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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of Controlled Trials (CENTRAL), and Web of Science Core Collection electronic databases and ClinicalTrials.gov for unpublished studies were searched from inception to March 2, 2024.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 -
Cancer Medicine Sep 2023HPV infection can cause cancer, and standard treatments often result in recurrence. The extent to which liquid biopsy using HPV circulating tumor DNA (HPV ctDNA) can be... (Meta-Analysis)
Meta-Analysis
BACKGROUND
HPV infection can cause cancer, and standard treatments often result in recurrence. The extent to which liquid biopsy using HPV circulating tumor DNA (HPV ctDNA) can be used as a promising marker for predicting recurrence in HPV-related cancers remains to be validated. Here we conducted a systematic review and meta-analysis to assess its effectiveness in predicting treatment response.
METHODS
We conducted a systematic literature search of online databases, including PubMed, Embase, Scopus, and the Cochrane Library, up to December 2022. The goal was to identify survival studies that evaluated the potential of plasma HPV ctDNA at baseline and end-of-treatment (EoT) in predicting recurrence of related cancers. Hazard ratios were estimated directly from models or extracted from Kaplan-Meier plots.
RESULTS
The pooled effect of HPV ctDNA presence on disease recurrence was estimated to be HR = 7.97 (95% CI: [3.74, 17.01]). Subgroup analysis showed that the risk of recurrence was HR = 2.17 (95% CI: [1.07, 4.41]) for baseline-positive cases and HR = 13.21 (95% CI: [6.62, 26.36]) for EoT-positive cases. Significant associations were also observed between recurrence of oropharyngeal squamous cell carcinoma (HR = 12.25 (95% CI: [2.62, 57.36])) and cervical cancer (HR = 4.60 (95% CI: [2.08, 10.17])) in plasma HPV ctDNA-positive patients.
CONCLUSIONS
The study found that HPV ctDNA detection can predict the rate of relapse or recurrence after treatment, with post-treatment measurement being more effective than baseline assessment. HPV ctDNA could be used as a surrogate or incorporated with other methods for detecting residual disease.
Topics: Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Circulating Tumor DNA; Neoplasm Recurrence, Local; Head and Neck Neoplasms
PubMed: 37492996
DOI: 10.1002/cam4.6377 -
Cancers Feb 2024The study cohort consisted of 83 patients with a mean age of 49.55 (SD 13.72) with a female preponderance (60 patients). Here, 32.14% of patients had primary LTS; the... (Review)
Review
The study cohort consisted of 83 patients with a mean age of 49.55 (SD 13.72) with a female preponderance (60 patients). Here, 32.14% of patients had primary LTS; the remaining were metastases. Clinical presentation included nonspecific back pain (57.83%), weakness (21.69%) and radicular pain (18.07%). History of uterine neoplasia was found in 33.73% of patients. LTS preferentially affected the thoracic spine (51.81%), followed by the lumbar (21.67%) spine. MRI alone was the most common imaging modality (33.33%); in other cases, it was used with CT (22.92%) or X-ray (16.67%); 19.23% of patients had Resection/Fixation, 15.38% had Total en bloc spondylectomy, and 10.26% had Corpectomy. A minority of patients had laminectomy and decompression. Among those with resection, 45.83% had a gross total resection, 29.17% had a subtotal resection, and 16.67% had a near total resection. Immunohistochemistry demonstrated positivity for actin (43.37%), desmin (31.33%), and Ki67 (25.30). At a follow-up of 19.3 months, 61.97% of patients were alive; 26.25% of 80 patients received no additional treatment, 23.75% received combination radiotherapy and chemotherapy, only chemotherapy was given to 20%, and radiotherapy was given to 17.5%. Few (2.5%) had further resection. For an average of 12.50 months, 42.31% had no symptoms, while others had residual (19.23%), other metastasis (15.38%), and pain (7.69%). On follow-up of 29 patients, most (68.97%) had resolved symptoms; 61.97% of the 71 patients followed were alive.
PubMed: 38398139
DOI: 10.3390/cancers16040748 -
Minimal residual disease in systemic light chain amyloidosis: a systematic review and meta-analysis.Journal of Cancer Research and Clinical... Apr 2024Minimal residual disease (MRD) is a validated prognostic factor in several hematological malignancies. However, its role in systemic light chain (AL) amyloidosis remains... (Meta-Analysis)
Meta-Analysis
PURPOSE
Minimal residual disease (MRD) is a validated prognostic factor in several hematological malignancies. However, its role in systemic light chain (AL) amyloidosis remains controversial, and this systematic review and meta-analysis aims to fill this gap.
METHODS
We searched for relevant studies on Pubmed, Embase, and Cochrane Controlled Register of Trials, nine studies involving 451 patients were included and meta-analyzed. This systematic review has been registered in PROSPERO (CRD42023494169).
RESULTS
Our study found that in the group of patients who achieved very good partial response (VGPR) or better, MRD negativity was correlated with higher cardiac and renal response rates [pooled risk ratio (RR) = 0.74 (95% CI 0.62-0.89), 0.74 (95% CI 0.64-0.87), respectively]. Patients with MRD positivity had a higher hematologic progression rate within two years after MRD detection [pooled RR = 10.31 (95% CI 2.02-52.68)]; and a higher risk of hematologic + organ progression in the first year [pooled RR = 12.57 (95% CI 1.73-91.04)]. Moreover, MRD negativity was correlated with a better progression-free survival (PFS) [pooled hazard ratio (HR) = 0.27 (95% CI 0.17-0.45)]; but it did not significantly improve the overall survival (OS) [pooled HR = 0.34 (95% CI 0.11-1.07)].
CONCLUSION
In AL amyloidosis, our study supports that MRD negativity correlates with higher cardiac or renal response rates and indicates a better PFS in the follow-up. However, the correlation between OS and the status of MRD is not significant.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Neoplasm, Residual; Amyloidosis; Hematologic Neoplasms; Kidney
PubMed: 38619663
DOI: 10.1007/s00432-024-05733-2 -
Oncology Letters Oct 2023Further adjuvant chemotherapy treatment can provide benefits to certain patients with triple-negative breast cancer (TNBC) that fail to achieve pathological complete...
Prognostic relevance of tumor‑infiltrating lymphocytes in residual tumor tissue from patients with triple‑negative breast cancer following neoadjuvant chemotherapy: A systematic review and meta‑analysis.
Further adjuvant chemotherapy treatment can provide benefits to certain patients with triple-negative breast cancer (TNBC) that fail to achieve pathological complete response (pCR) after the administration of a neoadjuvant chemotherapy (NAC) regimen. However, biomarkers suitable for identifying patients likely to experience poor prognostic outcomes after undergoing additional adjuvant chemotherapy are currently lacking. Accordingly, the present meta-analysis was conducted to explore the relationship between tumor-infiltrating lymphocytes (TILs) or TIL subtypes (CD4 or CD8) in residual tumor (RT) tissue following NAC and TNBC patient prognosis. Relevant studies published through March 2023 were identified in Pubmed, The Cochrane Library, Embase and Web of Science databases. After excluding irrelevant studies, data were extracted from the remaining reports, while study quality was analyzed with the Newcastle-Ottawa Scale. Subsequent analyses were performed with Stata 14.0 and Review Manager 5.3. In total, seven relevant studies incorporating 1,202 patients were identified, all of which were retrospective cohort studies. Pooled analyses demonstrated that those patients exhibiting higher levels of RT TIL infiltration following NAC exhibited significantly improved recurrence-free, metastasis-free and event-free survival (RFS/MFS/EFS) compared with patients with lower RT TIL infiltration levels, together with an improved distant recurrence-free interval (DRFI) [hazard ratio (HR)=0.52; 95% confidence interval (CI)=0.39-0.69; P<0.00001]. In addition, patients exhibiting high RT TIL infiltration exhibited improved overall survival (OS) and breast cancer-specific survival (BCSS; HR=0.49; 95% CI=0.38-0.65; P<0.00001). Additional subgroup analyses revealed that patients with higher TIL infiltration levels or TIL subtype (CD4 or CD8) infiltration exhibited improved RFS/MFS/EFS/DRFI as compared with patients with lower levels of overall TIL or TIL subtype (CD4 or CD8) infiltration in RT tissue (HR=0.35, 95% CI=0.20-0.59, P<0.0001; HR=0.49, 95% CI=0.33-0.71, P=0.0002). Consistently, the OS/BCSS of patients exhibiting high levels of overall TIL or TIL subtype (CD4 or CD8) infiltration was increased compared with patients with lower levels of such infiltration (HR=0.33, 95% CI=0.19-0.59, P=0.0002; HR=0.55, 95% CI=0.41-0.76, P=0.0002). These data thus demonstrate that levels of overall TIL infiltration or infiltration by CD4 or CD8 TILs in RT following NAC can be used as a biomarker to reliably predict prognostic outcomes in patients with TNBC, in addition to highlighting possible targets that may guide the further immunotherapeutic management of these patients.
PubMed: 37664648
DOI: 10.3892/ol.2023.14028 -
Surgical Neurology International 2024Non-functioning pituitary adenomas (NFPAs) are well-differentiated benign tumors originating from the adenohypophyseal cells of the pituitary gland. They present with... (Review)
Review
Comparing redo surgery and stereotactic radiosurgery for recurrent, residual, and/or tumors showing progression in nonfunctioning pituitary adenomas: A systematic review and meta-analysis.
BACKGROUND
Non-functioning pituitary adenomas (NFPAs) are well-differentiated benign tumors originating from the adenohypophyseal cells of the pituitary gland. They present with headaches, visual disorders, or cranial nerve deficits. NFPAs can recur, progress, or present as residual tumors. We, therefore, conducted this review to compare the effects of both revision surgery and stereotactic surgery on tumor size, visual status, endocrine status, and complications.
METHODS
A systematic review of published literature on recurrent, residual, or progressing NFPAs that underwent redo surgery or stereotactic radiosurgery from the inception till June 2020 was conducted as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Thirteen records (1209 patients) were included, and risk ratio (RR) and 95% confidence intervals (CIs) estimated from each study were pooled using a random-effects meta-analysis model.
RESULTS
Redo surgery was the preferred intervention in patients presenting with larger tumor sizes and was more effective in reducing the tumor size as compared to stereotactic radiosurgery (SRS) (risk ratio [RR] 56.14; 95% CI, 16.45-191.58). There was more visual loss with revision surgery as compared to SRS (risk ratio [RR] 0.08; 95% CI, 0.03-0.20). However, SRS was associated with fewer complications, such as new diabetes insipidus, as compared to the redo surgery (risk ratio [RR] 0.01; 95% CI 0.01-0.03).
CONCLUSION
Redo surgery is the superior choice in the treatment of recurrent/residual or progressing NFPAs if the tumor size is large and an immediate reduction in tumor burden through debulking is warranted. However, redo surgery is associated with a higher risk of visual loss, new endocrinopathies, and other complications, in contrast to SRS.
PubMed: 38468659
DOI: 10.25259/SNI_907_2023 -
Digestive and Liver Disease : Official... Dec 2023There is debate over the impact of residual microscopic disease after ileocecal resection in Crohn's disease (CD) to predict recurrence. We conducted a meta-analysis to... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
There is debate over the impact of residual microscopic disease after ileocecal resection in Crohn's disease (CD) to predict recurrence. We conducted a meta-analysis to evaluate the impact of positive histological margins and plexitis after ileocecal resection on the risk of postoperative recurrence.
METHODS
Using a systematic search, we identified. 30 studies evaluating the impact of inflammatory margins on CD recurrence. The primary outcome was the postoperative clinical recurrence and secondary outcomes were surgical, and endoscopic recurrence. We performed random-effects meta-analysis and estimated odds ratio (OR) and 95% CIs.
RESULTS
Thirty studies were analyzed, seven focused on myenteric plexitis, six on submucosal plexitis and twenty-three on positive margins. Inflammatory margins were associated with a higher rate of clinical and surgical recurrences: respectively 14 studies - OR 2.38; 95% CI, 1.54 - 3.68- I2 = 68.2%, Q test-p = 0.0003 and 8 studies - OR, 1.52; 95% CI, 1.07-2.16 - I2 =0%; Q test-p = 0.43. The presence of myenteric plexitis was associated with a higher rate of clinical recurrence (4 studies- OR, 1.60; 95%CI, 1.12-2.29; I2= 0%, Q-test-p = 0.61), and of endoscopic recurrence (4 studies - OR, 4.25; 95%CI; 2.06-8.76; I2= 0%, Q test-p = 0.97). Submucosal plexitis was not associated with an increased risk of endoscopic recurrence (4 studies - OR, 0.94; 95%CI; 0.58-1.52; I2= 0%, Q test-p = 0.79).
CONCLUSION
Inflammatory margins and/or plexitis were associated with postoperative recurrence after ileocecal resection for CD. These elements should be taken into account in future algorithm for prevention of postoperative recurrence.
Topics: Humans; Ileum; Prognosis; Neoplasm Recurrence, Local; Cecum; Crohn Disease; Margins of Excision; Recurrence; Retrospective Studies
PubMed: 36658042
DOI: 10.1016/j.dld.2022.12.021 -
Clinical and Experimental Medicine Sep 2023Circulating tumor DNA (ctDNA) detection holds promise for genetic analyses and quantitative assessment of tumor burden. A systematic review and meta-analysis were... (Meta-Analysis)
Meta-Analysis
Circulating tumor DNA (ctDNA) detection holds promise for genetic analyses and quantitative assessment of tumor burden. A systematic review and meta-analysis were conducted to investigate the clinical relevance of ctDNA among patients with localized non-small cell lung cancer (NSCLC). PubMed, EMBASE, and the Cochrane Library were searched for eligible studies published from January 2001 to April 2022. After quality assessments and data extraction, diagnostic accuracy variables and prognostic data were calculated and analyzed by Meta-Disc 1.4, Review Manager 5.4.1, and STATA 17.0. Eight prospective studies and one retrospective study including 784 patients with localized NSCLC were used in our meta-analysis. The pooled sensitivity and specificity of ctDNA for minimal residual disease (MRD) detection were 0.58 and 0.93, respectively. The pooled positive and negative likelihood ratios were 7.57 (95% confidence interval (CI) 2.84-20.20) and 0.45 (95% CI 0.37-0.55), respectively. The area under the summary receiver operating characteristic curve was 0.8967, and the diagnostic odds ratio was 32.26 (95% CI 14.63-71.12). In addition, both precurative-treatment and postcurative-treatment ctDNA positivity was associated with worse recurrence-free survival (hazard ratio (HR), 3.82 and 8.32, respectively) and worse overall survival (HR, 3.82 and 4.73, respectively). The findings suggested that ctDNA detection has beneficial utility regarding MRD detection specificity; moreover, positive ctDNA was associated with poor prognosis in patients with localized NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Circulating Tumor DNA; Lung Neoplasms; Clinical Relevance; Prospective Studies; Retrospective Studies; Biomarkers, Tumor
PubMed: 36315311
DOI: 10.1007/s10238-022-00924-y -
Neurosurgery Apr 2024Schwannomas originating from the lower cranial nerves (LCNS) are rare and pose a significant surgical challenge. Resection is the mainstay treatment; however, risk of...
BACKGROUND AND OBJECTIVES
Schwannomas originating from the lower cranial nerves (LCNS) are rare and pose a significant surgical challenge. Resection is the mainstay treatment; however, risk of treatment morbidity is considerable, and the available literature regarding differential treatment outcomes in this vulnerable population is sparse.
METHODS
A single-institution cohort study and systematic literature review of LCNS were performed.
RESULTS
Fifty-eight patients were included: 34 underwent surgical resection and 24 underwent stereotactic radiosurgery (SRS). The median age at diagnosis was 48 years (range 17-74). Presenting symptoms were dysphagia (63%), dysarthria/hypophonia (47%), imbalance (33%), and hearing loss/tinnitus (30%). Tumor size was associated with surgical resection, as compared with initial SRS (4.1 cm vs 1.5 cm, P = .0001). Gross total resection was obtained in 52%, with tumor remnants predominantly localized to the jugular foramen (62%). Post-treatment worsening of symptoms occurred in 68% of surgical and 29% of SRS patients ( P = .003). Postoperative symptoms were mostly commonly hypophonia/hoarseness (63%) and dysphagia (59%). Seven patients (29%) had new neurological issues after SRS treatment, but symptoms were overall milder. The median follow-up was 60 months (range 12-252); 98% demonstrated meaningful clinical improvement. Eighteen surgical patients (53%) underwent adjuvant radiation at a median of 5 months after resection (range 2-32). At follow-up, tumor control was 97% in the surgical cohort and 96% among SRS patients.
CONCLUSION
Although LCNS resection is potentially morbid, most postoperative deficits are transient, and patients achieve excellent tumor control-particularly when paired with adjuvant SRS. For minimally symptomatic patients undergoing surgical intervention, we advise maximally safe resection with intracapsular dissection to preserve nerve integrity where possible. For residual or as a primary treatment modality, SRS is associated with low morbidity and high rates of long-term tumor control.
Topics: Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Cohort Studies; Deglutition Disorders; Neurilemmoma; Treatment Outcome; Cranial Nerves; Radiosurgery; Retrospective Studies; Follow-Up Studies
PubMed: 37874134
DOI: 10.1227/neu.0000000000002735 -
Surgical Endoscopy Jun 2024To systematically review and meta-analyze the efficacy and safety of salvage endoscopy for residual or recurrence of colorectal tumors after endoscopic resection. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically review and meta-analyze the efficacy and safety of salvage endoscopy for residual or recurrence of colorectal tumors after endoscopic resection.
METHODS
Multiple databases including PubMed, EMBASE and the Cochrane Library were searched to screen for eligible studies and perform data extraction and pooled analysis.
RESULTS
Sixteen studies on salvage endoscopy for residual or recurrent colorectal cancer after endoscopic resection were included, covering approximately 994 patients. The results of the meta-analysis demonstrated that salvage endoscopic therapy for residual or recurrent colorectal tumors following endoscopic resection achieved an en bloc resection rate of 92% (95% CI 0.85-0.97; I = 91%) and an R0 resection rate of 82% (95% CI 0.75-0.87; I = 78%). The rates of intraoperative or postoperative bleeding and perforation were 10%/1% and 5%/2%, and the recurrence rate was 2%.
CONCLUSIONS
Salvage endoscopic resection is an effective and safe treatment strategy for residual or recurrent colorectal tumors after endoscopic resection.
Topics: Humans; Colorectal Neoplasms; Salvage Therapy; Neoplasm Recurrence, Local; Neoplasm, Residual; Treatment Outcome; Colonoscopy
PubMed: 38744694
DOI: 10.1007/s00464-024-10879-8