TGFß in pancreas and colorectal cancer: opportunities to overcome therapeutic resistance.

TGFß is a pleiotropic signaling pathway, which plays a pivotal role in regulating a multitude of cellular functions. TGFß has a dual role in cell regulation where it induces growth inhibition and cell death; however, it can switch to a growth-promoting state under cancerous conditions. TGFß is upregulated in CRC and pancreatic cancer, altering the tumor microenvironment, immune system, and promoting a mesenchymal state. The upregulation of TGFß in certain cancers leads to resistance to immunotherapy, and attempts to inhibit TGFß expression have led to reduced therapeutic resistance when combined with chemo- and immunotherapy. Here, we review the current TGFß inhibitor drugs in clinical trials for pancreatic and colorectal cancer, with the goal of uncovering advances in improving clinical efficacy for TGFß combinational treatments in patients. Furthermore, we discuss the relevance of alterations in TGFß signaling and germline variants in the context of personalizing treatment for patients who show lack of response to current therapeutics.

Immune Checkpoint Inhibitors and Their Cardiovascular Adverse Effects.

Immune checkpoint inhibitors (ICIs) have reshaped and have become a well-established treatment modality for multiple advanced-stage malignancies. ICIs block the immune system regulatory checkpoints, namely CTLA-4 and PD-1/PDL1, which provokes excess immune response against self-antigens. Immune modulation with ICIs can result in diverse immune-related adverse events targeting organ systems. Several cases of ICI-related cardiotoxicity were reported, while the actual incidence was likely underestimated due to heterogeneous clinical presentation. These include, but are not limited to, myocarditis, pericarditis, atherosclerosis, and arrhythmia. EKG, Troponin, Echocardiogram (TTE), and Cardiac MRI (CMRI) are indispensable diagnostic tools to aid in the management of cardiac adverse effects. Herein, we review the ICI-mediated cardiovascular adverse events, diagnosis, treatment strategies, and reintroduction of ICIs post-cardiotoxicity.

Advances in understanding and management of high-grade pancreatic neuroendocrine neoplasm: a comprehensive review.

High-grade (HG) pancreatic neuroendocrine neoplasms (PAN-NENs) are aggressive and have a poor prognosis. Yet, our understanding and treatment approaches for these tumors have rapidly evolved in the past decade, despite a lack of prospective and randomized trials. It is essential to differentiate grade 3 (G3) neuroendocrine tumors (NETs) from neuroendocrine carcinomas (NECs) due to their different prognostic and treatment implications. The molecular landscape of HG PAN-NENs is complex, with mutations in key cancer-related genes, extensive genomic rearrangements, and chromosomal instability. Advanced studies have provided insights into the significant genetic heterogeneity of HG PAN-NENs and potential therapeutic targets. Several therapeutic strategies have emerged from molecular characterization studies. These include agents targeting the mammalian target of rapamycin (mTOR) pathway, DNA repair pathways, and epigenetic modifiers. Moreover, high programmed cell death ligand 1 (PD-L1) expression in some tumors indicates potential for immunotherapy. However, many challenges remain, with a deeper understanding of the genetic and epigenetic alterations in these tumors necessary to develop novel therapeutic strategies and improve patient outcomes. Treatment strategies for HG PAN-NENs vary. Looking to the future, many clinical trials are exploring novel therapies or combinations of known therapies to improve outcomes. It is evident that understanding the molecular landscape of PAN-NECs, alongside personalized therapeutic strategies, is crucial to developing effective treatment options and improving patient outcomes. In this discourse, our emphasis will be on the molecular landscape and available treatment strategies for HG PAN-NECs.

Role of chemoradiation in gallbladder cancer-a single institution retrospective analysis.

Background: Gallbladder cancer is one of the highest fatal malignancy. We conducted a retrospective analysis to study the outcomes of gallbladder malignancy in an academic care setting. Methods: Data was collected retrospectively on patients treated at University of Alabama at Birmingham between January 2005 and June 2015 from the electronic medical record using a standardized data collection tool (Redcap). We evaluated for predictors of overall survival (OS) and progression-free survival (PFS). Results: Of the 93 patients in this study, 66.7% were female. Adjuvant chemotherapy (CT) was given to 11% and adjuvant chemoradiation (CRT) to 14%. On multivariate analysis, albumin >3.5 g/dL, uninvolved margins, absence of lymphovascular invasion, and peri-neural invasion were independent predictors of OS and PFS. The overall median survival time was 24.3 months with a 5-year survival rate at 23.7%. Surgery with CRT for the full cohort had a median OS of 54.4 vs. 15.6 months (P=0.0048) compared to surgery CT alone. The OS in stage 3-4 patients with surgery alone vs. surgery & CT was 5.5 vs. 28.7 months, respectively (P=0.0061). The PFS for the same group was 4.6 vs. 17.5 months (P=0.0052). Conclusions: The dismal survival rates of gallbladder cancer made adjuvant therapy (CT or CRT) critically important. Concurrent CRT needs to be evaluated in randomized clinical trials for potential improvement in clinical outcomes compared to currently approved standard of care, adjuvant CT alone.

Predictive Value of MUC5AC Signature in Pancreatic Ductal Adenocarcinoma: A Hypothesis Based on Preclinical Evidence.

Mucin 5AC (MUC5AC) glycoprotein plays a crucial role in carcinogenesis and drug sensitivity in pancreatic ductal adenocarcinoma (PDAC), both individually and in combination with other mucins. Its function and localization are glycoform-specific. The immature isoform (detected by the CLH2 monoclonal antibody, or mab) is usually in the perinuclear (cytoplasmic) region, while the mature (45 M1, 2-11, Nd2) variants are in apical and extracellular regions. There is preclinical evidence suggesting that mature MUC5AC has prognostic and predictive (response to treatment) value. However, these findings were not validated in clinical studies. We propose a MUC5AC signature with three components of MUC5AC-localization, variant composition, and intensity-suggesting a reliable marker in combination of variants than with individual MUC5AC variants alone. We also postulate a theory to explain the occurrence of different MUC5AC variants in abnormal pancreatic lesions (benign, precancerous, and cancerous). We also analyzed the effect of mature MUC5AC on sensitivity to drugs often used in PDAC management, such as gemcitabine, 5-fluorouracil, oxaliplatin, irinotecan, cisplatin, and paclitaxel. We found preliminary evidence of its predictive value, but there is a need for large-scale studies to validate them.

Impact of the COVID-19 Pandemic on Management of Patients with Metastatic Pancreatic Ductal Adenocarcinoma in the United States.

BACKGROUND: The purpose of this study was to understand how the COVID-19 pandemic has affected health care patterns and outcomes for patients diagnosed with metastatic pancreatic ductal adenocarcinoma (mPDAC) in 2020 compared with those diagnosed with mPDAC in 2019. PATIENTS AND METHODS: We used the Flatiron Health database to identify adults diagnosed with mPDAC from March 1 to September 30, 2019 (pre-COVID-19 cohort) and March 1 to September 30, 2020 (post-COVID-19 cohort). Between-cohort comparisons included demographic and clinical characteristics and year-over-year data for diagnosis of mPDAC, newly treated patients, time to and types of first-line therapy, and adverse events (AEs) during first-line therapy. Overall survival (OS) and milestone survival rates were evaluated. Kaplan-Meier methods were used to assess OS. RESULTS: Pre-COVID-19 (n = 923) and post-COVID-19 (n = 796) cohorts had similar baseline demographic characteristics. A smaller proportion of patients in the pre-COVID-19 cohort were initially diagnosed with stage IV disease versus the post-COVID-19 cohort (62.2% vs 69.7%). Between 2019 and 2020, there was a 13.8% decrease in diagnosis of mPDAC and a 13.0% decrease in newly treated patients. Median (interquartile range) times to first-line treatment were similar (21 [13-40] and 19 [12-32] days). Median OS (months) was significantly longer in the pre-COVID-19 cohort (8·4 [95% CI: 7·5, 9·0]) versus the post-COVID-19 cohort (6·1 [95% CI: 5·4, 6·9]; P < .001). Survival rates were higher in the pre-COVID-19 versus post-COVID-19 cohorts. CONCLUSIONS: During the pandemic, patients were initially diagnosed with PDAC at more advanced stages. While patients in both cohorts appeared to receive similar care, survival outcomes were adversely affected.

Use of Single-Item Self-Rated Health Measure to Identify Frailty and Geriatric Assessment-Identified Impairments Among Older Adults with Cancer.

BACKGROUND: Poor self-rated health (SRH) is a known predictor of frailty and mortality in the general population; however, its role among older adults with cancer is unknown. We evaluated the role of SRH as a potential screening tool to identify frailty and geriatric assessment (GA)-identified impairments. MATERIALS AND METHODS: Adults ≥60 years diagnosed with cancer in the UAB Cancer & Aging Resilience Evaluation (CARE) registry underwent a GA at the time of initial consultation. We measured SRH using a single-item from the Patient-Reported Outcomes Measurement Information System global health scale and dichotomized responses as poor (poor, fair) and good (good, very good, and excellent). We evaluated the diagnostic performance of SRH in measuring frailty, and GA impairment (≥2 deficits among a set of seven GA domains). We examined the impact of SRH with survival using a Cox model adjusting for confounders, exploring the mediating role of frailty. RESULTS: Six hundred and three older adults with cancer were included, with a median age of 69 years. Overall, 45% (n = 274) reported poor SRH. Poor SRH demonstrated high sensitivity and specificity for identifying frailty (85% and 78%, respectively) and GA impairment (75% and 78%, respectively). In a Cox regression model, poor SRH was associated with inferior survival (HR = 2.26; 95% CI 1.60-3.18) after adjusting for confounders; frailty mediated 69% of this observed relationship. CONCLUSION: Self-rated health may be used as a screening tool to identify older adults with cancer with frailty and GA impairments. Poor SRH is associated with inferior survival, which is mediated by frailty.

Metastatic Alveolar Rhabdomyosarcoma with Extensive Bone Marrow Replacement in an Older Adult.

Rhabdomyosarcoma is extremely rare in adults. Metastatic rhabdomyosarcoma can resemble other malignancies, which can delay diagnosis and prompt treatment. This case illustrates an example of metastatic alveolar rhabdomyosarcoma with concurrent bone marrow infiltration. A 67-year-old woman presented with epistaxis and diffuse bone pain. She developed progressive thrombocytopenia requiring platelet transfusions. The patient was initially thought to have leukemia. She was found to have a large sinonasal mass with extensive metastatic disease and bone marrow infiltration. The patient was ultimately diagnosed with metastatic alveolar rhabdomyosarcoma. She was started on chemotherapy with vincristine, actinomycin, and cyclophosphamide. Unfortunately, she died prior to discharge home. Alveolar rhabdomyosarcoma can resemble a primary bone marrow malignancy when it infiltrates the bone marrow. Further investigation is needed to clarify its clinical behavior and expedite diagnosis and treatment.

Association Between Chronologic Age and Geriatric Assessment-Identified Impairments: Findings From the CARE Registry.

BACKGROUND: The NCCN Guidelines for Older Adult Oncology recommend that, when possible, older adults with cancer undergo a geriatric assessment (GA) to provide a comprehensive health appraisal to guide interventions and appropriate treatment selection. However, the association of age with GA-identified impairments (GA impairments) remains understudied and the appropriate age cutoff for using the GA remains unknown. PATIENTS AND METHODS: We designed a cross-sectional study using the Cancer and Aging Resilience Evaluation (CARE) registry of older adults with cancer. We included adults aged ≥60 years diagnosed with gastrointestinal malignancy who underwent a patient-reported GA prior to their initial consultation at the gastrointestinal oncology clinic. We noted the presence of GA impairments and frailty using Rockwood's deficit accumulation approach. We studied the relation between chronologic age and GA impairments/frailty using Spearman rank correlation and chi-square tests of trend. RESULTS: We identified 455 eligible older adults aged ≥60 years with gastrointestinal malignancies; the median age was 68 years (range, 64-74 years) and colorectal (33%) and pancreatic (24%) cancers were the most common cancer type. The correlation between chronologic age and number of geriatric impairments was weak and did not reach statistical significance (Spearman ρ, 0.07; P=.16). Furthermore, the prevalence of domain-specific impairments or frailty was comparable across the 3 age groups (60-64 years, 65-74 years, ≥75 years) with the exception of comorbidity burden. Notably, 61% of patients aged 60 to 64 years had ≥2 GA impairments and 35% had evidence of frailty, which was comparable to patients aged 65 to 74 years (66% and 36%, respectively) and ≥75 years (70% and 40%, respectively). CONCLUSIONS: Using chronologic age alone to identify which patients may benefit from GA is problematic. Future studies should identify screening tools that may identify patients at high risk of frailty and GA impairments.

Efficacy and tolerability of the combination of nano-liposomal irinotecan and 5-fluorouracil/leucovorin in advanced pancreatic adenocarcinoma: post-approval clinic experience.

BACKGROUND: Nano-liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) is the regimen of choice in the 2nd line setting for advanced pancreatic adenocarcinoma (PAC). However, real-world data is limited. Our objectives were to elicit the real-word effectiveness and safety of this combination as an advanced line of therapy in pancreatic cancer patients and analyze the impact of prior lines of therapy on survival outcomes with this regimen. METHODS: We conducted a retrospective cohort study of 58 patients with locally advanced unresectable or metastatic PAC, who were treated with at least one dose of nal-IRI + 5-FU/LV following cancer progression on prior therapies between August 2015 and December 2018 at the Kansas University Medical Center (KUMC) and University of Alabama at Birmingham (UAB). RESULTS: Median OS was 5.4 (range, 4.2-7) months. Disease control rate (DCR) was highest (84%) for patients given nal-IRI + 5-FU/LV as 2nd line agent after progression on a 1st line gemcitabine-based regimen. However, no significant survival difference was observed between those given nal-IRI + 5-FU/LV after 1st line or beyond the 2nd line (P=0.17). Among those given nal-IRI + 5-FU/LV as 2nd line, use of gemcitabine-inclusive chemotherapy as the 1st line agent did not impact survival (P=0.68). Prior irinotecan exposure and baseline CA 19-9 level did not affect the overall survival (OS) but patients with a higher CA 19-9 level had a significant risk of progression (HR =3.2, P=0.02). Grade 3/4 toxicities were reported in only 19% patients. CONCLUSIONS: Our report suggests that nal-IRI + 5-FU/LV offers a modest survival benefit with a tolerable safety profile as an advanced line of treatment in patients with advanced PAC.

Predictors of Survival among Early Onset Pancreatic Adenocarcinoma Patients A Tertiary Care Center Experience.

OBJECTIVES: To characterize clinical features of early onset pancreatic adenocarcinoma (EOPC) patients and explore prognostic factors affecting their survival. Methods: Retrospective review of 95 patients, 45 years old, who presented to the University of Alabama Hospitals with pancreatic adenocarcinoma from September 1998 to June 2018. Results: Median survival time was 12.9 months for all patients. Obesity, male gender, race, and tumor location were not associated with survival. Smoking at time of diagnosis increased risk of death by three folds (HR 3.05, 95% CI, 1.45 - 6.40). Risk of death decreased by 64% (HR 0.36, 95% CI, 0.16 - 0.78) if patients underwent surgery. Median survival was 119.5 months for stage I, 29.9 months for stage II, 23.23 months for stage III, and 6.3 months for stage IV patients. The survival benefit of chemotherapy was only significant with the use of FOLFIRINOX. Conclusions: Some established prognostic features in typical pancreatic adenocarcinoma patients are not predictive of survival in young patients. Cigarette smoking, a known risk factor for the development of EOPC, is also a significant predictor of survival in this patient population. Efforts to improve prognosis of EOPC include early detection, tobacco control, individualized treatment protocols, and studying the biological behavior.

Depression among older adults with gastrointestinal malignancies.

BACKGROUND: Depression among older adults with cancer is under recognized and under treated. This study characterizes the burden of depression in older adults with gastrointestinal (GI) malignancies prior to chemotherapy and its relationship with geriatric assessment (GA) domains, health-related quality of life (HRQOL), and self-reported healthcare utilization. METHODS: Patients ≥60 years in GI oncology clinics at UAB were asked to complete a GA entitled the Cancer & Aging Resilience Evaluation (CARE). We examined depression using the Patient-Reported Outcomes Measurement Information System (PROMIS®) Depression four-item short form; moderate/severe depression was defined by a t-score ≥ 60. Multivariate analysis was used to examine associations between those with and without moderate/severe depression. RESULTS: Of 355 included patients, 46 had mild depression (13%) and an additional 46 patients had moderate/severe depression (13%). After adjustment for age, sex, education, cancer type, and cancer stage, those who reported moderate/severe depression had a significantly increased odds of reporting falls (adjusted odds ratio [aOR] 4.01, 95% confidence interval [CI] 1.94-8.26), dependence in IADLs (aOR 7.06,CI 2.91-17.1), dependence in ADLs (aOR 6.23, CI 2.89-13.4), malnutrition (aOR 5.86, CI 2.40-14.3), frailty (aOR 13.7, CI 5.80-32.1), and fatigue (aOR 11.2, CI 3.31-37.6). Moderate/severe depression was also significantly associated with worse physical (aOR 7.58, CI 3.30-17.4) and mental (aOR 26.3, CI 10.1-68.8) HRQOL sub-scores, without significant differences in healthcare utilization. CONCLUSIONS: More than one out of eight older adults with a GI malignancy reported moderate/severe depression prior to chemotherapy, which was associated with impairments in several GA domains and HRQOL.

CAR T Cell Therapy in Pancreaticobiliary Cancers: a Focused Review of Clinical Data.

OBJECTIVE: CAR T cell therapy is an innovative approach to treat cancers in the modern era. It utilizes the application of chimeric antigen receptors targeted against specific antigens expressed by the tumor cells. Although its efficacy is established in hematological malignancies, the safety and efficacy of this therapy in solid tumors, especially pancreaticobiliary cancers, is a highly investigated aspect. A focused review of clinical data was conducted to examine the outcomes of this therapy in pancreaticobiliary cancers. METHODS: A comprehensive literature search was done on Medline and Embase databases through April 24, 2020 for studies that evaluated the outcomes of CAR T cell therapy in pancreaticobiliary cancers. RESULTS: There were six phase 1 trials, while one was phase 1/2. Some of these trials were specifically done for pancreaticobiliary cancers, while others included patients of various solid organ cancers, including pancreatic and biliary tract cancers. The target antigens for therapy in these trials included mesothelin, CD133, prostate stem cell antigen, claudin 18.2, epidermal growth factor receptor, and human epidermal growth factor receptor 2. CAR T cell therapy has shown very few grade 3 and 4 side effects. Most of the adverse events are associated with cytokine release syndrome. CONCLUSION: CAR T cell therapy has a manageable safety profile based on phase 1 studies, and efficacy assessments are currently ongoing in dose expansion and phase 2 studies.

Financial Distress Among Older Adults With Cancer.

PURPOSE: Financial distress (FD) among older adults with cancer is not well studied. We sought to characterize prevalence and factors associated with FD among older adults with cancer and the association of FD with geriatric assessment (GA) -identified deficits. PATIENTS AND METHODS: We included adults age ≥ 60 years with cancer in the University of Alabama at Birmingham Cancer and Aging Resilience Evaluation Registry who underwent GA during initial consultation with a medical oncologist before starting systemic therapy. We captured FD using a single-item question: "Do you have to pay for more medical care than you can afford?" We built multivariable models to study the impact of sociodemographic/clinical factors on FD as well as the association of FD with GA impairments. RESULTS: We identified 447 older adults with a median age of 69 years; 60% were men, 75% were White, and colorectal (26%) and pancreatic (19%) cancers were the most common. Overall, 27% (n = 121) reported having FD. Factors associated with FD included being Black (v White; odds ratio [OR], 2.26; 95% CI, 1.35 to 3.81; P = .002), being disabled/unemployed (v employed; OR, 2.60; 95% CI, 1.17 to 5.76; P = .019), and having an advanced degree (v less than high school; OR, 0.13; 95% CI, 0.03 to 0.65; P = .012). Patients with FD were more likely to report several GA impairments, including depression (OR, 2.10; 95% CI, 1.06 to 4.18; P = .034) and impaired health-related quality of life in physical (ß = -2.82; P = .014) and mental health domains (ß = -3.31; P = .002). CONCLUSION: More than a quarter of older adults with cancer reported FD at the time of initial presentation to an oncologist. Several demographic factors and GA impairments were associated with FD.

Association between Primary Perioperative CEA Ratio, Tumor Site, and Overall Survival in Patients with Colorectal Cancer.

There are differences in the incidence, clinical presentation, molecular pathogenesis, and outcome of colorectal cancer (CRC) based on tumor location. Emerging research suggests that the perioperative carcinoembryonic antigen (CEA) ratio (post-op/pre-op CEA) is a prognostic factor for CRC patients. We aimed to determine the association between CEA ratio, tumor location, and overall survival (OS) among patients with CRC. We analyzed 427 patients who underwent resection for CRC at the University of Kansas Medical Center. After excluding those without pre- or post-operative CEA data, 207 patients were classified as either high (≥0.5) or low (<0.5) ratio. Primary outcomes were as follows: (1) OS stratified by CEA ratio; (2) OS stratified by tumor location; (3) OS stratified by tumor location among those with CEA elevation > 5 ng/mL at the time of recurrence. The Kaplan-Meier method was used to estimate survival rates. The median age was 62 years (inter-quartile range 51-71), 55% were male, 41% were smokers, 71% had left-sided tumors, the median pre-operative CEA was 3.1 ng/mL (inter-quartile range (IQR) 1.5-9.7), and 57% had a CEA ratio ≥0.5. The OS rates were 65.1% and 86.3% in patients with high versus low CEA ratios, respectively (log-rank p-value = 0.045). The OS rates were 64.4% and 77.3% in patients with right-sided vs. left-sided tumors, respectively (log-rank p-value = 0.5). Among patients with CEA levels greater than 5 at the time of recurrence, the OS rates were 42.9% and 43.4% in patients with right-sided vs. left-sided tumors, respectively (log-rank p-value = 0.7). There was a significantly higher survival among patients with low CEA ratios than among those with high CEA ratios. There was no difference in OS between left- versus right-sided tumors. Among patients with CEA elevation > 5 ng/mL at the time of recurrence, there was no difference in OS between left versus right-sided tumors. These findings warrant validation in a larger cohort as our sample size was limited.

Survival Outcomes of Pancreatic Intraepithelial Neoplasm (PanIN) versus Intraductal Papillary Mucinous Neoplasm (IPMN) Associated Pancreatic Adenocarcinoma.

Pancreatic intraepithelial neoplasms (PanINs) and intraductal papillary mucinous neoplasms (IPMNs) are common pancreatic adenocarcinoma precursor lesions. However, data regarding their respective associations with survival rate and prognosis are lacking. We retrospectively evaluated 72 pancreatic adenocarcinoma tumor resection patients at the University of Kansas Hospital between August 2009 and March 2019. Patients were divided into one of two groups, PanIN or IPMN, based on the results of the surgical pathology report. We compared baseline characteristics, overall survival (OS), and progression free survival (PFS) between the two groups, as well as OS and PFS based on local or distant tumor recurrence for both groups combined. 52 patients had PanINs and 20 patients had IPMNs. Patients who had an IPMN precursor lesion had better median PFS and OS when compared to patients with PanIN precursor lesions. However, the location of tumor recurrence (local or distant) did not show a statistically significant difference in OS.

Association of malnutrition with geriatric assessment impairments and health-related quality of life among older adults with gastrointestinal malignancies.

BACKGROUND: A majority of older adults with cancer develop malnutrition; however, the implications of malnutrition among this vulnerable population are poorly understood. The goal of this study was to quantify the prevalence of nutrition related-symptoms and malnutrition among older adults with gastrointestinal (GI) malignancies and the association of malnutrition with geriatric assessment (GA) impairment, health-related quality of life (HRQoL), and health care utilization. METHODS: We performed a cross-sectional study of older adults (≥60 years) who were referred to the GI Oncology clinic at the University of Alabama at Birmingham. Participants underwent the Cancer & Aging Resilience Evaluation survey that includes the abbreviated Patient-Generated Subjective Global Assessment of nutrition. Nutrition scores were dichotomized into normal (0-5) and malnourished (≥6), and multivariate analyses adjusted for demographics, cancer type, and cancer stage were used to examine associations with GA impairment, HRQoL, and health care utilization. RESULTS: A total of 336 participants were included (men, 56.8%; women, 43.2%), with a mean age of 70 years (standard deviation, ±7.2 years) and colorectal cancer (33.6%) and pancreatic cancer (24.4%) being the most common diagnoses. Overall, 52.1% of participants were identified as malnourished. Malnutrition was associated with a higher prevalence of several GA impairments, including 1 or more falls (adjusted odds ratio [aOR], 2.1), instrumental activities of daily living impairment (aOR, 4.1), and frailty (aOR, 8.2). Malnutrition was also associated with impaired HRQoL domains; both physical (aOR, 8.7) and mental (aOR, 5.0), and prior hospitalizations (aOR, 2.2). CONCLUSION: We found a high prevalence of malnutrition among older adults with GI malignancies that was associated with increased GA impairments, reduced HRQoL, and increased health care utilization.

The Clinical Benefit of Adjuvant Therapy in Long-Term Survival of Early-Stage Ampullary Carcinoma: A Single Institutional Experience.

BACKGROUND: The role of adjuvant chemotherapy (CT) or combination chemoradiation (CRT) remains uncertain for ampullary carcinoma (AC). In this analysis, we reviewed our institution's experience with early-stage AC. METHODS: AC patients who had definitive surgical intervention at the University of Alabama, Birmingham, between 2005 and 2015, were identified. Clinicopathologic factors and disease statuses were obtained from chart review. The univariate Cox proportional hazard model was conducted for evaluating the parameters associated with overall survival (OS). Kaplan-Meier method and log-rank method were used to compare the time-to-events. We estimated the survival for the patients who had definitive surgery (pancreaticoduodenectomy (PD) or ampullectomy), and followed them up with assessing the influence of adjuvant treatment (chemoradiotherapy or CT) alone on the survival in the early-stage (stage I/II) AC. RESULTS: A total of 63 patients had definitive surgery. The median OS and progression-free survival (PFS) for all the patients who had definitive surgery were 40.5 months and 28 months, respectively. Adjuvant treatment was administered in 60% of patients with early-stage (stage I/II) AC (CT 36% and CRT 24%), while 22% were on surveillance post surgery. The pathological stage ≥ 2, Lymph node (LN) metastasis, peri-nodal extension (PNE) and peri-pancreatic extension (PPE) were found to be the determinants for poor OS and PFS by univariate analysis. Multiple Cox regression of these variables showed a significant influence of PPE and pathological staging on the OS and PFS, respectively. In the early-stage AC with no high-risk features, adjuvant therapy did not improve the survival over surgery alone (40.5 vs. 51.7 months, P = 0.93). The addition of radiation to CT did not yield improved outcome in early-stage cancers. For CRT and CT, OS was 22.8 versus 65.7 months (P = 0.3975), and PFS was 25.3 versus 65.7 months (P = 0.4699). CONCLUSIONS: In the early-stage AC, adjuvant therapy may not improve the outcome in the short term but may benefit over a long period. It should be considered, especially in patients with adverse risk factors. Radiation therapy may not be useful in managing AC in the adjuvant setting.

Second-line treatment for metastatic pancreatic cancer.

Pancreatic cancer is the fourth-leading cause of cancer-related death. It is commonly diagnosed at an advanced stage, when no curative options exist. Over the last decade, combination chemotherapy has shown a survival benefit compared with single-agent gemcitabine and has become established as first-line therapy in metastatic pancreatic cancer. The choice of frontline regimen, which is based on clinical factors, plays an important role in subsequent management. Limited second-line standard therapeutic options are available. Studies have not definitively established that chemotherapy with a fluoropyramidine (5-fluorouracil or capecitabine), gemcitabine, oxaliplatin, irinotecan, or a combination of oxaliplatin and irinotecan improves patient survival after the failure of first-line chemotherapy. Nanoliposomal irinotecan has been approved for use in patients who have progressive disease while on gemcitabine-based treatment. Although combination chemotherapy is associated with a modest survival benefit, this comes at the expense of increased toxicity and costs. Furthermore, the optimal sequencing of these agents in subsequent lines of treatment is unknown. Randomized controlled trials provide little evidence of greater benefit from second-line therapy compared with best supportive care alone. Therefore, treatment decisions should be patient-centered and based on functional status, medical comorbidities, and anticipated adverse effects. The clinical context and prior treatment-related toxicities have a significant influence on the choice of optimal salvage treatment. We review the published data focused on second-line treatment for advanced pancreatic cancer.