Irreversible electroporation, electrochemotherapy, and other electroporation-based therapies represent a treatment paradigm for difficult-to-treat solid tumors; the potent combination of high-volta... This review summarizes the use of high-voltage electrical pulses (HVEPs) in clinical oncology to treat solid tumors with irreversible electroporation (IRE) and electrochemotherapy (ECT). HVEPs incr...

A panel of experts reached consensus on recommendations on when to assess oncologic outcomes per patient, per session, and per tumor; definitions of starting and ending times; definitions of surviv... There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes st...

Percutaneous irreversible electroporation in patients with locally advanced and recurrent pancreatic cancer seems to prolong survival (median overall survival, 17 months) compared with standard of ... Background Patients with locally advanced pancreatic cancer have a dismal prognosis, with a median overall survival (OS) of 12–14 months with systemic therapies. Irreversible electroporation (IRE),...

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with high mortality. The vast majority of patients present with unresectable, advanced stage disease, for whom standard of care chemo(radio)therapy may improve survival by several months. Immunotherapy has led to a fundamental shift in the treatment of several advanced cancers. However, its efficacy in PDAC in terms of clinical benefit is limited, possibly owing to the immunosuppressive, inaccessible tumor microenvironment. Still, various immunotherapies have demonstrated the capacity to initiate local and systemic immune responses, suggesting an immune potentiating effect. In this review, we address PDAC’s immunosuppressive tumor microenvironment and immune evasion methods and discuss a wide range of immunotherapies, including immunomodulators (i.e., immune checkpoint inhibitors, immune stimulatory agonists, cytokines and adjuvants), oncolytic viruses, adoptive cell therapies (i.e., T cells and natural killer cells) and cancer vaccines. We provide a general introduction to their working mechanism as well as evidence of their clinical efficacy and immune potentiating abilities in PDAC. The key to successful implementation of immunotherapy in this disease may rely on exploitation of synergistic effects between treatment combinations. Accordingly, future treatment approaches should aim to incorporate diverse and novel immunotherapeutic strategies coupled with cytotoxic drugs and/or local ablative treatment, targeting a wide array of tumor-induced immune escape mechanisms.

The guidelines for metastatic colorectal cancer crudely state that the best local treatment should be selected from a ‘toolbox’ of techniques according to patient- and treatment-related factors. We created an interdisciplinary, consensus-based algorithm with specific resectability and ablatability criteria for the treatment of colorectal liver metastases (CRLM). To pursue consensus, members of the multidisciplinary COLLISION and COLDFIRE trial expert panel employed the RAND appropriateness method (RAM). Statements regarding patient, disease, tumor and treatment characteristics were categorized as appropriate, equipoise or inappropriate. Patients with ECOG≤2, ASA≤3 and Charlson comorbidity index ≤8 should be considered fit for curative-intent local therapy. When easily resectable and/or ablatable (stage IVa), (neo)adjuvant systemic therapy is not indicated. When requiring major hepatectomy (stage IVb), neo-adjuvant systemic therapy is appropriate for early metachronous disease and to reduce procedural risk. To downstage patients (stage IVc), downsizing induction systemic therapy and/or future remnant augmentation is advised. Disease can only be deemed permanently unsuitable for local therapy if downstaging failed (stage IVd). Liver resection remains the gold standard. Thermal ablation is reserved for unresectable CRLM, deep-seated resectable CRLM and can be considered when patients are in poor health. Irreversible electroporation and stereotactic body radiotherapy can be considered for unresectable perihilar and perivascular CRLM 0-5cm. This consensus document provides per-patient and per-tumor resectability and ablatability criteria for the treatment of CRLM. These criteria are intended to aid tumor board discussions, improve consistency when designing prospective trials and advance intersociety communications. Areas where consensus is lacking warrant future comparative studies.

The aim of this study was to assess primary tumor sidedness of colorectal cancer (CRC), rat sarcoma viral oncogene homolog (RAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) mutations and microsatellite instability (MSI) status as prognostic factors predicting complications, survival outcomes, and local tumor progression (LTP) following surgery and thermal ablation in patients with colorectal liver metastases (CRLM). This Amsterdam Colorectal Liver Met Registry (AmCORE) based study included 520 patients, 774 procedures, and 2101 tumors undergoing local treatment (resection and/or thermal ablation) from 2000 to 2021. Outcomes following local treatment were analyzed for primary tumor sidedness of CRC, RAS, and BRAF mutations and MSI status. The Kaplan–Meier method was used to estimate local tumor progression-free survival (LTPFS), local control (LC), distant progression-free survival (DPFS), and overall survival (OS). Uni- and multivariable analyses were performed based on Cox proportional hazards model. The chi-square test was used to analyze complications. Complications (p = 0.485), OS (p = 0.252), LTPFS (p = 0.939), and LC (p = 0.423) was not associated with tumor-sidedness. Compared to right-sided colon cancer (CC) (reference HR 1.000), DPFS was superior for left-sided CC and rectal cancer (p = 0.018) with an HR for left-sided CC of 0.742 (95% CI, 0.596–0.923) and for RC of 0.760 (95% CI, 0.597–0.966). Regarding RAS mutations, no significant difference was found in OS (p = 0.116). DPFS (p = 0.001), LTPFS (p = 0.039), and LC (p = 0.025) were significantly lower in the RAS mutation group. Though no difference in LTPFS was found between RAS wildtype and RAS mutated CRLM following resection (p = 0.532), LTPFS was worse for RAS mutated tumors compared to RAS wildtype following thermal ablation (p = 0.037). OS was significantly lower in the BRAF mutation group (p < 0.001) and in the MSI group (p < 0.001) following local treatment, while both did not affect DPFS, LTPFS, and LC. This AmCORE based study suggests the necessity of wider margins to reduce LTP rates in patients with RAS mutated CRLM, especially for thermal ablation. Upfront knowledge regarding molecular biomarkers may contribute to improved oncological outcomes.