bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resection rate of locally advanced pancreatic cancer in gemcitabine plus nab-paclitaxel versus FOLFIRINOX.
Authors: Sharif Shahriar , Zureikat Amer H. , Novelli Paula M. , Lopez Charles D. , Kardosh Adel , Chung Ki Y. , Jones Wesley B. , Hatoum Hassan , Meredith Kenneth Lee , Zervos Emmanuel E. , Ucar Antonio , Gandhi Ripal T , Nazemzadeh Reza , Kasi Pashtoon Murtaza , Vandestraeten Erik , Decaestecker Jochen , Delaunoit Thierry , Li Charles Charles , Agah Ramtin , Pishvaian Michael J. 
Published: January 2021

381 Background: There is no established treatment for locally advanced pancreatic cancer (LAPC), but by utilizing the regimens approved for metastatic pancreatic cancer, hope remains for rendering tumors resectable with chemotherapy. In this context, we looked at the resection rate in patients receiving gemcitabine plus nab-paclitaxel (Gem-Nab) in a prospective trial of patients with LAPC. Methods: TIGeR-PaC is an ongoing phase III clinical trial, studying the role of intra-arterial Gemcitabine (IA-Gem) in LAPC. The trial is designed with an induction phase where patients receive 3 cycles of Gem-Nab and a cycle of radiation after which they are randomized to IA-Gem or continuing with 4 cycles of Gem-Nab. We studied the resection rate in patients receiving Gem-Nab during induction who had subsequently continued receiving Gem-Nab post-randomization. Results: As of July 2020, 80 patients have been enrolled in the study. From this report, 30 patients were excluded because they had not completed induction and/or active treatment or were randomized to IA-Gem at the time of analysis. From the remaining 50 patients, 5 underwent resection for an overall resection rate of 10%. The median age for the total cohort was 67 years (range 47-83). Most of the resections were performed on the younger cohort of patients under 65 years (median age 60, range 47-65) in whom the resection rate was 4 out of 22 (18.2%). Conclusions: In the younger cohort of patients, TIGeR-PaC results are in line with the 15% resection rate in the LAPACT trial of patients with median age of 65 years, as reported by Phillip et al., 2020. In the TIGeR-PaC study the resection rate for LAPC treated with Gem-Nab was 10% overall, and 18.2% for younger patient population. These resection rates are comparable to the other reports for Gem-Nab and are similar to retrospective reports for the younger patients undergoing resection after treatment with FOLFIRINOX. Clinical trial information: NCT03257033.
Efficacy and safety of liposomal irinotecan plus fluorouracil/leucovorin after progression on conventional irinotecan-containing chemotherapy for metastatic pancreatic adenocarcinoma.
Authors: Bang Kyunghye , Cheon Jaekyung , Jeong Jae Ho , Im Hyeon-Su , Kim Kyu-Pyo , Ryoo Baek-Yeol , Yoo Changhoon 
Published: January 2021

382 Background: Liposomal irinotecan (nal-IRI) plus fluorouracil/leucovorin (5-FU/LV) has demonstrated its clinical benefit in patients with metastatic pancreatic adenocarcinoma (mPAC) who progressed on prior gemcitabine-based chemotherapy. However, its role in patients who previously treated with conventional irinotecan has not been investigated. We analyzed clinical outcomes of nal-IRI + 5-FU/LV in mPAC patients after progression on conventional irinotecan-containing chemotherapy. Methods: In this multicenter retrospective analysis, a total of 35 patients with mPAC who received nal-IRI + 5-FU/LV after progression on irinotecan-containing regimen, between January 2017 and March 2020, were included. The ratio of time-to-progression (TTP) with nal-IRI + 5-FU/LV to TTP with conventional irinotecan (TTPr) was correlated with duration and cumulative dose of prior conventional irinotecan. Results: The median age was 58 years (range, 35-73) and 16 patients (46%) were male. All patients received prior irinotecan as the component of FOLFIRINOX. The median duration of prior irinotecan was 4.6 months (range, 0.5-16.8) and median cumulative dose of prior irinotecan was 1230 mg (range, 150-4650). Objective response rate of nal-IRI + 5-FU/LV was 2.9% (1 partial response) and stable disease was achieved in 31.4% (n = 11). With median follow-up duration of 9.2 months [95% CI, 7.8-10.5], the median PFS and OS were 2.0 months [95% CI, 1.4-2.6] and 4.4 months [95% CI, 3.6-5.7], respectively. 6-month PFS rate was 16.3% and OS rate was 37.5%. The median TTPr was 0.41 (range 0.07-2.07) and this showed negative correlation between cumulative dose of prior irinotecan (R = -0.37, p = 0.041). There was a tendency for the negative correlation between TTPr and duration of prior irinotecan (R = -0.35, p = 0.062). Most common grade 3-4 toxicities were neutropenia (20%) and fatigue (8.6%). Conclusions: Nal-IRI + 5-FU/LV showed only modest efficacy for mPAC patients who progressed on conventional irinotecan-containing chemotherapy. Cumulative dose of prior conventional irinotecan may be correlated with the efficacy of nal-IRI + 5-FU/LV.
Real-world outcomes in recurrent versus de novo metastatic pancreatic adenocarcinoma.
Authors: Miotke Laura , Nevala-Plagemann Christopher Duane , Ying Jian , Florou Vaia , Haaland Benjamin , Garrido-Laguna Ignacio 
Published: January 2021

387 Background: Optimal management of patients with recurrent pancreatic ductal adenocarcinoma (PDAC) is unknown. In the clinical trials that established a survival benefit with combination chemotherapy compared to single agent gemcitabine, patients with recurrent PDAC were either excluded (PRODIGE-4) or severely underrepresented (MPACT). In this study, we evaluated clinical outcomes of recurrent PDAC patients who receive systemic therapy and compared outcomes to patients with de novo advanced PDAC. Methods: Patients diagnosed with advanced PDAC between 2014 and October of 2019 were included using the nationwide Flatiron Health EHR-derived de-identified database. Patients without a clinic visit or initiation of treatment within 90 days of diagnosis were excluded. Patients were characterized as either de novo or recurrent PDAC based on stage at diagnosis and history of surgery. Patients with recurrent PDAC were further stratified based on time to recurrent disease. Overall survival (OS) was summarized within groups via Kaplan-Meier survival estimates, and compared between groups in the context of univariable and multivariable Cox proportional hazards models. The covariates adjusted for were gender, age, race, ECOG, smoking status, primary site, CA199, albumin, lymphocytes, neutrophils and monocytes. Results: We included 5170 patients with advanced PDAC, of which 1101 (21.3%) met criteria for recurrent disease. Patients with recurrent PDAC were more likely to have tumors in the head of the pancreas (71% vs 40%, p < 0.001) and had lower median CA19-9 (92.8 vs 617, p < 0.001), compared to the de novo PDAC patients. Median OS for the recurrent group was 10.8 m (95% CI = 9.9-11.7) vs. 7.3 m (95% CI = 7.0-7.7) in the de novo group (p < 0.001, both univariate and multivariable adjusted analyses). The most common first line palliative chemotherapy in patients with recurrent disease was Nab-paclitaxel plus gemcitabine (41%) or FOLFIRINOX (21%). Patients who recurred within six months of surgery (28%) had an OS of 10.0 m (95% CI = 8.7 -11) vs. 11.6 m (95% CI 10-12, p = 0.256) in those who recurred greater than six months from surgery. Conclusions: Our data suggest that patients with recurrent disease have significantly better survival outcomes compared to patients with de novo metastatic disease. We did not observe a significant difference in survival of patients who recurred within 6 months of resection compared to those who recurred greater than six months after surgery. These data support the inclusion of patients with recurrent PDAC in clinical trials, including those who develop recurrent disease within 6 months of surgery, with appropriate stratification for these variables.
Comparison of first-line (1L) treatment (tx) patterns and overall survival by age at diagnosis among patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).
Authors: Elias Rawad , Cockrum Paul , Surinach Andy , Wang Shu , Chu Bong Chul 
Published: January 2021

388 Background: Pancreatic cancer is mostly diagnosed in patients (pts) aged ≥ 65 years and the mortality rate is the highest among older adults. As the population ages, it is expected that there will be a significant rise in the number of older pts with mPDAC but guidance regarding their management is limited as these pts are under-represented in clinical trials. The oncological care of older adults in daily practice is challenged by various age-related conditions. Therefore, a better understanding of the real-world population will help in the development of more effective tx strategies. This study describes the proportion of pts with mPDAC who were treated, the types of regimens received, and the associated survival outcomes by age at diagnosis. Methods: Data were extracted for pts diagnosed with mPDAC between Jan 2015 and Mar 2020 from the Flatiron Health database. Pts were stratified into three age groups at diagnosis: <70y, 70-79y, and ≥ 80y. The proportion of pts was evaluated who received 1L tx and the types of regimens received in the metastatic setting. ECOG performance scores (PS) at tx initiation were described. Overall survival (OS) from the start of 1L was estimated using Kaplan-Meier methods. Results: Overall, of the 8,382 pts identified, 71.3% (n=5,973) received tx. Among pts who received tx, 55.5% (n=3,313) were aged <70y at diagnosis, 33.0% (n=1,972) were 70-79y, and 11.5% (n=688) were 80y+. Among those with data available, ECOG PS ≥2 was observed in 15.9% (n=381) of pts <70y, 21.0% (n=309) of pts 70-79y, and 29.9% (n=147) of pts 80y+(p < 0.001). The proportion of pts who received tx decreased with increasing age at diagnosis: 74.9%, 70.9%, and 58.5% for pts aged <70y, 70-79y, and 80y+, respectively. Gemcitabine monotherapy (gem-mono) and gemcitabine + nab-paclitaxel (GNP) accounted for > 70% of regimens prescribed to pts aged 80y+. The median OS (mOS) for patients treated with GNP, gem-mono, FOLFIRINOX, and liposomal irinotecan-based regimens are presented in the table. Conclusions: This study of treatment patterns among pts with mPDAC found that older pts were more likely to have a decreased performance status and are less likely to receive treatment. However, older adults who received systemic therapy had comparable survival outcomes to younger pts treated with a similar regimen. The results of this large descriptive analysis suggest that the treatment strategy of mPDAC should not be based on age but rather on an overall assessment of the performance/functional status and geriatric profile of older pts. [Table: see text]
Real-world safety data and differentiation of second-line (2L) 5-fluorouracil (5-FU) based regimens among patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).
Authors: Kim George P. , Cockrum Paul , Chudnovsky Aleksander , Surinach Andy , Wainberg Zev A. , Wang Shu , Yakubu Amin 
Published: January 2021

390 Background: Chemotherapy related adverse events (AEs) can impact the treatment of patients, reducing quality of life and leading to dose delays and treatment discontinuation. This study examined the proportion of patients (pts) with mPDAC treated with 5-FU-based regimens in the 2L setting who experienced AEs during treatment. Methods: Data were extracted for pts diagnosed with mPDAC who initiated 2L treatment between January 2016 and July 2020 from the Flatiron Health electronic health database. Pts included in the study were treated with FOLFIRINOX (FFX), FOLFOX, FOLFIRI, or a regimen containing liposomal irinotecan. The occurrence of grade 3 (G3) and grade 4 (G4) neutropenia, G3/G4 elevated alanine transaminase (ALT) and anemia where transfusion was indicated were determined using lab results and the grading criteria from the Common Terminology Criteria for Adverse Events v4.03. The occurrence of diarrhea, fatigue, nausea and vomiting (N/V), and neuropathy were identified from structured diagnosis records through ICD-10-CM codes. Duration of therapy (DOT) was assessed for each regimen. Descriptive statistics for AEs and DOT were reported. Results: Of the 804 pts included in the study, 28.4% (n=228) received FFX, 39.8% (n=320) received regimens containing liposomal irinotecan, 24.8% (n=199) received FOLFOX, and 7.1% (n=57) received FOLFIRI. The median DOT (IQR) was 86 days (d) (43 – 206), 79d (41 – 169), 72d (43 – 166), and 84d (46 – 148) for pts who received FFX, liposomal irinotecan, FOLFOX, and FOLFIRI, respectively. G3/G4 neutropenia (<1000/mm3) presented in 28.1% (n=64) of pts treated with FFX, 11.9% (n=38) of pts treated with liposomal irinotecan, 17.1% (n=34) of pts treated with FOLFOX, and 36.8% (n=21) of pts treated with FOLFIRI. NV occurred in 14.9% (n=34), 13.1% (n=42), 12.6% (n=25), and 10.5% (n=6), respectively. The full AE results are summarized in the table. Conclusions: In this assessment of often dose-limiting AEs among pts with mPDAC treated in 2L, pts who received liposomal irinotecan had the lowest proportion of neutropenia. No clear pattern was noted for N/V, neuropathy, fatigue, anemia, and elevated ALT. Further research is necessary to determine the real-world cost implications of AEs in this patient population. [Table: see text]
The pattern of brain metastasis in colorectal cancer: Efficacy of metastasectomy, chemotherapy.
Authors: Goksu Suleyman Yasin , Beg Muhammad Shaalan , Sanjeevaiah Aravind , Gumusgoz Emrah , Hsieh David , Ozer Muhammet , Jones Amy Little , Kainthla Radhika , Verma Udit , Al Mutar Salwan , Olson Craig , Pogacnik Javier Salgado , Sanford Nina Niu , Kazmi Syed Mohammad Ali 
Published: January 2021

40 Background: Colorectal cancer patients with brain metastases experience poor outcomes; however treatment strategies are understudied. In this study, we investigated the impact of different treatments for colorectal cancer patients with brain metastases. Methods: We identified stage 4 colorectal adenocarcinoma patients with brain metastasis using the National Cancer Database diagnosed between 2010 and 2015. Patients with unknown survival data, other histologies, and multiple primary sites were excluded. Patients with and without brain metastasis were compared using the Chi-square test. Kaplan-Meier method was performed to calculate univariable overall survival (OS). We used the Cox regression model for multivariable analysis after adjusting by age, race/ethnicity, comorbidity score, surgery, chemotherapy, and radiotherapy. Results: Among 75,901 patients with stage 4 colorectal adenocarcinoma, 1.6% had brain metastasis. Patients with brain metastasis were more likely to have bone (23% vs. 5%, p < 0.001) and lung metastasis (52% vs. 21%, p < 0.001), but less likely to have liver metastasis (56% vs. 72%, p < 0.001) compared to patients without brain metastasis. Patients with brain metastasis had higher KRAS mutation rate (54% vs. 43%, p < 0.001). Patients with brain metastasis were more likely to be age ≥ 50 years (85% vs. 83%, p = 0.01), white race (76% vs. 71%, p = 0.001), and receive radiotherapy (63% vs. 12%, p < 0.001). Total 26.4% of patients with brain metastasis underwent metastasectomy, and those patients had better OS compared to patients with non-metastasectomy (median OS 12 vs. 4 months, p < 0.001). Median OS in all patients with brain metastasis was 5.5 months. Patients with brain metastasis who received multiagent chemotherapy had improved OS compared with patients who received single-agent chemotherapy (mOS 13 vs. 6 months, p < 0.001). Patients with brain metastasis who received brain radiotherapy had better OS (mOS 6.3 vs. 3.7 months, p = 0.005) than those who did not. On multivariable analysis, metastasectomy (HR 0.65 95% CI [0.57-0.75]) and receipt of multiagent chemotherapy (HR 0.68 95% CI [0.54-0.86]) were associated with favorable prognosis, but brain radiotherapy was not (HR 1.04 95% CI [0.91-1.19]). Conclusions: Brain metastases are rare in colorectal cancer but portend poor survival. Lung and bone metastases are found more frequently in these patients. Treatment with metastasectomy or multiagent chemotherapy is associated with improved overall survival.
Projected 30-day out-of-pocket and total spending on pancreatic enzyme replacement therapy under Medicare Part D.
Authors: Gupta Arjun , Premnath Naveen , Beg Muhammad Shaalan , Khera Rohan , Dusetzina Stacie 
Published: January 2021

401 Background: Pancreatic enzyme replacement therapy (PERT) can reduce symptoms of indigestion and improve nutrition in patients with exocrine pancreatic insufficiency. PERT is under-prescribed, and this may be related to actual costs and prescriber sensitivity to these costs. Thus, we aimed to assess PERT costs. Methods: We used Medicare Part D formulary and pricing files for the first quarter of 2020 to conduct a patient-level modeling study to describe point-of-sale and out-of-pocket costs for each PERT formulation among Part D stand-alone and Medicare Advantage prescription drug plans. We calculated costs across nationwide plans under three scenarios: (1) standard benefit design ($435 deductible and 25% coinsurance after the deductible is met); (2) 25% coinsurance (for fills after the deductible and in the coverage gap until the patient spends $6,350 out-of-pocket); and (3) 5% coinsurance (once catastrophic coverage is reached). PERT doses are identified by the lipase content per capsule (in United States Pharmacopeia, USP, units). We calculated the number of units for each PERT formulation/ dose form that would provide optimally dosed PERT for the average US adult (250,000 USP units of lipase per day), based on guidelines and consensus. We first calculated costs for a single unit of PERT. Next, we calculated the number of units needed daily for each formulation/ dose form to provide optimally dosed PERT, and multiplied it by 30 to generate 30-day requirements and costs. Results: Across 3,974 plans nationwide, five PERT formulations in seventeen different doses were covered by Medicare plans in 2020. The range of lipase content in a single unit ranged from 3,000 to 40,000 USP units, and the per-unit list price ranged from $1.44 to $13.89. The point-of-sale price for a 30-day supply of optimally dosed PERT ranged from $2,109 to $4,840. For patients, the expected out-of-pocket costs for a 30-day supply of optimally dosed PERT averaged $999 across formulations (range, $853 to $1536) for those paying a deductible and coinsurance, $673 (range, $527 to $1210) for fills made after meeting the deductible until reaching catastrophic coverage, and $135 (range, $105 to $242) after reaching catastrophic coverage. Conclusions: In this analysis of 2020 Medicare Part D plans, the estimated out-of-pocket cost for just a 30-day supply of optimally dosed PERT was high— at least $100 in the catastrophic phase and approximately $1,000 in the initial phase. In the setting of pancreas cancer, already associated with heavy symptom burden and distress, the financial burden from a supportive care intervention (such as PERT) has been underappreciated. These costs may serve as a barrier to Medicare beneficiary drug access and contribute to financial toxicity.
Nanoliposomal irinotecan-based chemotherapy after regular irinotecan-based chemotherapy in patients with pancreas cancer.
Authors: Smith Caleb J , Bekaii-Saab Tanios S. , Cook Kathryn , Eiring Rachel , Halfdanarson Thorvardur Ragnar , Hanna Mina Samir Erian , Jin Zhaohui , Jochum Jacob A. , Ma Wen Wee , Mitchell Jessica L , Pitot Henry C. , Jatoi Aminah 
Published: January 2021

402 Background: Pancreas cancer is an aggressive malignancy with limited therapeutic options. Nanoliposomal irinotecan (Nal-IRI) is a preferred second-line treatment, and current guidelines recommend its use in the absence of prior irinotecan. This study aimed to assess whether patients who had received regular irinotecan derive benefit from Nal-IRI. Methods: Medical records of metastatic pancreas cancer patients who had received regular irinotecan and then Nal-IRI were reviewed. The following information was extracted from each medical record: patient demographics, confirmation of a diagnosis of exocrine pancreas cancer, initial cancer stage, dates of administration of the drugs of interest, adverse events that occurred with Nal-IRI treatment, reasons for stopping regular irinotecan, and reasons for starting and stopping Nal-IRI. The primary endpoint was overall survival after the initiation of Nal-IRI (an a priori threshold of > 4 months defined success). Survival data were censored based on date of last follow up. Direct quotes from the medical record were documented to provide insight on prescribing Nal-IRI when guidelines advised the contrary. Results: Sixty four patients met eligibility criteria with a median age of 65 years (range: 36, 80 years). Prior to Nal-IRI, 61 patients had received FOLFIRINOX, and 3 FOLFIRI. Of these, 32 patients manifested progressive disease on regular irinotecan-based therapy. Nal-IRI was prescribed with a fluoropyrimidine; only one patient received monotherapy. At time of analysis, 54 patients had died. Median overall survival from initiation of Nal-IRI was 5.1 months (95% confidence interval (CI): 5.6, 4.3, months). An exploratory comparison, based on no cancer progression with regular irinotecan versus progression, showed improved survival with Nal-IRI in the former group: 6.1 months (95% CI: 9.3, 5.1 months) versus 4.3 months (95% CI: 4.8, 2.3 months); p=0.0006. Nal-IRI adverse events occurred as expected. Qualitative data illustrated several themes, including “limited treatment options,” which appeared to drive the decision to prescribe Nal-IRI. Conclusions: Nal-IRI might be considered in pancreas cancer patients who had received regular irinotecan, particularly in the absence of disease progression with the latter.