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International Journal of Nursing Studies Feb 2021Extensive surgery and chemo/radiation therapy (C/RT) to manage head and neck cancer (HNC) patients affects their ability to swallow food and liquids, risk of aspiration... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Extensive surgery and chemo/radiation therapy (C/RT) to manage head and neck cancer (HNC) patients affects their ability to swallow food and liquids, risk of aspiration and greatly influences their quality of life (QOL).
OBJECTIVES
Ascertain the effectiveness of swallowing exercises on improving swallowing function, performance status, mouth opening, risk of aspiration/penetration and QOL in HNC patients.
DESIGN
Systematic review and meta-analysis of randomized controlled trials DATA SOURCES: PubMed, Ovid-Medline, Embase, Cochrane Library, CINAHL and Web of Science and included all available RCTs.
REVIEW METHODS
We followed the PRISMA guidelines and standard methods for conducting a systematic review and meta-analysis. Comprehensive Meta-analysis 3.0 using the random effects model was used for data analysis.
RESULTS
In total, 19 RCTs with 1100 participants were identified and included in the current review. Swallowing exercises had significant small effect on swallowing function 0.33 (95%CI = 0.00-0.65) and moderate effect on mouth opening 0.60 (95%CI = 0.21-0.99) immediately after intervention and small effect at 6-month follow-up 0.46 (95%CI = 0.11-0.81). However, non-significant effects were observed on risk of aspiration/penetration, performance status and all domains of QOL.
CONCLUSION
Swallowing exercises demonstrated effectiveness in improving swallowing function and mouth opening in HNC patients undergoing multimodal treatment. This is the first comprehensive systematic review and meta-analysis of RCTs to assess the effect of swallowing exercises in HNC patients undergoing multimodal treatment. Nurses can play an important role in assisting the delivery of oropharyngeal swallowing exercises including jaw exercises, tongue exercises and swallowing maneuvers with assistance and guidance from speech pathologists to help improve HNC complications and QOL for HNC survivors.
Topics: Deglutition; Deglutition Disorders; Exercise Therapy; Head and Neck Neoplasms; Humans; Quality of Life
PubMed: 33352439
DOI: 10.1016/j.ijnurstu.2020.103827 -
The Cochrane Database of Systematic... Dec 2020Different bone-modifying agents like bisphosphonates and receptor activator of nuclear factor-kappa B ligand (RANKL)-inhibitors are used as supportive treatment in men... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Different bone-modifying agents like bisphosphonates and receptor activator of nuclear factor-kappa B ligand (RANKL)-inhibitors are used as supportive treatment in men with prostate cancer and bone metastases to prevent skeletal-related events (SREs). SREs such as pathologic fractures, spinal cord compression, surgery and radiotherapy to the bone, and hypercalcemia lead to morbidity, a poor performance status, and impaired quality of life. Efficacy and acceptability of the bone-targeted therapy is therefore of high relevance. Until now recommendations in guidelines on which bone-modifying agents should be used are rare and inconsistent.
OBJECTIVES
To assess the effects of bisphosphonates and RANKL-inhibitors as supportive treatment for prostate cancer patients with bone metastases and to generate a clinically meaningful treatment ranking according to their safety and efficacy using network meta-analysis.
SEARCH METHODS
We identified studies by electronically searching the bibliographic databases Cochrane Controlled Register of Trials (CENTRAL), MEDLINE, and Embase until 23 March 2020. We searched the Cochrane Library and various trial registries and screened abstracts of conference proceedings and reference lists of identified trials.
SELECTION CRITERIA
We included randomized controlled trials comparing different bisphosphonates and RANKL-inihibitors with each other or against no further treatment or placebo for men with prostate cancer and bone metastases. We included men with castration-restrictive and castration-sensitive prostate cancer and conducted subgroup analyses according to this criteria.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the quality of trials. We defined proportion of participants with pain response and the adverse events renal impairment and osteonecrosis of the jaw (ONJ) as the primary outcomes. Secondary outcomes were SREs in total and each separately (see above), mortality, quality of life, and further adverse events such as grade 3 to 4 adverse events, hypocalcemia, fatigue, diarrhea, and nausea. We conducted network meta-analysis and generated treatment rankings for all outcomes, except quality of life due to insufficient reporting on this outcome. We compiled ranking plots to compare single outcomes of efficacy against outcomes of acceptability of the bone-modifying agents. We assessed the certainty of the evidence for the main outcomes using the GRADE approach.
MAIN RESULTS
Twenty-five trials fulfilled our inclusion criteria. Twenty-one trials could be considered in the quantitative analysis, of which six bisphosphonates (zoledronic acid, risedronate, pamidronate, alendronate, etidronate, or clodronate) were compared with each other, the RANKL-inhibitor denosumab, or no treatment/placebo. By conducting network meta-analysis we were able to compare all of these reported agents directly and/or indirectly within the network for each outcome. In the abstract only the comparisons of zoledronic acid and denosumab against the main comparator (no treatment/placebo) are described for outcomes that were predefined as most relevant and that also appear in the 'Summary of findings' table. Other results, as well as results of subgroup analyses regarding castration status of participants, are displayed in the Results section of the full text. Treatment with zoledronic acid probably neither reduces nor increases the proportion of participants with pain response when compared to no treatment/placebo (risk ratio (RR) 1.46, 95% confidence interval (CI) 0.93 to 2.32; per 1000 participants 121 more (19 less to 349 more); moderate-certainty evidence; network based on 4 trials including 1013 participants). For this outcome none of the trials reported results for the comparison with denosumab. The adverse event renal impairment probably occurs more often when treated with zoledronic acid compared to treatment/placebo (RR 1.63, 95% CI 1.08 to 2.45; per 1000 participants 78 more (10 more to 180 more); moderate-certainty evidence; network based on 6 trials including 1769 participants). Results for denosumab could not be included for this outcome, since zero events cannot be considered in the network meta-analysis, therefore it does not appear in the ranking. Treatment with denosumab results in increased occurrence of the adverse event ONJ (RR 3.45, 95% CI 1.06 to 11.24; per 1000 participants 30 more (1 more to 125 more); high-certainty evidence; 4 trials, 3006 participants) compared to no treatment/placebo. When comparing zoledronic acid to no treatment/placebo, the confidence intervals include the possibility of benefit or harm, therefore treatment with zoledronic acid probably neither reduces nor increases ONJ (RR 1.88, 95% CI 0.73 to 4.87; per 1000 participants 11 more (3 less to 47 more); moderate-certainty evidence; network based on 4 trials including 3006 participants). Compared to no treatment/placebo, treatment with zoledronic acid (RR 0.84, 95% CI 0.72 to 0.97) and denosumab (RR 0.72, 95% CI 0.54 to 0.96) may result in a reduction of the total number of SREs (per 1000 participants 75 fewer (131 fewer to 14 fewer) and 131 fewer (215 fewer to 19 fewer); both low-certainty evidence; 12 trials, 5240 participants). Treatment with zoledronic acid and denosumab likely neither reduces nor increases mortality when compared to no treatment/placebo (zoledronic acid RR 0.90, 95% CI 0.80 to 1.01; per 1000 participants 48 fewer (97 fewer to 5 more); denosumab RR 0.93, 95% CI 0.77 to 1.11; per 1000 participants 34 fewer (111 fewer to 54 more); both moderate-certainty evidence; 13 trials, 5494 participants). Due to insufficient reporting, no network meta-analysis was possible for the outcome quality of life. One study with 1904 participants comparing zoledronic acid and denosumab showed that more zoledronic acid-treated participants than denosumab-treated participants experienced a greater than or equal to five-point decrease in Functional Assessment of Cancer Therapy-General total scores over a range of 18 months (average relative difference = 6.8%, range -9.4% to 14.6%) or worsening of cancer-related quality of life.
AUTHORS' CONCLUSIONS
When considering bone-modifying agents as supportive treatment, one has to balance between efficacy and acceptability. Results suggest that Zoledronic acid likely increases both the proportion of participants with pain response, and the proportion of participants experiencing adverse events However, more trials with head-to-head comparisons including all potential agents are needed to draw the whole picture and proof the results of this analysis.
Topics: Adult; Alendronate; Antineoplastic Agents, Hormonal; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Bone Neoplasms; Clodronic Acid; Denosumab; Diphosphonates; Etidronic Acid; Humans; Male; Network Meta-Analysis; Pamidronate; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Quality of Life; RANK Ligand; Randomized Controlled Trials as Topic; Risedronic Acid; Zoledronic Acid
PubMed: 33270906
DOI: 10.1002/14651858.CD013020.pub2 -
Head and Neck Pathology Jun 2021Primary intraosseous oral squamous cell carcinoma (PIOSCC) is a rare malignant neoplasm that affects the jaws. Despite its aggressive biological behavior, there are no...
Primary intraosseous oral squamous cell carcinoma (PIOSCC) is a rare malignant neoplasm that affects the jaws. Despite its aggressive biological behavior, there are no studies that evaluated the clinicopathological features of this tumor and parameters associated with its prognosis. The objective of the present study was to conduct a systematic review of the available data on oral and maxillofacial PIOSCC in order to determine its clinicopathological characteristics and biological behavior. We conducted a systematic review in May 2020 in multiple databases using a specific search strategy. Cases diagnosed as PIOSCC in the oral cavity and maxillofacial complex that had sufficient histopathological data, absence of ulceration in the oral mucosa, a negative result for a distant primary tumor, and radiographic evidence of an osteolytic lesion that was entirely or mostly surrounded by the jaw bones were included. A total of 109 published articles were included in our systematic review, corresponding to 257 cases. PIOSCC showed a male predilection (69.3%) and a preference for the mandible (7:1), with the posterior region being the most commonly affected site. The mean age at diagnosis was 57.3 years. Cortical expansion, pain, and lip/facial paresthesia were the most common clinical features. Regarding histopathological features, most PIOSCC were well-differentiated and the solid subtype was the most common. Statistical analysis showed that PIOSCC located in the mandible (p = 0.03) and recurrence (p < 0.01) were significantly associated with a higher mortality rate. PIOSCC has a poor prognosis, with high rates of mortality.
Topics: Female; Humans; Jaw Neoplasms; Male; Middle Aged; Squamous Cell Carcinoma of Head and Neck
PubMed: 33044723
DOI: 10.1007/s12105-020-01234-z -
Medicina Oral, Patologia Oral Y Cirugia... Mar 2021to systematically review the literature, comparing the healing of osteoradionecrosis (ORN) among the therapeutic alternatives: surgical, pharmacological and combined.
BACKGROUND
to systematically review the literature, comparing the healing of osteoradionecrosis (ORN) among the therapeutic alternatives: surgical, pharmacological and combined.
MATERIAL AND METHODS
The review was organized according to the PRISMA protocol with regards to the following PICO question: patients with ORN of the jaws (P=Patient); all interventions reported (I = intervention); between all therapies (C=Comparison); healing of lesions (O=outcome).
RESULTS
Surgical treatment was the most common choice (46.3%) followed by pharmacological treatment, exclusively (25.9%) or combined (26.9%). Treatment exclusively by surgical intervention seems to be most effective option, with 51.2% of the lesions healed, OR for healing of 5.7 (CI95% 1.9-16.9, p=0.002). Only 1 case (0.9%) corresponded to low level laser therapy.
CONCLUSIONS
It seems clear that early intervention with conservative surgical combined with pharmacological methods improves the prognosis of ORN.
Topics: Head and Neck Neoplasms; Humans; Jaw; Jaw Diseases; Osteoradionecrosis; Prognosis
PubMed: 33037800
DOI: 10.4317/medoral.24132 -
Radiotherapy and Oncology : Journal of... Oct 2020Trismus is a common complication of cancer treatment, particularly radiotherapy, for head and neck cancer. We investigated whether exercise therapy could prevent or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Trismus is a common complication of cancer treatment, particularly radiotherapy, for head and neck cancer. We investigated whether exercise therapy could prevent or manage limited mouth opening in patients before or after the cancer treatment.
METHODS
We performed a systematic review and meta-analysis to evaluate the effectiveness of exercise therapy combined with a jaw-mobilizing device in the prevention and treatment of cancer treatment-induced trismus. The electronic databases PubMed, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials were searched for articles on trismus published before July 2020 with no language restrictions. The primary outcome for prevention was trismus incidence. The treatment outcome for trismus was the improvement of maximal interincisal opening (MIO).
RESULTS
Thirteen randomized controlled trials (RCTs) involving 733 patients were identified. Six studies assessed MIO and found that exercise therapy adjuvant to the use of a jaw-mobilizing device significantly improved the MIO from 4.48 (95% confidence interval [CI] = 0.20, 8.75) to 14.20 (95% CI = 10.73, 17.67) mm. Seven studies evaluating the preventive outcome of incidence of trismus found no significant difference between standard usual care and exercise therapy adjuvant to the use of a jaw-mobilizing device (risk ratio = 1.20; 95% CI = 0.61, 2.34).
CONCLUSIONS
The current evidence from RCTs revealed that exercise therapy can lead to MIO improvement following the development of cancer treatment-induced trismus, but does not prevent trismus in patients being treated for head and neck cancer. The clinical exercise programs used in the studies were heterogeneous; therefore, additional high-quality RCTs are required.
Topics: Exercise Therapy; Head and Neck Neoplasms; Humans; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome; Trismus
PubMed: 32890607
DOI: 10.1016/j.radonc.2020.08.024 -
Clinical Therapeutics Aug 2020Bone metastases from solid tumors and multiple myeloma (MM) represent an important source of morbidity. The present meta-analysis was performed with the purpose of... (Meta-Analysis)
Meta-Analysis
PURPOSE
Bone metastases from solid tumors and multiple myeloma (MM) represent an important source of morbidity. The present meta-analysis was performed with the purpose of comparing the efficacy and tolerability of denosumab versus zoledronic acid (ZA) in the prevention of skeletal-related events (SREs) in patients with bone metastases secondary to solid tumors or bone lesions in multiple myeloma.
METHODS
We searched PubMed, PubMed Central, EMBASE, the Cochrane Library, and ClinicalTrials.gov for relevant studies published until April 23, 2020. We included randomized, controlled trials that investigated the efficacy and tolerability of denosumab 120 mg SC versus ZA 4 mg IV, given every 4 weeks, in patients with bone lesions in multiple myeloma or bone metastases secondary to advanced solid tumors. Two reviewers independently identified studies, assessed the risk for bias, and extracted the data. Times to event outcomes were analyzed using hazard ratios (HRs) and 95% CIs. We analyzed tolerability outcomes using risk ratios (RRs) and 95% CIs, with a fixed-effects model.
FINDINGS
Four randomized, controlled trials (7379 patients) were identified as suitable for analysis. The pooled data indicated that denosumab was more favorable than ZA in delaying the time to first on-study SRE (HR = 0.86; 95% CI, 0.80-0.93; P = 0.0001) as well as the time to first and subsequent on-study SREs (HR = 0.83; 95% CI, 0.76-0.90; P < 0.0001); however, the results on overall survival and disease progression were similar between the 2 drugs. Additionally, denosumab was associated with lower risks for bone pain (risk ratio [RR] = 0.88; 95% CI, 0.80-0.97; P = 0.01), osteonecrosis of the jaw (RR = 0.75; 95% CI, 0.61-0.93; P = 0.007), and acute-phase reactions (RR = 0.47; 95% CI, 0.40-0.56; P < 0.00001).
IMPLICATIONS
Compared with ZA, denosumab demonstrated efficacy in significantly delaying on-study SREs. Furthermore, it showed a better tolerability profile, despite being associated with potential yet manageable adverse events. This study was registered with PROSPERO (identifier: CRD42019126390).
Topics: Bone Density Conservation Agents; Bone Neoplasms; Denosumab; Humans; Multiple Myeloma; Randomized Controlled Trials as Topic; Zoledronic Acid
PubMed: 32718784
DOI: 10.1016/j.clinthera.2020.05.019 -
Long-term impact of bone-modifying agents for the treatment of bone metastases: a systematic review.Supportive Care in Cancer : Official... Feb 2021Bone-modifying agents (BMAs) for bone metastases are commonly prescribed for many years even though randomized clinical trials are only 1-2 years in duration. A...
PURPOSE
Bone-modifying agents (BMAs) for bone metastases are commonly prescribed for many years even though randomized clinical trials are only 1-2 years in duration. A systematic review on the risk-benefit of BMA use for > 2 years in breast cancer or castrate-resistant prostate cancer was conducted.
METHODS
MEDLINE, Embase, and Cochrane databases were searched (1970-February 2019) for randomized and observational studies, and case series reporting on BMA efficacy (skeletal-related events and quality of life) and toxicity (osteonecrosis of the jaw, renal impairment, hypocalcemia, and atypical femoral fractures) beyond 2 years.
RESULTS
Of 2107 citations, 64 studies were identified. Three prospective and 9 retrospective studies were eligible. Data beyond 2 years was limited to subgroup analyses in all studies. Only one study (n = 181) reported skeletal-related event rates based on bisphosphonate exposure, with decreased rates from 27.6% (0-24 months) to 15.5% (> 24 months). None reported on quality of life. All 12 studies (denosumab (n = 948), zoledronate (n = 1036), pamidronate (n = 163), pamidronate-zoledronate (n = 522), ibandronate (n = 118)) reported ≥ 1 toxicity outcome. Seven bisphosphonate studies (n = 1077) and one denosumab study (n = 948) reported on osteonecrosis of the jaw. Across three studies (n = 1236), osteonecrosis of the jaw incidence ranged from 1 to 4% in the first 2 years to 3.8-18% after 2 years. Clinically significant hypocalcemia ranged from 1 to 2%. Severe renal function decline was ≤ 3%. Atypical femoral fractures were rare.
CONCLUSIONS
Evidence informing the use of BMA beyond 2 years is heterogeneous and based on retrospective analysis. Prospective randomized studies with greater emphasis on quality of life are needed.
PROSPERO REGISTRATION NUMBER
CRD42019126813.
Topics: Bone Density Conservation Agents; Bone Neoplasms; Breast Neoplasms; Diphosphonates; Female; Humans; Male; Observational Studies as Topic; Prospective Studies; Prostatic Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Retrospective Studies
PubMed: 32535678
DOI: 10.1007/s00520-020-05556-0 -
Oral and Maxillofacial Surgery Sep 2020The purpose of this study is to find out if the biological behavior and the capacity of the odontogenic keratocyst (OKC) in maintaining pathologic cells alive are more...
The purpose of this study is to find out if the biological behavior and the capacity of the odontogenic keratocyst (OKC) in maintaining pathologic cells alive are more similar to the dentigerous cyst or to the ameloblastoma by assessing bcl-2. We searched MEDLINE, Web of Science, and Scopus for immunohistochemical studies reporting OKCs, dentigerous cysts, and ameloblastomas. Risk difference between the lesions expressing bcl-2 was the effect measure and a P value < 0.05 was considered to provide evidence to the effect estimates. OKCs have an estimated difference of 91% in the probability to express the bcl-2 over dentigerous cysts, but there is no difference in the expression of bcl-2 between OKCs and ameloblastomas. The present study demonstrated a great risk difference in the expression of bcl-2 between OKCs and dentigerous cysts and no risk difference between OKCs and ameloblastomas. OKC's growth may indirectly be attributed to the anti-apoptotic effect of bcl-2 in the cystic epithelium and not only to the increase of its intraluminal pressure. Therefore, the classification of this lesion into keratocystic odontogenic tumor should be carefully reconsidered.
Topics: Dentigerous Cyst; Humans; Immunohistochemistry; Jaw Neoplasms; Odontogenic Cysts; Odontogenic Tumors; Proto-Oncogene Proteins c-bcl-2
PubMed: 32488544
DOI: 10.1007/s10006-020-00856-5 -
Medicina Oral, Patologia Oral Y Cirugia... May 2020The aim of the present study was to analyse the incidence, risk ratio (RR) and prognoses of two types of medication-related osteonecrosis of the jaws (MRONJ):... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of the present study was to analyse the incidence, risk ratio (RR) and prognoses of two types of medication-related osteonecrosis of the jaws (MRONJ): denosumab-related osteonecrosis of the jaws (DRONJ) and Bisphosphonate-Related Osteonecrosis of the Jaws (BRONJ) in cancer patients under treatment with denosumab or zoledronic acid (ZA).
MATERIAL AND METHODS
An electronic and manual search was conducted for randomized controlled trials (RCTs) until May 2019. Assessment of the identified studies, risk of bias and data extraction were performed independently by two reviewers. The incidence of DRONJ and BRONJ and the RR to develop MRONJ were calculated at 1 year, 2 years and 3 years of exposure. It was also calculated the odds ratio (OR) of their respective prognoses. They were calculated normalizing the values of the individual studies to 1 year, 2 years or 3 years when necessary through robust regression models using a statistical program.
RESULTS
From 1.277 references identified, 8 RCTs were included, which comprised a total of 13.857 patients with a variety of neoplasms. The incidence of DRONJ in cancer patients under treatment with denosumab ranged from 0.5 to 2.1% after 1 year, 1.1 to 3.0% after 2 years, and 1.3 to 3.2% after 3 years of exposure. The incidence of BRONJ in cancer patients under treatment with ZA ranged from 0.4 to 1.6% after 1 year of exposure, 0.8 to 2.1% after 2 years, and 1.0 to 2.3% after 3 years of exposure. Statistically significant differences were found between denosumab and ZA in the risk of developing MRONJ after 1, 2 and 3 years of exposure. Nevertheless, there were no significant differences in terms of patient prognosis.
CONCLUSIONS
Denosumab is associated with a significantly higher risk of developing MRONJ compared to ZA. Nevertheless, no differences were found in its prognoses.
Topics: Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Denosumab; Diphosphonates; Humans; Neoplasms; Zoledronic Acid
PubMed: 32271321
DOI: 10.4317/medoral.23324 -
Journal of Stomatology, Oral and... Sep 2020Primordial odontogenic tumour (POT) is a novel entity that was described in 2014 and that is included in the group of benign mixed epithelial and mesenchymal odontogenic...
BACKGROUND
Primordial odontogenic tumour (POT) is a novel entity that was described in 2014 and that is included in the group of benign mixed epithelial and mesenchymal odontogenic tumours. In recent years, several papers have added new cases with some clinical and histopathological aspects that slightly differ from those described in the original report. The aim of this systematic review is to update all available data on POT published in the literature and to identify those features of the neoplasm that require further investigation.
MATERIALS AND METHODS
A systematic review of literature was conducted using PubMed, Embase, Web of Science and Scopus. Additional sources were also checked. Publications reporting cases with enough clinicopathological information were included, without any time or language restrictions. Histopathological or radiological studies were considered for qualitative analysis.
RESULTS
A total of 30 publications were included. Seventeen papers were used for quantitative analysis while 13 papers were used only for qualitative analysis. A total of 18 cases of POT were identified. Some clinical, radiographic, histopathological and therapeutic features were common in all reported cases, while other aspects of the neoplasm were inconsistent through published cases. This inconsistency was particularly remarkable when dealing with the histopathological features of the neoplasm.
DISCUSSION
Some issues about POT remain unclear and deserve to be clarified by future reports. The description of the odontogenic epithelium covering the ectomesenchyme is often contradictory, while it remains debatable whether peripheral ameloblastic epithelial islands or hard dental tissue deposition can occasionally occur within the tumour.
Topics: Epithelium; Humans; Odontogenic Tumors
PubMed: 32145435
DOI: 10.1016/j.jormas.2020.02.008