Introduction
The peritoneum is a predilection site for gastric cancer metastases. Current standard treatment for gastric cancer patients with synchronous peritoneal metastases is palliative systemic ...therapy. However, its efficacy is largely unknown. The aim of this study was to investigate the incidence, treatment and survival patterns of gastric cancer patients with synchronous peritoneal metastases in the Netherlands.
Methods
All newly diagnosed gastric adenocarcinoma patients with synchronous peritoneal metastases between 1999 and 2017 were selected from the Netherlands Cancer Registry (NCR). Incidence, treatment and survival patterns were analyzed.
Results
In total, 3,773 patients were identified from the NCR. The incidence of synchronous peritoneal metastases in gastric cancer patients increased from 18% in 2008 to 27% in 2017. The use of systemic therapy increased from 15% in 1999–2002 to 43% in 2013–2017 (
p
< 0.001). The median survival of the entire cohort did not significantly increase over time. Median survival of patients treated with systemic therapy increased from 7.4 months in 1999–2002 to 9.4 months in 2013–2017 (
p
= 0.005). In contrast, median survival of patients
not
treated with systemic therapy decreased from 3.3 months in 1999–2002 to 2.1 months in 2013–2017 (
p
< 0.001). Some clinical and pathological data such as the extent of the peritoneal metastases were not available.
Conclusion
Synchronous peritoneal metastases are increasingly diagnosed in gastric cancer patients. In recent years, more patients were treated with systemic treatment and survival of these patients increased. However, as survival of the entire group did not improve over time, the effect of systemic therapy remains unknown.
Oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (PIPAC-OX) is an emerging palliative treatment for patients with unresectable colorectal peritoneal metastases. Previously, our ...study group reported that patients experienced abdominal pain for several weeks after PIPAC-OX. However, it is unknown how this compares to abdominal pain after regular colorectal cancer surgery. To provide some perspective, this study compared the presence of abdominal pain after PIPAC-OX to the presence of abdominal pain after primary tumor surgery. Patient reported abdominal pain scores (EORTC QLQ-CR-29), from two prospective, Dutch cohorts were used in this study. Scores ranged from 0 to 100, a higher score represents more abdominal pain. Abdominal pain at baseline and at four weeks after treatment were compared between the two groups. Twenty patients who underwent PIPAC-OX and 322 patients who underwent primary tumor surgery were included in the analysis. At baseline, there were no differences in abdominal pain between both groups (mean 20 vs. 18, respectively; p = 0.688). Four weeks after treatment, abdominal pain was significantly worse in the PIPAC group (39 vs 15, respectively; p < 0.001; Cohen's d = 0.99). The differential effect over time for abdominal pain differed significantly between both groups (mean difference: 19 vs - 3, respectively; p = 0.004; Cohen's d = 0.88). PIPAC-OX resulted in significantly worse postoperative abdominal pain than primary tumor surgery. These results can be used for patient counseling and stress the need for adequate analgesia during and after PIPAC-OX. Further research is required to prevent or reduce abdominal pain after PIPAC-OX.Trial registration CRC-PIPAC: Clinicaltrails.gov NCT03246321 (01-10-2017).
The peritoneum is a common metastatic site in gastric cancer. This systematic review provides an overview of the incidence, risk factors and survival of synchronous peritoneal metastases from gastric ...cancer. A systematic search was performed to identify studies wherein the incidence, risk factors and survival of gastric cancer with peritoneal metastases were investigated. Of all 38 potentially eligible studies, 17 studies were included based on the eligibility criteria. The incidence of synchronous gastric peritoneal metastases was reviewed for population-based studies (10–21%), for observational cohort studies (2–15%) and for surgical cohort studies (13–40%). Potential risk factors for synchronous gastric peritoneal metastases were younger age, non-cardia gastric cancer, female sex, signet ring cell carcinoma, diffuse type histology or linitis plastica, T4 stage, Hispanic ethnicity and more than one metastatic location. Synchronous peritoneal metastases are commonly diagnosed in patients with gastric cancer with an incidence up to 21% in recent population-based studies. Furthermore, prognosis of patients with gastric peritoneal metastases is poor with median overall survival ranging from 2 to 9 months. The high incidence and poor prognosis require intensive research on diagnostic features and effective treatment options to improve survival.
Background
Despite its increasing use, pressurized intraperitoneal aerosol chemotherapy with oxaliplatin (PIPAC-OX) has never been prospectively investigated as a palliative monotherapy for ...colorectal peritoneal metastases in clinical trials. This trial aimed to assess the safety (primary aim) and antitumor activity (key secondary aim) of PIPAC-OX monotherapy in patients with unresectable colorectal peritoneal metastases.
Methods
In this two-center, single-arm, phase II trial, patients with isolated unresectable colorectal peritoneal metastases in any line of palliative treatment underwent 6-weekly PIPAC-OX (92 mg/m
2
). Key outcomes were major treatment-related adverse events (primary outcome), minor treatment-related adverse events, hospital stay, tumor response (radiological, biochemical, pathological, ascites), progression-free survival, and overall survival.
Results
Twenty enrolled patients underwent 59 (median 3, range 1–6) PIPAC-OX procedures. Major treatment-related adverse events occurred in 3 of 20 (15%) patients after 5 of 59 (8%) procedures (abdominal pain, intraperitoneal hemorrhage, iatrogenic pneumothorax, transient liver toxicity), including one possibly treatment-related death (sepsis of unknown origin). Minor treatment-related adverse events occurred in all patients after 57 of 59 (97%) procedures, the most common being abdominal pain (all patients after 88% of procedures) and nausea (65% of patients after 39% of procedures). Median hospital stay was 1 day (range 0–3). Response rates were 0% (radiological), 50% (biochemical), 56% (pathological), and 56% (ascites). Median progression-free and overall survival were 3.5 months (interquartile range IQR 2.5–5.7) and 8.0 months (IQR 6.3–12.6), respectively.
Conclusions
In patients with unresectable colorectal peritoneal metastases undergoing PIPAC-OX monotherapy, some major adverse events occurred and minor adverse events were common. The clinical relevance of observed biochemical, pathological, and ascites responses remains to be determined, especially since radiological response was absent.
Background Obesity is a major global health problem and an important risk factor for colorectal cancer (CRC) is increased body weight. Obesity plays a role in the peritoneal dissemination of cancer; ...however, it is unclear whether this also applies for peritoneal dissemination of CRC. The purpose of this study was to provide insight in the role of obesity on the peritoneal dissemination of colorectal cancer. Methods Of all patients diagnosed with CRC in the Netherlands in the first half of 2015, follow-up data was completed in 2019. Weight at time of primary diagnosis was categorized as underweight, normal weight, overweight, or obese. Logistic regression modelling was used to assess the association between weight and the presence of synchronous colorectal peritoneal metastases (CPM), and Cox regression modelling was used to assess the association between weight and metachronous CPM. Patient and tumor characteristics were taken into account. The analyses were adjusted for tumor stage, nodal stage, tumor location, and tumor histology. Results In total, 6436 patients were included in this study. Two-hundred ninety-three (4.6%) patients presented with synchronous CPM at the time of primary diagnosis, while another 278 (5.1%) patients developed metachronous CPM after a median time of 16.5 months. Univariable and multivariable logistic regression modelling did not identify an effect of weight on the presence of synchronous CPM. Neither underweight (odds ratio OR 1.10, 95% CI 0.48-2.54), nor overweight (OR 0.96, 95% CI 0.71-1.29), or obesity (OR 0.84, 95% CI 0.56-1.26) was either positively or negatively associated with the presence of synchronous peritoneal metastases as compared to normal weight. Univariable and multivariable Cox regression modelling did not identify an effect of weight on the development of metachronous CPM. Neither underweight (HR 0.162, 95% CI 0.02-1.16), nor overweight (HR 1.07, 95% CI 0.82-1.39), or obesity (HR 1.02, 95% CI 0.73-1.16) was either positively or negatively associated with the presence of synchronous peritoneal metastases as compared to normal weight. Conclusion CRC patients who are overweight or obese are not more at risk for the presence of synchronous CPM nor development of metachronous CPM than their normal-weight counterparts. Keywords: Colorectal neoplasms, Peritoneal metastases, Body mass index (BMI), Weight, Colorectal cancer, Risk factors
Background
Electrostatic pressurized intraperitoneal aerosol chemotherapy (ePIPAC) is a palliative treatment for unresectable peritoneal metastases from various primary cancers. However, little is ...known about the systemic pharmacokinetics of oxaliplatin after ePIPAC.
Methods
Twenty patients with unresectable colorectal peritoneal metastases were treated with repetitive ePIPAC monotherapy with oxaliplatin (92 mg/m
2
) and a simultaneous intravenous bolus of leucovorin (20 mg/m
2
) and 5-fluorouracil (400 mg/m
2
). Samples were collected during each ePIPAC: whole blood at
t
= 0,
t
= 5,
t
= 10,
t
= 20,
t
= 30,
t
= 60,
t
= 120,
t
= 240,
t
= 360 and
t
= 1080 min for plasma and plasma ultrafiltrate concentrations; urine at
t
= 0,
t
= 1,
t
= 3,
t
= 5 and
t
= 7 days. Samples were analyzed using atomic absorption spectrometry. Pharmacokinetics were analyzed using nonlinear mixed-effects modeling.
Results
Four patients received one ePIPAC, three patients received two ePIPAC, and thirteen patients received ≥ 3 ePIPAC. The population pharmacokinetic models adequately described the pharmacokinetics of oxaliplatin after ePIPAC. The plasma ultrafiltrate
C
max
of oxaliplatin reached 1.36–1.90 µg/mL after 30 min with an AUC
0–24 h
of 9.6–11.7 µg/mL * h. The plasma
C
max
reached 2.67–3.28 µg/mL after 90 min with an AUC
0–24 h
of 49.0–59.5 µg/mL * h. The absorption rate constant (Ka) was 1.13/h. Urine concentrations of oxaliplatin rapidly decreased to less than 3.60 µg/mL in 90% of the samples at day 7.
Discussion
Systemic exposure to oxaliplatin after ePIPAC seemed comparable to that after systemic chemotherapy, as described in other literature. Since this is an indirect comparison, future research should focus on the direct comparison between the systemic exposure to oxaliplatin after ePIPAC and after systemic chemotherapy.
Trial registration:
NCT03246321, Pre-results; ISRCTN89947480, Pre-results; NTR6603, Pre-results; EudraCT: 2017-000927-29, Pre-results.
Background
This study aimed to assess the impact of open or laparoscopic resection of primary colorectal cancer (CRC) on the development of metachronous colorectal peritoneal metastases (CPM) in a ...population-based cohort.
Materials and methods
This was a retrospective, population-based study of CRC patients who underwent open or laparoscopic resection of the primary tumour in the Netherlands between January 1st and June 30th 2015. Patients with synchronous metastases were excluded. CPM were considered metachronous if diagnosed ≥ 90 days after resection of primary CRC. Multivariable cox regression analysis was performed to correct for tumour location, histology, differentiation, and stage, nodal stage, tumour perforation, primary surgery type, and unclear resection margins.
Results
In total, 1516 CRC patients underwent open resection and 3236 CRC patients underwent laparoscopic resection, with a 3-year cumulative incidence of metachronous CPM of 7.3% and 3.7%, respectively (
p
< 0.001), after median follow-up of 42 months. Open surgical approach was significantly associated with the development of metachronous CPM: HR 1.4 95%CI 1.1–1.8. Other prognostic factors were mucinous adenocarcinoma histology (HR 1.6, 95%CI 1.0–2.5), T4 stage (HR 3.2, 95%CI 2.3–4.5), N1 stage (HR 2.9, 95%CI 2.1–4.0), and N2 stage (HR 4.2, 95%CI 2.9–6.1).
Conclusions
Patients treated with open resection had a significantly higher risk to develop metachronous CPM than patients treated with laparoscopic resection. The mechanisms underlying this phenomenon remain unknown but might be related to differences in per-operative specimen handling, tumour spill, surgical trauma and pro-inflammatory response. This finding might imply the need for a personalized follow-up after primary resection of CRC.
The PRODIGE 7-trial investigated the additional value of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to cytoreductive surgery (CRS) for patients with colorectal peritoneal metastases (CPM). The ...results of PRODIGE 7 were presented at the 2018 ASCO meeting showing that 30 min oxaliplatin-based HIPEC did not improve overall survival. The current study investigated the impact of PRODIGE 7 on the worldwide practice of CRS and HIPEC.
CRS-HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning the current CRS-HIPEC practice in their hospital and country, and were asked to appraise the effect of PRODIGE 7.
The survey was completed by 18/19 experts. Although their personal opinions of CRS-HIPEC were barely influenced by PRODIGE 7, they reported a substantial impact on daily practice. This included a switch towards Mitomycin-C based HIPEC-regimens and prolongation of HIPEC perfusion time, a reduction in the number of referrals from non-HIPEC centers, a reduction in national consensus, the removal of HIPEC from national guidelines, and a reduced reimbursement rate.
The PRODIGE 7 has had a major impact on the practice of CRS-HIPEC for CPM worldwide. HIPEC remains an attractive option with potential for control and eradication of disease and further studies into the optimal HIPEC-regimen are urgently needed. Meanwhile, given the complexity of the treatment of patients with CPM, and the proven benefits of optimal CRS, referral of patients with potentially resectable CPM to expert centers is recommended whilst the precise role of HIPEC is further evaluated.
PDF
