The Sequential Radiographic Effects of Preoperative Chemotherapy and (Chemo)Radiation on Tumor Anatomy in Patients with Localized Pancreatic Cancer

Perri, Giampaolo; Prakash, Laura R.; Malleo, Giuseppe; Caravati, Andrea; Varadhachary, Gauri R.; Fogelman, David R.; Pant, Shubham; Koay, Eugene J.; Herman, Joseph M.; Maggino, Laura; Milella, Michèle; Kim, Michael; Ikoma, Naruhiko; Tzeng, Ching Wei D.; Salvia, Roberto; Lee, Jeffrey E.; Bassi, Claudio; Katz, Matthew H.

doi:10.1245/s10434-020-08427-4

Cited by 14 publications

(8 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a previous study with review of The National Cancer Data Base, it was demonstrated that the addition of radiotherapy to neoadjuvant chemotherapy was associated with higher downstaging and complete pathologic response rates than chemotherapy alone (23). Additionally, there was about 6.0-14.4% downstaging rate after chemoradiotherapy for LAPC (23)(24)(25), which was similar to that (9.3%) in our study. Nevertheless, chemoradiation did not confer a survival benefit compared with chemotherapy alone (23).…”

Section: Discussionsupporting

confidence: 90%

Development and Validation of Multicenter Predictive Nomograms for Locally Advanced Pancreatic Cancer After Chemoradiotherapy

et al. 2021

View full text Add to dashboard Cite

ObjectiveDue to common practice of hypofractionated radiotherapy in pancreatic cancer and heterogeneous chemotherapy regimens in previous studies, modified nomograms are required. Therefore, we aim to develop and validate prognostic nomograms for locally advanced pancreatic cancer (LAPC) after stereotactic body radiation therapy (SBRT) and chemotherapy.MethodsThe development cohort comprised 925 patients with LAPC receiving SBRT and gemcitabine-based chemotherapy in our center, while 297 patients from another two centers formed the validation cohort. Nomograms were created from COX models and internally validated by bootstrap. Model discriminations were evaluated by calibration plots and concordance index (C-index). A decision curve analysis (DCA) was performed to evaluate clinical benefits of nomograms. Additionally, recursive partitioning analysis (RPA) was used for stratifications of survival probability based on the total score of each patient calculated by nomograms.ResultsWeight loss, tumor diameter, radiation dose, CA19-9 kinetics after treatment and surgical resection were included in the nomogram for overall survival (OS), while the five factors plus performance status formed the nomogram for progression free survival (PFS). The corrected C-indexes for estimated 1-year and 2-year OS of the development cohort were 0.88 (95% CI: 0.85-0.91) and 0.86 (95% CI: 0.83-0.90). For those of the validation cohort, it was 0.88 (95% CI: 0.82-0.94) and 0.83 (95% CI: 0.74-0.91). Additionally, the corrected C-index for predicted 1-year PFS in the development and validation cohort was 0.83 (95% CI: 0.81-0.86) and 0.82 (95% CI: 0.78-0.87), respectively. The calibration plots showed good agreement of 1- and 2-year OS and 1-year PFS between the estimations and actual observations. Potential clinical benefits were demonstrated with DCA. Additionally, for 1- and 2-year OS and 1-year PFS, patients were stratified into four groups with different survival probability by RPA.ConclusionThe validated nomograms provided useful predictions of OS and PFS for LAPC with chemoradiotherapy.

show abstract

Section: Discussionsupporting

confidence: 90%

Development and Validation of Multicenter Predictive Nomograms for Locally Advanced Pancreatic Cancer After Chemoradiotherapy

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In a previous study with review of The National Cancer Data Base, it was demonstrated that the addition of radiotherapy to neoadjuvant chemotherapy was associated with higher downstaging and complete pathologic response rates than chemotherapy alone [23]. Additionally, there was about 6.0-14.4% downstaging rate after chemoradiotherapy for LAPC [23][24][25], which was similar with that (9.3%) in our study. Nevertheless, chemoradiation did not confer a survival bene t compared with chemotherapy alone [23].…”

Section: Discussionsupporting

confidence: 89%

Development and Validation of Multicenter Predictive Nomograms for Locally Advanced Pancreatic Cancer after Chemoradiotherapy

Zhu

Liu

Cao

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Due to common practice of hypofractionated radiotherapy in pancreatic cancer and heterogeneous chemotherapy regimens in previous studies, modified nomograms are required. Therefore, we aim to develop and validate prognostic nomograms for locally advanced pancreatic cancer (LAPC) after stereotactic body radiation therapy (SBRT) and chemotherapy.Methods: The development cohort comprised 925 patients with LAPC receiving SBRT and gemcitabine-based chemotherapy in our center, while 297 patients from another two centers formed the validation cohort. Nomograms were created from COX models and internally validated by bootstrap. Model discriminations were evaluated by calibration plots and concordance index (C-index). A decision curve analysis (DCA) was performed to evaluate clinical benefits of nomograms. Additionally, recursive partitioning analysis (RPA) was used for stratifications of survival probability based on the total score of each patient calculated by nomograms.Results: Weight loss, tumor diameter, radiation dose, CA19-9 kinetics after treatment and surgical resection were included in the nomogram for overall survival (OS), while the five factors plus performance status formed the nomogram for progression free survival (PFS). The corrected C-indexes for estimated 1-year and 2-year OS of the development cohort were 0.88 (95% CI: 0.85-0.91) and 0.86 (95% CI: 0.83-0.90). For those of the validation cohort, it was 0.88 (95% CI: 0.82-0.94) and 0.83 (95% CI: 0.74-0.91). Additionally, the corrected C-index for predicted 1-year PFS in the development and validation cohort was 0.83 (95% CI: 0.81-0.86) and 0.82 (95% CI: 0.78-0.87), respectively. The calibration plots showed good agreement of 1- and 2-year OS and 1-year PFS between the estimations and actual observations. Potential clinical benefits were demonstrated with DCA. Additionally, for 1- and 2-year OS and 1-year PFS, patients were stratified into four groups with different survival probability by RPA.Conclusion: The validated nomograms provided useful predictions of OS and PFS for LAPC with chemoradiotherapy.

show abstract

“…FOLFIRINOX treatment often leads to a stabilization of the disease, or partial response occurs in a minority of the PDAC patients, while others do not respond by showing disease progression during treatment ( 6 ). However, even among the responders, most patients develop rapid therapy resistance, resulting in disease progression after treatment.…”

Section: Introductionmentioning

confidence: 99%

Organoids Derived from Neoadjuvant FOLFIRINOX Patients Recapitulate Therapy Resistance in Pancreatic Ductal Adenocarcinoma

Farshadi

Chang

Sampadi

et al. 2021

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: We investigated whether organoids can be generated from resected tumors of patients who received eight cycles of neoadjuvant FOLFIRINOX chemotherapy before surgery, and evaluated the sensitivity/resistance of these surviving cancer cells to cancer therapy. Experimental Design:We generated a library of 10 PDAC organoid lines: five each from treatment-naive and FOLFIRINOX-treated patients. We, first, assessed the histological, genetic, and transcriptional characteristics of the organoids and their matched primary PDAC tissue. Next, the organoids' response to treatment with single agents -5-FU, irinotecan, and oxaliplatinof the FOLFIRINOX regimen as well as combined regimen was evaluated.Finally, global mRNA-seq analyses were performed to identify FOLFIRINOX resistance pathways.Results: All 10 patient-derived PDAC organoids recapitulate histological, genetic, and transcriptional characteristics of their primary tumor tissue. Neoadjuvant FOLFIRINOXtreated organoids display resistance to FOLFIRINOX (5/5), irinotecan (5/5) and oxaliplatin (4/5) when compared to treatment-naive organoids (FOLFIRINOX: 1/5, irinotecan: 2/5, oxaliplatin: 0/5). 5-FU treatment responses between naive and treated organoids were similar.Comparative global transcriptome analysis of treatment-naive and FOLFIRINOX samplesin both organoids and corresponding matched tumor tissuesuncovered modulated pathways mainly involved in genomic instability, energy metabolism, and innate immune system. Conclusion:Resistance development in neoadjuvant FOLFIRINOX organoids, recapitulating their primary tumor resistance, suggests continuation of FOLFIRINOX therapy as an adjuvant treatment may not be advantageous for these patients. Gene expression profiles of PDAC organoids identify targetable pathways involved in chemoresistance development upon neoadjuvant FOLFIRINOX treatment, thus opening up combination therapy possibilities.Research.

show abstract

The Sequential Radiographic Effects of Preoperative Chemotherapy and (Chemo)Radiation on Tumor Anatomy in Patients with Localized Pancreatic Cancer

Cited by 14 publications

References 23 publications

Development and Validation of Multicenter Predictive Nomograms for Locally Advanced Pancreatic Cancer After Chemoradiotherapy

Development and Validation of Multicenter Predictive Nomograms for Locally Advanced Pancreatic Cancer After Chemoradiotherapy

Development and Validation of Multicenter Predictive Nomograms for Locally Advanced Pancreatic Cancer after Chemoradiotherapy

Organoids Derived from Neoadjuvant FOLFIRINOX Patients Recapitulate Therapy Resistance in Pancreatic Ductal Adenocarcinoma

Contact Info

Product

Resources

About