Dataset Information

Local Control and Survival After Induction Chemotherapy and Ablative Radiation Versus Resection for Pancreatic Ductal Adenocarcinoma With Vascular Involvement.

ABSTRACT:

Objective

We sought to compare overall survival (OS) and disease control for patients with localized pancreatic ductal adenocarcinoma (PDAC) treated with ablative dose radiotherapy (A-RT) versus resection.

Summary background data

Locoregional treatment for PDAC includes resection when possible or palliative RT. A-RT may offer durable tumor control and encouraging survival.

Methods

This was a single-institution retrospective analysis of patients with PDAC treated with induction chemotherapy followed by A-RT [≥98 Gy biologically effective dose (BED) using 15-25 fractions in 3-4.5 Gy/fraction] or pancreatectomy.

Results

One hundred and four patients received A-RT (49.8%) and 105 (50.2%) underwent resection. Patients receiving A-RT had larger median tumor size after induction chemotherapy [3.2 cm (undetectable-10.9) vs 2.6 cm (undetectable-10.7), P < 0.001], and were more likely to have celiac or hepatic artery encasement (48.1% vs 11.4%, P <0.001), or superior mesenteric artery encasement (43.3% vs 9.5%, P < 0.001); however, there was no difference in the degree of SMV/PV involvement (P = 0.123). There was no difference in locoregional recurrence/progression at 18-months between A-RT and resection; cumulative incidence was 16% [(95% confidence interval (CI) 10%-24%] versus 21% (95% CI 14%-30%), respectively (P= 0.252). However, patients receiving A-RT had a 19% higher 18-month cumulative incidence of distant recurrence/progression [58% (95% CI 48%-67%) vs 30% (95% CI 30%-49%), P= 0.004]. Median OS from completion of chemotherapy was 20.1 months for A-RT patients (95% CI 16.4-23.1 months) versus 32.9 months (95% CI 29.7-42.3 months) for resected patients (P < 0.001).

Conclusion

Ablative radiation is a promising new treatment option for PDAC, offering locoregional disease control similar to that associated with resection and encouraging survival.

SUBMITTER: Jolissaint JS

PROVIDER: S-EPMC8599622 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Local Control and Survival After Induction Chemotherapy and Ablative Radiation Versus Resection for Pancreatic Ductal Adenocarcinoma With Vascular Involvement.

Jolissaint Joshua S JS Reyngold Marsha M Bassmann Jared J Seier Kenneth P KP Gönen Mithat M Varghese Anna M AM Yu Kenneth H KH Park Wungki W O'Reilly Eileen M EM Balachandran Vinod P VP D'Angelica Michael I MI Drebin Jeffrey A JA Kingham T Peter TP Soares Kevin C KC Jarnagin William R WR Crane Christopher H CH Wei Alice C AC

Annals of surgery 20211201 6

<h4>Objective</h4>We sought to compare overall survival (OS) and disease control for patients with localized pancreatic ductal adenocarcinoma (PDAC) treated with ablative dose radiotherapy (A-RT) versus resection.<h4>Summary background data</h4>Locoregional treatment for PDAC includes resection when possible or palliative RT. A-RT may offer durable tumor control and encouraging survival.<h4>Methods</h4>This was a single-institution retrospective analysis of patients with PDAC treated with induct ...[more]

PMID: 34269717

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Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating and painful cancers. It is often highly resistant to therapy owing to inherent chemoresistance and the desmoplastic response that creates a barrier of fibrous tissue preventing transport of chemotherapeutics into the tumor. The growth of the tumor in pancreatic cancer often leads to invasion of other organs and partial or complete biliary obstruction, inducing intense pain for patients and necessitating tumor resection or repeated stenting. Here, we have developed a delivery device to provide enhanced palliative therapy for pancreatic cancer patients by providing high concentrations of chemotherapeutic compounds locally at the tumor site. This treatment could reduce the need for repeated procedures in advanced PDAC patients to debulk the tumor mass or stent the obstructed bile duct. To facilitate clinical translation, we created the device out of currently approved materials and drugs. We engineered an implantable poly(lactic-co-glycolic)-based biodegradable device that is able to linearly release high doses of chemotherapeutic drugs for up to 60 days. We created five patient-derived PDAC cell lines and tested their sensitivity to approved chemotherapeutic compounds. These in vitro experiments showed that paclitaxel was the most effective single agent across all cell lines. We compared the efficacy of systemic and local paclitaxel therapy on the patient-derived cell lines in an orthotopic xenograft model in mice (PDX). In this model, we found up to a 12-fold increase in suppression of tumor growth by local therapy in comparison to systemic administration and reduce retention into off-target organs. Herein, we highlight the efficacy of a local therapeutic approach to overcome PDAC chemoresistance and reduce the need for repeated interventions and biliary obstruction by preventing local tumor growth. Our results underscore the urgent need for an implantable drug-eluting platform to deliver cytotoxic agents directly within the tumor mass as a novel therapeutic strategy for patients with pancreatic cancer.

Project description:BackgroundDistinguishing postoperative fibrosis from isolated local recurrence (ILR) after resection of pancreatic ductal adenocarcinoma (PDAC) is challenging. A prognostic model that helps to identify patients at risk of ILR can assist clinicians when evaluating patients' postoperative imaging. This nationwide study aimed to develop a clinically applicable prognostic model for ILR after PDAC resection.Patients and methodsAn observational cohort study was performed, including all patients who underwent PDAC resection in the Netherlands (2014-2019; NCT04605237). On the basis of recurrence location (ILR, systemic, or both), multivariable cause-specific Cox-proportional hazard analysis was conducted to identify predictors for ILR and presented as hazard ratios (HRs) with 95% confidence intervals (CIs). A predictive model was developed using Akaike's Information Criterion, and bootstrapped discrimination and calibration indices were assessed.ResultsAmong 1194/1693 patients (71%) with recurrence, 252 patients (21%) developed ILR. Independent predictors for ILR were resectability status (borderline versus resectable, HR 1.42; 95% CI 1.03-1.96; P = 0.03, and locally advanced versus resectable, HR 1.11; 95% CI 0.68-1.82; P = 0.66), tumor location (head versus body/tail, HR 1.50; 95% CI 1.00-2.25; P = 0.05), vascular resection (HR 1.86; 95% CI 1.41-2.45; P < 0.001), perineural invasion (HR 1.47; 95% CI 1.01-2.13; P = 0.02), number of positive lymph nodes (HR 1.04; 95% CI 1.01-1.08; P = 0.02), and resection margin status (R1 < 1 mm versus R0 ≥ 1 mm, HR 1.64; 95% CI 1.25-2.14; P < 0.001). Moderate performance (concordance index 0.66) with adequate calibration (slope 0.99) was achieved.ConclusionsThis nationwide study identified factors predictive of ILR after PDAC resection. Our prognostic model, available through www.pancreascalculator.com , can be utilized to identify patients with a higher a priori risk of developing ILR, providing important information in patient evaluation and prognostication.

Project description:Background and purposeConsolidatory radiotherapy in form of stereotactic body radiation therapy (SBRT) with an ablative dose following induction chemotherapy is emerging as a promising treatment scheme for unresectable pancreatic cancer. Outcomes of given treatment at a single center for contiguous patients with unresectable pancreatic cancer were evaluated to build the optimal treatment strategy.Materials and methodsIn this retrospective study, a total of 50 patients with unresectable pancreatic cancer who underwent induction chemotherapy and ablative dose SBRT were included. SBRT dose was 40-50 Gy in five fractions. Two strategies were adopted to adhere to the organs at risk (OAR) dose constraints: simultaneous integrated protection (SIP) technique and magnetic resonance (MR)-guided adaptive technique. Overall survival (OS) and local progression-free survival (LPFS) were calculated from the start date of SBRT.ResultsThe median follow-up period for survivors was 21.1 months (range, 6.2-61.0 months). Eleven (22.0%) patients underwent resection after SBRT, which were all R0 resection. In patients with non-metastatic disease, the median OS was 26.5 months (range, 4.1-61.0 months), and the 1- and 3-year LPFS were 90.0% (95% confidence interval [CI], 72.0-96.7%) and 57.4% (95% CI, 31.7-76.4%), respectively. Patients with oligometastatic disease had inferior survival outcomes, but there was no survival difference among responders to induction chemotherapy. In the multivariable analysis, tumor size ≤4 cm, non-metastatic status, and good response to induction chemotherapy were associated with improved LPFS. In dosimetric analysis, GTV Dmin ≥50.5 Gy was the strongest prognosticator against local progression. Grade ≥3 adverse events occurred in two (4.0%) patients with non-adaptive RT, but none in patients with MR-guided adaptive RT.ConclusionAblative dose SBRT following induction chemotherapy is an effective strategy for selected patients with unresectable pancreatic cancer. The SIP technique and MR-guided adaptive RT were attributed to minimizing the risk of adverse events. Further studies are needed to identify the best candidates for consolidatory SBRT in unresectable pancreatic cancer.

Project description:BackgroundIntrahepatic cholangiocarcinoma (CCA) is amongst the most common primary liver tumors worldwide. CCA carries a bad prognosis prompting research to establish new treatment modalities other than surgery and the current chemotherapeutic regimens adopted. Hence, this trial explores a new therapeutic approach, to combine stereotactic body radiation therapy (SBRT) and immunotherapy (Nivolumab), and asses its clinical benefit and safety profile after induction chemotherapy in CCA.MethodologyThis is a Phase II open-label, single-arm, multicenter study that investigates Nivolumab (PD-1 inhibitor) treatment at Day 1 followed by SBRT (30 Gy in 3 to 5 fractions) at Day 8, then monthly Nivolumab in 40 patients with non-resectable locally advanced, metastatic or recurrent intrahepatic or extrahepatic CCA. Eligible patients were those above 18 years of age with a pathologically and radiologically confirmed diagnosis of non-resectable locally advanced or metastatic or recurrent intrahepatic or extrahepatic CCA, following 4 cycles of cisplatin-based chemotherapy with an estimated life expectancy of more than 3 months, among other criteria. The primary endpoint is the progression free survival (PFS) rate at 8 months and disease control rate (DCR). The secondary endpoints are overall survival (OS), tumor response rate (TRR), duration of response, evaluation of biomarkers: CD3 + , CD4 + and CD8 + T cell infiltration, as well as any change in the PD-L1 expression through percutaneous core biopsy when compared with the baseline biopsy following 1 cycle of Nivolumab and SBRT.DiscussionSRBT alone showed promising results in the literature by both inducing the immune system locally and having abscopal effects on distant metastases. Moreover, given the prevalence of PD-L1 in solid tumors, targeting it or its receptor has become the mainstay of novel immunotherapeutic drugs use. A combination of both has never been explored in the scope of CCA and that is the aim of this study.Trial registrationClinicalTrials.gov NCT04648319 , April 20, 2018.

Project description:BackgroundWe evaluated the diagnostic capability of photon-counting detector computed tomography (PCD-CT) spectral variables in late arterial phase (LAP) and portal venous phase (PVP) to discriminate between local tumor recurrence (LTR) and postoperative changes (POC) after pancreatic ductal adenocarcinoma (PDAC) resection.MethodsSeventy-three consecutive PCD-CT scans in 73 patients with postoperative soft-tissue lesions (PSLs) were included, 42 with POC and 31 with LTR. Regions of interest were drawn in each PSL, and spectral variables were calculated: iodine concentration (IC), normalized IC (NIC), fat fraction, attenuation at 40, 70, and 90 keV, and slope of the spectral curve between 40-90 keV. Multivariable binary logistic regression models were constructed. Diagnostic performance was assessed for LAP and PVP using receiver operating characteristic analysis.ResultsIn LAP, all variables except fat fraction showed significant differences between LTR and POC (p ≤ 0.025). In PVP, all variables except NIC and fat fraction demonstrated significant differences between LTR and POC (p ≤ 0.005). Logistic regression analysis included NIC and 70 keV in the LAP-based model and IC and 90 keV in the PVP-based model. Both models achieved a higher area under the curve (AUC) than individual spectral variables in each phase. The LAP-based model achieved an AUC of 0.919 with 94% sensitivity, 84% specificity, and 87% accuracy, while the PVP-based model reached 0.820, 71%, 88%, and 81%, respectively.ConclusionSpectral variables from PCD-CT help distinguish between LTR and POC in LAP and PVP post-PDAC resection. Multivariable logistic regression improves diagnostic performance, especially in LAP.Relevance statementMeasuring normalized iodine concentration and attenuation at 70 keV in late arterial phase, or iodine concentration and attenuation at 90 keV in portal venous phase, and incorporating these values into a logistic regression model can help differentiate between local tumor recurrence and postoperative changes after pancreatic ductal adenocarcinoma resection.Key pointsDistinguishing recurrence from postoperative changes on CT after pancreatic ductal adenocarcinoma resection is challenging. PCD-CT spectral variable values differed significantly between local tumor recurrence (LTR) and postoperative changes (POC). Logistic regression of spectral variables can help distinguish LTR from POC. The late arterial phase-based model reached an AUC of 0.919 with 94% sensitivity and 84% specificity.

Dataset Information

Local Control and Survival After Induction Chemotherapy and Ablative Radiation Versus Resection for Pancreatic Ductal Adenocarcinoma With Vascular Involvement.

Objective

Summary background data

Methods

Results

Conclusion

Publications

Local Control and Survival After Induction Chemotherapy and Ablative Radiation Versus Resection for Pancreatic Ductal Adenocarcinoma With Vascular Involvement.

Similar Datasets

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