Background: For patients with pancreatic ductal adenocarcinoma (PDAC), surgical resection remains the only potentially curative treatment. Surgery is generally followed by postoperative chemotherapy associated with improved survival, yet neoadjuvant therapy is a rapidly emerging concept requiring to be explored and validated in terms of treatment options and oncological outcomes. In this context, stereotactic body radiation (SBRT) appears feasible and can be safely integrated into a neoadjuvant chemotherapy regimen of modified FOLFIRINOX (mFFX) with promising benefits in terms of R0 resection, local control and survival. However, the optimal therapeutic sequence is still not known, especially for borderline resectable PDAC, and the role of adding SBRT to chemotherapy in the neoadjuvant setting needs to be evaluated in randomised controlled trials. The aim of the STEREOPAC trial is to assess the impact and efficacy of adding isotoxic high-dose SBRT (iHD-SBRT) to neoadjuvant mFFX or Gemcitabine/Nab-Paclitaxel (Gem/Nab-P) in patients with borderline resectable PDAC. Methods: This is a randomised comparative multicentre phase II trial, planning to enrol patients (n = 256) diagnosed with a borderline resectable biopsy-confirmed PDAC. Patients will receive 4 cycles of mFFX (or 6 doses of Gem/Nab-P). After full disease restaging, non-progressive patients will be randomised for receiving either 4 additional mFFX cycles (or 6 doses of Gem/Nab-P) (Arm A), or 2 mFFX cycles (or 3 doses of Gem/Nab-P) + iHD-SBRT (35 to 55 Gy in 5 fractions) + 2 mFFX cycles (or 3 doses of Gem/Nab-P) (Arm B). Then curative surgery will be performed followed by adjuvant chemotherapy according to patient’s condition. The co-primary endpoints are R0 resection and disease-free survival after the complete sequence strategy. The secondary endpoints include resection rate, overall survival, locoregional failure / distant metastasis free interval, pathologic complete response, toxicity, postoperative complications and quality of life assessment. Discussion: This trial will help define the best neoadjuvant treatment sequence for borderline resectable PDAC and aims to evaluate if a total neoadjuvant treatment integrating iHD-SBRT improves the patients’ oncological outcomes. Trial registration: The study was registered at ClinicalTrails.gov (NCT05083247) on October 19th, 2021, and in the Clinical Trials Information System (CTIS) EU CT database (2022-501181-22-01) on July 2022.

This review provides an overview of the cross-sectional imaging features of gastrointestinal (GI) metastases presenting with a linitis plastica (LP) pattern and illustrates these findings through a series of cases from various primary tumors. It also addresses key diagnostic challenges, with particular attention to differential diagnosis. The term linitis plastica (LP) refers to the macroscopic appearance of a hollow organ with diffuse mural tumor infiltration, leading to loss of parietal distensibility. Although rare, primary LP can occur throughout the gastrointestinal (GI) tract. First described in the stomach—the most common site—it is typically associated with undifferentiated adenocarcinoma composed of poorly cohesive cells, often with signet ring morphology. Beyond primary GI tumors, LP-like metastases may also arise from extragastrointestinal primaries, most notably breast carcinoma (particularly the lobular subtype), as well as urinary bladder and prostate carcinomas. LP-like GI metastases typically manifest as circumferential, enhancing wall thickenings with exaggerated zonal anatomy and luminal narrowing. Due to diffuse parietal tumor infiltration—often with mucosal preservation—the submucosa and serosa appear disproportionately thickened and show greater enhancement relative to the muscularis propria (MP). This specific imaging appearance is known as the malignant target sign, which must be distinguished from the benign target sign, where the most prominent low-density layer corresponds to edematous submucosa. Additional key features include homogeneous enhancement with loss of layer differentiation on delayed-phase imaging and a concentric ring pattern on MR. Secondary findings may also be present, such as intestinal obstruction and concomitant peritoneal carcinomatosis (PC). Gastrointestinal metastases with an LP pattern present a significant diagnostic challenge, as they can mimic both primary tumors and benign inflammatory or infectious conditions. Accurate diagnosis is critical because management strategies differ substantially. Since the mucosa is often spared, endoscopy and superficial biopsies may yield false-negative results. Therefore, while immunohistochemistry (IHC) remains essential for confirmation, radiologists play a pivotal role in raising suspicion for LP-like GI metastases and recommending deep, extensive biopsies to obtain adequate representative tissue. Furthermore, in cases of an unknown primary tumor, recognition of the LP pattern can provide important clues to the potential site of origin.

Immune checkpoint inhibitors and immune-related biomarkers are increasingly investigated in rectal cancer (RC). We retrospectively analysed PD-L1 expression in diagnostic biopsy and resection samples from RC patients treated at our centre between 2000 and 2020. PD-L1 immunostaining (22C3 clone) was evaluated according to tumour proportion (TPS), immune cell (ICS), and the combined positive score (CPS). Eighty-three patients were included. At diagnosis, PD-L1 expression ≥1%/≥5% was observed in 15.4%/0%, 80.7%/37.4%, and 69.2%/25.6% of patients based on TPS, ICS, and CPS, respectively. At surgery, the respective figures were 4.6%/1.5%, 60.2%/32.5%, and 50.7%/26.2%. Using the 1% cut-off and regardless of the scoring system, PD-L1 was less expressed in surgery than biopsy samples (p ≤ 0.04). In paired specimens, PD-L1-ICS reduction was especially observed following neoadjuvant long-course (chemo)radiotherapy (p = 0.03). PD-L1-ICS of ≥5% in surgical samples (HR: 0.17; p = 0.02), and a biopsy-to-surgery increase in PD-L1-ICS (HR: 0.19; p = 0.04) was predictive for longer disease-free survival, while the PD-L1-ICS of either ≥1% (HR 0.28; p = 0.04) or ≥5% (HR 0.19; p = 0.03) in surgical samples and the biopsy-to-surgery increase in PD-L1-ICS (HR: 0.20; p = 0.04) were associated with better overall survival. Our study suggests that PD-L1 expression in RC is largely reflective of immune cell infiltration, and its presence/increase in surgical samples predicts better outcomes.

BACKGROUND This review aims to summarize the imaging features on cross-sectional imaging mo-dalities of metastases to the gastrointestinal tract (GI) with a linitis plastica (LP) pat-tern and to present a series of cases from different primary tumours. Challenging questions concerning their diagnosis will be discussed in detail, including their differ-ential diagnosis. The term LP is to describe the macroscopic appearance of any hollow organ with dif-fuse mural tumour infiltration, responsible for the loss of parietal distensibility. Pri-mary LP, however rare, may be found throughout the GI tract. First described in the stomach, which represents the most frequent location, it is associated with undifferen-tiated adenocarcinoma with poorly cohesive cells, often presenting signet ring fea-tures. In addition to primary GI LP, LP-like metastases may occur in association with prima-ry tumours arising beyond the GI tract, namely breast (especially the lobular type), urinary bladder and prostate carcinomas. MAIN TEXT LP-like GI metastases appear as circumferential and enhancing thickenings of the GI, with an exaggerated zonal anatomy and a narrowed lumen. As a result of the diffuse parietal tumour infiltration that frequently preserves the mucosa, the infiltrated sub-mucosa and serosa appear disproportionately expanded with increased enhancement compared to the muscularis propria (MP). This appearance constitutes the malignant target sign, which is to be differentiated from its non-tumoral counterpart, the benign target sign, where the low density intervening and most prominent layer is the edem-atous submucosa. A homogeneous enhancement with loss of layer differentiation at the delayed phase and a concentric ring pattern on MR have also been described as key imaging features, in addition to associated findings, such as secondary intestinal occlusion and concom-itant peritoneal carcinomatosis (PC). CONCLUSIONS GI metastases with LP pattern cause a diagnostic challenge as they may mim-ic primary tumours as well as benign conditions such as inflammatory/infectious dis-eases. Achieving the correct diagnosis is crucial, as patient management differs. Since the mucosa may be spared, endoscopies and biopsies are frequently negative. Thus, alt-hough immunohistochemistry (IHC) studies are essential, radiologists play a para-mount role in suggesting LP-like GI metastases and proposing deep and extensive bi-opsies to obtain substantial representative tissue to confirm the diagnosis. Moreover, in the event of an unknown primary tumour, recognition of the LP pattern may be extremely helpful in suggesting possible primary tumours.