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JAMA Network Open Jun 2024Treatment of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiotherapy plus total mesorectal excision and adjuvant chemotherapy. However, total... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Treatment of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiotherapy plus total mesorectal excision and adjuvant chemotherapy. However, total neoadjuvant therapy (TNT) protocols (ie, preoperative chemotherapy in addition to radiotherapy) may allow better adherence and early treatment of distant micrometastases and may increase pathological complete response (pCR) rates.
OBJECTIVE
To assess the efficacy and tolerability of TNT protocols for LARC.
DATA SOURCES
MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science Core Collection electronic databases and ClinicalTrials.gov for unpublished studies were searched from inception to March 2, 2024.
STUDY SELECTION
Randomized clinical trials including adults with LARC who underwent rectal resection as a final treatment were included. Studies including nonoperative treatment (watch-and-wait strategy), treatments other than rectal resection, immunotherapy, or antiangiogenic agents were excluded. Among the initially identified studies, 2.9% met the selection criteria.
DATA EXTRACTION AND SYNTHESIS
Two authors independently screened the records and extracted data. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-compliant pairwise and network meta-analyses with a random-effects model were performed in a frequentist framework, and the certainty of evidence was assessed according to the confidence in network meta-analysis approach.
MAIN OUTCOMES AND MEASURES
The primary outcome was pCR, defined as the absence of residual tumor at pathological assessment after surgery. Secondary outcomes included tolerability, toxic effects, perioperative outcomes, and long-term survival.
RESULTS
Of 925 records identified, 27 randomized clinical trials, including 13 413 adults aged 18 years or older (median age, 60.0 years [range, 42.0-63.5 years]; 67.2% male) contributed to the primary network meta-analysis. With regard to pCR, long-course chemoradiotherapy (L-CRT) plus consolidation chemotherapy (relative risk [RR], 1.96; 95% CI, 1.25-3.06), short-course radiotherapy (S-RT) plus consolidation chemotherapy (RR, 1.76; 95% CI, 1.34-2.30), and induction chemotherapy plus L-CRT (RR, 1.57; 95% CI, 1.09-2.25) outperformed standard L-CRT with single-agent fluoropyrimidine-based chemotherapy. Considering 3-year disease-free survival, S-RT plus consolidation chemotherapy (RR, 1.08; 95% CI, 1.01-1.14) and induction chemotherapy plus L-CRT (RR, 1.12; 95% CI, 1.01-1.24) outperformed L-CRT, in spite of an increased 5-year locoregional recurrence rate of S-RT plus consolidation chemotherapy (RR, 1.65; 95% CI, 1.03-2.63).
CONCLUSIONS AND RELEVANCE
In this systematic review and network meta-analysis, 3 TNT protocols were identified to outperform the current standard of care in terms of pCR rates, with good tolerability and optimal postoperative outcomes, suggesting they should be recognized as first-line treatments.
Topics: Rectal Neoplasms; Humans; Neoadjuvant Therapy; Network Meta-Analysis; Female; Middle Aged; Male; Randomized Controlled Trials as Topic; Adult
PubMed: 38833249
DOI: 10.1001/jamanetworkopen.2024.14702 -
Heliyon Jun 2024In recent years, the combination of targeted drugs, such as Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, with endocrine therapy (ET), has emerged as a new research...
BACKGROUND
In recent years, the combination of targeted drugs, such as Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, with endocrine therapy (ET), has emerged as a new research focus in the treatment of hormone receptor-positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) breast cancer. This network meta-analysis aimed to systematically evaluate the efficacy and safety of CDK4/6 inhibitors combined with ET for HR+/HER2-breast cancer.
METHODS
A systematic search was conducted across PubMed, Web of Science, Cochrane Library, and GeenMedical databases to identify randomized controlled trials investigating the use of CDK4/6 inhibitors in combination with endocrine therapy for the treatment of HR+/HER2-breast cancer. The search period spanned from the inception of each database up to February 29, 2024. Data analysis was conducted using Stata 14.0 and R 4.1.0 software.
RESULTS
A total of 20 randomized controlled trials (RCTs) were included in this study, investigating the effectiveness of four CDK4/6 inhibitors-Abemaciclib, Dalpiciclib, Ribociclib, and Palbociclib-when combined with ET for the treatment of HR+/HER2-breast cancer. The results indicated that Abemaciclib + ET, Dalpiciclib + ET, Palbociclib + ET, and Ribociclib + ET exhibited similar therapeutic effects in terms of improving objective response rate (ORR), disease control rate (DCR) and reducing the occurrence of fatigue, all of which were superior to ET alone. However, in terms of prolonging progression-free survival (PFS) and overall survival (OS), Dalpiciclib + ET significantly improved PFS compared to Ribociclib + ET, Palbociclib + ET, Abemaciclib and Palbociclib. Ribociclib + ET significantly improved OS compared to Palbociclib + ET. Regarding overall adverse reaction events (AREs), Dalpiciclib + ET had a higher incidence compared to Ribociclib + ET. The incidence of neutropenia caused by Dalpiciclib + ET was significantly higher compared to Palbociclib + ET, Ribociclib + ET, Abemaciclib, and Palbociclib. Abemaciclib + ET demonstrated the worst safety profile concerning diarrhea.
CONCLUSION
Abemaciclib + ET likely represents the most effective option in terms of therapeutic effects, but it is prone to causing diarrhea and fatigue. On the other hand, Dalpiciclib + ET likely demonstrates the best efficacy in terms of PFS but exhibits the poorest safety profile, particularly in relation to neutropenia. Therefore, clinicians should exercise increased vigilance in monitoring and managing adverse effects when prescribing Abemaciclib + ET and Dalpiciclib + ET.
PubMed: 38832268
DOI: 10.1016/j.heliyon.2024.e31583 -
Therapeutic Advances in Hematology 2024Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological cancer. Due to its low incidence, researchers struggle to gather sufficient... (Review)
Review
BACKGROUND
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological cancer. Due to its low incidence, researchers struggle to gather sufficient prospective data to inform clinical treatment.
OBJECTIVES
We sought to summarize the clinical characteristics and current treatment methods of BPDCN and provide more specific guidance on treatment options.
DESIGN
A systematic literature review using data from 74 Chinese BPDCN patients.
DATE RESOURCES AND METHODS
We retrospectively analyzed the clinical manifestations, treatment response, survival outcomes, and prognostic factors of six BPDCN patients treated at the First Affiliated Hospital of Zhengzhou University and 68 patients described in 28 articles published in the China Knowledge Network database since 2019.
RESULTS
In Chinese patients, the disease occurred with a male-to-female ratio of 2.52 and a median age of onset of 50 years in adults and 10 years in pediatric patients. Immunohistochemical analysis revealed distinctive immune phenotypes of BPDCN cells, characterized by high expression levels of CD4, CD56, CD123, and HLA-DR, while showing minimal to no expression of myeloperoxidase (MPO), CD20, and CD79a. There was no significant difference in the initial complete remission (CR) rate, relapse rate, and the overall survival (OS) time of patients receiving acute myeloid leukemia-like, acute lymphocytic leukemia-like, or non-Hodgkin's lymphoma-like chemotherapy regimens. Univariate analysis identified CD3 expression, male gender, and central nervous system infiltration as hazardous factors. In multivariate analysis, age proved to be an independent prognostic indicator, indicating better prognosis and longer OS time in younger patients. Notably, hematopoietic stem cell transplantation (HSCT) emerged as a significant factor in improving the survival outcomes for individuals diagnosed with BPDCN. However, further investigation is needed to explore the role of HSCT and the best timing for its implementation in pediatric BPDCN patients.
CONCLUSION
Administering HSCT during the initial CR state following inductive chemotherapy might extend the OS and improve the prognosis of patients with BPDCN.
PubMed: 38832237
DOI: 10.1177/20406207241251602 -
International Forum of Allergy &... Jul 2024Sinonasal malignancies (SNMs) frequently present with orbital invasion. Orbital exenteration (OE) can lead to significant morbidity. Induction chemotherapy (IC) is a... (Review)
Review
BACKGROUND
Sinonasal malignancies (SNMs) frequently present with orbital invasion. Orbital exenteration (OE) can lead to significant morbidity. Induction chemotherapy (IC) is a promising treatment alternative that may allow for orbit preserving (OP) treatments without compromising patient survival. This systematic review was conducted to synthesize the published data on SNM patients with orbital invasion who underwent IC, including tumor response, orbital outcomes, and survival.
METHODS
The study protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Databases Embase, Cochrane, Medline, and Scopus, from inception to July 17, 2023, were searched.
RESULTS
Nineteen studies were included, encompassing 305 SNM patients with orbital invasion treated with IC. Fourteen studies reported an overall IC response rate (positive response defined as complete or partial tumor volume reduction) of 77.2%. Among included studies, OE rates after IC ranged from 0 to 40%. Three studies reported a high rate of posttreatment functional orbital preservation (89.8-96.0%). Five studies specifically reported that 62.5% (60 out of 96) of patients were downgraded from planned OE to OP treatment following IC. Three studies reported a significant overall survival (OS) improvement in IC responders versus IC nonresponders. Following IC, 5-year OS ranged from 44.2 to 55.5%. Patients with olfactory neuroblastoma demonstrated the highest IC response rate and lowest OE rate (100 and 0%, respectively) versus those with sinonasal undifferentiated carcinomas (68.4 and 0%) or squamous cell carcinomas (76.7 and 16%).
CONCLUSIONS
For select patients, IC may allow for OP in locally advanced SNMs with orbital involvement.
Topics: Humans; Paranasal Sinus Neoplasms; Induction Chemotherapy; Orbital Neoplasms; Neoplasm Invasiveness; Treatment Outcome; Orbit
PubMed: 38829173
DOI: 10.1002/alr.23380 -
Frontiers in Pharmacology 2024FLT3 mutations are closely associated with the occurrence of hematological and solid malignancies, especially with acute myeloid leukemia. Currently, several FLT3...
FLT3 mutations are closely associated with the occurrence of hematological and solid malignancies, especially with acute myeloid leukemia. Currently, several FLT3 inhibitors are in clinical trials, and some have been applied in clinic. However, the safety, efficacy and pharmacodynamics of these FLT3 inhibitors have not been systemically analyzed before. We searched and reviewed clinical trial reports on the monotherapy of 13 FLT3 inhibitors, including sorafenib, lestaurtinib, midostaurin, gilteritinib, quizartinib, sunitinib, crenolanib, tandutinib, cabozantinib, pexidartinib, pacritinib, famitinib, and TAK-659 in patients with hematological and solid malignancies before May 31, 2023. Our results showed the most common adverse events (AEs) were gastrointestinal adverse reactions, including diarrhea, hand-foot syndrome and nausea, while the most common hematological AEs were febrile neutropenia, anemia, and thrombocytopenia. Based on the published data, the mean overall survival (OS) and the mean progression-free survival (PFS) were 9.639 and 5.905 months, respectively. The incidence of overall response rate (ORR), complete remission (CR), partial response (PR), and stable disease (SD) for all these FLT3 inhibitors was 29.0%, 8.7%, 16.0%, and 42.3%, respectively. The ORRs of FLT3 inhibitors in hematologic malignancies and solid tumors were 40.8% and 18.8%, respectively, indicating FLT3 inhibitors were more effective for hematologic malignancies than for solid tumors. In addition, time to maximum plasma concentration () in these FLT3 inhibitors ranged from 0.7-12.0 hours, but the elimination half-life () range was highly variable, from 6.8 to 151.8 h. FLT3 inhibitors monotherapy has shown significant anti-tumor effect in clinic, and the effectiveness may be further improved through combination medication.
PubMed: 38828446
DOI: 10.3389/fphar.2024.1294668 -
BMC Cancer Jun 2024Colorectal cancer is the leading cause of cancer death worldwide. The first and second lines of treatment for metastatic colorectal cancer (mCRC) include chemotherapy... (Meta-Analysis)
Meta-Analysis
Colorectal cancer is the leading cause of cancer death worldwide. The first and second lines of treatment for metastatic colorectal cancer (mCRC) include chemotherapy based on 5-fluorouracil. However, treatment following progression on the first and second line is still unclear. We searched PubMed, Scopus, Cochrane, and Web of Science databases for studies investigating the use of trifluridine-tipiracil with bevacizumab versus trifluridine-tipiracil alone for mCRC. We used RStudio version 4.2.3; and we considered p < 0.05 significant. Seven studies and 1,182 patients were included - 602 (51%) received trifluridine-tipiracil plus bevacizumab. Compared with control, the progression-free survival (PFS) (HR 0.52; 95% CI 0.42-0.63; p < 0.001) and overall survival (OS) (HR 0.61; 95% CI 0.52-0.70; p < 0.001) were significantly higher with bevacizumab. The objective response rate (ORR) (RR 3.14; 95% CI 1.51-6.51; p = 0.002) and disease control rate (DCR) (RR 1.66; 95% CI 1.28-2.16; p = 0.0001) favored the intervention. Regarding adverse events, the intervention had a higher rate of neutropenia (RR 1.38; 95% CI 1.19-1.59; p = 0.00001), whereas the monotherapy group had a higher risk of anemia (RR 0.60; 95% CI 0.44-0.82; p = 0.001). Our results support that the addition of bevacizumab is associated with a significant benefit in PFS, OS, ORR and DCR.
Topics: Humans; Colorectal Neoplasms; Bevacizumab; Trifluridine; Thymine; Antineoplastic Combined Chemotherapy Protocols; Pyrrolidines; Drug Combinations; Neoplasm Metastasis; Progression-Free Survival; Uracil; Drug Resistance, Neoplasm
PubMed: 38825703
DOI: 10.1186/s12885-024-12447-8 -
Foot and Ankle Surgery : Official... May 2024In the past decade, the transfibular approach to Total Ankle Replacement (TAR) has emerged as an alternative to anterior approach with reduced bone resection. The...
BACKGROUND
In the past decade, the transfibular approach to Total Ankle Replacement (TAR) has emerged as an alternative to anterior approach with reduced bone resection. The purpose of this systematic review is to report survival, complications, and reoperation rates of transfibular TAR.
METHODS
We conducted a systematic search of studies that evaluated complications, reoperations, and survival of transfibular TAR following PRISMA guidelines across PubMed, Scopus and Web of Science.
RESULTS
Our review included data from 12 cohorts, comprising 919 patients across 7 countries, with an average age of 62 years (59% posttraumatic). Over an average follow-up period of 3 years, adverse events occurred in 23% of cases, with 18% requiring surgical reintervention, mostly due to hardware removal. The survival rate of the transfibular TAR metal components was 97% at the final follow-up.
CONCLUSION
Transfibular TAR demonstrates a 97% survival rate at a 3-year follow-up.
LEVEL OF EVIDENCE
Level II.
PubMed: 38821820
DOI: 10.1016/j.fas.2024.05.007 -
Clinical Breast Cancer May 2024Although HER2-low breast cancer (BC) constitutes almost 50% of all BC types, its impact on the pathological complete response (pCR) rate and survival in early BC is... (Review)
Review
Comparison of the Pathological Complete Response Rate and Survival Between HER2-Low and HER2-Zero Breast Cancer in Neoadjuvant Chemotherapy Setting: A Systematic Review and Meta-Analysis.
Although HER2-low breast cancer (BC) constitutes almost 50% of all BC types, its impact on the pathological complete response (pCR) rate and survival in early BC is uncertain. As a result, a systematic review was conducted to compare the pCR rate and survival of HER2-low and HER2-zero BC in the neoadjuvant chemotherapy (NACT) setting. Two reviewers independently performed literature searches using EMBASE, PubMed, and Cochrane Libraries internet databases up to June 2023. Finally, 29 studies with 178,294 patients were included. HER2-low BC had a considerably lower pCR rate compared to HER2-zero BC in the entire population (Risk Ratio [RR] = 0.68, P < .001) and in the hormone receptor (HR)-positive subgroup (RR = 0.73, P = .009), but not in the HR-negative subgroup (RR = 0.99, P = .755). Furthermore, patients with HER2-low BC exhibited prolonged disease-free survival (DFS) and overall survival (OS) compared to those with HER2-zero BC, observed in both the entire cohort (DFS: P = .004; OS: P = .008) and the HR-negative subgroup (DFS: P = .009; OS: P < .001). In the HR-positive population, OS was superior in HER2-low BC patients (P < .001), whereas no significant differences in DFS were observed (P = .064). Our findings imply that the pCR rate and prognosis of HER2-low BC are distinguished from those of HER2-zero BC in early BC treated with NACT, which contributes to a better knowledge of the BC subgroup.
PubMed: 38821742
DOI: 10.1016/j.clbc.2024.05.001 -
The Journal of Evidence-based Dental... Jun 2024Schiegnitz E, Reinicke K, Sagheb K, König J, Al-Nawas B, Grötz KA. Dental implants in patients with head and neck cancer-A systematic review and meta-analysis of the... (Meta-Analysis)
Meta-Analysis
ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION
Schiegnitz E, Reinicke K, Sagheb K, König J, Al-Nawas B, Grötz KA. Dental implants in patients with head and neck cancer-A systematic review and meta-analysis of the influence of radiotherapy on implant survival. Clinical oral implants research. 2022 Oct;33(10):967-99.
SOURCE OF FUNDING
Open access funding enabled by Project DEAL.
TYPE OF STUDY/DESIGN
Systematic review with meta-analysis of data (SRMA).
Topics: Humans; Head and Neck Neoplasms; Dental Implants; Dental Implantation, Endosseous
PubMed: 38821653
DOI: 10.1016/j.jebdp.2023.101967 -
Cancer Treatment Reviews Jul 2024There is a need to improve the outcomes of patients with head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC), especially in recurrent...
A systematic review of antibody-drug conjugates and bispecific antibodies in head and neck squamous cell carcinoma and nasopharyngeal carcinoma: Charting the course of future therapies.
INTRODUCTION
There is a need to improve the outcomes of patients with head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC), especially in recurrent unresectable and metastatic (R/M) setting. Antibody-drug conjugates (ADC) and bispecific antibodies (BsAb) may deliver promising results.
METHODS
We conducted a systematic literature review to identify ADC and BsAb clinical trials, involving patients with HNSCC and NPC, from database creation to December 2023. We reported trial characteristics, overall response rate (ORR), overall survival (OS), and grade ≥ 3 treatment-related adverse events (trAEs).
RESULTS
23 trials (65 % phase I) were found, involving 540 R/M patients (355 [20trials] HNSCC and 185 [5trials] NPC). There were 13 ADC (n = 343) and 10 BsAb (n = 197) trials. 96 % patients were refractory to standard of care treatments. ORR ranged from 0 to 100 %, with the highest ORR for GEN1042 plus chemoimmunotherapy. ORRs for monotherapies were 47 % for ADC, and 0-37 % for BsAb. MRG003 reached in HNSCC 43 % and NPC 47 %. BL-B01D1 54 % in NPC. Longest median OS was seen with MRG003 and KN046. Grade ≥ 3 trAEs were 28-60 % in ADC trials, and 3-33 % BsAb. Grade ≥ 3 myelosuppressive trAEs were typically seen in 8 ADC trials, while 4 BsAb showed infusion-related reactions (IRR). Four treatment-related deaths were reported (1 pneumonitis), all ADC trials.
CONCLUSION
ADC and BsAb antibodies show promise in R/M HNSCC and NPC. Results are premature by small sample sizes and lack of control arm. ADC mainly caused myelosuppression and a pneumonitis case, and BsAb IRR. Further research is warranted in this setting.
Topics: Humans; Antibodies, Bispecific; Head and Neck Neoplasms; Immunoconjugates; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck
PubMed: 38820656
DOI: 10.1016/j.ctrv.2024.102772