Turkish Journal of Surgery

Turkish Journal of Surgery

ISSN: 2564-6850
e-ISSN: 2564-7032


Yasemin Benderli Cihan

Department of Radiation Oncology, Kayseri Training and Research Hospital, Kayseri, Turkey

Pancreatic neuroendocrine tumors (PNETs) are a heterogeneous group of tumors with highly variable biological behaviors and clinical course. Despite being rare, its incidence is steadily increasing over time. In recent years, advances have been made in the treatment of these tumors in parallel to the increase in the incidence of PNETs. Although a multidisciplinary approach is required for the clinical management of PNETs, resection remains to be the single curative treatment in early disease. In retrospective studies, it has been reported that surgical resection alone provides better outcomes than other treatment modalities; however, patients eligible for resection comprise only 39% of the patients (1-3). Chemotherapy, radiofrequency ablation, transarterial chemoembolization, biotherapy, polypeptide radionuclide receptor therapy, anti-angiogenic treatment and selective internal radiotherapy alone can be used in advanced PNETs. However, studies have failed to demonstrate long-term survival benefit in these alternative approaches. Today, there is no effective treatment modality for locally advanced PNETs due to high malignancy potential and resistance to conventional chemotherapy. However, it has been attempted to use targeted therapies such as Everolimus or Sutent, radiotherapy and chemotherapy in combination strategies (1-5).

Although there are several studies attempting to define the role and importance of radiotherapy in PNETs in the literature, many uncertainties are present regarding these tumors. Role of external beam radiation therapy (EBRT) is largely unknown in the management of PNETs, and data are limited to anecdotal reports. In general, it is thought that PNETs are resistant to radiotherapy. However, in recent years, there have been studies indicating that PNETs respond to both radiotherapy and chemotherapy. In a study by Saif et al., radiotherapy (50.4 Gy/1.8 Gy fractions) plus capecitabine or infusional 5’-flurouracyl has been given to patients uundergoing surgery due to locally advanced PNET. Authors have reported that chemoradiotherapy was tolerable and provided good local control in the treatment of PNET (1). In a study by Contessa et al., 36 patients with PNET have been treated by external beam radiation therapy. Authors have reported that no local failure was observed at doses > 32 BED (2 Gy) (2). In a study on patients with pancreatic PNET, Zagar et al. have stratified patients into two groups as patients treated with surgical resection alone and those received combined chemoradiotherapy following surgery. In the combination group, patients received radiotherapy (50.4 Gy/1.8 Gy fraction) plus fluoropyrimidine-based chemotherapy. Authors have reported that there was no significant difference in disease-free survival and overall survival between the groups (4). Another study has compared patients undergoing surgery alone with those that received adjuvant radiotherapy among PNET cases with positive surgical margins. Authors have reported that recurrence rate was comparable between the groups and that radiotherapy could be helpful in achieving local control (5). It has been emphasized that radiotherapy is a good palliative modality in patients with unresectable tumor and symptomatic findings (2). In another study, it has been suggested that local radiotherapy can achieve debulking in unresectable or locally advanced tumors (6).

Despite being rare, PNETs are treatable tumors increasingly diagnosed by advancing imaging modalities. They have highly variable clinical course with life expectancy varying from months to years. Several modalities have been used in the management of PNET. Due to lack of prospective, randomized studies, it is unknown which criteria should be used to select treatment modality. In the last decade, significant advances have been achieved in the treatment of PNETs by radiotherapy and chemoradiotherapy. In inoperable or locally advanced PNETs, local control, decrease in tumor burden, regression in clinical symptoms, decelerated disease progression and prolonged progression-free survival can be achieved by radiotherapy and chemoradiotherapy. It will be possible to determine the role of radiotherapy by multicenter, prospective studies with larger sample size, providing relatively uniform analysis and specific assessment of tumor groups. The selection of eligible patients, well-constructed treatment plan, and well-planned clinical and radiological follow-up should be the mainstay of studies in this field.

Cite this article as: Benderli Cihan Y. Are PNETs radiotherapy resistant? Turk J Surg 2020; 36 (2): 238-239

Conflict of Interest

The authors have no conflicts of interest to declare.

Financial Disclosure

The authors declared that this study has received no financial support.


  1. Saif MW, Ove R, Ng J, Russo S. Radiotherapy in the management of pancreatic neuroendocrine tumors (PNET): experience at three institutions. Anticancer Res 2013; 33 (5): 2175-7.
  2. Contessa JN, Griffith KA, Wolff E, Ensminger W, Zalupski M, Lawrence TS, et al. Radiotherapy for pancreatic neuroendocrine tumors. Int J Radiat Oncol Biol Phys 2009; 75 (4): 1196-200. doi: 10.1016/j.ijrobp.2008.12.044. Epub 2009 Mar 26.
  3. Iwata T, Ueno H, Itami J, Ito Y, Inaba K, Morizane C, et al. Efficacy of radiotherapy for primary tumor in patients with unresectable pancreatic neuroendocrine tumors. Jpn J Clin Oncol 2017; 47 (9): 826-31. doi: 10.1093/jjco/hyx081.
  4. Zagar TM, White RR, Willett CG, Tyler DS, Papavassiliou P, Papalezova KT, et al. Resected pancreatic neuroendocrine tumors: patterns of failure and disease-related outcomes with or without radiotherapy. Int J Radiat Oncol Biol Phys 2012; 83 (4): 1126-31. doi: 10.1016/j.ijrobp.2011.09.041. Epub 2012 Jan 21.
  5. Arvold ND, Willett CG, Fernandez-del Castillo C, Ryan DP, Ferrone CR, Clark JW, et al. Pancreatic neuroendocrine tumors with involved surgical margins: prognostic factors and the role of adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 2012; 83 (3): e337-43. doi: 10.1016/j.ijrobp.2011.12.068. Epub 2012 Mar 11.
  6. Maidment BW, Ellison T, Herman JM, Sharma NK, Laheru D, Regine W, et al. Radiation in the management of pancreatic neuroendocrine tumors. J Clin Oncol 2012; 30 (Suppl 4): S335.