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Despite of new therapeutic approaches, including both systemic and local therapy, locally advanced pancreatic cancer (LAPC) has a poor prognosis. Standard doses of conventionally fractionated radiation have had minimal to no impact on the survival duration of patients with LAPC. However, stereotactic body radiotherapy (SBRT) using CyberKnife (CK), a highly conformal high-dose radiation per fraction, allows the precise delivery of a large ablative radiation dose to a tumour volume while sparing surrounding organs and tissues. This study was designed to evaluate the short-term efficacy and toxicity of image-guided robotic stereotactic radiosurgery- CK for locally advanced pancreatic cancer.

We analysed 9 patients with LAPC, ranging in age from 40 to 86 years (mean: 65), treated with robotic stereotactic radiosurgery-CK, from February 2017 to December 2020. All patients had previous systemic therapy, with no or minimal response. The median total prescription dose was 36 Gy (range 33-40 Gy) delivered in 3 to 6 fractions. The median BED was 111 Gy (range 87-144 Gy). The planning target volume (PTV) was defined as gross tumour volume (GTV) plus 2-3 mm, and at least 95% PTV should be covered by 80% isodose surface. The median volume of PTV was 63 cm³ (22-120 cm³).

Of the 9 patients, 5 were male and 4 female. In 5 cases, the tumour was located at the pancreatic head and 4 at the pancreatic body. The median follow-up was 10 months (range 3-31 months). All patients completed the treatment prescribed, with a good tolerance.  Two patients presented grade I nausea, and there was a case of grade II vomiting. There were no grade III/IV toxicity. The evaluation was performed with a CT scan and/or PET-CT scan. Local control was achieved in 7 patients, 4 with complete response and 3 with partial response. Two patients presented disease progression, mainly with hepatic metastases. The median OS was 10 months (range 3-31). By the time of the present analysis, and with a mean follow-up of 10 months, 4 patients remain with no evidence of disease.

The conformity and rapid dose fall-off associated with SBRT offer the potential for dose escalation. Image-guided robotic stereotactic radiosurgery with CK may be considered a treatment option to achieve local control of locally advanced pancreatic cancer, with limited toxicity to normal surrounding tissues. The use of a multi-fraction regimen and high total dose as allowable based on dose-volume constraints to organs at risk should be considered to minimize toxicity and improve local control outcomes. In the present study 44,4% of the patients remains with no evidence of disease, with a mean follow-up period of 10 months.

Better understanding of biological mechanisms for tumour response underlying stereotactic radiosurgery treatment for LAPC, will allow for additional improvements in disease control.

However, long-term follow-up is necessary to evaluate the survival and late toxicity.