ABSTRACT
BACKGROUND: Assessment of individual tumor biology and response to systemic therapy in pancreatic ductal adenocarcinoma (PDAC) remains a clinical challenge. The significance of anthropometric (body composition) changes during chemotherapy as a surrogate for tumor biology in the setting of localized PDAC is unknown. METHODS: A retrospective, single-institution analysis of patients with PDAC who received neoadjuvant therapy (NAT) and pancreatectomy from 2017 to 2021 was performed. Radiologic anthropometric analysis used artificial intelligence-driven software to segment and compute total and sub-compartment muscle area, adipose tissue area, and attenuation values at the level of the L3 vertebra. Kaplan-Meier survival estimates, log-rank tests, and multivariable Cox regression models were used in survival analyses. RESULTS: The inclusion criteria were met by 138 patients. Although decreases in muscle and adipose tissue areas during NAT were predominant, a subset of patients experienced an increase in these compartments. Increases in muscle greater than 5% (hazard ratio [HR], 0.352; 95% confidence interval [CI] 0.135-0.918; p = 0.033) and increases in adipose tissue greater than 15% (HR, 0.375; 95% CI 0.144-0.978; p = 0.045), were significantly associated with improved survival, whereas loss of visceral fat greater than 15% was detrimental (HR 1.853; CI 1.099-3.124; p = 0.021). No significant associations with single time-point anthropometrics were observed. Gains in total muscle and adipose mass were associated with improved pathologic response to systemic therapy and less advanced pathologic tumor stage. CONCLUSIONS: Dynamic anthropometric analysis during NAT for PDAC is a stronger prognostic indicator than measurements taken at a single point in time. Repeated anthropometric analysis during preoperative chemotherapy may serve as a biomarker for individual tumor biology and response to therapy.
ABSTRACT
INTRODUCTION: It is common for cancer patients to seek a second opinion for a variety of reasons. Understanding what drives patients to choose to receive treatment with their second opinion provider may uncover opportunities to improve the second opinion process. Therefore, we sought to identify the patient, disease, and treatment characteristics that were associated with second opinion retention rates in patients seeking a second surgical opinion for breast, colon, and pancreatic cancer. METHODS: We conducted a retrospective cohort study to evaluate patients who sought a second opinion within a large academic health-care system for breast, colon, and pancreatic cancer. Electronic medical records were reviewed for second opinions. Patient demographics and characteristics were collected and compared between the retained group and the nonretained groups. RESULTS: A total of 237 patients obtained second opinions for breast, colorectal, and pancreatic cancer. Patients that were offered a different treatment plan at their second opinion were more likely to be retained for systemic therapy (P = 0.009) for pancreatic cancer and any treatment for colon cancer (P = 0.003). Seeing a radiation oncologist (P = 0.007) or a plastic surgeon (P = 0.02) during the multidisciplinary consultation increased retention rates for breast cancer. CONCLUSIONS: Surgeons can better identify patients that are more likely to be retained after a second opinion by the individual patient characteristics and treatment factors. Understanding the factors that lead to retention for these three cancer types may help physicians provide the best possible resources for most patients presenting for second opinion evaluations.
ABSTRACT
Background: Metastatic renal cell carcinoma (mRCC) is a heterogenous disease with poor 5-year overall survival (OS) at 14%. Patients with mRCC to endocrine organs historically have prolonged OS. Pancreatic metastases are uncommon overall, with mRCC being the most common etiology of pancreatic metastases. In this study, we report the long-term outcomes of patients with mRCC to the pancreas in two separate cohorts. Methods: We performed a multicenter, international retrospective cohort study of patients with mRCC to the pancreas at 15 academic centers. Cohort 1 included 91 patients with oligometastatic disease to the pancreas. Cohort 2 included 229 patients with multiples organ sites of metastases including the pancreas. The primary endpoint for Cohorts 1 and 2 was median OS from time of metastatic disease in the pancreas until death or last follow up. Findings: In Cohort 1, the median OS (mOS) was 121 months with a median follow up time of 42 months. Patients who underwent surgical resection of oligometastatic disease had mOS of 100 months with a median follow-up time of 52.5 months. The mOS for patients treated with systemic therapy was not reached. In Cohort 2, the mOS was 90.77 months. Patients treated with first-line (1L) VEGFR therapy had mOS of 90.77 months; patients treated with IL immunotherapy (IO) had mOS of 92 months; patients on 1L combination VEGFR/IO had mOS of 74.9 months. Interpretations: This is the largest retrospective cohort of mRCC involving the pancreas. We confirmed the previously reported long-term outcomes in patients with oligometastatic pancreas disease and demonstrated prolonged survival in patients with multiple RCC metastases that included the pancreas. In this retrospective study with heterogeneous population treated over 2 decades, mOS was similar when stratified by first-line therapy. Future research will be needed to determine whether mRCC patients with pancreatic metastases require a different initial treatment strategy. Funding: Statistical analyses for this study were supported in part by the University of Colorado Cancer Center Support Grant from the NIH/NCI, P30CA046934-30.
ABSTRACT
BACKGROUND: After surgical resection of pancreatic ductal adenocarcinoma, 14% of patients have lung-only recurrence. We hypothesize that in patients with isolated lung metastases from pancreatic ductal adenocarcinoma, pulmonary metastasectomy offers a survival benefit with minimal additional morbidity after resection. METHODS: This was a single-institution, retrospective study of patients who underwent definitive resection of pancreatic ductal adenocarcinoma and later developed isolated lung metastases between 2009 and 2021. Patients were included if they carried a diagnosis of pancreatic ductal adenocarcinoma, underwent pancreatic resection with curative intent, and subsequently developed lung metastases. Patients were excluded if they developed multiple sites of recurrence. RESULTS: We identified 39 patients with pancreatic ductal adenocarcinoma and isolated lung metastases, 14 of whom underwent pulmonary metastasectomy. During the study period, 31 (79%) patients died. Across all patients, there was an overall survival of 45.9 months, a disease-free interval of 22.8 months, and survival after recurrence of 22.5 months. Survival after recurrence was significantly longer in patients who underwent pulmonary metastasectomy than those who did not (30.8 months vs 18.6 months, P < .01). There was no difference in overall survival between groups. However, patients who underwent pulmonary metastasectomy were significantly more likely to be alive 3 years after their diagnosis (100.0% vs 64%, P = .02) and 2 years after recurrence (79% vs 32%, P < .01) than those in who did not undergo pulmonary metastasectomy. No mortalities occurred related to pulmonary metastasectomy, and procedure-related morbidity was 7%. CONCLUSION: Patients who underwent pulmonary metastasectomy for isolated pulmonary pancreatic ductal adenocarcinoma metastases had significantly longer survival after recurrence and clinically meaningful survival benefit with minimal additional morbidity after pulmonary resection.
Subject(s)
Carcinoma, Pancreatic Ductal , Lung Neoplasms , Metastasectomy , Pancreatic Neoplasms , Humans , Retrospective Studies , Survival Rate , Lung/pathology , Neoplasm Recurrence, Local , Prognosis , Disease-Free Survival , Pancreatic NeoplasmsABSTRACT
BACKGROUND: Current evidence on overall survival (OS) between invasive pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) is limited to single-center reports. We aimed to compare the characteristics, management, and OS of invasive PDAC vs. IPMN using a national United States (US) database. METHODS: Invasive PDAC or IPMN adult (≥18 years) patients were identified in the National Cancer Database (2004-2016). OS was assessed with the Kaplan-Meier method and the stratified log-rank test. RESULTS: We included 101,190 patients (100,834 PDAC, 356 IPMN). A higher proportion of PDAC vs. IPMN patients had clinical N1 (36.8% vs. 15.7%, p < 0.001) and M1 disease (41.2% vs. 5.9%, p < 0.001). A lower proportion of PDAC patients underwent surgery (25.5% vs. 80.3%, p < 0.001), but a higher proportion received chemotherapy (65.4% vs. 46.1%, p < 0.001) or radiation (25.3% vs. 20.5%, p = 0.04). A higher proportion of surgical patients with PDAC vs. IPMN underwent margin-positive resection (23.0% vs. 14.0%, p = 0.001). The median OS for PDAC vs. IPMN was 8.3 vs. 33.4 months. In the stratified analysis for N0M0 disease, the median OS for PDAC vs. IPMN was 12.8 vs. 43.3 months, for N1M0, it was 11.5 vs. 17.0 months, while for M1, it was 4.0 vs. 7.0 months. In both diagnoses, surgery yielded improved OS, while stratified analysis in the surgical cohort demonstrated similar findings. CONCLUSIONS: Invasive PDAC is more aggressive than invasive IPMN, yet in the case of metastasis, OS is equally poor. Excellent long-term OS is achievable with surgical resection in highly selected cases, and efforts should focus on facilitating surgical treatment.
ABSTRACT
BACKGROUND: Neoadjuvant treatment is important for improving the rate of R0 surgical resection and overall survival outcome in treating patients with pancreatic ductal adenocarcinoma (PDAC). However, the true efficacy of radiotherapy (RT) for neoadjuvant treatment of PDAC is uncertain. This retrospective study evaluated the treatment outcome of neoadjuvant RT in the treatment of PDAC. METHODS: Collected from the National Cancer Database, information on patients with PDAC who underwent neoadjuvant chemotherapy (NAC) and pancreatectomy between 2010 to 2016 was used in this study. Short- and long-term outcomes were compared between patients who received neoadjuvant chemoradiotherapy (NACRT) and NAC. RESULTS: The study included 6936 patients, of whom 3185 received NACRT and 3751 NAC. The groups showed no difference in overall survival (NACRT 16.1 months versus NAC 17.4 months; P = 0.054). NACRT is associated with more frequent margin negative resection (86.1 versus 80.0 per cent; P < 0.001) but a more unfavourable 90-day mortality than NAC (6.4 versus 3.6 per cent; P < 0.001). The odds of 90-day mortality were higher in the radiotherapy group (odds ratio 1.81; P < 0.001), even after adjusting for significant covariates. Patients who received NACRT received single-agent chemotherapy more often than those who received NAC (31.5 versus 10.7 per cent; P < 0.001). CONCLUSION: This study failed to show a survival benefit for NACRT over NAC alone, despite its association with negative margin resection. The significantly higher mortality in NACRT warrants further investigation into its efficacy in the treatment of pancreatic cancer.
Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/therapy , Chemoradiotherapy , Humans , Neoadjuvant Therapy , Retrospective Studies , Pancreatic NeoplasmsABSTRACT
OBJECTIVE: To identify objective preoperative prognostic factors that are able to predict long-term survival of patients affected by PDAC. SUMMARY OF BACKGROUND DATA: In the modern era of improved systemic chemotherapy for PDAC, tumor biology, and response to chemotherapy are essential in defining prognosis and an improved approach is needed for classifying resectability beyond purely anatomic features. METHODS: We queried the National Cancer Database regarding patients diagnosed with PDAC from 2010 to 2016. Cox proportional hazard models were used to select preoperative baseline factors significantly associated with survival; final models for overall survival (OS) were internally validated and formed the basis of the nomogram. RESULTS: A total of 7849 patients with PDAC were included with a median follow-up of 19 months. On multivariable analysis, factors significantly associated with OS included carbohydrate antigen 19-9, neoadjuvant treatment, tumor size, age, facility type, Charlson/Deyo score, primary site, and sex; T4 stage was not independently associated with OS. The cumulative score was used to classify patients into 3 groups: good, intermediate, and poor prognosis, respectively. The strength of our model was validated by a highly significant randomization test, Log-rank test, and simple hazard ratio; the concordance index was 0.59. CONCLUSION: This new PDAC nomogram, based solely on preoperative variables, could be a useful tool to patients and counseling physicians in selecting therapy. This model suggests a new concept of resectability that is meant to reflect the biology of the tumor, thus partially overcoming existing definitions, that are mainly based on tumor anatomic features.
Subject(s)
Carcinoma, Pancreatic Ductal/surgery , Nomograms , Pancreatic Neoplasms/surgery , Adolescent , Adult , Age Factors , Aged , CA-19-9 Antigen/blood , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/pathology , Comorbidity , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Proportional Hazards Models , Sex Factors , Tumor Burden , Young AdultABSTRACT
Pancreatic cancer (PC) is likely to become the second leading cause of malignancy-associated mortality within the next 10 years and surgery remains the best hope for cure. The introduction of effective neoadjuvant treatment (NAT) has increased the resection rate of PC in the era of contemporary pancreatology. This review summarizes the surgical selection criteria for locally advanced PC (LAPC), by focusing on the commonly used predictors for resectability and better overall survival outcome. Based on the currently available evidence, the role of change in carbohydrate antigen 19-9 (CA 19-9) and patient's tumor response to NAT are critical in surgical candidacy selection. Although, consensus on surgical candidacy selection for LAPC still needs to be made, several data have shown that surgery provides the most optimistic chance of cure for PC. Surgery is, therefore, recommended whenever the benefits of pancreatectomy outweigh surgical complications, and the chance of local or distant metastases in the postoperative setting is low. This review also provided our insight for and experience in selecting surgical candidates by focusing on optimizing the overall survival of LAPC patients. Nevertheless, a collaborative approach to formulating standardized criteria for surgical candidate selection and treatment guidelines for LAPC is a common goal that pancreatologists worldwide should focus on.
ABSTRACT
Intraductal papillary mucinous neoplasms (IPMN) are common but difficult to manage since accurate tools for diagnosing malignancy are unavailable. This study tests the diagnostic value of the main pancreatic duct (MPD) diameter for detecting IPMN malignancy using a meta-analysis of published data of resected IPMNs. Collected from a comprehensive literature search, the articles included in this analysis must report malignancy cases (high-grade dysplasia (HGD) and invasive carcinoma (IC)) and MPD diameter so that two MPD cut-offs could be created. The sensitivity, specificity, and odds ratios of the two cutoffs for predicting malignancy were calculated. A review of 1493 articles yielded 20 retrospective studies with 3982 resected cases. A cutoff of ≥5 mm is more sensitive than the ≥10 mm cutoff and has pooled sensitivity of 72.20% and 75.60% for classification of HGD and IC, respectively. Both MPD cutoffs of ≥5 mm and ≥10 mm were associated with malignancy (OR = 4.36 (95% CI: 2.82, 6.75) vs. OR = 3.18 (95% CI: 2.25, 4.49), respectively). The odds of HGD and IC for patients with MPD ≥5 mm were 5.66 (95% CI: 3.02, 10.62) and 7.40 (95% CI: 4.95, 11.06), respectively. OR of HGD and IC for MPD ≥10 mm cutoff were 4.36 (95% CI: 3.20, 5.93) and 4.75 (95% CI: 2.39, 9.45), respectively. IPMN with MPD of >5 mm could very likely be malignant. In selected IPMN patients, pancreatectomy should be considered when MPD is >5 mm.
ABSTRACT
Stromal fibrosis activates prosurvival and proepithelial-to-mesenchymal transition (EMT) pathways in pancreatic ductal adenocarcinoma (PDAC). In patient tumors treated with neoadjuvant stereotactic body radiation therapy (SBRT), we found upregulation of fibrosis, extracellular matrix (ECM), and EMT gene signatures, which can drive therapeutic resistance and tumor invasion. Molecular, functional, and translational analysis identified two cell-surface proteins, a disintegrin and metalloprotease 10 (ADAM10) and ephrinB2, as drivers of fibrosis and tumor progression after radiation therapy (RT). RT resulted in increased ADAM10 expression in tumor cells, leading to cleavage of ephrinB2, which was also detected in plasma. Pharmacologic or genetic targeting of ADAM10 decreased RT-induced fibrosis and tissue tension, tumor cell migration, and invasion, sensitizing orthotopic tumors to radiation killing and prolonging mouse survival. Inhibition of ADAM10 and genetic ablation of ephrinB2 in fibroblasts reduced the metastatic potential of tumor cells after RT. Stimulation of tumor cells with ephrinB2 FC protein reversed the reduction in tumor cell invasion with ADAM10 ablation. These findings represent a model of PDAC adaptation that explains resistance and metastasis after RT and identifies a targetable pathway to enhance RT efficacy. SIGNIFICANCE: Targeting a previously unidentified adaptive resistance mechanism to radiation therapy in PDAC tumors in combination with radiation therapy could increase survival of the 40% of PDAC patients with locally advanced disease.See related commentary by Garcia Garcia et al., p. 3158 GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/12/3255/F1.large.jpg.
Subject(s)
ADAM10 Protein/metabolism , Amyloid Precursor Protein Secretases/metabolism , Carcinoma, Pancreatic Ductal/radiotherapy , Epithelial-Mesenchymal Transition , Fibrosis/pathology , Gamma Rays/adverse effects , Membrane Proteins/metabolism , Pancreatic Neoplasms/radiotherapy , Radiation Injuries/pathology , ADAM10 Protein/antagonists & inhibitors , ADAM10 Protein/genetics , Amyloid Precursor Protein Secretases/antagonists & inhibitors , Amyloid Precursor Protein Secretases/genetics , Animals , Antifibrotic Agents/therapeutic use , Apoptosis , Carcinoma, Pancreatic Ductal/pathology , Cell Movement , Cell Proliferation , Ephrin-B2/blood , Female , Fibrosis/drug therapy , Fibrosis/etiology , Fibrosis/metabolism , Humans , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/genetics , Mice , Mice, Inbred C57BL , Pancreatic Neoplasms/pathology , Prognosis , Radiation Injuries/drug therapy , Radiation Injuries/etiology , Radiation Injuries/metabolism , Survival Rate , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND: The role of neoadjuvant stereotactic body radiation therapy (SBRT) in patients with borderline resectable pancreas cancer (BRPC) and locally advanced pancreas cancer (LAPC) remains controversial. METHODS: We retrospectively evaluated BRPC and LAPC patients treated at our institution who underwent 2-3 months of chemotherapy followed by SBRT to a dose of 30-33 Gy. Overall survival (OS) and recurrence-free survival (RFS) were estimated and compared by Kaplan-Meier and log-rank methods. RESULTS: We identified 103 (85 BRPC and 18 LAPC) patients treated per our neoadjuvant paradigm between 2011 and 2018, with resectability based on NCCN definitions. Median follow up was 25 months. Of patients completing neoadjuvant therapy, 73 (71%) underwent definitive resection. Seventy-one (97%) patients with definitively resected tumors had R0 resection and 5 (7%) had a complete pathologic response CR to neoadjuvant therapy. The median overall survival (OS) of the cohort was 24 months. Those with a complete or marked pathologic response had significantly better OS than those with a moderate response (41 vs 24 months, p < 0.02) and patients unable to undergo definitive surgery (17 months, p < 0.0003). Six resected patients experienced grade ≥3 surgical complications. CONCLUSIONS: Neoadjuvant chemotherapy and SBRT are associated with promising pathologic response rates and R0 resection rates, with acceptable perioperative morbidity.
Subject(s)
Pancreatic Neoplasms , Radiosurgery , Antineoplastic Combined Chemotherapy Protocols , Dose Fractionation, Radiation , Humans , Neoadjuvant Therapy/adverse effects , Pancreatic Neoplasms/surgery , Radiosurgery/adverse effects , Retrospective StudiesABSTRACT
BACKGROUND/OBJECTIVES: Pancreatic cystic neoplasms (PCNs) are common, among which 13%-23% are serous cystic neoplasms (SCNs). However, diffuse and multifocal variants of SCNs are extremely rare. The differential diagnosis of SCNs from other PCNs is important as the former entities are benign and do not become invasive. OBJECTIVE: This study analyzes the clinical characteristics of multifocal/diffuse SCN through a systematic review of the literature and a case report. METHODS: A comprehensive literature search was executed in the Ovid MEDLINE, Embase, and Google Scholar databases. The search strategy was designed to capture the concept of multifocal/diffuse SCN cases with sufficient clinical information for detailed analysis. Using the final included articles, we analyzed tumor characteristics, diagnostic modalities used, initial management and indications, and patient outcomes. RESULTS: A review of 262 articles yielded 19 publications with 22 cases that had detailed clinical information. We presented an additional case from our institution database. The systematic review of 23 cases revealed that the diffuse variant is more common than the multifocal variant (15 vs 8 cases, respectively). Patients were managed with surgical intervention, conservative treatment, or conservative treatment followed by surgical intervention. Indications for surgery following conservative management mainly included new onset or worsening of symptoms. Only one case reported significant tumor growth after attempting an observational approach. No articles reported recurrence of SCN after pancreatectomy, and no articles reported mortality related to multifocal/diffuse SCNs. CONCLUSION: Despite their expansive-growing and space-occupying characteristics, multifocal/diffuse SCNs should be treated similarly to their more common unifocal counterpart.
Subject(s)
Adenoma/epidemiology , Cystadenocarcinoma, Serous/epidemiology , Cystadenoma, Serous/epidemiology , Pancreatic Neoplasms/epidemiology , Adenoma/pathology , Adenoma/therapy , Cystadenocarcinoma, Serous/pathology , Cystadenocarcinoma, Serous/therapy , Cystadenoma, Serous/pathology , Cystadenoma, Serous/therapy , Humans , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/therapyABSTRACT
PURPOSE: This study was designed to compare quality of life (QoL) among patients who underwent open versus laparoscopic pancreatic resection, including distal pancreatectomy and pancreaticoduodenectomy, and to identify clinical characteristics that are associated with changes in QoL. METHODS: Quality of life (QoL) was assessed in patients undergoing pancreatic resection with the Functional Assessment of Cancer Therapy-Hepatobiliary questionnaire preoperatively and 2 weeks, 1, 3, and 6 months postoperatively. Multilevel regression modeling was used to determine the variability in each QoL domain within the first 2 weeks (postoperative period) and thereafter (recovery period). RESULTS: Among 159 patients, 60.4% underwent open and 39.6% underwent laparoscopic surgery. Physical, functional, hepatobiliary, and total QoL scores decreased in the postoperative period but returned to baseline levels by 6 months postoperatively. Emotional QoL improved from baseline by 2 weeks after surgery (p < 0.001) and social QoL improved from baseline by 3 months after surgery (p < 0.001). Emotional QoL was the only domain where significant differences were observed in QoL in the postoperative and recovery periods between patients who underwent open and laparoscopic pancreatic resection. Controlling for surgical approach, patients who experienced a grade III or IV complication experienced greater declines in physical, functional, hepatobiliary, and total QoL in the postoperative period. The negative impact of complications on QoL resolved by 6 months postoperatively. CONCLUSIONS: The impact of pancreatic resection on QoL was comparable between patients who underwent laparoscopic versus open pancreatic resection. Complications were strongly associated with changes in postoperative QoL, suggesting that performing a safe operation is the best approach for optimizing patient reported QoL.
Subject(s)
Laparoscopy/methods , Pancreatectomy/methods , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy/methods , Postoperative Complications , Quality of Life , Aged , Female , Follow-Up Studies , Humans , Male , Prognosis , Prospective StudiesABSTRACT
CONTEXT: Neoadjuvant chemotherapy is increasingly used in borderline resectable and locally advanced pancreatic cancer to facilitate surgical resection. OBJECTIVE: To compare progression free survival and overall survival in patients receiving neoadjuvant FOLFIRINOX with those receiving gemcitabine/abraxane. DESIGN: Retrospective cohort study. SETTING: University of Colorado Hospital from 2012-2016. PARTICIPANTS: Patients with pancreatic adenocarcinoma. INTERVENTIONS: Neoadjuvant FOLFIRINOX or gemcitabine/abraxane. OUTCOME MEASURES: Perioperative outcomes, progression free survival, and overall survival were compared between groups. A multivariate Cox proportional hazard model was applied to evaluate survival outcomes. RESULTS: We identified 120 patients: 83 (69.2%) FOLFIRINOX and 37 (30.8%) gemcitabine/abraxane. The FOLIFRINOX group was younger and had a lower ECOG performance status (p<0.05). Patients in the FOLFIRINOX group were more likely to undergo surgical resection compared to gemcitabine/abraxane (66.3% vs. 32.4%, p=0.002). Among all patients, median follow up was 16.9 months and FOLFIRINOX was associated with improved PFS (15.3 vs. 8.2 months, p=0.006), but not overall survival (23.5 vs. 18.7 months, p=0.228). In these patients, insulin-dependent diabetes was associated with a worse progression free survival and overall survival and surgical resection was protective. Among surgically resected patients, median follow up was 21.1 months and there was no difference in progression free survival (19.5 vs. 15.1 months) or overall survival (27.4 vs. 19.8 months) between the FOLFIRINOX and gemcitabine/abraxane groups, respectively (p>0.05). Insulin-dependent diabetes and a poor-to-moderate pathologic response was associated with worse progression free survival and overall survival. CONCLUSION: Neoadjuvant FOLFIRINOX may improve progression free survival by increasing the proportion of patients undergoing surgical resection. Improved understanding of the role for selection bias and longer follow up are needed to better define the impact of neoadjuvant FOLFIRINOX on overall survival.
ABSTRACT
BACKGROUND AND OBJECTIVES: To compare outcomes in patients receiving neoadjuvant stereotactic body radiation therapy (SBRT) with those receiving intensity-modulated radiation therapy (IMRT) for pancreatic adenocarcinoma. METHODS: We analyzed patients receiving neoadjuvant SBRT for borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) (2012-2016). Differences in baseline characteristics, perioperative outcomes, progression-free survival (PFS), and overall survival (OS) were compared. RESULTS: Seventy-five (82.4%) patients received SBRT and 16 (17.6%) received IMRT. There were no differences in surgical resection rates in the SBRT (n = 38, 50.7%) and IMRT (n = 11, 68.8%) groups (P = 0.188). Among resected patients, there was no difference in postoperative outcomes or pathologic outcomes including lymph node status, margin status, lymphovascular and perineural invasion, or pathologic response to neoadjuvant treatment (P > 0.05). Among all patients, median PFS and OS were 9.9 and 23.5 months in the SBRT group, respectively, and 15.3 and 21.8 months in the IMRT group, respectively (P > 0.05). Similarly, there was no difference in PFS or OS between groups when stratified by BRPC, LAPC, and surgically resected patients (P > 0.05). CONCLUSIONS: In the neoadjuvant setting, SBRT and IMRT appear to have similar rates of resection, perioperative outcomes, and survival outcomes, but additional studies with increased sample size and longer follow up are needed.
Subject(s)
Adenocarcinoma/mortality , Neoadjuvant Therapy/mortality , Pancreatic Neoplasms/mortality , Radiosurgery/mortality , Radiotherapy, Intensity-Modulated/mortality , Adenocarcinoma/radiotherapy , Adenocarcinoma/surgery , Aged , Aged, 80 and over , Combined Modality Therapy , Dose Fractionation, Radiation , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pancreatic Neoplasms/radiotherapy , Pancreatic Neoplasms/surgery , Perioperative Care , Prognosis , Prospective Studies , Retrospective Studies , Survival Rate , Pancreatic NeoplasmsABSTRACT
BACKGROUND: The purpose of this study is to present the largest reported series comparing open pancreaticoduodenectomy (OPD) to total laparoscopic pancreaticoduodenectomy (TLPD) in patients with ampullary neoplasms. METHODS: Patients undergoing OPD or TLPD for ampullary neoplasms from June 2012 to August 2016 were retrospectively identified. Perioperative outcomes were compared using a Wilcoxon rank-sum test, Student's t test, and Chi square analysis where appropriate. Kaplan-Meier estimates for progression-free survival (PFS) and overall survival (OS) were compared between the groups using the log-rank test. RESULTS: We identified 47 patients with ampullary neoplasms (adenocarcinoma n = 36, neuroendocrine tumor n = 7, undifferentiated n = 1, adenoma n = 3) undergoing OPD (n = 25) and TLPD (n = 22). The proportion of patients being offered TLPD has progressively increased every year over 5 years: 0% (2012) to 50% (2015). There were no differences in baseline variables between the two groups. TLPD was associated with less blood loss (300 vs. 500 mL, p < 0.001) and shorter operative times (314 vs. 359 min, p = 0.024). No patient required conversion to an open procedure and there were no perioperative deaths in either group. TLPD was associated with lower rates of intra-abdominal abscess (0 vs. 16.0%, p = 0.049), but there were no differences in rates of pancreatic fistula, bile leak, delayed gastric emptying, wound infection, length of stay, and readmission (all p > 0.05). Among patients with adenocarcinoma, there was no difference in pathological features between the two groups (p > 0.05) and all patients had negative margins. At a median follow up of 25 months, there was no difference in PFS or OS between the two groups. CONCLUSIONS: TLPD in patients with ampullary neoplasms results in improved perioperative outcomes while having equivalent short and long-term oncologic outcomes compared to the traditional open approach.
Subject(s)
Adenocarcinoma/surgery , Adenoma/surgery , Ampulla of Vater , Common Bile Duct Neoplasms/surgery , Laparoscopy/methods , Neuroendocrine Tumors/surgery , Pancreaticoduodenectomy/methods , Adenocarcinoma/mortality , Adenoma/mortality , Adult , Aged , Common Bile Duct Neoplasms/mortality , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neuroendocrine Tumors/mortality , Operative Time , Retrospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND: Solid-pseudopapillary neoplasms are rare pancreatic neoplasms with low malignant potential that predominantly arise in young women. We sought to characterize this population and the evolving trend at our institution towards laparoscopic management. METHODS: We identified all patients at our institution that were surgically treated for solid-pseudopapillary neoplasm from 2008-2015. Demographic and clinical information were queried from the medical record, and descriptive statistics were performed. Student's t test and chi-square analysis were used for comparison where appropriate. RESULTS: We identified 11 women and 1 man (average age 26 years; range 14-48 years) who were surgically treated for solid-pseudopapillary neoplasms; 5 with distal pancreatectomy (4 open, 1 laparoscopic), 6 with pancreaticoduodenectomy (3 open, 3 laparoscopic), and 1 open enucleation. From 2008 to 2013, seven of eight (87 %) procedures were performed open. Since 2014, three of four (75 %) procedures have successfully been completed laparoscopically (see video clips). Length of stay was similar for patients who had open versus laparoscopic procedures (8 vs. 9 days, p = 0.61). Two-thirds of patients (5/8) who had open procedures experienced postoperative complications compared with half (2/4) of patients who had laparoscopic procedures (p = 0.28). There have been no recurrences. CONCLUSIONS: Minimally invasive surgical management of solid-pseudopapillary neoplasms is becoming more popular, can be performed safely, and appears to have comparable outcomes to an open approach. Quality of life is an important metric for this relatively young population and may be improved with a laparoscopic approach, which warrants further investigation.
Subject(s)
Laparoscopy/trends , Pancreatectomy/methods , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy/methods , Adolescent , Adult , Female , Humans , Length of Stay , Male , Middle Aged , Pancreatectomy/adverse effects , Pancreaticoduodenectomy/adverse effects , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: The multidisciplinary approach to GI cancer is becoming more widespread as a result of multimodality therapy. At the University of Colorado Hospital (UCH), we utilize a formal multidisciplinary approach through specialized clinics across a variety of settings, including pancreas and biliary cancer, esophageal and gastric cancer, liver cancer and neuroendocrine tumors (NET), and colorectal cancer. Patients with these suspected diagnoses are seen in a multidisciplinary clinic. We evaluated whether implementation of disease-specific multidisciplinary programs resulted in a change in diagnosis and/or change in management for these patients. METHODS: Data from 1747 patients were prospectively collected from inception of each multidisciplinary program through December 31, 2015. Change in diagnosis was defined as a change in radiographic or endoscopic findings that resulted in a change in cancer stage or clinical diagnosis and/or a change in pathologic diagnosis. Reports of incidental findings unrelated to primary diagnosis on radiographic evaluation were also assessed, but not included in overall change in diagnosis findings. We further evaluated if patients had a change in the management of their disease compared with outside recommendations. RESULTS: Of 1747 patients evaluated, change occurred in 38 % (pancreas and biliary), 13 % (esophageal and gastric); 22 % (liver and NET), and 16 % (colorectal). Change in management for each multidisciplinary program occurred in 35 % (pancreas and biliary), 20 % (esophageal and gastric), 27 % (liver and NET), and 13 % (colorectal). CONCLUSIONS: The use of a multidisciplinary clinic to manage GI cancer has a substantial impact in change in diagnosis and/or management in more than one-third of patients evaluated.
Subject(s)
Digestive System Neoplasms/diagnosis , Digestive System Neoplasms/therapy , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/therapy , Patient Care Planning , Patient Care Team , Aged , Clinical Decision-Making , Digestive System Neoplasms/pathology , Endoscopy, Digestive System , Humans , Incidental Findings , Middle Aged , Neoplasm Staging , Neuroendocrine Tumors/pathology , RadiographyABSTRACT
The management of esophageal and gastric cancer is complex and involves multiple specialists in an effort to optimize patient outcomes. Utilizing a multidisciplinary team approach starting from the initial staging evaluation ensures that all members are in agreement with the plan of care. Treatment selection for esophageal and gastric cancer often involves a combination of chemotherapy, radiation, surgery, and palliative interventions (endoscopic and surgical), and direct communication between specialists in these fields is needed to ensure appropriate clinical decision making. At the University of Colorado, the Esophageal and Gastric Multidisciplinary Clinic was created to bring together all experts involved in treating these diseases at a weekly conference in order to provide patients with coordinated, individualized, and patient-centered care. This review details the essential elements and benefits of building a multidisciplinary program focused on treating esophageal and gastric cancer patients.
ABSTRACT
While most providers support the concept of a multidisciplinary approach to patient care, challenges exist to the implementation of successful multidisciplinary clinical programs. As patients become more knowledgeable about their disease through research on the Internet, they seek hospital programs that offer multidisciplinary care. At the University of Colorado Hospital, we utilize a formal multidisciplinary approach across a variety of clinical settings, which has been beneficial to patients, providers, and the hospital. We present a reproducible framework to be used as a guide to develop a successful multidisciplinary program.