Stereotactic Body Radiation Therapy plus Induction Chemotherapy versus Stereotactic Body Radiation Therapy plus Adjuvant Chemotherapy for Early Stage but Medically Inoperable Pancreatic Cancer: A Propensity Score Matched Analysis

Abstract

Although surgical resection has been confirmed as the only strategy for cure, especially for resectable pancreatic cancer, only 15-20% of the patients were amenable to this curative-intent treatment at the initial diagnose. However, there was no consensus or clinical trials about optimal multimodality treatment for patients with resectable but medically inoperable pancreatic cancer. Hence, radiotherapy and chemotherapy may be the alternatives if patients are not candidates for surgery. Stereotactic body radiation therapy (SBRT) has become a promising option due to its precise treatment delivery. Therefore, we sought to evaluate the efficacy and safety of SBRT plus chemotherapy and the treatment sequences and identify clinical factors associated with survival in a large cohort of patients with early stage but medically inoperable pancreatic cancer. All patients included in this study were biopsy-proven radiographically resectable pancreatic cancer. Only when they were intolerant of or declined operations, subsequent radiotherapy or chemotherapy was taken into considerations. All patients were required to complete a planned chemotherapy with 6 cycles. The chemotherapy regimen was gemcitabine plus S-1. The interval between induction or adjuvant chemotherapy and SBRT was 2 to 3 weeks. Patients who had completed induction chemotherapy would receive PET-CT to preclude metastasis. Those with metastasis were excluded from the study and received other treatment based on the multidisciplinary approach. CA19-9 response was defined as the level of CA19-9 decrease by 50% from baseline levels of ≥74 U/ml. Hence, three groups were formed for univariate analysis: CA19-9 levels ≥74 U/ml with response vs. CA19-9 levels ≥74 U/ml with no response (including CA19-9 levels within the normal range before SBRT while increased after SBRT) vs. CA19-9 levels <74 U/ml (before SBRT and during follow-up). Factors were investigated for their association with overall survival (OS) and progression free survival (PFS) using univariate log-rank comparisons and then COX regression model. Propensity score matched analyses were performed to further assess the efficacy of different treatment sequences. Forty-eight patients received induction chemotherapy and fifty-two with adjuvant chemotherapy from 2012 to 2016. Only radiation doses were higher in adjuvant chemotherapy group. After multivariate analysis, patients with adjuvant chemotherapy (P<0.001), CA19-9 response (P<0.001) and BED10≥60Gy (P=0.024) had a longer OS, while the former two correlated with PFS. After propensity score matched analysis, patients with adjuvant chemotherapy had OS (23.1 months vs. 15.6, P<0.001) and PFS benefits (18.0 months vs. 11.6 months, P<0.001) than those with induction chemotherapy. SBRT plus chemotherapy, especially adjuvant chemotherapy, may be an alternative for patients with early stage pancreatic cancer but not eligible for surgical resection.