Colorectal Carcinomatosis Research Articles

Tailored chemotherapy for colorectal cancer peritoneal metastases based on a drug-screening platform in patient-derived organoids: a case report.

Peritoneal metastasis from colorectal cancer (CRC) has limited therapeutic options and poor prognosis. Systemic chemotherapy combined with cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) or pressurized intraperitoneal aerosol chemotherapy (PIPAC) have yielded initial promising results. However, standard local therapies with oxaliplatin and mitomycin are not optimal and a better individualized management of these patients remains as an unmet clinical need. Patient-derived organoid (PDO) technology allows to culture in three dimensions normal and cancer stem cells (CSC) that self-organize in multicellular structures that recapitulates some of the features of the particular organ or tumor of origin, emerging as a promising tool for drug-testing and precision medicine. This technology could improve the efficacy of systemic and intraperitoneal chemotherapy and avoid unnecessary treatments and side effects to the patient. Here we report a case of a 45-year-old man with a rectal adenocarcinoma with liver, lymph node and peritoneal metastases. The patient was treated with systemic chemotherapy (FOLFOXIRI plus Bevacizumab) and was subjected to mitomycin-based PIPAC. We generated patient-derived peritoneal carcinomatosis organoids in order to screen the activity of drugs for a personalized treatment. Both 5-FU and SN-38, the active irinotecan derivative, displayed strong cytotoxicity, while the response to oxaliplatin was much lower. Although the development of a colo-cutaneous fistulae prevented from further PIPAC, the patient continued with fluoropirimidine maintenance treatment based on standard clinical practice and the drug-screening test performed on organoids. Our results suggest that the peritoneal implant shows chemoresistance to oxaliplatin, while it might still be sensitive to irinotecan and 5-FU, which supports a potential benefit of these two drugs in the local and/or systemic treatment of our patient. This study shows the strength of the utility of the establishment of organoids for drug response assays and thus, for the personalized treatment of colorectal carcinomatosis patients.

Abstract B027: Circulating tumor DNA in colorectal carcinomatosis: Detection and prognostic value

Abstract Background: Circulating tumor DNA (ctDNA) of patients with colorectal peritoneal metastases (PM) was obtained to identify prognostic factors associated for ctDNA detection and with overall survival (OS). Prior studies have identified a correlation between ctDNA detection and OS in colorectal liver metastases (CRLM) and after resection of primary tumors. However, detection rates for PM may be lower than other metastatic sites. Methods: Peripheral blood was drawn from 152 patients after diagnosis with PM with or without other synchronous sites of disease. Patients who underwent cytoreduction were excluded. Next-generation sequencing of a panel of 70 genes commonly mutated in colorectal cancer was performed on all samples. Mutations were identified and variant allele frequencies (VAFs) calculated. Clinical data including OS from time of CRCC diagnosis, tumor grade, tumor histology, synchronous non-peritoneal metastases and patient demographics were obtained from medical records .Chi-squared tests were performed to compare differences in ctDNA detection based on clinical factors, and Cox regression analyses were performed to identify associations with ctDNA characteristics and OS. Results: The overall detection rate of any mutation in ctDNA was 74.3% (110/145 patients). The most frequently detected mutations were TP53 (55%), APC (47%), KRAS (32%), and PIK3CA (14%). Sensitivity for detecting individual mutations ranged from 50%-63%. Mucinous and signet-ring cell histology were more common in patients with PM alone (Mucinous: 37% vs 24%, p=0.0003, Signet Ring Cell: 10% vs. 2.2%, p=0.0001) and associated with lower sensitivity (mucinous: 59%, signet-ring cell: 57% and adenocarcinoma 85%, p=0.002). Synchronous CRLM were associated with increased detection compared to PM alone (88% vs. 68%, p=0.011). After adjustment for differences in histology, synchronous CRLM (OR 3.32, 95CI: 1.52-8.02, p=0.016) was associated with higher detection rates. Grade was not associated with detection (moderately differentiated: 79%, poorly differentiated: 74%, p=0.81). Detection of any ctDNA was associated with a trend towards worse OS (HR 2.18, 95% CI: 0.98-4.95, p=0.06). KRAS (HR 2.02, 95% CI: 1.14-3.60, p=0.017) and PIK3CA (HR 2.26, 95% CI: 1.07-4.78, p=0.033) ctDNA detection was associated worse OS. Detection of multiple mutations (HR: 0.85, 95% CI 0.50-1.42, p=0.52) and maximum VAF (HR 0.99, 95% CI: 0.97- 1.01, p=0.17) were not associated with OS. Conclusion: ctDNA detection is lower in patients with PM alone compared to those with PM and CRLM. Mucinous tumors had lower rates of ctDNA detection after accounting for extra-PM metastases. Presence of ctDNA is associated with a trend towards worse OS, especially for patients with detectable mutations in KRAS or PIK3CA. Quantification of ctDNA by number of mutations or VAF was not associated with OS. Interpretation of ctDNA results for PM patients should take into consideration the lower sensitivity in the absence of other metastatic sites, but may have prognostic utility. Citation Format: Abhineet Uppal, Michael G. White, George J. Chang, Scott Kopetz, John Paul Y. C. Shen. Circulating tumor DNA in colorectal carcinomatosis: Detection and prognostic value [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr B027.

Safety and efficacy of pressurized intraperitoneal aerosolized chemotherapy in appendiceal and colorectal cancer patients with peritoneal carcinomatosis: A first-in-US phase I study.

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.

Immune Reprogramming Precision Photodynamic Therapy of Peritoneal Metastasis by Scalable Stem-Cell-Derived Extracellular Vesicles

The dissemination of tumor metastasis in the peritoneal cavity, also called peritoneal metastasis (PM) or carcinomatosis, represents a late stage of gastrointestinal and gynecological cancer with very poor prognosis, even when cytoreductive surgery is effective, due to residual microscopic disease. Photodynamic therapy (PDT) in the management of peritoneal metastasis has been clinically limited by the low tumor selectivity of photosensitizers (PS) and important adverse effects. Here, we propose extracellular nanovesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) as the fourth generation of immune active PS vectors that are able to target peritoneal metastasis with superior selectivity, potentiate PDT cytotoxicity at the tumor site without affecting healthy tissues, modulate the tumor microenvironment of immunocompetent colorectal and ovarian carcinomatosis models, and promote an antitumor immune response. A pioneering strategy was developed for high yield, large-scale production of MSC-EVs encapsulating the drug meta(tetrahydroxyphenyl)chlorin (mTHPC) (EVs-mTHPC) that is compatible with requirements of clinical translation and also preserves the topology and integrity of naturally produced EVs. Intraperitoneal injection of EVs-mTHPC showed an impressive enhancement of tumoral selectivity in comparison to the free drug and to the liposomal formulation Foslip (mean ratio of PS in tumors/organs of 40 for EVs-mTHPC versus 1.5 for the free PS and 5.5 for Foslip). PDT mediated by EVs-mTHPC permitted an important tumoral necrosis (55% of necrotic tumoral nodules versus 18% for Foslip (p < 0.0001)) and promoted antitumor immune cell infiltration, mainly proinflammatory M1-like CD80+ and CD8+ T cell effector. Intratumor proliferation was significantly decreased after PDT with EVs-mTHPC. Overall EVs vectorization of mTHPC afforded important tumoral selectivity while overcoming the PDT toxicity of the free drug and prolonged mice survival in the colorectal carcinomatosis model. MSC-EVs produced by our scalable manufacturing method appears like the clinically relevant fourth-generation PDT vehicle to overcome current limitations of PDT in the treatment of peritoneal metastasis and promote a hot tumor immune environment in PM.

Indications for hyperthermic intraperitoneal chemotherapy with cytoreductive surgery: a clinical practice guideline.

The purpose of the present review was to provide evidence-based guidance about the provision of cytoreductive surgery (crs) with hyperthermic intraperitoneal chemotherapy (hipec) in the treatment of peritoneal cancers. The guideline was developed by the Program in Evidence-Based Care together with the Surgical Oncology Program at Ontario Health (Cancer Care Ontario) through a systematic review of relevant literature, patient- and caregiver-specific consultation, and internal and external reviews. Recommendation 1a: For patients with newly diagnosed stage iii primary epithelial ovarian or fallopian tube carcinoma, or primary peritoneal carcinoma, hipec should be considered for those with at least stable disease after neoadjuvant chemotherapy at the time that interval crs (if complete) or optimal cytoreduction is achieved. Recommendation 1b: There is insufficient evidence to recommend the addition of hipec when primary crs is performed for patients with newly diagnosed advanced primary epithelial ovarian or fallopian tube carcinoma, or primary peritoneal carcinoma, outside of a clinical trial. Recommendation 2: There is insufficient evidence to recommend hipec with crs in patients with recurrent ovarian cancer outside the context of a clinical trial. Recommendation 3: There is insufficient evidence to recommend hipec with crs in patients with peritoneal colorectal carcinomatosis outside the context of a clinical trial. Recommendation 4: There is insufficient evidence to recommend hipec with crs for the prevention of peritoneal carcinomatosis in colorectal cancer outside the context of a clinical trial; however, hipec using oxaliplatin is not recommended. Recommendation 5: There is insufficient evidence to recommend hipec with crs for the treatment of gastric peritoneal carcinomatosis outside the context of a clinical trial. Recommendation 6: There is insufficient evidence to recommend hipec with crs for the prevention of gastric peritoneal carcinomatosis outside the context of a clinical trial. Recommendation 7: There is insufficient evidence to recommend hipec with crs as a standard of care in patients with malignant peritoneal mesothelioma; however, patients should be referred to hipec specialty centres for assessment for treatment as part of an ongoing research protocol. Recommendation 8: There is insufficient evidence to recommend hipec with crs as a standard of care in patients with disseminated mucinous neoplasm in the appendix; however, patients should be referred to hipec specialty centres for assessment for treatment as part of an ongoing research protocol.

Hepatic resection and blood transfusion increase morbidity after cytoreductive surgery and HIPEC for colorectal carcinomatosis.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is an effective but complex treatment for peritoneal metastasis (PM). Our objective was to identify risk factors for postoperative morbidity and mortality following CRS-HIPEC. Retrospective study of prospectively collected data of patients undergoing CRS-HIPEC for PM arises from colorectal cancer between January 2008 and December 2017. Perioperative variables were correlated with morbidity outcomes using a logistic regression model. Sixty-seven patients underwent CRS-HIPEC, and overall morbidity and mortality were 31.3% and 4.5% respectively. Major morbidity rate was 19.4%; 7.5% of patients were re-operated. Intraoperative blood transfusion (p = 0.01), liver resection (p < 0.01), and intestinal anastomosis (p < 0.01) were associated with a higher morbidity in univariate analysis. A multivariate analysis identified blood transfusion and liver resection as independent risk factors (OR 3.66, IC 1.13-16.54; OR 4.33, IC 1.17-11.46, respectively). Extension of visceral resection did not correlate with morbidity. Patients with lymph-node infiltration had a higher major complication rate (p = 0.01). CRS-HIPEC is a feasible treatment for colorectal PM with an acceptable morbi-mortality rate in experienced centers. In our study, digestive anastomosis, perioperative blood transfusion, hepatic resection, and lymph-node infiltration were associated with higher morbidity rates.

Heated Intraperitoneal Chemotherapy for Colorectal Carcinomatosis: Emerging Evidence

Heated Intraperitoneal Chemotherapy for Colorectal Carcinomatosis: Emerging Evidence

The Association of Tumor Laterality and Survival After Cytoreduction for Colorectal Carcinomatosis

BackgroundPrimary tumor location has emerged as an important surrogate for tumor biology in metastatic colorectal cancer treated with systemic chemotherapy. It is unclear if primary tumor location is associated with survival after cytoreductive surgery (CRS) with or without heated intraperitoneal chemotherapy (HIPEC) for colorectal carcinomatosis. MethodsStudy of a contemporary cohort merged data from the California Cancer Registry, 2004-2012, and the Office of Statewide Health Planning and Development inpatient database. For patients undergoing CRS/HIPEC, clinicopathologic variables, treatment characteristics, and survival were compared by right versus left colon primary site. Survival was analyzed by Cox proportional hazards. ResultsOf 272 patients identified, 128 (47.1%) had right-sided tumors. Left- and right-sided cohorts had similar patient, tumor, and treatment factors. Patients with left-sided primary tumors had significantly prolonged overall survival (mean 34 versus 15.5 mo, P = 0.0010). Factors independently associated with decreased overall survival included age >80 (HR 7.0, P < 0.0001), advanced T4 stage (HR 3.6, P = 0.0031), and positive lymph nodes (HR 2.2, P = 0.0004). Metachronous peritoneal involvement (HR 0.38, P < 0.0001) and left-sided primary tumors (HR 0.72, P = 0.041) were independently associated with improved overall survival. ConclusionsThis study identifies location of primary tumor as an important determinant of long-term survival after CRS/HIPEC. Patients with left-sided tumors have a more favorable prognosis.

Short-termoutcome of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy used as treatment of colo-rectal carcinomatosis: a multicentric study.

The aim of this study is to assess the morbidity and mortality related to cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colo-rectal carcinomatosis. A retrospective multi-institutional study from seven Italian Centers was performed. One hundred and seventy-two patients, submitted to cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) to treat carcinomatosis of colorectal origin, were recorded. Postoperative morbidity was evaluated in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Post-operative mortality was evaluated as patients' death within 60days from surgical procedures. Predictors of morbidity were evaluated with univariate and multivariate analyses. Post-operative morbidity occurred in 83 patients (48.3%): grades 1-2 in 29 cases (16.9%), and grades 3-4 in 54 (31.4%). Mortality occurred in four cases (2.3%). Number of anastomoses (OR 1.45; 95% CI 1.05-2.00; p = 0.024), number of blood transfusions (OR 1.31; 95% CI 1.11-1.54; p = 0.001) and chemotherapy regimen [Oxaliplatin (OX): OR 2.87; 95% CI 1.22-6.75; p = 0.015] remained, in multivariate analysis, in a statistically significant correlation with overall morbidity. The only variable that was proven to have statistically significant correlation with 3-4 morbidity was the number of blood transfusions (OR 1.25; 95% CI 1.07-1.46; p = 0.005). Morbidity and mortality do not preclude the use of CRS plus HIPEC in the treatment of peritoneal carcinomatosis of colorectal origin.

More questions regarding HIPEC in colorectal carcinomatosis

More questions regarding HIPEC in colorectal carcinomatosis

Survival outcomes in patients aged 75years and over with peritoneal colorectal carcinomatosis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC): multicenter study of the Spanish Group of Peritoneal Cancer Surgery (GECOP).

The attitude toward cytoreductive surgery with HIPEC in peritoneal carcinomatosis from colorectal cancer is unclear. The aim of this study is to report the perioperative outcomes after cytoreductive surgery with HIPEC in patients ≥ 75years. This retrospective multicenter study collected the data the Spanish Group of Peritoneal Cancer Surgery. Thirty-six patients with peritoneal carcinomatosis from colorectal cancer met the selection criteria for the study. Morbidity, mortality, disease-free and overall survival were analyzed. Morbidity (grade III-IV) was 17% and 2 patients died of complications related to the procedure (5.4%). Median disease-free survival (DFS) was 16months. DFS at 1 and 3years was 81% and 42%, respectively. Overall survival at 1 and 3years was 96% and 75%. In the univariate analysis, preoperative comorbidities (p = 0.01), liver metastases (p = 0.02), blood transfusion (p = 0.001) and postoperative complications (p = 0.001); and in the multivariate analysis, perioperative blood transfusion (OR 2.56, 95% CI 1.95-6.24, p = 0.03) and postoperative complications (OR 3.25, 95% CI 2.35-7.56, p = 0.02) were associated with a lower overall survival. Age is not an absolute contraindication to perform cytoreduction surgery with HIPEC in highly selected elderly patients with colorectal peritoneal carcinomatosis.

ASO Author Reflections: Tending Towards a Personalized Medicine for Colorectal Carcinomatosis by Adding the RAS Mutation Status in the Workup for CRS and HIPEC

ASO Author Reflections: Tending Towards a Personalized Medicine for Colorectal Carcinomatosis by Adding the RAS Mutation Status in the Workup for CRS and HIPEC

Bacterial ghosts as adjuvant to oxaliplatin chemotherapy in colorectal carcinomatosis

Bacterial ghosts as adjuvant to oxaliplatin chemotherapy in colorectal carcinomatosis

Improved anti-colorectal carcinomatosis effect of tannic acid co-loaded with oxaliplatin in nanoparticles encapsulated in thermosensitive hydrogel

Tannic acid, a hydrolysable tannin, exists commonly in food plants. Tannic acid has already been shown various anticancer mechanisms such as inhibiting the proliferation, inducing a higher apoptotic rate and slowing down the metastasis of different cancers. Moreover, tannic acid was reported to reduce the side effects caused by chemotherapeutics on patients. But whether the tannic acid can improve the treatment of oxaliplatin on colorectal carcinomatosis has yet been studied. In this study, we developed an injectable drug delivery system by physical incorporation of oxaliplatin (OXA) and tannic acid (TA) polymeric nanoparticles (OXA/TA NPs) into a thermo-sensitive hydrogel, OXA/TA NPs-hydrogel (OXA/TA NPs-H). The OXA/TA NPs-H was injected into the peritoneal cavity for the treatment of colorectal peritoneal carcinoma. Firstly, a water-in-oil-in-water double-emulsion (w/o/w) method and solvent-evaporation procedure were used in the preparation of the biodegradable OXA/TA NPs. Then, we prepared the biodegradable thermo-sensitive poly(3-caprolactone) (PCL)-10R5-PCL (PCLR) hydrogel with a low critical solution temperature (LCST) which undergoes gelation process at body temperature. Transmission electron microscopy (TEM) showed the spherical profile of OXA/TA NPs. Fourier-transform infrared (FTIR) spectra demonstrated that OXA and TA were both encapsulated into the OXA/TA NPs. In this study, intraperitoneal application of OXA/TA NPs-H restricted the growth of CT26 peritoneal colon cancer in vivo, improved the quality of life and prolonged the survival time of the model mice. Our study suggested that OXA/TA NPs-H might have potential application in the treatment of colorectal cancer.

854 - Intraoperative Molecular Imaging with a Tumor Hypoxia Targeted Near Infrared Contrast Agent Identifies Subcentimeter Tumor Deposits in a Murine Colorectal Carcinomatosis Model

854 - Intraoperative Molecular Imaging with a Tumor Hypoxia Targeted Near Infrared Contrast Agent Identifies Subcentimeter Tumor Deposits in a Murine Colorectal Carcinomatosis Model

Bacterial ghosts as adjuvant to oxaliplatin chemotherapy in colorectal carcinomatosis

ABSTRACTColorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer mortality worldwide. At late stage of the disease CRC often shows (multiple) metastatic lesions in the peritoneal cavity which cannot be efficiently targeted by systemic chemotherapy. This is one major factor contributing to poor prognosis. Oxaliplatin is one of the most commonly used systemic treatment options for advanced CRC. However, drug resistance – often due to insufficient drug delivery – is still hampering successful treatment. The anticancer activity of oxaliplatin includes besides DNA damage also a strong immunogenic component. Consequently, the aim of this study was to investigate the effect of bacterial ghosts (BGs) as adjuvant immunostimulant on oxaliplatin efficacy. BGs are empty envelopes of gram-negative bacteria with a distinct immune-stimulatory potential. Indeed, we were able to show that the combination of BGs with oxaliplatin treatment had strong synergistic anticancer activity against the CT26 allograft, resulting in prolonged survival and even a complete remission in this murine model of CRC carcinomatosis. This synergistic effect was based on an enhanced induction of immunogenic cell death and activation of an efficient T-cell response leading to long-term anti-tumor memory effects. Taken together, co-application of BGs strengthens the immunogenic component of the oxaliplatin anticancer response and thus represents a promising natural immune-adjuvant to chemotherapy in advanced CRC.

Preoperative nutritional risk assessment in patients undergoing cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for colorectal carcinomatosis

Background: Malnutrition is associated with increased postoperative morbidity in colorectal surgery. This study aimed to determine if preoperative nutritional markers could predict postoperative outcomes for patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for peritoneal metastasis (PM) of colorectal origin.Methods: All patients who underwent a complete CRS-HIPEC for colorectal PM between January 2009 and December 2014 were evaluated. Preoperative clinical and biological nutritional factors, including Body Mass Index (BMI), preoperative albumin and prealbumin levels were analysed. Preoperative computed tomography was used to measure the cross-sectional surface of the visceral and subcutaneous adipose tissue, at the third lumbar vertebrae, to assess the abdominal fat composition. Skeletal muscle mass was measured to assess for sarcopenia.Results: Among 214 patients, 14 (6.5%) had a BMI ≥ 35 kg/m2, 90 (42%) were sarcopenic, 19 (9%) presented albumin <35 g/L and 2 (1%) had pre-albumin <20 mg/dL. Median values for visceral and subcutaneous fat surfaces were 99.2 cm2 and 198 cm2, respectively. Hypoalbuminemia was associated with worse overall survival (23 vs. 59 months, p = 0.015). The other nutritional factors did not impact overall or progression free survival after CRS-HIPEC for colorectal PM. In multivariate analysis, major post-operative complication and hypoalbuminemia were independently associated with decreased overall survival.Conclusions: Hypoalbuminemia appears as a strong predictive factor for decreased overall survival in patients presenting PM of colorectal origin undergoing CRS-HIPEC.

Intraoperative Near-Infrared Fluorescence Imaging using indocyanine green in colorectal carcinomatosis surgery: Proof of concept

PurposesThis study assesses the value of using Intraoperative Near Infrared Fluorescence Imaging and Indocyanine green to detect colorectal carcinomatosis during oncological surgery. In colorectal carcinomatosis cancer, two of the most important prognostic factors are completeness of staging and completeness of cytoreductive surgery. Presently, intraoperative assessment of tumoral margins relies on palpation and visual inspection.The recent introduction of Near Infrared fluorescence image guidance provides new opportunities for surgical roles, particularly in cancer surgery. MethodsThe study was a non-randomized, monocentric, pilot “ex vivo” blinded clinical trial validated by the ethical committee of University Hospital of Saint Etienne.Ten patients with colorectal carcinomatosis cancer scheduled for cytoreductive surgery were included. Patients received 0.25 mg/kg of Indocyanine green intravenously 24 h before surgery. A Near Infrared camera was used to detect “ex-vivo” fluorescent lesions. ResultsThere was no surgical mortality. Each analysis was done blindly. In a total of 88 lesions analyzed, 58 were classified by a pathologist as cancerous and 30 as non-cancerous. Among the 58 cancerous lesions, 42 were correctly classified by the Intraoperative Near-Infrared camera (sensitivity of 72.4%). Among the 30 non-cancerous lesions, 18 were correctly classified by the Intraoperative Near-Infrared camera (specificity of 60.0%). ConclusionsNear Infrared fluorescence imaging is a promising technique for intraoperative tumor identification. It could help the surgeon to determine resection margins and reduce the risk of locoregional recurrence.

Is preoperative chemotherapy related to the survival of patient operated for peritoneal colorectal carcinomatosis and can it induce complete pathological response?

e15159Background: Preoperative Systemic chemotherapy (pCT) often complements cytoreductive surgery and intraperitoneal chemotherapy in the peritoneal colorectal carcinomatosis (PCC) treatment. But ...

Pretreatment with VEGF(R)-inhibitors reduces interstitial fluid pressure, increases intraperitoneal chemotherapy drug penetration, and impedes tumor growth in a mouse colorectal carcinomatosis model.

Cytoreductive surgery combined with intraperitoneal chemotherapy (IPC) is currently the standard treatment for selected patients with peritoneal carcinomatosis of colorectal cancer. However, especially after incomplete cytoreduction, disease progression is common and this is likely due to limited tissue penetration and efficacy of intraperitoneal cytotoxic drugs. Tumor microenvironment-targeting drugs, such as VEGF(R) and PDGFR inhibitors, can lower the heightened interstitial fluid pressure in tumors, a barrier to drug delivery. Here, we investigated whether tumor microenvironment-targeting drugs enhance the effectiveness of intraperitoneal chemotherapy. A mouse xenograft model with two large peritoneal implants of colorectal cancer cells was developed to study drug distribution and tumor physiology during intraperitoneal Oxaliplatin perfusion. Mice were treated for six days with either Placebo, Imatinib (anti-PDGFR, daily), Bevacizumab (anti-VEGF, twice) or Pazopanib (anti-PDGFR, -VEGFR; daily) followed by intraperitoneal oxaliplatin chemotherapy. Bevacizumab and Pazopanib significantly lowered interstitial fluid pressure, increased Oxaliplatin penetration (assessed by laser ablation inductively coupled plasma mass spectrometry) and delayed tumor growth of peritoneal implants (assessed by MRI). Our findings suggest that VEGF(R)-inhibition may improve the efficacy of IPC, particularly for patients for whom a complete cytoreduction might not be feasible.