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Cancer Metastasis Reviews Mar 2015A nearly universal feature of pancreatic ductal adenocarcinoma (PDAC) is an extensive presence of activated stroma. This stroma is thought to aid in various... (Review)
Review
A nearly universal feature of pancreatic ductal adenocarcinoma (PDAC) is an extensive presence of activated stroma. This stroma is thought to aid in various tumor-promoting processes and hampers response to therapy. Here, we aim to evaluate the evidence that supports this role of the stroma in PDAC with functional experiments in relevant models, discuss the clinical trials that have aimed to target the stroma in this disease, and examine recent work that explains why these clinical trials based on stroma-targeting strategies have thus far not achieved the expected success. We systematically searched PubMed through August 2014 with no restrictions to identify published peer-reviewed research articles assessing the effect of targeting the stroma on tumor growth or metastases in preclinical animal models. Five hundred and thirty articles were extracted of which 31 were included in the analysis. Unfortunately, due to the large variety in models and outcome measures, we could not perform a meta-analysis of our data. We find that despite an abundance of positive outcomes reported in previous studies on stroma targeting, a strong discrepancy exists with the outcomes of clinical trials and the more recent preclinical work that is in line with these trials. We explain the incongruities by the duration of stroma targeting and propose that chronic stroma targeting treatment is possibly detrimental in the treatment of this disease.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Humans; Pancreas; Pancreatic Neoplasms; Stromal Cells; Treatment Outcome; Tumor Microenvironment
PubMed: 25566685
DOI: 10.1007/s10555-014-9541-1 -
Annals of Surgical Oncology Jun 2023Preoperative instead of standard postoperative partial breast irradiation (PBI) after breast-conserving surgery (BCS) has the advantage of reducing the irradiated breast... (Review)
Review
BACKGROUND
Preoperative instead of standard postoperative partial breast irradiation (PBI) after breast-conserving surgery (BCS) has the advantage of reducing the irradiated breast volume, toxicity, and number of radiotherapy sessions and can allow tumor downstaging. In this review, we assessed tumor response and clinical outcomes after preoperative PBI.
PATIENTS AND METHODS
We conducted a systematic review of studies on preoperative PBI in patients with low-risk breast cancer using the databases Ovid Medline, Embase.com, Web of Science (Core Collection), and Scopus (PROSPERO registration CRD42022301435). References of eligible manuscripts were checked for other relevant manuscripts. The primary outcome measure was pathologic complete response (pCR).
RESULTS
A total of eight prospective and one retrospective cohort study were identified (n = 359). In up to 42% of the patients, pCR was obtained and this increased after a longer interval between radiotherapy and BCS (0.5-8 months). After a maximum median follow-up of 5.0 years, three studies on external beam radiotherapy reported low local recurrence rates (0-3%) and overall survival of 97-100%. Acute toxicity consisted mainly of grade 1 skin toxicity (0-34%) and seroma (0-31%). Late toxicity was predominantly fibrosis grade 1 (46-100%) and grade 2 (10-11%). Cosmetic outcome was good to excellent in 78-100% of the patients.
CONCLUSIONS
Preoperative PBI showed a higher pCR rate after a longer interval between radiotherapy and BCS. Mild late toxicity and good oncological and cosmetic outcomes were reported. In the ongoing ABLATIVE-2 trial, BCS is performed at a longer interval of 12 months after preoperative PBI aiming to achieve a higher pCR rate.
Topics: Humans; Female; Breast Neoplasms; Prospective Studies; Retrospective Studies; Breast; Mastectomy, Segmental
PubMed: 36869253
DOI: 10.1245/s10434-023-13233-9 -
Head & Neck Apr 2016Significant evidence exists supporting the use of platinum-based chemoradiotherapy (CRT) as a primary curative approach in locoregionally advanced head and neck cancer... (Review)
Review
BACKGROUND
Significant evidence exists supporting the use of platinum-based chemoradiotherapy (CRT) as a primary curative approach in locoregionally advanced head and neck cancer (HNSCC). Despite these aggressive protocols, 70% of patients die within 5 years because of locoregional recurrence or distant metastasis. To increase the response and survival of patients with HNSCC, CRT has been combined with molecular agents targeting distinct kinases.
METHODS
This study was performed using a systematic literature review.
RESULTS
The effect of targeted therapy on patient survival in the context of CRT remains controversial, with toxicities tending to be more severe but still acceptable.
CONCLUSION
Supplementing CRT with target therapeutics might only improve survival in some patients with locally advanced HNSCC. Therefore, future studies must address the underlying biological mechanisms that can have an impact on treatment response. Such knowledge is essential in order to facilitate the effective and personalized treatment of patients with locally advanced HNSCC by combining CRT and targeted therapy. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2173-E2181, 2016.
Topics: Carcinoma, Squamous Cell; Chemoradiotherapy; Head and Neck Neoplasms; Humans; Molecular Targeted Therapy; Platinum Compounds; Treatment Outcome
PubMed: 25783524
DOI: 10.1002/hed.24031 -
Dose-response : a Publication of... 2019Radiation therapy induces acute and chronic radiological toxicity, in particular hematological toxicity (HT). This study aimed to explore the mechanistic clue and... (Review)
Review
Analysis of mRNA Expression Patterns in Peripheral Blood Cells of 3 Patients With Cancer After the First Fraction of 2 Gy Irradiation: An Integrated Case Report and Systematic Review.
BACKGROUND
Radiation therapy induces acute and chronic radiological toxicity, in particular hematological toxicity (HT). This study aimed to explore the mechanistic clue and potential predictors at the messenger RNA (mRNA) level.
MATERIALS AND METHODS
Peripheral blood was collected from 3 patients with cervical cancer (CC), nasopharynx cancer (NC), and tongue cancer (TC) after the first 2 Gy fraction of radiotherapy (RT). High-throughput sequencing was used to assess mRNA profiles.
RESULTS
Eleven genes, such as ALAS2(5-aminolevulinate synthase), SLC4A1(solute carrier family 4 member 1), (hemoglobin subunit gamma 2), (TNF α-induced protein 3), (period circadian clock 1), (coiled-coil domain containing 136), (chromosome 9 open reading frame 84), (interleukin 1β), (FosB protooncogene), (nuclear receptor subfamily 4), (polymerase family member 15), had overlapping expression changes in all 3 cancers of which 3 (, and ) are suggested as potential predictors for the early diagnosis of HT after RT.
CONCLUSIONS
may be useful predictors of HT in patients after RT. Eleven overlapping expression mRNAs among 3 cancers might be potential predictors for early diagnosis of radiation toxicity in patients.
PubMed: 30833875
DOI: 10.1177/1559325819833474 -
Brain Sciences Jul 2022Background: High-dose ionizing radiation (IR) (>0.5 Gy) is an established risk factor for cognitive impairments, but this cannot be concluded for low-to-moderate IR... (Review)
Review
Background: High-dose ionizing radiation (IR) (>0.5 Gy) is an established risk factor for cognitive impairments, but this cannot be concluded for low-to-moderate IR exposure (<0.5 Gy) in adulthood as study results are inconsistent. The objectives are to summarize relevant epidemiological studies of low-to-moderate IR exposure in adulthood and to assess the risk of non-cancerous CNS diseases. Methods: A systematic literature search of four electronic databases was performed to retrieve relevant epidemiological studies published from 2000 to 2022. Pooled standardized mortality ratios, relative risks, and excess relative risks (ERR) were estimated with a random effect model. Results: Forty-five publications were included in the systematic review, including thirty-three in the quantitative meta-analysis. The following sources of IR-exposure were considered: atomic bomb, occupational, environmental, and medical exposure. Increased dose-risk relationships were found for cerebrovascular diseases incidence and mortality (ERRpooled per 100 mGy = 0.04; 95% CI: 0.03−0.05; ERRpooled at 100 mGy = 0.01; 95% CI: −0.00−0.02, respectively) and for Parkinson’s disease (ERRpooled at 100 mGy = 0.11; 95% CI: 0.06−0.16); Conclusions: Our findings suggest that adult low-to-moderate IR exposure may have effects on non-cancerous CNS diseases. Further research addressing inherent variation issues is encouraged.
PubMed: 35892428
DOI: 10.3390/brainsci12080984 -
Oncotarget Sep 2017Poly-(ADP-Ribose)-Polymerase (PARP) inhibitors are becoming important actors of anti-neoplasic agents landscape, with recent but narrow FDA's approvals for ovarian BRCA... (Review)
Review
BACKGROUND
Poly-(ADP-Ribose)-Polymerase (PARP) inhibitors are becoming important actors of anti-neoplasic agents landscape, with recent but narrow FDA's approvals for ovarian BRCA mutated cancers and prostatic cancer. Nevertheless, PARP inhibitors are also promising drugs for combined treatments particularly with radiotherapy. More than seven PARP inhibitors have been currently developed. Central Role of PARP in DNA repair, makes consider PARP inhibitor as potential radiosensitizers, especially for tumors with DNA repair defects, such as BRCA mutation, because of synthetic lethality. Furthermore the replication-dependent activity of PARP inhibitor helps to maintain the differential effect between tumoral and healthy tissues. Inhibition of chromatin remodeling, G2/M arrest, vasodilatory effect induced by PARP inhibitor, also participate to their radio-sensitization effect.
MATERIALS AND METHODS
Here, after highlighting mechanisms of PARP inhibitors radiosensitization we methodically searched PubMed, Google Scholar, Cochrane Databases and meeting proceedings for human pre-clinical and clinical studies that evaluated PARP inhibitor radiosensitizing effect. Enhancement ratio, when available, was systematically reported.
RESULTS
Sixty four studies finally met our selection criteria and were included in the analysis. Only three pre-clinical studies didn't find any radiosensitizing effect. Median enhancement ratio vary from 1,3 for prostate tumors to 1,5 for lung cancers. Nine phase I or II trials assessed safety data.
CONCLUSION
PARP inhibitors are promising radiosensitizers, but need more clinical investigation. The next ten years will be determining for judging their real potential.
PubMed: 28978184
DOI: 10.18632/oncotarget.19079 -
Technology in Cancer Research &... 2020It is well known that radiation damage of the pharyngeal constrictor muscles, the glottic larynx, and the supraglottic larynx may lead to dysphagia, an unwanted effect... (Meta-Analysis)
Meta-Analysis
It is well known that radiation damage of the pharyngeal constrictor muscles, the glottic larynx, and the supraglottic larynx may lead to dysphagia, an unwanted effect of head and neck radiotherapy. The reduction of radiotherapy-induced dysphagia might be achieved by adaptive radiotherapy. Although the number of studies concerning adaptive radiotherapy of head and neck cancer is continuously increasing, there are only a few studies concerning changes in dysphagia-related structures during radiotherapy.The goal of this review is to summarize the current knowledge about volumetric, dosimetric, and other changes of the pharyngeal constrictor muscles associated with head and neck radiotherapy. A literature search was performed in the MEDLINE database according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The conclusions of 8 studies that passed the criteria indicate a significant increase in the volume and the thickness of the pharyngeal constrictor muscles during radiotherapy. Moreover, the changes in magnetic resonance imaging signal intensity of the pharyngeal constrictor muscles correlate with the absorbed dose (typically higher than 50 Gy) and also with the grade of dysphagia. This systematic review presents 2 variables, which are suitable for estimation of radiotherapy-related pharyngeal constrictor muscles changes-magnetic resonance imaging signal intensity and the thickness. In the case of the thickness, there is no consensus in the level of the measurement-C2 vertebra, C3 vertebra, and the middle of the craniocaudal axis are used. It seems that reference to a position associated with a vertebral body could be more reproducible and beneficial for future research. Although late pharyngeal toxicity remains a challenge in head and neck cancer treatment, better knowledge of radiotherapy-related changes in the pharyngeal constrictor muscles contributes to adaptive radiotherapy development and thus improves the treatment results.
Topics: Deglutition Disorders; Head and Neck Neoplasms; Humans; Magnetic Resonance Imaging; Organs at Risk; Pharyngeal Muscles; Radiotherapy Dosage; Tomography, X-Ray Computed
PubMed: 32734851
DOI: 10.1177/1533033820945805 -
Oral Oncology Oct 2014Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) generates microvascular parameters from the tracer kinetic analysis of a series of MRI images obtained in... (Review)
Review
Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) generates microvascular parameters from the tracer kinetic analysis of a series of MRI images obtained in under 15 min. DCE-MRI parameters are associated with tumour hypoxia, which is well-established as a cause of treatment failure in head and neck squamous cell carcinoma (HNSCC). A systematic review was conducted of prospective DCE-MRI parameter studies in HNSCC in the English language literature. Exclusion criteria were case reports and retrospective series. Six DCE-MRI marker studies in HNSCC met the inclusion criteria. Four studies contained 21-74 patients and two studies recruited 13 and 14 patients. In studies measuring the transfer coefficient (K(trans)), higher overall K(trans) or lower skewness of K(trans) were predictive of a good outcome following chemoradiation. DCE-MRI parameters have the potential to guide treatment in HNSCC. Progress in the field requires standardisation of methods, data sharing and large multi-centre collaborative validation studies.
Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Contrast Media; Head and Neck Neoplasms; Humans; Magnetic Resonance Imaging
PubMed: 25116700
DOI: 10.1016/j.oraloncology.2014.07.011 -
Critical Reviews in Oncology/hematology Sep 2020Current research that combines radiation with targeted therapy may dramatically improve prognosis of pancreatic ductal adenocarcinoma (PDAC). We investigated preclinical... (Review)
Review
BACKGROUND
Current research that combines radiation with targeted therapy may dramatically improve prognosis of pancreatic ductal adenocarcinoma (PDAC). We investigated preclinical outcomes of DNA repair inhibitor targeted therapy associated with radiotherapy.
METHODS
We searched Pubmed database to identify publications assessing DNA damage targeted therapies in preclinical models of PDACin vitro and in vivo. Standard enhancement ratio, median survival and growth delay were extracted.
RESULTS
We identified fourteen publications using DNA repair targeted therapies in preclinical models of PDAC. Ten publications comprising twenty-eight experiments evaluated radiosensitization with different DNA repair inhibitors in vitro and displayed cell killing by a factor of 1.35 ± 0.047. Moreover, 86 % (24/28) of in vitro experiments showed radiosensitization with DNA damage response inhibitor. However, only 60 % (9/15) of the in vivo experiments presented radiosensitization effects.
CONCLUSION
DNA repair targeted therapies use promising radiosensitizers for PDAC and could successfully be translated into clinical trials.
Topics: Carcinoma, Pancreatic Ductal; DNA Damage; DNA Repair; Humans; Pancreatic Neoplasms; Radiation-Sensitizing Agents
PubMed: 32707435
DOI: 10.1016/j.critrevonc.2020.103060 -
Scientific Reports Sep 2018Targeted therapy is lagging behind in esophageal adenocarcinoma (EAC). To guide the development of new treatment strategies, we provide an overview of the prognostic... (Meta-Analysis)
Meta-Analysis
Targeted therapy is lagging behind in esophageal adenocarcinoma (EAC). To guide the development of new treatment strategies, we provide an overview of the prognostic biomarkers in resectable EAC treated with curative intent. The Medline, Cochrane and EMBASE databases were systematically searched, focusing on overall survival (OS). The quality of the studies was assessed using a scoring system ranging from 0-7 points based on modified REMARK criteria. To evaluate all identified prognostic biomarkers, the hallmarks of cancer were adapted to fit all biomarkers based on their biological function in EAC, resulting in the features angiogenesis, cell adhesion and extra-cellular matrix remodeling, cell cycle, immune, invasion and metastasis, proliferation, and self-renewal. Pooled hazard ratios (HR) and 95% confidence intervals (CI) were derived by random effects meta-analyses performed on each hallmarks of cancer feature. Of the 3298 unique articles identified, 84 were included, with a mean quality of 5.9 points (range 3.5-7). The hallmarks of cancer feature 'immune' was most significantly associated with worse OS (HR 1.88, (95%CI 1.20-2.93)). Of the 82 unique prognostic biomarkers identified, meta-analyses showed prominent biomarkers, including COX-2, PAK-1, p14ARF, PD-L1, MET, LC3B, IGFBP7 and LGR5, associated to each hallmark of cancer.
Topics: Adenocarcinoma; Biomarkers, Tumor; Esophageal Neoplasms; Humans; Prognosis; Proportional Hazards Models; Survival Analysis
PubMed: 30185893
DOI: 10.1038/s41598-018-31548-6