Stereotactic Body Radiotherapy in Pancreatic Cancer
Stereotactic Body Radiotherapy in Pancreatic Cancer
The management of pancreatic cancer continues to be challenging. Despite surgical, genetic and molecular advances, its overall prognosis remains poor. Surgical resection is the only modality that offers a chance for a cure, with an overall survival rate of 10–20% at 5 years. However, only 20% of the patients are surgical candidates because of locally advanced disease or systemic stage at presentation. Conventional radiotherapy, with or without chemotherapy, has been used to treat patients with advanced-stage pancreatic cancer, an approach with high rates of local recurrence. Stereotactic body radiation therapy, also known as stereotactic ablative radiotherapy has emerged as a treatment modality that allows the precise delivery of a large ablative radiation dose to a tumor volume while sparing surrounding organs and tissues. Phase I and II studies have shown good rates of local control of the disease but rates of distant metastasis remain significant. Strategies to combine novel systemic therapy and stereotactic body radiation therapy are to be explored.
The management of pancreatic cancer continues to be challenging. Although it is the tenth most frequent malignancy, it is the fourth leading cause of cancer mortality for both sexes in the USA. It is estimated that 43,920 new cases of pancreatic cancer were diagnosed in the USA in 2012, with 37,390 related deaths. Overall, despite the surgical, genetic and molecular advances, there has been little change in the overall prognosis over the last decades, with an overall 5-year survival of 5%.
The onset of pancreatic cancer is often insidious. The frequent lack of symptoms at its onset allows the cancer to progress to a more advanced stage prior to its diagnosis. Surgical resection is the only modality providing a chance of cure, with a 5-year survival of 10–20% with an R0 resection. In a recent report based on Radiation Therapy Oncology Group 9704, where patients were randomized to either pre- and post-chemoradiotherapy gemcitabine or pre- and post-chemoradiotherapy 5-fluorouracil, the 5-year survival rates were 22 and 18%, respectively. Unfortunately, only 20% of the patients are candidates for a curative resection due to local invasion of the tumor or metastatic spread. The treatment of patients with unresectable disease involves chemoradiotherapy, with a median survival of 7.8–18.8 months and few long-term survivors. In these patients, local control is a goal, not only to slow the progression of the disease, but to prevent the obstruction and pain that quickly become detrimental to a patient's quality of life. Despite attempts to improve local control, local failure occurs in almost half of patients after chemoradiotherapy, affecting quality of life. Furthermore, approximately 42% of the patients undergoing pancreatic resection have positive margins (R1 resection). The Royal College of Pathologists currently recommend that microscopic evidence of tumor within 1 mm of a resection margin should be classified as R1 for pancreatoduodenectomy specimen reporting. In a study from University of Liverpool (Liverpool, UK), patients were found to have poorer survival if they had R1 resection, with incorporation of The Royal College of Pathologists recommendation. No difference in overall survival was found between patients with positive resection margins and those with microscopic evidence of tumor within 1 mm of a resection margin. R2 resections have also been performed in patients with pancreatic cancer. With an increased risk of morbidity and mortality, a median survival of 8.2 months has been reported.
Conventional radiotherapy has drawbacks, including the limitation of the amount of radiation that can be delivered to the GI tract, the relatively high number of treatments involved (typically 25–30 fractions) and the side effects. There had been some uncertainty regarding the efficacy of chemoradiotherapy compared with chemotherapy alone. Recently, a Phase III randomized study from the Eastern Cooperative Oncology Group (ECOG) showed that patients with locally advanced disease receiving concurrent radiotherapy with gemcitabine had improved survival compared with those receiving gemcitabine alone. Local therapy evidently plays an important part in the management of locally advanced pancreatic cancer, although the local failure rate remains high. Trials of chemoradiotherapy with standard fractionation have shown a high local failure rate of up to 30–60%. The role of local therapy may thus be to delay the local progression of the disease. Stereotactic body radiotherapy (SBRT) is a recent advancement that allows for the precise delivery of a large ablative radiation dose to the tumor in one to five fractions. SBRT has been investigated in unresectable pancreatic cancer for local tumor control. The aim of this article is to review the emerging role of SBRT in the management of pancreatic cancer.
Abstract and Introduction
Abstract
The management of pancreatic cancer continues to be challenging. Despite surgical, genetic and molecular advances, its overall prognosis remains poor. Surgical resection is the only modality that offers a chance for a cure, with an overall survival rate of 10–20% at 5 years. However, only 20% of the patients are surgical candidates because of locally advanced disease or systemic stage at presentation. Conventional radiotherapy, with or without chemotherapy, has been used to treat patients with advanced-stage pancreatic cancer, an approach with high rates of local recurrence. Stereotactic body radiation therapy, also known as stereotactic ablative radiotherapy has emerged as a treatment modality that allows the precise delivery of a large ablative radiation dose to a tumor volume while sparing surrounding organs and tissues. Phase I and II studies have shown good rates of local control of the disease but rates of distant metastasis remain significant. Strategies to combine novel systemic therapy and stereotactic body radiation therapy are to be explored.
Introduction
The management of pancreatic cancer continues to be challenging. Although it is the tenth most frequent malignancy, it is the fourth leading cause of cancer mortality for both sexes in the USA. It is estimated that 43,920 new cases of pancreatic cancer were diagnosed in the USA in 2012, with 37,390 related deaths. Overall, despite the surgical, genetic and molecular advances, there has been little change in the overall prognosis over the last decades, with an overall 5-year survival of 5%.
The onset of pancreatic cancer is often insidious. The frequent lack of symptoms at its onset allows the cancer to progress to a more advanced stage prior to its diagnosis. Surgical resection is the only modality providing a chance of cure, with a 5-year survival of 10–20% with an R0 resection. In a recent report based on Radiation Therapy Oncology Group 9704, where patients were randomized to either pre- and post-chemoradiotherapy gemcitabine or pre- and post-chemoradiotherapy 5-fluorouracil, the 5-year survival rates were 22 and 18%, respectively. Unfortunately, only 20% of the patients are candidates for a curative resection due to local invasion of the tumor or metastatic spread. The treatment of patients with unresectable disease involves chemoradiotherapy, with a median survival of 7.8–18.8 months and few long-term survivors. In these patients, local control is a goal, not only to slow the progression of the disease, but to prevent the obstruction and pain that quickly become detrimental to a patient's quality of life. Despite attempts to improve local control, local failure occurs in almost half of patients after chemoradiotherapy, affecting quality of life. Furthermore, approximately 42% of the patients undergoing pancreatic resection have positive margins (R1 resection). The Royal College of Pathologists currently recommend that microscopic evidence of tumor within 1 mm of a resection margin should be classified as R1 for pancreatoduodenectomy specimen reporting. In a study from University of Liverpool (Liverpool, UK), patients were found to have poorer survival if they had R1 resection, with incorporation of The Royal College of Pathologists recommendation. No difference in overall survival was found between patients with positive resection margins and those with microscopic evidence of tumor within 1 mm of a resection margin. R2 resections have also been performed in patients with pancreatic cancer. With an increased risk of morbidity and mortality, a median survival of 8.2 months has been reported.
Conventional radiotherapy has drawbacks, including the limitation of the amount of radiation that can be delivered to the GI tract, the relatively high number of treatments involved (typically 25–30 fractions) and the side effects. There had been some uncertainty regarding the efficacy of chemoradiotherapy compared with chemotherapy alone. Recently, a Phase III randomized study from the Eastern Cooperative Oncology Group (ECOG) showed that patients with locally advanced disease receiving concurrent radiotherapy with gemcitabine had improved survival compared with those receiving gemcitabine alone. Local therapy evidently plays an important part in the management of locally advanced pancreatic cancer, although the local failure rate remains high. Trials of chemoradiotherapy with standard fractionation have shown a high local failure rate of up to 30–60%. The role of local therapy may thus be to delay the local progression of the disease. Stereotactic body radiotherapy (SBRT) is a recent advancement that allows for the precise delivery of a large ablative radiation dose to the tumor in one to five fractions. SBRT has been investigated in unresectable pancreatic cancer for local tumor control. The aim of this article is to review the emerging role of SBRT in the management of pancreatic cancer.