Isotoxic High-Dose Stereotactic Body Radiotherapy (iHD-SBRT) Versus Conventional Chemoradiotherapy for Localized Pancreatic Cancer: A Single Cancer Center Evaluation

Abstract

Given the lack of direct comparative evidence, we aimed to compare the oncological outcomes of localized pancreatic ductal adenocarcinoma (PDAC) treated in the same tertiary cancer center with isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT) or conventional chemoradiotherapy (CRT). Biopsy-proven borderline/locally advanced patients treated with iHD-SBRT (35 Gy in 5 fractions with a simultaneous integrated boost up to 53 Gy) or CRT (45–60 Gy in 25–30 fractions) were retrospectively included from January 2006 to January 2021. The median overall survival (mOS) was evaluated trough uni- and multivariate analyses. The progression free survival (PFS) and the 1-year local control (1-yLC) were also reported. Eighty-two patients were included. The median follow-up was 19.7 months. The mOS was in favour of the iHD-SBRT group (22.5 vs. 15.9 months, p < 0.001), including after multivariate analysis (HR 0.39 [CI95% 0.18–0.83], p = 0.014). The median PFS and the 1-yLC were also significantly better for iHD-SBRT (median PFS: 16.7 vs. 11.5 months, p = 0.011; 1-yLC: 75.8 vs. 39.3%, p = 0.004). In conclusion, iHD-SBRT is a promising RT option and may offer an improvement in OS in comparison to CRT for localized PDAC. Further validation is required to confirm the exact role of iHD-SBRT and the optimal therapeutic sequence for the treatment of localized PDAC.

Neoadjuvant chemotherapy may be the best neoadjuvant therapy modality for non-metastatic pancreatic cancer: a population based study

“…In the A021501 study ( 14 ), the maximum BED (55Gy) of SBRT was far lower than the ablation dose required for SBRT, which may be the reason for the poor efficacy of the SBRT group. Improved radiotherapy technology, such as Isotoxic High-Dose Stereotactic Body Radiotherapy (iHD-SBRT), can individually adjust the radiotherapy dose and fractionation times to maximize the killing of tumor cells and minimize damage to surrounding normal tissues ( 28 , 31 ). In addition, combined radiotherapy and immunotherapy may be a potential therapeutic strategy, although the effects of immunotherapy alone are limited in pancreatic cancer due to the characteristics of low tumor mutation load and immunosuppressive microenvironment ( 32 , 33 ).…”

Favorable histo-molecular remodeling of pancreatic ductal adenocarcinoma after Total Neoadjuvant Therapy including Stereotactic Body Radiotherapy

“…For sixteen patients, FFX was followed by iHD-SBRT as previously described in details in [14, 50], according to the TNT strategy implemented in our hospital since January 2018 for localized PDAC. A surgical exploration was performed in case of no progression 4 to 7 weeks after iHD-SBRT.…”

“…In an IDP, the dose prescription is not based on the coverage of the planning target volume (PTV) but on the predetermined limiting dose constraints to the neighbouring organs at risks in order to control toxicity. [14, 50] The following dose constraints were applied: for planning organ at risk volumes (PRVs) stomach, duodenum, colon and small bowel, D max (0.5cc) <35Gy, V 30Gy <2cc; PRV spinal cord, V 20Gy <1cc and for kidneys, D mean <10Gy and V 12Gy <25%).…”

Neoadjuvant chemotherapy associated with isotoxic high‐dose stereotactic body radiotherapy does not increase postoperative complications after pancreaticoduodenectomy for nonmetastatic pancreatic cancer

“…In case of bad tolerance or absence of radiological tumoral response, regimen was switched to gemcitabine/nab-paclitaxel according to the following protocol: nab-paclitaxel 125 mg/m 2 and gemcitabine 1000 mg/m 2 and on Days 1, 8, and 15 of a 28-day cycle. Chemotherapy (6-8 cycles) was followed within 2-4 weeks by iHD-SBRT, with 35 Gy delivered in five consecutive daily fractions to the planning tumor volume (PTV) with simultaneous-integrated boost up to 50 Gy, as described in details by Bouchart et al 7,9 PTV1 encompassed the interval target volumes plus a 3 mm margin. PTV2 was created by subtracting the sum of critical gastrointestinal planning organ at risk volumes (PRVs) from the PTV1.…”

“…Since 2017, patients suffering from nonmetastatic PC with suspicion of local macrovascular involvement benefit from preoperatively delivered isotoxic high-dose SBRT (iHD-SBRT), after six to eight cycles of FFX. [7][8][9] iHD-SBRT consists of delivering high biologically effective dose in five sessions, for a better local tumoral control, and maintaining similar toxicity on neighboring structures.…”