Resectability and Ablatability Criteria for the Treatment of Liver Only Colorectal Metastases:Multidisciplinary Consensus Document from the COLLISION Trial Group

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.</p

Colorectal liver metastases: Surgery versus thermal ablation (COLLISION) - a phase III single-blind prospective randomized controlled trial

Background: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods: In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion: If thermal ablation proves to be non-inferior in treating lesions ≤3cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration:NCT03088150 , January 11th 2017

The value of leukapheresis for treatment of priapism as presenting feature of chronic myeloid leukemia—Case report and review of literature

Abstract Priapism is a rare presenting feature of chronic myeloid leukemia (CML) in male patients. Treatment aims to relieve symptoms and to prevent erectile dysfunction. Several treatment modalities exist, however no standard treatment is recommended. We evaluated literature concerning different treatment approaches and evaluate the value of leukapheresis in treatment of priapism. The literature search resulted in 57 included articles, consisting of 53 studied patients. Patients had a mean age of 25.3 years, average time from onset to presentation at the hospital was 2 days, and mean white blood cell (WBC) count was 344 × 109/L. Most patients (67.9%) were treated with a combined approach (different modalities were radiological, urological, and oncological treatment). Twelve patients, with a mean WBC count of 365 × 109/L, received leukapheresis. Only two of them reported erectile dysfunction after treatment. Priapism is an urological emergency requiring urgent multidisciplinary treatment. We highlight the importance of local urological therapy combined with systemic therapy for CML. Therapeutic leukapheresis should be applied when available and with no other contraindications

Needle-guided ablation of locally advanced pancreatic cancer: Cytoreduction or immunomodulation by in vivo vaccination?

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive forms of cancer with a dismal prognosis. About a third of all patients with pancreatic cancer present with locally advanced inoperable disease and are currently designated to palliative systemic chemotherapy. Despite improved chemotherapeutic treatment by the introduction of FOLFIRINOX, median overall survival remains poor at approximately 14 months. Several needle-guided ablative therapies are investigated as treatment option for patients with locally advanced pancreatic cancer (LAPC). This review aims to give an overview of literature of the following needle-guided ablative techniques for the treatment of patients with LAPC: radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, and irreversible electroporation (IRE). The immunomodulatory effects of the ablative techniques in PDAC are also discussed. These effects in combination with immunotherapy may provide an opportunity to enhance clinical efficacy and endow local ablation with systemic tumor control. Especially less immunogenic tumors like PDAC may benefit from this new approach. Preclinical and clinical findings, possible mechanisms of action, and future research directions are addressed

Irreversible Electroporation for Locally Advanced Pancreatic Cancer

Several minimally invasive image guided tumor ablation techniques have been added to the treatment spectrum for locally advanced pancreatic cancer (LAPC). Irreversible electroporation (IRE) might have a significant additive value in the management of this difficult-to-treat disease. As opposed to thermal ablative techniques, IRE induces cell death by the delivery of high-voltage electrical pulses. The electrical energy disrupts the cellular membrane integrity, causes loss of cellular homeostasis and ultimately results in cell death. The extracellular matrix of connective tissue in surrounding delicate structures such as bile ducts, bowel wall, and larger blood vessels is spared. The preservation of these structures makes IRE attractive for the treatment of pancreatic cancers that are unresectable due to their anatomical location (ie, LAPC and local recurrence after surgical resection). In addition to its cytoreductive abilities, evidence is emerging on IRE's capability to induce systemic immunomodulation through active in vivo vaccination against pancreatic cancer cells. These effects in combination with immunotherapy may offer a new treatment paradigm for tumors with low immunogenic potential like pancreatic ductal adenocarcinoma (PDAC). This review discusses several practical and technical issues of IRE for LAPC: clinical evaluation, indications, patient preparations, procedural steps, imaging characteristics, clinical results, and “tricks of the trade” used to improve the safety and efficacy of the treatment. Future directions such as the combination of IRE with immunotherapy will be shortly addressed

Locoregional treatment of metastatic pancreatic cancer utilizing resection, ablation and embolization: A systematic review

The prognosis of metastatic pancreatic ductal adenocarcinoma (mPDAC) remains univer-sally poor, requiring new and innovative treatment approaches. In a subset of oligometastatic PDAC patients, locoregional therapy, in addition to systemic chemotherapy, may improve survival. The aim of this systematic review was to explore and evaluate the current evidence on locoregional treatments for mPDAC. A systematic literature search was conducted on locoregional techniques, including resection, ablation and embolization, for mPDAC with a focus on hepatic and pulmonary metastases. A total of 59 studies were identified, including 63,453 patients. Although subject to significant bias, radical-intent local therapy for both the primary and metastatic sites was associated with a superior median overall survival from metastatic diagnosis or treatment (hepatic mPDAC 7.8–19 months; pulmonary mPDAC 22.8–47 months) compared to control groups receiving chemotherapy or best supportive care (hepatic mPDAC 4.3–7.6 months; pulmonary mPDAC 11.8 months). To recruit patients that may benefit from these local treatments, selection appears essential. Most significant is the upfront possibility of local radical pancreatic and metastatic treatment. In addition, a patient’s response to neoadjuvant systemic chemotherapy, performance status, metastatic disease load and, to a lesser degree, histological differentiation grade and tumor marker CA19-9 serum levels, are powerful prognostic factors that help identify eligible subjects. Although the exact additive value of locoregional treatments for mPDAC patients cannot be distillated from the results, locoregional primary pancreatic and metastatic treatment seems beneficial for a highly selected group of oligometastatic PDAC patients. For definite recommendations, well-designed prospective randomized controlled trials with strict in-and exclusion criteria are needed to validate these results

Resectability and Ablatability Criteria for the Treatment of Liver Only Colorectal Metastases: Multidisciplinary Consensus Document from the COLLISION Trial Group

Contains fulltext : 221694.pdf (publisher's version ) (Open Access

Locally Advanced Pancreatic Cancer: Percutaneous Management Using Ablation, Brachytherapy, Intra-arterial Chemotherapy, and Intra-tumoral Immunotherapy

Purpose of Review: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplasms, bearing a terrible prognosis. Stage III tumors, also known as locally advanced pancreatic cancer (LAPC), are unresectable, and current palliative chemotherapy regimens have only modestly improved survival in these patients. At this stage of disease, interventional techniques may be of value and further prolong life. The aim of this review was to explore current literature on locoregional percutaneous management for LAPC. Recent Findings: Locoregional percutaneous interventional techniques such as ablation, brachytherapy, and intra-arterial chemotherapy possess cytoreductive abilities and have the potential to increase survival. In addition, recent research demonstrates the immunomodulatory capacities of these treatments. This immune response may be leveraged by combining the interventional techniques with intra-tumoral immunotherapy, possibly creating a durable anti-tumor effect. This multimodality treatment approach is currently being examined in several ongoing clinical trials. Summary: The use of certain interventional techniques appears to improve survival in LAPC patients and may work synergistically when combined with immunotherapy. However, definitive conclusions can only be made when large prospective (randomized controlled) trials confirm these results

High-Voltage Electrical Pulses in Oncology: Irreversible Electroporation, Electrochemotherapy, Gene Electrotransfer, Electrofusion, and Electroimmunotherapy

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 increase the membrane permeability of cells, a phenomenon known as electroporation. Unlike alternative ablative therapies, electroporation does not affect the structural integrity of surrounding tissue, thereby enabling tumors in the vicinity of vital structures to be treated. IRE uses HVEPs to cause cell death by inducing membrane disruption, and it is primarily used as a radical ablative therapy in the treatment of soft-tissue tumors in the liver, kidney, prostate, and pancreas. ECT uses HVEPs to transiently increase membrane permeability, enhancing cellular cytotoxic drug uptake in tumors. IRE and ECT show immunogenic effects that could be augmented when combined with immunomodulatory drugs, a combination therapy the authors term electroimmunotherapy. Additional electroporation-based technologies that may reach clinical importance, such as gene electrotransfer, electrofusion, and electroimmunotherapy, are concisely reviewed. HVEPs represent a substantial advancement in cancer research, and continued improvement and implementation of these presented technologies will require close collaboration between engineers, interventional radiologists, medical oncologists, and immuno-oncologists

The role of neoadjuvant chemotherapy in repeat local treatment of recurrent colorectal liver metastases: A systematic review and meta‐analysis

The additive value of neoadjuvant chemotherapy (NAC) prior to repeat local treatment of patients with recurrent colorectal liver metastases (CRLM) is unclear. A systematic search was performed in PubMed, Embase, Web of Science, and an additional search in Google Scholar to find articles comparing repeat local treatment by partial hepatectomy and/or thermal ablation with versus without NAC. The search included randomized trials and comparative observational studies with univariate/multivariate analysis and/or matching as well as (inter)national guidelines assessed using the AGREE II instrument. The search identified 21,832 records; 172 were selected for full‐text review; 20 were included: 20 comparative observational studies were evaluated. Literature to evaluate the additive value of NAC prior to repeat local treatment was limited. Outcomes of NAC were often reported as subgroup analyses and reporting of results was frequently unclear. Assessment of the seven studies that qualified for inclusion in the meta‐analysis showed conflicting results. Only one study reported a significant difference in overall survival (OS) favoring NAC prior to repeat local treatment. However, further analysis revealed a high risk for residual bias, because only a selected group of chemo‐responders qualified for repeat local treatment, disregarding the non‐responders who did not qualify. All guidelines that specifically mention recurrent disease (3/3) recommend repeat local treatment; none provide recommendations about the role of NAC. The inconclusive findings of this meta‐analysis do not support recommendations to routinely favor NAC prior to repeat local treatment. This emphasizes the need to investigate the additive value of NAC prior to repeat local treatment of patients with recurrent CRLM in a future phase 3 randomized controlled trial (RCT)