Abstract
PurposeThe role of radiotherapy for unresectable pancreatic cancer is controversial. A benefit of additional radiotherapy is supported by some observations. A dose-effect relationship was recently found by dose escalation employing image guided and intensity modulated radiotherapy.MethodsWe retrospectively evaluated 28 consecutive patients, all with history of extensive prior therapies for unresectable locally advanced/ recurrent pancreatic cancer (LAPC/LRPC). Treatment was delivered by helical tomotherapy after daily position verification with computed tomography. Dose to the planned target volume (PTV) was 51 Gy, while the dose to the macroscopic tumor was escalated by a simultaneous integrated boost to a median cumulative dose of 66 Gy (60–66 Gy). Concomitant chemotherapy consisted mainly of capecitabine (n = 23).Results10 of 28 patients presented acute toxicities > grade 2, one patient succumbed to gastrointestinal bleeding after treatment. No correlations of toxicities and dose volume histograms (DVH) of retrospectively delineated small bowel loops were observed, although average small bowel volume receiving ≥ 20 Gy was 374 ml. DVH analyses revealed a correlation of splenic parameters and acute toxicity: Vomiting, anorexia, dehydration, hematologic toxicity, fatigue, combined gastro-intestinal toxicity wit R-values between 0.392 and 0.561 (all p-values > 0.05). Only one patient developed late toxicities > grade 2. With an average follow-up time in surviving patients of 14 months median overall survival time was 19 months and median time to local recurrence 13 months. In 8 patients with available imaging of local recurrence: 5 in field recurrences, 2 marginal recurrences and one lymph node recurrence outside the high dose radiation field were observed. In univariate analysis only ΔCA-19-9 during radiotherapy was associated with local control (p = 0.029) and overall survival (p = 0.049).ConclusionDose escalated normo-fractionated radiotherapy for LAPC/LRPC seems feasible and suitable to prolong local control and in consequence long-term survival. However, in-field local progression is still frequently observed and possibilities to increase the local effectiveness should be evaluated. Exposure of the spleen was predictive for acute toxicity and should be further investigated.
Highlights
Pancreatic cancer is an aggressive disease with unfavourable prognosis
dose volume histograms (DVH) analyses revealed a correlation of splenic parameters and acute toxicity: Vomiting, anorexia, dehydration, hematologic toxicity, fatigue, combined gastro-intestinal toxicity wit R-values between 0.392 and 0.561
Exposure of the spleen was predictive for acute toxicity and should be further investigated
Summary
Pancreatic cancer is an aggressive disease with unfavourable prognosis. Even for localized stages, the 5 year overall survival rate after curative resection and adjuvant chemotherapy is only around 20% [1,2]. For locally advanced stages (LAPC) unable to undergo surgery, the patientsoutcome is dismal and the goal of the treatment is survival prolongation and symptom control with a median overall survival (OS) between 5 to 11 months [3]. The prognosis for isolated locally recurrent pancreatic carcinomas is similar to initial LAPC with reported median overall survival around 6 months [4] if patients are not eligible for re-surgery [5,6]. The role of radiotherapy (RT) for LAPC (or LRPC) is controversial due to the high prevalence of distant metastases (long-term up to 70%) and the radiosensitivity of surrounding organs at risk (OAR) in the upper abdomen. Second the intolerances in the upper abdomen can mislead to prescribe ineffective radiotherapy schedules in order to avoid high toxicity
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