-
Pancreatology : Official Journal of the... Nov 2022Pancreatic cancer has a dismal prognosis. So far, imaging has been proven incapable of establishing an early enough diagnosis. Thus, biomarkers are urgently needed for... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Pancreatic cancer has a dismal prognosis. So far, imaging has been proven incapable of establishing an early enough diagnosis. Thus, biomarkers are urgently needed for early detection and improved survival. Our aim was to evaluate the pooled diagnostic performance of DNA alterations in pancreatic juice.
METHODS
A systematic literature search was performed in EMBASE, MEDLINE Ovid, Cochrane CENTRAL and Web of Science for studies concerning the diagnostic performance of DNA alterations in pancreatic juice to differentiate patients with high-grade dysplasia or pancreatic cancer from controls. Study quality was assessed using QUADAS-2. The pooled prevalence, sensitivity, specificity and diagnostic odds ratio were calculated.
RESULTS
Studies mostly concerned cell-free DNA mutations (32 studies: 939 cases, 1678 controls) and methylation patterns (14 studies: 579 cases, 467 controls). KRAS, TP53, CDKN2A, GNAS and SMAD4 mutations were evaluated most. Of these, TP53 had the highest diagnostic performance with a pooled sensitivity of 42% (95% CI: 31-54%), specificity of 98% (95%-CI: 92%-100%) and diagnostic odds ratio of 36 (95% CI: 9-133). Of DNA methylation patterns, hypermethylation of CDKN2A, NPTX2 and ppENK were studied most. Hypermethylation of NPTX2 performed best with a sensitivity of 39-70% and specificity of 94-100% for distinguishing pancreatic cancer from controls.
CONCLUSIONS
This meta-analysis shows that, in pancreatic juice, the presence of distinct DNA mutations (TP53, SMAD4 or CDKN2A) and NPTX2 hypermethylation have a high specificity (close to 100%) for the presence of high-grade dysplasia or pancreatic cancer. However, the sensitivity of these DNA alterations is poor to moderate, yet may increase if they are combined in a panel.
Topics: Humans; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Early Detection of Cancer; Mutation; Pancreatic Juice; Pancreatic Neoplasms
PubMed: 35864067
DOI: 10.1016/j.pan.2022.06.260 -
International Journal of Surgery... Nov 2019Previous studies have indicated that there may be a difference in tumor biology between intraductal papillary mucinous carcinoma (IPMC) and pancreatic ductal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies have indicated that there may be a difference in tumor biology between intraductal papillary mucinous carcinoma (IPMC) and pancreatic ductal adenocarcinoma (PDAC). However, the data are still controversial. The aim of this systematic review and meta-analysis was to summarize and compare the outcome of IPMC and PDAC after surgical resection.
METHODS
Studies comparing IPMC and PDAC were identified using Medline and Embase search engines. Primary outcomes of interest were survival and recurrence. Secondary outcomes were clinicopathological characteristics. Meta-analysis of data was conducted using a random-effects model.
RESULTS
A total of 14 studies were included. Pooled analysis revealed an improved 5-year overall survival (OS) for IPMC compared to PDAC (OR 0.23, 95% CI 0.09-0.56). Both colloid and tubular IPMC showed improved 5-year OS compared to PDAC (OR 0.12, 95% CI 0.05-0.25 and OR 0.38, 95% CI 0.26-0.54, respectively). Median survival time ranged from 21 to 58 months in the IPMC group compared to 12-23 months in the PDAC group. No meta-analysis could be performed on recurrence or on time-to-event data. Descriptive data showed no survival difference for higher TNM stages. IPMC was more often found at a TNM-stage of 1 (OR 4.40, 95% CI 2.71-7.15) and had lower rates of lymph node spread (OR 0.43, 95% CI 0.32-0.57).
CONCLUSION
Available data suggest that IPMC has a more indolent course with a better 5-year OS compared to PDAC. The histopathological features are less aggressive in IPMC. The reason may be earlier detection. However, for IPMC with higher TNM stages the survival seems to be similar to that of PDAC.
Topics: Adenocarcinoma, Mucinous; Adenocarcinoma, Papillary; Aged; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Pancreatic Ductal; Female; Humans; Middle Aged; Neoplasm Staging; Pancreatic Neoplasms; Survival Rate
PubMed: 31546033
DOI: 10.1016/j.ijsu.2019.09.014 -
HPB : the Official Journal of the... May 2020Several randomised controlled trials (RCTs) have reported various systemic adjuvant therapy regimens following resection of pancreatic ductal adenocarcinoma (PDAC). The... (Meta-Analysis)
Meta-Analysis Review
A systematic review and network meta-analysis of phase III randomised controlled trials for adjuvant therapy following resection of pancreatic ductal adenocarcinoma (PDAC).
BACKGROUND
Several randomised controlled trials (RCTs) have reported various systemic adjuvant therapy regimens following resection of pancreatic ductal adenocarcinoma (PDAC). The most commonly applied include modified FOLFRINOX (mFFX), Gemcitabine/Capecitabine (GemCap) and S1, usually compared to gemcitabine (Gem) alone. However, many of these regimens have not been directly compared in RCTs. This network meta-analysis aims to characterise the impact of adjuvant therapies on overall and disease-free survival in patients having resection of PDAC.
METHODS
A systematic review was conducted using MEDLINE, EMBASE, Cochrane Central and American Society of Clinical Oncology (ASCO) abstracts to identify published phase III RCTs articles up to 9th May 2019 that examined adjuvant systemic therapy in resected pancreatic cancer. Data including study characteristics and outcomes including overall survival (OS) and disease-free survival (DFS) were extracted. Indirect comparisons of all regimens were simultaneously compared using random-effects network meta-analyses (NMA) which maintains randomisation within trials.
RESULTS
Twelve phase III RCTs involving 4947 patients and nine different regimens (5-Flourouracil/Folinic acid (5-FU/FA), Gemcitabine, Gemcitabine/Erlotinib (GemErl), GemCap), mFFX, S1, chemoradiotherapy (CRT), CRT with either 5-FU or Gemcitabine) were identified. S1 was ranked best for overall and disease-free survival followed by mFFX. Whilst there were no significant difference between S1 and mFFX for overall survival (mean difference: 1.6 months, p = 0.8), S1 had significantly longer disease-free survival than mFFX (mean difference: 2.8 months, p < 0.001). Furthermore, S1 was ranked best for lowest overall and haematological grade 3/4 toxicities.
CONCLUSION
This network meta-analysis demonstrates that chemotherapy with S1 or mFFX is superior to GemCap for adjuvant treatment for PDAC, improves survival after surgical resection and should be considered as reasonable standard treatment options in the adjuvant setting and as control arm for future adjuvant clinical trials.
Topics: Carcinoma, Pancreatic Ductal; Chemoradiotherapy; Chemotherapy, Adjuvant; Combined Modality Therapy; Humans; Network Meta-Analysis; Pancreatic Neoplasms; Randomized Controlled Trials as Topic
PubMed: 31894014
DOI: 10.1016/j.hpb.2019.12.001 -
Cureus Aug 2023Pancreatic ductal adenocarcinoma (PDAC) is a significant challenge due to its silent progression and well-advanced, unresectable, complicated presentation. Detecting... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is a significant challenge due to its silent progression and well-advanced, unresectable, complicated presentation. Detecting this disease early on is crucial, and researchers have been investigating various potential biological markers, such as carbohydrate antigen 19-9 (CA 19-9), hoping to find indicators that can aid in its early detection. The primary focus of this review is on the diagnostic usefulness of CA 19-9 in detecting pancreatic cancer (PC) in the beginning stage and its usefulness in predicting progression. The database search of articles from PubMed, PMC, the Cochrane Library, and Google Scholar identified 227 articles published from 2013 to 2023. The keyword mix used in the search technique included terms like "CA 19-9," "pancreatic cancer," "diagnosis," and "early detection." This study provides evidence of CA 19-9's ability in detecting PDAC in the pre-diagnostic stage. But since the outcomes were inconsistent among the included trials, further analysis is required to develop standardized diagnostic criteria and methodologies. Furthermore, because of the variability of the study, it is not easy to make firm conclusions on CA 19-9's sensitivity as well as specificity in the first stage of pancreatic neoplasm. This in-depth overview of the available literature provides new insights into using CA 19-9 as a biological marker for detecting undiagnosed PC before progressing into the advanced stage, and was proven beneficial. However, this has to be shown in broader research with adequate sample size. Although it shows promise as a diagnostic tool, further study is required to confirm these findings.
PubMed: 37671217
DOI: 10.7759/cureus.44382 -
Cancers Jul 2023LAPC is associated with a poor prognosis and requires a multimodal treatment approach. However, the role of radiation therapy in LAPC treatment remains controversial.... (Review)
Review
UNLABELLED
LAPC is associated with a poor prognosis and requires a multimodal treatment approach. However, the role of radiation therapy in LAPC treatment remains controversial. This systematic review aimed to explore the role of proton and photon therapy, with varying radiation techniques and fractionation, in treatment outcomes and their respective toxicity profiles.
METHODS
Clinical studies published from 2012 to 2022 were systematically reviewed using PubMed, MEDLINE (via PubMed) and Cochrane databases. Different radiotherapy-related data were extracted and analyzed.
RESULTS
A total of 31 studies matched the inclusion criteria. Acute toxicity was less remarkable in stereotactic body radiotherapy (SBRT) compared to conventionally fractionated radiotherapy (CFRT), while in proton beam therapy (PBT) grade 3 or higher acute toxicity was observed more commonly with doses of 67.5 Gy (RBE) or higher. Late toxicity was not reported in most studies; therefore, comparison between groups was not possible. The range of median overall survival (OS) for the CFRT and SBRT groups was 9.3-22.9 months and 8.5-20 months, respectively. For the PBT group, the range of median OS was 18.4-22.3 months.
CONCLUSION
CFRT and SBRT showed comparable survival outcomes with a more favorable acute toxicity profile for SBRT. PBT is a promising new treatment modality; however, additional clinical studies are needed to support its efficacy and safety.
PubMed: 37568587
DOI: 10.3390/cancers15153771 -
Frontiers in Oncology 2020Pancreatic ductal adenocarcinoma (PDAC) leads to the majority of cancer-related deaths due to its morbidity with similar mortality. Lack of effective prognostic...
Pancreatic ductal adenocarcinoma (PDAC) leads to the majority of cancer-related deaths due to its morbidity with similar mortality. Lack of effective prognostic biomarkers are the main reason for belated post-operative intervention of recurrence which causes high mortality. Numerous systematic reviews and meta-analyses have explored the prognostic value of biomarkers in PDAC so far. In this article, we performed an umbrella review analyzing these studies to provide an overview of associations between prognostic biomarkers and PDAC survival outcome and synthesized these results to guide better clinical practice. Systematic reviews and meta-analyses investigating the associations between PDAC survival outcomes and prognostic biomarkers were acquired via the PubMed and Embase databases from inception till February 1, 2020. Associations supported by nominally statistically significant results were classified into strong, highly suggestive, suggestive, and weak based on several critical factors such as the statistical significance of summary estimates, the number of events, the estimate of the largest study included, interstudy heterogeneity, small-study effects, 95% predictive interval (PI), excess significance bias, and the results of credibility ceiling sensitivity analyses. We included 41 meta-analyses containing 63 associations between PDAC survival outcomes and prognostic biomarkers. Although, none was supported by strong evidence among these associations, an association between C-reactive protein to albumin ratio (CAR) and PDAC overall survival (OS) and an association between neutrophil-lymphocyte ratio (NLR) and PDAC OS were supported by highly suggestive evidence. Otherwise, the association between lactate dehydrogenase (LDH) and PDAC OS was supported by suggestive evidence. The remaining 60 associations were supported by weak or not suggestive evidence. Associations between CAR or NLR and PDAC OS were supported by highly suggestive evidence. And the association between LDH and PDAC OS was supported by suggestive evidence. Although the methodological quality of the included systematic reviews and meta-analyses which were evaluated by AMSTAR2.0 is generally poor, the identification of the relatively robust prognostic biomarkers of PDAC may guide better post-operative intervention and follow-up to prolong patients' survival.
PubMed: 33042793
DOI: 10.3389/fonc.2020.01466 -
Indian Journal of Cancer 2022Patients with ductal adenocarcinoma of the body and tail of the pancreas usually remain asymptomatic until late in the course of the disease, and the survival of such... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with ductal adenocarcinoma of the body and tail of the pancreas usually remain asymptomatic until late in the course of the disease, and the survival of such patients depends on multiple factors, which may affect the therapeutic approach and patient survival. Hence, the aim of this study was to investigate such risk factors by pooling various available studies.
METHODS
A systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines between January 1, 2007, and December 31, 2016, using the following databases: Medline, Scopus, the Cochrane Library, and Google Scholar. Studies were selected according to the predesigned eligibility criteria, and information was extracted for demographics, clinical features, and survival outcomes. Data were pooled using fixed- or random-effects models.
RESULTS
Sixteen studies were included (5,660 patients) with a median age of 64.8 years and a median survival of 28.5 (range 13-38) months. Identified significant factors for overall survival were higher age (hazard ratio [HR] = 1.211), men (HR = 1.182), presence of lymph node metastasis (HR = 1.964), multivisceral resection (HR = 1.947), N stage (1 versus 0; HR = 1.601), surgical margin (R0 versus No R0; HR = 0.519) and tumor size (>3 cm; HR = 1.890).
CONCLUSION
The pooled results of this study revealed several risk factors for overall survival in patients with left-sided pancreatic cancer.
Topics: Male; Humans; Infant; Child, Preschool; Prognosis; Pancreatic Neoplasms; Margins of Excision; Lymphatic Metastasis
PubMed: 36412310
DOI: 10.4103/ijc.IJC_1150_20 -
Journal of Cachexia, Sarcopenia and... Dec 2023Sarcopenia has been considered an adverse prognostic factor in cancer patients. Intramuscular adipose tissue content, as a new marker of sarcopenia, can effectively... (Meta-Analysis)
Meta-Analysis Review
Sarcopenia has been considered an adverse prognostic factor in cancer patients. Intramuscular adipose tissue content, as a new marker of sarcopenia, can effectively reflect skeletal muscle quality. The aim of this study was performed to evaluate the association between high intramuscular adipose tissue content (IMAC) and survival outcomes and postoperative complications in cancer patients. Specific databases, including the Web of Science, Embase and Web of Science, were systematically searched to identify relevant articles evaluating the prognostic value of IMAC in cancer patients. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were utilized for comprehensive analysis. All data analyses were performed using STATA 12.0 software. A total of 25 studies from 24 articles including 5663 patients were enrolled in the study. Meta-analysis showed that high IMAC was associated with unfavourable overall survival (OS) (HR: 2.21, 95% CI: 1.70-2.86, P < 0.001), relapse-free survival (RFS) (HR: 1.51, 95% CI: 1.30-1.75, P < 0.001) and disease-specific survival (DSS) (HR: 1.64, 95% CI: 1.19-2.28, P = 0.003). Subgroup analysis revealed that high IMAC remained an adverse prognostic factor when stratified by different country, treatment methods, cancer type or analysis type. High IMAC had better predictive value for gallbladder carcinoma (GBC) (HR: 3.50, 95% CI: 1.98-6.17, P < 0.001), hepatocellular carcinoma (HCC) (HR: 1.84, 95% CI: 1.45-2.33, P < 0.001), pancreatic cancer (PC) (HR: 2.11, 95% CI: 1.67-2.66, P < 0.001) and colorectal cancer (CRC) (HR: 2.54, 95% CI: 1.27-5.10, P = 0.009). High IMAC was also identified as a significant risk factor for postoperative complications (OR: 2.05, 95% CI: 1.22-3.46, P = 0.007). High IMAC was associated with an adverse prognosis and an increased risk of postoperative complications in cancer patients. IMAC may be a good indicator of sarcopenia.
Topics: Humans; Carcinoma, Hepatocellular; Sarcopenia; Liver Neoplasms; Retrospective Studies; Prognosis; Adipose Tissue; Postoperative Complications
PubMed: 37990969
DOI: 10.1002/jcsm.13371 -
Cancer Reports (Hoboken, N.J.) Oct 2021While adjuvant chemotherapy benefits patients with pancreatic ductal adenocarcinoma (PDAC), the importance of the time to initiation of adjuvant therapy remains unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
While adjuvant chemotherapy benefits patients with pancreatic ductal adenocarcinoma (PDAC), the importance of the time to initiation of adjuvant therapy remains unclear.
AIM
This study seeks to better understand whether the timing of postoperative chemotherapy initiation affects long-term outcomes in PDAC.
METHODS AND RESULTS
A systematic literature search was performed in Medline, Embase, and Cochrane Library in March 2020. Studies focused on the association between the timing of adjuvant therapy on long-term outcomes in resected PDAC patients were included. The impact of early and delayed therapy as defined by the respective studies was evaluated using forest plot analysis. Overall survival (OS) and disease-free survival (DFS) served as primary endpoints. Out of 3099 published articles, 10 retrospective studies met inclusion criteria. Combined, these studies included clinical data of 13 344 patients. The cut off used to define "early" and "delayed" treatment groups varied in the included studies ranging from 3 to 12 weeks. Due to this heterogeneity, a sub-group analysis of three time cut offs was performed: 3 to 5 weeks, 6 to 8 weeks, and 9 to 12 weeks. There was a significant decrease in OS and DFS when adjuvant therapy was delayed by 3 to 5 weeks after surgery (OS, pooled hazard ratio [HR] = 1.86, 95% confidence interval [CI] = 1.25-2.78; DFS, pooled HR = 1.62, 95% CI = 1.12-2.34). However, due to small sample size and limited studies in this subgroup analysis, the results may be indeterminate. There was no significant decrease in OS with delayed initiation of adjuvant therapy by 6 to 8 weeks and 9 to 12 weeks. Similarly, delay in adjuvant therapy beyond 3-5 weeks.
CONCLUSIONS
There was no conclusive evidence suggesting improved survival in patients starting treatment at various time cut offs. Studies investigating the extreme ends of the time-to-treatment spectrum may prove more informative.
Topics: Chemotherapy, Adjuvant; Humans; Pancreatic Neoplasms; Prognosis; Survival Rate; Time-to-Treatment
PubMed: 34245139
DOI: 10.1002/cnr2.1390 -
Medicine Jul 2022Clinically relevant postoperative pancreatic fistula (CR-POPF) is a common and troublesome complication after pancreatoduodenectomy (PD). We conducted a systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clinically relevant postoperative pancreatic fistula (CR-POPF) is a common and troublesome complication after pancreatoduodenectomy (PD). We conducted a systematic review and meta-analysis to identify the risk factors of CR-POPF after PD.
METHODS
We searched PubMed, EMBASE, and Cochrane Library databases for studies related to risk factors of CR-POPF after PD. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were extracted from the included studies, then a meta-analysis was conducted. If necessary, sensitivity analysis would be performed by changing the effect model or excluding 1 study at a time. Publication bias was assessed by funnel plot and Begg test and Egger test.
RESULTS
A total of 27 studies with 24,740 patients were included, and CR-POPF occurred in 3843 patients (incidence = 17%, 95% CI: 16%-19%). Male (OR = 1.56, 95% CI: 1.42-1.70), body mass index >25 kg/m2 (OR = 1.98, 95% CI: 1.23-3.18), pancreatic duct diameter <3 mm (OR = 1.87, 95% CI: 1.66-2.12), soft pancreatic texture (OR = 3.49, 95% CI: 2.61-4.67), and blood transfusion (OR = 3.10, 95% CI: 2.01-4.77) can significantly increase the risk of CR-POPF. Pancreatic adenocarcinoma (OR = 0.54, 95% CI: 0.47-0.61), vascular resection (OR = 0.57, 95% CI: 0.39-0.83), and preoperative chemoradiotherapy (OR = 0.68, 95% CI: 0.57-0.81) can significantly decrease the factor of CR-POPF. Diabetes mellitus was not statistically associated with CR-POPF (OR = 0.66, 95% CI: 0.40-1.08). However, the analysis of body mass index, pancreatic texture, and diabetes mellitus had a high heterogeneity, then sensitivity analysis was performed, and the result after sensitivity analysis showed diabetes mellitus can significantly decrease the risk of CR-POPF. There was no significant publication bias in this meta-analysis.
CONCLUSIONS
The current review assessed the effects of different factors on CR-POPF. This can provide a basis for the prevention and management of CR-POPF. Effective interventions targeting the above risk factors should be investigated in future studies for decreasing the occurrence of CR-POPF.
Topics: Adenocarcinoma; Humans; Male; Pancreatic Fistula; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Retrospective Studies; Risk Factors
PubMed: 35776984
DOI: 10.1097/MD.0000000000029757