Chemotherapy and intensity-modulated radiation therapy for locally advanced pancreatic cancer achieves a high rate of R0 resection*

Abstract

Background To assess local control, survival, and conversion to resectability among locally advanced pancreatic cancer (LAPC) patients treated with induction chemotherapy (ICT) followed by chemoradiotherapy treatment using intensity-modulated radiation therapy (IMRT). Material and Methods Between 2007 and 2012, 134 LAPC patients were treated with ICT followed by IMRT. After chemoradiotherapy, 40 patients received maintenance chemotherapy. Results With a median follow-up of 20 months, median overall survival (OS) was 23 months. One-year and 2-year OS was 85% and 47%, respectively. On multivariate analysis, progression of disease after IMRT was associated with worse overall survival. Cumulative incidence of local failure was 10% at 1 year and 36% at 2 years. Twenty-six patients (19%) underwent resection after chemoradiotherapy including 22 patients (85%) with negative margins. On multivariate analysis, response to IMRT was associated with surgery (p=0.01). Acute grade 3–4 hematologic and non-hematologic toxicity rates were 26% and 4.5%, respectively. Conclusion IMRT is safe in patients with LAPC. Patients with non-progressive LAPC after ICT and who received IMRT had high rates of local control and prolonged survival.

Using adaptive magnetic resonance image‐guided radiation therapy for treatment of inoperable pancreatic cancer

“…In addition, post-RT pancreatectomy rates did not change with the high-dose regimens, and the overall rate of resection of 14% was low in this study as compared to historical series. 9,10 Determining resectability radiographically is difficult after neoadjuvant therapy due to tissue fibrosis complicating imaging interpretation. 24 Use of high-dose regimens may increase the risk of fibrosis even further.…”

“…[2][3][4][5][6][7][8] Multiple institutions have demonstrated favorable survival results with intensity-modulated radiation therapy (IMRT) after induction chemotherapy. 9,10 Krishnan et al have demonstrated that dose escalation using simultaneous integrated boost (SIB) with IMRT improved survival and local control in LAPC compared to standard radiotherapy doses in a single-institution retrospective study. 11 These techniques suggest opportunities to potentially improve outcomes with dose escalation with RT.…”

Multiagent induction chemotherapy followed by chemoradiation is associated with improved survival in locally advanced pancreatic cancer

“…22 The use of multiagent iCRT improved not only overall survival, presumably through the optimization of distant disease control, but also improved local disease management, ultimately increasing the proportion of patients able to undergo pancreatectomy to 9.8%. 27,28 It is important to note that, in the recently published European Study Group for Pancreatic Cancer-4 (ESPAC-4) study, upfront resection led to positive margins in 60% of patients. [23][24][25] Ferrone et al further raised the issue that imaging alone may not be enough to declare unresectability.…”

“…Truty et al and Huguet and colleagues reported similar findings with CRT. 27,28 It is important to note that, in the recently published European Study Group for Pancreatic Cancer-4 (ESPAC-4) study, upfront resection led to positive margins in 60% of patients. 29 The high rates of R0 resection in that analysis are consistent with historical data indicating that <10% of patients have positive margins after receiving neoadjuvant CT or CRT.…”

Neoadjuvant radiation followed by resection versus upfront resection for locally advanced pancreatic cancer patients: a propensity score matched analysis

“…In studies simultaneously involving neoadjuvant therapy and immediate surgery, researchers identified significantly higher rate of R0 resection in pancreatic cancer patients of various stages receiving neoadjuvant therapy [ 27 – 29 , 35 ]. Remarkably high R0 resection rate was reported in selective studies involving borderline resectable and locally advanced pancreatic carcinoma patients amendable to surgery after neoadjuvant therapy: ranging from 75.5% to 100% [ 21 , 36 – 40 ]. In addition, perineural and lymphatic invasion rates were also reportedly significantly lower in neoadjuvant setting [ 29 , 33 ].…”