Ruxolitinib (Rux), a Jak1/2 inhibitor, results in reduced spleen size and improvement in constitutional symptoms in the majority of patients with myelofibrosis (MF). Therefore Rux, when given prior ...to hematopoietic cell transplantation (HCT) in patients with MF was hypothesized to improve engraftment, decrease incidence and severity of graft-versus-host disease, and lower non-relapse mortality (NRM). We conducted a phase II prospective trial to assess the effects of pre-HCT Rux on post-HCT outcomes in patients with MF. The primary endpoint was 2-year overall survival. To date, 28 patients (median age 56 years) have been transplanted. The median time on Rux pre-HCT was 7 months. Twenty-three patients received myeloablative and five reduced intensity conditioning. Donors included 14 HLA-matched siblings, 11 matched unrelated, 1 allele mismatched unrelated, and 3 umbilical cord blood. There have been no episodes of cytokine release syndrome and all patients achieved sustained engraftment. Two patients died from NRM and two patients relapsed. With a median follow-up of 13 months, overall survival is 93% (95% CI: 0.73, 0.98) at 1 year and 86% (95% CI: 0.61, 0.96) at 2 years post-HCT. This study demonstrates that pre-HCT Rux is well tolerated and suggests that pre-HCT Rux may improve post-HCT outcome.
Abstract
Background
Decreased mammography drives breast cancer disparities. Black women have lower rates of mammography completion than White women, and this contributes to disparities in outcomes. ...Points of disparity along the continuum for screening mammography remain underresearched.
Methods
The authors compared mammography referrals for Black and White women aged 40–74 years at a heterogeneous academic medical center. Completion of steps of the screening mammography continuum was compared between Black and White women within two age cohorts: 40–49 and 50–74 years. Multivariable logistic regression was used to evaluate the association between race and mammogram completion.
Results
Among 26,476 women, 3090 (12%) were Black, and 23,386 (88%) were White. Among Black women aged 50–74 years who were due for mammography, 40% had referrals, 39% were scheduled, and 21% completed mammography; the corresponding values for White women were 42%, 41%, and 27%, respectively. Similar differences in referral outcomes were noted for women aged 40–49 years, although Black women had lower rates of provider‐initiated referrals (9% vs. 13%). Adjusted analyses for those aged 40–49 and 50–74 years demonstrated an association between Black race and lower rates of mammography completion (odds ratio OR for 40–49 years, 0.74; 95% CI, 0.57–0.95;
p
= .02; OR for 50–74 years, 0.85; 95% CI, 0.74–0.98;
p
= .02). In multivariable analyses, noncommercial insurance and higher comorbidity were associated with lower rates of mammography. Provider‐initiated referral was positively correlated to mammogram completion.
Conclusions
Black race was associated with 15%–26% lower mammography completion (adjusted). Both groups experienced the highest attrition after scheduling mammograms, although attrition was more precipitous for Black women. These findings have implications for future interventions, including increasing provider‐initiated referrals and decreasing barriers to attending scheduled mammograms.
Black race was associated with 15%–26% lower mammography completion (adjusted), and Black women experienced the highest attrition after scheduling mammograms. These findings have implications for future interventions, including increasing provider‐initiated referrals and decreasing barriers to attending scheduled mammograms.
The purpose of our study was to determine the frequency of patients who achieved a therapeutic drug level after receiving posaconazole (PCZ) delayed-release tablets (DRT) for prophylaxis or treatment ...of invasive fungal infections (IFIs) and to examine the effect of demographic traits and treatment characteristics on PCZ serum levels. A retrospective single-center study was conducted on high-risk inpatients at the University of Washington Medical Center (UWMC) that had received PCZ and obtained PCZ serum levels for either treatment or prophylaxis between 1 August 2014 and 31 August 2015. High-risk patients were defined as those undergoing chemotherapy for a primary hematologic malignancy and those undergoing hematopoietic cell transplantation (HCT) or solid organ transplantation. Serum trough concentrations of ≥700 μg/liter and ≥1,000 μg/liter were considered appropriate for prophylaxis and treatment, respectively. The most frequent underlying medical condition was a hematological malignancy (43/53, 81%). Twenty-six of 53 patients (49%) received PCZ for prophylaxis; the rest received PCZ for treatment. A total of 37/53 (70%) patients had PCZ serum levels of ≥700 μg/liter regardless of indication, including 22/26 (85%) that received PCZ for prophylaxis. Of the patients that received PCZ for treatment, only 12/27 (44%) had PCZ serum levels of ≥1,000 μg/liter. The odds of having therapeutic PCZ serum levels were not statistically different in patients with a weight of ≥90 kg, a diarrhea grade of ≥2, a mucositis grade of ≥2, or poor dietary intake. However, the odds of having therapeutic PCZ serum levels was 5.85 times higher in patients without graft-versus-host disease (GVHD) treatment than in those with GVHD treatment. Four patients on prophylaxis (15%) developed breakthrough IFIs, one of which had a subtherapeutic level. We concluded that the use of PCZ DRT provided adequate concentrations in only 70% of our patients and that recommended dosing may lead to insufficient levels in patients treated for IFIs. Lower concentrations noted among high-risk patients with GVHD suggest a need for prospective studies evaluating therapeutic drug monitoring and/or dose adjustments among these patients.
Differences in bladder cancer outcomes have been demonstrated by sex and race/ethnicity, with studies showing a higher burden of adverse outcomes among women and racially minoritized populations. ...Despite these epidemiologic differences, populations with disproportionally adverse outcomes are often underrepresented in genomic cohorts. This exclusion impacts the accuracy and generalizability of genomic studies in bladder cancer and has the potential to widen disparities by sex and/or race/ethnicity.
We analyzed pooled somatic mutational data from publicly available cohorts in the cBioPortal open access platform.
A total of 796 unique patients were identified. Average age for the cohort was 67 years (range: 25-98 years), 188 (24%) were female, and the majority were White (n = 423, 85% among those who report race). Median total mutation count was 91 (IQR: 20, 202) per patient. We used multivariable logistic regression to independently evaluate the association between race/sex and mutation status in each of 122 genes of interest, identified from TCGA, adjusting for age and bladder cancer invasive status. In adjusted analyses, male sex was associated with increased risk of mutation in ARID1A, CHD6, and NCOR1 compared with female sex. White race was associated with increased risk of mutation in ARID1A, EP300, PIK3CA, and TP53 and decreased risk of mutation in HRAS compared with non-White race.
These differences highlight the importance of enriching cohorts for female and non-White patients in genomic studies and clinical trials, especially as we test the use of molecular biomarkers to personalize care for patients with bladder cancer.
Anthracycline-based therapy is standard first-line treatment for most patients with advanced and metastatic sarcomas. Although multiple trials have attempted to show improved outcomes in patients ...with soft-tissue sarcoma over doxorubicin monotherapy, each has fallen short of demonstrating improved outcomes.
To evaluate the safety and efficacy of doxorubicin in combination with pembrolizumab in patients with advanced, anthracycline-naive sarcomas.
This nonrandomized clinical trial used a 2-stage phase 2 design and was performed at a single, academic sarcoma specialty center. Patients were adults with good performance status and end-organ function. Patients with all sarcoma subtypes were allowed to enroll with the exception of osteosarcoma, Ewing sarcoma, and alveolar and embryonal rhabdomyosarcoma.
Two dose levels of doxorubicin (45 and 75 mg/m2) were tested for safety in combination with pembrolizumab.
Objective response rate (ORR) was the primary end point. Overall survival (OS) and progression-free survival (PFS) were secondary end points. Correlative studies included immunohistochemistry, gene expression, and serum cytokines.
A total of 37 patients (22 men; 15 women) were treated in the combined phase 1/2 trial. The median (range) patient age was 58.4 (25-80) years. The most common histologic subtype was leiomyosarcoma (11 patients). Doxorubicin plus pembrolizumab was well tolerated without significant unexpected toxic effects. The ORR was 13% for phase 2 patients and 19% overall. Median PFS was 8.1 (95% CI, 7.6-10.8) months. Median OS was 27.6 (95% CI, 18.7-not reached) months at the time of this analysis. Two of 3 patients with undifferentiated pleomorphic sarcoma and 2 of 4 patients with dedifferentiated liposarcoma had durable partial responses. Tumor-infiltrating lymphocytes were present in 21% of evaluable tumors and associated with inferior PFS (log-rank P = .03). No dose-limiting toxic effects were observed.
In this nonrandomized clinical trial, doxorubicin plus pembrolizumab was well tolerated. Although the primary end point for ORR was not reached, the PFS and OS observed compared favorably with prior published studies. Further studies are warranted, especially those focusing on undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma.
ClinicalTrials.gov Identifier: NCT02888665.
Improved understanding of the effect of HIV infection on Kaposi sarcoma (KS) presentation and outcomes will guide development of more effective KS staging and therapeutic approaches. We enrolled a ...prospective cohort of epidemic (HIV-positive; HIV + KS) and endemic (HIV-negative; HIV - KS) KS patients in Uganda to identify factors associated with survival and response.
Adults with newly diagnosed KS presenting for care at the Uganda Cancer Institute (UCI) in Kampala, Uganda, between October 2012 and December 2019 were evaluated. Participants received chemotherapy per standard guidelines and were followed over 1 year to assess overall survival (OS) and treatment response.
Two hundred participants were enrolled; 166 (83%) had HIV + KS, and 176 (88%) were poor-risk tumor (T1) stage. One-year OS was 64% (95% confidence interval CI 57-71%), with the hazard of death nearly threefold higher for HIV + KS (hazard ratio HR = 2.93; P = 0.023). Among HIV + KS, abnormal chest X-ray (HR = 2.81; P = 0.007), lower CD4 + T-cell count (HR = 0.68 per 100 cells/μl; P = 0.027), higher HIV viral load (HR = 2.22 per log 10 copies/ml; P = 0.026), and higher plasma Kaposi sarcoma-associated herpesvirus (KSHV) copy number (HR = 1.79 per log 10 copies/ml; P = 0.028) were associated with increased mortality. Among HIV - KS, factors associated with mortality included Karnofsky score <70 (HR = 9.17; P = 0.045), abnormal chest X-ray (HR = 8.41; P = 0.025), and higher plasma KSHV copy number (HR = 6.21 per log 10 copies/ml; P < 0.001).
Although survival rates were better for HIV - KS than HIV + KS, the high mortality rate seen in both groups underscores the urgent need to identify new staging and therapeutic approaches. Factors associated with mortality, including high plasma KSHV, may serve as important targets of therapy.
Individuals with adenomatous colorectal polyps undergo repeated colonoscopy surveillance to identify and remove metachronous adenomas. However, many patients with adenomas do not develop recurrent ...adenomas. Better methods to evaluate who benefits from increased surveillance are needed. We evaluated the use of altered EVL methylation as a potential biomarker for risk of recurrent adenomas.
Patients with ≥1 colonoscopy had EVL methylation (mEVL) measured with an ultra-accurate methylation-specific droplet digital PCR assay on normal colon mucosa. The association between EVL methylation levels and adenoma or colorectal cancer was evaluated using three case/control definitions in three models: unadjusted (model 1), adjusting for baseline characteristics (model 2), and an adjusted model excluding patients with colorectal cancer at baseline (model 3).
Between 2001 and 2020, 136 patients were included; 74 healthy patients and 62 patients with a history of colorectal cancer. Older age, never smoking, and baseline colorectal cancer were associated with higher levels of mEVL (P ≤ 0.05). Each log base 10 difference in mEVL was associated with an increased risk of adenoma(s) or cancer at/after baseline for model 1 OR, 2.64; 95% confidence interval (CI), 1.09-6.36, and adenoma(s) or cancer after baseline for models 1 (OR, 2.01; 95% CI, 1.04-3.90) and model 2 (OR, 3.17; 95% CI, 1.30-7.72).
Our results suggest that EVL methylation level detected in the normal colon mucosa has the potential to be a biomarker for monitoring the risk for recurrent adenomas.
These findings support the potential utility of EVL methylation for improving the accuracy for assigning risk for recurrent colorectal adenomas and cancer.
Pancreatic ductal adenocarcinoma (PDA) is the third most common cause of cancer death in the United States. Most patients who undergo resection develop recurrence. Standard treatment confers a median ...overall survival (OS) of 24 months. Exposure to alternate regimens may prevent chemoresistance. This study evaluated multiagent perioperative therapy for potentially resectable PDA patients to improve OS.
A single center, phase 2, trial of patients with resectable or borderline resectable PDA. Patients received neoadjuvant therapy with induction chemotherapy (gemcitabine, docetaxel, capecitabine) for 3 cycles, chemoradiation (intensity-modulated radiation therapy with capecitabine and oxaliplatin) followed by surgery, and 2 months of adjuvant gemcitabine and oxaliplatin and 2 months of gemcitabine. The primary endpoint was OS. The secondary endpoint was recurrence-free survival (RFS).
Thirty-two eligible patients were enrolled. Twenty-two patients underwent surgical resection. After a median follow-up of 56.8 months, mOS was 31.6 months (95% confidence interval CI, 14.2-58.1) for all patients, 58.1 months (95% CI, 31.6 to NR) for those who completed surgery. The mRFS was 31.3 months (95% CI, 12.5 to NR).
Perioperative therapy with GTX, chemoradiotherapy, and adjuvant GemOx/Gem resulted in promising survival of 58 months for patients who underwent resection and may represent another treatment option for PDA.
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