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Siddhartha Yadav, Sri Harsha Tella, Anuhya Kommalapati, Kristin Mara, Kritika Prasai, Mohamed Hamdy Mady, Mohamed Hassan, Rory L. Smoot, Sean P. Cleary, Mark J. Truty, Lewis R. Roberts and Amit Mahipal
Background: Current staging systems for gallbladder cancer (GBC) are primarily based on surgical pathology and therefore are not relevant for unresectable patients and those undergoing neoadjuvant chemotherapy. Methods: Patients with a confirmed diagnosis of GBC managed at a tertiary referral center (2000–2016) were included. Independent predictors of overall survival (OS) were identified using multivariable analysis (MVA). A combination of these variables was then assessed to identify a set of factors that provided maximal accuracy in predicting OS, and a nomogram and a new staging system were created based on these factors. Harrell’s C-statistic was calculated to evaluate the predictive accuracy of the nomogram and staging system. Results: A total of 528 patients were included in the final analysis. On MVA, factors predictive of poor OS were older age, ECOG performance status, hemoglobin level <9 g/dL, presence of metastases, and alkaline phosphatase (ALP) level >200 U/L. A nomogram and a 4-tier staging system predictive of OS were created using age at diagnosis, ECOG status, tumor size, presence or absence of metastasis, and ALP level. The C-statistic for this novel staging system was 0.71 compared with 0.69 for the TNM staging system (P=.08). In patients who did not undergo surgery, the C-statistics of the novel and TNM staging systems were 0.60 and 0.51, respectively (P<.001). Conclusions: We created a novel, clinically based staging system for GBC based on nonoperative information at the time of diagnosis that was superior to the TNM staging system in predicting OS in patients who did not undergo surgery, and that performed on par with TNM staging in surgical patients.
Luke R.G. Pike, Trevor J. Royce, Amandeep R. Mahal, Daniel W. Kim, William L. Hwang, Brandon A. Mahal and Nina N. Sanford
Background: Socioeconomic factors affecting outcomes of HPV-associated squamous cell carcinoma of the head and neck (SCCHN) are poorly characterized. Methods: A custom SEER database identified adult patients with primary nonmetastatic SCCHN and known HPV status diagnosed in 2013 through 2014. Multivariable logistic regression defined associations between patient characteristics and HPV status, with adjusted odds ratios (aORs) and 95% confidence intervals reported. Fine-Gray competing risks regression estimated adjusted hazard ratios (aHRs) and 95% confidence intervals for cancer-specific mortality (CSM), including a disease subsite * HPV status * race interaction term. Results: A total of 4,735 patients with nonmetastatic SCCHN and known HPV status were identified. HPV-associated SCCHN was positively associated with an oropharyngeal primary, male sex, and higher education, and negatively associated with uninsured status, single marital status, and nonwhite race (P≤.01 for all). For HPV-positive oropharyngeal SCCHN, white race was associated with lower CSM (aHR, 0.55; 95% CI, 0.34–0.88; P=.01) and uninsured status was associated with higher CSM (aHR, 3.12; 95% CI, 1.19–8.13; P=.02). These associations were not observed in HPV-negative or nonoropharynx SCCHN. Accordingly, there was a statistically significant disease subsite * HPV status * race interaction (Pinteraction<.001). Conclusions: Nonwhite race and uninsured status were associated with worse CSM in HPV-positive oropharyngeal SCCHN, whereas no such associations were observed in HPV-negative or nonoropharyngeal SCCHN. These results suggest that despite having clinically favorable disease, nonwhite patients with HPV-positive oropharyngeal SCCHN have worse outcomes than their white peers. Further work is needed to understand and reduce socioeconomic disparities in SCCHN.
Joseph A. Greer, Jamie M. Jacobs, Nicole Pensak, Lauren E. Nisotel, Joel N. Fishbein, James J. MacDonald, Molly E. Ream, Emily A. Walsh, Joanne Buzaglo, Alona Muzikansky, Inga T. Lennes, Steven A. Safren, William F. Pirl and Jennifer S. Temel
Background: Patients with cancer are increasingly prescribed oral therapies, bearing greater responsibility for self-management of treatment adherence and adverse events. We conducted a randomized trial to test the use of a smartphone mobile app to improve symptoms and adherence to oral cancer therapy. Materials and Methods: From February 18, 2015, through December 31, 2016, 181 patients with diverse cancers who were prescribed oral therapy were randomized to receive either the smartphone mobile app or standard care. The mobile app included a medication plan with reminders, a symptom-reporting module, and patient education. Primary outcomes were adherence (per electronic pill caps), symptom burden (per MD Anderson Symptom Inventory), and quality of life (per the Functional Assessment of Cancer Therapy–General). Participants also completed self-report measures of medication adherence, anxiety and depression symptoms, social support, quality of care, and healthcare utilization. Linear regression was used to assess intervention effects on adherence and change in self-report outcomes from baseline to week 12, controlling for baseline scores and social support. Results: Study groups did not differ across any outcome measure, with an overall mean adherence of 78.81% (SD, 26.66%) per electronic pill caps. However, moderation analyses showed that intervention effects on the primary adherence measure varied by baseline self-reported adherence and anxiety symptoms. Specifically, adherence rates per electronic pill caps were higher in patients randomized to the mobile app versus standard care within the subsamples of patients who reported baseline adherence problems (mean difference, –22.30%; 95% CI, –42.82 to –1.78; P=.034) and elevated anxiety (mean difference, –16.08%; 95% CI, –31.74 to –0.41; P=.044). Conclusions: Although the mobile app may not improve outcomes for all patients prescribed oral cancer therapy, the intervention may be beneficial for those with certain risk factors, such as difficulties with adherence or anxiety.
Nina N. Sanford, David J. Sher, Xiaohan Xu, Chul Ahn, Anthony V. D’Amico, Ayal A. Aizer and Brandon A. Mahal
Background: Alcohol use is an established risk factor for several malignancies and is associated with adverse oncologic outcomes among individuals diagnosed with cancer. The prevalence and patterns of alcohol use among cancer survivors are poorly described. Methods: We used the National Health Interview Survey from 2000 to 2017 to examine alcohol drinking prevalence and patterns among adults reporting a cancer diagnosis. Multivariable logistic regression was used to define the association between demographic and socioeconomic variables and odds of self-reporting as a current drinker, exceeding moderate drinking limits, and engaging in binge drinking. The association between specific cancer type and odds of drinking were assessed. Results: Among 34,080 survey participants with a known cancer diagnosis, 56.5% self-reported as current drinkers, including 34.9% who exceeded moderate drinking limits and 21.0% who engaged in binge drinking. Younger age, smoking history, and more recent survey period were associated with higher odds of current, exceeding moderate, and binge drinking (P<.001 for all, except P=.008 for excess drinking). Similar associations persisted when the cohort was limited to 20,828 cancer survivors diagnosed ≥5 years before survey administration. Diagnoses of melanoma and cervical, head and neck, and testicular cancers were associated with higher odds of binge drinking (P<.05 for all) compared with other cancer diagnoses. Conclusions: Most cancer survivors self-report as current alcohol drinkers, including a subset who seem to engage in excessive drinking behaviors. Given that alcohol intake has implications for cancer prevention and is a potentially modifiable risk factor for cancer-specific outcomes, the high prevalence of alcohol use among cancer survivors highlights the need for public health strategies aimed at the reduction of alcohol consumption.
Carlotta Palumbo, Francesco A. Mistretta, Sophie Knipper, Angela Pecoraro, Zhe Tian, Shahrokh F. Shariat, Fred Saad, Claudio Simeone, Alberto Briganti, Alessandro Antonelli and Pierre I. Karakiewicz
Background: Conditional survival (CS) may reveal important differences in cancer-specific mortality (CSM) among patients with nonmetastatic renal cell carcinoma (nmRCC). This study assessed CS according to T and N stages in patients treated surgically for nmRCC. Patients and Methods: Within the SEER database (2001–2015), all patients with nmRCC treated with either partial or radical nephrectomy were identified. CSM-free estimates according to T and N stage and substage groupings (pT1aN0–pT4N0 and pTanyN1) and multivariable Cox regression models with adjustment for Fuhrman grade and histologic subtype were assessed. Results: According to T and N stage and substage groupings, the following patients were included in the study: 35,966 (46.2%) with pT1aN0 disease; 18,858 (24.2%) with pT1bN0; 5,977 (7.7%) with pT2aN0; 2,511 (3.2%) with pT2bN0; 11,839 (15.2%) with pT3aN0; 1,037 (1.3%) with pT3b–cN0; 402 (0.5%) with pT4N0; and 1,302 (1.7%) with pTanyN1. Conditional CSM-free survival estimates were 98.2% at 1 year versus 98.0% at 10 years of event-free follow-up for patients with pT1aN0 disease, relative to baseline. Conversely, pT4N0/pTanyN1 conditional CSM-free survival estimates were 55.8% at 1 year versus 77.9% at 8 years of event-free follow-up. Attrition due to mortality was highest in patients with pT4N0/pTanyN1 disease. In multivariable Cox regression analyses, T stage, tumor grade, and histologic subtype represented independent predictors, but no interactions were identified. Conclusions: Tumor stage and its substages represent extremely important determinants of prognosis after lengthy event-free follow-up. The recorded observations have critical importance for physicians regarding patient follow-up and counseling.
Claire de Oliveira, Joyce Cheng, Kelvin Chan, Craig C. Earle, Murray Krahn and Nicole Mittmann
Background: Although high-cost (HC) patients make up a small proportion of patients, they account for most health system costs. However, little is known about HC patients with cancer or whether some of their care could potentially be prevented. This analysis sought to characterize HC patients with cancer and quantify the costs of preventable acute care (emergency department visits and inpatient hospitalizations). Methods: This analysis examined a population-based sample of all HC patients in Ontario in 2013. HC patients were defined as those above the 90th percentile of the cost distribution; all other patients were defined as non–high-cost (NHC). Patients with cancer were identified through the Ontario Cancer Registry. Sociodemographic and clinical characteristics were examined and the costs of preventable acute care for both groups by category of visit/condition were estimated using validated algorithms. Results: Compared with NHC patients with cancer (n=369,422), HC patients with cancer (n=187,770) were older (mean age 70 vs 65 years), more likely to live in low-income neighborhoods (19% vs 16%), sicker, and more likely to live in long-term care homes (8% vs 0%). Although most patients from both cohorts tended to be diagnosed with breast, prostate, or colorectal cancer, those with multiple myeloma or pancreatic or liver cancers were overrepresented among the HC group. Moreover, HC patients were more likely to have advanced cancer at diagnosis and be in the initial or terminal phase of treatment compared with NHC patients. Among HC patients with cancer, 9% of spending stemmed from potentially preventable/avoidable acute care, whereas for NHC patients, this spending was approximately 30%. Conclusions: HC patients with cancer are a unique subpopulation. Given the type of care they receive, there seems to be limited scope to prevent acute care spending among this patient group. To reduce costs, other strategies, such as making hospital care more efficient and generating less costly encounters involving chemotherapy, should be explored.
Daniel Boakye, Viola Walter, Lina Jansen, Uwe M. Martens, Jenny Chang-Claude, Michael Hoffmeister and Hermann Brenner
Background: Comorbidities and old age independently compromise prognosis of patients with colorectal cancer (CRC). The impact of comorbidities could thus be considered as conveying worse prognosis already at younger ages, but evidence is lacking on how much worsening of prognosis with age is advanced to younger ages in comorbid versus noncomorbid patients. We aimed to quantify, for the first time, the impact of comorbidities on CRC prognosis in “age advancement” of worse prognosis. Methods: A total of 4,602 patients aged ≥30 years who were diagnosed with CRC in 2003 through 2014 were recruited into a population-based study in the Rhine-Neckar region of Germany and observed over a median period of 5.1 years. Overall comorbidity was quantified using the Charlson comorbidity index (CCI). Hazard ratios and age advancement periods (AAPs) for comorbidities were calculated from multivariable Cox proportional hazards models for relevant survival outcomes. Results: Hazard ratios for CCI scores 1, 2, and ≥3 compared with CCI 0 were 1.25, 1.53, and 2.30 (P<.001) for overall survival and 1.20, 1.48, and 2.03 (P<.001) for disease-free survival, respectively. Corresponding AAP estimates for CCI scores 1, 2, and ≥3 were 5.0 (95% CI, 1.9–8.1), 9.7 (95% CI, 6.1–13.3), and 18.9 years (95% CI, 14.4–23.3) for overall survival and 5.5 (95% CI, 1.5–9.5), 11.7 (95% CI, 7.0–16.4), and 21.0 years (95% CI, 15.1–26.9) for disease-free survival. Particularly pronounced effects of comorbidity on CRC prognosis were observed in patients with stage I–III CRC. Conclusions: Comorbidities advance the commonly observed deterioration of prognosis with age by many years, meaning that at substantially younger ages, comorbid patients with CRC experience survival rates comparable to those of older patients without comorbidity. This first derivation of AAPs may enhance the empirical basis for treatment decisions in patients with comorbidities and highlight the need to incorporate comorbidities into prognostic nomograms for CRC.