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OBJECTIVE: The aim of this study was to compare infectious complications in pancreatoduodenectomy (PD) patients with biliary stents treated with short, medium, or long durations of prophylactic antibiotics. BACKGROUND: Pre-existing biliary stents have historically been associated with higher infection risk after PD. Patients are administered prophylactic antibiotics, but the optimal duration remains unknown. METHODS: This single-institution retrospective cohort study included consecutive PD patients from October 2016 to April 2022. Antibiotics were continued past the operative dose per surgeon discretion. Infection rates were compared by short (≤24 h), medium (>24 but ≤96 h), and long (>96 h) duration antibiotics. Multivariable regression analysis was performed to evaluate associations with a primary composite outcome of wound infection, organ-space infection, sepsis, or cholangitis. RESULTS: Among 542 PD patients, 310 patients (57%) had biliary stents. The composite outcome occurred in 28% (34/122) short, 25% (27/108) medium, and 29% (23/80) long-duration ( P =0.824) antibiotic patients. There were no differences in other infection rates or mortality. On multivariable analysis, antibiotic duration was not associated with infection rate. Only postoperative pancreatic fistula (odds ratio 33.1, P <0.001) and male sex (odds ratio 1.9, P =0.028) were associated with the composite outcome. CONCLUSIONS: Among 310 PD patients with biliary stents, long-duration prophylactic antibiotics were associated with similar composite infection rates to short and medium durations but were used almost twice as often in high-risk patients. These findings may represent an opportunity to de-escalate antibiotic coverage and promote risk-stratified antibiotic stewardship in stented patients by aligning antibiotic duration with risk-stratified pancreatectomy clinical pathways.
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Sistema Biliar , Pancreaticoduodenectomía , Humanos , Masculino , Pancreaticoduodenectomía/efectos adversos , Estudios Retrospectivos , Antibacterianos/uso terapéutico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/tratamiento farmacológico , Profilaxis Antibiótica , Stents/efectos adversosRESUMEN
OBJECTIVE: We aimed to determine if advances in neoadjuvant therapy affected recurrence patterns and survival outcomes after pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Data are limited on how modern multimodality therapy affects PDAC recurrence and post-recurrence survival. METHODS: Patients who received neoadjuvant therapy followed by curative-intent pancreatectomy for PDAC during 1998-2018 were identified. Treatments, recurrence sites and timing, and survival were compared between patients who completed neoadjuvant therapy and pancreatectomy in 1998-2004, 2005-2011, and 2012-2018. RESULTS: The study included 727 patients (203, 251, and 273 in the 1998-2004, 2005-2011, and 2012-2018 cohorts, respectively). Use of neoadjuvant induction chemotherapy increased over time, and regimens changed over time, with >80% of patients treated in 2012-2018 receiving FOLFIRINOX or gemcitabine with nab-paclitaxel. Overall, recurrence sites and incidence (67.5%, 66.1%, and 65.9%) remained stable, and 85% of recurrences occurred within 2 years of surgery. However, compared to earlier cohorts, the 2012-2018 cohort had lower conditional risk of recurrence in postoperative year 1 and higher risk in postoperative year 2. Overall survival increased over time (median, 30.6, 33.6, and 48.7 mo, P < 0.005), driven by improved post-recurrence overall survival (median, 7.8, 12.5, and 12.6 mo; 3-year rate, 7%, 10%, and 20%; P < 0.005). CONCLUSIONS: We observed changes in neoadjuvant therapy regimens over time and an associated shift in the conditional risk of recurrence from postoperative year 1 to postoperative year 2, although recurrence remained common. Overall survival and post-recurrence survival remarkably improved over time, reflecting improved multimodality regimens for recurrent disease.
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BACKGROUND: The prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) is poor. Secondary brain metastasis (Br-M) occurs in less than 1% of patients. Clinical characteristics and molecular alterations have not been characterized in this rare patients' subset. MATERIALS AND METHODS: The Foundry software platform was used to retrospectively query electronic health records for patients with Br-M secondary to PDAC from 2005 to 2023; clinical, molecular, and overall survival (OS) data were analyzed. RESULTS: Br-M was diagnosed in 44 patients with PDAC. Median follow-up was 78 months; median OS from initial PDAC diagnosis was 47 months. Median duration from PDAC diagnosis to Br-M detection was 24 months; median OS from Br-M diagnosis was 3 months. At Br-M diagnosis, 82% (nâ =â 36) of patients had elevated CA19-9. Lung was the most common preexisting metastatic location (71%) with Br-M, followed by liver (66%). Br-M were most frequently observed in the frontal lobe (34%, nâ =â 15), cerebellar region (23%, nâ =â 10), and leptomeninges (18%, nâ =â 8). KRAS mutations were detected in 94.1% (nâ =â 16) of patients who had molecular data available (nâ =â 17) with KRASG12V being the most frequent subtype 47% (nâ =â 8); KRASG12D in 29% (nâ =â 5); KRASG12R in 18% (nâ =â 3). Patients who underwent Br-M surgical resection (nâ =â 5) had median OS of 8.6 months, while median OS following stereotactic radiosurgery only (nâ =â 11) or whole-brain radiation only (nâ =â 20) was 3.3 and 2.8 months, respectively. CONCLUSION: Br-M is a late PDAC complication, resulting in an extremely poor prognosis especially in leptomeningeal disease. KRAS was mutated in 94.1% of the patients and the KRASG12V subtype was prevalent.
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The purpose of this editorial is to review the American College of Surgeons Commission on Cancer Standard 5.6, which pertains to curative intent colon resections performed for cancer. We first provide a broad overview of the Operative Standard, followed by the underlying rationale, technical components, and documentation requirements.
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Colectomía , Neoplasias del Colon , Humanos , Colectomía/normas , Neoplasias del Colon/cirugía , Estados UnidosRESUMEN
BACKGROUND: Financial toxicity (FT) refers to the adverse impact of cancer treatment costs on patients' experiences, potentially leading to poor adherence to treatment and outcomes. However, the prevalence of FT among patients undergoing major upper gastrointestinal cancer operations, as well as factors associated with FT, remain unclear. METHODS: We conducted a cross-sectional study by sending the Comprehensive Score for financial Toxicity (COST) survey and Surgery-Q (a survey specifically developed for this study) to patients who underwent gastrectomy or pancreatectomy for malignant disease at our institution in 2019-2021. RESULTS: We sent the surveys to 627 patients and received responses from 101 (16%) patients. The FT prevalence (COST score <26) was 48 (48%). Patients likely to experience FT were younger than 50 years of age, of non-White race, earned an annual income <$75,000, and had credit scores <740 (all p < 0.05). Additionally, longer hospital stay (p = 0.041), extended time off work for surgery (p = 0.011), and extended time off work for caregivers (p = 0.005) were associated with FT. Procedure type was not associated with FT; however, patients who underwent minimally invasive surgery (MIS) had a lower FT probability (p = 0.042). In a multivariable analysis, age <50 years (p = 0.031) and credit score <740 (p < 0.001) were associated with high FT risk, while MIS was associated with low FT risk (p = 0.024). CONCLUSIONS: Patients with upper gastrointestinal cancer have a major risk of FT. In addition to predicting the FT risk before surgery, facilitating quicker functional recovery with the appropriate use of MIS is considered important to reducing the FT risk.
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Gastrectomía , Pancreatectomía , Humanos , Pancreatectomía/efectos adversos , Pancreatectomía/economía , Femenino , Masculino , Gastrectomía/efectos adversos , Gastrectomía/economía , Persona de Mediana Edad , Estudios Transversales , Prevalencia , Estudios de Seguimiento , Anciano , Pronóstico , Estrés Financiero/epidemiología , Estrés Financiero/etiología , Adulto , Neoplasias Pancreáticas/cirugía , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricos , Costos de la Atención en SaludRESUMEN
BACKGROUND: Postoperative adverse events (AEs) in patients with borderline resectable pancreatic ductal adenocarcinoma (BR-PC) treated with neoadjuvant therapy and pancreatectomy in the national cooperative group setting have not been previously characterized. We conducted a preplanned secondary analysis of patients enrolled on the Alliance A021501 clinical trial to quantify perioperative AE rates. METHODS: The A021501 phase 2 trial randomized patients with BR-PC to receive 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX and hypofractionated radiotherapy (Arm 2), followed by pancreatectomy (December 31, 2016 to May 31, 2019). Adverse events were assessed 90 days after pancreatectomy. RESULTS: Of 126 enrolled patients, 51 (40%) underwent pancreatectomy (n = 32, Arm 1; n = 19, Arm 2) at 28 institutions. Five (10%) patients required reoperation within 90 days; 56% of patients (n = 27/48) experienced at least one grade 3 or higher AE (50% vs. 67%, p = 0.37). Ninety-day mortality was 2.0%. Readmission was less frequent in Arm 1 (16% vs. 42%, p = 0.05), but there were no differences between study arms in rates of reoperation (13% vs. 5%), pancreatic fistula or intra-abdominal abscess requiring drainage (9% vs. 16%), or wound infection (6% vs. 16%). Pancreatic fistula or intra-abdominal abscess requiring drainage was associated with receipt of adjuvant therapy (p = 0.012). No difference in overall survival was observed based on occurrence of postoperative AEs (hazard ratio = 1.1; 95% confidence interval 0.5-2.6). CONCLUSIONS: In this multicenter study, rates of postoperative AEs were consistent with those previously reported. Multimodality trials of preoperative therapy for BR-PC may be performed in the cooperative group setting with careful quality assurance and safety monitoring. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02839343.
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BACKGROUND: In response to growing evidence that proper performance of operative techniques during cancer surgery is associated with improved patient outcomes, the American College of Surgeons (ACS) implemented six operative standards as part of Commission on Cancer (CoC) accreditation. This study aimed to assess surgeon familiarity with these standards when first introduced and 2 years after their adoption. METHODS: The ACS Cancer Surgery Standards Program distributed an anonymous 36-question survey to CoC-accredited cancer programs in 2021 and 2023. Questions specific to operative techniques determined the Surgery Score, and those specific to the accreditation standards determined the Standards Score. Mean scores were compared using one-way analysis of variance (ANOVA) and t tests. RESULTS: The survey was completed by 376 surgeons in 2021 and 380 surgeons in 2023. The Surgery Scores were higher than the Standards Scores in 2021 and 2023. The surgeons who practiced at institutions with CoC accreditation had significantly higher Standards Scores than the surgeons at non-accredited institutions in 2021 (p = 0.005) and 2023 (p = 0.004), but not significantly different Surgery Scores. CONCLUSIONS: The baseline survey in 2021 demonstrated significant knowledge of technical aspects of cancer surgery among a broad surgeon base, but a need for greater understanding of the accreditation standards. The repeat survey distribution 2 years after rollout of the operative standards and associated educational programing showed increased awareness surrounding the operative standards in 2023 and a trend toward improvement in knowledge of the accreditation standards across all specialties. Further evaluation will be directed toward compliance with the accreditation standards.
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INTRODUCTION: To improve the detection and management of perioperative hyperglycemia at our tertiary cancer center, we implemented a glycemic control quality improvement initiative. The primary goal was to decrease the percentage of diabetic patients with median postoperative glucose levels > 180 mg/dL during hospitalization by 15% within 2 years. METHODS: A multidisciplinary team standardized preoperative screening, preoperative, intraoperative, and postoperative hyperglycemia management. We included all patients undergoing nonemergent inpatient and outpatient operations. We used a t test, rank sum, chi-square, or Fisher's exact test to assess differences in outcomes between patients at baseline (BL) (10/2018-4/2019), during the first phase (P1) (10/2019-4/2020), second phase (P2) (5/2020-12/2020), and maintenance phase (M) (1/2021-10/2022). RESULTS: The analysis included 9891 BL surgical patients (1470 with diabetes), 8815 P1 patients (1233 with diabetes), 10,401 P2 patients (1531 with diabetes) and 30,410 M patients (4265 with diabetes). The percentage of diabetic patients with median glucose levels >180 mg/dL during hospitalization decreased 32% during the initiative (BL, 20.1%; P1, 16.9%; P2, 12.1%; M, 13.7% [P < .001]). We also saw reductions in the percentages of diabetic patients with median glucose levels >180 mg/dL intraoperatively (BL, 34.0%; P1, 26.6%; P2, 23.9%; M, 20.3% [P < .001]) and in the postanesthesia care unit (BL, 36.0%; P1, 30.4%; P2, 28.5%; M, 25.8% [P < .001]). The percentage of patients screened for diabetes by hemoglobin A1C increased during the initiative (BL, 17.5%; P1, 52.5%; P2, 66.8%; M 74.5% [P < .001]). CONCLUSIONS: Our successful initiative can be replicated in other hospitals to standardize and improve glycemic control among diabetic surgical patients.
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Diabetes Mellitus , Hiperglucemia , Neoplasias , Humanos , Glucemia , Hiperglucemia/diagnóstico , Hiperglucemia/etiología , Diabetes Mellitus/diagnóstico , Hemoglobina Glucada , Atención Perioperativa , Estudios RetrospectivosRESUMEN
INTRODUCTION: About 25% of patients with localized pancreatic adenocarcinoma have non-elevated serum carbohydrate antigen (CA) 19-9 levels at baseline, hampering evaluation of response to preoperative treatment. Serum carcinoembryonic antigen (CEA) is a potential alternative. METHODS: This retrospective cohort study from five referral centers included consecutive patients with localized pancreatic adenocarcinoma (2012-2019), treated with one or more cycles of (m)FOLFIRINOX, and non-elevated CA19-9 levels (i.e., < 37 U/mL) at baseline. Cox regression analyses were performed to assess prognostic factors for overall survival (OS), including CEA level at baseline, restaging, and dynamics. RESULTS: Overall, 277 patients were included in this study. CEA at baseline was elevated (≥5 ng/mL) in 53 patients (33%) and normalized following preoperative therapy in 14 patients (26%). In patients with elevated CEA at baseline, median OS in patients with CEA normalization following preoperative therapy was 33 months versus 19 months in patients without CEA normalization (p = 0.088). At time of baseline, only elevated CEA was independently associated with (worse) OS (hazard ratio [HR] 1.44, 95% confidence interval [CI] 1.04-1.98). At time of restaging, elevated CEA at baseline was still the only independent predictor for (worse) OS (HR 1.44, 95% CI 1.04-1.98), whereas elevated CEA at restaging (HR 1.16, 95% CI 0.77-1.77) was not. CONCLUSIONS: Serum CEA was elevated in one-third of patients with localized pancreatic adenocarcinoma having non-elevated CA19-9 at baseline. At both time of baseline and time of restaging, elevated serum CEA measured at baseline was the only predictor for (worse) OS. Therefore, serum CEA may be a useful tool for decision making at both initial staging and time of restaging in patients with non-elevated CA19-9.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirugía , Antígeno Carcinoembrionario , Antígeno CA-19-9 , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores de Tumor , Pronóstico , Estudios Retrospectivos , Adenocarcinoma/cirugía , Irinotecán , Oxaliplatino , Leucovorina , FluorouraciloRESUMEN
BACKGROUND: Pancreatic adenocarcinoma located in the pancreatic body might require a portomesenteric venous resection (PVR), but data regarding surgical risks after distal pancreatectomy (DP) with PVR are sparse. Insight into additional surgical risks of DP-PVR could support preoperative counseling and intraoperative decision making. This study aimed to provide insight into the surgical outcome of DP-PVR, including its potential risk elevation over standard DP. METHODS: We conducted a retrospective, multicenter study including all patients with pancreatic adenocarcinoma who underwent DP ± PVR (2018-2020), registered in four audits for pancreatic surgery from North America, Germany, Sweden, and The Netherlands. Patients who underwent concomitant arterial and/or multivisceral resection(s) were excluded. Predictors for in-hospital/30-day major morbidity and mortality were investigated by logistic regression, correcting for each audit. RESULTS: Overall, 2924 patients after DP were included, of whom 241 patients (8.2%) underwent DP-PVR. Rates of major morbidity (24% vs. 18%; p = 0.024) and post-pancreatectomy hemorrhage grade B/C (10% vs. 3%; p = 0.041) were higher after DP-PVR compared with standard DP. Mortality after DP-PVR and standard DP did not differ significantly (2% vs. 1%; p = 0.542). Predictors for major morbidity were PVR (odds ratio [OR] 1.500, 95% confidence interval [CI] 1.086-2.071) and conversion from minimally invasive to open surgery (OR 1.420, 95% CI 1.032-1.970). Predictors for mortality were higher age (OR 1.087, 95% CI 1.045-1.132), chronic obstructive pulmonary disease (OR 4.167, 95% CI 1.852-9.374), and conversion from minimally invasive to open surgery (OR 2.919, 95% CI 1.197-7.118), whereas concomitant PVR was not associated with mortality. CONCLUSIONS: PVR during DP for pancreatic adenocarcinoma in the pancreatic body is associated with increased morbidity, but can be performed safely in terms of mortality.
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BACKGROUND: Surgery in selected patients with locally advanced pancreatic cancer after induction chemotherapy may have drawbacks related to surgical risks and breaks or delays in oncological treatment, in particular when curative intent resection is not possible (that is non-therapeutic laparotomy). The aim of this study was to assess the incidence and oncological impact of a non-therapeutic laparotomy in patients with locally advanced pancreatic cancer treated with induction (m)FOLFIRINOX chemotherapy. METHODS: This was a retrospective international multicentre study including patients diagnosed with pathology-proven locally advanced pancreatic cancer treated with at least one cycle of (m)FOLFIRINOX (2012-2019). Patients undergoing a non-therapeutic laparotomy (group A) were compared with those not undergoing surgery (group B) and those undergoing resection (group C). RESULTS: Overall, 663 patients with locally advanced pancreatic cancer were included (67 patients (10.1%) in group A, 425 patients (64.1%) in group B, and 171 patients (25.8%) in group C). A non-therapeutic laparotomy occurred in 28.2% of all explorations (67 of 238), with occult metastases in 30 patients (30 of 67, 44.8%) and a 90-day mortality rate of 3.0% (2 of 67). Administration of palliative therapy (65.9% versus 73.1%; P = 0.307) and median overall survival (20.4 [95% c.i. 15.9 to 27.3] versus 20.2 [95% c.i. 19.1 to 22.7] months; P = 0.752) did not differ between group A and group B respectively. The median overall survival in group C was 36.1 (95% c.i. 30.5 to 41.2) months. The 5-year overall survival rates were 11.4%, 8.7%, and 24.7% in group A, group B, and group C, respectively. Compared with group B, non-therapeutic laparotomy (group A) was not associated with reduced overall survival (HR = 0.88 [95% c.i. 0.61 to 1.27]). CONCLUSION: More than a quarter of surgically explored patients with locally advanced pancreatic cancer after induction (m)FOLFIRINOX did not undergo a resection. Such non-therapeutic laparotomy does not appear to substantially impact oncological outcomes.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Laparotomía , Estudios Retrospectivos , Fluorouracilo , Leucovorina/uso terapéutico , Terapia Neoadyuvante , Irinotecán , OxaliplatinoRESUMEN
BACKGROUND AND OBJECTIVES: Patients with pancreatic and gastroesophageal (PGE) cancers experience high symptom burden, but patient experience throughout multimodality treatment remains unclear. We aimed to delineate the experience and symptom burden of patients throughout their perioperative course. METHODS: Qualitative interviews were performed with 17 surgical patients with PGE cancer. Interview transcripts were analyzed and symptoms were ranked by frequency. An expert panel assessed the relevance of these symptom inventory items. RESULTS: Of the 17 patients included, 35% (n = 6) underwent gastrectomy, 30% (n = 5) underwent esophagectomy, and 35% (n = 6) underwent pancreatectomy; 76% (n = 13) received neoadjuvant systemic chemotherapy and/or chemoradiation. Overall, 32 symptoms were reported, and 19 were reported by over 20% of patients. An expert panel rated nine symptoms to be relevant or very relevant to PGE surgical patients. These symptoms (difficulty swallowing, heartburn/reflux, diarrhea, constipation, flushing/sweating, stomach feeling full, malaise, dizziness, or feeling cold) were added to the core MD Anderson Symptom Inventory (MDASI) if they were commonly reported or reached a threshold relevancy score. CONCLUSIONS: In this qualitative study, we developed a provisional symptom inventory for patients undergoing surgery for PGE cancer. This symptom inventory module of the MDASI for PGE surgical patients will be psychometrically tested for validity and reliability.
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Esofagectomía , Medición de Resultados Informados por el Paciente , Investigación Cualitativa , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/psicología , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/psicología , Neoplasias Pancreáticas/terapia , Gastrectomía , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/terapia , Neoplasias Gástricas/psicología , Neoplasias Gástricas/patología , Adulto , Entrevistas como Asunto , Pancreatectomía , PronósticoRESUMEN
BACKGROUND: Although robotic pancreatectomy may facilitate an earlier functional recovery, the impact of a robotic pancreatectomy program during its early experience on the timing of return to intended oncologic therapy (RIOT) after surgery is unknown. METHODS: In this retrospective cohort study, we used propensity score matching with a 1:2 ratio to compare patients who underwent robotic or open surgery (distal pancreatectomy or pancreatoduodenectomy) for pancreatic ductal adenocarcinoma (PDAC) during the first 3 years of our robotic pancreatectomy experience (January 2018-December 2021). Generalized estimating equations modeling was used to evaluate the effect of surgical approach on early RIOT, defined as adjuvant chemotherapy initiation within 8 weeks after surgery, and late RIOT, defined as initiation within 12 weeks after surgery. RESULTS: The matched cohort included 26 patients who underwent robotic pancreatectomy and 52 patients who underwent open pancreatectomy. Rates of receipt of adjuvant chemotherapy were 96.2% and 78.9%, respectively. Rate of early RIOT in the robotic group (73.1% was higher than that in the open group (44.2%; P = 0.018). In multivariable analysis, a robotic approach was associated with early RIOT (odds ratio, 3.54; 95% confidence interval 1.08-11.62; P = 0.038). Surgical approach did not impact late RIOT (odds ratio, 3.21; 95% confidence interval 0.71-14.38; P = 0.128). CONCLUSIONS: Compared with open pancreatectomy, robotic pancreatectomy did not delay RIOT. In fact, odds of early RIOT were increased, which supports the oncological safety of our robotic pancreatectomy program during its implementation.
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BACKGROUND: Stereotactic body radiotherapy (SBRT) has the potential to ablate localised pancreatic ductal adenocarcinoma. Selective dismutase mimetics sensitise tumours while reducing normal tissue toxicity. This trial was designed to establish the efficacy and toxicity afforded by the selective dismutase mimetic avasopasem manganese when combined with ablative SBRT for localised pancreatic ductal adenocarcinoma. METHODS: In this adaptive, randomised, double-blind, placebo-controlled, phase 1b/2 trial, patients aged 18 years or older with borderline resectable or locally advanced pancreatic cancer who had received at least 3 months of chemotherapy and had an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled at six academic sites in the USA. Eligible patients were randomly assigned (1:1), with block randomisation (block sizes of 6-12) with a maximum of 24 patients per group, to receive daily avasopasem (90 mg) or placebo intravenously directly before (ie, within 180 min) SBRT (50, 55, or 60 Gy in five fractions, adaptively assigned in real time by Bayesian estimates of 90-day safety and efficacy). Patients and physicians were masked to treatment group allocation, but not to SBRT dose. The primary objective was to find the optimal dose of SBRT with avasopasem or placebo as determined by the late onset EffTox method. All analyses were done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT03340974, and is complete. FINDINGS: Between Jan 25, 2018, and April 29, 2020, 47 patients were screened, of whom 42 were enrolled (median age was 71 years [IQR 63-75], 23 [55%] were male, 19 [45%] were female, 37 [88%] were White, three [7%] were Black, and one [2%] each were unknown or other races) and randomly assigned to avasopasem (n=24) or placebo (n=18); the placebo group was terminated early after failing to meet prespecified efficacy parameters. At data cutoff (June 28, 2021), the avasopasem group satisfied boundaries for both efficacy and toxicity. Late onset EffTox efficacy response was observed in 16 (89%) of 18 patients at 50 Gy and six (100%) of six patients at 55 Gy in the avasopasem group, and was observed in three (50%) of six patients at 50 Gy and nine (75%) of 12 patients at 55 Gy in the placebo group, and the Bayesian model recommended 50 Gy or 55 Gy in five fractions with avasopasem for further study. Serious adverse events of any cause were reported in three (17%) of 18 patients in the placebo group and six (25%) of 24 in the avasopasem group. In the placebo group, grade 3 adverse events within 90 days of SBRT were abdominal pain, acute cholangitis, pyrexia, increased blood lactic acid, and increased lipase (one [6%] each); no grade 4 events occurred. In the avasopasem group, grade 3-4 adverse events within 90 days of SBRT were acute kidney injury, increased blood alkaline phosphatase, haematoma, colitis, gastric obstruction, lung infection, abdominal abscess, post-surgical atrial fibrillation, and pneumonia leading to respiratory failure (one [4%] each).There were no treatment-related deaths but one late death in the avasopasem group due to sepsis in the setting of duodenal obstruction after off-study treatment was reported as potentially related to SBRT. INTERPRETATION: SBRT that uses 50 or 55 Gy in five fractions can be considered for patients with localised pancreatic ductal adenocarcinoma. The addition of avasopasem might further enhance disease outcomes. A larger phase 2 trial (GRECO-2, NCT04698915) is underway to validate these results. FUNDING: Galera Therapeutics.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Radiocirugia , Humanos , Masculino , Femenino , Anciano , Adenocarcinoma/radioterapia , Adenocarcinoma/tratamiento farmacológico , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/tratamiento farmacológico , Radiocirugia/efectos adversos , Teorema de Bayes , Carcinoma Ductal Pancreático/radioterapia , Carcinoma Ductal Pancreático/tratamiento farmacológico , Método Doble Ciego , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
OBJECTIVE: We sought to evaluate symptomatic adverse event (AE) rates among patients with pancreatic cancer receiving neoadjuvant therapy on clinical trial (A021501) using the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE). BACKGROUND: To date, pancreatic cancer clinical trials have measured AEs using standard physician reporting [Common Terminology Criteria for Adverse Events (CTCAE)]. Patient-reported symptomatic AEs have been incompletely characterized. METHODS: A021501 (December 31, 2016-January 1, 2019) randomized patients with borderline resectable pancreatic ductal adenocarcinoma to 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX+hypofractionated radiotherapy (Arm 2), followed by pancreatectomy and adjuvant FOLFOX6. Patients completed PRO-CTCAE assessments at baseline, on day 1 of each chemotherapy cycle, and daily during radiotherapy. RESULTS: Of 126 patients, 96 (76%) initiated treatment and completed a baseline plus at least 1 postbaseline PRO-CTCAE assessment. Diarrhea and fatigue were the only symptomatic grade 3 or higher AEs identified in at least 10% of patients using CTCAE. At least 10% of all patients reported an adjusted PRO-CTCAE composite grade 3 AE during neoadjuvant treatment for 10 of 15 items: anxiety (10%), bloating of abdomen (16%), decreased appetite (18%), diarrhea (13%), dry mouth (21%), fatigue (36%), nausea (18%), generalized pain (16%), abdominal pain (21%), and problems tasting (32%). Decreased appetite was higher in Arm 2 than in Arm 1 ( P =0.0497); no other differences between study arms were observed. CONCLUSION: Symptomatic AEs during neoadjuvant therapy were common and were reported more frequently by patients using PRO-CTCAE than were recorded by clinicians using standard CTCAE.
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Adenocarcinoma , Neoplasias , Neoplasias Pancreáticas , Humanos , Terapia Neoadyuvante/efectos adversos , Neoplasias Pancreáticas/tratamiento farmacológico , Medición de Resultados Informados por el Paciente , Neoplasias/tratamiento farmacológico , Neoplasias PancreáticasRESUMEN
OBJECTIVE: We sought to characterize differences in pancreatectomy recommendation rates to surgically eligible patients with pancreatic ductal adenocarcinoma of the pancreatic head across age and racial groups. BACKGROUND: Pancreatectomy is not recommended in almost half of otherwise healthy patients with stage I/II pancreatic ductal adenocarcinoma lacking a surgical contraindication. We characterized differences in pancreatectomy recommendation among surgically eligible patients across age and racial groups. METHODS: Non-Hispanic White (NHW) and Non-Hispanic Black (NHB) patients were identified in the National Cancer Database with clinical stage I/II pancreatic head adenocarcinoma, Charlson Comorbidity Index of 0 to 1, and age 40 to 89 years. Rates of surgery recommendation and overall survival (OS) by age and race were compared. A Pancreatectomy Recommendation Equivalence Point (PREP) was defined as the age at which the rate of not recommending surgery matched the rate of recommending and completing surgery. Marginal standardization was used to identify association of age and race with recommendation. OS was compared using Kaplan-Meier and Cox regression models. RESULTS: Among 40,866 patients, 36,133 (88%) were NHW and 4733 (12%) were NHB. For the entire cohort, PREP was 79 years. PREP was 5 years younger in NHB patients than in NHW patients (75 vs 80 years). Adjusted rates of not recommending surgery were significantly higher for NHB than for NHW patients in each age group. After adjusting for surgery recommendation, we found no difference in OS between NHW and NHB patients (hazard ratio 0.98 [95% CI 0.94-1.02]). CONCLUSIONS: PREP of NHB patients was 5 years younger than NHW patients, and in every age group, the rate of not recommending pancreatectomy was higher in NHB patients. Age and race disparities in treatment recommendations may contribute to shorter longevity of NHB patients.
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Adenocarcinoma , Población Blanca , Humanos , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Hispánicos o Latinos , Negro o Afroamericano , Etnicidad , Adenocarcinoma/cirugía , Neoplasias PancreáticasRESUMEN
OBJECTIVE: To characterize associations between carbohydrate antigen 19-9 (CA19-9) dynamics during neoadjuvant therapy (NT) and survival for patients with pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Although normalization of CA19-9 during NT is associated with improved outcomes following PDAC resection, we hypothesize that CA19-9 dynamics during NT can improve prognostication. METHODS: Characteristics for patients with PDAC undergoing NT (July 2011-October 2018) with ≥3 CA19-9 results (bilirubin<2mg/dL) were collected and grouped by CA19-9 dynamics. Nonproducers (<1 U/ml) were excluded, and normal was ≤35 U/ml. Postresection survival was compared among groups. RESULTS: Of 431 patients, 166 had eligible CA19-9 values. Median baseline CA19-9 was 98 U/ml. Overall 2-year postresection recurrence-free survival (RFS) and overall survival (OS) were 37% and 63%, respectively. Patients with normalization (53%) had improved 2-year RFS (47% vs. 28%, P = 0.01) and OS (75% vs. 49%, P = 0.01). CA19-9 dynamics during NT were analyzed by shape, direction, and normalization creating response types ("A-B-C-D-E"). Type A was "Always" decreasing to normalization, B "Bidirectional" with eventual normalization, C "Consistently" normal, D any "Decrease" without normalization, and E "Elevating" without normalization. Types A and B responses were associated with the longest postresection 2-year RFS (51% and 56%) and OS (75% and 92%, respectively) whereas Types D and E had the worst outcomes. After adjusting for node-positivity, perineural invasion, and margin-positivity, CA19-9 response types were independently associated with both RFS and OS, and predicted outcomes are better than CA19-9 normalization alone (likelihood ratio test RFS P < 0.001, OS P = 0.01). CONCLUSIONS: This novel A-B-C-D-E classification of CA19-9 dynamics during NT was associated with postresection outcomes more precisely than CA19-9 normalization alone.
Asunto(s)
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirugía , Antígeno CA-19-9 , Adenocarcinoma/cirugía , Terapia Neoadyuvante , Estudios Retrospectivos , Pronóstico , Carcinoma Ductal Pancreático/cirugíaRESUMEN
OBJECTIVE: Within a learning health system paradigm, this study sought to evaluate reasons for readmission to identify opportunities for improvement. SUMMARY BACKGROUND DATA: Post-pancreatectomy readmission rates have remained constant despite improved index hospitalization metrics. METHODS: We performed a single-institution case-control study of consecutive pancreatectomy patients (October 2016 - April 2022). Complications were prospectively graded in biweekly faculty and advanced practice provider meetings. We analyzed risk factors during index hospitalization and categorized indications for 90-day readmissions. RESULTS: A total of 835 patients, median age 65 years and 51% (427/835) males, underwent 64% (534/835) pancreatoduodenectomies, 34% (280/835) distal pancreatectomies, and 3% (21/835) other resections. 24% (204/835) of patients were readmitted. Primary indication for readmission was technical in 51% (105/204), infectious in 17% (35/204), and medical/metabolic in 31% (64/204) of patients. Procedures were required in 77% (81/105) and 60% (21/35) of technical and infectious readmissions, respectively, while 66% (42/64) of medical/metabolic readmissions were managed non-invasively. During the index hospitalization, benign pathology (OR 1.8, P=0.049), biochemical pancreatic leak (OR 2.3, P=0.001), bile/gastric/chyle leak (OR 6.4, P=0.001), organ-space infection (OR 3.4, P=0.007), undrained fluid on imaging (OR 2.4, P=0.045), and increasing white blood cell count (OR 1.7, P=0.045) were independently associated with odds of readmission. CONCLUSIONS: Most readmissions following pancreatectomy were technical in origin. Patients with complications during index hospitalization, increasing white blood cell count, or undrained fluid before discharge were at highest risk for readmission. Pre-discharge risk-stratification of readmission risk factors and augmentation of in-clinic resources may be strategies to reduce readmission rates.
RESUMEN
OBJECTIVE: To determine the effects of a preoperative, home-based exercise program on fitness and physical function in patients with pancreatic cancer. BACKGROUND: We previously established a well-tolerated preoperative exercise program after finding a high frequency of sarcopenia and frailty in patients with pancreatic cancer. METHODS: In this randomized, controlled trial (NCT03187951), patients with pancreatic cancer were randomized to Arm A: enhanced usual care or Arm B: prescribed aerobic and resistance exercise during neoadjuvant therapy. Patients received nutrition counseling and activity trackers. The primary endpoint was a 6-minute walk distance (6MWD; ≥14 meters improvement was clinically meaningful). Secondary endpoints included additional physical function tests, health-related quality of life, and clinical outcomes. RESULTS: One hundred fifty-one patients were randomized. Objectively measured weekly activity (153.2±135.6 and 159.8±122.8 min in Arm A and B, respectively, P =0.62) and self-reported weekly moderate-to-strenuous physical activity (107.4±160.4 and 129.6±161.6 min in Arm A and Arm B, respectively, P =0.49) were similar, but weekly strength training sessions increased more in Arm B (by 1.8±1.8 vs 0.1±2.4 sessions, P <0.001). 6MWD improved in both Arm A (mean change 18.6±56.8 m, P =0.01) and Arm B (27.3±68.1 m, P =0.002). Quality of life and clinical outcomes did not significantly differ between arms. Pooling patients in both study groups, exercise, and physical activity was favorably associated with physical performance and clinical outcomes. CONCLUSIONS: In this randomized trial of prescribed exercise versus enhanced usual care during neoadjuvant therapy for pancreatic cancer, a high volume of physical activity and increased exercise capacity were observed in both arms, highlighting the importance of activity among patients preparing for surgery.
Asunto(s)
Neoplasias Pancreáticas , Calidad de Vida , Humanos , Terapia Neoadyuvante , Ejercicio Físico , Terapia por Ejercicio , Neoplasias Pancreáticas/terapiaRESUMEN
BACKGROUND: Achieving optimal surgical outcomes in pancreatic adenocarcinoma requires a combination of both curative-intent resection to oncologic standards and stage-specific neoadjuvant or adjuvant therapy. This investigation sought to examine factors associated with receipt of standard-adherent surgery (SAS) and guideline-recommended therapy (GRT) and determine the impact of compliance on patient survival. PATIENTS AND METHODS: From the 2006-2016 National Cancer Database, 21,304 patients underwent resection for nonmetastatic pancreatic adenocarcinoma. SAS was defined as pancreatic resection with negative margins and ≥ 15 lymph nodes examined. Stage-specific GRT was defined by current National Comprehensive Cancer Network guidelines. Multivariable models were used to determine predictors of adherence to SAS and GRT and prognostic impact on overall survival. RESULTS: Overall, SAS was achieved in 39% and GRT in 65% of patients, but only 30% received both SAS and GRT. Increasing age, minority race, uninsured status, and greater comorbidities were associated with a decreased odds of receiving both SAS and GRT (all p < 0.05). SAS (HR 0.79; CI 0.76-0.81; p < 0.001) and GRT (HR 0.67; CI 0.65-0.69; p < 0.001) were each independently associated with a survival advantage. Receipt of both SAS and GRT was associated with significant improvement in median OS compared with receiving neither (2.2 years vs 1.1 years; p < 0.001) which was independently associated with a 78% increased risk of death (HR 1.78; CI 1.70-1.86; p < 0.001). CONCLUSIONS: Despite survival benefits associated with adherence to operative standards and receipt of guideline-recommended therapy, compliance remains poor. Future efforts must be directed toward improved education and implementation efforts around both operative standards and therapy guidelines.