CA-125: an inaccurate surveillance tool immediately after cytoreductive surgery and hyperthermic intraoperative chemotherapy (CRS-HIPEC)?

Objective: This study seeks to evaluate pre and post-operative CA-125 in patients undergoing complete cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and understand the time frame before values normalise allowing use as a surveillance tool to resume.

Methods: A retrospective review was carried out of 94 patients undergoing CRS-HIPEC to compare pre-operative CA-125 values, measured within one week prior to surgery to post-operative readings within the first 30 d. Raised CA-125 was defined using as a value >35?U/ml.

Results: Of 63 (67%) patients with normal pre-operative CA-125, 22 (35%) had raised post-operative CA-125, and consisted of patients with colorectal (n?=?8), appendiceal (n?=?6), ovarian (n?=?4) or other (n?=?4) cancers. The average peak CA-125 was 80?U/ml occurring on median 10th post-operative day (POD) (range 7–30). The median day of normalisation for patients with normal pre-operative and raised post-operative CA-125 was 57 (range 28–115). The median day of normalisation for patients with raised pre-operative CA-125 was POD 41 (range 1–114). Notably 10 patients had initial normalisation (median POD 1, range 1–6), followed by subsequent raised value (median POD 10, range 5–40) and re-normalisation (median POD 47, range 19–104).

Discussion: For patients with raised pre-operative CA-125 an immediate post-operative CA-125 within 3 d may be useful to assess normalisation following surgery. Aside from immediate measurement CA-125 is misleading and should not be measured post-operatively within the first 3 months after surgery following which its use as a surveillance marker can resume.     

Identification of risk factors associated with postoperative acute kidney injury after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a retrospective study

Background: Acute kidney injury (AKI) is a postoperative complication associated with significant morbidity and mortality. The incidence and risks factors for AKI after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) have not been fully studied. The purpose of this study was to identify perioperative risk factors predictive of AKI after CRS-HIPEC.

Methods: This retrospective study collected demographic, tumour-related, intraoperative and postoperative data from 475 patients who underwent CRS-HIPECs. AKI was defined using the acute kidney injury network criteria and calculated on postoperative days 1, 2, 3, 7 and day of hospital discharge. We conducted univariate and multivariate analyses to assess the association between variables of interest and AKI. A p value of <0.05 was considered statistically significant.

Results: The incidence of AKI was 21.3%. The multivariate analysis identified six predictor factors independently associated with the development of AKI (OR: [95%CI]); age: 1.16 (1.05–1.29, p?p?=?0.05) and obesity: 2.88 (1.47–5.63), p?p?p?p?p?Conclusions: Our study demonstrates that the incidence of AKI is high. While other studies have reported that AKI is associated with platinum-based infusion, age and obesity, we report for the first time a negative association between pregabalin use and AKI. More studies are needed to confirm our results.     

Direct surgery with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for patients with colorectal peritoneal metastases

IntroductionNeoadjuvant chemotherapy is widely used in treatment of peritoneal metastases from colorectal cancer, but there is little scientific evidence for this approach. This study aimed to study survival in patients treated with direct surgery with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), i.e. without neoadjuvant chemotherapy.Material and methodsPatients with histopathologically confirmed peritoneal metastases from colorectal cancer that underwent first-time CRS-HIPEC with complete cytoreduction (CC0 or 1) at Karolinska University Hospital 2012–2019 were included. Patients with synchronous extraperitoneal metastases were excluded if not treated before end of follow-up. Factors associated with overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method and Cox regression models. The multivariable models were adjusted for sex, age, synchronous/metachronous peritoneal metastases, peritoneal carcinomatosis index (PCI), extraperitoneal metastases and the pathological tumor (T) and lymph node (N) stage of the primary tumor.ResultsIn all, 131 patients underwent complete CRS-HIPEC for peritoneal metastases without neoadjuvant chemotherapy. The median OS and DFS were 40.3 months and 12.5 months, respectively, in patients treated with direct surgery. In the multivariable model, PCI≥16 was the only variable associated with decreased OS, whereas elevated PCI, metachronous development of peritoneal metastases and synchronous extraperitoneal metastases were associated with decreased DFS. Age was not associated with an impaired prognosis.ConclusionPatients who underwent direct surgery with CRS-HIPEC had a good prognosis, with a median OS of more than 3 years. The results from this study question the need of neoadjuvant chemotherapy in all patients eligible for CRS-HIPEC.     

The impact of radiological retroperitoneal lymphadenopathy on survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases

ObjectivesTo investigate the impact of retroperitoneal lymphadenopathy (RPLP) on pre-operative CT scan on overall survival (OS) and disease-free survival (DFS) after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for peritoneal metastases (PM) of colorectal cancer.BackgroundIn patients with PM enlarged retroperitoneal lymph nodes (RPLP) are usually considered extra-regional lymph node metastases and therefore these patients may be excluded from CRS-HIPEC. This is a clinical dilemma since it is often hard to obtain histology from these nodes.MethodsIn this multicenter, retrospective study all consecutive patients with colorectal PM treated with CRS-HIPEC between 2004 and 2013 were included. The preoperative CT-scan was re-analyzed for the presence of RPLP based on the radiological appearance of enlarged lymph nodes. Outcomes were OS and DFS. Kaplan-Meier methods and Cox regression modeling were used to analyze the impact of RPLP on OS and DFS.ResultsIn 25 of 401 patients (6.1%) RPLP was observed on the preoperative CT-scan. Patient, tumor and surgical characteristics did not statistically significantly differ between groups with and without RPLP. After a median follow-up of 46 months, the one-, three- and five-year survival was 80%, 59%, 38% and 90%, 50%, 36% in the group with and without RPLP respectively. Median OS (47 vs. 35 months, logrank: p = 0.70) and median DFS (14 vs. 15 months, logrank: p = 0.81) did not statistically significantly differ between groups. In multivariable analysis, RPLP did not significantly influence survival.ConclusionEnlarged retroperitoneal lymph nodes on a pre-operative CT-scan should not automatically exclude patients from CRS-HIPEC.     

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.     

Perioperative systemic chemotherapy in peritoneal carcinomatosis of lymph node positive colorectal cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

BackgroundCytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the preferred treatment of peritoneal carcinomatosis (PC) of colorectal carcinoma. Patients with positive lymph node status have worse survival after CRS-HIPEC, which is probably due to higher rates of systemic failure. In this study, we analysed the effect of administration and timing of systemic chemotherapy on the outcome of lymph node positive colorectal carcinoma patients treated with CRS-HIPEC.Patients and MethodsA prospective database was reviewed to identify lymph node positive patients with PC treated with CRS-HIPEC within 1 year after primary tumour diagnosis between 2004 and 2012. Medical history of the patients was studied for the administration of perioperative systemic chemotherapy and follow-up. Outcome parameters were progression-free survival (PFS), overall survival (OS) and pattern of recurrence.ResultsSeventy-three patients treated with CRS-HIPEC for PC from lymph node positive colorectal carcinoma were identified. Fourteen patients received pre-CRS-HIPEC chemotherapy only, 32 patients underwent post-CRS-HIPEC chemotherapy only, 9 patients received chemotherapy both pre- and post-CRS-HIPEC and 16 patients did not receive any systemic chemotherapy. Of the 47 patients who did not receive pre-CRS-HIPEC chemotherapy, 11 (23%) did not receive any chemotherapy due to major postoperative complications. PFS and OS were significantly higher in patients who received systemic chemotherapy (PFS: median 15 versus 4 months, P = 0.024; OS: median 30 versus 14 months, P = 0.015), although this difference was attenuated after adjustment for major complications. Different chemotherapy timings did not differ significantly in either survival or recurrence patterns.ConclusionsIn patients with PC from lymph node positive colorectal carcinoma, perioperative systemic chemotherapy is associated with increased OS and PFS, although this difference may be partly explained by the occurrence of major postoperative complication; with no evidence of difference in PFS, OS and systemic recurrence rate by timing of systemic chemotherapy.     

First-line chemotherapy with pemetrexed plus cisplatin for malignant peritoneal mesothelioma

Background: Mesothelioma of peritoneal origin has wider variation in treatment outcomes than mesothelioma of pleural origin, likely because peritoneal mesothelioma comprises borderline malignant variants and aggressive malignant peritoneal mesothelioma (MPeM). This study retrospectively evaluates the efficacy of first-line systemic pemetrexed and cisplatin chemotherapy in MPeM.

Research design and methods: Twenty-four patients with histologically proven MPeM were treated with pemetrexed plus cisplatin as a first-line systemic chemotherapy. The response was evaluated radiologically according to standard Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Twenty-two patients underwent ¹⁸F-fluorodeoxyglucose positron emission tomography/(FDG-PET)/computed tomography(CT) at baseline, and 13 were eligible for metabolic assessment.

Results: Two complete responses and 9 partial responses were achieved. Overall response rate and disease control rate were 45.8% and 91.7%, respectively. Median progression-free survival and median overall survival were 11.0 months and 15.8 months, respectively. Wet- type MPeM had significantly longer survival (40.9 months median) than other clinical types (15.5 months) (P = 0.045). The baseline maximum standardized uptake value in 22 patients was 8.93 (range, 2.5–16.77).

Conclusions: Systemic pemetrexed plus cisplatin is active for MPeM. Disparity with the outcome of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) needs to receive more emphasis, since peritoneal mesothelioma has a 5-year survival rate of 50%.     

Diffuse malignant peritoneal mesothelioma: Evaluation of systemic chemotherapy with comprehensive treatment through the RENAPE Database: Multi-Institutional Retrospective Study

PurposeDiffuse malignant peritoneal mesothelioma (DMPM) is a severe disease with mainly locoregional evolution. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the reported treatment with the longest survival. The aim of this study was to evaluate the impact of perioperative systemic chemotherapy strategies on survival and postoperative outcomes in patients with DMPM treated with curative intent with CRS-HIPEC, using a multi-institutional database: the French RENAPE network.Patients and methodsFrom 1991 to 2014, 126 DMPM patients underwent CRS-HIPEC at 20 tertiary centres. The population was divided into four groups according to perioperative treatment: only neoadjuvant chemotherapy (NA), only adjuvant chemotherapy (ADJ), perioperative chemotherapy (PO) and no chemotherapy before or after CRS-HIPEC (NoC).ResultsAll groups (NA: n = 42; ADJ: n = 16; PO: n = 16; NoC: n = 48) were comparable regarding clinicopathological data and main DMPM prognostic factors. After a median follow-up of 61 months, the 5-year overall survival (OS) was 40%, 67%, 62% and 56% in NA, ADJ, PO and NoC groups, respectively (P = 0.049). Major complications occurred for 41%, 45%, 35% and 41% of patients from NA, ADJ, PO and NoC groups, respectively (P = 0.299). In multivariate analysis, NA was independently associated with worse OS (hazard ratio, 2.30; 95% confidence interval, 1.07–4.94; P = 0.033).ConclusionThis retrospective study suggests that adjuvant chemotherapy may delay recurrence and improve survival and that NA may impact negatively the survival for patients with DMPM who underwent CRS-HIPEC with curative intent. Upfront CRS and HIPEC should be considered when achievable, waiting for stronger level of scientific evidence.     

Ninety-day post-operative morbidity and mortality using the National Cancer Institute’s common terminology criteria for adverse events better describe post-operative outcome after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Background: The post-operative morbidity and mortality after CRS-HIPEC has been widely evaluated. However, there is a major discrepancy between rates reported due to different metrics and time of analysis used.

Objective: To evaluate the legitimacy of 90-day morbidity and mortality based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0 classification as criteria of quality for cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).

Methods: A prospective database of all patients undergoing CRS-HIPEC for peritoneal carcinomatosis between 2004 and 2015 was queried for 90-day morbidity and mortality and survival.

Results: Among 881 patients, the 90-day major complication rate based on NCI-CTCAE classification and Clavien-Dindo’s classification were 51% (n?=?447 patients) and 25% (n?=?222 patients), respectively. Among patients who presented with a 90-day complication based on the NCI-CTCAE classification, 50% (n?=?225 patients) presented a medical complication not reported by Clavien-Dindo’s classification. After surgery, 24 patients (2.7%) died of post-operative complications, for only 10 (42%) of them the death occurred within 30-day after surgery. Occurrence of major complication based on either NCI-CTCAE classification, Clavien-Dindo’s classification or the medical complication not reported by Clavien-Dindo’s classification all negatively impacts the overall survival.

Conclusion: Among commonly reported morbidity’s classification, 90-day morbidity based on NCI-CTCAE classification represents a legitimate metric of CRS-HIPEC quality. Post-operative morbidity after CRS-HIPEC should be reported using 90-day NCI-CTCAE classification.     

The pre-operative neutrophil–lymphocyte ratio predicts overall and disease-free survival following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with pseudomxyoma peritonei of appendiceal origin

Aim: The neutrophil–lymphocyte ratio (NLR) and other inflammation-based scores have been used as a prognostic tool to predict survival in solid tumours including pseudomyxoma peritonei (PMP). The aim was to evaluate the prognostic value of this marker and risk stratify PMP patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods: Retrospective analysis was conducted of a prospectively collected database of patients with PMP who underwent CRS and HIPEC between 1994 and 2015. The NLR was calculated by dividing the pre-operative neutrophil count by lymphocyte count. Predicted overall survival (OS) and disease-free interval (DFI) were calculated using a Kaplan–Meier survival model.

Results: The study included 699 patients, stratified into four groups as defined by their NLR. Group A: 200 (28.6%) patients (NLR?=?0.10–2.00), Group B: 160 (22.8%) patients (NLR?=?2.10–2.78), Group C: 184 (26.3%) patients (NLR?=?2.79–4.31) and Group D: 155 (22.2%) patients (NLR?≥?4.32). The median follow-up for this cohort was 36?months. The predicted DFI was 132.2, 113.1, 84.4 and 47.9?months and the OS was 141.1, 117.6, 88.7 and 51.2?months for Groups A, B, C and D, respectively. As the NLR increases, there is a reduction in long-term survival.

Conclusion: The pre-operative NLR is cost effective and has equivalent prognostic value to pre-operative tumour markers for patients with PMP treated with CRS and HIPEC. The NLR is a reliable tool that may have a role in predicting outcomes following CRS and HIPEC for patients with PMP of appendiceal origin.     

Impact of Chronic Kidney Disease and Acute Kidney Injury on Safety and Outcomes of CAR T-Cell Therapy in Lymphoma Patients

IntroductionChimeric antigen receptor T-cell (CAR-T) therapy is standard-of-care in relapse/refractory aggressive B-cell non-Hodgkin lymphoma. There are limited data regarding the impact of pre-existing chronic kidney disease (CKD) and acute kidney injury (AKI) post CAR-T and we sought to evaluate these in our patients.MethodIn this single center retrospective analysis CKD cohort was defined KDIGO staging with eGFR of <60 mL/min/1.73 m2 (Stage ...3) at the time of pre-CAR-T assessment. Remaining patients constituted the no CKD group. AKI was defined by CTCAEv.4 and data were abstracted through Day 100 post-CAR-T therapy. The primary outcome was impact of pre-existing CKD on progression-free survival (PFS), overall survival (OS) and adverse events. Additionally, we also analyzed the impact of AKI on PFS and OS.ResultsThirty-two patients were identified with 7 having pre-existing CKD. Among the patients with or without CKD, the median PFS was 8.8 and 2.9 months respectively (pvalue 0.78). The median OS was 10 and 7 months respectively (p-value 0.64). AKI developed in a total of 9 patients (29%) post CAR-T, including 7 patients without CKD at baseline. The median PFS was 3.6 and 2.8 months for patients not developing AKI and developing AKI (p-value 0.84). Median OS in similar order was 10 and 3.9 months respectively (p-value 0.2). On univariate analysis, creatinine at baseline (p-value 0.018) and ICANS grade 2+ (p-value 0.016) were associated with an increased risk of developing AKI.ConclusionsCKD or AKI after CAR-T showed no impact on post procedure OS and PFS.     

Seeing the whole picture: Added value of MRI for extraperitoneal findings in CRS-HIPEC candidates

PurposeIn colorectal cancer (CRC) patients the selection of suitable cytoreductive surgery and hyperthermic peritoneal chemotherapy (CRS-HIPEC) candidates is based on the location and extent of peritoneal metastases (PM) and presence of extraperitoneal metastases. MRI is increasingly being used to accurately assess the extent of PM, however, the significance of extraperitoneal findings in these scans has never been evaluated before.MethodsCRC patients who had undergone an additional MRI scan after standard work-up with CT for preoperative staging between January 2016–January 2020 were selected. CT and MRI reports were reviewed for new abdominopelvic extra-peritoneal findings on MRI (MR-EPF) and MR-EPFs concerning lesions previously indicated as equivocal (uncertain benign/malignant) on CT. Reference standard were surgical results or follow-up imaging.ResultsIn 158 included patients 60 MR-EPFs (in 58/158 patients) were noted: twenty-six (43%) were new findings and thirty-four (57%) were equivocal findings on CT. Of the 34 equivocal findings 27 were ‘rejected/less likely malignant’ and 7 ‘confirmed/more likely malignant’ based on MRI. In 29 patients (18%) the MR-EPFs had direct influence on treatment planning. Three patients (2%), eligible for CRS-HIPEC on CT, were deemed inoperable due to MR-EPFs.ConclusionMRI had an added value in more than a third of the patients due to abdominopelvic extraperitoneal findings that were undetected or indeterminate on CT and therefore influenced the treatment in a substantial part of the patients. Combined with the known accurate detection of peritoneal disease on MRI, MRI seems a logical addition to the diagnostic workup of potential CRS-HIPEC candidates.     

Surgery after intraperitoneal and systemic chemotherapy for gastric cancer with peritoneal metastasis or positive peritoneal cytology findings

Background

Despite recent progress in systemic chemotherapy, the prognosis of gastric cancer patients with peritoneal metastasis (P1) or positive peritoneal cytology findings (CY1) is still poor. We developed a regimen combining intraperitoneal (IP) paclitaxel (PTX) with S-1 and PTX, which can produce notable efficacy with regard to peritoneal lesions. Surgery after response to combination chemotherapy is a promising option for P1 or CY1 gastric cancer. A retrospective study was performed to evaluate the safety and efficacy.

Methods

This study enrolled 100 primary P1 or CY1 gastric cancer patients treated with IP PTX plus S-1 and PTX at the University of Tokyo Hospital between 2005 and 2011. Radical gastrectomy was performed when peritoneal cytology findings became negative, and the disappearance or obvious shrinkage of peritoneal metastasis was confirmed by laparoscopy. The same chemotherapy regimen was restarted after surgery and repeated with appropriate dose reduction.

Results

Gastrectomy was performed in 64 (P1 56, P0CY1 8) of 100 (P1 90, P0CY1 10) patients. R0 resection was achieved in 44 patients (69%). The median survival time was 30.5 months [95% confidence interval (CI) 23.6–37.7 months] from the initiation of intraperitoneal chemotherapy and 34.6 months (95% CI 26.8–39.4 months) from the diagnosis of gastric cancer. Postoperative complications included anastomotic leakage and pancreatic fistula, each in two patients, which were cured conservatively. There were no treatment-related deaths. The median survival time of the 36 patients who did not undergo surgery was 14.3 months (95% CI 10.0–17.8 months).

Conclusions

Surgery after response to intraperitoneal and systemic chemotherapy is safe and may prolong the survival of P1 and CY1 gastric cancer patients.

     

Complete cytoreductive surgery plus HIPEC for peritoneal metastases from unusual cancer sites of origin: results from a worldwide analysis issue of the Peritoneal Surface Oncology Group International (PSOGI)

Abstract

Aim: The aim of this study was to assess the outcomes of patients operated on for peritoneal metastases from unusual cancer sites of origin, meaning apart from peritoneal metastases (PM) from colorectal, gastric and epithelial ovarian carcinomas, pseudomyxoma peritonei and mesothelioma.

Patients and methods: A questionnaire concerning patients treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for PM arising from unusual cancer sites of origin was sent to all centres, which routinely performed HIPEC, through the Peritoneal Surface Oncology Group International and the RENAPE network.

Results: Between September 1990 and June 2016, 850 procedures for unusual cases were performed in 781 patients, in 53 centres worldwide. Nearly two-thirds of the procedures were performed for three indications: rare ovarian carcinoma (n?=?224), sarcoma (n?=?189) and neuroendocrine tumours (n?=?127). The median PCI was 12 [0–39]. Grade III–IV postoperative complications occurred in 272 patients (41%). Nineteen patients (2.9%) died postoperatively. After a median follow-up of 46?months, median overall survival (OS) was 39?months [33.18–44.05]. Five-year OS rate was 38.7%. For the three main indications, 5-year OS was significantly greater in patients with PM from rare ovarian carcinoma (57.7%), than that of patients with PM from neuroendocrine tumours (39.9%), and from sarcoma (29.3%) (p?<?0.0001).

Conclusions: CRS and HIPEC appear to be safe and effective in patients with peritoneal metastases from unusual cancer sites of origin, especially from rare ovarian carcinomas, PM from neuroendocrine tumours. The respective roles of CRS and HIPEC remain unclear and should be evaluated.     

Residual tumour less than 0.25 centimetres and positive lymph nodes are risk factors for early relapse in recurrent ovarian peritoneal carcinomatosis treated with cytoreductive surgery,HIPEC and systemic chemotherapy

Aim: The cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has showed promising results for the survival in patients with recurrent ovarian carcinomatosis, however, some of them will recur within the first year. The aim of this study is focussed on identifying the risk factors to develop the recurrence within the first year after an optimal CRS-HIPEC in patients with recurrent ovarian carcinomatosis.

Methods: A total of 100 patients with peritoneal carcinomatosis from recurrent ovarian cancer treated by CRS?+?HIPEC were selected for analysis. Multivariate logistic regression analysis was performed to evaluate the relationship between the variables and the early recurrence.

Results: The mean follow-up was 42.5 months. The mean age was 56.2 years. Early recurrence was observed in the 36%. The group early recurrence presented a higher rate of optimal cytoreductions CC1 (16.2% vs. 3.5%), lymph nodes (32.5% vs. 15%) and the use of hemoderivates (40.5% vs. 33%). Others parameters as Peritoneal Cancer Index, major morbidity? 3, re-operations rate and time to adjuvant chemotherapy were similar in both groups. The five years OS was 58%, for the non-early recurrence was higher than the early recurrence group (64% vs. 41%). In the multivariate analysis, CC-1 (OR 5.73; 1.16–32.04) and positive lymph nodes (OR 2.26; 1.01–4.32) proved to be independent factors for the early recurrence.

Conclusion: The combination of both (CC1 and positive lymph nodes) makes that the indication of CRS and HIPEC should be individualised. However, the major morbidity, stage IV and the time to the adjuvant treatment were not associated with an early recurrence, so that, a major aggressiveness is recommended to achieve a CC0.     

Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Versus Surgery Without HIPEC for Goblet-Cell Carcinoids and Mixed Adenoneuroendocrine Carcinomas: Propensity Score–Matched Analysis of Centers in the Netherlands and Belgium

BackgroundThe value of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneally metastasized goblet-cell carcinoids (GCCs) and mixed adenoneuroendocrine carcinomas (MANECs) is currently unclear. We compared outcomes of CRS-HIPEC to surgery alone for peritoneally metastasized GCCs and MANECs.Patients and MethodsTwo cohorts were obtained from the Netherlands Cancer Registry (n = 569): patients with peritoneally metastasized GCCs and MANECs treated with CRS-HIPEC in Dutch and Belgian centers (n = 45), and patients treated with surgery alone. Primary outcome was overall survival (OS). Secondary outcomes were morbidity and hospital mortality. After propensity score matching, OS was compared in univariate and multivariate analyses. A systematic literature review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines from database inception to June 25, 2018.ResultsAfter matching for sex, tumor stage, lymph node stage, and liver metastases, CRS-HIPEC was associated with improved median OS in the combined GCC and MANEC group and the separate GCC subgroup in univariate (GCC + MANEC: 39 vs. 12 months, P < .001; GCC: 39 vs. 12 months, P = .017) and multivariate analysis (GCC + MANEC: hazard ratio 4.27, 95% confidence interval 1.88-9.66, P = .001; GCC: hazard ratio 2.77, 95% confidence interval 1.06-7.26, P = .038). Acceptable grade III-IV morbidity (17.5%) and mortality (0) were seen after CRS-HIPEC. The literature review supported these findings.ConclusionCRS-HIPEC is associated with substantial survival benefit in patients with peritoneally metastasized GCCs and MANECs compared to surgery alone and is a safe treatment option. These data support centralized care of GCC and MANEC patients with peritoneal spread in expert centers offering CRS-HIPEC.     

Risk Factors for Acute Kidney Injury During High-dose Chemotherapy and Outcomes for Patients With Relapsed Germ Cell Tumors

BackgroundPatients with relapsed germ cell tumors (GCTs) can be cured with salvage chemotherapy. We evaluated the risk factors and outcomes of patients who had developed acute kidney injury (AKI) during high-dose chemotherapy (HDCT) for relapsed GCT.Patients and MethodsAll patients were scheduled to receive 2 consecutive courses of HDCT per our standard protocol. The characteristics and outcomes of the patients with stage ≥ 3 AKI were analyzed and compared with those without stage ≥ 3 AKI.ResultsOf 462 patients, 21 (4.5%) developed stage ≥ 3 AKI. Of these 21 patients, 18 had required hemodialysis during HDCT and 6 had died during HDCT. Of the 15 patients who had survived HDCT, 10 experienced recovery of renal function to baseline. AKI had occurred in the first cycle of HDCT in 18 patients. These patients were also more likely to have received HDCT in a third-line setting or further, to have Eastern Cooperative Oncology Group performance status of 1 or 2, and to have experienced gastrointestinal, hepatic, pulmonary, and infectious grade ≥ 3 toxicities. At a median follow-up of 10 months after HDCT, 5 patients had no evidence of disease, 3 were alive with disease, 6 had died of disease, 6 had died of complications from HDCT, and 1 had been lost to follow-up.ConclusionsIrreversible AKI during HDCT for relapsed GCT is uncommon but is associated with greater rates of infectious, gastrointestinal, hepatic, and pulmonary complications and treatment-related death. These patients were also more heavily pretreated and had a lower baseline performance status. However, most surviving patients had recovered their renal function and 5 of 21 were alive with no evidence of disease.     

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis from colorectal cancer: The prognostic impact of baseline neutrophil-lymphocyte,platelet-lymphocyte and lymphocyte-monocyte ratios

PurposeIn this retrospective analysis we sought to determine if the preoperative neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR) were predictive of both operability and survival in those patients presenting with peritoneal carcinomatosis (PC) from colorectal cancer (CRC) who underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).MethodsAnalysis included all patients admitted between 2009 and 2017 with PC from CRC who were treated with curative intent by CRS-Mitomycin C-HIPEC. Patients were assessed pre- and intra-operatively by the PC index (PCI) and by a completeness of cytoreduction (CC) score with calculation of Kaplan-Meier survival curves and multivariate analysis of prognostic factors. Discrimination was made for NLR >3.5, PLR >168.8 and LMR >4.4.ResultsWe identified 98 CRC patients undergoing 105 CRS-HIPEC procedures. There were no associations detected between NLR/PLR/LMR and the rates of incomplete or abandoned CRS cases. Overall survival (OS) after CRS-HIPEC was worse with high versus low NLR (19.9 mths vs. 45.7 mths, respectively; P = 0.009) and also with low versus high LMR (27.1 mths vs. 53.2 mths, respectively; P = 0.01). On multivariate analysis, a low LMR (P = 0.008), the preoperative CT PCI value (P = 0.004), poor tumor differentiation (P = 0.023) and the preoperative CEA level (P < 0.001) were all independent variables associated with a worse OS after surgery.ConclusionsThe baseline LMR value may have potential value as a selection tool for CRS-HIPEC in patients with CRC-related PC.     

Treatment of peritoneal metastases from small bowel adenocarcinoma

Abstract

Background/purpose: Peritoneal metastases (PM) affect approximately one third of patients with metastatic small bowel adenocarcinoma (SBA). Treatment options are (1) systemic therapy?±?palliative surgery and (2) cytoreductive surgery with intraperitoneal chemotherapy (CRS?+?IPC). Due to scarce evidence, PM from SBA represents a therapeutic challenge. This narrative review summarised and discussed the evidence that investigated available treatment options.

Methods: Studies were discussed if they investigated first line systemic therapy for advanced SBA or CRS?+?IPC for PM from SBA. Extracted outcomes were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), disease-free survival (DFS), overall survival (OS), and grade III–V toxicity/morbidity.

Results: Eighteen studies (15 observational, 3 phase II) that investigated systemic therapy and six observational studies that investigated CRS?+?IPC were reviewed. In studies that investigated systemic therapy, ORR, DCR, median PFS, median OS, and grade III–V toxicity ranged from 6% to 50%, 50% to 90%, 3 to 11 months, 8 to 20 months, and 10% to 68%, respectively. Fluoropyrimidine–oxaliplatin revealed favourable survival outcomes compared to fluoropyrimidine–irinotecan, fluoropyrimidine–cisplatin, fluoropyrimidine monotherapy, and other regimens. In studies that investigated CRS?+?IPC, median DFS, median OS, and grade III–V morbidity ranged from 10 to 12 months, 16 to 47 months, and 12% to 35%, respectively.

Conclusion: Based on available evidence, fluoropyrimidine–oxaliplatin should be regarded as optimal first line systemic treatment. In selected patients, CRS?+?IPC appears safe and may be more effective than systemic therapy as single treatment. Future studies should evaluate survival and morbidity of CRS?+?IPC in larger cohorts, as well as the value of chemotherapy with targeted agents in metastatic SBA with subgroup analysis for PM from SBA.     

Treatment of ovarian metastases of colorectal and appendiceal carcinoma in the era of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Aim

To compare outcome of women with ovarian metastasis who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) to outcome of women without ovarian metastasis who underwent CRS-HIPEC.

Methods

A prospective CRS-HIPEC database was searched to identify women with surgically treated colorectal carcinoma between 2000 and 2012. Patients with ovarian metastasis were identified and patients with peritoneal carcinomatosis but without ovarian metastasis were included as control cases.

Results

75 patients with macroscopic ovarian metastasis underwent CRS-HIPEC with curative intent, while 50 female patients without ovarian metastasis were identified who underwent CRS-HIPEC. Patients with ovarian metastasis more often had a primary appendiceal tumour and had a more extensive intra-abdominal tumour load compared to patients without ovarian metastases. Median follow-up time was 45 months (95% confidence interval (CI): 37–53 months). Overall survival (OS) did not differ significantly between the two groups with a median OS in the ovarian metastasis group of 40 months (95% CI 26–54) compared to 64 months (95% CI 17–111, P = 0.478) in the non-ovarian metastasis group. Recurrence patterns did not differ significantly between groups (p = 0.183).

Conclusions

Patients with ovarian metastasis of colorectal and appendiceal origin who underwent CRS-HIPEC had similar outcome compared to patients without ovarian metastasis. Given the findings of high coincidence of peritoneal metastases with ovarian metastases and ovarian metastases not being an independent factor for survival after CRS-HIPEC, this procedure should be recommended for patients with peritoneal metastases and ovarian metastases of colorectal and appendiceal carcinoma.