Cumulative Target Volume Dose and Locoregional Failure in Pancreatic Cancer Patients With Treated With Ablative Stereotactic MR-Guided Adaptive Radiation Therapy (SMART)

Abstract

Materials/Methods: Twelve patients with large (mean = 7.0 cm, range: 5.2-7.8 cm, diameter) lung masses from at least Stage II non-small-cell lung cancer (NSCLC) or oligometastatic lung disease from a separate primary site underwent 50 Gy to the planning target volume (PTV) with a 60 Gy SIB to the volume approximately 1 cm interior to the standard gross tumor volume (GTV) margin in 5 fractions. Highly conformal SIB SBRT plans were generated using 3-6 non-coplanar partial VMAT arcs with 6MV-FFF beam and advanced Acuros-based dose engine for tissues heterogeneity corrections. Treatments were delivered every other day using online conebeam CT guidance. Plan quality and treatment delivery efficiency were reported. Outcomes reported include tumor local control (LC), distant failure (DF), lung and rib toxicity. Median follow-up interval was 8 months (1 to 22 months). Results: Mean GTV and PTV was 92.9 § 40.0 cc and 188.8 § 45.4 cc. Mean dose to GTV and PTV was 58.1 § 1.9 Gy and 55.5 § 1.2 Gy, translating to the corresponding average biological effective dose (BED10, with a/b = 10Gy) of 125 Gy and 117 Gy, respectively. All SIB SBRT plans met RTOG requirements for intermediate dose fall-off and organs at risk (OAR) sparing. Mean values of V20Gy, V10Gy and mean lung dose were 13.6 § 3.4%, 22.9 § 6.8%, and 7.5 § 1.8Gy, respectively. Average maximal doses to OAR were as follows: spinal cord < 12.5 Gy, heart < 33.9 Gy, esophagus < 17.7 Gy, ribs < 48.2 Gy and skin < 23.9 Gy. Average beam-on time was 3.5 § 0.3 min. Estimated mean treatment time including pre-treatment conebeam CT imaging and patient repositioning was within 15 min. All patients tolerated the SIB-SBRT treatment. 10 patients demonstrated LC, 1 had definite progression, and 1 had ostensible progression with atelectasis complicating the picture. The three patients with oligometastatic disease from stage IV head and neck or sarcoma progressed elsewhere, although the treated site was well controlled. One patient had evidence of grade 2 chest wall pain and treated with NSAIDS; however, 11 patients showed no evidence of rib fracture or chest wall pain. No patients developed grade 2+ pulmonary toxicity or radiation-induced pneumonitis. Conclusion: Escalating core tumor dose via SIB-SBRT (higher than 100Gy BED10) is safe, fast, and efficacious treatment for large lung masses with promising LC rates and no adverse treatment related toxicity. Fast delivery of SIB SBRT treatment could reduce intrafraction motion error due to coughing or pain, making geographic miss unlikely and improving the patient comfort and clinic workflow. Longer clinical follow up results in a larger patient population treated with this approach is warranted.

Induction Chemotherapy and Ablative Stereotactic Magnetic Resonance Image-Guided Adaptive Radiation Therapy for Inoperable Pancreas Cancer

“…Cumulative delivered dose may be associated with treatment efficacy and safety and may be useful to consider when optimizing each adapted fraction to improve the therapeutic ratio (14).…”

“…Lastly, the cumulative dose delivered across all adapted fractions is not readily assessable on any commercially available MR Linac. Cumulative delivered dose may be associated with treatment efficacy and safety and may be useful to consider when optimizing each adapted fraction to improve the therapeutic ratio ( 14 ).…”

“…A multi-institutional retrospective analysis by Rudra and colleagues demonstrated that dose escalation above a biologically effective dose (BED 10 ) >70 Gy 10 using a 0.35 Tesla (T) magnetic resonance (MR)-guided cobalt-60 treatment machine was associated with significantly improved OS ( 9 ). Subsequent single institution experiences of ablative SMART (A-SMART) prescribed up to 50 Gy in 5 fractions (BED 10 = 100 Gy 10 ) have also demonstrated minimal grade 3 or higher toxicity and favorable early efficacy ( 10 , 14 ).…”