Dose-escalated radiotherapy for unresectable or locally recurrent pancreatic cancer: Dose volume analysis, toxicity and outcome of 28 consecutive patients

TY - JOUR

T1 - Dose-escalated radiotherapy for unresectable or locally recurrent pancreatic cancer: Dose volume analysis, toxicity and outcome of 28 consecutive patients

AU - Zschaeck, Sebastian

AU - Blümke, Bibiana

AU - Wust, Peter

AU - Kaul, David

AU - Bahra, Marcus

AU - Riess, Hanno

AU - Klein, Fritz

AU - Sinn, Marianne

AU - Pelzer, Uwe

AU - Budach, Volker

AU - Ghadjar, Pirus

PY - 2017

Y1 - 2017

N2 - PURPOSE: The 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.METHODS: We 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).RESULTS: 10 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).CONCLUSION: Dose 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.

AB - PURPOSE: The 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.METHODS: We 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).RESULTS: 10 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).CONCLUSION: Dose 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.

KW - Aged

KW - Antineoplastic Agents/therapeutic use

KW - CA-19-9 Antigen/blood

KW - Dose Fractionation, Radiation

KW - Female

KW - Humans

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Neoplasm Grading

KW - Neoplasm Recurrence, Local

KW - Pancreatic Neoplasms/drug therapy

KW - Radiotherapy, Intensity-Modulated/methods

KW - Retrospective Studies

KW - Spleen/physiology

U2 - 10.1371/journal.pone.0186341

DO - 10.1371/journal.pone.0186341

M3 - SCORING: Journal article

C2 - 29023527

VL - 12

SP - e0186341

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 10

ER -