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Margaret A. Tempero, Mokenge P. Malafa, Mahmoud Al-Hawary, Stephen W. Behrman, Al B. Benson III, Dana B. Cardin, E. Gabriela Chiorean, Vincent Chung, Brian Czito, Marco Del Chiaro, Mary Dillhoff, Timothy R. Donahue, Efrat Dotan, Cristina R. Ferrone, Christos Fountzilas, Jeffrey Hardacre, William G. Hawkins, Kelsey Klute, Andrew H. Ko, John W. Kunstman, Noelle LoConte, Andrew M. Lowy, Cassadie Moravek, Eric K. Nakakura, Amol K. Narang, Jorge Obando, Patricio M. Polanco, Sushanth Reddy, Marsha Reyngold, Courtney Scaife, Jeanne Shen, Charles Vollmer Jr., Robert A. Wolff, Brian M. Wolpin, Beth Lynn, and Giby V. George

Pancreatic cancer is the fourth leading cause of cancer-related death among men and women in the United States. A major challenge in treatment remains patients’ advanced disease at diagnosis. The NCCN Guidelines for Pancreatic Adenocarcinoma provides recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pancreatic cancer. Although survival rates remain relatively unchanged, newer modalities of treatment, including targeted therapies, provide hope for improving patient outcomes. Sections of the manuscript have been updated to be concordant with the most recent update to the guidelines. This manuscript focuses on the available systemic therapy approaches, specifically the treatment options for locally advanced and metastatic disease.

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Zhi Ven Fong and Cristina R. Ferrone

Because of the biologic aggressiveness and late presentation of pancreatic ductal adenocarcinoma (PDAC), up to 80% of patients have locally advanced or metastatic disease at presentation. The success of multiagent chemotherapy regimens in the management of metastatic disease has been translated to patients with locally advanced PDAC. Both FOLFIRINOX (fluorouracil/folinic acid/irinotecan/oxaliplatin) and gemcitabine/nab-paclitaxel are used to downstage locally advanced PDAC to render it eligible for resection with curative intent. This paradigm shift has significantly expanded the pool of patients who are eligible for resection with curative intent. However, the generalizability of present studies and the patient selection process are unclear. This article provides an evidence-based review of patient selection considerations and management algorithms, and details our institution’s approach to patients with locally advanced PDAC after preoperative chemotherapy.

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Stephanie Alimena, Suvidya Lakshmi Pachigolla, Sarah Feldman, David Yang, Peter F. Orio III, Larissa Lee, and Martin King

Background: Although the incidence of cervical cancer among younger Black women is now equivalent to that of White women, it is unknown whether the reduced incidence has affected survival rates among younger Black women. The goal of this study was to assess differences in survival by age and race. Patients and Methods: A retrospective cohort study was performed using the National Cancer Database to analyze women with nonmetastatic cervical cancer diagnosed between 2004 and 2014. Women with unknown survival data and those who died within 3 months of diagnosis were excluded. Multivariable logistic regression models evaluated interactions between age and race (Black vs non-Black) for presentation with stage I disease and receipt of optimal treatment. A multivariable Cox regression model was used to evaluate survival differences by age and race. Results: Of 55,659 women included, 16.4% were Black. Compared with their non-Black counterparts, fewer Black women presented with stage I disease (37.8% vs 47.8%; P<.01) and received optimal treatment (46.2% vs 58.3%; P<.01). Fewer Black women had private insurance if they were aged <65 years (39.6% vs 55.7%; P<.01), but not if they were aged ≥65 years (11.7% vs 12.4%; P=.43). According to multivariable logistic regression, Black women aged ≤39 years were less likely to present with stage I disease, with a significant interaction term between age and race (P<.01 for interaction). Disparities in overall survival by race were greatest for Black women aged ≤39 years (adjusted hazard ratio, 1.32; 95% CI, 1.20–1.46; P<.01) but decreased with increasing age interval until no disparity was noted for women aged ≥65 years (P<.01 for interaction). Conclusions: Younger Black women with cervical cancer are at risk for presenting with higher-stage disease and having worse overall survival. These findings may be related to insurance-related disparities and inadequate follow-up for abnormal Papanicolaou test results. Younger Black women with cervical cancer may be a particularly vulnerable population.

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Ashley E. Rosko, Sarah Wall, Robert Baiocchi, Don M. Benson, Jonathan E. Brammer, John C. Byrd, Yvonne A. Efebera, Kami Maddocks, Kerry A. Rogers, Desiree Jones, Lara Sucheston-Campbell, Hancong Tang, Hatice Gulcin Ozer, Ying Huang, Christin E. Burd, and Michelle J. Naughton

Background: Gauging fitness remains a challenge among older adults with hematologic malignancies, and interventions to restore function are lacking. We pilot a structured exercise intervention and novel biologic correlates of aging using epigenetic clocks and markers of immunosenescence to evaluate changes in function and clinical outcomes. Methods: Older adults (n=30) with hematologic malignancy actively receiving treatment were screened and enrolled in a 6-month exercise intervention, the Otago Exercise Programme (OEP). The impact of the OEP on geriatric assessment metrics and health-related quality of life were captured. Clinical outcomes of overall survival and hospital utilization (inpatient length of stay and emergency department use) in relationship to geriatric deficits were analyzed. Results: Older adults (median age, 75.5 years [range, 62–83 years]) actively receiving treatment were enrolled in the OEP. Instrumental activities of daily living and physical health scores (PHS) increased significantly with the OEP intervention (median PHS: visit 1, 55 [range, 0–100]; visit 2, 70 [range, 30–100]; P<.01). Patient-reported Karnofsky performance status increased significantly, and the improvement was sustained (median [range]: visit 1, 80 [40–100]; visit 3, 90 [50–100]; P=.05). Quality of life (Patient-Reported Outcome Measurement Information System [PROMIS]) improved significantly by the end of the 6-month period (median [range]: visit 1, 32.4 [19.9–47.7]; visit 3, 36.2 [19.9–47.7]; P=.01]. Enhanced measures of gait speed and balance, using the Short Physical Performance Battery scores, were associated with a 20% decrease in risk of death (hazard ratio, 0.80; 95% CI, 0.65–0.97; P=.03) and a shorter hospital length of stay (decrease of 1.29 days; 95% CI, −2.46 to −0.13; P=.03). Peripheral blood immunosenescent markers were analyzed in relationship to clinical frailty and reports of mPhenoAge epigenetic analysis are preliminarily reported. Chronologic age had no relationship to overall survival, length of stay, or emergency department utilization. Conclusions: The OEP was effective in improving quality of life, and geriatric tools predicted survival and hospital utilization among older adults with hematologic malignancies.

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Seth A. Wander, Hyo S. Han, Mark L. Zangardi, Andrzej Niemierko, Veronica Mariotti, Leslie S.L. Kim, Jing Xi, Apurva Pandey, Siobhan Dunne, Azadeh Nasrazadani, Avinash Kambadakone, Casey Stein, Maxwell R. Lloyd, Megan Yuen, Laura M. Spring, Dejan Juric, Irene Kuter, Ioannis Sanidas, Beverly Moy, Therese Mulvey, Neelima Vidula, Nicholas J. Dyson, Leif W. Ellisen, Steven Isakoff, Nikhil Wagle, Adam Brufsky, Kevin Kalinsky, Cynthia X. Ma, Joyce O’Shaughnessy, and Aditya Bardia

Background: Inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) are widely used as first-line therapy for hormone receptor–positive metastatic breast cancer (HR+ MBC). Although abemaciclib monotherapy is also FDA-approved for treatment of disease progression on endocrine therapy, there is limited insight into the clinical activity of abemaciclib after progression on prior CDK4/6i. Patients and Methods: We identified patients with HR+ MBC from 6 cancer centers in the United States who received abemaciclib after disease progression on prior CDK4/6i, and abstracted clinical features, outcomes, toxicity, and predictive biomarkers. Results: In the multicenter cohort, abemaciclib was well tolerated after a prior course of CDK4/6i (palbociclib)-based therapy; a minority of patients discontinued abemaciclib because of toxicity without progression (9.2%). After progression on palbociclib, most patients (71.3%) received nonsequential therapy with abemaciclib (with ≥1 intervening non-CDK4/6i regimens), with most receiving abemaciclib with an antiestrogen agent (fulvestrant, 47.1%; aromatase inhibitor, 27.6%), and the remainder receiving abemaciclib monotherapy (19.5%). Median progression-free survival for abemaciclib in this population was 5.3 months and median overall survival was 17.2 months, notably similar to results obtained in the MONARCH-1 study of abemaciclib monotherapy in heavily pretreated HR+/HER2-negative CDK4/6i-naïve patients. A total of 36.8% of patients received abemaciclib for ≥6 months. There was no relationship between the duration of clinical benefit while on palbociclib and the subsequent duration of treatment with abemaciclib. RB1, ERBB2, and CCNE1 alterations were noted among patients with rapid progression on abemaciclib. Conclusions: A subset of patients with HR+ MBC continue to derive clinical benefit from abemaciclib after progression on prior palbociclib. These results highlight the need for future studies to confirm molecular predictors of cross-resistance to CDK4/6i therapy and to better characterize the utility of abemaciclib after disease progression on prior CDK4/6i.

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Eashwar Somasundaram, Adam Litzler, Raoul Wadhwa, and Jacob Scott

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Amye Tevaarwerk, Travis Osterman, Waddah Arafat, Jeffrey Smerage, Fernanda C.G. Polubriaginof, Tricia Heinrichs, Jessica Sugalski, and Daniel Martin