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.
Pancreatic ductal adenocarcinoma is one of the most lethal malignant diseases, with a mortality rate being close to incidence. Due to its heterogeneity and plasticity, as well as the lack of distinct symptoms in the early phases, it is very often diagnosed at an advanced stage, resulting in poor prognosis. Traditional tissue biopsies remain the gold standard for making a diagnosis, but have an obvious disadvantage in their inapplicability for frequent sampling. Blood-based biopsies represent a non-invasive method which potentially offers easy and repeated sampling, leading to the early detection and real-time monitoring of the disease and hopefully an accurate prognosis. Given the urgent need for a reliable biomarker that can estimate a patient’s condition and response to an assigned treatment, blood-based biopsies are emerging as a potential new tool for improving patients’ survival and surveillance. In this article, we discuss the current advances and challenges in using liquid biopsies for pancreatic cancer, focusing on circulating tumour DNA (ctDNA), extracellular vesicles (EVs), and circulating tumour cells (CTCs), and compare the performance and reliability of different biomarkers and combinations of biomarkers.
615 Background: The most frequently invaded surgical margins on pancreatoduodenectomy (PD) specimens of pancreatic ductal adenocarcinoma (PDAC) are vascular margins, especially the superior mesenteric artery (SMA), also called mesopancreatic margin. Considering embryology, it may be hypothesized that PDAC cells tend to infiltrate the retroperitoneum through the contents of mesopancreas, justifying the frequent SMA positive margin. Because the radiological aspect of mesopancreas has been poorly studied, the aim of this original research was to assess the mesopancreatic infiltration on diagnostic imaging, corroborate with the corresponding margin pathology and evaluate the impact on survival in PDAC patients who underwent PD. Methods: From 2015 to 2021, all patients who underwent PD for PDAC with curative intent were reviewed, excluding patients lost to follow-up, who died postoperatively or within the first year for non-oncological reason, and those with unavailable preoperative imaging. Surgical margins of pathological specimens were reassessed. Blinded reviewing of preoperative radiographic images was conducted. According to qualitative assessment, the mesopancreas tissue was defined as normal fat (NF), fat stranding (FS) or solid infiltration (SI). Results: 133 patients were included in the study, including 51 (38%) who received neoadjuvant therapy. The tumor location was into the head or the uncinate process in 54% and 46%, respectively. At diagnosis, PDAC were classified as resectable (51%), borderline resectable (28%) and locally advanced (9%) according to the NCCN classification. FS or SI in the mesopancreas was present in 45 (34%) and 18 (14%) patients, respectively. Tumor size on imaging, tumor location, chronic obstructive pancreatitis, vascular contacts and NCCN resectability status were predictive factors of mesopancreas infiltration (p<0.001). Median overall and disease-free survivals were significantly lower in case of SI compared to NF and FS in the mesopancreas. When comparing patients with mesopancreatic FS at diagnosis who received neoadjuvant therapy (n=20) to those who underwent upfront surgery (n=25), no significant impact was observed in survivals. R0 resection was obtained in 36%; in all patients with R1 resection, a vascular margin was involved. Tumor size at pathology, SMA margin and resection status were factors that were significantly influenced by the radiological infiltration of the mesopancreas. Conclusions: The SI of mesopancreas on diagnostic imaging was associated with a poor prognosis, but not FS, in patients who underwent PD for PDAC. SMA margin and resection status were correlated with the radiological texture of the mesopancreas, which suggests to further explore underlying mechanisms related to tumoral invasion of vascular margin and mesopancreas.
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive solid tumours with an estimated 5-year overall survival rate of 7% for all stages combined. In this highly resistant disease that is located in the vicinity of many radiosensitive organs, the role of radiotherapy (RT) and indications for its use in this setting have been debated for a long time and are still under investigation. Although a survival benefit has yet to be clearly demonstrated for RT, it is the only technique, other than surgery, that has been demonstrated to lead to local control improvement. The adjuvant approach is now strongly challenged by neoadjuvant treatments that could spare patients with rapidly progressive systemic disease from unnecessary surgery and may increase free margin (R0) resection rates for those eligible for surgery. Recently developed dose-escalated RT treatments, designed either to maintain full-dose chemotherapy or to deliver a high biologically effective dose, particularly to areas of contact between the tumour and blood vessels, such as hypofractionated ablative RT (HFA-RT) or stereotactic body RT (SBRT), are progressively changing the treatment landscape. These modern strategies are currently being tested in prospective clinical trials with encouraging preliminary results, paving the way for more effective treatment combinations using novel targeted therapies. This review summarizes the current literature regarding the use of RT for the treatment of primary PDAC, describes the limitations of conventional RT, and discusses the emerging role of dose-escalated RT and heavy-particle RT.
Pour les patients atteints d’un adénocarcinome canalaire pancréatique (ACP) dits à résécabilité borderline (RB), le recours à des thérapies néoadjuvantes avant la chirurgie est un concept émergent et la séquence thérapeutique optimale à employer dans le but d’un traitement curatif reste inconnue. Sur base des études récemment publiées par notre équipe et qui seront résumées dans cet article, il ressort que la radiothérapie stéréotaxique isotoxique à haute-dose (iHD-SBRT) peut être intégrée en toute sécurité au sein d’un schéma de chimiothérapie néoadjuvante avec des avantages prometteurs en termes de résection R0 (résection complète), de contrôle local et de survie. Dans ce contexte, nous avons créé et ouvert l’essai comparatif randomisé multicentrique de phase II, STEREOPAC, dont l’objectif est d’évaluer l’impact de l’ajout de l’iHD-SBRT à une chimiothérapie néoadjuvante chez 256 patients atteints d’un cancer du pancréas à RB. Après 4 cycles de mFOLFIRINOX (mFFX; ou 6 doses de Gemcitabine/nab-paclitaxel [Gem/Nab-P] en cas d’intolérance), les patients non évolutifs seront randomisés pour recevoir : 1/ 4 cycles de mFFX supplémentaires (ou 6 doses de Gem/Nab-P) (bras A), ou 2/ 2 cycles de mFFX (ou 3 doses de Gem/Nab-P) + iHD-SBRT (35 à 55Gy en 5 fractions) + 2 cycles de mFFX (ou 3 doses de Gem/Nab-P) (bras B). Ensuite, une chirurgie à visée curative sera effectuée suivie d’une chimiothérapie adjuvante en fonction de l’état général du patient. Les co-critères d’évaluation primaire de l’essai sont la résection R0 et la survie sans récidive de la maladie après la stratégie de traitement complète. L’essai STEREOPAC permettra donc de définir la meilleure séquence de traitement néoadjuvant pour les cancers du pancréas à résécabilité borderline et vise à évaluer si l’iHD-SBRT peut améliorer les résultats oncologiques de ces patients.
Radiotherapy is part of the standard of care treatment for a great majority of cancer patients. As a result of radiation, both tumor cells and the environment around them are affected directly by radiation, which mainly primes but also might limit the immune response. Multiple immune factors play a role in cancer progression and response to radiotherapy, including the immune tumor microenvironment and systemic immunity referred to as the immune landscape. A heterogeneous tumor microenvironment and the varying patient characteristics complicate the dynamic relationship between radiotherapy and this immune landscape. In this review, we will present the current overview of the immunological landscape in relation to radiotherapy in order to provide insight and encourage research to further improve cancer treatment. An investigation into the impact of radiation therapy on the immune landscape showed in several cancers a common pattern of immunological responses after radiation. Radiation leads to an upsurge in infiltrating T lymphocytes and the expression of programmed death ligand 1 (PD-L1) which can hint at a benefit for the patient when combined with immunotherapy. In spite of this, lymphopenia in the tumor microenvironment of ‘cold’ tumors or caused by radiation is considered to be an important obstacle to the patient’s survival. In several cancers, a rise in the immunosuppressive populations is seen after radiation, mainly pro-tumoral M2 macrophages and myeloid-derived suppressor cells (MDSCs). As a final point, we will highlight how the radiation parameters themselves can influence the immune system and, therefore, be exploited to the advantage of the patient.
