Alternate Fractionation in Radiotherapy by Mark Trombetta Jean-Philippe Pignol Paolo Montemaggi & Luther W. Brady

Author:Mark Trombetta, Jean-Philippe Pignol, Paolo Montemaggi & Luther W. Brady
Language: eng
Format: epub
Publisher: Springer International Publishing, Cham

4.3 Adjuvant Chemotherapy vs. Adjuvant Chemoradiation

Although there is some evidence to suggest that adjuvant therapy with CRT is beneficial compared to surgical resection alone, the bulk of prospective data favor adjuvant chemotherapy alone. Several large retrospective series including a National Cancer Database study and a large, multi-institutional pooled analysis have found a statistically significant benefit in median overall survival associated with adjuvant CRT compared to chemotherapy alone (Morganti et al. 2014; Kooby et al. 2013). Despite these large retrospective series, a meta-analysis of 9 prospective trials published in 2012 and another meta-analysis of 15 prospective trials with various chemotherapy regimens found that adjuvant chemotherapy was associated with improved patient outcomes but there was no statistically significant improvement in overall survival with adjuvant CRT (Ren et al. 2012; Liao et al. 2013). One particularly notable trial is the European Study Group for Pancreatic Cancer (ESPAC)-1, a multi-institution phase III trial with a 2 × 2 randomization of four patient groups: observation, adjuvant 5-FU-based chemotherapy, adjuvant concurrent CRT (using split-course radiation to 40 Gy and 5-FU-based chemotherapy), and adjuvant concurrent CRT followed by an additional six cycles of 5-FU/leucovorin. Survival outcomes favored adjuvant chemotherapy alone (21.6 months); however, the outcomes suggest that the addition of adjuvant radiation therapy to chemotherapy (19.9 months) was associated with improved survival outcomes than with observation alone (13.9 months) (Neoptolemos et al. 2009). Criticisms of this trial include the 2 × 2 randomization scheme, lack of radiation field guidelines or central review of radiation planning, and lack of restaging before adjuvant therapy (Herman et al. 2015b). The ongoing clinical trial RTOG 0848 will further clarify the role of adjuvant radiation therapy following surgical resection (Franke et al. 2015). Other analyses have explored identification of select patients who may benefit from adjuvant CRT. In a meta-analysis of four randomized controlled trials, Butturini et al. found that chemoradiotherapy in patients with microscopically positive margins (R1) resulted in 28% reduction in the risk of death (HR 0.72, 95% CI 0.47–1.1) (Butturini et al. 2008). This was also demonstrated in another meta-analysis of five randomized controlled adjuvant CRT trials that demonstrated that CRT was more effective in patients with positive resection margins (Stocken et al. 2005). Finally, in a retrospective series from the Johns Hopkins Hospital of adjuvant CRT following resection in patients with distal disease, a subgroup of patients with node-positive disease who received adjuvant CRT correlated with a survival benefit (16.7 vs. 12.1 months) (Redmond et al. 2010). Therefore, there are conflicting data with regard to adjuvant CRT as a standard option, but there may be a subgroup of patients with pathologic features who may benefit.

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