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Cancers Jan 2023As colorectal cancer (CRC) patients with peritoneal metastases (PM) have a poor prognosis, new treatment options are currently being investigated for CRC patients.... (Review)
Review
BACKGROUND
As colorectal cancer (CRC) patients with peritoneal metastases (PM) have a poor prognosis, new treatment options are currently being investigated for CRC patients. Specific biomarkers in the primary tumor could serve as a prediction tool to estimate the risk of distant metastatic spread. This would help identify patients eligible for early treatment.
AIM
To give an overview of previously studied DNA and RNA alterations in the primary tumor correlated to colorectal PM and investigate which gene mutations should be further studied.
METHODS
A systematic review of all published studies reporting genomic analyses on the primary tissue of CRC tumors in relation to PM was undertaken according to PRISMA guidelines.
RESULTS
Overall, 32 studies with 18,906 patients were included. mutations were analyzed in 17 articles, of which 10 found a significant association with PM. For all other reported genes, no association with PM was found. Two analyses with broader cancer panels did not reveal any new biomarkers.
CONCLUSION
An association of specific biomarkers in the primary tumors of CRC patients with metastatic spread into peritoneum could not be proven. The role of mutations should be further investigated. In addition, studies searching for potential novel biomarkers are still required.
PubMed: 36672497
DOI: 10.3390/cancers15020549 -
Pleura and Peritoneum Dec 2016Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly used to prevent or treat peritoneal metastases (PM) in... (Review)
Review
Randomized controlled trials evaluating cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in prevention and therapy of peritoneal metastasis: a systematic review.
BACKGROUND
Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly used to prevent or treat peritoneal metastases (PM) in selected indications. The objective of this article was to review published, recruiting or planned randomized controlled trials (RCTs) evaluating CRS and HIPEC versus standard of care. Comparator was systemic chemotherapy and/or CRS alone.
CONTENT
Systematic review according to PRISMA guidelines. Electronic searches for published RCT using PubMed (from 1980 to November 2016) and for ongoing RCT in the United States and European clinical databases (until November 2016). Current update on ongoing trials from the 10th PSOGI meeting in November 2016 in Washington DC. Fourteen RCTs on CRS and HIPEC were excluded for various reasons.
SUMMARY
Thirty-eight trials designed for randomizing 7,303 patients were identified: 11 in colorectal cancer (6 for prevention of PM, n=1,107 patients; 5 for therapy, n=781), 10 in ovarian cancer (5 in frontline therapy, n=438 patients; 5 for treating recurrence, n=1,062) and 17 in gastric cancer (14 for prevention of PM, n=3,659 patients; 3 for therapy, n=256). Results of 9 RCTs have been published: 1 in colorectal cancer (105 patients), 1 in ovarian cancer (130 patients) and 7 in gastric cancer (together 669 patients). Five RCTs have completed recruitment and follow-up is ongoing. There is a clear trend in recent trial design from therapeutic to preventive indications.
OUTLOOK
The number of published RCT evaluating CRS and HIPEC in prevention or therapy of PM is relatively small. There is some evidence that CRS and HIPEC improve survival in recurrent colorectal origin, evidence in ovarian and gastric cancer remains debated. A large number of studies is ongoing that might deliver additional evidence. Trial design and interpretation of results remain difficult because of multiple methodological challenges.
PubMed: 30911621
DOI: 10.1515/pp-2016-0027 -
Clinical & Experimental Metastasis Aug 2022For peritoneal metastases (PM), there are few curative treatment options, and they are only available for a select patient group. Recently, new therapies have been... (Review)
Review
For peritoneal metastases (PM), there are few curative treatment options, and they are only available for a select patient group. Recently, new therapies have been developed to deliver intraperitoneal chemotherapy for a prolonged period, suitable for a larger patient group. These drug delivery systems (DDSs) seem promising in the experimental setting. Many types of DDSs have been explored in a variety of animal models, using different cytostatics. This review aimed to provide an overview of animal studies using DDSs containing cytostatics for the treatment of gastro-intestinal PM and identify the most promising therapeutic combinations. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) guidelines. The 35 studies included revealed similar results: using a cytostatic-loaded DDS to treat PM resulted in a higher median survival time (MST) and a lower intraperitoneal tumor load compared to no treatment or treatment with a 'free' cytostatic or an unloaded DDS. In 65% of the studies, the MST was significantly longer and in 24% the tumor load was significantly lower in the animals treated with cytostatic-loaded DDS. The large variety of experimental setups made it impossible to identify the most promising DDS-cytostatic combination. In most studies, the risk of bias was unclear due to poor reporting. Future studies should focus more on improving the clinical relevance of the experiments, standardizing the experimental study setup, and improving their methodological quality and reporting.
Topics: Animals; Cytostatic Agents; Drug Delivery Systems; Gastrointestinal Neoplasms; Peritoneal Neoplasms; Peritoneum
PubMed: 35737252
DOI: 10.1007/s10585-022-10173-8 -
Current Oncology (Toronto, Ont.) Jul 2023Cytoreductive surgery (CRS) represents the cornerstone of surgical management for peritoneal carcinomatosis (PC) and involves peritonectomy procedures aimed at complete... (Review)
Review
Cytoreductive surgery (CRS) represents the cornerstone of surgical management for peritoneal carcinomatosis (PC) and involves peritonectomy procedures aimed at complete peritoneal tumour resection. Frequently, CRS is combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The combination of CRS + HIPEC is now considered the standard of care in patients with colorectal and ovarian PC. However, the role of this multi-modality treatment approach in patients with PC of neuroendocrine tumour origin (NET-PC) is less well understood. This systematic review provides a summary of available evidence on management strategies for patients with NET-PC. A systematic literature search was performed using Ovid Medline, EMBASE and Cochrane Library databases to identify studies reporting outcomes for patients with NET-PC undergoing surgical treatment. Eligible studies were assessed for methodological quality and design and evaluated for a method of surgical treatment, method of HIPEC delivery, oncological outcomes, and treatment-related morbidity. Eight studies, including a total of 1240 patients with NET-PC, met predefined inclusion criteria and have been included in this review. In three of the included studies, CRS alone was performed for patients with NET-PC, while five studies reported outcomes with combined treatment using CRS plus HIPEC. All studies were performed at tertiary peritoneal malignancy centres. Only one study directly compared outcomes in patients with NET-PC undergoing CRS plus HIPEC compared with CRS in isolation, with no significant difference in overall survival reported. Carefully selected patients with NET-PC may benefit from aggressive surgical treatment in the form of CRS +/- HIPEC. These procedures are best undertaken at centres with expertise in the management of both neuroendocrine tumours and peritoneal malignancy, as both are conditions that require tertiary-level care. The additional benefit of the HIPEC component in this group of patients remains unclear and warrants further investigation in clinical trials. Overall, the quality of data on this subject is restricted by the low number of studies and the variability in treatment methods employed. A multi-national data registry for patients with NET-PC may offer the opportunity to better define treatment algorithms. Translational research efforts in parallel should focus on developing a better biological understanding of NET-PC, with a view to identifying more effective intraperitoneal cytocidal agents.
Topics: Humans; Peritoneal Neoplasms; Hyperthermia, Induced; Combined Modality Therapy; Antineoplastic Combined Chemotherapy Protocols; Hyperthermic Intraperitoneal Chemotherapy
PubMed: 37504326
DOI: 10.3390/curroncol30070466 -
International Journal of Molecular... Feb 2022Mesothelioma is a rare tumor, frequently associated with asbestos exposure, arising from pleura and peritoneum. Traditionally, diagnosis and treatment have been...
Mesothelioma is a rare tumor, frequently associated with asbestos exposure, arising from pleura and peritoneum. Traditionally, diagnosis and treatment have been difficult in a clinical setting. The treatment is based on a trimodal approach involving surgery, chemotherapy, and radiotherapy. The introduction of chemotherapy improved the overall survival. However, the regimen of pemetrexed/cisplatin doublet has not been changed as a standard treatment since 2004. Novel combinations of ipilimumab and nivolumab have only been approved for clinical use in late 2020. The aim of this review was to systematically summarize findings on novel treatment options in mesothelioma. We searched available medical databases online, such as PubMed and Clinicaltrials.gov, to systematically review the literature on novel approaches in immunotherapy, vaccines, and Chimeric Antigen Receptor (CAR)-T cell therapy in mesothelioma. We manually screened 1127 articles on PubMed and 450 trials on ClinicalTrials.gov, and 24 papers and 12 clinical trials published in the last ten years were included in this review. Immunotherapy that was swiftly introduced to treat other thoracic malignancies was slow to reach desirable survival endpoints in mesothelioma, possibly due to limited patient numbers. Novel treatment approaches, such as CAR-T cell therapy, are being investigated. As the incidence of mesothelioma is still rising globally, novel treatment options based on a better understanding of the tumor microenvironment and the genetic drivers that modulate it are needed to support future precision-based therapies.
Topics: Animals; Cell- and Tissue-Based Therapy; Clinical Trials as Topic; Humans; Immunotherapy; Mesothelioma; Receptors, Chimeric Antigen; T-Lymphocytes; Tumor Microenvironment
PubMed: 35216091
DOI: 10.3390/ijms23041975 -
Pleura and Peritoneum Jun 2023Pressurized intraperitoneal aerosol chemotherapy (PIPAC) gives encouraging results in the treatment of peritoneal metastasis (PM). The current recommendations require at... (Review)
Review
OBJECTIVES
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) gives encouraging results in the treatment of peritoneal metastasis (PM). The current recommendations require at least 3 sessions of PIPAC. However, some patients do not complete the full treatment course and stop after only 1 or 2 procedures, hence the limited benefit. A literature review was performed, with search terms including "PIPAC" and "pressurised intraperitoneal aerosol chemotherapy."
CONTENT
Only articles describing the causes for premature termination of the PIPAC treatment were analysed. The systematic search identified 26 published clinical articles related to PIPAC and reporting causes for stopping PIPAC.
SUMMARY
The series range from 11 to 144 patients, with a total of 1352 patients treated with PIPAC for various tumours. A total of 3088 PIPAC treatments were performed. The median number of PIPAC treatments per patient was 2.1, the median PCI score at the time of the first PIPAC was 19 and the number of patients who did not complete the recommended 3 sessions of PIPAC was 714 (52.8%). Disease progression was the main reason for early termination of the PIPAC treatment (49.1%). The other causes were death, patients' wishes, adverse events, conversion to curative cytoreductive surgery and other medical reasons (embolism, pulmonary infection, etc…).
OUTLOOK
Further investigations are necessary to better understand the causes for interrupting PIPAC treatment and also improving the selection of patients who are most likely to benefit from PIPAC.
PubMed: 37304159
DOI: 10.1515/pp-2023-0004 -
Pleura and Peritoneum Sep 2019Early postoperative intraperitoneal chemotherapy (EPIC) can be used in combination with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)... (Review)
Review
BACKGROUND
Early postoperative intraperitoneal chemotherapy (EPIC) can be used in combination with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) to treat patients with peritoneal carcinomatosis (PC) of multiple origins. The present study is a systematic review to evaluate the role of EPIC after CRS + HIPEC for appendiceal and colorectal cancers with PC.
CONTENT
We conducted a systematic search in PubMed according to the PRISMA guidelines and included all studies published before June 27 of 2019 comparing EPIC to HIPEC or the combination of both. Our search found 79 articles. After excluding non-relevant articles, a total of 13 retrospective clinical studies reporting on the efficacy and safety of EPIC compared to HIPEC or as a combination therapy for lower gastrointestinal neoplasms were analyzed. Initial EPIC reports led to its declined usage because of concerns with increased postoperative morbidity and uncertain added benefit on survival. Recent retrospective studies have been promising, showing significant improvements in OS and fewer issues with complications when adding EPIC to CRS + HIPEC.
CONCLUSIONS
Current evidence is entirely retrospective and is conflicting. It is hoped that ongoing clinical trials and additional studies will clarify EPIC's role in the treatment of patients with PC.
PubMed: 31667329
DOI: 10.1515/pp-2019-0007 -
Pleura and Peritoneum Jun 2022Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has recently emerged as a palliative alternative for patients with unresectable peritoneal metastasis (PM).... (Review)
Review
BACKGROUND
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has recently emerged as a palliative alternative for patients with unresectable peritoneal metastasis (PM). Quality of life (QoL) has increasingly been used as an endpoint to evaluate treatment outcomes. This review aims to identify evidence on how PIPAC would impact the QoL of PM patients.
CONTENT
A systematic review was performed on articles identified from Medline, EMBASE, PsycInfo, and Web of Sciences. A meta-analysis was conducted on further selected studies. ACROBAT-NRSI was attempted to assess the risk of bias (RoB).
SUMMARY
Nine studies using the EORTC QLQ-C30 questionnaire to assess QoL after repeated PIPAC cycles were identified. Majority was found to be moderately biased and a great extent of heterogeneity was observed. Four studies on PM from either gastric cancer (GC) or epithelial ovarian cancer (EOC) were included for meta-analysis. In 31 GC patients and 104 EOC patients, QoL remained stable in 13/14 and 11/14 EORTC QLQ-C30 scales. PIPAC was inferior to cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in global QoL and functioning but superior in symptom reduction.
OUTLOOK
PIPAC is a well-tolerated option for most GC and EOC patients with irresectable PM. Future trials are warranted to confirm the findings.
PubMed: 35812010
DOI: 10.1515/pp-2021-0154 -
Oncotarget Feb 2017Although peritoneal cytology has been used to determine pancreatic cancer staging for more than three decades, its prognostic significance in potentially resectable... (Meta-Analysis)
Meta-Analysis Review
Although peritoneal cytology has been used to determine pancreatic cancer staging for more than three decades, its prognostic significance in potentially resectable pancreatic cancer is inconclusive. We therefore conducted this meta-analysis to investigate the impact of peritoneal cytology status on the clinicopathological features and survival outcomes in potentially resectable pancreatic cancer. Ten studies were identified for this meta-analysis after searching the PubMed, Web of Science and China National Knowledge Infrastructure (CNKI) electronic databases. Our results showed that positive peritoneal cytology was associated with tumor size (OR 11.65, P = 0.001), tumor location (OR 0.37, P = 0.000), serosal invasion (OR 3.89, P = 0.000), portal vein invasion (OR 1.82, P = 0.016), lymph vessel invasion (OR 2.71, P = 0.026), T stage (OR 2.65, P = 0.037) and N stage (OR 2.34, P = 0.001) in resectable pancreatic cancer. Patients with positive peritoneal cytology demonstrated poor overall survival (OS; HR 3.18, P = 0.000) and disease-free survival (DFS; HR 2.88, P = 0.000) times. Based on our meta-analysis, we conclude that positive peritoneal cytology is an indicator of advanced stage pancreatic cancer with a poor prognosis; hence, radical resection should not be performed on these patients.
Topics: Cytodiagnosis; Humans; Pancreatectomy; Pancreatic Neoplasms; Peritoneal Neoplasms; Peritoneum; Prognosis; Survival Rate
PubMed: 28122342
DOI: 10.18632/oncotarget.14745 -
Journal of Clinical Medicine Dec 2023Pancreatic cancer is notorious for its aggressive nature and low survival rate, with less than 10% of patients surviving beyond five years. Early detection is difficult,... (Review)
Review
BACKGROUND
Pancreatic cancer is notorious for its aggressive nature and low survival rate, with less than 10% of patients surviving beyond five years. Early detection is difficult, but skin metastases can be a rare but significant indicator. This systematic review focuses on the epidemiology, clinical features, and histology of skin metastases from pancreatic cancer to determine their importance in early diagnosis and overall management of the disease.
MATERIALS AND METHODS
Following PRISMA guidelines, we conducted an exhaustive search of MEDLINE/PubMed, EMBASE, and SCOPUS databases up to June 2023, using specific keywords. Four independent investigators screened the studies using predefined criteria, and two investigators checked the accuracy and consistency of the data extraction. We assessed the quality of the trials using adapted criteria from the Joanna Briggs Institute. A narrative synthesis rather than a meta-analysis was chosen because of the different study designs.
RESULTS
The final analysis included 57 patients with skin metastases from pancreatic cancer. Cutaneous metastases, although rare, presented with approximately equal gender distribution and a mean age of 63.4 years. Predominantly non-umbilical (77%), these metastases showed clinical diversity, ranging from asymptomatic nodules to painful or ulcerated lesions. Notably, skin metastases often preceded the diagnosis of primary pancreatic cancer (58%). Primary tumor characteristics revealed different localizations, with adenocarcinoma being the most prevalent histological type (77%). A significant association ( = 0.008) was observed between pancreatic tumor location and the timing of presentation of skin metastases. Tumors located in the body and tail of the pancreas were more likely to manifest skin metastases as an initial clinical manifestation (62.2%) than those in the head of the pancreas (20.8%).
CONCLUSIONS
In conclusion, although skin metastases are rare, they are important indicators of pancreatic cancer, highlighting the need for multidisciplinary healthcare collaboration and thorough skin examination. Recognizing them could lead to earlier diagnosis, which is crucial in a cancer with limited treatment options.
PubMed: 38202111
DOI: 10.3390/jcm13010104