Impact of Hypomethylating Agent Use on Hospital and Emergency Room Visits,and Predictors of Early Discontinuation in Patients With Higher-Risk Myelodysplastic Syndromes

BackgroundPrevious analyses using the SEER-Medicare database have reported substantial underutilization of hypomethylating agents (HMAs) among patients with higher-risk myelodysplastic syndromes (MDS), and an association between poor HMA persistence and high economic burden. We aimed to compare rates of hospitalizations and emergency room (ER) visits among patients with higher-risk MDS according to use or non-use of HMA therapy, and to explore factors associated with early discontinuation of HMA therapy.Patients and MethodsWe used the 2010–2016 SEER-Medicare database to identify patients aged ≥66 years with a new diagnosis of refractory anemia with excess blasts (RAEB; a surrogate for higher-risk MDS) between 2011 and 2015. New hospitalizations and ER visits during the 12 months following MDS diagnosis were determined. Treatment discontinuation was defined as stopping HMA therapy before 4 cycles.ResultsOverall, 664 (55.8%) patients were HMA users and 526 (44.2%) non-users. Non-users had more hospitalizations (mean 0.47 vs. 0.30, P < .001) and ER visits (mean 0.69 vs. 0.41, P = .005) per month than HMA users. Among HMA users, 193 (29.1%) discontinued HMA therapy before 4 cycles, and 91 (47.2%) of these after 1 cycle. Older age and poor performance status were associated with higher risk of HMA discontinuation.ConclusionAn increased rate of hospitalizations and ER visits occurred in HMA non-users vs. HMA users. Approximately one-third of patients discontinued HMA therapy early. Predictors of discontinuation included older age and poor performance status. Novel approaches are needed to improve utilization and persistence with HMA therapy and associated outcomes, particularly among these higher-risk groups.     

Early Real-World First-Line Treatment With Venetoclax Plus HMAs Versus HMA Monotherapy Among Patients With AML in a Predominately US Community Setting

BackgroundVenetoclax in combination with hypomethylating agents (HMAs) is standard-of-care in patients with newly diagnosed acute myeloid leukemia (AML) who are ≥ 75 years old or unfit for intensive chemotherapy. We examined early real-world treatment experience among patients with AML receiving venetoclax+HMAs or HMA monotherapy.Patients and methodsThis retrospective cohort study used an electronic health record-derived, deidentified, United States nationwide database comprised of patient-level structured and unstructured data, curated via technology-enabled abstraction. Patients with an AML diagnosis on or after January 1, 2014, who had ≥ 2 clinic visits, and initiated treatment with venetoclax+HMAs from June 1, 2018 to March 31, 2021, or HMA monotherapy from January 1, 2016 to May 31, 2018, were included. Kaplan–Meier analysis was used to estimate time to last administration (TTLA) and overall survival (OS).ResultsOverall, 619 patients treated with venetoclax+HMAs and 480 treated with HMA monotherapy were selected from the database. Median age at diagnosis was 76 and 78 years, respectively, most patients were treated in community practice (83.4% and 89.4%, respectively), and almost half had secondary AML (47.2% and 47.3%, respectively). Adjusted analyses showed both significantly longer TTLA (3.6 months vs. 2.3 months; hazard ratio [HR] = 0.69 [95% confidence interval (CI), 0.60-0.80], P< .0001) and OS (9.3 months vs. 5.9 months; HR = 0.71 [95% CI, 0.61-0.82], P < .0001) in patients treated with venetoclax+HMAs versus HMA monotherapy, respectively.ConclusionThis study shows benefit in real-world outcomes of venetoclax+HMAs relative to HMA monotherapy in patients with newly diagnosed AML, using a predominantly community-based database.     

Favorable Outcomes With Tumor Burden Reduction Following Administration of Hypomethylating Agents Before Allogeneic Hematopoietic Cell Transplantation in Patients With Higher Risk Myelodysplastic Syndrome

IntroductionThe clinical significance of tumor burden reduction following administration of hypomethylating agents (HMAs) for transplant-eligible patients with higher risk myelodysplastic syndrome (MDS) was evaluated.Patients and MethodsData of 79 transplant-eligible patients (< 65 years) diagnosed with higher-risk MDS between July 2002 and March 2013 were retrospectively analyzed. Among 79 patients, 30 (38%) underwent allogeneic hematopoietic cell transplantation (HCT group), and 49 (62%) were treated with HMA alone (non-HCT group).ResultsThe median follow-up duration was 732 days (range, 28-1952 days), and the 3-year overall survival (OS) rate of all patients was 30.6%. In the HCT group, early HCT showed a better 3-year OS rate than late HCT (67.1% vs. 25.7%; P = .035). In multivariate analysis, time/performance of allogenic transplant (no HCT vs. early HCT, hazard ratio, 0.18; 95% confidence interval, 0.04-0.81; P = .026) and follow-up higher risk International Prognostic Scoring System (hazard ratio, 6.22; 95% confidence interval, 2.09-18.51; P = .001) were significantly correlated with OS.ConclusionTo predict the clinical outcomes of patients with higher risk MDS, the optimal time for tumor burden evaluation is prior to follow-up rather than at the time of initial diagnosis. Patients with lower International Prognostic Scoring System risk groups after HMA treatment or early HCT had favorable OS.     

Hematologic outcomes of myelodysplastic syndromes treatment with hypomethylating agents in community practice

IntroductionHypomethylating agents (HMAs) treat myelodysplastic syndromes (MDS) through suppression of abnormal clones that may cause low hemoglobin (Hgb), platelet (PLT) deficiencies, and reduced absolute neutrophil count (ANC). Our study examined hematologic outcomes in MDS among patients treated with HMAs in a large community hematology-oncology practice.Materials and MethodsA retrospective study using electronic medical record data studied patients who received at least one cycle of a single HMA (decitabine [DAC] or azacitidine [AZA]) for MDS from June 1, 2006, to May 31, 2009, who had pretreatment and end-of-treatment Hgb, PLT counts, and ANC available. Multivariate logistic regression assessed predictors of end-of-treatment response (Hgb ≥ 11g/dL without transfusion or erythrocyte stimulating agent; PLT ≥ 100,000 cells/μL without transfusion; ANC ≥ 1000 cells/mm³ without colony stimulating factor) adjusting for baseline laboratory values, age, gender, and comorbidities. HMA choice was studied as a predictor of outcome.ResultsA total of 137 patients (mean age, 72.2 years; 57% male) met full inclusion criteria (DAC = 84, AZA = 53). Mean number of cycles was four (range, 1-16 cycles) for DAC and five (range, 1-23 cycles) for AZA. Total number of cycles significantly predicted Hgb, PLT, and ANC response (odds ratio [OR] 1.19, P = .029; OR 1.15, P = .031; OR 1.16, P = .047, respectively). Growth factor use at any point during HMA treatment was negatively associated with Hgb and ANC response (OR 0.85, P = .007; OR 0.96, P = .046). There was no difference between treatments in likelihood of PLT or ANC response.ConclusionsPatients treated with HMAs for MDS are more likely to achieve hematologic response when treated with a greater number of cycles.     

Injectable Hypomethylating Agents for Management of Myelodysplastic Syndromes: Patients’ Perspectives on Treatment

BackgroundUntil recently, patients with MDSs could receive HMAs via intravenous (IV) or subcutaneous (SC) administration. An oral HMA was recently approved as an alternative to IV/SC administration. This study assessed the impact of IV/SC HMA on MDS patients, and their experience of, challenges with, and views about oral MDS treatment.Patients and MethodsWe conducted an online cross-sectional survey among adult MDS patients (or caregivers as proxies) invited by 2 U.S. MDS patient advocacy groups. Patients were required to have received IV/SC HMA (ie, azacitidine or decitabine) within 6 months of the survey.ResultsThe survey was completed by 141 participants (120 patients, 21 caregiver proxies). Median patient age was 63.0 years, 53.9% were women, and 19.8%, 62.4%, and 17.7% had lower-, higher-, or unknown risk scores, respectively. HMA treatments received included SC azacitidine (37%), IV azacitidine (36%), and IV decitabine (27%). Among 89 IV HMA recipients, 74.2% and 69.7% reported treatment-related interference with their social and daily activities, respectively, and 66.3% reported pain related to treatment administration. Following an injection, SC HMA recipients reported pain (94.2%) and interference with daily (86.5%) and social (80.8%) activities. Among the 49.6% of patients who were working, 61.4% felt less productive due to treatment. Most (69.5%) MDS patients indicated they would prefer oral MDS treatment to IV/SC therapies.ConclusionPatients receiving IV/SC HMAs experienced pain/discomfort and interference with social and daily activities. The introduction of an oral HMA may alleviate some treatment challenges for MDS patients.     

Hypomethylating Agent Therapy in Myelodysplastic Syndromes With Chromosome 3 Abnormalities

BackgroundAbnormalities of chromosome 3 in myelodysplastic syndromes (MDS), that is, inversion 3 (inv[3]), translocation 3q (t[3q]), or deletion 3q (del[3q]), are defined as poor-risk karyotypes in the Revised International Prognostic Scoring System (IPSS-R). The objective of this study was to further define the outcomes of patients with MDS with chromosome 3 abnormalities and address the impact of hypomethylating agent (HMA) therapy on this patient subset.Patients and MethodsThrough the MDS Clinical Research Consortium, we identified 411 patients with chromosome 3 abnormalities and MDS or oligoblastic acute myeloid leukemia (20%-30% blasts).ResultsSpecific chromosome 3 aberrations and cytogenetic complexity were predictive of survival; patients with t(3q) and isolated chromosome 3 had improved overall survival (OS), albeit still poor, whereas patients with complex cytogenetics, including those with 3p abnormalities, had inferior OS. Overall response rates to HMAs among this patient population were similar to those of patients with nonchromosome 3–MDS (52%, with a 25% complete remission rate), although with higher response rates in decitabine-treated patients (69% vs. 45%, P = .008). HMA therapy improved the OS of patients with higher-risk MDS compared with intensive chemotherapy (median OS of 15.5 vs. 8.2 months; P = .017). This improvement remained significant in multivariate analyses (hazard ratio, 0.60; P = .018); however, there were no chromosome 3 aberrations among this subgroup predictive of improved response rates to or survival from HMAs.ConclusionPatients with MDS with chromosome 3 abnormalities represent a cytogenetic cohort with poor OS, and there is an urgent need for novel therapeutic strategies.     

Pattern of hypomethylating agents use among elderly patients with myelodysplastic syndromes

Little is known about how hypomethylating agents (HMAs) have been adopted into the treatment of myelodysplastic syndromes (MDS). We conducted a population-based study to assess the use of HMAs among 4416 MDS patients (age ≥66 years) who were diagnosed during 2001-2005 and followed up through the end of 2007. Multivariate logistic regression models were utilized to evaluate the role of various patient characteristics. 475 (10.8%) patients had received HMAs by 2007, with the proportion increasing over time. Patients who were white (odds ratio (OR) = 0.66, 95% confidence interval (CI): 0.46-0.95), male (OR = 1.47, 95% CI: 1.19-1.82), young (P_trend < 0.01), more recently diagnosed (OR = 1.90, 95% CI: 1.54-2.34), had fewer comorbidities (P_trend < 0.01), or had a history of other cancer (OR = 1.28, 95% CI: 1.00-1.63) were more likely to receive HMAs. Compared with patients with refractory anemia, those diagnosed with refractory anemia with excess blasts or refractory cytopenia with multilineage dysplasia had a higher chance to be treated with HMAs (OR = 3.52 and 2.32, respectively). Relatively few MDS patients were treated with HMAs during the introduction period of these agents, and multiple patient characteristics such as sex, comorbidities, and MDS subtype influence the likelihood a patient receives HMAs.     

Evidence for Selective Benefit of Sequential Treatment With Hypomethylating Agents in Patients With Myelodysplastic Syndrome

BackgroundHypomethylating agents (HMAs) remain the mainstay of treatment of patients with myelodysplastic syndrome (MDS). Azacitidine is the only agent shown to improve overall survival in higher risk MDS. The sequential use of HMAs is common practice, given the limited alternatives. The response rate to azacitidine after decitabine is unknown. To investigate the potential benefit of this approach, we reviewed all cases of sequential HMA treatment.Patients and MethodsThe Moffitt Cancer Center MDS database was reviewed, and 2 groups were identified. Group 1 had received decitabine after azacitidine failure and group 2 had received azacitidine after decitabine failure. The primary objective was to estimate the overall response rate according to the International Working Group 2006 criteria. The χ² test and t test were used for the categorical and continuous variables, respectively. The Kaplan-Meier method was used to estimate the median overall survival.ResultsThe overall response rate for hematologic improvement or better was 63% in group 1% and 50% in group 2. The response to second-line treatment in groups 1 and 2 was 19% and 40%, respectively. The median overall survival for group 1 from diagnosis was 48 months and for group 2 was 100 months (P = .7).ConclusionEnrollment in clinical trials should be strongly encouraged in the case of HMA failure. Sequential use of HMAs could be considered as an alternative approach in the treatment of MDS after first-line HMA failure if clinical trials are not available. The outcomes of patients with progressive disease after treatment with HMAs remain poor and continue to be an unmet need.     

The Real-Life Efficacy of Fixed-Dose Hypomethylating Agents in Older Patients With Acute Myeloid Leukemia: A 10-Year Experience

BackgroundHypomethylating agent (HMA) is one of recommended treatment for elderly patients with acute myeloid leukemia (AML); however, their high cost precludes their general use, especially in developing countries. Therefore, the fixed-dose HMAs approach was adopted to reduce the expenses. This study focuses on the clinical outcome of various treatment protocols, including intensive chemotherapy, fixed-dose HMAs, and palliative treatment in Thai elderly patients with AML. Fixed-dose HMAs include 5-azacitidine given at 100 mg per day for seven days and decitabine given at 30 mg per day for 5 days.Patients and MethodsWe conducted a 10-year cohort study focused on elderly AML patients aged over 60 years. The exclusion criteria were acute promyelocytic leukemia.ResultsA total of 243 AML patients were enrolled. Comparing 3 groups of treatment regimens (intensive chemotherapy, fixed-dose HMAs, and palliative treatment), the proportions of patients in each category accounted for 23.5%, 21.4%, and 55.1%, respectively. The median overall survival (OS) in each therapeutic option was 7.7, 11, and 2.5 months, respectively. From multivariate analysis, palliative treatment was significantly inferior OS comparing to the fixed-dose HMAs and intensive treatment (hazard ratio [HR]: 0.42; 95% CI, 0.29-0.60; P value <.001 and HR: 0.41; 95% CI, 0.28-0.61; P value <.001, respectively). Nevertheless, the OS outcome in patients with fixed-dose HMAs was comparable to those who received intensive treatment.ConclusionOur study demonstrates that the fixed-dose regimen of HMAs is the reasonable treatment for these patients, and this approach is not inferior to intensive therapy. Thai Clinical Trials Registry identifier: TCTR20210514007.     

Comparison of Upfront Transplantation and Pretransplant Cytoreductive Therapy for Advanced Myelodysplastic Syndrome

BackgroundAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for advanced myelodysplastic syndrome (MDS). However, the value of pretransplant cytoreduction remains debatable.Patients and MethodsWe retrospectively compared the outcomes of upfront transplantation and pretransplant cytoreduction. Of 69 patients, 39 received upfront allo-HSCT and 30 received pretransplant cytoreduction, including chemotherapy (n = 16), hypomethylating agents (HMAs, n = 6), and HMAs with chemotherapy (n = 8).ResultsThe upfront group achieved similar overall survival (OS) and a trend of better progression-free survival (PFS) from diagnosis compared with the cytoreduction group (3-year PFS, 64.0% vs. 44.4%, P = .076). Posttransplant outcomes were comparable between the two groups in terms of OS, relapse-free survival (RFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM). In patients with ≥2 mutations, the upfront group achieved better OS and PFS (3-year OS, 100.0% vs. 68.6%, P = .044; 3-year PFS: 92.3% vs. 43.9%, P = .016) than the cytoreduction group. Patients achieving remission in the cytoreduction group had outcomes similar to the upfront group, but those without remission before transplantation had a significantly worse posttransplant OS (3-year OS, 46.7% vs. 75.7%, P = .038). Patients with pretransplant HMAs had better PFS than those with chemotherapy or HMAs plus chemotherapy (P < 0.05).ConclusionCompared with pretransplant cytoreduction, upfront allo-HSCT might provide more benefit to some patients with advanced MDS if there are suitable donors. HMAs would be a good alternative during the donor search.     

Patient Preferences for Benefits,Risks, and Administration Route of Hypomethylating Agents in Myelodysplastic Syndromes

Introduction/BackgroundTherapy with infused or injected hypomethylating agents (HMAs) may lead to higher treatment administration burden (ie, local reaction, visit frequency and duration) vs. oral HMAs. ObjectivesTo reveal preferences of US and Canadian patients with myelodysplastic syndromes (MDS) for HMAs’ benefits, risks, and administration burden through an online discrete-choice experiment (DCE).Materials and MethodsChoice of DCE attributes and survey development were informed by literature review and interviews with clinicians, MDS patients, and caregivers serving as patient proxies, and patient advocacy groups (PAGs) representatives, including from AAMAC, AAMDS, and MDSF. DCE choice tasks were analyzed using random parameter logit models. Survey patients were recruited by the PAGs via their networks. To understand key preference drivers and how much patients were willing to trade between attributes, we calculated each attribute's relative attribute importance (RAI) and marginal rates of substitution.ResultsOne hundred eighty-four respondents (including 158 patients; mean age, 67.2 years; male, 50.5%; White, 50.5%; US residents, 88%) completed the survey. MDS risk was low (34.8%), high (30.9%), or unknown (34.2%). RAI (in decreasing order) was as follows: risk of AML (40%), fatigue level (33%), number of visits (12%), mode of administration (6%), visit duration (5%), and administration frequency (4%). Assuming the same risk of AML transformation or level of fatigue, most respondents (76.6%) were predicted to switch to an oral pill if it were available to them.ConclusionGiven equivalent effectiveness across HMAs, patients’ preferences for HMA administration method should be considered in treatment decision-making to minimize burden and facilitate adherence.     

Progression-free Survival Outcome Is Independent of Objective Response in Patients With Estrogen Receptor-positive,Human Epidermal Growth Factor Receptor 2-negative Advanced Breast Cancer Treated With Palbociclib Plus Letrozole Compared With Letrozole: Analysis From PALOMA-2

BackgroundIn PALOMA-2, palbociclib + letrozole significantly prolonged progression-free survival (PFS) versus placebo + letrozole in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER⁺/HER2⁻) advanced breast cancer (ABC). We investigated clinical outcomes of patients who achieved or did not achieve a confirmed objective response (OR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (data cutoff: May 31, 2017).Patients and MethodsPostmenopausal patients untreated for ER⁺/HER2⁻ ABC were randomized 2:1 to palbociclib + letrozole or placebo + letrozole. Median PFS, median duration of OR, baseline characteristics, and palbociclib exposure were compared in patients with or without OR by treatment arm.ResultsIn the intent-to-treat population, OR was achieved by 194 (44%) of 444 and 77 (35%) of 222 patients in the palbociclib and placebo arms, respectively (odds ratio, 1.5; 95% confidence interval [CI], 1.0-2.1; P = .0156). Regardless of treatment, more OR than non-OR patients had de novo metastatic disease (47%-50% and 28%-31%, respectively) and no prior endocrine therapy (55% and 35%-37%, respectively). Rates of palbociclib dose reduction owing to adverse events were similar regardless of OR (41% and 38%, respectively). Among the patients with OR during the study, approximately 50% achieved OR within the first 3 months regardless of treatment. The median PFS was significantly prolonged with palbociclib + letrozole versus placebo + letrozole in patients with measurable disease in both OR (37.2 months; 95% CI, 28.1 months to not estimable vs. 27.4 months; 95% CI, 22.2-31.1 months; hazard ratio, 0.66; 95% CI, 0.47-0.94; P = .009) and non-OR groups (10.9 months; 95% CI, 8.2-11.2 months vs. 5.6 months; 95% CI, 5.3-8.3 months; hazard ratio, 0.72; 95% CI, 0.54-0.97; P = .016).ConclusionsPalbociclib + letrozole provided significant clinical benefit versus placebo + letrozole to patients with ER⁺/HER2⁻ ABC regardless of achieving RECIST-defined OR.Pfizer; ClinicalTrials.gov: NCT01740427     

Treatment patterns in older patients with myelodysplastic syndromes: A population-based analysis reflecting the real world

IntroductionTreatment for myelodysplastic syndromes (MDS) is complex, options are limited, and insight into consecutive treatments is lacking. We performed this study to assess the outcomes in a real-world cohort of patients with MDS.Materials and MethodsAn observational population-based study was performed using the HemoBase registry. Treatment patterns and overall survival (OS) were analyzed with Kaplan-Meier analyses.ResultsIn 144 of 280 (51.4%) patients with MDS >50 years, first-line treatment was initiated. The median age was 75.1 years (range: 52.6–92.0); the majority were male (72.2%). Hypomethylating agents (HMA), intensive chemotherapy, lenalidomide, and erythropoiesis-stimulating agents (ESA) were given as first-line treatment to 31.1% (n = 45), 12.5% (n = 18), 2.8% (n = 4), and 53.5% (n = 77) of the population, respectively. The median treatment duration was 5.8 months (95% Confidence Interval [CI]: 1.1–10.4) for HMA, 1.7 months (95%CI: 0.9–2.6) for intensive chemotherapy, 10.8 months (95%CI: 4.7–17.0) for lenalidomide, and 14.8 months (95%CI: 11.4–18.1) for ESA. Consecutive treatments were given to 27.2% of patients. The main reasons for first-line treatment discontinuation were treatment failure (45.8%), toxicity (6.9%), or death (20.1%). Median OS after termination of the initial, second, and third treatment was 5.8 months (95%CI: 3.2–8.5), 9.3 months (95%CI: 0.0–19.6), and 1.0 months (95%CI: 0.0–5.1), respectively.DiscussionThis study shows the treatment outcomes in a real-world population of older patients with MDS. Treatment duration and median OS after treatment discontinuation were relatively limited. There is still an urgent need for new treatment options, strategies to further optimize duration of existing treatments, and communication of realistic treatment goals and expectations, especially for older, higher-risk patients with MDS with a poor prognosis.     

Predictive Model for Infection Risk in Myelodysplastic Syndromes,Acute Myeloid Leukemia,and Chronic Myelomonocytic Leukemia Patients Treated With Azacitidine; Azacitidine Infection Risk Model: The Polish Adult Leukemia Group Study

BackgroundMyelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) patients, including those treated with azacitidine, are at increased risk for serious infections. The aim of our study was to identify patients with higher infectious risk at the beginning of azacitidine treatment.Patients and MethodsWe performed a retrospective evaluation of 298 MDS/CMML/AML patients and included in the analysis 232 patients who completed the first 3 cycles of azacitidine therapy or developed Grade III/IV infection before completing the third cycle.ResultsOverall, 143 patients (62%) experienced serious infection, and in 94 patients (41%) infection occurred within the first 3 cycles. The following variables were found to have the most significant effect on the infectious risk in multivariate analysis: red blood cell transfusion dependency (odds ratio [OR], 2.38; 97.5% confidence interval [CI], 1.21-4.79), neutropenia <0.8 × 10⁹/L (OR, 3.03; 97.5% CI, 1.66-5.55), platelet count <50 × 10⁹/L (OR, 2.63; 97.5% CI, 1.42-4.76), albumin level <35 g/dL (OR, 2.04; 97.5% CI, 1.01-4.16), and Eastern Cooperative Oncology Group performance status ≥2 (OR, 2.19; 97.5% CI, 1.40–3.54). Each of these variables is assigned 1 point, and the combined score represents the proposed Azacitidine Infection Risk Model. The infection rate in the first 3 cycles of therapy in lower-risk (0-2 score) and higher-risk (3-5 score) patients was 25% and 73%, respectively. The overall survival was significantly reduced in higher-risk patients compared with the lower-risk cohort (8 vs. 29 months).ConclusionWe selected a subset with high early risk for serious infection and worse clinical outcome among patients treated with azacitidine.     

Association of Surgical Approach With Treatment Burden,Oncological Effectiveness,and Perioperative Morbidity in Adrenocortical Carcinoma

MicroabstractIn the National Cancer Database (NCDB), patients treated with minimally invasive adrenalectomy (MIA) for adrenocortical carcinoma (ACC) had similar oncological outcomes and cumulative treatment burden with less morbidity compared with open adrenalectomy (OA). Although OA remains the standard of care for adrenal lesions concerninge for malignancy, MIA in appropriately selected patients may offer equivalent oncological outcomes.Introduction/BackgroundWe investigated the cumulative treatment burden, oncological effectiveness, and perioperative morbidity in patients undergoing MIA compared with (OA) for patients with ACC.Patients and MethodsWe reviewed the NCDB for patients undergoing surgical resection (MIA vs. OA) for ACC from 2010 to 2017. Inverse probability of treatment weighted logistic regression, negative binomial, and Cox proportional hazards models were fit to assess for an association of surgical approach with cumulative treatment burden (any adjuvant therapy, radiation therapy [RT], and systemic therapy), oncological effectiveness (positive surgical margins [PSM], lymph node yield [LNY], and overall survival [OS]), and perioperative morbidity (length of stay [LOS] and readmission) as appropriate.ResultsWe identified 776 patients that underwent adrenalectomy for ACC, of which 307 underwent MIA. We noted patients with larger tumors (OR 0.82, 95% CI 0.78-0.86, P < .001) were less likely to have MIA prior to IPTW. We did not appreciate a significant association of MIA with cumulative treatment burden or the use of any adjuvant therapy (OR 0.85, 95% CI 0.60-1.21, P = .375), adjuvant RT (OR 0.94, 95% CI 0.59-1.50, P = .801), or adjuvant systemic therapy (OR 0.84, 95% CI 0.58-1.21, P = .352). Patients undergoing MIA had similar oncological effectiveness of surgery and OS when compared with patients which underwent OA. Patients that underwent MIA had a significantly shorter LOS (IRR: 0.74, 95% CI 0.62-0.88, P = .001) and lower odds of readmission (OR 0.46, 95% CI 0.23-0.91, P = .026).ConclusionsAlthough the standard of care for adrenal lesions suspicious for ACC remains OA, in appropriately selected patients, MIA may offer similar oncological effectiveness and cumulative treatment burden, with less morbidity, than OA.     

Patient Demographic Characteristics and Disease Stage as Drivers of Disparities in Mortality in Prostate Cancer Patients Who Receive Care at a Safety Net Academic Medical Center

IntroductionThe purpose of this study was to examine the effect of patient demographic characteristics and tumor stage at diagnosis on mortality in prostate cancer patients who receive care at a safety net, academic medical center with a diverse patient population.Patients and MethodsEight hundred sixty-nine patients were diagnosed with prostate cancer at our institution between August 2004 and October 2011. Patient demographic characteristics were determined as follows: race and/or ethnicity, primary language, insurance type, age at diagnosis, marital status, income (determined by zip code), and American Joint Committee on Cancer (AJCC) tumor stage. Fisher exact or Pearson χ² test was used to test for differences in categorical variables. Multivariate logistic regression analysis was performed to identify factors related to mortality recorded at the end of follow-up in March of 2012.ResultsMortality was significantly decreased in patients who spoke Haitian Creole (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.04-0.74; P = .017). Distribution of insurance type, age, income, and prostate-specific antigen level differed between English and Haitian Creole speakers. Increased mortality was observed in patients who were single (OR, 1.99; 95% CI, 1.06-3.73; P = .032), older than 70 (OR, 15.5; 95% CI, 3.03-79.45; P = .001), had Medicaid and/or free care (OR, 4.98; 95% CI, 1.72-14.4; P = .003), or had AJCC stage IV cancer (OR, 9.56; 95% CI, 4.89-18.69; P < .001). There was no significant difference in mortality according to race and/or ethnicity or income in the multivariate-adjusted model.ConclusionIn this retrospective study, prostate cancer patients who spoke Haitian Creole had a lower incidence of mortality compared with English speakers. Consistent with similar large-scale studies, being single or having Medicaid and/or free care insurance predicted worse outcomes, reinforcing their roles as drivers of disparities.     

TP53 and IDH2 Somatic Mutations Are Associated With Inferior Overall Survival After Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome

BackgroundNext-generation sequencing has identified somatic mutations that are prognostic of cancer.Patients and MethodsWe evaluated the incidence and prognostic significance of somatic mutations in 89 myelodysplastic syndrome (MDS) patients who received an allogeneic hematopoietic cell transplantation. Next-generation sequencing was performed on paraffin embedded bone marrow, which was obtained at a median of 31 days before initiating the preparative regimen.ResultsThe 3 most common subtypes of MDS were refractory anemia with excess blasts (RAEB)-1 (35%), RAEB-2 (29%), and refractory cytopenia with multilineage dysplasia (18%). Most patients (91%) received a myeloablative regimen of fludarabine with intravenous busulfan. Somatic mutations (> 0) were identified in 39 (44%) of analyzed samples. The 6 most commonly identified gene mutations were ASXL1 (8%), DNMT3A (8%), RUNX1 (7%), KRAS (6%), IDH2 (4%), and TP53 (4%). The low incidence of mutations in our study sample might be explained by tissue source and stringent variant-calling methodology. Moreover, we speculate that the low incidence of mutations might, perhaps, also be explained by previous azacitidine treatment in 82% of cases. Multivariate analysis identified TP53 (hazard ratio [HR], 3.82; 95% confidence interval [CI], 1.12-13.09; P = .03) and IDH2 mutations (HR, 4.74; 95% CI, 1.33-16.91; P = .02) as predictors of inferior 3-year overall survival.ConclusionThis study furthers implementation of clinical genomics in MDS and identifies TP53 and IDH2 as targets for pre- or post-transplant therapy.     

Disparities in Risk Reduction Therapy Recommendations for Young Women With Lobular Carcinoma In-Situ

BackgroundEndocrine therapy (ET) significantly reduces the risk of breast cancer development in high-risk patients diagnosed with lobular carcinoma in situ (LCIS). However, the variables impacting recommendation and use of ET in young adults (YAs) is not well-studied. We examined the role of provider recommendation and patient acceptance for ET for YAs with LCIS.Materials and MethodsThe National Cancer Database was queried for women aged < 40 years with primary LCIS between 2000 and 2012. Socioeconomic, demographic, and treatment variables were examined to determine their impact on ET provider recommendation and initial patient acceptance of risk-reducing therapy.ResultsAmong 1650 YA patients with LCIS, only 749 (45.4%) were recommended ET. On multivariable analysis, women > 30 years of age were more likely recommended ET than women < 30 years (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.10-2.47), African Americans more than other ethnicities (OR, 1.48; 95% CI, 1.1-2.0), and YAs treated in New England were more likely than those in the rest of the country (OR, 3.26; 95% CI, 2.0-5.2). Among YA women recommended ET, only 20.2% had a documented refusal. Only geography appeared to independently impact the likelihood of refusal, with YAs in the Southeastern-Central United States being most likely to refuse ET (OR, 5.4; 95% CI, 1.2-24.0).ConclusionET is underutilized for risk-reduction in YAs with LCIS. This underuse appears dependent on disparities in provider recommendation practices rather than non-acceptance of therapy. This may reflect regional practice patterns, community standards of care, or provider bias regarding the significance of LCIS as a risk factor for development of invasive cancer.     

Factors Associated With Acute Toxicity in Pediatric Patients Treated With Proton Radiation Therapy: A Report From the Pediatric Proton Consortium Registry

PurposeLimited prospective information regarding acute toxicity in pediatric patients receiving proton therapy (PT) exists. In this study, Pediatric Proton Consortium Registry (PPCR) data was analyzed for factors associated with development of acute toxicity in children receiving passively scattered or pencil beam scanning PT.Methods and MaterialsPediatric patients treated with PT and enrolled on the PPCR from 2016 to 2017 at 7 institutions were included. Data were entered on presence versus absence of acute general, cardiac, endocrine, eye, gastrointestinal, genitourinary, hematologic, mouth, musculoskeletal, neurologic, psychological, respiratory, and skin toxicities before (baseline) and at the end of PT (acute). Associations between patient and treatment variables with development of acute toxicity were assessed with multivariable modeling.ResultsOf 422 patients included, PT technique was passively scattered in 241 (57%), pencil beam scanning in 180 (43%), and missing in 1 (<1%) patient. Median age was 9.9 years. Daily anesthesia for treatment was used in 169 (40%). Treatments were categorized as craniospinal irradiation (CSI; n = 100, 24%), focal central nervous system PT (n = 157, 38%), or body PT (n = 158, 38%). Passively scattered PT was associated with increased risk of hematologic toxicity compared with pencil beam scanning PT (odds ratio [OR]: 3.03; 95% confidence interval [CI], 1.38-6.70; P = .006). There were no other differences toxicities between PT techniques. Uninsured patients had increased risk of GI (OR: 2.71; 95% CI, 1.12-6.58; P = .027) and hematologic toxicity (OR: 10.67; 95% CI, 2.68-42.46; P <.001). Patients receiving concurrent chemotherapy were more likely to experience skin (OR: 2.45; 95% CI, 1.23-4.88; P = .011), hematologic (OR: 2.87; 95% CI, 1.31-6.25; P = .008), GI (OR: 2.37; 95% CI, 1.33-4.21; P = .003), and mouth toxicities (OR: 2.03; 95% CI, 1.10-3.73; P = .024). Patients receiving 49 to 55 Gy were more likely to experience skin (OR: 2.18; 95% CI, 1.06-4.44; P = .033) toxicity than those receiving <49 Gy.ConclusionsThe PPCR registry highlights broad differences in acute toxicity rates in children receiving PT, and identifies opportunities for improvements in prevention, monitoring, and treatment of toxicities.