Risk of secondary cancers after breast conserving therapy in Japan.

256 Background: There is a growing body of evidence that vast majority of patients with early breast cancer who underwent breast conserving therapy (BCT) live their longer ‘cancer survivor’ lives through modern sophisticated treatment. Accordingly, second malignancies after BCT are on the rise, which are sticky dilemmas accompanied by additional anxiety and need for further medical care. Investigation of secondary malignancies should be made the first priority in Japan as the world's top country for longevity. Methods: In order to investigate the second malignancies after BCT, a cohort study was conducted based on our database from 1982 to mid-2015. Actuarial rates of second malignancies, overall (OS) and cause-specific survival (CSS), were calculated by using the Kaplan-Meier method. We calculated standardized incidence ratios (SIR) for each cancer type corresponding to the national registry. Results: 1,557 patients (49.5%) were followed-up for more than 10 years. At a median follow-up of 113 months, 180 patients had developed a second malignancy. The increases in risk were for leukemia (SIR: 3.89 (1.76–6.84)) and ovarian cancer (SIR: 3.65 (2.26–5.38)). Trends toward increased risk was seen in reno-ureteral cancer (SIR: 2.25 (0.96–4.08)) and endometrial cancer (SIR: 1.59 (0.92–2.43)) though it was not statistically significant. No increased risk was observed for other gastrointestinal and genitourinary cancer, malignant melanoma, lymphoma, thyroid or head and neck cancer. Overall 10-year cumulative incidence of OS was 93.3%, and overall 10-year cumulative incidence of CSS was 95.0%. Overall 10-year incidence of secondary cancer was 5.9%. A total number of secondary malignancies within 10 years was 157 and this number explained 84.4% of all cases observed during follow-up. Secondary cancers continued to occur afterward, and cumulative incidence at 15- and 20-years were 8.4% , and 9.6%, respectively. Conclusions: Secondary cancers after BCT continue to arise as long as patients survive. Given its nature of life-threatening to cancer survivors, attending care team must pay persistent attention to secondary malignancies especially in Japan with the longest life-span.

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Incidence and Risk Factors for Second Malignancies after Transplant in Long Term Survivors of Allogeneic Haematopoietic Stem Cell Transplant: A Single Centre Experience

Blood ◽

10.1182/blood-2018-99-114229 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3417-3417

Author(s):

Mohammed Snober ◽

Richard Syzdlo ◽

Jane Apperley ◽

Aristeidis Chaidos ◽

Edward Kanfer ◽

...

Keyword(s):

Stem Cell ◽

Cumulative Incidence ◽

Haematopoietic Stem Cell ◽

Cell Transplant ◽

Second Malignancy ◽

Second Malignancies ◽

Additional Information ◽

Increased Risk ◽

High Index Of Suspicion

Abstract Second malignancies are well recognised complications of haematopoietic stem cell transplantation (HCT). The incidence increases with time after HCT with no evidence of plateau with follow up times of 15-20 years. In this study we have investigated patients over a 37-year period to include all patients transplanted at The Hammersmith hospital since 1979 who survived a minimum of two years after transplant. We aimed to describe the post-transplant malignancies (PTM) that occurred and calculate the cumulative incidence with time. Methods Data was gathered through internal databases and supplemented with case notes with all patients giving consent for their data to be used in clinical studies. Additional information on patients who had died at the time of analysis included review of death certificates for evidence of a second malignancy. If a patient had not been seen within 5 years evidence of death was sought on the NHS Spine and if apparently still alive, the date of last follow up was taken as follow up time. Second malignancies included second solid neoplasms (SSN), non-melanoma skin cancer (NMSC) and leukemias/lymphomas. These were recorded and categorised in accordance with the international classification of disease for oncology (ICD-O). Results 697 patients survived a minimum of two years after HCT between 1979-2018, 60% of whom were male. Follow up was prolonged with 20% of our 2-year survivors followed up for more than 20 years. The majority of patient (80%) were aged between 20-50 at time of HCT. (median age 35.6y, range 4-69) with only 7 patients < 10 y at HCT. The most frequent diagnoses were CML (n=463) or AML (n=103). The majority of patients (n=538, 77%) had received TBI, and the most frequently used conditioning was Cyclo-TBI (479 patients, 69%). At the time of analysis, 222 patients had died and of the remaining 475, 107 were lost to follow up. We identified 97 PTM in 87 patients a median of 14.2 years post HCT (range 0.8-35.9 years). These included 58 cases of SSN, 28 cases of NMSC and 11 cases of leukemia or lymphoma. The most frequent SSN were breast (n=12), tongue (n=7), colorectal (n=6), melanoma (n=5), bladder (n=4), thyroid (n=3) and oesophagus (n=3). Of 28 patients with NMSC, 19 developed one or more BCC and 9 developed SCC. The cumulative incidence of PTMs did not plateau with time. Cumulative incidences were as follows with 95% confidence intervals (CI) in parentheses: 4.9% (3.3-7.3) at 10 years, 12.2% (9.1-16.2) at 15 years, 22.5% (17.6-28.9) at 20 years, 39% (30.3-48.4) at 25 years and 53% (41.6-64.1) at 30 years. These data reflected the substantial increases in the CI of SSN and NMSC between these time points. For SSN the cumulative incidence increased from 3% (1.8-5) at 10 years to 37.9% (27.4-49.6) at 30 years; for NMSC the cumulative incidence increased from 1.3% (0.6-2.7) at 10 years 16.6% (9.2-28.2) at 30 years. In multivariate analyses older age (>50) at time of transplant was associated with significantly increased (p<0.01) risk of PTM with a relative risk (RR) of 4.53 (2.1-9.6). On subgroup analysis this was only relevant to SSN where the RR was 5.17 (2.2-12.1). Patient/donor sex combinations other than male patient/male donor were also at increased risk of PTM, RR 1.797 (1.1-2.9), p=0.033, and again this was only significant for SSN (RR 2.11, 1.13-3.93). Discussion and conclusions In this predominantly adult study, the cumulative incidence of SSN and NMSC increased substantially with time after HCT beyond a 10-year follow-up period. The risk was increased in patients who were >50 at time of HCT. Prolonged expert follow-up with a high index of suspicion for second malignancy in these patients is recommended to facilitate early diagnosis. Disclosures Apperley: Novartis: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Incyte: Honoraria, Speakers Bureau. Milojkovic:Incyte: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau.

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Secondary cancers after breast-conserving therapy in Tokyo database.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.26_suppl.139 ◽

2013 ◽

Vol 31 (26_suppl) ◽

pp. 139-139

Author(s):

Kenshiro Shiraishi ◽

Keiichi Nakagawa ◽

Jiro Kawamori ◽

Kenji Ibukuro ◽

Atsushi Fukuuchi ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Survivors ◽

Cumulative Incidence ◽

Weight Control ◽

Breast Cancer Survivors ◽

Breast Conserving Therapy ◽

Rank Test ◽

Secondary Cancer ◽

Secondary Cancers ◽

Increased Risk

139 Background: The more patients overcome early breast cancer and become cancer survivors as a result of modern sophisticated approach, the more secondary cancers inevitably arise. The second malignancies after breast conserving therapy (BCT) are well-known sticky dilemma because of additional anxiety and need for medical care for longer-time. However, it is unclear whether secondary cancers negatively affect prognosis of breast cancer survivors. Methods: We performed a retrospective study of long-term cancer survivors after BCT for locoregional invasive or noninvasive breast cancer diagnosed between 1982 and mid-2012. Actuarial rates of overall (OS) and cause-specific survival (CSS) were calculated by using the Kaplan-Meier method. We compared between-group differences using the log-rank test. Results: Eight hundred sixty patients (32%) were followed-up for more than 10 years. At a median follow-up of 90 months, 146 patients had developed a second malignancy. The greatest increases in risk were for leukemia (Standardized incidence ratio (SIR): 4.24 (1.52–8.31)), ovarian cancer (SIR: 4.12 (2.40–6.31)), reno-ureteral cancer (SIR: 3.18 (1.14–6.23)), endometrial cancer (SIR: 2.48 (1.27–4.08)), and pancreatic cancer (SIR: 2.32 (1.11–3.99)). No increased risk was observed for other gastrointestinal and genitourinary cancer, malignant melanoma, lymphoma, thyroid or head and neck cancer. Overall 10-year cumulative incidence of OS without secondary cancer was 93.3%, and 10-year cumulative incidence of OS with secondary cancer was 81.5%. (p<0.001)Overall 10-year cumulative incidence of CSS without secondary cancer was 94.2%, and 10-year cumulative incidence of CSS with secondary cancer was 92.8%. (p=0.749). This likelihood of survival disadvantage is similar to that with ipsilateral breast tumor recurrecnce. Conclusions: Secondary cancers after BCT negatively impact on OS. Given the life-threatening nature to cancer survivors, lifetime caution such as smoking cessation, alcohol intake abstention, weight control, physical activity, and other healthy lifestyle must be paid.

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Second Malignancies Following Treatment of Chronic Myeloid Leukemia in the Tyrosine Kinase Inhibitor Era

Blood ◽

10.1182/blood.v124.21.154.154 ◽

2014 ◽

Vol 124 (21) ◽

pp. 154-154

Author(s):

Niklas Gunnarsson ◽

Stenke Leif ◽

Martin Höglund ◽

Fredrik Sandin ◽

Magnus Björkholm ◽

...

Keyword(s):

Research Funding ◽

Chronic Phase ◽

Cancer Type ◽

Second Malignancy ◽

Second Malignancies ◽

Non Melanoma Skin Cancer ◽

Increased Risk ◽

Before And After ◽

Tki Treatment

Abstract Background: Since continuous treatment with tyrosine kinase inhibitors (TKIs) has dramatically improved the survival of patients with chronic myeloid leukemia (CML), it is of interest to examine the possible risk of long-term adverse events. Previous studies have presented conflicting results regarding risk of second malignancies. Our aim was to examine the development of second malignancies (except acute myeloid or lymphoblastic leukemia, myelodysplastic syndromes or non-melanoma skin cancer) in CML chronic phase patients diagnosed after the introduction of TKI treatment. Materials and methods: We studied the development of second malignancies in 868 patients diagnosed with CML in chronic phase 2002 to 2011 using the Swedish CML register, cross-linked to the Swedish Cancer register. Each patient was followed from the time of CML diagnosis until death from any cause, date of allogeneic hematopoietic stem cell transplantation (SCT) or end of study on December 31, 2011, whichever came first. SCT was used as an endpoint because of the well established increased risk of second malignancies after this procedure. Standardized Incidence Ratios (SIR) were calculated to assess the risk of a second malignancy by dividing the number of observed second malignancies with the number of expected malignancies in the Swedish population, using data from the Swedish Cancer Register. The expected numbers of malignancies were determined by dividing the CML population according to 5-year age groups, sex, region of residence (6 regions) and calendar year. The number of person-years in each stratum was multiplied with the incidence of malignancies or deaths found in the corresponding strata in the general population. Results: With a median follow-up of 3.7 (range 0-9.9) years, 65 (7.5%) patients developed 75 second cancers (non-hematologic), 49 of these of invasive type. Compared to expected rates in the background population matched by age, sex, region of residence (6 regions) and calendar year, the risk of second malignancies was significantly higher in the CML cohort, with a Standardized Incidence Ratio (SIR) of 1.5 (95 % CI 1.13-1.99). SIR before and after the second year following diagnosis of CML was 1.6 (95 % CI 1.004-2.38) and 1.5 (95 % CI 0.98-2.11), respectively. Looking at CML subpopulations, the increased risk of developing a second malignancy reached statistical significance for females (SIR: 1.8; 95 % CI 1.18-1.99), but not for males (SIR: 1.3; 95 % CI 0.85-1.91), and for patients above 60 years of age at diagnosis (SIR: 1.5; 95 % CI 1.05–1.96). Assessment of risk by cancer type was hampered by small numbers. However, the data at hand indicate an increased risk for gastrointestinal cancer (SIR: 3.0; 95 % CI 1.60-5.16), as well as nose and throat cancer (SIR: 37.1; 95 % CI 7.46-108.40), table 1. Conclusions: Utilizing large, population-based registries with data accumulated during the TKI era, our results indicate that CML patients, compared to the normal control population, are at an 50% increased risk of developing a second malignancy. Similar SIR before and after the second year following the diagnosis of CML may indicate that these findings are linked to the CML disease itself, rather than to the TKI treatment. Further studies and longer follow-up seem however warranted. Physicians caring for CML patients should be aware of signs and symptoms of other malignancies in this patient population. Table 1 Standardized Incidence Ratios for second malignancies (excluding cases of non-melanoma skin cancer, AML, ALL and MDS) among 868 Swedish CML patients diagnosed between 2002 and 2011. Total follow up time 3293 person-years (median 3.7 years). Variable Observed Expected SIR (Observed/Expected) 95 % CI for SIR Overall 52 34 1.5 1.13–1.99 Men 26 20 1.3 0.85–1.91 Women 26 14 1.8 1.18–2.66 Age <60 years 10 5 1.9 0.89–3.42 Age ³ 60 years 42 28 1.5 1.05–1.96 Second cancer type Prostate 14 8 1.8 0.96–2.94 Gastrointestinal 13 4 3.0 1.60–5.16 Gynecological 4 1 3.6 0.98–9.30 Nose and Throat 3 0,1 37.1 7.46-108.40 Lung 2 2,7 0.7 0.08-2.67 Breast 4 4,2 0.98 0.26-2.45 Disclosures Björkholm: Novartis: Research Funding; Shire: Research Funding; Merck: Research Funding; Amgen: Honoraria, Research Funding; Pfizer: Research Funding; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Akinon: Honoraria; Nordic Nanovector: Honoraria. Richter:Ariad: Honoraria; Bristol-Myers Squibb: Honoraria; Novartis: Honoraria. Själander:Novartis: Honoraria.

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Clinical Factors Associated with Progression to AIDS in the Italian Cohort of HIV-Positive Hemophiliacs

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648807 ◽

1994 ◽

Vol 72 (01) ◽

pp. 033-038 ◽

Cited By ~ 7

Author(s):

N Schinaia ◽

A M G Ghirardini ◽

M G Mazzucconi ◽

G Tagariello ◽

M Morfini ◽

...

Keyword(s):

Cumulative Incidence ◽

National Registry ◽

Factor Ix ◽

Clotting Factor ◽

Coagulation Disorders ◽

Factors Associated ◽

Kaplan Meier ◽

Significant Difference ◽

Congenital Coagulation Disorders ◽

Clotting Factor Concentrates

SummaryThis study updates estimates of the cumulative incidence of AIDS among Italian patients with congenital coagulation disorders (mostly hemophiliacs), and elucidates the role of age at seroconversion, type and amount of replacement therapy, and HBV co-infection in progression. Information was collected both retrospectively and prospectively on 767 HIV-1 positive patients enrolled in the on-going national registry of patients with congenital coagulation disorders. The seroconversion date was estimated as the median point of each patient’s seroconversion interval, under a Weibull distribution applied to the overall interval. The independence of factors associated to faster progression was assessed by multivariate analysis. The cumulative incidence of AIDS was estimated using the Kaplan-Meier survival analysis at 17.0% (95% Cl = 14.1-19.9%) over an 8-year period for Italian hemophiliacs. Patients with age greater than or equal to 35 years exhibited the highest cumulative incidence of AIDS over the same time period, 32.5% (95% Cl = 22.2-42.8%). Factor IX recipients (i.e. severe B hemophiliacs) had higher cumulative incidence of AIDS (23.3% vs 14.2%, p = 0.01) than factor VIII recipients (i.e. severe A hemophiliacs), as did severe A hemophiliacs on less-than-20,000 IU/yearly of plasma-derived clotting factor concentrates, as opposed to A hemophiliacs using an average of more than 20,000 IU (18.8% vs 10.9%, p = 0.02). No statistically significant difference in progression was observed between HBsAg-positive vs HBsAg-negative hemophiliacs (10.5% vs 16.4%, p = 0.10). Virological, immunological or both reasons can account for such findings, and should be investigated from the laboratory standpoint.

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Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors

Scientific Reports ◽

10.1038/s41598-021-89216-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Robert Terziev ◽

Dimitri Psimaras ◽

Yannick Marie ◽

Loic Feuvret ◽

Giulia Berzero ◽

...

Keyword(s):

Risk Factors ◽

Cumulative Incidence ◽

High Grade Glioma ◽

High Grade ◽

Nucleotide Polymorphisms ◽

Increased Risk ◽

Radiation Induced ◽

Long Term Survivors

AbstractThe incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.

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Atrial fibrillation associated with increased risk of venous thromboembolism

Thrombosis and Haemostasis ◽

10.1160/th14-05-0405 ◽

2015 ◽

Vol 113 (01) ◽

pp. 185-192 ◽

Cited By ~ 23

Author(s):

Chun-Cheng Wang ◽

Cheng-Li Lin ◽

Guei-Jane Wang ◽

Chiz-Tzung Chang ◽

Fung-Chang Sung ◽

...

Keyword(s):

Atrial Fibrillation ◽

Venous Thromboembolism ◽

Incidence Rates ◽

Vein Thrombosis ◽

Kaplan Meier ◽

Increased Risk ◽

Long Term Follow Up ◽

Deep Vein

SummaryWhether atrial fibrillation (AF) is associated with an increased risk of venous thromboembolism (VTE) remains controversial. From Longitudinal Health Insurance Database 2000 (LHID2000), we identified 11,458 patients newly diagnosed with AF. The comparison group comprised 45,637 patients without AF. Both cohorts were followed up to measure the incidence of deep-vein thrombosis (DVT) and pulmonary embolism (PE). Univariable and multivariable competing-risks regression model and Kaplan-Meier analyses with the use of Aelon-Johansen estimator were used to measure the differences of cumulative incidences of DVT and PE, respectively. The overall incidence rates (per 1,000 person-years) of DVT and PE between the AF group and non-AF groups were 2.69 vs 1.12 (crude hazard ratio [HR] = 1.92; 95 % confidence interval [CI] = 1.54-2.39), 1.55 vs 0.46 (crude HR = 2.68; 95 % CI = 1.97-3.64), respectively. The baseline demographics indicated that the members of the AF group demonstrated a significantly older age and higher proportions of comorbidities than non-AF group. After adjusting for age, sex, and comorbidities, the risks of DVT and PE remained significantly elevated in the AF group compared with the non-AF group (adjusted HR = 1.74; 95 %CI = 1.36-2.24, adjusted HR = 2.18; 95 %CI = 1.51-3.15, respectively). The Kaplan-Meier curve with the use of Aelon-Johansen estimator indicated that the cumulative incidences of DVT and PE were both more significantly elevated in the AF group than in the non-AF group after a long-term follow-up period (p<0.01). In conclusion, the presence of AF is associated with increased risk of VTE after a long-term follow-up period.

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Abstract 13315: Long-term Risk of Cardiovascular Events Following Hospitalization for Sepsis: A Systematic Review and Meta-analysis

Circulation ◽

10.1161/circ.142.suppl_3.13315 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Leah B Kosyakovsky ◽

Federico Angriman ◽

Emma Katz ◽

Neill Adhikari ◽

Lucas C Godoy ◽

...

Keyword(s):

Systematic Review ◽

Cumulative Incidence ◽

Meta Analysis ◽

Hazard Ratios ◽

Increased Risk ◽

Significant Difference ◽

Sepsis Survivors ◽

Risk Ratios

Introduction: Sepsis results in dysregulated inflammation, coagulation, and metabolism, which may contribute to increased cardiovascular disease (CVD) risk. We conducted a systematic review and meta-analysis to determine the association between sepsis and subsequent long-term CVD events. Methods: MEDLINE, Embase, and the Cochrane Controlled Trials Register and Database of Systematic Reviews were searched from inception to May 2020 to identify observational studies of adult sepsis survivors (defined by diagnostic codes or consensus definitions) measuring long-term CV outcomes. The primary outcome was a composite of myocardial infarction, CV death, and stroke. Random-effects models estimated the pooled cumulative incidence and adjusted hazard ratios of CV events relative to hospital or population controls. Odds ratios were included as risk ratios assuming <10% incidence in non-septic controls, and risk ratios were taken as hazard ratios (HR) assuming no censoring. Outcomes were analyzed at maximum follow-up (primary analysis) and stratified by time (<1 year, 1-2 years, and >2 years) since sepsis. Results: Of 11,235 abstracts screened, 25 studies (22 cohort studies, 2 case-crossover studies, and 1 case-control) involving 1,949,793 sepsis survivors were included. The pooled cumulative incidence of CVD events was 9% (95% CI; 5-14%). Sepsis was associated with an increased risk (HR 1.59, 95% CI 1.37-1.86) of CVD events at maximum follow-up ( Figure ); between-study heterogeneity was substantial (I 2 =97.3%). There was no significant difference when comparing studies using population and hospital controls. Significantly elevated risk was observed up to 5 years following sepsis. Conclusions: Sepsis survivors experience an approximately 50% increased risk of CVD events, which may persist for years following the index episode. These results highlight a potential unmet need for early cardiac risk stratification and optimization in sepsis survivors.

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Incidence, timing, and predictors of CNS metastasis in patients (Pts) with clinically localized cutaneous melanoma (CM).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9580 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9580-9580

Author(s):

Merve Hasanov ◽

Denai R. Milton ◽

Sapna Pradyuman Patel ◽

Hussein Abdul-Hassan Tawbi ◽

Isabella Claudia Glitza ◽

...

Keyword(s):

Primary Tumor ◽

Cumulative Incidence ◽

Tumor Location ◽

Initial Diagnosis ◽

Stage I ◽

Acral Lentiginous Melanoma ◽

Primary Tumor Location ◽

Cns Metastasis ◽

Increased Risk

9580 Background: Surveillance for CNS metastasis (mets) is not routinely performed in pts with clinically localized CM. Improved understanding of the incidence, timing and risk factors for the development of CNS metastasis in these pts may inform surveillance strategies. Methods: Under an IRB-approved protocol, demographics, tumor characteristics, and clinical events were collected for pts diagnosed from 1998 to 2019 with AJCC 8th edition stage I or II CM at MD Anderson Cancer Center. Dates of initial diagnosis, regional, distant non-CNS, and CNS mets were recorded. Symptoms and the extent of disease (brain, LMD, both) were recorded for pts with CNS mets. Cumulative incidence of distant mets (CNS and non-CNS) was determined using the competing risks method, including death; pts without CNS mets and alive at last follow-up were censored. Differences in cumulative incidence between groups were assessed using Gray’s test. Associations between measures of interest and cumulative incidence were determined using proportional subdistribution hazards regression models. All statistical tests used a significance level of 5%. Results: 5,179 Stage I-II CM pts were identified. At a median follow up of 82 (0.0-268.8) months, 703 (13.6%) pts were diagnosed with distant mets, including 355 (6.9%) with CNS mets. Cumulative incidence of CNS mets was 0%, 2%, and 5% at 1, 2, and 5 years, respectively. Among pts with distant mets, the first site of distant mets was CNS only for 29 (4%), non-CNS only for 557 (79%), and both for 116 (17%) pts. At initial diagnosis of CNS mets, 195 (55%) pts were asymptomatic, and 46 (13%) had no active extracranial disease. Median time to any distant met was longer for pts who were diagnosed with CNS mets [40.0 (1.9-238.0) months] vs pts diagnosed with non-CNS mets only [31.4 (1.1-185.7) months, p < 0.001]. On multivariable analysis, risk of CNS mets was significantly associated with primary tumor location of scalp [Hazard Ratio (HR) 3.4, 95% Confidence interval (CI) 1.9-5.9], head/neck (HR 3.3, 95% CI 2.0-5.3), or trunk (HR 2.3, 95% CI 1.5-3.5) (vs upper extremity); acral lentiginous melanoma subtype (HR 2.0, 95% CI 1.2-3.6) (vs superficial spreading); increased T category (T2 HR 1.5, 95% CI 1.1-2.2; T3 HR 1.9, 95% CI 1.2-3.0; T4 HR 2.1, 95% CI 1.1-3.8; vs T1), Clark level (CL) (CL4 HR 2.1, 95% CI 1.2-3.7 vs CL2), and mitotic rate (MR) (MR 5-9/mm2 HR 2.1, 95% CI 1.5-3.0; MR > 9/mm2 HR 2.0, 95% CI 1.3-3.0; vs MR 0-4/mm2). While high ( > 9/mm2) MR was associated with increased risk of CNS and non-CNS mets, intermediate (5-9/mm2) was associated with CNS mets only. Conclusions: Primary tumor location, tumor thickness, and MR were strongly associated with risk of CNS mets. MR rate was more strongly associated with risk of CNS than non-CNS mets. Validation in independent cohorts may provide evidence to support CNS surveillance strategies in select pts with stage I-II CM who are deemed high risk for CNS mets.

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Cardiac Morbidity in Adolescents and Young Adult Survivors of Hodgkin Lymphoma

Blood ◽

10.1182/blood-2020-136454 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 18-19

Author(s):

Kristin C. Marr ◽

Jonathan Simkin ◽

Andrea C. Lo ◽

Joseph M. Connors ◽

Alina S. Gerrie ◽

...

Keyword(s):

Cumulative Incidence ◽

Research Funding ◽

Index Date ◽

Population Based ◽

Stage Disease ◽

Increased Risk ◽

Matched Case ◽

Cv Disease ◽

Relapsed Disease

INTRODUCTION Adolescents and young adult (AYA) survivors of Hodgkin lymphoma (HL) are potentially at increased risk of cardiovascular (CV) disease due to anthracycline exposure, in addition to use of mediastinal radiotherapy (RT). Although the risk has been well described in the pediatric age-group, the impact in the AYA population has been less well characterized. Capturing the incidence of these late effects is challenging given that events can occur more than a decade after therapy completion. Using population-based administrative data, we evaluated the incidence of CV disease (combined heart failure (HF) and ischemic heart disease (IHD)) in a cohort of AYA survivors treated for classical HL (cHL) using ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) or equivalent chemotherapy. METHODS Patients with cHL aged 16-39 years (y), diagnosed between 1992-2013 and treated with an ABVD or equivalent therapy, were identified in the BC Cancer Lymphoid Cancer Database. Patients must have survived to an Index Date defined as 2 y from most recent HL event (primary diagnosis or if applicable, most recent relapse) and have had a minimum follow-up of 1 y beyond their Index Date. Patients were excluded if they had history of prior malignancy or HIV positivity. Limited stage disease was defined as stage IA, IB or IIA and absence of bulky disease (≥10cm); all others had advanced stage disease. Cases were linked with population-based databases of BC Cancer Registry; BC Radiation Oncology Database; and BC Ministry of Health (MOH) Chronic Disease Registry (CDR) that captures all BC residents registered with medical service plan coverage during the study period. The outcome variables, including HF and IHD, were defined by the BC MOH CDR using Standardized Case Definitions. To focus on late onset CV complications, only events that occurred after the Index Date were included in the analysis. A 10:1 individually-matched control population was identified from the CDR based on age, sex, and health authority region on the Index Date of the matched case. Controls were excluded if they had a pre-existing malignancy, HF, or IHD prior to the study window. Individual outcomes were collected from the Index Date of the matched case until December 31, 2015 or until an individual was censored due to loss to follow-up or death. Kaplan Meier (K-M) methodology and log-rank test was used to estimate cumulative incidence. A competing risk regression analysis was used to evaluate relative risk (RR) and p-values less than 0.05 were considered significant. RESULTS With a median follow-up time of 11 y (range 3-24 y) from most recent HL event, 764 AYA 2-y survivors were identified, aged 20 to 61 y (median 38 y) at the end of study period. The proportion of limited and advanced stage disease was 34.2% and 65.6%, respectively; and 49.9% were male. Eighty-eight patients (11.5%) had relapsed disease; eighty-six (11.3%) underwent high dose chemotherapy and autologous stem cell transplantation as part of their salvage therapy. In total, 268 patients (36.4%) were treated with mediastinal RT for primary therapy or for relapsed disease. Fifty-three percent received cumulative anthracycline dose ≥300 mg/m2. Survivors had a 3-fold increased risk of CV disease relative to controls (p<0.0001). The onset of CV disease in survivors occurred at median of 11.7 y after most recent treatment (range 2.2-19.2 y), and at a median age of 44.3 y (range 21 - 58 y). At 15 y, the estimated cumulative incidence of CV disease was 6.3% in survivors compared to 2.3% in controls (Figure A). In the 496 survivors that received chemotherapy only, the incidence of CV disease at 15 y was 4.6% vs 2.3% in controls, and those that received anthracyclines and mediastinal RT had significantly higher incidence at 8.6% (Figure B). The increase in risk was greatest for a diagnosis of HF (RR 6.92, p<0.0001): at 15 y, the cumulative incidence of HF was 2.2% vs 0.6% in controls. The RR of IHD was 2.63 (p<0.0001) with incidence of 5.1% in cases compared to 1.8% in controls. CONCLUSION Similar to the pediatric population, AYA cHL survivors are at increased risk of both HF and IHD after completion of treatment. The majority of patients had received ABVD alone and had a lower incidence of CV disease at 15 y when compared to those that received treatment that included mediastinal RT. These results will inform counseling regarding risk factor modification and aid in the development of surveillance guidelines for AYA survivors. Disclosures Gerrie: Sandoz: Consultancy; Roche: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Astrazeneca: Consultancy, Research Funding. Villa:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; AZ: Consultancy, Honoraria, Research Funding; Kite/Gilead: Consultancy, Honoraria; Nano String: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Sandoz Canada: Consultancy, Honoraria; Immunovaccine: Consultancy, Honoraria; Purdue Pharma: Consultancy, Honoraria. Scott:NIH: Consultancy, Other: Co-inventor on a patent related to the MCL35 assay filed at the National Institutes of Health, United States of America.; Roche/Genentech: Research Funding; Celgene: Consultancy; NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoString, Research Funding; Abbvie: Consultancy; AstraZeneca: Consultancy; Janssen: Consultancy, Research Funding. Sehn:AstraZeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Genentech, Inc.: Consultancy, Honoraria, Research Funding; Acerta: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Teva: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Apobiologix: Consultancy, Honoraria; Verastem Oncology: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria; Chugai: Consultancy, Honoraria. Savage:BeiGene: Other: Steering Committee; Roche (institutional): Research Funding; Merck, BMS, Seattle Genetics, Gilead, AstraZeneca, AbbVie, Servier: Consultancy; Merck, BMS, Seattle Genetics, Gilead, AstraZeneca, AbbVie: Honoraria.

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Fate of mild-to-moderate bicuspid aortic valve disease untreated during ascending aorta replacement

10.22541/au.160901985.50675267/v1 ◽

2020 ◽

Author(s):

Alessandro Verzini ◽

Marta Bargagna ◽

Guido Ascione ◽

Alessandra Sala ◽

Davide Carino ◽

...

Keyword(s):

Aortic Valve ◽

Bicuspid Aortic Valve ◽

Ascending Aorta ◽

Term Survival ◽

Kaplan Meier ◽

Aortic Root Surgery ◽

Increased Risk ◽

Aorta Replacement ◽

Ascending Aorta Replacement

Background: Bicuspid aortic valve (BAV) is the most common congenital heart defect and it is responsible for an increased risk of developing aortic valve and ascending aorta complications. In case of mild to moderate BAV disease in patients undergoing supracoronary ascending aorta replacement, it is unclear whether a concomitant aortic valve replacement should be performed. Methods: From June 2002 to January 2020, 75 patients with mild-to-moderate BAV regurgitation (± mild-to-moderate stenosis) who underwent isolated supracoronary ascending aorta replacement were retrospectively analyze. Clinical and echocardiographic follow-up was 100% complete (mean: 7.4±3.9 years, max 16.4). Kaplan Meier estimates were employed to analyze long-term survival. Cumulative incidence function for time to re-operation, recurrence of aortic regurgitation (AR)≥3+ and aortic stenosis (AS) greater than moderate, with death as competing risk, were computed. Results: There was no hospital mortality and no cardiac death occurred. Overall survival at 12 years was 97.4±2.5%, 95% CI [83.16-99.63]. At follow-up there were no cases of aortic root surgery whereas 3 patients underwent AV replacement. At 12 years the CIF of reoperation was 2.6±2.5%, 95% CI [0.20-11.53]. At follow up, AR 3+/4+ was present in 1 pt and AS greater than moderate in 3. At 12 years the CIF of AR>2+/4+ was 5.1±4.98% and of AS>moderate 6.9±3.8%. Conclusions: In our study mild to moderate regurgitation of a BAV did not significantly worse at least up to 10 years after isolated supracoronary ascending aorta replacement.

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