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1.
Int J Gynecol Cancer ; 34(5): 751-759, 2024 May 06.
Article En | MEDLINE | ID: mdl-38719274

OBJECTIVE: To assess social determinants of health impacting patients undergoing gynecologic oncology versus combined gynecologic oncology and urogynecology surgeries. METHODS: We identified patients who underwent gynecologic oncology surgeries from 2016 to 2019 in the National Inpatient Sample using the International Classification of Diseases-10 codes. Demographics, including race and insurance status, were compared for patients who underwent gynecologic oncology procedures only (Oncologic) and those who underwent concurrent incontinence or pelvic organ prolapse procedures (Urogynecologic-Oncologic). A logistic regression model assessed variables of interest after adjustment for other relevant variables. RESULTS: From 2016 to 2019 the National Inpatient Sample database contained 389 (1.14%) Urogynecologic-Oncologic cases and 33 796 (98.9%) Oncologic cases. Urogynecologic-Oncologic patients were less likely to be white (62.1% vs 68.8%, p=0.02) and were older (median 67 vs 62 years, p<0.001) than Oncologic patients. The Urogynecologic-Oncologic cohort was less likely to have private insurance as their primary insurance (31.9% vs 38.9%, p=0.01) and was more likely to have Medicare (52.2% vs 42.8%, p=0.01). After multivariable analysis, black (adjusted odds ratio (aOR) 1.41, 95% CI 1.05 to 1.89, p=0.02) and Hispanic patients (aOR 1.53, 95% CI 1.11 to 2.10, p=0.02) remained more likely to undergo Urogynecologic-Oncologic surgeries but the primary expected payer no longer differed significantly between the two groups (p=0.95). Age at admission, patient residence, and teaching location remained significantly different between the groups. CONCLUSIONS: In this analysis of a large inpatient database we identified notable racial and geographical differences between the cohorts of patients who underwent Urogynecologic-Oncologic and Oncologic procedures.


Genital Neoplasms, Female , Humans , Female , Middle Aged , Aged , Genital Neoplasms, Female/surgery , United States/epidemiology , Databases, Factual , Gynecologic Surgical Procedures/statistics & numerical data , Socioeconomic Factors , Adult , Pelvic Organ Prolapse/surgery
2.
Article En | MEDLINE | ID: mdl-38412867

OBJECTIVE: The objective was to determine whether baseline fatty acid intake and erythrocyte omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) can predict risk of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in older women. METHODS: This was a prospective analysis of 34,990 women in the Women's Health Initiative. Dietary fatty acids were estimated from food frequency questionnaires. Imputed erythrocyte PUFAs were available in a subcohort of 3,428 women. Arthroplasty (THA and TKA), used as a surrogate of severe osteoarthritis, was identified via linked Medicare data. Cox proportional hazards models were constructed to estimate risk of arthroplasty. RESULTS: Risk of THA was associated with higher intake of arachidonic acid, (multivariable hazard ratio [HR] quartile 4 [Q4] vs Q1: 1.16; 95% confidence interval [CI] 1.01-1.34; P = 0.03) and higher intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA; HR Q4 vs Q1: 1.20; 95% CI 1.05-1.39; P = 0.003). There was a linear trend (P = 0.04) for patients to have a higher risk of THA with higher erythrocyte EPA and DHA in body mass index-adjusted models; however, there was no significant difference in patients who had THAs by quartiles of erythrocyte EPA and DHA (P = 0.10). Dietary fatty acids and erythrocyte PUFAs were not significantly associated with risk of TKA. CONCLUSION: Higher baseline intakes of arachidonic acid and EPA and DHA were associated with a modestly higher risk of THA. No association was found between fatty acids and patients who had TKAs. Further research in populations with direct measures of osteoarthritis severity is needed to better understand the importance of PUFAs in modulating osteoarthritis and arthroplasty risk.

3.
Gynecol Oncol ; 182: 51-56, 2024 Mar.
Article En | MEDLINE | ID: mdl-38262238

OBJECTIVES: The use of a platinum doublet for the treatment of platinum-sensitive epithelial ovarian cancer (EOC) recurrence is well established. The impact of the non­platinum chemotherapy used as part of a platinum doublet on PARP inhibitor (PARPi) and platinum sensitivity it not known. We aimed to describe oncologic outcomes in cases of recurrent EOC receiving PARPi as maintenance therapy based on preceding platinum doublet. METHODS: Retrospective study of patients with platinum-sensitive recurrent ovarian, fallopian tube or primary peritoneal cancer treated with platinum doublet followed by maintenance PARPi from 1/1/2015 and 1/1/2022. Comparisons were made between patients receiving carboplatin + pegylated liposomal doxorubicin (CD) versus other platinum doublets (OPDs). Descriptive statistics, Kaplan-Meier and univariate survival analyses were performed. RESULTS: 100 patients received PARPi maintenance following a platinum doublet chemotherapy regimen for platinum-sensitive recurrence. 25/100 (25%) received CD and 75/100 (75%) received OPDs. Comparing CD and OPDs, median progression-free survival was 8 versus 7 months (p = 0.26), median time to platinum resistance was 15 versus 13 months (p = 0.54), median OS was 64 versus 90 months (p = 0.28), and median OS from starting PARPi was 25 versus 26 months (p = 0.90), respectively. CONCLUSIONS: Using pegylated liposomal doxorubicin as part of a platinum doublet preceding maintenance PARPi for platinum-sensitive recurrence does not seem to hasten PARPi resistance or platinum resistance compared to OPDs. Although there was a non-significant trend towards increased OS among patients who received a platinum doublet other than CD prior to PARPi, the OS from PARPi start was similar between groups. Given the retrospective nature of this study and small study population, further research is needed to evaluate if the choice of platinum doublet preceding PARPi maintenance impacts PARPi resistance, platinum resistance and survival.


Doxorubicin/analogs & derivatives , Ovarian Neoplasms , Humans , Female , Carcinoma, Ovarian Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Retrospective Studies , Platinum/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Polyethylene Glycols
4.
Leuk Lymphoma ; 65(3): 301-311, 2024 Mar.
Article En | MEDLINE | ID: mdl-38093530

Aggressive T-cell lymphomas (TCL) account for 10-15% of non-Hodgkin lymphomas (NHL) with weaker responses and shorter durations to chemotherapy than other types of NHL. Current therapies for patients with relapsed/refractory Cutaneous T-cell lymphoma (CTCL) have limited efficacy, and short durations of response. Gemcitabine and liposomal doxorubicin have shown single-agent activity in TCL and combined have activity in relapsed B-cell lymphomas. We evaluated outcomes of 18 patients with relapsed/refractory aggressive TCL (13 CTCL, 5 PTCL) treated with a gemcitabine plus liposomal doxorubicin (GemDox) combination and evaluated outcomes with a specific focus on CTCL patients. Significant responses were observed in CTCL patients with an overall response rate of over 80%. In all patients, objective responses were seen in eight patients (50%), with six patients (5 CTCL) able to proceed to allogeneic stem cell transplant. Given limited treatment options for r/r CTCL, GemDox should be considered a therapeutic option in relapsed/refractory CTCL.


Doxorubicin/analogs & derivatives , Lymphoma, Non-Hodgkin , Lymphoma, T-Cell , Humans , Gemcitabine , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/etiology , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, T-Cell/drug therapy , Lymphoma, T-Cell/etiology , Treatment Outcome , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Polyethylene Glycols
6.
Cancers (Basel) ; 15(19)2023 Sep 30.
Article En | MEDLINE | ID: mdl-37835515

BACKGROUND: A fundamental understanding of the impact of bariatric surgery (BRS) on mechanisms of colorectal carcinogenesis is limited. For instance, studies report a reduced risk of colorectal cancer in females but not in males after BRS. We examined whether this sex-specific difference existed at the earlier polyp development stage. METHODS: This retrospective cohort study included 281,417 adults from the 2012-2020 MarketScan database. We compared polyps rates on colonoscopy in four groups: post- vs. pre-BRS (treatment) to post- vs. pre-severe obesity (SO) diagnosis (control). We focused our main analysis on a propensity-matched sample that yielded a balanced distribution of covariates in our four groups (n = 9680 adults, 21.9% males). We also adjusted for important covariates. RESULTS: Metabolic syndrome parameters improved after bariatric surgery and worsened after severe obesity diagnosis (p < 0.05). The rate of polyps was 46.7% at a median of 0.5 years pre-BRS and 47.9% at a median of 0.6 years pre-SO diagnosis. The polyps rate was 45.4% at a median (range) of 3.2 (1.0-8.5) years post-BRS. Conversely, 53.8% of adults had polyps at 3.0 (1.0-8.6) years post-SO. There was no change in the risk of colorectal polyps in males or females post- vs. pre-BRS. However, the risk of polyps was higher in males (OR = 1.32, 95% CI: 1.02-1.70) and females (OR = 1.29, 95% CI: 1.13-1.47) post- vs. pre-SO. When compared to the control group (SO), the odds ratios for colorectal polyps were lower for males and females after bariatric surgery (OR = 0.63, 95% CI: 0.44-0.90, and OR = 0.79, 95% CI: 0.66-0.96, respectively). CONCLUSIONS: Obesity is associated with an increased risk of colorectal polyps, an effect that is ameliorated after bariatric surgery. These data are relevant for studies investigating colorectal carcinogenesis mechanisms.

7.
J Cancer Surviv ; 2023 Sep 05.
Article En | MEDLINE | ID: mdl-37668940

OBJECTIVE: To evaluate changes in physical function (PF) for older women with endometrial cancer (EC) + / - adjuvant therapy in the Women's Health Initiative Life and Longevity after Cancer cohort. MATERIALS AND METHODS: This study examined women ≥ 70 years of age with EC with available treatment records. Change in PF was measured using the RAND-36 and compared between groups using Wilcoxon rank-sum tests. Multivariable median regression was used to compare the changes in scores while adjusting for confounding variables. RESULTS: Included in the study were 287 women, 150 (52.3%) women who did not receive adjuvant therapy and 137 (47.7%) who received adjuvant therapy. When comparing PF scores, there was a statistically significant difference in the median percent change in functional decline, with a greater decline in those who received adjuvant therapy (- 5.9% [- 23.5 to 0%]) compared to those who did not (0 [- 18.8 to + 6.7%]), p = 0.02). Results were not statistically significant after multivariable adjustment, but women who underwent chemotherapy had a greater percent change (median ∆ - 13.8% [- 35.5 to 0%]) compared to those who received radiation alone (median ∆ - 5.9% [- 31.3 to 0%]) or chemotherapy and radiation (median ∆ - 6.5% [- 25.8 to + 5.7%]. CONCLUSIONS: Older women with EC who received adjuvant therapy experienced greater change in PF than those who did not receive adjuvant therapy, particularly women who received chemotherapy. These results were not statistically significant on multivariate analysis. IMPLICATIONS FOR CANCER SURVIVORS: EC survivors may experience changes in PF because of chemotherapy and/or radiation therapy. Additional supportive care may need to be provided to older women to mitigate functional decline.

8.
Gynecol Oncol ; 177: 46-52, 2023 Oct.
Article En | MEDLINE | ID: mdl-37639902

OBJECTIVE: To determine the prevalence of Type 2 diabetes mellitus (T2DM) diagnoses during the peri-operative and survivorship periods in patients following surgical management of endometrial cancer (EC). METHODS: An IRB-approved, retrospective single-institution cohort study was performed in patients who underwent surgical management of EC from 2014 to 2020. The perioperative period was defined as the 30 days before and after surgery. T2DM diagnoses occurring during survivorship were recorded. T2DM diagnoses were defined by a HgbA1c ≥6.5% or a random blood glucose ≥200 mg/dL. Sequelae of peri-operative T2DM and predictors of future T2DM were examined utilizing univariate analysis. RESULTS: Of 519 patients meeting inclusion criteria, 37 (7.1%) were diagnosed with T2DM in the perioperative period. Patients diagnosed with T2DM in the perioperative period had significantly higher BMI (p = 0.006) compared to no T2DM, but there were no significant differences in age (p = 0.20), ethnicity/race (p > 0.05) or ECOG score (p = 0.19). The rates of intraoperative complications between groups did not significantly differ, except for vascular complications (p = 0.005), and the incidence of any postoperative complication was higher in the perioperative T2DM group (p = 0.01). With a median follow-up of 29 months [range 11.6-49.0 months], an additional 18.3% (n = 88) of the cohort met diagnostic criteria for T2DM. BMI (p < 0.001), perioperative glucose (p < 0.001), and HgbA1c (p = 0.002) demonstrate risk for a T2DM diagnosis during survivorship. CONCLUSION(S): In this retrospective cohort of EC patients, 25.4% were diagnosed with T2DM, with the majority diagnosed in the survivorship period. Surgical management and subsequent surveillance of EC presents an opportunity to diagnose at-risk patients with T2DM.

10.
J Intensive Med ; 3(3): 254-260, 2023 Jul 31.
Article En | MEDLINE | ID: mdl-37533810

Background: Fluid resuscitation is a key treatment for sepsis, but limited data exists in patients with existing heart failure (HF) and septic shock. The objective of this study was to determine the impact of initial fluid resuscitation volume on outcomes in HF patients with reduced or mildly reduced left ventricular ejection fraction (LVEF) with septic shock. Methods: This multicenter, retrospective, cohort study included patients with known HF (LVEF ≤50%) presenting with septic shock. Patients were divided into two groups based on the volume of fluid resuscitation in the first 6 h; <30 mL/kg or ≥30 mL/kg. The primary outcome was a composite of in-hospital mortality or renal replacement therapy (RRT) within 7 days. Secondary outcomes included acute kidney injury (AKI), initiation of mechanical ventilation, and length of stay (LOS). All related data were collected and compared between the two groups. A generalized logistic mixed model was used to assess the association between fluid groups and the primary outcome while adjusting for baseline LVEF, Acute Physiology and Chronic Health Evaluation (APACHE) II score, inappropriate empiric antibiotics, and receipt of corticosteroids. Results: One hundred and fifty-four patients were included (93 patients in <30 mL/kg group and 61 patients in ≥30 mL/kg group). The median weight-based volume in the first 6 h was 17.7 (12.2-23.0) mL/kg in the <30 mL/kg group vs. 40.5 (34.2-53.1) mL/kg in the ≥30 mL/kg group (P <0.01). No statistical difference was detected in the composite of in-hospital mortality or RRT between the <30 mL/kg group compared to the ≥30 mL/kg group (55.9% vs. 45.9%, P=0.25), respectively. The <30 mL/kg group had a higher incidence of AKI, mechanical ventilation, and longer hospital LOS. Conclusions: In patients with known reduced or mildly reduced LVEF presenting with septic shock, no difference was detected for in-hospital mortality or RRT in patients who received ≥30 mL/kg of resuscitation fluid compared to less fluid, although this study was underpowered to detect a difference. Importantly, ≥30 mL/kg fluid did not result in a higher need for mechanical ventilation.

11.
J Pharm Pract ; : 8971900231191154, 2023 Jul 22.
Article En | MEDLINE | ID: mdl-37480556

BACKGROUND: Few randomized controlled trials have evaluated the use of ketamine vs opiate-based analgosedation. METHODS: A retrospective cohort analysis of 169 mechanically ventilated patients admitted to the medical intensive care unit (MICU) at an academic medical center was conducted to evaluate efficacy of ketamine vs opiate-based analgosedation by comparing the percentage of time within target sedation range. The primary outcome was percentage of time within target sedation range (RASS -1 to +1) within first 72 hours of primary sedation initiation. Secondary outcomes including percentage of time under-sedated, over-sedated, and in coma; use of concomitant analgesic, sedative, and antipsychotic agents; presence of delirium; percentage of CPOT scores at goal; and hemodynamic effects were also evaluated. RESULTS: After weighting, the mean percentage of time at RASS goal for ketamine patients was 43.0% compared to 41.4% for opiate-based sedation patients. Ketamine was not significantly non-inferior to opiate-based sedation for the mean percentage of time at RASS goal (P = .11). The median percentage of CPOT scores at goal was 13.3% higher in the ketamine group (P = .042). Patients in the ketamine group received significantly less additional sedative agents than the patients in the opiate-based sedation group. CONCLUSION: A similar percent of time at RASS goal was found for the ketamine analgosedation group compared to the opiate-based sedation group, although this did not reach statistical signicance for non-inferiority due to lack of statistical power. This study found a higher percentage of CPOT scores within goal with less additional sedative agents required compared to an opiate-based sedation regimen.

12.
Gynecol Oncol Rep ; 48: 101227, 2023 Aug.
Article En | MEDLINE | ID: mdl-37415961

Objective: To determine the safety and feasibility of same-day discharge (SDD) following minimally invasive hysterectomy (MIH) for elderly patients and to evaluate associations between age, frailty, and postoperative outcomes. Methods: Retrospective review was conducted of patients aged ≥ 70 who underwent MIH within a single gynecologic oncology institution from 2018 to 2020. Demographics, peri-operative factors, postoperative complications, and 30-day readmission rates were collected. Frailty was determined by an 11-point modified frailty index ≥ 2. Outcomes were compared between SDD and observation groups using Fisher's exact and Wilcoxon rank-sum tests. Results: Of 169 patients included in the analysis, 8.9% (n = 15) underwent SDD, and 91.1% (n = 154) were admitted for OBS following MIH. Demographics, peri-operative factors, and frailty rates (33% SDD vs 43.5% observation; p = 0.59) were similar between groups. 86.7% (n = 13) of SDD cases were completed before 12PM, and none were completed after 6PM. No SDD patients had early post-operative complications or hospital readmissions. Early postoperative complications were diagnosed in 9 (5.8%) patients admitted for OBS, and the 30-day hospital readmission rate for patients who underwent OBS was 8.4% (n = 13). While elderly patients who met objective frailty criteria (n = 72) did not have a higher likelihood of early post-operative complications (44.4% vs 55.6%; p = 0.909), they did have a higher likelihood of ED visit within 30 days of discharge (15.3 vs 3.1%; p = 0.009), and a trend was noted toward a higher rate of 30-day hospital readmission (12.5% vs 4.1%; p = 0.080). Conclusions: Elderly patients undergoing SDD following MIH did not have increased morbidity or mortality. Elderly patients who meet objective criteria for frailty, however, represent a more vulnerable population.

13.
Oncologist ; 28(11): 996-1004, 2023 Nov 02.
Article En | MEDLINE | ID: mdl-37498515

BACKGROUND: This study explored the risk mitigation practices of multidisciplinary oncology health-care personnel for the nonmedical use of opioids in people with cancer. METHODS: An anonymous, cross-sectional descriptive survey was administered via email to eligible providers over 4 weeks at The Ohio State University's Arthur G. James Cancer Hospital. The survey asked about experiences and knowledge related to opioid use disorders. RESULTS: The final sample of 773 participants included 42 physicians, 213 advanced practice providers (APPs consisted of advanced practice nurses, physician assistants, and pharmacists), and 518 registered nurses. Approximately 40% of participants responded feeling "not confident" in addressing medication diversion. The most frequent risk reduction measure was "Checking the prescription drug monitoring program" when prescribing controlled medications, reported by physicians (n = 29, 78.4%) and APPs (n = 164, 88.6%). CONCLUSION: People with cancer are not exempt from the opioid epidemic and may be at risk for nonmedical opioid use (NMOU) and substance use disorders. Implementing risk reduction strategies with every patient, with a harm reduction versus abstinence focus, minimizes harmful consequences and improves. This study highlights risk mitigation approaches for NMOU, representing an opportunity to improve awareness among oncology health-care providers. Multidisciplinary oncology teams are ideally positioned to navigate patients through complex oncology and health-care journeys.


Neoplasms , Opioid-Related Disorders , Physicians , Humans , Analgesics, Opioid/therapeutic use , Cross-Sectional Studies , Opioid-Related Disorders/epidemiology , Neoplasms/drug therapy , Practice Patterns, Physicians'
14.
Cancer Med ; 12(15): 16626-16636, 2023 08.
Article En | MEDLINE | ID: mdl-37381978

BACKGROUND: Published studies have demonstrated inconclusive relationships between serum lipid levels and mortality after cancer. METHODS: The primary objective was to evaluate the relationship between fasting lipid levels and mortality after cancer. Data were obtained on baseline lipids and outcomes after cancer from 1263 postmenopausal women diagnosed with 13 obesity-related cancers who were part of the Women's Health Initiative (WHI) lipid biomarkers cohort. Obesity-related cancers included incident invasive cancers of the breast, colorectum, endometrium, esophagus (adenocarcinoma), kidney, liver, gallbladder, pancreas, ovaries, small intestine, thyroid, stomach, as well as multiple myeloma. Baseline lipid measurements included high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, and non-HDL-cholesterol. Outcomes were all cause, cancer-specific, and CVD mortality. Multivariable Cox proportional hazards models were used to measure associations between lipid levels and mortality (all cause, cancer, and CVD) after a cancer diagnosis, with lipids analyzed as continuous variables. RESULTS: Among women with obesity-related cancer, there were 707 deaths, of which 379 (54%) were due to cancer and 113 (16%) were due to CVD. Mean time from blood draw to cancer diagnosis was 5.1 years (range: 0.05-10 years). LDL-C values above the 95th percentile were associated with higher risk of all-cause mortality (p < 0.001), and cancer-specific mortality (p < 0.001), but not mortality due to CVD. Non-HDL-C values above the 65th percentile were associated with higher risk of all-cause mortality (p = 0.01) and mortality due to CVD (p = 0.003), but not cancer-specific mortality (p = 0.37). HDL-C values above the 95th percentile were associated with lower all-cause mortality (p = 0.002), and above the 65th percentile with lower cancer-specific mortality (p = 0.003), but no significant relationship with mortality due to CVD was observed. CONCLUSIONS: The relationship between pre-diagnosis fasting lipid levels and mortality after cancer diagnosis is complex. These results suggest that improved lipid control through lifestyle and anti-lipid medications could have a meaningful impact on outcomes after cancer.


Cardiovascular Diseases , Multiple Myeloma , Female , Humans , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/etiology , Risk Factors , Women's Health , Obesity/complications , Biomarkers , Cholesterol , Multiple Myeloma/complications , Cholesterol, HDL
15.
Clin Breast Cancer ; 23(6): 658-663, 2023 08.
Article En | MEDLINE | ID: mdl-37296062

BACKGROUND: Palbociclib is indicated for the treatment of hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (MBC) in combination with an aromatase inhibitor or fulvestrant. Two retrospective studies found that concurrent proton pump inhibitor (PPI) use with palbociclib capsules significantly reduced progression free survival (PFS) versus patients without a PPI. Palbociclib tablets were released in 2020 without restriction on PPI use. No study to date has evaluated the combination of palbociclib tablets with concurrent PPI use. METHODS: Patients were retrospectively evaluated after they received palbociclib tablets for the treatment of HR+ HER2- MBC in the first line setting with or without a PPI. Patients were assigned to the no PPI use arm if they never used a PPI and the PPI use arm if they used a PPI for >50% of the duration of palbocicib therapy. The primary endpoint was PFS. The secondary endpoints included overall survival (OS) and adverse events. RESULTS: Eighty-two patients were identified; 50 in the no PPI use group and 32 in the PPI use group. The median PFS was 20.6 months (95% confidence interval [CI], 16.07 to not estimable) in the no PPI use arm versus 21.0 months (95% CI, 15.15 to not estimable) in the PPI use arm (P = 0.95). Median OS was not reached in either arm. Adverse effects did not differ between arms. CONCLUSION: Use of a concurrent PPI with palbociclib tablets does not significantly reduce PFS in patients treated for HR+ HER2- MBC.


Breast Neoplasms , Humans , Female , Breast Neoplasms/pathology , Proton Pump Inhibitors/therapeutic use , Retrospective Studies , Receptor, ErbB-2/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
16.
Blood ; 142(15): 1271-1280, 2023 10 12.
Article En | MEDLINE | ID: mdl-37352612

T-cell large granular lymphocytic leukemia (T-LGLL) is a clonal proliferation of cytotoxic T lymphocytes that can result in severe neutropenia, anemia, and bone marrow failure. Strong evidence from patients and mouse models demonstrate the critical role of interleukin-15 (IL-15) in T-LGLL pathogenesis. BNZ-1 is a pegylated peptide that selectively inhibits the binding of IL-15 and other γc cytokines to their cellular receptor complex, which has demonstrated efficacy in ex vivo T-LGLL cells and transgenic mice in preclinical studies. We conducted a phase 1/2 trial of BNZ-1 in patients with T-LGLL who had hematocytopenias (anemia or neutropenia) and required therapy. Clinical responses were assessed using hematologic parameters (improvement in hematocytopenias) based on response criteria from the Eastern Cooperative Oncology Group 5998 T-LGLL trial. BNZ-1 demonstrated clinical partial responses in 20% of patients with T-LGLL with minimal toxicity and the maximum tolerated dose was not reached. Furthermore, T-LGL leukemic cells showed significantly increased apoptosis in response to BNZ-1 treatment as early as day 2, including in clinical nonresponders, with changes that remained statistically different from baseline throughout treatment (P < .005). We report first-in-human proof that T-LGL leukemic cells are dependent on IL-15 and that intervention with IL-15 inhibition with BNZ-1 in patients with T-LGLL shows therapeutic effects, which carries important implications for the understanding of the pathogenesis of this disease. This trial was registered at www.clinicaltrials.gov as #NCT03239392.


Anemia , Leukemia, Large Granular Lymphocytic , Neutropenia , Mice , Animals , Humans , Cytokines/metabolism , Leukemia, Large Granular Lymphocytic/pathology , Interleukin-15
17.
J Natl Cancer Inst Monogr ; 2023(61): 77-83, 2023 05 04.
Article En | MEDLINE | ID: mdl-37139983

Patients with prior colorectal polyps are at high risk for metachronous colorectal neoplasia, especially in the presence of obesity. We assessed the impact of 2 common bariatric surgeries, vertical sleeve gastrectomy and roux-n-Y gastric bypass, on the risk of colorectal neoplasia recurrence. This nationally representative analysis included 1183 postbariatric adults and 3193 propensity score-matched controls, who all had prior colonoscopy with polyps and polypectomy. Colorectal polyps reoccurred in 63.8% of bariatric surgery patients and 71.7% of controls at a mean follow-up of 53.1 months from prior colonoscopy. There was a reduced odds of colorectal polyp recurrence after bariatric surgery compared with controls (odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.58 to 0.83). This effect was most pronounced in men (OR = 0.58, 95% CI = 0.42 to 0.79), and post roux-n-Y gastric bypass (OR = 0.57, 95% CI = 0.41 to 0.79). However, the risk of rectal polyps or colorectal cancer remained consistent between groups. This study is the first to our knowledge to show a reduction in risk of polyp recurrence following bariatric surgery.


Colonic Polyps , Colorectal Neoplasms , Gastric Bypass , Neoplasms, Second Primary , Adult , Male , Humans , Colonic Polyps/diagnosis , Colonic Polyps/epidemiology , Colonic Polyps/surgery , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/etiology , Neoplasm Recurrence, Local/prevention & control , Gastric Bypass/methods , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/etiology , Weight Loss , Neoplasms, Second Primary/diagnosis , Neoplasms, Second Primary/epidemiology , Neoplasms, Second Primary/etiology , Retrospective Studies
18.
Gynecol Oncol ; 173: 15-21, 2023 06.
Article En | MEDLINE | ID: mdl-37037083

OBJECTIVES: To describe stage, treatment patterns, and survival for glassy cell carcinoma of the cervix (GCCC), a poorly understood rare tumor. METHODS: Clinical data and survival were compared between GCCC and more common histologic types using the National Cancer Database (NCDB) from 2004 to 2017. A retrospective review of GCCC cases at our institution from 2012 to 2020 was simultaneously performed with staging updated according to 2018 FIGO staging. Descriptive statistics and survival analyses were performed, and outcomes compared to historical references. RESULTS: 143/89,001 (0.16%) NCDB cervical cancer cases were GCCC. Compared to other histologies, GCCC cases were younger, with 74.8% diagnosed before age 50. Stage distribution was similar. Stage I cases were less commonly treated with surgery alone (19/69, 27%). 79.4% of locally advanced (stage II-IVA) cases were treated with definitive chemoradiation. GCCC demonstrated worse OS for early-stage and locally-advanced disease. No survival differences were observed for patients with stage IVB disease. Our institutional review identified 14 GCCC cases. Median age at diagnosis was 34 years. All nine early-stage cases underwent radical hysterectomy. Adjuvant radiation was given for cases meeting Sedlis criteria (4/9, 44%). All five advanced stage cases were stage IIIC and received definitive chemoradiation. Recurrence rate was 0% (0/9) for early-stage and 60% (3/5) for advanced-stage cases. 3-year PFS was 100% for early-stage and 40% for advanced-stage. 3-year OS was 100% for early-stage and 60% for advanced-stage GCCC. CONCLUSIONS: GCCC presents at earlier ages than other cervical cancer histologic types. Although NCDB showed worse OS, our more contemporary institutional review, which incorporates updated staging and newer treatment modalities found outcomes more similar to historical references of more common histologic subtypes.


Uterine Cervical Neoplasms , Female , Humans , Adult , Middle Aged , Uterine Cervical Neoplasms/pathology , Neoplasm Staging , Cervix Uteri/pathology , Combined Modality Therapy , Retrospective Studies , Hysterectomy
19.
Gynecol Oncol Rep ; 46: 101173, 2023 Apr.
Article En | MEDLINE | ID: mdl-37082521

Objective: To determine the recurrence rate and survival among early-stage epithelial ovarian cancer cases considering homologous recombination deficiency (HRD) status. Methods: Single institution retrospective study of stage I/II EOC patients from 2017 to 2020. HRD was defined as evidence of germline or somatic BRCA mutation, or loss of heterozygosity (LOH)/genomic instability (GIS) as determined by companion diagnostic tests. Kaplan-Meier analyses were performed. Results: 89 stage I/II cases were included. 4/89 (4.5%) had a germline BRCA1/2 mutation, 8 (9%) were germline negative but had a somatic BRCA mutation, and 8 (9%) were BRCA wild-type but had evidence of LOH/GIS on somatic testing; these 20/89 (22%) cases comprised the HRD group. The remaining tumors were confirmed homologous recombination proficient (HRP, 35/89, 39%) or homologous recombination unknown (HRU, 34/89, 38%). The overall recurrence rate was 33/89 (37%). There were more recurrences among HRD cases (14/20, 70%) compared to HRP/HRU cases (19/69, 27.5%, p = 0.0012). Median Recurrence-Free Survival (RFS) was 35 months for HRD cases and 225 months for HRP/HRU cases (p = 0.001). At 2 years, there were 60% HRD cases and 88% HRP/HRU cases recurrence-free. At 5 years there were 29% HRD and 69% HRP/HRU cases recurrence-free (p = 0.001). Conclusions: Despite a high rate of complete surgical staging and six cycles of adjuvant chemotherapy, recurrence rate was high in this early-stage cohort. Higher recurrence rates were seen in the HRD group, however these data are likely biased by the clinical practice of tumor testing primarily at the time of recurrence rather than the upfront setting. RFS was significantly lower for HRD cases.

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J Gerontol B Psychol Sci Soc Sci ; 78(9): 1445-1458, 2023 08 28.
Article En | MEDLINE | ID: mdl-36933001

OBJECTIVES: A comprehensive examination of resilience by race, ethnicity, and neighborhood socioeconomic status (NSES) among women aged ≥80 is needed, given the aging of the U.S. population, increasing longevity, and growing racial and ethnic diversity. METHODS: Participants were women aged ≥80 enrolled in the Women's Health Initiative. Resilience was assessed with a modified version of the Brief Resilience Scale. Descriptive statistics and multiple linear regression examined the association of demographic, health, and psychosocial variables with resilience by race, ethnicity, and NSES. RESULTS: Participants (n = 29,367, median age = 84.3) were White (91.4%), Black (3.7%), Hispanic (1.9%), and Asian (1.7%) women. There were no significant differences by race and ethnicity on mean resiliency scores (p = .06). Significant differences by NSES were observed regarding mean resiliency scores between those with low NSES (3.94 ± 0.83, out of 5) and high NSES (4.00 ± 0.81). Older age, higher education, higher self-rated health, lower stress, and living alone were significant positive correlates of resilience in the sample. Social support was correlated with resilience among White, Black, and Asian women, but not for Hispanic women. Depression was a significant correlate of lower resilience, except among Asian women. Living alone, smoking, and spirituality were significantly associated with higher resilience among women with moderate NSES. DISCUSSION: Multiple factors were associated with resilience among women aged ≥80 in the Women's Health Initiative. Despite some differing correlates of resilience by race, ethnicity, and NSES, there were many similarities. These results may aid in the design of resilience interventions for the growing, increasingly diverse population of older women.


Resilience, Psychological , Social Class , Social Environment , Women's Health , Aged , Aged, 80 and over , Female , Humans , Male , Ethnicity , Hispanic or Latino , Smoking , Black or African American , White , Asian , United States/epidemiology , Racial Groups
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