD patients were more likely to undergo an operation with a curative intent, less likely to undergo an emergency procedure, and less likely to die within 30 days of their procedure (all p<0.001). With a median follow-up of 2 years, SD patients had improved cancer specific survival versus NSD patients (p<0.001). This remained significant on multivariate survival analysis (Cox proportional hazards) including age, sex, deprivation, emergency presentation, tumour site and stage, and curative surgery (p<0.001). Conclusions: Independent of established prognostic factors, SD patients have more favourable outcomes than those with NSD tumours. Therefore, further studies to improve the response rate to a screening invitation and the sensitivity of the current screening test are warranted.

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Age-Related Biology of Early-Stage Operable Breast Cancer and Its Impact on Clinical Outcome

Cancers ◽

10.3390/cancers13061417 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1417

Author(s):

Binafsha M. Syed ◽

Andrew R. Green ◽

Emad A. Rakha ◽

David A.L. Morgan ◽

Ian O. Ellis ◽

...

Keyword(s):

Breast Cancer ◽

Early Stage ◽

Histological Grade ◽

Survival Rates ◽

Growth Factor Receptor ◽

Progesterone Receptors ◽

Biological Characteristics ◽

Cancer Specific Survival ◽

Age Related ◽

Significant Difference

As age advances, breast cancer (BC) tends to change its biological characteristics. This study aimed to explore the natural progression of such changes. The study included 2383 women with clinically T0-2N0-1M0 BC, managed by primary surgery and optimal adjuvant therapy in a dedicated BC facility. Tissue micro-arrays were constructed from their surgical specimens and indirect immunohistochemistry was used for analysis of a large panel (n = 16) of relevant biomarkers. There were significant changes in the pattern of expression of biomarkers related to luminal (oestrogen receptor (ER), progesterone receptors (PgR), human epidermal growth factor receptor (HER-2), E-cadherin, MUC1, bcl2 CK7/8, CK18 and bcl2) and basal (CK5/6, CK14, p53 and Ki67) phenotypes, lymph node stage, histological grade and pathological size when decade-wise comparison was made (p < 0.05). The ages of 40 years and 70 years appeared to be the milestones marking a change of the pattern. There were significantly higher metastasis free and breast cancer specific survival rates among older women with ER positive tumours while there was no significant difference in the ER negative group according to age. Biological characteristics of BC show a pattern of change with advancing age, where 40 years and 70 years appear as important milestones. The pattern suggests <40 years as the phase with aggressive phenotypes, >70 years as the less aggressive phase and 40–70 years being the transitional phase.

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Radiomics is feasible for prediction of spread through air spaces in patients with nonsmall cell lung cancer

Scientific Reports ◽

10.1038/s41598-021-93002-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yuki Onozato ◽

Takahiro Nakajima ◽

Hajime Yokota ◽

Jyunichi Morimoto ◽

Akira Nishiyama ◽

...

Keyword(s):

Lung Cancer ◽

Predictive Model ◽

Cell Lung Cancer ◽

Early Stage ◽

Characteristic Curve ◽

Sublobar Resection ◽

Tumor Spread ◽

Early Stage Disease ◽

Significant Difference ◽

Spread Through Air Spaces

AbstractTumor spread through air spaces (STAS) in non-small-cell lung cancer (NSCLC) is known to influence a poor patient outcome, even in patients presenting with early-stage disease. However, the pre-operative diagnosis of STAS remains challenging. With the progress of radiomics-based analyses several attempts have been made to predict STAS based on radiological findings. In the present study, patients with NSCLC which is located peripherally and tumors ≤ 2 cm in size on computed tomography (CT) that were potential candidates for sublobar resection were enrolled in this study. The radiologic features of the targeted tumors on thin-section CT were extracted using the PyRadiomics v3.0 software package, and a predictive model for STAS was built using the t-test and XGBoost. Thirty-five out of 226 patients had a STAS histology. The predictive model of STAS indicated an area under the receiver-operator characteristic curve (AUC) of 0.77. There was no significant difference in the overall survival (OS) for lobectomy between the predicted-STAS (+) and (−) groups (p = 0.19), but an unfavorable OS for sublobar resection was indicated in the predicted-STAS (+) group (p < 0.01). These results suggest that radiomics with machine-learning helped to develop a favorable model of STAS (+) NSCLC, which might be useful for the proper selection of candidates who should undergo sublobar resection.

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Sedentary Behaviors, TV Viewing Time, and Risk of Young-Onset Colorectal Cancer

JNCI Cancer Spectrum ◽

10.1093/jncics/pky073 ◽

2018 ◽

Vol 2 (4) ◽

Cited By ~ 18

Author(s):

Long H Nguyen ◽

Po-Hong Liu ◽

Xiaobin Zheng ◽

NaNa Keum ◽

Xiaoyu Zong ◽

...

Keyword(s):

Colorectal Cancer ◽

Proportional Hazards ◽

Statistical Tests ◽

Cox Proportional Hazards ◽

Health Study ◽

Viewing Time ◽

Sedentary Behaviors ◽

Tv Viewing ◽

Young Onset ◽

Increased Risk

Abstract Background Colorectal cancer (CRC) diagnosed before age 50 years, or young-onset CRC, is increasing globally with undefined etiology. A sedentary lifestyle is an emerging risk factor for CRC after age 50 years, but its role in young-onset CRC is unknown. Methods We prospectively evaluated sedentary behaviors, primarily time watching television (TV), and risk of young-onset CRC among 89 278 women in the Nurses’ Health Study II ages 25–42 years at recruitment (1991–2011). We used Cox proportional hazards modelling to estimate relative risks (RR) and 95% confidence intervals (CIs). Statistical tests were two-sided. Results We documented 118 young-onset CRCs over 1 262 540 person-years. Sedentary TV viewing time was statistically significantly associated with increased risk of young-onset CRC, after adjusting for putative risk factors, including obesity and physical activity. Compared to no more than 7 hours per week, women with 7.1–14 hours per week of TV time had a multivariable relative risk (RR) of 1.12 (95% confidence interval [CI] = 0.72 to 1.75), further increased for greater than 14 hours per week (RR = 1.69, 95% CI = 1.07 to 2.67, Ptrend = .03). This association was observed among participants without a CRC family history and was more pronounced for rectal cancer (RR for >14 vs ≤7 hours per week 2.44, 95% CI = 1.03 to 5.78, Ptrend = .04). Overweight or obese participants may be more susceptible. Conclusion Independent of exercise and obesity, prolonged sedentary TV viewing time, a surrogate for a more inactive lifestyle, was associated with increased risk of young-onset CRC, particularly of the rectum. These findings provide further evidence on the importance of maintaining an active lifestyle.

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Ethnic Disparities in Imaging Utilization at Diagnosis of Non-Small Cell Lung Cancer

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djaa034 ◽

2020 ◽

Vol 112 (12) ◽

pp. 1204-1212 ◽

Cited By ~ 4

Author(s):

Rustain L Morgan ◽

Sana D Karam ◽

Cathy J Bradley

Keyword(s):

Lung Cancer ◽

Imaging Modality ◽

Statistical Tests ◽

Ethnic Disparities ◽

Cox Proportional Hazards ◽

Ct Imaging ◽

Secondary Outcome ◽

Fee For Service ◽

Cancer Specific Survival ◽

Initial Imaging

Abstract Background Prior research demonstrated statistically significant racial disparities related to lung cancer treatment and outcomes. We examined differences in initial imaging and survival between blacks, Hispanics, and non-Hispanic whites. Methods The linked Surveillance, Epidemiology, and End Results-Medicare database between 2007 and 2015 was used to compare initial imaging modality for patients with lung cancer. Participants included 28 881 non-Hispanic whites, 3123 black, and 1907 Hispanics, patients age 66 years and older who were enrolled in Medicare fee-for-service and diagnosed with lung cancer. The primary outcome was comparison of positron emission tomography (PET) imaging with computerized tomography (CT) imaging use between groups. A secondary outcome was 12-month cancer-specific survival. Information on stage, treatment, and treatment facility was included in the analysis. Chi-square test and logistic regression were used to evaluate factors associated with imaging use. Kaplan-Meier method and Cox proportional hazards regression were used to calculate adjusted hazard ratios and survival. All statistical tests were two-sided. Results After adjusting for demographic, community, and facility characteristics, blacks were less likely to undergo PET or CT imaging at diagnosis compared with non-Hispanic whites odds ratio (OR) = 0.54 (95% confidence interval [CI] = 0.50 to 0.59; P < .001). Hispanics were also less likely to receive PET with CT imaging (OR = 0.72, 95% CI = 0.65 to 0.81; P < .001). PET with CT was associated with improved survival (HR = 0.61, 95% CI = 0.57 to 0.65; P < .001). Conclusions Blacks and Hispanics are less likely to undergo guideline-recommended PET with CT imaging at diagnosis of lung cancer, which may partially explain differences in survival. Awareness of this issue will allow for future interventions aimed at reducing this disparity.

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The Outcome of CLL Patients with 97% Identity to Germline Is Inferior to Other ‘Mutated’ Cases Defined by a 98% Cut off

Blood ◽

10.1182/blood.v118.21.2842.2842 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2842-2842

Author(s):

Zadie Davis ◽

Anton Parker ◽

Daniel Catovsky ◽

David Oscier

Keyword(s):

Cox Regression ◽

Conflicts Of Interest ◽

Early Stage ◽

Prognostic Significance ◽

Published Data ◽

Early Stage Disease ◽

Ighv Gene ◽

Significant Difference ◽

Gene Usage ◽

The Uk

Abstract Abstract 2842 IGHV gene mutational load and use of specific IGHV genes and stereotypes have all been reported to have prognostic significance in CLL. In the UK CLL4 trial there were significant differences in response rate and progression free survival regardless of whether a 97% or 98% cut off was used, and the percentage of mutations which correlates best with clinical outcome remains controversial. We performed IGHV gene sequencing on 1071 patients with CLL or ‘clinical’ MBL (n= 153) in whom biomarkers, time to first treatment (TTFT) and overall survival (OS) were available. Four hundred and ninety six cases were entered into the UK CLL4 trial and 575 presented or were referred to the Royal Bournemouth Hospital. TTFT and OS were determined for cases with <96% identity and for each mutational point from 96% – 100% identity separately, excluding cases utilising IGHV3-21 assigned to stereotype subset 2. There was a significant difference in median TTFT and median OS between those with 97% identity (TTFT-20.9 and OS-99.3 months) and <97% identity (TTFT-118 and OS-191 months; p<0.001 and p<0.001), but not between cases with 97% and >97% identity (TTFT -13.1 months p=0.052 and OS-84.5 months p=0.177). When TTFT was determined for patients with early stage disease only (stage A CLL or CLL-like MBL, n=571), those with 97% identity, determined using either leader sequence or BIOMED 2 primers, had a significantly longer median TTFT than those with >97% identity (92.0 and 36.4 months respectively; p=0.012) and significantly shorter than those cases with <97% identity (273.1 months; p=0.012). If only stage A cases were analysed, those with 97% identity had a significantly longer median TTFT than those with >97% identity (TTFT; 68 vs. 26 months p=0.034). However, when compared to cases with <97% identity, there was a trend towards a shorter TTFT but significance was not reached (68 vs. 128 months p=0.060). A series of Cox Regression analyses were conducted to see if the prognostic value of the 98% cut off in MBL/stage A cases could be improved. In univariate analyses a model which incorporated <97%, 97%, >97% identity and stereotype subset 2 was the best discriminator of TTFT (p=0.0011) (Figure 1).Figure 1.Four subgroups of MBL/stage A CLL with differing TTFT based on stereotype subset 2 and relationship to 97% germline identityFigure 1. Four subgroups of MBL/stage A CLL with differing TTFT based on stereotype subset 2 and relationship to 97% germline identity Multivariate analysis, selected 97% and >97% identity as independent predictors of shorter TTFT (HR 2.5; 95% CI 1.3–4.9; p=0.007 and HR 4.2; 95% CI 2.9–6.1; p<0.001 respectively) in a model including <97%, 97%, >97% identity to germline, age at diagnosis, gender, expression of ZAP70, expression of CD38, del11q, del17p, stereotypy and stereotype subset 2 (Table 1). Further analyses were performed to investigate whether the differences in TTFT between cases with <97%, 97% or >97% identity could be explained by differences in IGHV gene usage. Sixty-one percent of cases with 97% identity to germline utilised only five genes; IGHV3-21, IGHV3-23, IGHV3-48, IGHV3-53 and IGHV1-18 and these genes were significantly over-represented in cases with 97% compared to either, cases with <97% (p>0.001) or >97% (p>0.001). When subset 2 cases were excluded, there was no difference in TTFT between cases using the above 5 genes and all other IGHV genes at this identity (p=0.288). In contrast to previously published data we found no difference in TTFT between mutated IGHV3-23 cases and other mutated cases (using a 98% cut-off), but IGHV3-23 cases with 97% identity had a shorter TTFT than cases with <97% identity (p<0.001). In conclusion the clinical course of cases with 97% identity, especially if diagnosed early in their disease, appears distinct from other cases defined as having mutated IGHV genes using the conventional 98% cut off. This is not accounted for by differences in IGHV gene usage, the incidence of stereotypy or other biomarkers and may reflect differences in response to BCR stimulation between cases with 97% and <97% identity.Table.Multivariate analysis for TTFT in MBL/stage A CLLOutcomeCovariateHazard Ratio (HR)95% CI for HRSignificance (p)TTFT97% identity2.51.3–4.90.007>97% identity4.22.9–6.1<0.001Subset 23.71.8–7.4<0.001Del11q1.71.1–2.70.014CD381.51.0–2.00.028Age at diagnosis0.980.96–0.99<0.001 Only covariates selected as significant are listed above. Disclosures: No relevant conflicts of interest to declare.

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