Band 9, Heft 3

Following the results of three randomized trials (GOG-213, DESKTOP-III, and SOC-1), secondary cytoreductive surgery (sCRS) is recommended as a therapeutic option for all patients with platinum-sensitive recurrence by the NCCN guidelines and for oligometastatic recurrence by the ESMO-ESGO guidelines. Criteria for predicting a complete gross resection (CGR) were used to select patients for sCRS in all three trials. No trial used surgical prognostic factors like disease sites or disease extent for stratification. The outcomes of sCRS varied in preplanned/post-hoc subgroup analyses. The survival following an incomplete CRS was worse than with systemic chemotherapy alone. Not all patients will benefit similarly from sCRS, even if a CGR is obtained. No trial evaluated the benefit of sCRS in patients receiving poly-ADP ribose polymerase (PARP) inhibitors. While GOG-213 showed no benefit of sCRS when bevacizumab was used, the role of bevacizumab in patients having a CGR was not evaluated. The use of targeted therapies during first-line therapy is increasing, affecting treatment decisions and future clinical trial designs. New trials on sCRS should stratify patients according to surgical prognostic factors; sub-group analyses should be performed only in patients with CGR. Highlights – Selection criteria used in all three randomized trials are predictive of a complete cytoreduction and not the benefit of surgery – Post-hoc & prespecified subgroup analyses indicate that not all patients undergoing secondary cytoreduction benefit from it – Post-hoc and sub-group analysis should be performed separately for patients undergoing a complete gross resection – Impact of incomplete cytoreduction on quality of life and subsequent therapy needs further evaluation – Future randomized trials should use surgical prognostic factors like disease sites and extent as stratification factors

Objectives Laparoscopic ultrasound (LUS) combines both laparoscopy and ultrasound imaging of the peritoneum liver and retroperitoneum. LUS has not been described in treatments with pressurized intraperitoneal aerosol chemotherapy (PIPAC). We present our experience with LUS in patients undergoing PIPAC. Methods Retrospective study of LUS findings from the prospective PIPAC-OPC2 trial. Main outcome was changes in overall treatment strategy due to LUS findings. Results PIPAC-OPC2 included 143 patients of which 33 patients were treated with electrostatic precipitation PIPAC. Nine patients were excluded due to primary non-access. During PIPAC 1, LUS was performed in 112 of 134 (84 %) PIPAC procedures and changed overall treatment strategy in one patient due to detection of multiple liver metastases unseen by baseline CT. During PIPAC 2 and 3 LUS was performed in 59 of 104 (57 %) and 42 of 78 (54 %) PIPAC procedures, respectively. Throughout PIPAC 1–3, LUS also detected pathological lymph nodes in 16 patients, and focal liver lesions in another four patients of uncertain origin. No further examinations were performed in these patients, and the overall treatment strategy was not changed according to the PIPAC-OPC2 protocol. One patient had a splenic capsule rupture related to the LUS itself. This was managed conservatively. Conclusions LUS may be safely performed during PIPAC. However, LUS has limited clinical impact in patients scheduled for PIPAC, and cannot be recommended as a routine procedure when performing PIPAC.

Objectives Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface malignancies. However, surgical morbidity is high, and prediction of severe postoperative complications (SPC) is limited. We hypothesized that the changes in thromboelastogram (TEG) values following CRS could be associated with SPC. Methods We retrospectively analyzed a cohort of CRS and HIPEC patients who had TEG measured before and after CRS. Clinical and postoperative data were retrieved from a prospectively maintained database. Results Our 37-patient cohort was comprised of 24 men and 13 women with an age (median, [interquartile range, IQR]) 55 (47–65) years, of whom six had SPC. The ones with SPC did not differ from the others in age, sex, tumor histology or preoperative chemotherapy. The extent of surgery as measured by the peritoneal carcinomatosis index and the number of organs resected was comparable between SPC group vs. no SPC [9 (3–10.5) vs. 9 (5–14), p=1.0; 2 (0.75–2.25) vs. 2 (1–3), p=0.88, respectively]. The TEG parameters showed increased R- and K- time for the patients with SPC compared to those without (6 ± 3.89 vs. 4.05 ± 1.24, p=0.01; 1.65 ± 0.63 vs. 1.25 ± 0.4, p=0.03, respectively). The TEG values were significantly associated with SPC in the multivariable analysis (odds ratio=1.53, p=0.05). Conclusions TEG changes are associated with SPC. Intra-operative markers of SPC could guide intraoperative decisions, such as stool diversion and postoperative triage of patients to an appropriate level of care.

Objectives Current therapies show limited efficacy against peritoneal metastases (PM) from pancreatic cancer. Pressurized intra-peritoneal aerosol chemotherapy (PIPAC) has emerged as a novel intraperitoneal drug delivery method. Recently, a dose-escalation study identified the safe dose of Nabpaclitaxel for PIPAC administration, an ideal intraperitoneal chemotherapy agent against pancreatic cancer. Combining systemic NabPaclitaxel-Gemcitabine with NabPaclitaxel-PIPAC may enhance disease control in pancreatic cancer patients with PM. Methods The Nab-PIPAC trial is a single-center, prospective, open-label, phase II study (ClinicalTrials.gov identifier: NCT05371223). Its primary goal is to evaluate the antitumor activity of the combined treatment based on Disease Control Rate (DCR) using RECISTv.1.1 criteria. Secondary objectives include feasibility, safety, pathological response, progression-free and overall survival, nutritional status, quality of life, pharmacokinetics of NabPaclitaxel-PIPAC, and PM molecular evolution via translational research. The treatment protocol consists of three courses, each with two cycles of intravenous NabPaclitaxel-Gemcitabine and one cycle of NabPaclitaxel-PIPAC, with standard metastatic pancreatic cancer doses for the former and 112.5 mg/m 2 for the latter. Sample size follows Simon’s two-stage design: 12 patients in stage one and 26 in stage two (80 % power, 0.1 alpha). Results Partial results will be available after first stage enrollment. Conclusions This trial aims to determine the antitumor efficacy and safety of combining NabPaclitaxel-PIPAC with systemic NabPaclitaxel-Gemcitabine in pancreatic cancer patients with PM.