Ablative Five-Fraction Stereotactic Body Radiation Therapy for Inoperable Pancreatic Cancer Using Online MR-Guided Adaptation

Comron Hassanzadeh, Soumon Rudra, Ani Bommireddy, William G Hawkins, Andrea Wang-Gillam, Ryan C Fields, Bin Cai, Justin Park, Olga Green, Michael Roach, Lauren Henke, Hyun Kim, Comron Hassanzadeh, Soumon Rudra, Ani Bommireddy, William G Hawkins, Andrea Wang-Gillam, Ryan C Fields, Bin Cai, Justin Park, Olga Green, Michael Roach, Lauren Henke, Hyun Kim

Abstract

Purpose: Patients with inoperable pancreatic adenocarcinoma have limited options, with traditional chemoradiation providing modest clinical benefit and an otherwise poor prognosis. Stereotactic body radiation therapy for pancreatic cancer is limited by proximity to organs-at-risk (OAR). However, stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) has shown promise in delivering ablative doses safely. We sought to demonstrate the benefits of SMART using a 5-fraction approach with daily on-table adaptation.

Methods and materials: Patients with locally advanced, nonmetastatic pancreatic adenocarcinoma were treated with 50 Gy in 5 fractions (biologically effective dose10 100 Gy) with a prescribed goal of 95% planning target volume coverage by 95% of prescription, prioritizing hard OAR constraints. Daily online adaptation was performed using magnetic resonance-guidance and on-table reoptimization. Patient outcomes, treatment factors, and daily adaptation were evaluated.

Results: Forty-four patients were treated with SMART at our institution from 2014 to 2019. Median follow-up from date of diagnosis was 16 months (range, 6.7-51.6). Late toxicity was limited to 2 (4.6%) grade 3 (gastrointestinal ulcers) and 3 (6.8%) grade 2 toxicities (duodenal perforation, antral ulcer, and gastric bleed). Tumor abutted OARs in 35 patients (79.5%) and tumor invaded OARs in 5 patients (11.1%). Reoptimization was performed for 93% of all fractions. Median overall survival was 15.7 months (95% confidence interval, 10.2-21.2), while 1-year and 2-year overall survival rates were 68.2% and 37.9%, respectively. One-year local control was 84.3%.

Conclusions: This is the first reported experience using 50 Gy in 5 fractions for inoperable pancreatic cancer. SMART allows this ablative dose with promising outcomes while minimizing toxicity. Additional prospective trials evaluating efficacy and safety are warranted.

© 2020 The Author(s).

Figures

Figure 1
Figure 1
Consolidated Standards of Reporting Trials (CONSORT) diagram.
Figure 2
Figure 2
Example of stereotactic magnetic resonance-guided adaptive radiation therapy (SMART), on-table adaptation. Seventy-six-year-old patient with lesion at pancreatic head invading duodenum who underwent adaptation for all 5 fractions. (A) Axial and sagittal original, predicted treatment plan for patient. (B) Treatment plan for the delivered fraction after adaptation. (C) The corresponding dose-volume histogram (DVH) with the solid representing the predicted, original plan and the dashed representing the delivered, adapted plan.
Figure 3
Figure 3
Kaplan-Meier estimates of survival for (A) progression-free survival and (B) overall survival. The 95% confidence intervals are included as dotted lines.

References

    1. Siegel R., Naishadham D., Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.
    1. Hammel P., Huguet F., Laethem J-L van. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: The LAP07 randomized clinical trial. JAMA. 2016;315:1844–1853.
    1. Huguet F., Hajj C., Winston C.B. Chemotherapy and intensity-modulated radiation therapy for locally advanced pancreatic cancer achieves a high rate of R0 resection. Acta Oncol Stockh Swed. 2017;56:384–390.
    1. Krishnan S., Chadha A.S., Suh Y. Focal radiation therapy dose escalation improves overall survival in locally advanced pancreatic cancer patients receiving induction chemotherapy and consolidative chemoradiation. Int J Radiat Oncol Biol Phys. 2016;94:755–765.
    1. Moraru I.C., Tai A., Erickson B. Radiation dose responses for chemoradiation therapy of pancreatic cancer: An analysis of compiled clinical data using biophysical models. Pract Radiat Oncol. 2014;4:13–19.
    1. Milano M.T., Chmura S.J., Garofalo M.C. Intensity-modulated radiotherapy in treatment of pancreatic and bile duct malignancies: Toxicity and clinical outcome. Int J Radiat Oncol Biol Phys. 2004;59:445–453.
    1. Herman J.M., Chang D.T., Goodman K.A. Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma. Cancer. 2015;121:1128–1137.
    1. Hoyer M., Roed H., Sengelov L. Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma. Radiother Oncol. 2005;76:48–53.
    1. Mahadevan A., Miksad R., Goldstein M. Induction gemcitabine and stereotactic body radiotherapy for locally advanced nonmetastatic pancreas cancer. Int J Radiat Oncol Biol Phys. 2011;81:e615–e622.
    1. Noel C.E., Parikh P.J., Spencer C.R. Comparison of onboard low-field magnetic resonance imaging versus onboard computed tomography for anatomy visualization in radiotherapy. Acta Oncol. 2015;54:1474–1482.
    1. Bohoudi O., Bruynzeel A.M.E., Senan S. Fast and robust online adaptive planning in stereotactic MR-guided adaptive radiation therapy (SMART) for pancreatic cancer. Radiother Oncol. 2017;125:439–444.
    1. Henke L., Kashani R., Yang D. Simulated online adaptive magnetic resonance–guided stereotactic body radiation therapy for the treatment of oligometastatic disease of the abdomen and central thorax: characterization of potential advantages. Int J Radiat Oncol. 2016;96:1078–1086.
    1. Henke L.E., Olsen J.R., Contreras J.A. Stereotactic MR-Guided Online Adaptive Radiation Therapy (SMART) for ultracentral thorax malignancies: results of a phase 1 trial. Adv Radiat Oncol. 2019;4:201–209.
    1. Henke L.E., Contreras J.A., Mazur T. Delineation of a cardiac planning organ-at-risk volume using real-time magnetic resonance imaging for cardiac protection in thoracic and breast radiation therapy. Pract Radiat Oncol. 2019;9:e298–e306.
    1. Rosenberg S.A., Henke L.E., Shaverdian N. A multi-institutional experience of MR-guided liver stereotactic body radiation therapy. Adv Radiat Oncol. 2019;14:142–149.
    1. Rudra S., Jiang N., Rosenberg S.A. Using adaptive magnetic resonance image-guided radiation therapy for treatment of inoperable pancreatic cancer. Cancer Med. 2019;8:2123–2132.
    1. Acharya S., Fischer-Valuck B.W., Kashani R. Online magnetic resonance image guided adaptive radiation therapy: first clinical applications. Int J Radiat Oncol. 2016;94:394–403.
    1. Henke L., Kashani R., Robinson C. Phase I trial of Stereotactic MR-guided online Adaptive Radiation Therapy (SMART) for the treatment of oligometastatic or unresectable primary malignancies of the abdomen. Radiother Oncol. 2018;126:519–526.
    1. Conroy T., Desseigne F., Ychou M. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–1825.
    1. Von Hoff D.D., Ervin T., Arena F.P. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–1703.
    1. Crane C.H. Hypofractionated ablative radiotherapy for locally advanced pancreatic cancer. J Radiat Res (Tokyo) 2016;57:i53–i57.
    1. Crane C.H., Chanda A.S., Koay E.J. Effect of dose-escalation of IMRT for unresectable pancreatic cancer 1 cm away from the luminal mucosa on long-term survival. J Clin Oncol. 2015;33 354-354.
    1. El-Bared N., Portelance L., Spieler B.O. Dosimetric benefits and practical pitfalls of daily online adaptive MRI-guided stereotactic radiation therapy for pancreatic cancer. Pract Radiat Oncol. 2019;9:e46–e54.
    1. Kharofa J., Mierzwa M., Olowokure O. Pattern of marginal local failure in a phase II trial of neoadjuvant chemotherapy and stereotactic body radiation therapy for resectable and borderline resectable pancreas cancer. Am J Clin Oncol. 2019;42:247–252.
    1. Iacobuzio-Donahue C.A., Fu B., Yachida S. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol. 2009;27:1806–1813.

Source: PubMed

3
Abonnere