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Reith R. Sarkar, Katherine E. Fero, Daniel M. Seible, Neil Panjwani, Rayna K. Matsuno and James D. Murphy

Background: Pancreatic cancer is an aggressive disease characterized by early and relentless tumor spread, thus leading healthcare providers to consider it a “distant disease.” However, local pancreatic tumor progression can lead to substantial morbidity. This study defines the long-term morbidity from local and nonlocal disease progression in a large population-based cohort. Methods: A total of 21,500 Medicare beneficiaries diagnosed with pancreatic cancer in 2000 through 2011 were identified. Hospitalizations were attributed to complications of either local disease (eg, biliary disorder, upper gastrointestinal ulcer/bleed, pain, pancreas-related, radiation toxicity) or nonlocal/distant disease (eg, thromboembolic events, cytopenia, dehydration, nausea/vomiting/motility problem, malnutrition and cachexia, ascites, pathologic fracture, and chemotherapy-related toxicity). Competing risk analyses were used to identify predictors of hospitalization. Results: Of the total cohort, 9,347 patients (43.5%) were hospitalized for a local complication and 13,101 patients (60.9%) for a nonlocal complication. After adjusting for the competing risk of death, the 12-month cumulative incidence of hospitalization from local complications was highest in patients with unresectable disease (53.1%), followed by resectable (39.5%) and metastatic disease (33.7%) at diagnosis. For nonlocal complications, the 12-month cumulative incidence was highest in patients with metastatic disease (57.0%), followed by unresectable (56.8%) and resectable disease (42.8%) at diagnosis. Multivariable analysis demonstrated several predictors of hospitalization for local and nonlocal complications, including age, race/ethnicity, location of residence, disease stage, tumor size, and diagnosis year. Radiation and chemotherapy had minimal impact on the risk of hospitalization. Conclusions: Despite the widely known predilection of nonlocal/distant disease spread in pancreatic cancer, local tumor progression also leads to substantial morbidity and frequent hospitalization.

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Nicholas Cardillo, Daniel M. Seible, Katherine E. Fero, Andrew R. Bruggeman, Reith R. Sarkar, Alexa Azuara, Daniel R. Simpson and James D. Murphy

Background: The high prevalence of distant metastatic disease among patients with pancreatic cancer often draws attention away from the local pancreatic tumor. This study aimed to define the complications and hospitalizations from local versus distant disease progression among a retrospective cohort of patients with pancreatic cancer. Methods: Records of 298 cases of pancreatic cancer treated at a single institution from 2004 through 2015 were retrospectively reviewed, and cancer-related symptoms and complications requiring hospitalization were recorded. Hospitalizations related to pancreatic cancer were attributed to either local or distant progression. Cumulative incidence analyses were used to estimate the incidence of hospitalization, and multivariable Fine-Gray regression models were used to identify factors predictive of hospitalizations. Results: The 1-year cumulative incidences of hospitalization due to local versus distant disease progression were 31% and 24%, respectively. Among 509 recorded hospitalizations, leading local etiologies included cholangitis (10%), biliary obstruction (7%), local procedure complication (7%), and gastrointestinal bleeding (7%). On multivariable analysis, significant predictors of hospitalization from local progression included unresectable disease (subdistribution hazard ratio [SDHR], 2.42; P<.01), black race (SDHR, 3.34; P<.01), younger age (SDHR, 1.02 per year; P=.01), tumor in the pancreatic head (SDHR, 2.19; P<.01), and larger tumor size (SDHR, 1.13 per centimeter; P=.02). Most patients who died in the hospital from pancreatic cancer (56%) were admitted for complications of local disease progression. Conclusions: Patients with pancreatic cancer experience significant complications of local tumor progression. Although distant metastatic progression represents a hallmark of pancreatic cancer, future research should also focus on improving local therapies.

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Eric J. Roeland, Daniel P. Triplett, Rayna K. Matsuno, Isabel J. Boero, Lindsay Hwang, Heidi N. Yeung, Loren Mell and James D. Murphy

Background: The role of palliative care has expanded over the past several decades, although the oncology-specific regional evolution of this specialty has not been characterized at the population-based level. Methods: This study defined the patterns of palliative care delivery using a retrospective cohort of patients with advanced cancer within the SEER-Medicare linked database. We identified 83,022 patients with metastatic breast, prostate, lung, and colorectal cancers. We studied trends between 2000 through 2009, and determined patient-level and regional-level predictors of palliative care delivery. Results: Palliative care consultation rates increased from 3.0% in 2000 to 12.9% in 2009, with most consultations occurring in the last 4 weeks of life (77%) in the inpatient hospital setting. The rates of palliative care delivery were highest in the West (7.6%) and lowest in the South (3.2%). The likelihood of palliative care consultation increased with decreasing numbers of regional acute care hospital beds per capita. The use of palliative care consultation increased with increasing numbers of regional physicians. The use of palliative care decreased with increasing regional Medicare expenditure with a $1,387 difference per beneficiary between the first and fourth quartiles of palliative care use. Conclusions: Geographic location influences a patient's options for palliative care in the United States. Although the overall rates of palliative care are increasing, future effort should focus on improving palliative care services in regions with the least access.

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Emily J. Martin, Eric J. Roeland, Madison B. Sharp, Carolyn Revta, James D. Murphy, Katherine E. Fero and Heidi N. Yeung

Background: Patient-controlled analgesia (PCA) is an effective approach to treat pain. However, data regarding patterns of PCA use for cancer pain are limited. The purpose of this study was to define the patterns of PCA use and related outcomes in hospitalized patients with cancer. Methods: We identified 90 patients with cancer admitted to a single academic center who received PCA for nonsurgical, cancer-related pain and survived to discharge between January 2013 and January 2014. Data collected included patient demographics, cancer diagnosis, type of cancer-related pain, PCA use, opioid-specific adverse events, and 30-day readmission rates for pain. Univariable and multivariable linear regression models were used to analyze the association between patient and clinical variables with PCA duration. Logistic regression models were used to evaluate the relationship between patient and clinical variables and 30-day readmission rates. Results: The median length of hospitalization was 10.2 days with a median PCA duration of 4.4 days. Hematologic malignancies were associated with longer PCA use (P=.0001), as was younger age (P=.032). A trend was seen toward decreased 30-day readmission rates with longer PCA use (P=.054). No correlation was found between 30-day readmission and any covariate studied, including age, sex, cancer type (solid vs hematologic), pain type, palliative care consult, or time from PCA discontinuation to discharge. Conclusions: This study suggests that there is longer PCA use in younger patients and those with hematologic malignancies admitted with cancer-related pain, with a trend toward decreased 30-day readmission rates in those with longer PCA use.

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Emily J. Martin, Andrew R. Bruggeman, Vinit V. Nalawade, Reith R. Sarkar, Edmund M. Qiao, Brent S. Rose and James D. Murphy

Background: Patients with advanced esophageal cancer often experience pain and dysphagia, yet the optimal palliative management remains unclear. This retrospective study evaluated outcomes and adverse effects of palliative radiotherapy (RT) compared with esophageal stenting among a cohort of U.S. veterans with metastatic esophageal cancer. Patients and Methods: We identified 1,957 veterans in the United States with metastatic esophageal cancer who received palliative RT to the esophagus or esophageal stenting, and assessed the risks of severe adverse effects, including esophageal fistula formation, perforation, obstruction, hemorrhage, and esophagitis. We determined palliative efficacy by evaluating pain and dysphagia scores before and after intervention. Multivariable analyses were used to control for potential confounding factors. Results: In our cohort, 1,593 patients underwent RT and 364 underwent esophageal stenting. The cumulative incidence of any severe adverse effect at 6 months was higher among patients who received stents compared with those who received RT (21.7% vs 12.4%; P<.0010). In multivariable analysis, patients who received stents had an increased risk of any severe adverse effect, including fistula, perforation, and hemorrhage (all P<.0500). Multivariable analysis also showed that, compared with stenting, RT was associated with more rapid and durable pain relief (P<.0010) with no difference in relief of dysphagia over time when accounting for pretreatment dysphagia scores (P=.1029). Conclusions: Compared with esophageal stenting, RT was associated with a decreased risk of adverse effects, greater pain relief, and equivalent relief of moderate to severe dysphagia over time. Unmeasured patient- or tumor-related factors could have influenced the choice of intervention, thereby impacting our study outcomes. To our knowledge, this is the largest study to date analyzing the comparative risks and benefits of palliative RT and esophageal stenting among patients with metastatic esophageal cancer.

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Lucas K. Vitzthum, Chris Straka, Reith R. Sarkar, Rana McKay, J. Michael Randall, Ajay Sandhu, James D. Murphy and Brent S. Rose

Background: The addition of androgen deprivation therapy to radiation therapy (RT) improves survival in patients with intermediate- and high-risk prostate cancer (PCa), but it is not known whether combined androgen blockade (CAB) with a gonadotropin-releasing hormone agonist (GnRH-A) and a nonsteroidal antiandrogen improves survival over GnRH-A monotherapy. Methods: This study evaluated patients with intermediate- and high-risk PCa diagnosed in 2001 through 2015 who underwent RT with either GnRH-A alone or CAB using the Veterans Affairs Informatics and Computing Infrastructure. Associations between CAB and prostate cancer–specific mortality (PCSM) and overall survival (OS) were determined using multivariable regression with Fine-Gray and multivariable Cox proportional hazards models, respectively. For a positive control, the effect of long-term versus short-term GnRH-A therapy was tested. Results: The cohort included 8,423 men (GnRH-A, 4,529; CAB, 3,894) with a median follow-up of 5.9 years. There were 1,861 deaths, including 349 resulting from PCa. The unadjusted cumulative incidences of PCSM at 10 years were 5.9% and 6.9% for those receiving GnRH-A and CAB, respectively (P=.16). Compared with GnRH-A alone, CAB was not associated with a significant difference in covariate-adjusted PCSM (subdistribution hazard ratio [SHR], 1.05; 95% CI, 0.85–1.30) or OS (hazard ratio, 1.02; 95% CI, 0.93–1.12). For high-risk patients, long-term versus short-term GnRH-A therapy was associated with improved PCSM (SHR, 0.74; 95% CI, 0.57–0.95) and OS (SHR, 0.82; 95% CI, 0.73–0.93). Conclusions: In men receiving definitive RT for intermediate- or high-risk PCa, CAB was not associated with improved PCSM or OS compared with GnRH alone.

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Al B. Benson III, Alan P. Venook, Mahmoud M. Al-Hawary, Lynette Cederquist, Yi-Jen Chen, Kristen K. Ciombor, Stacey Cohen, Harry S. Cooper, Dustin Deming, Paul F. Engstrom, Jean L. Grem, Axel Grothey, Howard S. Hochster, Sarah Hoffe, Steven Hunt, Ahmed Kamel, Natalie Kirilcuk, Smitha Krishnamurthi, Wells A. Messersmith, Jeffrey Meyerhardt, Mary F. Mulcahy, James D. Murphy, Steven Nurkin, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Elena M. Stoffel, Eden Stotsky-Himelfarb, Christopher G. Willett, Evan Wuthrick, Kristina M. Gregory and Deborah A. Freedman-Cass

The NCCN Guidelines for Anal Carcinoma provide recommendations for the management of patients with squamous cell carcinoma of the anal canal or perianal region. Primary treatment of anal cancer usually includes chemoradiation, although certain lesions can be treated with margin-negative local excision alone. Disease surveillance is recommended for all patients with anal carcinoma because additional curative-intent treatment is possible. A multidisciplinary approach including physicians from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology is essential for optimal patient care.

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Al B. Benson III, Alan P. Venook, Mahmoud M. Al-Hawary, Lynette Cederquist, Yi-Jen Chen, Kristen K. Ciombor, Stacey Cohen, Harry S. Cooper, Dustin Deming, Paul F. Engstrom, Jean L. Grem, Axel Grothey, Howard S. Hochster, Sarah Hoffe, Steven Hunt, Ahmed Kamel, Natalie Kirilcuk, Smitha Krishnamurthi, Wells A. Messersmith, Jeffrey Meyerhardt, Mary F. Mulcahy, James D. Murphy, Steven Nurkin, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Elena M. Stoffel, Eden Stotsky-Himelfarb, Christopher G. Willett, Evan Wuthrick, Kristina M. Gregory, Lisa Gurski and Deborah A. Freedman-Cass

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Rectal Cancer address diagnosis, staging, surgical management, perioperative treatment, management of recurrent and metastatic disease, disease surveillance, and survivorship in patients with rectal cancer. This portion of the guidelines focuses on the management of localized disease, which involves careful patient selection for curative-intent treatment options that sequence multimodality therapy usually comprised of chemotherapy, radiation, and surgical resection.

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Al B. Benson III, Alan P. Venook, Lynette Cederquist, Emily Chan, Yi-Jen Chen, Harry S. Cooper, Dustin Deming, Paul F. Engstrom, Peter C. Enzinger, Alessandro Fichera, Jean L. Grem, Axel Grothey, Howard S. Hochster, Sarah Hoffe, Steven Hunt, Ahmed Kamel, Natalie Kirilcuk, Smitha Krishnamurthi, Wells A. Messersmith, Mary F. Mulcahy, James D. Murphy, Steven Nurkin, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Elena M. Stoffel, Eden Stotsky-Himelfarb, Christopher G. Willett, Christina S. Wu, Kristina M. Gregory and Deborah Freedman-Cass

This portion of the NCCN Guidelines for Colon Cancer focuses on the use of systemic therapy in metastatic disease. Considerations for treatment selection among 32 different monotherapies and combination regimens in up to 7 lines of therapy have included treatment history, extent of disease, goals of treatment, the efficacy and toxicity profiles of the regimens, KRAS/NRAS mutational status, and patient comorbidities and preferences. Location of the primary tumor, the BRAF mutation status, and tumor microsatellite stability should also be considered in treatment decisions.

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Al B. Benson III, Alan P. Venook, Tanios Bekaii-Saab, Emily Chan, Yi-Jen Chen, Harry S. Cooper, Paul F. Engstrom, Peter C. Enzinger, Moon J. Fenton, Charles S. Fuchs, Jean L. Grem, Steven Hunt, Ahmed Kamel, Lucille A. Leong, Edward Lin, Wells Messersmith, Mary F. Mulcahy, James D. Murphy, Steven Nurkin, Eric Rohren, David P. Ryan, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Elena M. Stoffel, Eden Stotsky-Himelfarb, Christopher G. Willett, Kristina M. Gregory and Deborah A. Freedman-Cass

The NCCN Guidelines for Colon Cancer address diagnosis, pathologic staging, surgical management, perioperative treatment, posttreatment surveillance, management of recurrent and metastatic disease,and survivorship. This portion of the guidelines focuses on the use of systemic therapy in metastatic disease. The management of metastatic colorectal cancer involves a continuum of care in which patients are exposed sequentially to a variety of active agents, either in combinations or as single agents. Choice of therapy is based on the goals of treatment, the type and timing of prior therapy, the different efficacy and toxicity profiles of the drugs, the mutational status of the tumor, and patient preference.