Raoof, Mustafa

ABSTRACT Background Implementation of remote robotic‐assisted surgery (rRAS) has the potential to significantly improve access to high‐quality surgical care for patients worldwide. Advances in robotic systems and telecommunications now enable highly reliable, low latency, and cybersecure connectivity. These technological developments, together with the broader adoption of telemedicine, have driven an increasing interest in the implementation of rRAS. Methods The Clinical Robotic Surgery Association (CRSA) convened a conference to develop international clinical recommendations for rRAS using the Danish Model of Consensus. The society identified five key issue categories and invited a panel of experts to address specific questions for each. Panel members and a jury of 10 unbiased, non‐expert in rRAS professionals participated in a day‐long conference on November 19, 2025 (Los Angeles, USA). During the conference, participants presented, discussed, and reached consensus on specific guidelines relevant to each category. Immediately after the conference, the jury reviewed and approved the recommended guidelines. Results Multiple recommendations were approved for each of the following categories: Operating Models, Roles and Responsibilities (2 recommendations), Clinical Pathway (2 recommendations), Emergency Management (8 recommendations), Technical Considerations (5 recommendations), and Medico‐legal and Ethical Considerations (4 recommendations). Conclusions There was consensus that with recent advances in telecommunication and robotic technologies, rRAS can be offered safely and effectively if the identified safeguards are realized. Adoption of rRAS is expected to continue advancing rapidly.

Abstract Peritoneal Carcinomatosis (PC) is a metastatic cancer of the lining of the abdominal cavity, most often originating from the gastrointestinal or gynecological tracts. PC occurs in approximately 20% of colorectal cancer and 60% of ovarian cancer cases, with estimated 5-year survival rates as low as 6%. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a locoregional drug delivery modality administered via a minimally invasive laparoscopic approach. PIPAC shows promise in the treatment of peritoneal metastasis in early trials on colorectal cancer (CRC) or appendiceal cancer (AC) in patients who cannot undergo cytoreductive surgery. The spatial organization of the tumor microenvironment (TME) and the complex cellular interactions within profoundly shape biology and treatment response. Spatial transcriptomics offers an opportunity to characterize TME heterogeneity in its native architecture, allowing the identification of biomarkers, interactions, and gene expression programs as well as resistance mechanisms and new potential targets. We performed image-based spatial transcriptomic profiling of 152 tissue samples, including 50 pre-treatment and 65 post-treatment metastatic tumors and 17 pre-treatment and 20 post-treatment tumor-adjacent normal tissue samples from 19 patients who participated in a Phase I trial on Oxaliplatin PIPAC. Through a comprehensive characterization of transcriptional profiles of a total of 1,249,711 cells, as well as cellular neighborhood and ligand-receptor interactions, we describe the heterogeneity of PC in its spatial context. We have further characterized treatment-driven changes in pre- and post-treatment tumors of a subset of 7 patients who underwent PIPAC with mitomycin IP. Through cell-based niche and proximity analyses, we identify distinct shifts in the composition and architecture of treated tumors. Most notably, treatment resulted in an 87% decrease in the number of malignant cells, as well as an expansion of the plasma-barrier niche and an increased number of immune infiltrates. Further analysis revealed distinct differences in the abundance of specific cancer-associated fibroblast and immune subsets, demonstrating changes in TME architecture. Overall, our results provide an invaluable characterization of PC in CRC and AC, garnering new insight into their architecture, cellular composition, and cell-cell interactions at baseline and in response to regional chemotherapy. Further analyses and follow-up studies can identify and validate new, actionable biomarkers to target these hard-to-treat tumors. Citation Format: Heini Maaret Natri, Arianna L. Williams-Katek, Muhammad Talha Waheed, Tiana Li, Marwan Fakih, Mingye Feng, Amit Merchea, Sue Chang, Richard L. Whelan, Danielle Deperalta, Thanh H. Dellinger, Nicholas Banovich, Mustafa Raoof. Spatial transcriptomic profiling of peritoneal metastases identifies multicellular programs in patient tumors undergoing pressurized intraperitoneal aerosol chemotherapy (PIPAC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3958.

The peritoneum is the second most common site of metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). Up to half of all patients that undergo curative-intent resection eventually develop peritoneal metastasis (PM), which accounts for significant morbidity and drives mortality. Despite recent advances in management, PM is associated with very poor prognosis, which is often measured in weeks to months. Clinical manifestations including bowel obstruction, ascites, and urinary obstruction have profound impact on quality of life. Even with relatively advanced disease, PM often remains occult on imaging and thus tend to be underdiagnosed and understudied. Many patients with peritoneal-only PM are excluded from clinical trials because response cannot be measured by standard radiographic criteria. Furthermore, as patients with PM are not eligible for surgical resection and low-volume peritoneal disease is often not amenable to percutaneous biopsy, tissue samples for peritoneal-specific translational studies are limited. Intraperitoneal therapeutics have been proposed as an attractive option for PM, as better penetration of tumor tissue can be achieved with less systemic toxicity compared with intravenous chemotherapy. Heated intraperitoneal chemotherapy (HIPEC), typically combined with cytoreductive surgery (CRS), is an option for select patients with PM from gynecologic or gastrointestinal primary, and for patients with primary peritoneal mesothelioma. However, the incorporation of locoregional therapy for PM in patients with PDAC has been poorly studied given the aggressive nature of pancreatic cancer and overall poor prognosis. With recent advances in existing treatment options, there may be a subset of patients who may derive benefits from locoregional control with cytoreduction and/or intraperitoneal chemotherapy. Critically, additional work is needed to determine PM-favorable clinical and tumoral predictive biomarkers to identify patients who may benefit from a more aggressive approach. We describe the current state of management of patients with peritoneal metastasis from PDAC and review the available data exploring peritoneal-directed therapy with cytoreductive surgery and/or intraperitoneal chemotherapy.

5554 Background: Epithelial ovarian cancer (EOC) is characterized by chemoresistant recurrences primarily confined to the intraperitoneal cavity, frequently leading to malignant small bowel obstructions. Intraperitoneal (IP) chemotherapy has been incorporated in EOC, but only in the first-line setting. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a novel IP drug delivery method that optimizes tissue penetration depth and drug distribution, to treat recurrent peritoneal malignancies. Recent trials outside the U.S. demonstrated partial to stable response following PIPAC in recurrent EOC. To date, no clinical trials have been completed investigating the role of PIPAC in EOC in the United States. Methods: We performed a multicenter prospective phase I trial using IP cisplatin 10.5 mg/m2 and doxorubicin 2.1 mg/m2 via PIPAC at 6-week intervals. Patients were eligible if they had recurrent disease with peritoneal metastasis; extraperitoneal metastasis was allowed. The primary endpoint was dose-limiting toxicity (DLT). Secondary endpoints included progression free survival, PCI scoring, RECIST measurements, and quality of life (QoL). The patients with gastric and uterine cancers’ toxicity data were used but given inherent prognostic differences the treatment efficacy for these patients were not used in this analysis. Adverse event (AE) monitoring was graded using CTCAE spanning 18 weeks. Following completion of treatment (³2 PIPACs) patients were followed up every 12 weeks. QoL was measured using patient-reported assessments at 0, 6, 12, and 18 weeks. Baseline demographics were summarized. Mean change in PCI was calculated between cycle (C) 1 and 2, and cycle 2 and 3. Toxicities attributed to the surgery or PIPAC were reported with highest grade for each patient. Results: Nine heavily pretreated, recurrent patients were enrolled in the trial: 7 with platinum-resistant recurrent EOC, 1 with uterine cancer, and 1 with gastric cancer. PIPAC completion rate was 71.4%. Median age of participants was 65 years. Median prior lines of chemotherapy were 4 (range 2 - 10). No surgical complications occurred in the cohort. Two patients came off study: one for G3 abdominal pain and the other for G3 anorexia. For the EOC cohort, the median PCI reduction was -1.4% (C1 to C2) and -2.8% (C1 to C3). One low-grade serous EOC patient demonstrated a partial response based on RECIST criteria and received 6 cycles. Two EOC patients showed an initial response based on PCI reduction, but progressed following Cycle 2. Overall, QoL was stable. Conclusions: PIPAC with cisplatin/doxorubicin in platinum-resistant ovarian cancer is well tolerated. Intraperitoneal responses were seen in a subset of low-grade serous ovarian cancer patients, which may warrant further study. Heavily pretreated, platinum-resistant high-grade EOC patients derived limited intraperitoneal control from PIPAC monotherapy. Clinical trial information: NCT04329494 .

AbstractBackgroundCytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is increasingly performed for peritoneal surface malignancies but remains associated with significant morbidity. Scant research is available regarding the impact of insurance status on postoperative outcomes.MethodsPatients undergoing CRS/HIPEC between 2000 and 2017 at 12 participating sites in the US HIPEC Collaborative were identified. Univariate and multivariate analyses were used to compare the baseline characteristics, operative variables, and postoperative outcomes of patients with government, private, or no insurance.ResultsAmong 2268 patients, 699 (30.8%) had government insurance, 1453 (64.0%) had private, and 116 (5.1%) were uninsured. Patients with government insurance were older, more likely to be non‐white, and comorbid (p < 0.05). Patients with government (OR: 2.25, CI: 1.50−3.36, p < 0.001) and private (OR: 1.69, CI: 1.15−2.49, p = 0.008) insurance had an increased risk of complications on univariate analysis. There was no independent relationship on multivariate analysis. An American Society of Anesthesiologists score of 3 or 4, peritoneal carcinomatosis index score >15, completeness of cytoreduction score >1, and nonhome discharge were factors independently associated with a postoperative complication.ConclusionWhile there were differences in postoperative outcomes between the three insurance groups on univariate analysis, there was no independent association between insurance status and postoperative complications after CRS/HIPEC.

AbstractBackgroundThe feasibility of remote perioperative telemonitoring of patient‐generated physiologic health data and patient‐reported outcomes in a high risk complex general and urologic oncology surgery population is evaluated.MethodsComplex general surgical/urologic oncology patients wore a pedometer, completed ePROs (electronic patient‐reported outcome surveys) and record their vitals (weight, pulse, pulse oximetry, blood pressure, and temperature) via a telehealth app platform. Feasibility (% adherence) was assessed as the primary outcome measure.ResultsTwenty‐one patients with a median age 58 (32−82) years were included. The readmission rate was 33% and the incidence of ≥Grade 3a morbidity was 24%. Adherence to vital sign and ePRO measurements was 95% before surgery, 91% at discharge, and 82%, 68%, and 64% at postdischarge d2, 7, 14, and 30, respectively. There was significant worsening of mobility, self‐care and usual daily activity at postdischarge d2 compared to preoperative baseline (p < 0.05). Median daily preoperative steps taken by patients with <Grade 3a versus ≥Grade 3a postoperative morbidity was 6062 versus 4166 (p < 0.05). Of those interviewed, 87% (13/15) viewed vital sign devices as helpful in recovery.ConclusionsTelemonitoring is feasible in a general surgical and urologic oncology setting. Future studies will ascertain optimal patient selection, duration, and extent of perioperative monitoring.

Abstract Objectives Peritoneal metastasis (PM) from appendiceal cancer or colorectal cancer (CRC) has significant morbidity and limited survival. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a minimally invasive approach to treat PM. We aim to conduct a dose-escalation trial of mitomycin C (MMC)-PIPAC combined with systemic chemotherapy (FOLFIRI) in patients with PM from appendiceal cancer or CRC. Methods This is a multicenter Phase I study of MMC-PIPAC (NCT04329494). Inclusion criteria include treatment with at least 4 months of first- or second-line systemic chemotherapy with ineligibility for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Exclusion criteria are: progression on chemotherapy; extraperitoneal metastases; systemic chemotherapy intolerance; bowel obstruction; or poor performance status (ECOG>2). Escalating MMC-PIPAC doses (7–25 mg/m 2 ) will be administered in combination with standard dose systemic FOLFIRI. Safety evaluation will be performed on 15 patients (dose escalation) and six expansion patients: 21 evaluable patients total. Results The primary endpoints are recommended MMC dose and safety of MMC-PIPAC with FOLFIRI. Secondary endpoints are assessment of response (by peritoneal regression grade score; Response Evaluation Criteria in Solid Tumors [RECIST 1.1], and peritoneal carcinomatosis index), progression free survival, overall survival, technical failure rate, surgical complications, conversion to curative-intent CRS-HIPEC, patient-reported outcomes, and functional status. Longitudinal blood and tissue specimens will be collected for translational correlatives including pharmacokinetics, circulating biomarkers, immune profiling, and single-cell transcriptomics. Conclusions This Phase I trial will establish the recommended dose of MMC-PIPAC in combination with FOLFIRI. Additionally, we expect to detect an early efficacy signal for further development of this therapeutic combination.

125 Background: Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is being evaluated as a novel minimally invasive palliative treatment of peritoneal metastases (PM). Prior studies have established the feasibility and safety of repeated PIPAC treatments in gastrointestinal and gynecologic cancers. The goal of the present phase 1 trial was to establish the safety and feasibility of PIPAC oxaliplatin in a highly chemotherapy refractory colorectal and appendiceal cancer patient population. Methods: Patients with biopsy-proven peritoneal metastases from colorectal or appendiceal cancer underwent up to three PIPAC treatments using oxaliplatin (92 mg/m2) with a six-week interval at two academic centers. Patients with bowel obstruction, extra-peritoneal metastases, or poor performance status (ECOG>2) were excluded. PIPAC was nebulized over 5 min with a 30 min aerosol dwell time. Apart from the first PIPAC cycle, the patients also received a sensitizing dose of 5FU/LV (400mg/m2) within 24 hours of the procedure. Primary end point was safety as assessed by dose limiting toxicities within 6 weeks of the first PIPAC. Secondary endpoints included safety with the addition of 5FU/LV, efficacy, surgical morbidity, technical failure rate, progression-free and overall survival, pharmacokinetics (PK), and quality of life assessment. Results: A total of 8 patients were included: 5 colorectal; and 3 appendiceal. Median number of prior chemotherapy cycles was 2 (Interquartile range – IQR; 1.5-3.5). All patients were refractory to systemic oxaliplatin-based chemotherapy. Median time from diagnosis to PIPAC was 16 months (IQR; 5.6, 17.5) and Peritoneal Carcinomatosis Index was 29 (IQR; 20.5, 31.5). Five (62.5%) patients completed 3 PIPAC cycles while in 3 (37.5%) patients PIPAC was discontinued due to disease progression within the peritoneal cavity. No surgical complication or dose limiting toxicity was observed. Only one patient developed grade 3 treatment-related toxicity after first PIPAC (anemia), and another patient after second PIPAC (abdominal pain and anemia). At the completion of PIPAC treatment 5 patients had stable disease and 3 had disease progression. Pharmacokinetic, histologic response and preliminary survival data will be presented at the meeting. Conclusions: PIPAC with oxaliplatin is safe and feasible in a highly chemotherapy refractory cohort of appendiceal and colorectal carcinomatosis patients with or without sensitizing 5-FU/ LV. Clinical trial information: NCT04329494.