The Role of Radiation Therapy in Pancreatic Ductal Adenocarcinoma in the Neoadjuvant and Adjuvant Settings

Franke, Aaron J; Rosati, Lauren M.; Pawlik, Timothy M.; Kumar, Rachit; Herman, Joseph M.

doi:10.1053/j.seminoncol.2014.12.013

Cited by 21 publications

(21 citation statements)

References 109 publications

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“…One of the concepts under investigation is chemo-radiation therapy (CRT). The clinical benefit of CRT (e.g., as compared to chemotherapy alone) is a topic of ongoing research and debate [11], [12]. However, it should be noted that the standard mode of treatment in pancreatic cancer following surgery is additive and/or adjuvant chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

“…Several recently published studies have successfully highlighted molecular PDAC subtyping and stratification with a focus on response to chemotherapy [11], [12], [13], [14], [15], [16], [17]. In addition to establishing biological marker profiles of potential chemotherapy responders, these studies also yielded an improved understanding of the molecular basis of therapy resistance.…”

Section: Introductionmentioning

confidence: 99%

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Proteome Profiling of Primary Pancreatic Ductal Adenocarcinomas Undergoing Additive Chemoradiation Link ALDH1A1 to Early Local Recurrence and Chemoradiation Resistance

Oria

Bronsert

Thomsen

et al. 2018

Translational Oncology

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Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis with frequent post-surgical local recurrence. The combination of adjuvant chemotherapy with radiotherapy is under consideration to achieve a prolonged progression-free survival (PFS). To date, few studies have determined the proteome profiles associated with response to adjuvant chemoradiation. We herein analyzed the proteomes of primary PDAC tumors subjected to additive chemoradiation after surgical resection and achieving short PFS (median 6 months) versus prolonged PFS (median 28 months). Proteomic analysis revealed the overexpression of Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) and Monoamine Oxidase A (MAOA) in the short PFS cohort, which were corroborated by immunohistochemistry. In vitro, specific inhibition of ALDH1A1 by A37 in combination with gemcitabine, radiation, and chemoradiation lowered cell viability and augmented cell death in MiaPaCa-2 and Panc 05.04 cells. ALDH1A1 silencing in both cell lines dampened cell proliferation, cell metabolism, and colony formation. In MiaPaCa-2 cells, ALDH1A1 silencing sensitized cells towards treatment with gemcitabine, radiation or chemoradiation. In Panc 05.04, increased cell death was observed upon gemcitabine treatment only. These findings are in line with previous studies that have suggested a role of ALDH1A1 chemoradiation resistance, e.g., in esophageal cancer. In summary, we present one of the first proteome studies to investigate the responsiveness of PDAC to chemoradiation and provide further evidence for a role of ALDH1A1 in therapy resistance.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Proteome Profiling of Primary Pancreatic Ductal Adenocarcinomas Undergoing Additive Chemoradiation Link ALDH1A1 to Early Local Recurrence and Chemoradiation Resistance

Oria

Bronsert

Thomsen

et al. 2018

Translational Oncology

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“…Surgery is the only therapeutic option of treatment associated to adjuvant and neo-adjuvant radio-chemo therapy [8]. Surgery can lead to different complications and elevated intra-operative mortality rate, thus it should be performed by expert surgeons and preceded by a thorough and accurate staging.…”

Section: Introductionmentioning

confidence: 99%

Laparoscopic pancreatectomy: Did the indications change? A review from literature

Sperlongano

Esposito

et al. 2015

International Journal of Surgery

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Pancreatic Cancer (PC) is the fourth cause of death for tumors in Western countries. Symptoms are not specific, and can vary according to the tumor size and place. Diagnostic workup includes CA 19-9, CT and MRI. Surgery is the only treatment for PC, associated to radio-chemo therapy. Laparoscopic approaches are actually used for PC treatment in few specialized centers, and could be an alternative to laparotomic surgery. The aim of our study is to evaluate the efficacy of laparoscopy for PC treatment compared to laparotomy. We reviewed 19 articles in literature to assess the feasibility and efficacy of Laparoscopic Distal Pancreatectomy (LDP) and Laparoscopic Pancreaticoduodenectomy (LPD). The results have shown that LDP is nowadays a safe technique, and the outcomes are comparable to laparotomic surgery. Regarding to LPD instead, results are controversial and the data are still not sufficient to consider this technique as a valid alternative to laparotomic surgery.

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“…Radiotherapy [41] . Standard dose radiation therapy is usually 50.4 Gy in 1.8-Gy fractions, although some trials reported the use of a 30-36 Gy in 3-Gy fractions schedule [42] . Better outcomes could come from the use of newer radiotherapy techniques like intensity-modulated radiation therapy (IMRT) and SBRT, suited to deliver higher biological dose [42] .…”

Section: Current Knowledgementioning

confidence: 99%

“…Standard dose radiation therapy is usually 50.4 Gy in 1.8-Gy fractions, although some trials reported the use of a 30-36 Gy in 3-Gy fractions schedule [42] . Better outcomes could come from the use of newer radiotherapy techniques like intensity-modulated radiation therapy (IMRT) and SBRT, suited to deliver higher biological dose [42] . Indeed, in a phase 2 multi-institutional trial, SBRT was feasible without unexpected toxicities and obtained a 1-year local progression-free survival (PFS) of 78% [43] .…”

Section: Current Knowledgementioning

confidence: 99%

Current therapeutic strategies for advanced pancreatic cancer: A review for clinicians

Spadi¹

2016

WJCO

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Pancreatic cancer (PC) would become the second leading cause of cancer death in the near future, despite representing only 3% of new cancer diagnosis. Survival improvement will come from a better knowledge of risk factors, earlier diagnosis, better integration of locoregional and systemic therapies, as well as the development of more efficacious drugs rising from a deeper understanding of disease biology. For patients with unresectable, non-metastatic disease, combined strategies encompassing primary chemotherapy and radiation seems to be promising. In fit patients, new polychemotherapy regimens can lead to better outcomes in terms of slight but significant survival improvement associated with a positive impact on quality of life. The upfront use of these regimes can also increase the rate of radical resections in borderline resectable and locally advanced PC. Second line treatments showed to positively affect both overall survival and quality of life in fit patients affected by metastatic disease. At present, oxaliplatin-based regimens are the most extensively studied. Nonetheless, other promising drugs are currently under evaluation. Presently, in addition to surgery and conventional radiation therapy, new locoregional treatment techniques are emerging as alternative options in the multimodal approach to patients or diseases not suitable for radical surgery. As of today, in contrast with other types of cancer, targeted therapies failed to show relevant activity either alone or in combination with chemotherapy and, thus, current clinical practice does not include them. Up to now, despite the fact of extremely promising results in different tumors, also immunotherapy is not in the actual therapeutic armamentarium for PC. In the present paper, we provide a comprehensive review of the current state of the art of clinical practice and research in PC aiming to offer a guide for clinicians on the most relevant topics in the management of this disease.

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The Role of Radiation Therapy in Pancreatic Ductal Adenocarcinoma in the Neoadjuvant and Adjuvant Settings

Cited by 21 publications

References 109 publications

Proteome Profiling of Primary Pancreatic Ductal Adenocarcinomas Undergoing Additive Chemoradiation Link ALDH1A1 to Early Local Recurrence and Chemoradiation Resistance

Proteome Profiling of Primary Pancreatic Ductal Adenocarcinomas Undergoing Additive Chemoradiation Link ALDH1A1 to Early Local Recurrence and Chemoradiation Resistance

Laparoscopic pancreatectomy: Did the indications change? A review from literature

Current therapeutic strategies for advanced pancreatic cancer: A review for clinicians

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