Surgery for Liver Metastases From PDAC

Summary

Dissemination from pancreatic ductal adenocarcinoma (PDAC) occurs in clinical practice either in the form of recurrence after initial treatment with curative intent resection (metachronous) or more frequently prevails already at the time of diagnosis (synchronous). Traditionally, metastatic pancreatic cancer (mPDAC) is considered not to be eligible for meaningful aggressive therapies to be implemented. However, with the development of local as well as more effective systemic therapeutic regimens a variety of clinical situations have to be reevaluated. For instance, recent reports have indicated an option for maintained or even prolonged survival after resections and/or ablations of oligometastatic pancreatic cancer (OMDPDAC), as represented by a single or few liver metastasis (es). These reports are burdened by methodological weaknesses such as being retrospective, single institution and reporting only from highly selected case series. A common denominator of acceptable outcome is, however, that all metastatic lesions have been preoperatively treated and responded to chemotherapy, indicating an advantageous tumor biology. Hence an unbiased approach, including neo-adjuvant chemotherapy before any aggressive local treatment must be explored to the updated management opportunities in terms of assessing the prevalence, safety, feasibility, tolerability and possible disease control options. Primary objective (clinical): To prospectively investigate (on an intention to treat basis) the safety, feasibility, tolerability and clinical outcomes of all patients with PDAC presenting with limited metastatic disease, where a treatment option can be launched with the ambition of local disease control and eventually better survival. The cohorts to be included are: Primary cohort: Patients with liver limited (metachronous and synchronous) metastasis(es) due to PDAC. This cohort is further subdivided to: Limited liver disease. Extended liver disease. Secondary cohort: Patients with OMDPDAC and at least one extrahepatic manifestation of PDAC. Secondary objective (translational) is to improve the understanding of PDAC liver metastases biology by studying the mechanistic aspects of metastases invasion as well as intra- and peri-tumoral liver metastatic niche, and by charting the cellular composition of liver metastases on single cell level with a focus on the impact of cellular interactions on tumor cell growth and differentiation. Furthermore, the study aims to identify blood-based biomarkers of response to oncologic/surgical treatment.

Interventions

• Liver resection (ablation) · PROCEDURE

  Treatment of liver metastases from pancreatic cancer by surgery or ablation

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

Inclusion Criteria:

Confirmed PDAC with synchronous or metachronous dissemination isolated in the liver (primary cohort) or other dissemination as described in chapter 7.1. where the local tumour board find indication for curative treatment attempt.

The confirmation of PDAC before chemotherapy is not regulated by the protocol but EUS guided biopsies directed to the primary tumour or a site of recurrence/dissemination is recommended whereas a percutaneous approach towards liver lesion(s) can be an alternative diagnostic approach; radiology and elevated serum tumor markers may guide diagnosis in exceptional cases, for which, e.g., pathological sampling fails.

Metastases are defined as synchronous when liver tumors are detected simultaneously with the primary tumor or within the first 6 months thereafter. All other tumors are regarded as metachronous metastases or locally recurrent disease (when applicable).

The same definition applies to localized lesions detected intra- as well as extra-abdominally.

Patients treated due to the radiological appearance and or elevated CA-19.9 levels despite negative biopsies are accepted for inclusion into the study

To be included in "Limited liver desease":

Up to 4 liver metastases treatable with liver resections (without volume expansion of the future liver remnant)/thermal ablations/RFA/IRE (largest diameter \< 5 cm and for ablative techniques \< 2 cm).

Age 18 years or older ECOG 0-1 Any resectable (including borderline resectable, but without need for arterial reconstruction) (before or after neoadjuvant treatment) PDAC Patient can understand verbal and written information

Exclusion Criteria:

Age less than 18 years ECOG \>2 Patient is not able to understand the verbal and written information Progression of tumor (RECIST 1.1) during or after chemotherapy Distant metastases outside the liver (applies only to the primary cohort) Other malignancy within 2 years, the prognosis of which may affect the evaluation of the therapeutic outcome.

Major non-pancreatic surgery within 4 weeks prior to study treatment start, or lack of complete recovery from the effects of major surgery Uncontrolled (bacterial or fungal) infections Significant concomitant diseases preventing the safe administration of study drugs or likely to interfere with study assessments Uncontrolled angina pectoris; cardiac failure or clinically significant arrhythmias Continuous use of immunosuppressive agents (Corticoids are allowed) Neuropathy \>grade 1 (CTCAE, v 5.0) Pregnancy or breast feeding Patients (M/F) with reproductive potential not implementing adequate contraceptive measures Pre-defined need for arterial reconstruction to resect primary tumor

Sites (1)

• Linkoping University Hospital, Linköping, Sweden