Dataset Information

A step towards personalizing next line therapy for resected pancreatic and related cancer patients: A single institution's experience.

ABSTRACT:

Background

There is a lack of precision medicine in pancreatic ductal adenocarcinoma (PDA) and related cancers, and outcomes for patients with this diagnosis remain poor despite decades of research investigating this disease. Therefore, it is necessary to explore novel therapeutic options for these patients who may benefit from personalized therapies.

Objective

Molecular profiling of hepatopancreaticobiliary malignancies at our institution, including but not limited to PDA, was initiated to assess the feasibility of incorporating molecular profiling results into patient oncological therapy planning.

Methods

All eligible patients from Thomas Jefferson University (TJU) with hepatopancreaticobiliary tumors including PDA, who agreed to molecular testing profiling, were prospectively enrolled in a registry study from December 2014 to September 2017 and their tumor samples were tested to identify molecular markers that can be used to guide therapy options in the future. Next generation sequencing (NGS) and protein expression in tumor samples were tested at CLIA-certified laboratories. Prospective clinicopathologic data were extracted from medical records and compiled in a de-identified fashion.

Results

Seventy eight (78) patients were enrolled in the study, which included 65/78 patients with PDA (local and metastatic) and out of that subset, 52/65 patients had surgically resected PDA. Therapy recommendations were generated based on molecular and clinicopathologic data for all enrolled patients. NGS uncovered actionable alterations in 25/52 surgically resected PDAs (48%) which could be used to guide therapy options in the future. High expression of three proteins, TS (p = 0.005), ERCC1 (p = 0.001), and PD-1 (p = 0.04), was associated with reduced recurrence-free survival (RFS), while TP53 mutations were correlated with longer RFS (p = 0.01).

Conclusions

The goal of this study was to implement a stepwise strategy to identify and profile resected PDAs at our institution. Consistent with previous studies, approximately half of patients with resected PDA harbor actionable mutations with possible targeted therapeutic implications. Ongoing studies will determine the clinical value of identifying these mutations in patients with resected PDA.

SUBMITTER: Lowder CY

PROVIDER: S-EPMC7498307 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

A step towards personalizing next line therapy for resected pancreatic and related cancer patients: A single institution's experience.

Lowder Cinthya Y CY Dhir Teena T Goetz Austin B AB Thomsett Henry L HL Bender Joseph J Tatarian Talar T Madhavan Subha S Petricoin Emanuel F EF Blais Edik E Lavu Harish H Winter Jordan M JM Posey James J Brody Jonathan R JR Pishvaian Michael J MJ Yeo Charles J CJ

Surgical oncology 20200208

<h4>Background</h4>There is a lack of precision medicine in pancreatic ductal adenocarcinoma (PDA) and related cancers, and outcomes for patients with this diagnosis remain poor despite decades of research investigating this disease. Therefore, it is necessary to explore novel therapeutic options for these patients who may benefit from personalized therapies.<h4>Objective</h4>Molecular profiling of hepatopancreaticobiliary malignancies at our institution, including but not limited to PDA, was in ...[more]

PMID: 32561076

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Project description:BackgroundTo investigate the effect of stereotactic body radiation therapy (SBRT) on pulmonary oligometastases and to analyze the clinical factors and dose parameters affecting local recurrence-free survival (LRFS) and overall survival (OS).MethodsThis study retrospectively enrolled a total of 84 patients (148 lesions) treated in our department from May 2015 to November 2018. Pulmonary oligometastases was defined as up to 5 metastatic lesions in the lung and with both the primary tumor and any extra-thoracic metastases being controlled. Patients receiving a BED10 (biological effective dose, α/β =10) of SBRT ≥75 Gy and a dose/fraction ≥4 Gy were enrolled. The patient group consisted of 52 men (61.9%) and 32 women (38.1%), with a median age 56 years (range, 29-80 years). Median tumor diameter was 1.71cm (range, 1.2-5.0 cm). The BED10 was 75-119 Gy in 4-15 fractions. Univariate and multivariate Cox regression analyses were performed on factors predicting the outcomes.ResultsAll patients completed the treatment as planned, and the median follow-up time was 20.3 months. The median OS for the entire group was 34.3 months, with an actuarial 1-, 2-, 3- and 5-year OS of 74.7%, 59.4%, 49.7%, and 36.8%, respectively. Among the 148 lesions in the whole group, 19 (12.8%) lesions had local recurrence (LR). The median LRFS time for all patients was 56.9 months. The LRFS rate was 93.6%, 83.5%, 81.4%, and 76.6% at 1, 2, 3, and 5 years, respectively. No patient developed acute grade 3 or 4 toxicity. On univariate analysis, age ≥63 years old, primary site of colorectal cancer, BED10 <85.2 Gy, pathological type of adenocarcinoma, planning target volume (PTV) min BED10 <76.6 Gy, and gross tumor volume (GTV) ≥8.8 cc, were significantly associated with poorer LRFS. Multivariate analysis showed that age ≥63 years old, primary site of colorectal cancer, and PTV min BED10 <76.6 Gy were significant risk factors affecting LRFS.ConclusionsSBRT is feasible for pulmonary oligometastasis with favorable local control and minimal toxicity. Multiple dose parameters, instead of a prescription dose only, in combination with clinical parameters, should be considered for optimal local control.

Dataset Information

A step towards personalizing next line therapy for resected pancreatic and related cancer patients: A single institution's experience.

Background

Objective

Methods

Results

Conclusions

Publications

A step towards personalizing next line therapy for resected pancreatic and related cancer patients: A single institution's experience.

Similar Datasets

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