Second Cancers Affect the Clinical Outcomes of Patients with Chronic Lymphocytic Leukemia (CLL) Treated with Frontline FCR-Based Therapy.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2900-2900 ◽  
Author(s):  
Long Xuan Trinh ◽  
Young Kwang Chae ◽  
Preetesh Jain ◽  
Susan Lerner ◽  
Ohad Benjamini ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Outcomes ◽  
Second Cancer ◽  
Second Cancers ◽  
History Of ◽  
Richter’S Transformation ◽  
Richter's Transformation ◽  
Prior Malignancy ◽  
Melanoma Skin

Abstract Abstract 2900 Increasing use of chemo-immunotherapy in CLL has raised concerns over the carcinogenic effect of FCR regimen. Fludarabine based regimen in relapsed CLL has been reported to be predisposed to a higher risk of other cancers as compared to healthy individual. However, an association between the CLL treatment and the development of other cancers is not evident in the frontline FCR setting. We retrospectively studied the frequency, characteristics, and clinical outcomes of second malignancy in patients with CLL who were treated with frontline FCR-based therapy at University of Texas, MD Anderson Cancer Center from 2004 to 2010. Patients who developed other malignancies after the initiation of FCR-based therapy were considered as patients with second cancer post CLL treatment (n=39). Patients who had history of other malignancies before the initiation of FCR-based therapy were considered as patients with prior malignancy history (n=90). Patients who neither have history of other cancers nor patients developed second cancer during the study period were assigned as patients without second cancer group (n=82). There were 24 patients (n=24) who experienced Richter's transformation post FCR-based therapy. The overall survival (OS) was measured from the initiation of CLL treatment until death from any causes or last follow-up. Progression-free survival (PFS) was measured from the initiation of CLL treatment until disease progression, relapse or death. Kaplan-Meier method was used to estimate outcomes in four groups. Cox-proportional hazard regression model was used to assess the association between patient characteristics and survival outcomes. Pre-treatment characteristics were similar among these groups except for chromosome abnormalities. Ten patients (44%) out of 24 patients with Richter's transformation had TP53 gene mutation (p <0.05). Ninety patients (38%) of 235 patients had prior malignancy history includes non-melanoma skin cancer (n=32, 36%), melanoma (n=12, 13%), prostate cancer (n=15, 17%), colon cancer (n=5, 6%), renal cancer (n=2, 2%) and follicular lymphoma (n=1, 1%). Among 145 patients without prior malignancy history, there were 39 patients (27%) who developed second cancer including other leukemia, and 24 patients (17%) who developed Richter's transformation after the FCR-based therapy. The median time from initiation of FCR-based therapy to the development of Richter' transformation was 13.53 months (range, 1.63 to 40.87). There was no patient with prior history of other malignancies had recurrent cancers during the study. Thirty nine patients who developed second cancer includes non-melanoma skin (n=10, 26%), melanoma (n=2, 5%), head and neck (n=1, 2.5), Merkel cell (n=1, 2.5%), prostate (n=6, 15%), breast (n=1, 2.5%), lung (n=2, 5%) renal (n=1, 2.5%), gastric (n=2, 5%), liver (n=1, 2.5%), Hodgkin (n=1, 2.5%), and therapy-related MDS-AML (n=11, 28%). The estimated median PFS in the whole cohort was 4.57 years (95% CI: 3.678 to 5.462). PFS in patients without second cancer was not reached (NR) compared to 3.31 years (95% CI: 2.178 to 3.542) in patients with second cancer post CLL treatment (p<0.05). PFS in patients with Richter's transformation was 1.02 years (95% CI: .625 to 1.415). The median follow up duration for all 235 patients was 3.29 years (range, 0.08–8.51 years) with total of 61 deaths. The median overall survival in either group of patients with prior malignancy history or in patients without second cancers were not reached (NR) compared with 3.81 years (95% CI: 2.231 to 5.389) in patients with second cancer (p < 0.05). OS in patients with Richter's transformation was 3.84 years (95% CI, 1.434 to 6.246) There were 8 patients (10%) who died among 82 patients without second cancer as compared to 20 patients (49%) who died among 39 patients with second cancer (p <0.05). Second cancers in patients with CLL treated with FCR regimen are significantly associated with inferior clinical outcomes. We observed the high incidence of skin cancer, prostate and Richter's transformation in patients with CLL who underwent treatment with frontline FCR-based therapy. Further studies are warranted to determine the association between FCR regimen and the development of second cancer, especially Richter's transformation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Outcome of Patients with Second Cancer after Hematopoietic Stem Cell Transplantation: On Behalf of the Complications and Quality of Life Working Party of the EBMT

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3441-3441
Author(s):  
André Tichelli ◽  
Eric Beohou ◽  
Myriam Labopin ◽  
Gérard Socié ◽  
Alicia Rovó ◽  
...  
Keyword(s):  
Overall Survival ◽  
General Population ◽  
Cancer Patients ◽  
Late Complications ◽  
Second Cancer ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Second Cancers ◽  
Autologous Hsct

Abstract Background Hematopoietic stem cell transplantation (HSCT) is potentially a curative treatment for a number of life-threatening malignant and non-malignant disorders. Despite significant improvements in outcome over time, long-term survivors are at risk for late complications and their mortality remains higher than expected. Second cancers are well-known late complications, associated with substantial mortality. Although we know the incidence and risk factors for many second cancers there is a paucity of data on their outcome after HSCT. We aimed to estimate the outcome of second cancers after HSCT using a large cohort of patients from the EBMT registry, and to compare their survival to similar cancers from a general population. Method This retrospective observational study was based on the mandatory minimum data set centers report to the EBMT. We identified all patients with second cancers (excluding malignant hematopoietic and lymphoid neoplasms; non-melanoma skin cancers) treated with HSCT in Europe (including Turkey and Israel), between 1977-2015. Primary diagnoses were acute leukemia (23%), chronic leukemia (9%), lymphoma (34%), plasma cell disorders (23%), solid tumors (4%), myelodysplastic syndromes and myeloproliferative neoplasms (6%) and acquired marrow failure syndromes (1%). For the different types of solid tumors, median and overallsurvival werecalculated (from time of diagnosis of the second cancer). Results were analyzed separately for patients treated with autologous and allogeneic HSCT (table 1). For six prevalent second cancers (breast, lung, melanoma, oropharyngeal, colorectal, prostate; table 2), the age-standardized 5-year overall survival (according to the International Cancer Survival Standard; ICSS) of HSCT patients with second cancer diagnosed since the year 2000 was compared to cancer patients from a general population (EUROCARE, European Cancer Registry, period 2000-2007). Results From the EBMT registry 4152 second cancers out of 220617 (1.88%) HSCT patients were extracted: 1450 (1.79%) out of 80784 patients after allogeneic, and 2702 (1.93%) out of 139833 patients after autologous HSCT. The median age of the patients at HSCT and at diagnosis of second cancer was 53 years (range 1.2-86) and 59 years (3.2-88), respectively. For allogeneic HSCT is was 46 years (1.2-73) and 54 years (3.2-77), for autologous HSCT, 56 years (1.7-86) and 62 years (4.5-88), respectively. The median follow-up time since transplantation of all patients was 121 months (range 5-409); it was 146 months (12-409) for allogeneic, and 114 months (5-354) for autologous HSCT. The median follow-up time since diagnosis of second cancer was 35 months (range 0-240); it was 38 months (0-240) for allogeneic, and 33 months (0-228) for autologous HSCT. The distribution and survival outcomes of second cancers are shown on table 1. Overall survival following diagnosis of second cancers depends mostly on the type of cancer. No relevant differences in median survival and 5-year overall survival were seen between patients treated with autologous or allogeneic HSCT (table 1). For second breast, lung and prostate cancers no difference in 5-year overall survival wasobserved,compared to cancer patients from a general population (table 2). Melanoma and colorectal cancers had worse, and oropharyngeal cancer better overall survival, compared to the EUROCARE control group. Conclusion This large population-based analysis on second cancers among HSCT survivors showed that the outcome for patients developing a second cancer after HSCT is mainly dependent on the type of cancer. It seems that for a number of second cancer overall survival is comparable to cancer patients from a general population. A systematic comparison is now required for all post HSCT second cancers. Disclosures No relevant conflicts of interest to declare.

Dementia screening in elderly high-risk patients following heart failure decompensation may predict unfavorable long-term clinical outcomes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Stepien ◽  
P Furczynska ◽  
M Zalewska ◽  
K Nowak ◽  
A Wlodarczyk ◽  
...  
Keyword(s):  
Heart Failure ◽  
High Risk ◽  
Clinical Outcomes ◽  
Mmse Score ◽  
Coronary Revascularization ◽  
High Risk Population ◽  
Risk Population ◽  
History Of

Abstract Background Recently heart failure (HF) has been found to be a new dementia risk factor, nevertheless their relations in patients following HF decompensation remain unknown. Purpose We sought to investigate whether a screening diagnosis for dementia (SDD) in this high-risk population may predict unfavorable long-term clinical outcomes. Methods 142 patients following HF decompensation requiring hospitalization were enrolled. Within a median time of 55 months all patients were screened for dementia with ALFI-MMSE scale whereas their compliance was assessed with the Morisky Medication Adherence Scale. Any incidents of myocardial infarction, coronary revascularization, stroke or transient ischemic attack (TIA), revascularization, HF hospitalization and bleedings during follow-up were collected. Results SDD was established in 37 patients (26%) based on the result of an ALFI-MMSE score of &lt;17 points. By multivariate analysis the lower results of the ALFI-MMSE score were associated with a history of stroke/TIA (β=−0.29, P&lt;0.001), peripheral arterial disease (PAD) (β=−0.20, P=0.011) and lower glomerular filtration rate (β=0.24, P=0.009). During the follow-up, patients with SDD were more often rehospitalized following HF decompensation (48.7% vs 28.6%, P=0.014) than patients without SDD, despite a similar level of compliance (P=0.25). Irrespective of stroke/TIA history, SDD independently increased the risk of rehospitalization due to HF decompensation (HR 2.22, 95% CI 1.23–4.01, P=0.007). Conclusions As shown for the first time in literature patients following decompensated HF, a history of stroke/TIA, PAD and impaired renal function independently influenced SDD. In this high-risk population, SDD was not associated with patients' compliance but irrespective of the stroke/TIA history it increased the risk of recurrent HF hospitalization. The survival free of rehospitalization Funding Acknowledgement Type of funding source: None

Shifting Treatment Patterns and Clinical Outcomes in Veterans Diagnosed with Waldenstrom Macroglobulinemia from 2006 to 2018

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-12
Author(s):  
Hsu-Chih Chien ◽  
Deborah Kay Morreall ◽  
Vikas Patil ◽  
Kelli M Rasmussen ◽  
Christina Yong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Outcomes ◽  
Real World ◽  
Research Funding ◽  
Practice Patterns ◽  
Treatment Patterns ◽  
Clinical Settings ◽  
Treatment Groups ◽  
Treatment Regimens

Background Waldenström's Macroglobulinemia (WM) is a rare indolent lymphoma with an estimated 1,500 new cases diagnosed each year in the United States (US). Over the last decade, several treatments have been introduced into the WM therapeutics landscape including, bendamustine, bortezomib, and most recently oral Bruton's kinase inhibitor (ibrutinib). There is limited information in the adoption of these WM treatments in real-world clinical settings in the US. We describe the practice patterns and clinical outcomes of first-line (1L) treatment of WM in a nationwide cohort of Veterans. Methods Using Veteran Affairs electronic health records (EHR) data, we identified Veterans who were diagnosed and received 1L treatment for WM between January 2006 and December 2018 in the Veterans Health Administration (VHA). Human annotation of EHR clinical records confirmed the diagnosis and 1L treatment regimens. Patients with another cancer diagnosis or patients with documentation that 1L treatment was received outside the VHA were excluded. Eligible patients were followed until loss to follow-up, death, or the end of the study period (June 30, 2019). Patient demographics, disease characteristics, and treatment patterns were identified. Local polynomial regression model curves were generated to demonstrate treatment changes over time. Unadjusted progression-free survival (PFS) and the unadjusted overall survival (OS) are also provided. Results We identified 505 patients diagnosed with WM in VHA between January 2006 thru December 2018. Of these, 318 patients received 1L treatment, with a median time from diagnosis to 1L treatment of 1.2 months (95% confidence interval [CI]: 0.5-5 months). The median age of WM patients was 69.9 years (standard deviation [SD]: 9.4 years), with approximately 73% of WM patients ≥65 years old. Prior to 1L treatment, the median hemoglobin and platelets observed were similar across all treatment groups, regardless of first 1L treatment. However, the median immunoglobulin M (IgM) was substantially lower in patient's treated with ibrutinib (2,570 mg/dL [range: 422-9,001 mg/dL]) and single-agent rituximab (R), 2,855 mg/dL (range: 84-7,880 mg/dL) when compared to those treated with chlorambucil +/- rituximab (4,416 mg/dL [range: (9-8,130 mg/dL]) and bortezomib/dexamethasone +/- rituximab (BDR), 4,086 mg/dL (range: 16-9,944 mg/dL). MYD88 testing occurred in 40 (13%) of patients, with testing most frequently occurring in patients treated with bendamustine +/- rituximab (BR), ibrutinib, and BDR- likely reflecting increased adoption in later periods. Hepatitis C testing occurred in 61 (19%) of patients, with testing most frequently occurring in patients treated with dexamethasone, rituximab, and cyclophosphamide (DRC), BDR, and BR. Over the study observation period, 1L practice patterns shift significantly with increased adoption of BR, BDR and ibrutinib and de-adoption of chemotherapy (Figure 1). The median follow-up time for all patients was 44 months (range: 1-147 months), although a shorter median follow-up time was observed in patients treated with therapeutics in recent years, such as ibrutinib (18 months [range: 2-53 months]) and BR (23 months [range: 4-86 months]). The median unadjusted PFS for all WM patients was 44 months (95% CI: 37-58 months) and the median unadjusted overall survival (OS) was 94 months (95% CI: 82-117 months). Conclusions The introduction of numerous therapeutic options throughout the past decade has profoundly altered the treatment landscape for WM, suggesting a shift in 1L practices from chlorambucil to BDR, BR, and most recently ibrutinib which has been increasingly adopted, since its approval in 2015, especially in older patients, suggesting that it may provide an effective therapeutic option for patients who may not be able to tolerate more aggressive treatment regimens. Limitations of this study include the differences observed in follow-up time as well as the limited number of patients in some 1L treatment groups. Further research is required to establish the long-term benefits and potential treatment-related toxicities of WM treatments in real-world clinical settings. Disclosures Sauer: Roche: Research Funding; Genentech, Inc.: Research Funding; Pharmacyclics: Research Funding; AbbVie: Research Funding. Halwani:AbbVie: Research Funding; Takeda: Research Funding; Roche: Research Funding; Genentech, Inc.: Research Funding; Miragen: Research Funding; Immunedesign: Research Funding; Kyowa Hakko Kirin: Research Funding; Seattle Genetics: Research Funding; Amgen: Research Funding; Pharmacyclics: Research Funding; Bristol Myers Squibb: Research Funding.

Long-Term Follow-up of Patients with HIV-Related Diffuse Large B-Cell Lymphoma (DLBCL) Treated in the Phase II Study with Rituximab and CHOP (R-CHOP)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4980-4980
Author(s):  
Josep-Maria Ribera ◽  
Mireia Morgades ◽  
Albert Oriol ◽  
Eva González-Barca ◽  
Pilar Miralles ◽  
...  
Keyword(s):  
Phase Ii ◽  
Opportunistic Infections ◽  
Conflicts Of Interest ◽  
B Cell Lymphoma ◽  
Cumulative Probability ◽  
Second Cancer ◽  
Second Cancers ◽  
Long Term Follow Up

Abstract Abstract 4980 Background and objective. In the highly active antiretroviral treatment (HAART) era R-CHOP based chemotherapy has proven to be feasible and effective in HIV-related DLBCL. However, the available information on long-term follow-up of patients in remission of lymphoma is scarce. In addition, solid tumors constitute an emerging cause of cancer in HIV-infected patients under HAART. The follow-up of patients in complete response (CR) included in a phase II clinical trial of R-CHOP every 21 days conducted by the Spanish PETHEMA, GESIDA, GELTAMO and GELCAB groups (Ribera JM et al. Br J Haematol 2007; 140: 411–419) has been analyzed. Patients and methods. Out of 81 patients included in the trial 55 patients were in CR. The following data were recorded in these patients: NHL relapse, opportunistic infections (OI) and other cancers. Cumulative probabilities of OI and second cancers, as well as overall survival (OS) and event-free survival (EFS) were calculated. Results. Median follow-up of alive patients was 6.4 yr (range: 4.6–9.5). One patient was lost of follow-up in CR, 8 relapsed, 5 had OI (meningoencephalitis [2], Pneumocystis jiroveci pneumonia [1], varicella pneumonia [1], pneumoccal pneumonia [1], esophageal candidiasis [1], and CMV colitis [1]; 2 patients suffered 2 OI during their evolution) and 5 developed a second cancer (invasive carcinoma of cervix [1], squamous lung cancer [1], lung adenocarcinoma [1], pancreatic adenocarcinoma [1], and metastatic sarcoma of unknown origin [1]). Eight-year cumulative probability for OI was 15% (95%CI: 7%-23%) and for second cancer was 12% (95%CI: 2%-22%). Fourteen patients have died: 5 due to lymphoma relapse, 3 due to OI, 4 due to second cancer and 2 due to other reasons (sudden death and assassinate). Eight-year OS probability for the 55 patients in first CR of the lymphoma was 67% (95%CI: 48%-86%) and EFS probability was 59% (95%CI: 42%-76%). Conclusions. HIV-infected patients with DLBCL treated with R-CHOP and HAART followed for long-time have a significant frequency of OI and second cancers, with impact on their survival probability. Supported in part with grants RD06/0020/1056 from RTICC, Instituto Carlos III, 36606/06 from FIPSE and P-EF/10 from FJC. Disclosures: No relevant conflicts of interest to declare.

Is Chronic Lymphocytic Leukemia Still Incurable?

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3929-3929
Author(s):  
Michael J. Keating ◽  
Constantine S Tam ◽  
William G. Wierda ◽  
Susan O'Brien ◽  
Deborah A. Thomas ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Residual Disease ◽  
Lymphocytic Leukemia ◽  
Fish Analysis ◽  
Cell Transplant ◽  
Second Malignancies ◽  
Mutation Status ◽  
Richter’S Transformation ◽  
Richter's Transformation

Abstract Abstract 3929 Introduction Up until now, Chronic Lymphocytic Leukemia (CLL) has been considered incurable except with an allogeneic stem cell transplant. In the last 10 years, evidence has demonstrated that chemo-immuotherapy with fludarabine, cyclophosphamide, and rituximab, (FCR) has significantly improved CR rates, overall survival (OS), and progression free survival 1. Long term follow up data for FCR at MDACC demonstrated that a significant proportion of patients (pts.) were free at 8 years2 raising the question of whether pts. are potentially cured. Definition of cure in a chronic disease such as CLL has not been addressed. To investigate this possibility we evaluated the outcome characteristics of 222 of the 300 patients (who commenced FCR more than 10 years ago) in our previously reported study of initial therapy with FCR in CLL2. Seventy eight (35%) pts were free of relapse and 127 (58%) were alive at 10 years (Fig. 1). Thirty three patients died in CR/PR of infection (5), second malignancies (8), Richter's transformation (8). MDS (9), and other causes (3). One hundred and sixty three pts. (73%) achieved CR, 22 pts. (10%) a nodular PR (nPR), 27 pts. (12%) a PR, and 10 (5%) failed treatment. The 10 year PFS correlates strongly with response, CR (41%), nPR+PR (15%) (Fig. 2). None of these patients were transplanted in remission. FISH analysis was not available at the time of this study. Conventional karyotyping demonstrated +12 (24 pts), del 11q (15), del 17p (4), other abnormalities (15), diploid (105), and in 59 patients the test was not done or had no metaphases. The worst outcomes were del 17p and del 11q each significantly inferior to diploid (+12) patients had the best time-to-treatment failure (TTF) with P<.09 compared to diploid. The 10-year TTF was significantly higher for Rai <3 versus 3 – 4 (P=.02), serum beta-2-microglobulin (β2M) value of ≤ 4 mg/L (p<.001), mutation status of IgVh (P<.001) and number of courses of FCR received. (Table 1) The causes for receiving <6 courses of FCR were persistent cytopenia (15), infections (6), resistance (5), Richter's transformation and other malignancies (9), autoimmune hemolysis (5), and other causes and lost to follow-up (16). Of the 77 patients who are still in remission at 10 years, two have relapsed and one developed Richter's transformation. Four of 21 patients checked had no residual disease in their blood at 10 years by 4-parameter flow cytometry. All other 10 yr. TTF patients are being contacted to provide blood for 4-parameter flow residual disease. Conclusion The present data suggest that one-third of patients treated with chemoimmunotherapy are potentially cured of CLL. The characteristics most strongly associated with 10 yr. TTF were Rai stage, serum β2M level, mutation status, and tolerance of chemotherapy. Second malignancies and transformations are emerging as significantly impairing the likelihood of cure. Disclosures: No relevant conflicts of interest to declare.

Characteristics and Prognosis of Patients with Aggressive Chronic Lymphocytic Leukemia and Richter's Transformation: Correlation Between FDG/PET, Histology and Clinical Outcomes

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 927-927
Author(s):  
Lorenzo Falchi ◽  
Long Xuan Trinh ◽  
Edith M. Marom ◽  
Mylene Truong ◽  
Ellen Schlette ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Clinical Outcomes ◽  
Fdg Pet ◽  
Conflicts Of Interest ◽  
Chronic Phase ◽  
Lymphocytic Leukemia ◽  
Bulky Disease ◽  
Standardized Uptake Values ◽  
Richter’S Transformation ◽  
Richter's Transformation

Abstract Abstract 927 Introduction. Richter's transformation (RT) occurs in 2–8% of pts with chronic lymphocytic leukemia (CLL) and is associated with poor prognosis. Moreover, pts with CLL often show clinical and/or histologic features of aggressive disease, but do not fulfill the histological criteria for RT. FDG/PET is a diagnostic tool in hematologic malignancies. Standardized uptake values (SUV) measured by FDG/PET correlates with tumor cell proliferation and aggressiveness. FDG/PET is increasingly used to evaluate pts suspicious for RT. We therefore reviewed the experience with FDG/PET in the diagnosis and management of pts with aggressive CLL and RT seen at our Institution and correlated FDG/PET data, histology, and clinical outcomes in these pts. Methods. We studied pts assessed with FDG/PET and concurrent lymph node biopsy (or marrow diagnosis of transformation). According to the histological characteristics pts were grouped in 3 categories: chronic phase (CP), increased aggressiveness (IA) or overt RT. IA was defined for this report by the presence of either increased number of large cells or ≥10% prolymphocytes in the tissue specimen. The extent of disease was assessed by FDG/PET and defined: limited = hypermetabolic sites with SUVbwmax≥5 on one side of the diaphragm; extensive = hypermetabolic sites with SUVbwmax≥5 on both sides of the diaphragm. After therapy, restaging FDG/PET was analyzed, when available, for response assessment. Results. 750 pts with CLL had at least 1 complete FDG/PET report, 422 were excluded from this analysis because of: no biopsy in 341 pts, no FDG/PET at time of biopsy in 34, concurrent cancer in 25, benign histology in 18, CP histology in pt with past RT/IA in 4. 328 pts had both FDG/PET and histological characterization and are the focus of this report. 93 pts had RT, 116 had IA and 119 had CP. Patient characteristics are summarized in table 1. We analyzed FDG/PET results in these 328 pts. Median highest SUV (SUVbwmax) was 17.9 (0-56.3) for pts with RT, 6.7 (0-37.8) for pts with IA and 3.6 (0-14.3) for pts with CP. Using an SUVbwmax cutoff of 5 sensitivity, specificity, positive and negative predictive value for the detection of RT were 88%, 48%, 40% and 91%, respectively. We next correlated FDG/PET result, histology and survival. Median overall survival (OS) was 7.9, 19.7, and 77.3 months in pts with RT, IA and CP, respectively. SUVbwmax correlated with OS. An SUVbwmax cutoff of 10 showed the highest discriminatory power: median OS was 56.4 months (95% CI: 36.4 – 71.3) in pts with SUVbwmax<10 vs 7.3 months (95% CI: 5.0 – 8.6) in pts with SUVbwmax≥10. OS of pts with RT or IA was similar for pts with SUVbwmax<10 (29.5 vs 21.4 months, p=.62) or ≥10 (7.6 vs. 5.9 months, p=.71). Sixty %, 38% and 13% of pts with RT, IA, and CP, respectively, had extensive disease. OS was not significantly different between pts with limited vs extended disease within pt groups with SUVbwmax<10 or ≥10 (p=.45 vs .06, respectively). Factors independently associated with inferior OS in multi variable analysis were: RT histology, age ≥65 ys, PS ≥2, bulky disease, prior therapy, and SUVbwmax≥10. All pts with RT or IA, and 71% of pts with CP received treatment. 95 pts had a FDG/PET performed as restaging. In these pts OS was not reached in pts with ≥66% reduction in SUVbwmax after therapy and 15.3 months in those without such reduction (p <.0001). Conclusion. In our experience, FDG/PET accurately suggested the presence of RT in pts with CLL. SUVbwmax correlates with OS in pts with transformed CLL, independently of disease histology and extension. Restaging FDG/PET also predicted OS in pts with RT or IA. Prospective studies to validate the role of FDG/PET in the evaluation and management of pts with CLL are ongoing Disclosures: No relevant conflicts of interest to declare.

Central Neurocytoma

Neurosurgery ◽  
2012 ◽  
Vol 72 (3) ◽  
pp. 407-414 ◽  
Author(s):  
Jin Wook Kim ◽  
Dong Gyu Kim ◽  
In Kyeong Kim ◽  
Yong Hwy Kim ◽  
Seung Hong Choi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Outcomes ◽  
Functional Outcomes ◽  
Management Strategies ◽  
Treatment Strategies ◽  
Central Neurocytoma ◽  
Tumor Control ◽  
Seizure Outcome

Abstract BACKGROUND: A thorough investigation of the long-term outcomes of central neurocytoma (CN) after different treatments is required to establish optimal management strategies. OBJECTIVE We retrospectively reviewed the long-term clinical outcomes of patients with CN according to various treatments and suggest treatment strategies based on 30 years of experience in a single institution. METHODS: Fifty-eight consecutive patients with CN were treated at our institution between 1982 and 2008. Patient demographics, overall survival, local control rates according to multimodal treatments, and functional outcomes were evaluated. The mean clinical and radiological follow-up periods were 119 months (range, 18-304 months) and 98 months (range, 13-245 months), respectively. RESULTS: The initial treatment modality was classified into 4 subgroups: operation only (34 patients), operation followed by radiation therapy (7 patients) or radiosurgery (7 patients), and radiosurgery alone (10 patients). The actuarial overall survival was 91% at 5 years and 88% at 10 years. The actuarial overall survival and local tumor control rate did not differ significantly according to the various treatments and the initial extent of the surgical resection. However, functional outcomes, such as the postoperative seizure outcome at the last follow-up, differed according to the surgical approach. CONCLUSION: The long-term clinical outcomes of CN after multimodal treatment seem to be excellent. Our study suggests that treatment strategies for CN should focus on the patient's quality of life, as well as on tumor control, because of the benign nature of CN.

scholarly journals Long term prognosis of out-of-hospital cardiac arrest due to idiopathic ventricular fibrillation - a tertiary center experience

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
R Alves Pinto ◽  
T Proenca ◽  
M Martins Carvalho ◽  
PD Grilo ◽  
CX Resende ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Ventricular Fibrillation ◽  
Clinical Outcomes ◽  
Cardiac Death ◽  
Previous History ◽  
Provocative Test ◽  
Tertiary Center ◽  
History Of

Abstract Funding Acknowledgements Type of funding sources: None. Background  Sudden cardiac death (SCD) is an uncommon event in the absence of structural heart disease. However, ventricular fibrillation (VF) may occur in patients with unknown cardiac disease and a comprehensive work-up is needed to further improve diagnostic. Still, a significant and heterogenous group of patients remains labelled of Idiopathic VF and limited data is available regarding their natural history. Purpose The aim of this study was to evaluate the clinical outcomes of survivors of an aborted sudden cardiac death due to idiopathic VF or pulseless ventricular tachycardia (VT) and to assess possible predictors of recurrence. Methods  Patients who survived an idiopathic VF or pulseless VT between 2005 and 2019 referred to a cardiac defibrillator (ICD) implantation were included. Patients were followed for 1 to 15 years (median follow-up of 7 years). Clinical and device data were collected. Results A population of 29 patients, 59% male, with a median age of 50 years (age ranging from 18 to 76) at the time of the aborted SCD was studied. All patients implanted an ICD (69% single chamber, 24% dual chamber and 3% subcutaneous) at the index hospitalization. The initial rhythm was VF in 76% and pulseless VT in 24%. In relation to the context of the arrhythmic event, 48.3% occurred during daily life activities, 13.8% after an emotional stress, 6.9% during efforts and a similar percentage occurred either in rest or asleep. Of note, 12.5% of patients had previous history of syncope. Normal ECG was present in 83% of patients. Family history of SCD was present in 12% of the cases. As for the cardiovascular risk factors, 61.5% had hypertension, 19% dyslipidemia, 17% diabetes, 31% were smokers or previous smokers. Paroxysmal atrial fibrillation was present in 15% of patients. To exclude possible causes of VF, all patients were submitted to coronary angiogram and echocardiogram, 64% to genetic testing, 68% to cardiac magnetic resonance, 20% to electrophysiologic study, 12% to pharmacological provocative test and 4% were submitted to endomyocardial biopsy. At follow-up, an etiological diagnosis was established in 31% of patients: 3 events were attributed to coronary vasospasm, 3 to short coupled polymorphic VT, 1 patient had long QT syndrome, 1 had Brugada syndrome and in 1 patient an ANK2 mutation was identified. As for the clinical outcomes, 8% patients died (from non-arrhythmic causes), 31% patients received appropriate therapies and 19% had unappropriated shocks (of those 60% for sinus tachycardia and 40% for supraventricular tachycardia). Conclusion Etiologic diagnosis and prediction of recurrence of arrhythmic events in patients with idiopathic VF is challenging, even with a long-term follow-up and more sophisticated diagnostic evaluation.  Idiopathic VF is a rare but serious condition with recurrence in about one third of patients. Although not free of complications, ICD remains the gold standard of treatment.

scholarly journals Near-Tetraploidy Is Strongly Associated with Development of Richter's Transformation in Chronic Lymphocytic Leukemia Patients Receiving Ibrutinib

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3198-3198
Author(s):  
Cecelia R. Miller ◽  
Amy S. Ruppert ◽  
Nyla A. Heerema ◽  
Kami J. Maddocks ◽  
Jadwiga Labanowska ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Board Of Directors ◽  
Research Funding ◽  
Lymphocytic Leukemia ◽  
Complex Karyotype ◽  
Advisory Committees ◽  
Data Set ◽  
Richter’S Transformation ◽  
Richter's Transformation

Abstract Ibrutinib is a promising targeted therapy for chronic lymphocytic leukemia (CLL). However, a small subset of patients progress on ibrutinib either through progressive CLL or Richter's transformation. Patients responding to ibrutinib and then progressing with Richter's transformation do so most commonly within the first 2 years of treatment and have an extremely poor prognosis. Identifying biomarkers associated with this transformation is of utmost importance. Near-tetraploidy (4 copies of most chromosomes within a cell) has been reported in various lymphomas; however, its incidence in CLL has not been described. We investigated the prevalence of near-tetraploidy in CLL patients prior to starting ibrutinib and identified it as a pre-treatment biomarker for Richter's transformation. We examined near-tetraploidy in a large series of CLL patients enrolled across four ibrutinib clinical trials at the Ohio State University, for which extensive correlative studies and follow up data are available (previously described by Maddocks et al., JAMA Oncol, 2015). We identified this abnormality in 9 of 300 patients (3.0%, 95% CI: 1.4-5.6) in blood or bone marrow samples taken prior to starting therapy. Near-tetraploidy was detected by the presence of four signals with four or more fluorescence in situ hybridization (FISH) probes and confirmed in the metaphase karyotype of each patient in at least one cell. Near-tetraploidy was associated with aggressive disease characteristics including: Rai stage 3/4 (p=0.03), deletion 17p (p=0.03), and complex karyotype (p=0.01), as well as trisomy 12 (p=0.05). With a median follow-up time of 40.5 months, in patients positive with near-tetraploidy, one patient (11%) progressed with CLL on ibrutinib, six patients (67%) progressed with Richter's transformation, and two patients (22%) were still on treatment. Cumulative incidence of Richter's transformation was significantly higher in patients with near-tetraploidy (Figure; p<0.0001). Notably, near-tetraploidy was not associated with progression with CLL alone (p=0.53). In a multivariable model, both near-tetraploidy (HR 8.66, 95% CI 3.83-19.59, p<0.0001) and complex karyotype (HR 4.78, 95% CI 1.42-15.94, p=0.01) were independent risk factors for discontinuing ibrutinib due to Richter's transformation. Our results suggest that near-tetraploidy is a distinct biomarker to assess in patients initiating ibrutinib which would predict a high risk for Richter's transformation. As a biomarker it will be important to confirm this association in a second independent data set as well as interrogate the distinct pathophysiology of this genomic subset of CLL. Figure Figure. Disclosures Lozanski: Stemline Therapeutics Inc.: Research Funding; Boehringer Ingelheim: Research Funding; Genentech: Research Funding; Beckman Coulter: Research Funding. Jones:Pharmacyclics, LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Andritsos:Hairy Cell Leukemia Foundation: Research Funding. Awan:Novartis Oncology: Consultancy; Pharmacyclics: Consultancy; Innate Pharma: Research Funding. Blum:Pharmacyclics: Research Funding. Woyach:Acerta: Research Funding; Morphosys: Research Funding; Karyopharm: Research Funding.

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