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Cancers Dec 2021Cardiotoxicity represents the most frequent cause with higher morbidity and mortality among long-term sequelae affecting classical Hodgkin lymphoma (cHL) and diffuse... (Review)
Review
Late Cardiological Sequelae and Long-Term Monitoring in Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: A Systematic Review by the Fondazione Italiana Linfomi.
Cardiotoxicity represents the most frequent cause with higher morbidity and mortality among long-term sequelae affecting classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) patients. The multidisciplinary team of Fondazione Italiana Linfomi (FIL) researchers, with the methodological guide of Istituto di Ricerche Farmacologiche "Mario Negri", conducted a systematic review of the literature (PubMed, EMBASE, Cochrane database) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in order to analyze the following aspects of cHL and DLBCL survivorship: (i) incidence of cardiovascular disease (CVD); (ii) risk of long-term CVD with the use of less cardiotoxic therapies (reduced-field radiotherapy and liposomal doxorubicin); and (iii) preferable cardiovascular monitoring for left ventricular (LV) dysfunction, coronary heart disease (CHD) and valvular disease (VHD). After the screening of 659 abstracts and related 113 full-text papers, 23 publications were eligible for data extraction and included in the final sample. There was an increased risk for CVD in cHL survivors of 3.6 for myocardial infarction and 4.9 for congestive heart failure (CHF) in comparison to the general population; the risk increased over the years of follow-up. In addition, DLBCL patients presented a 29% increased risk for CHF. New radiotherapy techniques suggested reduced risk of late CVD, but only dosimetric studies were available. The optimal monitoring of LV function by 2D-STE echocardiography should be structured according to individual CV risk, mainly considering as risk factors a cumulative doxorubicine dose >250 mg per square meter (m) and mediastinal radiotherapy >30 Gy, age at treatment <25 years and age at evaluation >60 years, evaluating LV ejection fraction, global longitudinal strain, and global circumferential strain. The evaluation for asymptomatic CHD should be offered starting from the 10th year after mediastinal RT, considering ECG, stress echo, or coronary artery calcium (CAC) score. Given the suggested increased risks of cardiovascular outcomes in lymphoma survivors compared to the general population, tailored screening and prevention programs may be warranted to offset the future burden of disease.
PubMed: 35008222
DOI: 10.3390/cancers14010061 -
Medicine Aug 2021It is well known that liposome-based delivery of cytotoxic chemotherapeutics has been proposed as a putative strategy to enhance drug tolerability and efficacy compared... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It is well known that liposome-based delivery of cytotoxic chemotherapeutics has been proposed as a putative strategy to enhance drug tolerability and efficacy compared to the conventional chemotherapy. However, its potential effect on improving prognosis remains largely unknown. The current meta-analysis is to explore the prognosis of cancer patients undergoing liposomal doxorubicin-based chemotherapy.
METHODS
A detailed review of English and Chinese literature was conducted up to March 21, 2020. We evaluate its possible correlations using hazard ratios (HRs) with 95% confidence intervals (CIs). The pooled data were calculated by STATA software and Review Manager 5.3 software.
RESULTS
Consequently, 26 studies including 7943 patients were satisfied in current analysis. There were no significant differences between liposomal and conventional chemotherapy in OS (HR = 0.98, 95%CI: 0.93-1.04, P = .544) and PFS (HR = 1.00, 95%CI: 0.92-1.10, P = .945). Likewise, subgroup-analysis regarding country, cancer type, and sample sizes also showed the similar results of the 2 paired groups.
CONCLUSION
Taken together, our finding has demonstrated that there was no association of undergoing liposomal doxorubicin-based chemotherapy with cancer prognosis. However, detailed and further studies are needed to confirm our conclusion.
Topics: Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Humans; Multicenter Studies as Topic; Neoplasms; Polyethylene Glycols; Proportional Hazards Models; Randomized Controlled Trials as Topic
PubMed: 34449454
DOI: 10.1097/MD.0000000000026690 -
British Journal of Haematology Aug 2015'Double-hit lymphomas' (DHL), defined by concurrent MYC and BCL2 (or, alternatively, BCL6) rearrangements, have a very poor outcome compared to standard-risk, diffuse... (Meta-Analysis)
Meta-Analysis Review
Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis.
'Double-hit lymphomas' (DHL), defined by concurrent MYC and BCL2 (or, alternatively, BCL6) rearrangements, have a very poor outcome compared to standard-risk, diffuse large B-cell lymphomas (DLBCL). Consequently, dose-intensive (DI) therapies and/or consolidation with high-dose therapy and transplant have been explored in DHL, although benefit has been debated. This meta-analysis compared survival outcomes in DHL patients receiving dose-escalated regimens [DI: R-Hyper-CVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone) or R-CODOX-M/IVAC (rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high dose cytarabine); or intermediate-dose: R-EPOCH (rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone)] versus standard-dose regimens (R-CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) in the first-line setting. Data were synthesized to estimate hazard ratios of dose-escalated treatments versus R-CHOP using a Weibull proportional hazards model within a Bayesian meta-analysis framework. Eleven studies examining 394 patients were included. Patients were treated with either front-line R-CHOP (n = 180), R-EPOCH (n = 91), or R-Hyper-CVAD/rituximab, methotrexate, cytarabine (R-M/C), R-CODOX-M/R-IVAC (DI) (n = 123). Our meta-analysis revealed that median progression-free survival (n = 350) for the R-CHOP, R-EPOCH and DI groups was 12·1, 22·2, and 18·9 months, respectively. First-line treatment with R-EPOCH significantly reduced the risk of a progression compared with R-CHOP (relative risk reduction of 34%; P = 0·032); however, overall survival (n = 374) was not significantly different across treatment approaches. A subset of patients might benefit from intensive induction with/without transplant. Further investigation into the role of transplant and novel therapy combinations is necessary.
Topics: Antineoplastic Combined Chemotherapy Protocols; DNA-Binding Proteins; Disease-Free Survival; Humans; Lymphoma, Large B-Cell, Diffuse; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-bcl-6; Proto-Oncogene Proteins c-myc; Survival Rate
PubMed: 25907897
DOI: 10.1111/bjh.13463 -
Cancers Aug 2023Patients with diffuse large B-cell lymphoma (DLBCL) are treated with rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).... (Review)
Review
Consolidative Radiotherapy after Complete Remission following R-CHOP Immunochemotherapy in Stage III-IV Diffuse Large B-Cell Lymphoma Patients: A Systematic Review and Meta-Analysis.
Patients with diffuse large B-cell lymphoma (DLBCL) are treated with rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). The role of consolidative radiation therapy (RT) remains unclear among patients with advanced DLBCL who achieved complete remission (CR) after R-CHOP immunochemotherapy. The current systematic review and meta-analysis aimed to clarify the role of consolidative RT among these patients. The MEDLINE, Embase, and Cochrane Library databases were searched for studies comparing RT to no RT following CR after R-CHOP immunochemotherapy in Ann Arbor stage III-IV DLBCL patients. Overall survival (OS) was the primary endpoint, and disease-free survival (DFS) was the secondary endpoint. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the primary and secondary outcomes. Review Manager (version 5.4) was used to analyze the data. Six retrospective studies involving 813 patients who received R-CHOP ± consolidative RT were identified. OS was higher in the consolidative RT group, with an HR of 2.01 and a 95% CI of 1.30 to 3.12 ( = 0.002). DFS was also higher in the RT group, with an HR of 2.18 and a 95% CI of 1.47 to 3.24 ( < 0.0001). The results suggested that consolidative RT improved OS and DFS compared to no RT among advanced-stage DLBCL patients. Further research is needed to determine the optimal radiation fields and the appropriate indications for consolidative RT for advanced-stage DLBCL patients in the rituximab era.
PubMed: 37568756
DOI: 10.3390/cancers15153940 -
Frontiers in Oncology 2021Stress granule (SG) formation is a well-known cellular mechanism for minimizing stress-related damage and increasing cell survival. In addition to playing a critical... (Review)
Review
Stress granule (SG) formation is a well-known cellular mechanism for minimizing stress-related damage and increasing cell survival. In addition to playing a critical role in the stress response, SGs have emerged as critical mediators in human health. It seems logical that SGs play a key role in cancer cell formation, development, and metastasis. Recent studies have shown that many SG components contribute to the anti-cancer medications' responses through tumor-associated signaling pathways and other mechanisms. SG proteins are known for their involvement in the translation process, control of mRNA stability, and capacity to function in both the cytoplasm and nucleus. The current systematic review aimed to include all research on the impact of SGs on the mechanism of action of anti-cancer medications and was conducted using a six-stage methodological framework and the PRISMA guideline. Prior to October 2021, a systematic search of seven databases for eligible articles was performed. Following the review of the publications, the collected data were subjected to quantitative and qualitative analysis. Notably, Bortezomib, Sorafenib, Oxaliplatin, 5-fluorouracil, Cisplatin, and Doxorubicin accounted for the majority of the medications examined in the studies. Overall, this systematic scoping review attempts to demonstrate and give a complete overview of the function of SGs in the mechanism of action of anti-cancer medications by evaluating all research.
PubMed: 35004322
DOI: 10.3389/fonc.2021.797549 -
The Cochrane Database of Systematic... Apr 2008Chemotherapeutic agents such as topotecan can be used to treat ovarian cancer. The effects of using topotecan as a therapeutic agent have not been previously been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chemotherapeutic agents such as topotecan can be used to treat ovarian cancer. The effects of using topotecan as a therapeutic agent have not been previously been systematically reviewed.
OBJECTIVES
To systematically evaluate the effectiveness and safety of topotecan for the treatment of ovarian cancer.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), (Issue 4, 2006); Cochrane Gynaecological Cancer Review Group (CGCRG) Specialised Register (Cochrane Library Issue 4, 2006); MEDLINE (January 1990 to 27 July 2006); EMBASE (January 1990 to 27 July 2006); The European Organization for the Research and Treatment of Cancer (EORTC) database (to 1 August 2006); CBM (Chinese Biomedical Database) (January 1990 to 27 July 2006).
SELECTION CRITERIA
Randomised controlled trials (RCTs) which randomized patients with ovarian cancer to single or combined use of topotecan versus interventions without topotecan, or different remedies of topotecan.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted and analysed data.
MAIN RESULTS
Six studies including 1323 participants were eligible for this review (Gordon 2004a; Gore 2001a; Gore 2002; Hoskins 1998; Huinink 2004; Placido 2004) All studies, as reported, were identified as being of poor methodological quality. Topotecan had comparable effectiveness to prolong progression-free survival (PFS) compared with pegylated liposomal doxorubicin (PLD), (16.1 weeks versus 17.0 weeks; p = 0.095). Overall survival (OS) time was similar in participants using PLD compared with topotecan (56.7 weeks versus 60 weeks; p = 0.341). Topotecan was more hematologically toxic compared with paclitaxel or PLD, relative risks (RRs) of hematological events: ranged from 1.03 to 14.46 and 1.73 to 27.12 respectively. A 21-day cycle of topotecan was more toxic than a 42-day cycle (RRs of hematological and non-hematological events ranged from 1.03 to 8). Intravenous and oral topotecan had comparable toxicity. Topotecan delayed progression more effectively compared with paclitaxel (23.1 weeks versus 14 weeks, p = 0.0021). Participants were more likely to respond to topotecan on a 21-day cycle as opposed to a 42-day cycle (RR 7.23, 95% CI 0.94 to 55.36). Small tumor diameter, sensitivity to platinum-based chemotherapy was associated with better prognosis. Small sample size, methodological flaws and poor reporting of the included trials made measurement bias of the trials difficult to assess.
AUTHORS' CONCLUSIONS
Topotecan appears to have a similar level of effectiveness as paclitaxel and PLD, though with different patterns of side effects. Larger, well-designed RCTs are required in order to define an optimal regime.
Topics: Antineoplastic Agents; Doxorubicin; Female; Humans; Ovarian Neoplasms; Paclitaxel; Polyethylene Glycols; Randomized Controlled Trials as Topic; Topotecan
PubMed: 18425923
DOI: 10.1002/14651858.CD005589.pub2 -
Cureus Dec 2023Intravascular lymphoma (IVL) is an aggressive systemic large B-cell lymphoma that is a rare cause of stroke. The clinical characteristics of stroke associated with IVL... (Review)
Review
Intravascular lymphoma (IVL) is an aggressive systemic large B-cell lymphoma that is a rare cause of stroke. The clinical characteristics of stroke associated with IVL remain underexplored, contributing to diagnostic complexities and a high mortality rate. This study endeavors to elucidate the salient clinical and investigative features of stroke linked to this condition. A systematic review was performed using the PubMed database from the incident to August 2023 including search categories for IVL and stroke. All studies, excluding review articles, were included in this study. There were 58 cases with a confirmed diagnosis of IVL associated with stroke, with a mean age of 62.9 ± 9.6 years (female 50%). Classical lateralizing stroke symptoms were noted in only 69% of cases. Other clinical syndromes included altered sensorium (31%), rapidly progressive cognitive impairment (23%), seizures (22%), and gait disturbances (19%). Common hematological abnormalities included elevated lactate dehydrogenase (LDH, 97%), erythrocyte sedimentation rate (ESR, 79%), C-reactive protein (CRP, 61%), interleukin-2, microglobulins, and cerebrospinal fluid (CSF) protein. CSF flow cytometry was not diagnostic, and cytology was mostly negative. The dynamic pattern for DWI/T2 lesions was predominant and primarily located in the subcortical regions. Diffuse background slowing (64%) was a major finding in the electroencephalogram. Seventy-one percent of cases died (n=45) mostly due to delayed diagnosis. Only 31% were treated with first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, prednisone) chemotherapy, among whom 25% died. This study suggests that IVL-associated strokes carry a high mortality rate, largely due to challenges in timely diagnosis and therapy. Unlike classical stroke syndrome, key indicators to aid in early diagnosis include a clinical syndrome of multiple non-lateralizing neurological symptoms, dynamic MRI DWI/T2-lesions primarily located in subcortical regions, elevated serum LDH, ESR, CRP, interleukins, microglobulin, CSF protein, and CSF polymerase chain reaction analysis, apart from tissue examination. Larger studies should be performed to establish diagnostic and predictive scores.
PubMed: 38249220
DOI: 10.7759/cureus.50896 -
Cancers Jul 2021MYC/BCL2 protein co-expression (i.e., double expressor) has been shown to be a negative predictor of outcome in diffuse large B-cell lymphoma (DLBCL). We aimed to... (Review)
Review
MYC/BCL2 protein co-expression (i.e., double expressor) has been shown to be a negative predictor of outcome in diffuse large B-cell lymphoma (DLBCL). We aimed to establish the incidence of double expressor status in patients with de novo DLBCL and identify the predictive value of this biomarker on treatment response through systematic review and meta-analysis. PubMed and Embase were searched for studies published through December 2019 that reported proportions of double expressor DLBCL. The pooled proportions of MYC and BCL2 expression, both alone and in combination, were computed using the inverse variance method for calculating weights and by the DerSimonian-Laird method. The pooled odds ratios (ORs) of complete remission (CR) rate were calculated, and meta-regression analysis was conducted to explore heterogeneity. Forty-one studies (7054 patients) were included. The pooled incidence of double expressor status in DLBCL was 23% (95% confidence interval [CI], 20-26%), with an adjusted estimate of 31% (95% CI, 27-36%). Neither MYC/BCL2 protein cutoff values, race, mean, or median age of included patients, or overall study quality was a significant factor of heterogeneity ( ≥ 0.20). Cases without double expressor status demonstrated a higher probability of CR to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone treatment (OR, 2.69; 95% CI, 1.55-4.67). Our results reaffirm the predictive power of this important biomarker.
PubMed: 34282799
DOI: 10.3390/cancers13133369 -
The Cochrane Database of Systematic... Mar 2018Pancreatic cancer (PC) is a highly lethal disease with few effective treatment options. Over the past few decades, many anti-cancer therapies have been tested in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic cancer (PC) is a highly lethal disease with few effective treatment options. Over the past few decades, many anti-cancer therapies have been tested in the locally advanced and metastatic setting, with mixed results. This review attempts to synthesise all the randomised data available to help better inform patient and clinician decision-making when dealing with this difficult disease.
OBJECTIVES
To assess the effect of chemotherapy, radiotherapy or both for first-line treatment of advanced pancreatic cancer. Our primary outcome was overall survival, while secondary outcomes include progression-free survival, grade 3/4 adverse events, therapy response and quality of life.
SEARCH METHODS
We searched for published and unpublished studies in CENTRAL (searched 14 June 2017), Embase (1980 to 14 June 2017), MEDLINE (1946 to 14 June 2017) and CANCERLIT (1999 to 2002) databases. We also handsearched all relevant conference abstracts published up until 14 June 2017.
SELECTION CRITERIA
All randomised studies assessing overall survival outcomes in patients with advanced pancreatic ductal adenocarcinoma. Chemotherapy and radiotherapy, alone or in combination, were the eligible treatments.
DATA COLLECTION AND ANALYSIS
Two review authors independently analysed studies, and a third settled any disputes. We extracted data on overall survival (OS), progression-free survival (PFS), response rates, adverse events (AEs) and quality of life (QoL), and we assessed risk of bias for each study.
MAIN RESULTS
We included 42 studies addressing chemotherapy in 9463 patients with advanced pancreatic cancer. We did not identify any eligible studies on radiotherapy.We did not find any benefit for chemotherapy over best supportive care. However, two identified studies did not have sufficient data to be included in the analysis, and many of the chemotherapy regimens studied were outdated.Compared to gemcitabine alone, participants receiving 5FU had worse OS (HR 1.69, 95% CI 1.26 to 2.27, moderate-quality evidence), PFS (HR 1.47, 95% CI 1.12 to 1.92) and QoL. On the other hand, two studies showed FOLFIRINOX was better than gemcitabine for OS (HR 0.51 95% CI 0.43 to 0.60, moderate-quality evidence), PFS (HR 0.46, 95% CI 0.38 to 0.57) and response rates (RR 3.38, 95% CI 2.01 to 5.65), but it increased the rate of side effects. The studies evaluating CO-101, ZD9331 and exatecan did not show benefit or harm when compared with gemcitabine alone.Giving gemcitabine at a fixed dose rate improved OS (HR 0.79, 95% CI 0.66 to 0.94, high-quality evidence) but increased the rate of side effects when compared with bolus dosing.When comparing gemcitabine combinations to gemcitabine alone, gemcitabine plus platinum improved PFS (HR 0.80, 95% CI 0.68 to 0.95) and response rates (RR 1.48, 95% CI 1.11 to 1.98) but not OS (HR 0.94, 95% CI 0.81 to 1.08, low-quality evidence). The rate of side effects increased. Gemcitabine plus fluoropyrimidine improved OS (HR 0.88, 95% CI 0.81 to 0.95), PFS (HR 0.79, 95% CI 0.72 to 0.87) and response rates (RR 1.78, 95% CI 1.29 to 2.47, high-quality evidence), but it also increased side effects. Gemcitabine plus topoisomerase inhibitor did not improve survival outcomes but did increase toxicity. One study demonstrated that gemcitabine plus nab-paclitaxel improved OS (HR 0.72, 95% CI 0.62 to 0.84, high-quality evidence), PFS (HR 0.69, 95% CI 0.58 to 0.82) and response rates (RR 3.29, 95% CI 2.24 to 4.84) but increased side effects. Gemcitabine-containing multi-drug combinations (GEMOXEL or cisplatin/epirubicin/5FU/gemcitabine) improved OS (HR 0.55, 95% CI 0.39 to 0.79, low-quality evidence), PFS (HR 0.43, 95% CI 0.30 to 0.62) and QOL.We did not find any survival advantages when comparing 5FU combinations to 5FU alone.
AUTHORS' CONCLUSIONS
Combination chemotherapy has recently overtaken the long-standing gemcitabine as the standard of care. FOLFIRINOX and gemcitabine plus nab-paclitaxel are highly efficacious, but our analysis shows that other combination regimens also offer a benefit. Selection of the most appropriate chemotherapy for individual patients still remains difficult, with clinicopathological stratification remaining elusive. Biomarker development is essential to help rationalise treatment selection for patients.
Topics: Albumins; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Deoxycytidine; Epirubicin; Fluorouracil; Humans; Paclitaxel; Pancreatic Neoplasms; Pyrimidines; Randomized Controlled Trials as Topic; Treatment Outcome; Gemcitabine
PubMed: 29557103
DOI: 10.1002/14651858.CD011044.pub2 -
European Journal of Cancer (Oxford,... Mar 2022Cancer in neonates and infants is a rare but challenging entity. Treatment is complicated by marked physiological changes during the first year of life, excess rates of... (Review)
Review
Cancer in neonates and infants is a rare but challenging entity. Treatment is complicated by marked physiological changes during the first year of life, excess rates of toxicity, mortality, and late effects. Dose optimisation of chemotherapeutics may be an important step to improving outcomes. Body size-based dosing is used for most anticancer drugs used in infants. However, dose regimens are generally not evidence based, and dosing strategies are frequently inconsistent between tumour types and treatment protocols. In this review, we collate available pharmacological evidence supporting dosing regimens in infants for a wide range of cytotoxic drugs. A systematic review was conducted, and available data ranked by a level of evidence (1-5) and a grade of recommendation (A-D) provided on a consensus basis, with recommended dosing approaches indicated as appropriate. For 9 of 29 drugs (busulfan, carboplatin, cyclophosphamide, daunorubicin, etoposide, fludarabine, isotretinoin, melphalan and vincristine), grade A was scored, indicating sufficient pharmacological evidence to recommend a dosing algorithm for infants. For busulfan and carboplatin, sufficient data were available to recommend therapeutic drug monitoring in infants. For eight drugs (actinomycin D, blinatumomab, dinutuximab, doxorubicin, mercaptopurine, pegaspargase, thioguanine and topotecan), some pharmacological evidence was available to guide dosing (graded as B). For the remaining drugs, including commonly used agents such as cisplatin, cytarabine, ifosfamide, and methotrexate, pharmacological evidence for dosing in infants was limited or non-existent: grades C and D were scored for 10 and 2 drugs, respectively. The review provides clinically relevant evidence-based dosing guidance for cytotoxic drugs in neonates and infants.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Carboplatin; Etoposide; Humans; Infant; Infant, Newborn
PubMed: 34865945
DOI: 10.1016/j.ejca.2021.11.001