Effect of multiagent chemotherapy and chemoradiotherapy on rates of resection and survival in patients with locally advanced pancreatic cancer: a National Cancer Database Analysis.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 391-391
Author(s):  
John David ◽  
Sungjin Kim ◽  
Eric Anderson ◽  
Arman Torossian ◽  
Simon Lo ◽  
...  

391 Background: The role of multiagent chemotherapy (MAC) has not been prospectively investigated in LAPC and data are extrapolated from randomized trials in patients with metastatic disease. Data regarding the use of chemoradiation (CRT) for LAPC is mixed and similarly there is no prospective data investigating its use after MAC. Herein, we investigate clinical outcomes associated with the use of MAC and CRT. Methods: The National Cancer Database (NCDB) was utilized to identify LAPC patients treated with single agent chemotherapy (SAC), MAC, surgery, and/or CRT. Univariate (UVA) and multivariate (MVA) Cox regression were performed to identify the impact of MAC and CRT on surgical resection and median overall survival (mOS) rates. Results: From 2004-2014, a total of 10139 patients were identified. The median age was 66 years (range 22-90) with median follow up of 49 months (46-52 months); 49.9% were male and 50.1% female. All patients had clinical stage 3/T4 disease irrespective of nodal metastases. All patients who received post-op RT were excluded. Surgical resection was performed in 506 (5%) patients. Median OS rates for patients who received SAC vs. MAC was 9.8 months vs 13.7 months (p < 0.001), respectively. Median OS rates for patients who received SAC/MAC vs. SAC/MAC+CRT was 9.9 months vs. 12.9 months (p < 0.001), respectively. Odds ratio for undergoing surgical resection in patients receiving MAC vs. MAC+RT was not significant. Of the 5% of patients who underwent resection after neoadjuvant therapy, mOS for those who received MAC vs. MAC+RT were 19.4 months and 25.6 months (p = 0.001), respectively. Conclusions: Median OS was improved in patients receiving MAC versus SAC. The use of CRT after chemotherapy led to increased mOS compared to chemotherapy alone. In all patients undergoing surgical resection, the addition of neoadjuvant CRT after MAC led to improved mOS rates. Treatment with MAC followed by CRT should be utilized for all patients with LAPC.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 392-392
Author(s):  
John David ◽  
Sungjin Kim ◽  
Erik Anderson ◽  
Arman Torossian ◽  
Simon Lo ◽  
...  

392 Background: Numerous studies have shown that treatment at a high volume facility (HVF) for patients (pts) with pancreatic cancer is associated with improved outcomes, particularly with pancreatectomy. In fact, a recent study showed that pts undergoing a pancreatectomy at an academic center (AC) is independently associated with improved outcomes. However, the role of chemotherapy (CT) and radiation (RT) in the treatment of locally advanced pancreatic cancer (LAPC) at HVF and AC, to our knowledge, has not been studied. Herein, we investigate the benefit of treatment at HVF and AC compared to low volume facilities (LVF) and non-academic centers (NAC) with CT or chemoradiation (CRT) in pts with LAPC. Methods: The National Cancer Database (NCDB) was utilized to identify LAPC patients treated at all facility types. All patients were treated with CT or CRT. Univariate (UVA) and multivariate (MVA) Cox regression were performed to identify the impact of HVF and AC on overall survival (OS) when compared to LVF and NAC, respectively. HVF was defined as the top 5% of facilities by number of pts treated. Results: From 2004 – 2014, a total of 10139 pts were identified. The median age was 66 years (range 22-90) with median follow up of 48.8 months (46-52.1 months); 49.9% were male and 50.1% female. All pts had clinical stage 3/T4 disease irrespective of nodal metastases. Of these, 4779 pts were treated at an AC and 5260 were treated at a NAC and 588 were treated at HVF and 9551 were treated at LVF. On UVA, age, high median income, high education level, comorbidities, and recent year of diagnosis were associated with improved OS. ACs were associated with improved OS when compared to non-AC (HR 0.92 95% CI 0.88 – 0.96, p = 0.004), as were HVF when compared to LVH (HR 0.84 95% CI 0.76 – 0.92, p < 0.001). Odds ratio for undergoing surgical resection at HVF and AC was 1.68 and 1.37 (p < 0.001), respectively, when compared to LVF and NAC. Conclusions: The treatment of LAPC patients with CT or CRT at an AC led to significantly improved rate of surgical resection and OS. In the absence of prospective data, these results support the referral of pts with LAPC to HVF and/or AC for evaluation and treatment.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 685-685 ◽  
Author(s):  
Atsushi Oba ◽  
Christopher Hanyoung Lieu ◽  
Cheryl Lauren Meguid ◽  
Sarah Lindsey Davis ◽  
Alexis Diane Leal ◽  
...  

685 Background: For borderline resectable (BRPC) or locally advanced pancreatic cancer (LAPC), neoadjuvant (NAT) FOLFIRINOX or gemcitabine plus nab-paclitaxel (GnP) are standard treatment options and these regimens have shown a survival advantage over single-agent gemcitabine. However, the role of these modern therapeutic regimens in elderly patients is debatable. In this analysis, we evaluated the outcomes of neoadjuvant treatment (NAT) with combination chemotherapy in elderly patients. Methods: 230 consecutive patients who underwent neoadjuvant treatment for BRPC/LAPC discussed and planned for NAT at the University of Colorado Cancer Center from January 2011 to March 2019 were reviewed. 214 patients who received FOLFIRINOX (n = 143) or GnP (n = 71) were eligible for analysis. We divided all patients into three groups ( < 70, 70-74, ≥75 years) and compared the short-term and long-term outcomes. Results: Of 214 patients, patients < 70 (n = 147) received FOLFIRINOX more frequently than the other groups (p < 0.001): FOLFIRINOX: 115 cases, GnP: 32 cases, 70-74 years (n = 33): FOLFIRINOX: 15 cases, GnP: 18 cases, and ≥75 years (n = 34): FOLFIRINOX: 13 cases, GnP: 21 cases. Resection rates were not statistically different between three groups ( < 70: 62%, 70-74: 70%, ≥75 years: 56%, p = 0.504). There was a slight trend towards worse survival in the two older groups (Median Survival Time [MST]: < 70: 23.2 mo., 70-74: 19.5 mo., ≥75 years: 17.6 mo., p = 0.075) The FOLFIRINOX group was superior to GnP group in all three groups (MST: < 70: 25.6 vs 18.2 mo., p = 0.017; 70-74: 33.2 vs 16.1mo., p = 0.029; ≥75 years: not reached vs 16.1 mo., p = 0.135). There were no toxic deaths or 30 day mortality after pancreatectomy in the study population. Conclusions: Neoadjuvant combination chemotherapy regimens were safe and feasible for elderly patients. Neoadjuvant therapy with FOLFIRINOX was associated with a survival advantage vs GnP and is an good option for fit and elderly patients ≥75 years.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 473-473 ◽  
Author(s):  
Annabelle Teng ◽  
Trang Nguyen ◽  
Anton Bilchik ◽  
Victoria O'Connor ◽  
David Y Lee

473 Background: For patients with pancreatic adenocarcinoma (PA), the optimal time interval between neoadjuvant chemoradiation (CR) to surgical resection has not been well established. The National Cancer Database (NCDB) was used to evaluate the impact of radiation-surgery (RS) interval on outcomes. Methods: The NCDB from 2006-2014 was queried for patients ≥18 years old diagnosed with PA who received CR prior to surgery. Survival and short-term outcomes were compared between patients who had a Whipple procedure performed ≤12 weeks and > 12 weeks after completion of CR therapy. Results: 1610 patients met selection criteria. Average RS interval was 58.2 ± 39.5 days. 1419 patients had RS interval ≤12 weeks (mean 47.4 days) and 191 had RS interval > 12 weeks (mean 138.8 days). Age, race, gender, income, type of treatment facility, CA 19-9 levels, types of chemotherapy and radiation dosage administered were similar between the two groups. Mean tumor size was 32.2 mm in the ≤12 week group and 34.9 mm in the > 12 week group (p = 0.021). There was a higher proportion of patients with clinical stage III cancers in the > 12 weeks group than in the ≤12 weeks group (33.5% vs 14%). Short-term morbidity and mortality was not significantly different between the two groups in terms of length of stay, readmission within 30 days, 30-day and 90-day mortality. However, a long-term survival benefit was observed in the > 12 week group (median 25.8 months in ≤12 weeks vs 30.2 months in > 12 weeks, p = 0.049) that appears to persist. An interval > 12 weeks was associated with significantly prolonged survival on multivariate analysis (HR 0.80 (0.65-0.99 95% CI, p = 0.042)). Higher clinical stage and positive surgical margins were independently associated with worse survival. Conclusions: Surgical resection beyond 12 weeks after CR for PA did not worsen surgical outcomes. Waiting may contribute to better patient selection, especially those with larger tumors and higher clinical stage. In the absence of progressive disease, patients need to be continuously evaluated for surgical resection after CR.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4123-4123
Author(s):  
Nobumasa Mizuno ◽  
Akira Fukutomi ◽  
Junki Mizusawa ◽  
Hiroshi Katayama ◽  
Satoaki Nakamura ◽  
...  

4123 Background: JCOG1106 is a randomized selection phase 2 trial to evaluate the efficacy and safety of CRT (S-1 concurrent RT) with (Arm B) or without (Arm A) induction CT of gemcitabine (GEM) for LAPC. In the final analysis, we selected Arm A as a promising regimen due to a poorer 2-year overall survival (OS) of Arm B, in spite of a favorable 1-year OS with crossing of the survival curves around 1-year (Ioka, ESMO2016). Therefore, this study aimed to explore subgroups benefit more from either treatment. IN statuses defined by such as serum C-reactive protein (CRP) and serum albumin (Alb) are recognized as prognostic and predictive factors in patients (pts) with various cancers receiving CT or CRT. We hypothesized that IN status may modify the effect of induction CT. Methods: Subjects were all eligible pts who were enrolled in JCOG1106 (n = 51/49 in Arm A/B). Glasgow Prognostic Score (GPS) was classified by baseline CRP and Alb. Pts with a CRP ≤ 10 mg/L and Alb ≥ 35 g/L were allocated to GPS 0, with a CRP > 10 mg/L or Alb < 35 g/L to GPS 1, and with a CRP > 10 mg/L and Alb < 35 g/L to GPS 2. This exploratory subgroup analysis was performed by Cox regression analysis to investigate the impact of IN status at baseline on OS. Less than 0.1 of P-value for interaction was regarded as significant. Results: GPS, CRP and Alb showed significant treatment interactions in terms of OS. HRs of Arm B to Arm A were 1.35 (0.82–2.23) and 0.59 (0.24–1.50) in the GPS 0 (n = 44/34 in Arm A/B) and GPS 1/2 group (n = 7/15) ( P-interaction = 0.06). HRs were 2.57 (1.36–4.86) and 0.70 (0.37–1.32) in the low CRP group (≤ 1.35 mg/L, n = 25/25) and high CRP ( > 1.35 mg/L, n = 26/24) ( P= 0.01). HRs were 1.62 (0.77–3.40), 2.70 (1.17–6.23) and 0.52 (0.24–1.13) in the 1st (≤ 0.7 mg/L, n = 16/16), 2nd ( > 0.7, ≤ 3.0 mg/L, n = 20/16), and 3rd tertiary CRP group ( > 3.0 mg/L, n = 15/17) ( P= 0.01). HRs were 2.29 (1.11–4.69) and 0.89 (0.51–1.54) in the high Alb group ( > 40 g/L, n = 23/17) and low Alb (≤ 40 g/L, n = 28/32) ( P= 0.04). Arm B showed better survival in subgroups of GPS 1/2, higher CRP or lower Alb compared to Arm A. Conclusions: Pts with poor IN status may have treatment benefit of induction CT followed by CRT for LAPC. Clinical trial information: UMIN000006811.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 373-373
Author(s):  
Eric Anderson ◽  
John David ◽  
Simon Lo ◽  
Nicholas N. Nissen ◽  
Andrew Eugene Hendifar ◽  
...  

373 Background: Margin negative oncologic resection drastically improves survival in pancreatic cancer (PC) with low morbidity and mortality rates. Increasing age at the time of surgery may have an impact on overall survival (OS) in PC. We aimed to describe the likelihood of receiving surgery in elderly patients (EP) compared to younger patients and whether this predicted OS. Methods: Non-metastatic PC patients were identified in the National Cancer Database (NCDB). Baseline demographics, clinical, and pathologic factors were compared between patients older (EP) and younger (YP) than age 75. Kaplan-Meier survival methods were used to describe differences in OS. Cox regression methods were performed to describe the impact of multiple variables on OS. Results: From 2004-2014, there were 39,804 PC patients with median age 69 years (range 19-90) and median follow up 47.2 months. Of 12,337 (31.0%) EPs, 2598 (21.1%) underwent surgery, while 9809 of 27467 YPs (35.7%) underwent surgery (p < 0.001). EP were less likely to receive surgery across clinical stages (CS, p < 0.001): CS 1 - 29.5% EP vs. 55.6% YP, CS 2 - 23.4% EP vs. 40.3% YP, CS 3 - 3.1% EP vs. 7.5% YP. EP receiving surgery were more likely to have baseline medical comorbidities (38.8% vs. 35.9%, (p = 0.065) and less likely to receive chemotherapy (47.4% vs. 73.6%, (p < 0.001). Improvement of median OS was seen in EPs undergoing resection (16.9 months vs. 6.4 months, p < 0.001), as well as YP undergoing resection (22.8 vs. 11.2 months, p < 0.001). Multivariate Cox regression revealed that surgical intervention (HR 0.47, 95% CI 0.45-0.48, p < 0.001) and younger age (0.62, 0.60-0.63, p < 0.001) were highly protective. Patient medical comorbidities (1.15, 1.12-1.18, p < 0.001) and T stage (1.38, 1.31-1.44, p < 0.001) predicted poor OS. Conclusions: EPs with PC are less likely to receive definitive surgical resection in the setting of higher or similar medical comorbidities. EPs are also less likely to receive chemotherapy for their non-metastatic disease. In spite of this, surgery portends a significant increase in median OS for these EPs. Given adequate risk stratification and functional assessment, EPs should be strongly considered for surgical resection.


2014 ◽  
Vol 32 (27) ◽  
pp. 2983-2990 ◽  
Author(s):  
Andrew R. Davies ◽  
James A. Gossage ◽  
Janine Zylstra ◽  
Fredrik Mattsson ◽  
Jesper Lagergren ◽  
...  

Purpose Neoadjuvant chemotherapy is established in the management of most resectable esophageal and esophagogastric junction adenocarcinomas. However, assessing the downstaging effects of chemotherapy and predicting response to treatment remain challenging, and the relative importance of tumor stage before and after chemotherapy is debatable. Methods We analyzed consecutive resections for esophageal or esophagogastric junction adenocarcinomas performed at two high-volume cancer centers in London between 2000 and 2010. After standard investigations and multidisciplinary team consensus, all patients were allocated a clinical tumor stage before treatment, which was compared with pathologic stage after surgical resection. Survival analysis was conducted using Kaplan-Meier analysis and Cox regression analysis. Results Among 584 included patients, 400 patients (68%) received neoadjuvant chemotherapy. Patients with downstaged tumors after neoadjuvant chemotherapy experienced improved survival compared with patients without response (P < .001), and such downstaging (hazard ratio, 0.43; 95% CI, 0.31 to 0.59) was the strongest independent predictor of survival after adjusting for patient age, tumor grade, clinical tumor stage, lymphovascular invasion, resection margin status, and surgical resection type. Patients downstaged by chemotherapy, compared with patients with no response, experienced lower rates of local recurrence (6% v 13%, respectively; P = .030) and systemic recurrence (19% v 29%, respectively; P = .027) and improved Mandard tumor regression scores (P < .001). Survival was strongly dictated by stage after neoadjuvant chemotherapy, rather than clinical stage at presentation. Conclusion The stage of esophageal or esophagogastric junction adenocarcinoma after neoadjuvant chemotherapy determines prognosis rather than the clinical stage before neoadjuvant chemotherapy, indicating the importance of focusing on postchemotherapy staging to more accurately predict outcome and eligibility for surgery. Patients who are downstaged by neoadjuvant chemotherapy benefit from reduced rates of local and systemic recurrence.


2021 ◽  
pp. 20210044
Author(s):  
Florence Huguet ◽  
Victoire Dabout ◽  
Eleonor Rivin del Campo ◽  
Sébastien Gaujoux ◽  
Jean Baptiste Bachet

At diagnosis, about 15% of patients with pancreatic cancer present with a resectable tumour, 50% have a metastatic tumour, and 35% a locally advanced tumour, non-metastatic but unresectable due to vascular invasion, or borderline resectable. Despite the technical progress made in the field of radiation therapy and the improvement of the efficacy of chemotherapy, the prognosis of these patients remains very poor. Recently, the role of radiation therapy in the management of pancreatic cancer has been much debated. This review aims to evaluate the role of radiation therapy for patients with locally advanced tumours.


2012 ◽  
Vol 98 (5) ◽  
pp. 643-651 ◽  
Author(s):  
Maria Picchio ◽  
Elisabetta Giovannini ◽  
Paolo Passoni ◽  
Elena Busnardo ◽  
Claudio Landoni ◽  
...  

2019 ◽  
Vol 03 (02) ◽  
pp. 138-142
Author(s):  
Gray R. Lyons ◽  
Brian J. Schiro ◽  
Govindarajan Narayanan

AbstractLocally advanced pancreatic cancer is often refractory to conventional therapy, thus warranting new approaches. Irreversible electroporation is an ablative modality that has the potential to deliver targeted anticancer treatment with minimal damage to surrounding structures. Indications for irreversible electroporation in pancreatic cancer patients include palliation for metastatic disease, downstaging for surgery in locally advanced disease, and treatment of local recurrence following operative resection. Benefits of the modality in pancreatic cancer include a minimally invasive approach, precise delivery that minimizes nontarget ablation, and upregulation of anticancer immune response. Early studies have demonstrated an acceptable safety profile for irreversible electroporation; however, more data are needed to define the role of IRE in the treatment algorithm of pancreatic cancer.


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