Gemcitabine-Based Neoadjuvant Treatment in Borderline Resectable Pancreatic Ductal Adenocarcinoma: A Meta-Analysis of Individual Patient Data

Background: Non-randomized studies have investigated multi-agent gemcitabinebased neo-adjuvant therapies (GEM-NAT) in borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC). Treatment sequencing and specific elements of neoadjuvant treatment are still under investigation. The present meta-analysis aims to assess the effectiveness of GEM-NAT on overall survival (OS) in BR-PDAC. Patients and Methods: A meta-analysis of individual participant data (IPD) on GEMNAT for BR-PDAC were performed. The primary outcome was OS after treatment with GEM-based chemotherapy. In the Individual Patient Data analysis data were reappraised and confirmed as BR-PDAC on provided radiological data. Results: Six studies investigating GEM-NAT were included in the IPD metanalysis. The IPD metanalysis was conducted on 271 patients who received GEM-NAT. Pooled median patient-level OS was 22.2 months (95%CI 19.1–25.2). R0 rates ranged between 81 and 95% (I 2 = 0%, p = 0.64), respectively. Median OS was 27.8 months (95%CI 23.9–31.6) in the patients who received NAT-GEM followed by resection compared to 15.4 months (95%CI 12.3–18.4) for NAT-GEM without resection and 13.0 months (95%CI 7.4–18.5) in the group of patients who received upfront surgery (p < 0.0001). R0 rates ranged between 81 and 95% (I 2 = 0%, p = 0.64), respectively. Overall survival in the R0 group was 29.3 months (95% CI 24.3–34.2) vs. 16.2 months (95% CI 7·9–24.5) in the R1 group (p = 0·001). Conclusions: The present study is the first meta-analysis combining IPD from a number of international centers with BR-PDAC in a cohort that underwent multi-agent gemcitabine neoadjuvant therapy (GEM-NAT) before surgery. GEM-NAT followed by surgical resection improve sur

Preoperative radiochemotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC trial): Study protocol for a multicentre randomized controlled trial

Background: Pancreatic cancer is the fourth largest cause of cancer death in the United States and Europe with over 100,000 deaths per year in Europe alone. The overall 5-year survival ranges from 2-7 % and has hardly improve

Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer

Background: Studies comparing upfront surgery with neoadjuvant treatment in pancreatic cancer may report only patients who underwent resection and so survival will be skewed. The aim of this study was to report survival by intention to treat in a comparison of upfront surgery versus neoadjuvant treatment in resectable or borderline resectable pancreatic cancer. Methods: MEDLINE, Embase and the Cochrane Library were searched for studies reporting median overall survival by intention to treat in patients with resectable or borderline resectable pancreatic cancer treated with or without neoadjuvant treatment. Secondary outcomes included overall and R0 resection rate, pathological lymph node rate, reasons for unresectability and toxicity of neoadjuvant treatment. Results: In total, 38 studies were included with 3484 patients, of whom 1738 (49·9 per cent) had neoadjuvant treatment. The weighted median overall survival by intention to treat was 18·8months for neoadjuvant treatment and 14·8months for upfront surgery; the difference was larger among patients whose tumours were resected (26·1 versus 15·0months respectively). The overall resection rate was lower with neoadjuvant treatment than with upfront surgery (66·0 versus 81·3 per cent; P<0·001), but the R0 rate was higher (86·8 (95 per cent c.i. 84·6 to 88·7) versus 66·9 (64·2 to 69·6) per cent; P<0·001). Reported by intention to treat, the R0 rates were 58·0 and 54·9 per cent respectively (P=0·088). The pathological lymph node rate was 43·8 per cent after neoadjuvant therapy and 64·8 per cent in the upfront surgery group (P<0·001). Toxicity of at least grade III was reported in up to 64 per cent of the patients. Conclusion: Neoadjuvant treatment appears to improve overall survival by intention to treat, despite lower overall resection rates for resectable or borderline resectable pancreatic cancer. PROSPERO registration number: CRD42016049374

Predictive value of baseline serum carbohydrate antigen 19-9 level on treatment effect of neoadjuvant chemoradiotherapy in patients with resectable and borderline resectable pancreatic cancer in two randomized trials

BACKGROUND: Guidelines suggest that the serum carbohydrate antigen (CA19-9) level should be used when deciding on neoadjuvant treatment in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer). In patients with resectable pancreatic cancer, neoadjuvant therapy is advised when the CA19-9 level is 'markedly elevated'. This study investigated the impact of baseline CA19-9 concentration on the treatment effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable and borderline resectable pancreatic cancers.METHODS: In this post hoc analysis, data were obtained from two RCTs that compared neoadjuvant CRT with upfront surgery in patients with resectable and borderline resectable pancreatic cancers. The effect of neoadjuvant treatment on overall survival was compared between patients with a serum CA19-9 level above or below 500 units/ml using the interaction test.RESULTS: Of 296 patients, 179 were eligible for analysis, 90 in the neoadjuvant CRT group and 89 in the upfront surgery group. Neoadjuvant CRT was associated with superior overall survival (HR 0.67, 95 per cent c.i. 0.48 to 0.94; P = 0.019). Among 127 patients (70, 9 per cent) with a low CA19-9 level, median overall survival was 23.5 months with neoadjuvant CRT and 16.3 months with upfront surgery (HR 0.63, 0.42 to 0.93). For 52 patients (29 per cent) with a high CA19-9 level, median overall survival was 15.5 months with neoadjuvant CRT and 12.9 months with upfront surgery (HR 0.82, 0.45 to 1.49). The interaction test for CA19-9 level exceeding 500 units/ml on the treatment effect of neoadjuvant CRT was not significant (P = 0.501).CONCLUSION: Baseline serum CA19-9 level defined as either high or low has prognostic value, but was not associated with the treatment effect of neoadjuvant CRT in patients with resectable and borderline resectable pancreatic cancers, in contrast with current guideline advice.</p

Emerging insights on neoadjuvant chemoradiotherapy in pancreatic cancer

The overall survival of patients with resectable or borderline-resectable pancreatic ductal adenocarcinoma (PDAC) has hardly improved over the last decade with a rise in studies investigating the role of preoperative (neoadjuvant) chemoradiotherapy. Since neoadjuvant chemoradiotherapy has not proven its efficacy yet, little is known about the radiotherapy aspects of pancreatic cancer. As a consequence, no standard guideline is available on delineation of pancreatic tumors in the neoadjuvant setting. It is known that tumor delineation can be challenging, with poor contrast between the tumor and surrounding tissue. This thesis aimed to study the role of neoadjuvant chemoradiotherapy in patients with resectable or borderline-resectable PDAC and investigate the radiotherapeutic aspects: delineation and treatment planning of neoadjuvant radiotherapy. Within this thesis, the suggestion was found that neoadjuvant chemoradiotherapy is beneficial in patients with resectable and borderline-resectable PDAC, especially in the latter group. Further improvements in neoadjuvant chemotherapy using FOLFIRINOX and gemcitabine/nab-Paclitaxel should be investigated, but also should focus on the efficacy of neoadjuvant radiotherapy. Considerable interobserver variation was found in both CT and MRI delineation, and further improvements in radiotherapeutic approaches to reduce the treating volumes are needed, such as MR-guided stereotactic radiotherapy, breathhold or midposition radiotherapy

Clinical Implementation of Single Visit Palliative Adaptive Radiotherapy without Prior CT Simulation

Purpose/Objectives Standard workflows of radiotherapy for metastatic disease palliation often involve long waiting times or multiple clinic visits. Fast palliation completed during a single clinic visit can be achieved by omitting a planning CT scan and using available diagnostic imaging for treatment planning. The use of diagnostic CT can be challenging due to differences in patient positioning and location of target and organs at risk (OAR), but adaptive treatment platforms provide possible solutions. We integrated a fast palliative workflow using diagnostic imaging for pre-planning, with subsequent on couch contour and plan adaption based on a synthetic CT derived from the cone-beam CT imaging (CBCT), and report our clinical and dosimetric experiences. Material/methods An ethics-approved protocol for fast palliation (FAST-METS) was implemented in November 2021. Patients referred for palliative radiotherapy of painful bony metastatic disease of any primary site, available recent diagnostic imaging (Results Data of the first eight patients are presented. The treated metastases were located in the lumbar (2) or thoracic (3) spine and pelvis (3). In all patients, the on-couch re-optimized plan was used for treatment as clinical plan, with a PTVV95% coverage of ≥95%. In three patients, target and OAR volumes were adapted on-couch by the radiation oncologist. All patients completed their consult and treatment within 2 hours. Plan re-optimization time was Conclusion A fast workflow for a single visit palliative IMRT delivery without dedicated planning CT scan was implemented for patients with bone metastases. All patients completed consultation and treatment within 2 hours on average, and indicated satisfaction with the procedure

Fast delivery of IMRT to metastatic disease without planning CT simulation.

Purpose Radiotherapy (RT) is an effective treatment for metastatic disease. Fast treatment is desirable for patients requiring pain control and result in shorter interruptions of any systemic treatments. However, significant delays can arise if a dedicated planning CT-scan (pCT) has to be scheduled before target contouring and treatment planning is performed. Most patients have a recent diagnostic CT-scan or PET-CT scan available but patient positioning and tumor extension could be different during RT-delivery. We developed a palliative workflow that involved performing pre-planning on available diagnostic CTs (dCT), and subsequently used plan adaption to account for any changes in target anatomy changes using a cone-beam CT-scan (CBCT) prior to RT-delivery. This retrospective study assessed the feasibility of this workflow. Material/methods Fifteen patients were selected from the hospital database based on the following criteria: palliative treatment of metastatic disease to the spine or ribs (1x8Gy), time between a dCT and pCT of Results All TPa met clinical acceptance criteria. Minor adaption of CTV, which was defined as contour adaptation in 4 slices) were needed in 4 patients, and 4 patients required no CTV adaptions. Figure 1 shows an improvement in target coverage in the TPa versus TPd,, while achieving similar target coverage as TPref (Figure 2). Doses delivered to OARs by the TPA were all within clinical acceptance criteria, and differences seen were due to changes in target volume arising from tumor progression between the dCT and treatment. Conclusion This study found that online adaption of palliative treatment plans that were initially generated using dCTs, was feasible using on-couch CBCT scans on the Ethos platform. We will now implement this workflow in our clinic, with expected benefits in both departmental logistics and patient experience