Introduction
Pancreatic exocrine tumours are fatal in the majority of the patients, due to late diagnosis and poor response to combined treatment. Patients with locally advanced unresectable or metastatic pancreatic cancer represent a clear majority among all patients with pancreatic cancer (1–4).
Pancreatic cancer is the fourth leading cause of cancer-related mortality, with a 5-year overall survival (OS) rate of 6% (3–7). Cancers that are detected incidentally are likely to be treated surgically, with or without adjuvant therapy. However, the median survival time is limited to 11–23 months and the 5-year survival rate is <20% (2,4–6).
The majority of the patients present with incurable disease and several experience rapid clinical deterioration, without any improvement over several decades (7,8).
Determining whether a tumour is resectable is not well reflected by TNM system staging, as demonstrated by the wide range of survival figures reported for each stage.
To be determined as resectable, tumours must show no evidence of extrapancreatic disease or direct tumour extension to the celiac axis and superior mesenteric artery. However, the evidence of non-obstructive superior mesenteric-portal vein confluence does not always preclude tumour resection.
Complete surgical resection is the only potentially curative treatment available.
For ~35–40% of the patients who have locally advanced disease at the time of diagnosis, chemoradiation (CRT) is one of the most common treatments (9). CRT is an effective palliative treatment, although it has notable limitations. Studies have shown improved median survival times in patients treated with CRT compared with either chemotherapy (6) or RT alone. Patients with locally advanced disease may present with major local symptoms.
Optimal symptomatic treatment may play a key role in the management of metastatic disease. This may require stenting or bypass surgery for obstructive jaundice or gastric outlet obstruction. The most common symptom from local extension is pain, which may significantly affect the patient's quality of life. RT is used to control these symptoms, as was reported in locally advanced gastric cancer (10,11).
Discussion
Most clinicians are cautious when recommending an active treatment modality for pancreatic cancer in their clinical practice, due to the poor prognosis of this disease, the wishes of the patients or advanced age, although patients may be in a reasonably good medical condition. Based on the results of Krzyżanowska et al (14) in a cohort study on locally advanced pancreatic cancer, 44% of the patients received some form of cancer-directed therapy [24% received concurrent CRT therapy (CCRT), 13% received RT alone and 7% received chemotherapy alone].
According to that study, any type of active treatment was found to prolong survival.
Park et al (15), in a subgroup analysis of 340 patients with unresectable, locally advanced, or metastatic pancreatic cancer, found that stage III patients treated with either CCRT (median OS, 10.4 months) or chemotherapy alone (median OS, 11.3 months) exhibited a survival benefit over supportive care (median OS, 6.4 months), whereas stage IV patients treated with chemotherapy alone (median OS, 6.4 months) showed a survival benefit over supportive care (median OS, 3.1 months). The majority of patients who have pancreatic cancer in their initial evaluation have a combination of factors, such as advanced age, poor performance status, medical comorbidity or tumour-related conditions, such as anorexia; thus, they are poor candidates for aggressive therapy, such as CRT. It is important to perform a stratification of patients into treatment groups on the basis of prognostic factors (16,17).
Morganti et al (18) evaluated 12 patients to observe whether a short RT treatment (30 Gy, 3.0 Gy/fraction) exhibited analgesic efficacy in patients with unresectable pancreatic carcinoma. They concluded that, in patients excluded from standard concomitant CRT, hypofractionated RT is feasible and results in pain relief in the majority of the patients. Our observations also included a reduced need for analgesics.
Pain due to pancreatic cancer is a manifestation of neural invasion and obstructive ductal physiological pain in nearly all patients. Intervention in the form of celiac neurolysis with chemical agents decreases pain (19) and may actually improve survival. Celiac neurolysis may be performed intraoperatively, percutaneously, or endoscopically under ultrasound guidance (20,21).
Other methods for reducing pain are advanced RT techniques, such as stereotactic body RT, which are associated with low rates of adverse effects and good local control in patients with locally advanced pancreatic cancer (22,23). However, not all patients are good candidates for this type of sophisticated treatment.
This study indicates that more active treatments should be attempted, even in cases of locally advanced unresectable pancreatic cancer. Palliative RT is a last resort to improve local pain control in patients with unresectable pancreatic cancer (24). A total of 30 Gy in 10 fractions is one of the most commonly used dose-fractionation regiments of palliative RT in cases with brain metastasis, bone metastasis and bleeding from advanced gastric cancer (25). Wong et al (26) compared the scheme of 30 Gy in 10 fractions and the scheme of >30 Gy with concurrent infusions of 5-FU, and the median survival times were similar with both schemes. Considering the median survival time (5 months) following RT, this regimen appears to be adequate for patients with poor prognosis.
The classical endpoints of palliative treatment are survival, tumour response and quality of life. Patients who were treated with palliative RT gained clinical benefits. Undoubtedly, these treatments have reinforced the role of analgesic drugs.
Palliative treatment is often the only remaining option in the management of pancreatic carcinoma, but its efficacy is poor due to low tumour sensitivity and inadequate treatment protocols. There are several options for palliative treatment, with either an antitumor effect as immunotherapy (27,28) or as supportive care. The present study demonstrated that patients with locally advanced pancreatic cancer who receive palliative RT have better survival rates compared with those who receive supportive care alone. RT, when used as a palliative treatment, was well-tolerated and was associated with a good median OS rate. Hence, palliative RT remains a non-invasive treatment option for improving pain control in patients with locally advanced or metastatic pancreatic cancer.