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Journal of Cachexia, Sarcopenia and... Apr 2024There is no consensus on the optimal endpoint(s) in cancer cachexia trials. Endpoint variation is an obstacle when comparing interventions and their clinical value. The... (Review)
Review
There is no consensus on the optimal endpoint(s) in cancer cachexia trials. Endpoint variation is an obstacle when comparing interventions and their clinical value. The aim of this systematic review was to summarize and evaluate endpoints used to assess appetite and dietary intake in cancer cachexia clinical trials. A search for studies published from 1 January 1990 until 2 June 2021 was conducted using MEDLINE, Embase and Cochrane Central Register of Controlled Trials. Eligible studies examined cancer cachexia treatment versus a comparator in adults with assessments of appetite and/or dietary intake as study endpoints, a sample size ≥40 and an intervention lasting ≥14 days. Reporting was in line with PRISMA guidance, and a protocol was published in PROSPERO (2022 CRD42022276710). This review is part of a series of systematic reviews examining cachexia endpoints. Of the 5975 articles identified, 116 were eligible for the wider review series and 80 specifically examined endpoints of appetite (65 studies) and/or dietary intake (21 studies). Six trials assessed both appetite and dietary intake. Appetite was the primary outcome in 15 trials and dietary intake in 7 trials. Median sample size was 101 patients (range 40-628). Forty-nine studies included multiple primary tumour sites, while 31 studies involved single primary tumour sites (15 gastrointestinal, 7 lung, 7 head and neck and 2 female reproductive organs). The most frequently reported appetite endpoints were visual analogue scale (VAS) and numerical rating scale (NRS) (40%). The appetite item from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30/C15 PAL (38%) and the appetite question from North Central Cancer Treatment Group anorexia questionnaire (17%) were also frequently applied. Of the studies that assessed dietary intake, 13 (62%) used food records (prospective registrations) and 10 (48%) used retrospective methods (24-h recall or dietary history). For VAS/NRS, a mean change of 1.3 corresponded to Hedge's g of 0.5 and can be considered a moderate change. For food records, a mean change of 231 kcal/day or 11 g of protein/day corresponded to a moderate change. Choice of endpoint in cachexia trials will depend on factors pertinent to the trial to be conducted. Nevertheless, from trials assessed and available literature, NRS or EORTC QLQ C30/C15 PAL seems suitable for appetite assessments. Appetite and dietary intake endpoints are rarely used as primary outcomes in cancer cachexia. Dietary intake assessments were used mainly to monitor compliance and are not validated in cachexia populations. Given the importance to cachexia studies, dietary intake endpoints must be validated before they are used as endpoints in clinical trials.
Topics: Humans; Appetite; Cachexia; Eating; Neoplasms; Prospective Studies; Quality of Life; Retrospective Studies; Clinical Trials as Topic
PubMed: 38343065
DOI: 10.1002/jcsm.13434 -
Critical Reviews in Oncology/hematology Mar 2024Exercise has been shown to play an important role in managing chemotherapy-related side effects, preserving skeletal muscle mass, and attenuating decline in...
BACKGROUND
Exercise has been shown to play an important role in managing chemotherapy-related side effects, preserving skeletal muscle mass, and attenuating decline in cardiorespiratory fitness associated with chemotherapy treatment, however, the feasibility of how these exercise programs are being delivered has yet to be synthesized. The objective of this review was to measure the rates of recruitment, adherence, and retention to exercise programs delivered for cancer patients during chemotherapy.
METHODS
Relevant studies were identified through a search of MEDLINE, Cochrane, EMBASE and CINAHL databases from January 2002 to July 2022 using keywords relating to exercise interventions during chemotherapy. Title and abstract screening, full text review, data extraction, and quality assessment were all performed independently by two reviewers.
RESULTS
A total of 36 studies were included in the review. The mean recruitment rate for the included studies was 62.39% (SD = 19.40; range 25.7-95%). Travel was the most common reason for declining recruitment in these trials. Adherence rates ranged from 17-109%, however the definition of adherence varied greatly between studies. Mean retention rates for the exercise groups was 84.1% (SD = 12.7; range 50-100%), with chemotherapy side effects being the most common reason why participants dropped out of these trials.
CONCLUSION
Multiple challenges exist for cancer patients during chemotherapy and careful consideration needs to be given when designing an exercise program for this population. Future research should include public and patient involvement to ensure exercise programs are pragmatic and patient centred.
Topics: Humans; Exercise Therapy; Neoplasms
PubMed: 38272152
DOI: 10.1016/j.critrevonc.2024.104272 -
Frontiers in Immunology 2023This meta-analysis aims to evaluate the efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors [PD-(L)1 inhibitors] for muscle-invasive bladder carcinoma... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
This meta-analysis aims to evaluate the efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors [PD-(L)1 inhibitors] for muscle-invasive bladder carcinoma (MIBC).
MATERIALS AND METHODS
Four databases (Medline, Embase, Web of Science, and 21 CENTRAL) were searched for articles studying neoadjuvant PD-(L)1 inhibitors for MIBC. The search time period was from the establishment of each database to 21 July 2023. Meta-analyses of pCR, pPR, Grade≥ 3 irAEs rate, RFS, and OS were performed.
RESULTS
In total, 22 studies were included for meta-analysis. The overall pooled pCR of neoadjuvant PD-(L)1 inhibitors was 0.36 (95%CI=0.30-0.42, p=0.00). In subgroup meta-analysis, the pooled PCR of PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI, and PD-(L)1 inhibitors plus chemotherapy was 0.27 (95%CI=0.19-0.35, p=0.1), 0.41 (95%CI=0.21-0.62, p=0.01), 0.43 (95%CI=0.35-0.50, p=0.06), respectively. The overall pooled pPR of neoadjuvant PD-(L)1 inhibitors was 0.53 (95%CI=0.46-0.60, p=0.00). In subgroup meta-analysis, the pooled pPR of PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI, and PD-(L)1 inhibitors plus chemotherapy was 0.36 (95%CI=0.22-0.51, p=0.01), 0.51 (95%CI=0.39-0.62, p=0.43), and 0.61 (95%CI=0.53-0.69, p=0.01), respectively. Kaplan-Meier curves for OS and RFS were reconstructed, but there was no significant difference among three groups in terms of OS or RFS. The pooled result of Grade≥ 3 irAEs rate for neoadjuvant PD-(L)1 inhibitors was 0.15 (95%CI=0.09-0.22, p=0.00%). In subgroup analysis, the pooled result of Grade≥ 3 irAEs rate for PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI, and PD-(L)1 inhibitors plus chemotherapy was 0.07 (95%CI=0.04-0.11, p=0.84), 0.31 (95%CI=0.16-0.47, p=0.06), and 0.17 (95%CI=0.06-0.31, I = 71.27%, p=0.01), respectively.
CONCLUSION
Neoadjuvant PD-(L)1 inhibitors were feasible and safe for muscle invasive bladder cancer. Compared with PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI and PD-(L)1 inhibitors plus chemotherapy were associated with higher pCR and pPR, but higher Grade≥3 irAEs. Kaplan-Meier curves for OS and RFS indicated that neoadjuvant PD-(L)1 inhibitors had an acceptable long-term prognostic, but it was not possible to discern statistical differences between the three neoadjuvant subgroups.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023452437, identifier PROSPERO (CRD42023452437).
Topics: Humans; Databases, Factual; Immune Checkpoint Inhibitors; Muscles; Neoadjuvant Therapy; Urinary Bladder Neoplasms
PubMed: 38264649
DOI: 10.3389/fimmu.2023.1332213 -
Toxins Dec 2023This systematic review investigates the effect of botulinum neurotoxin (BoNT) therapy on cancer-related disorders. A major bulk of the literature is focused on BoNT's... (Review)
Review
This systematic review investigates the effect of botulinum neurotoxin (BoNT) therapy on cancer-related disorders. A major bulk of the literature is focused on BoNT's effect on pain at the site of surgery or radiation. All 13 published studies on this issue indicated reduction or cessation of pain at these sites after local injection of BoNTs. Twelve studies addressed the effect of BoNT injection into the pylorus (sphincter between the stomach and the first part of the gut) for the prevention of gastroparesis after local resection of esophageal cancer. In eight studies, BoNT injection was superior to no intervention; three studies found no difference between the two approaches. One study compared the result of intra-pyloric BoNT injection with preventive pyloromyotomy (resection of pyloric muscle fibers). Both approaches reduced gastroparesis, but the surgical approach had more serious side effects. BoNT injection was superior to saline injection in the prevention of esophageal stricture after surgery (34% versus 6%, respectively, = 0.02) and produced better results (30% versus 40% stricture) compared to steroid (triamcinolone) injection close to the surgical region. All 12 reported studies on the effect of BoNT injection into the parotid region for the reduction in facial sweating during eating (gustatory hyperhidrosis) found that BoNT injections stopped or significantly reduced facial sweating that developed after parotid gland surgery. Six studies showed that BoNT injection into the parotid region prevented the development of or healed the fistulas that developed after parotid gland resection-parotidectomy gustatory hyperhidrosis (Frey syndrome), post-surgical parotid fistula, and sialocele. Eight studies suggested that BoNT injection into masseter muscle reduced or stopped severe jaw pain after the first bite (first bite syndrome) that may develop as a complication of parotidectomy.
Topics: Humans; Botulinum Toxins, Type A; Sweating, Gustatory; Gastroparesis; Pain; Neoplasms
PubMed: 38133193
DOI: 10.3390/toxins15120689 -
PloS One 2023One of the most complex surgeries including radical cystectomy (RC) has a high rate of morbidity. The standard approach for the muscle-invasive bladder is conventional... (Meta-Analysis)
Meta-Analysis
BACKGROUND
One of the most complex surgeries including radical cystectomy (RC) has a high rate of morbidity. The standard approach for the muscle-invasive bladder is conventional transperitoneal radical cystectomy. However, the procedure is associated with significant morbidities like ileus, urinary leak, bleeding, and infection. The aim of this study is to compare the transperitoneal RC approach with the extraperitoneal RC approach in the treatment of bladder cancer patients. The outcomes of this study are Operative time, Estimated Blood Loss, Hospital Stay, Post-Operative Ileus, Infection, and Major Complication (Clavien-Dindo Grade 3-5).
METHODS
PubMed, Cochrane Library, and Science Direct were systematically searched for different publications related to the meta-analysis. Keywords used for searching were Radical Cystectomy AND Extraperitoneal AND Transperitoneal up until 31st August 2022. The studies were screened for our eligibility criteria. Demographic parameters, perioperative variables, and postoperative complications were recorded and analyzed. The Newcastle-Ottawa Scale was used to evaluate the risk of bias in each study. The Review Manager (RevMan) software version 5.4.1 was used for statistical analysis.
RESULTS
Eight studies (3 laparoscopic and 5 open methods) involving 1207 subjects (588 patients using the extraperitoneal approach and 619 using the transperitoneal approach) were included. The incidence of postoperative ileus is significantly lower after the extraperitoneal approach compared to the transperitoneal approach (p < 0.00001). The two techniques did not differ in operative time, estimated blood loss, duration of hospital stay, total infection, and major complication events.
CONCLUSION
This meta-analysis shows that extraperitoneal radical cystectomy benefits in terms of reduced postoperative ileus.
Topics: Humans; Cystectomy; Urinary Bladder; Treatment Outcome; Urinary Bladder Neoplasms; Postoperative Complications; Ileus
PubMed: 38032964
DOI: 10.1371/journal.pone.0294809 -
Journal of Cachexia, Sarcopenia and... Dec 2023Sarcopenia has been considered an adverse prognostic factor in cancer patients. Intramuscular adipose tissue content, as a new marker of sarcopenia, can effectively... (Meta-Analysis)
Meta-Analysis Review
Sarcopenia has been considered an adverse prognostic factor in cancer patients. Intramuscular adipose tissue content, as a new marker of sarcopenia, can effectively reflect skeletal muscle quality. The aim of this study was performed to evaluate the association between high intramuscular adipose tissue content (IMAC) and survival outcomes and postoperative complications in cancer patients. Specific databases, including the Web of Science, Embase and Web of Science, were systematically searched to identify relevant articles evaluating the prognostic value of IMAC in cancer patients. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were utilized for comprehensive analysis. All data analyses were performed using STATA 12.0 software. A total of 25 studies from 24 articles including 5663 patients were enrolled in the study. Meta-analysis showed that high IMAC was associated with unfavourable overall survival (OS) (HR: 2.21, 95% CI: 1.70-2.86, P < 0.001), relapse-free survival (RFS) (HR: 1.51, 95% CI: 1.30-1.75, P < 0.001) and disease-specific survival (DSS) (HR: 1.64, 95% CI: 1.19-2.28, P = 0.003). Subgroup analysis revealed that high IMAC remained an adverse prognostic factor when stratified by different country, treatment methods, cancer type or analysis type. High IMAC had better predictive value for gallbladder carcinoma (GBC) (HR: 3.50, 95% CI: 1.98-6.17, P < 0.001), hepatocellular carcinoma (HCC) (HR: 1.84, 95% CI: 1.45-2.33, P < 0.001), pancreatic cancer (PC) (HR: 2.11, 95% CI: 1.67-2.66, P < 0.001) and colorectal cancer (CRC) (HR: 2.54, 95% CI: 1.27-5.10, P = 0.009). High IMAC was also identified as a significant risk factor for postoperative complications (OR: 2.05, 95% CI: 1.22-3.46, P = 0.007). High IMAC was associated with an adverse prognosis and an increased risk of postoperative complications in cancer patients. IMAC may be a good indicator of sarcopenia.
Topics: Humans; Carcinoma, Hepatocellular; Sarcopenia; Liver Neoplasms; Retrospective Studies; Prognosis; Adipose Tissue; Postoperative Complications
PubMed: 37990969
DOI: 10.1002/jcsm.13371 -
Systematic Reviews Nov 2023Prehabilitation programs focusing on exercise training as the main component are known as a promising alternative for improving patients' outcomes before cancer surgery....
BACKGROUND
Prehabilitation programs focusing on exercise training as the main component are known as a promising alternative for improving patients' outcomes before cancer surgery. This systematic review determined the benefits and harms of prehabilitation programs compared with usual care for individuals with cancer.
METHODS
We searched CENTRAL, MEDLINE, and EMBASE from inception to June 2022, and hand searched clinical trial registries. We included randomized-controlled trials (RCTs) in adults, survivors of any type of cancer, that compared prehabilitation programs that had exercise training as the major component with usual care or other active interventions. Outcome measures were health-related quality of life (HRQL), muscular strength, postoperative complications, average length of stay (ALOS), handgrip strength, and physical activity levels. Two reviewers independently screened the studies, extracted data, and assessed the risk of bias and the certainty of the evidence.
RESULTS
Twenty-five RCTs (2682 participants) published between 2010 and 2022 met our inclusion criteria. Colorectal and lung cancers were the most common diagnoses. The studies had methodological concerns regarding outcome measurement, selective reporting, and attrition. Five prehabilitation programs were compared to usual care (rehabilitation): combined training, aerobic training, respiratory muscle training plus aerobic training, respiratory muscle training plus resistance training, and pelvic floor training. The studies provided no clear evidence of an effect between groups. We assessed the overall certainty of the evidence as very low, downgraded due to serious study limitations and imprecision.
CONCLUSION
Prehabilitation programs focusing on exercise training may have an effect on adults with cancer, but the evidence is very uncertain. We have very little confidence in the results and the true effect is likely to be substantially different from these. Further research is needed before we can draw a more certain conclusion.
SYSTEMATIC REVIEW REGISTRATION
CRD42019125658.
Topics: Adult; Humans; Preoperative Exercise; Exercise; Exercise Therapy; Neoplasms; Resistance Training; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 37978411
DOI: 10.1186/s13643-023-02373-4 -
Annals of Medicine 2023The optimal cycle of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) remains controversial. This study aimed to compare the efficacy of three... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The optimal cycle of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) remains controversial. This study aimed to compare the efficacy of three and four cycles of NAC in the treatment of MIBC through a systematic review and meta-analysis of the literature.
MATERIALS AND METHODS
Relevant studies were systematically collected and reviewed in PubMed, Medline, Embase, Web of Science Databases, and the Cochrane Library. Relative ratios (RRs), Hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to estimate outcome measures. Studies comparing the pathological response and prognosis of three versus four cycles of NAC for MIBC were included.
RESULTS
Five studies were included in this meta-analysis, including 2190 patients, of whom 1016 underwent three cycles of NAC and 1174 underwent four cycles of NAC. All studies were retrospective cohort studies. We found that 4 cycles of NAC had significantly better cancer-specific survival than 3 cycles (HR = 1.31, 95%CI,1.03-1.67, = 0.029). There was no significant difference in overall survival between patients who received 3 and 4 cycles of chemotherapy (HR = 1.18, 95%CI = 0.83-1.69, = 0.345). Similarly, no significant difference was observed in pathological objective response (RR = 0.95, 95%CI= 0.81-1.11, = 0.515) and complete response rates (RR = 0.87, 95%CI = 0.69-1.11, = 0.256) in MIBC after 3 or 4 cycles of NAC.
CONCLUSIONS
Three and four cycles of NAC had similar pathological responses and prognosis for MIBC, although the cancer-specific survival rate of four cycles was better than that of three cycles.
Topics: Humans; Neoadjuvant Therapy; Retrospective Studies; Chemotherapy, Adjuvant; Urinary Bladder Neoplasms; Muscles
PubMed: 37963224
DOI: 10.1080/07853890.2023.2281654 -
BMC Cancer Nov 2023In muscle-invasive bladder cancer (MIBC), neoadjuvant chemotherapy (NAC) combined with radical cystectomy (RC) is critical in reducing disease recurrence, with GC... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In muscle-invasive bladder cancer (MIBC), neoadjuvant chemotherapy (NAC) combined with radical cystectomy (RC) is critical in reducing disease recurrence, with GC (gemcitabine and cisplatin) being one of the most commonly used NACs. Different GC schedules have been used, but the best neoadjuvant regimen is still unknown. The clinical outcomes of 3 and 4 cycles of neoadjuvant GC are compared in this systematic review and meta-analysis to determine which is best for patients with MIBC.
METHODS
We searched PubMed, Embase, Web of Science, Cochrane Library, CBM, CNKI, WAN FANG DATA, and meeting abstracts to identify relevant studies up to March 2023. Studies that compared 3 and 4 cycles of neoadjuvant GC for MIBC were included. The primary outcomes were pCR, pDS, OS, and CSS. The secondary outcome was recurrence and SAEs.
RESULTS
A total of 3 studies, with 1091 patients, were included in the final analysis. Patients that received 4 cycles of GC had a higher pCR (OR = 0.66; 95% CI, 0.50-0.87; p = 0.003) and pDS (OR = 0.63; 95% CI, 0.48-0.84; p = 0.002) than those who received 3 cycles. Regarding recurrence rate (OR = 1.23; 95% CI, 0.91-1.65; p = 0.18), there were no appreciable differences between the 3 and 4 cycles of GC. Survival parameters such as OS (HR, 1.35; 95% CI, 0.86-2.12; p = 0.19) and CSS (HR, 1.06; 95% CI, 0.82-1.38; p = 0.20) were similar. Only one trial reported on the outcomes of SAEs. And there were no statistically significant differences in thrombocytopenia, infection rate, neutropenic fever, anemia, or decreased renal function between patients. The neutropenia of patients was statistically different (OR = 0.72; 95% CI, 0.52-0.99; p = 0.04).
CONCLUSION
The 4-cycle GC regimen was superior to the 3-cycle regimen in only the pCR and pDS results. Survival and recurrence rates were similar between the two regimens. In both treatment regimes, the toxicity profile was manageable. However, due to the inherent drawbacks of retrospective research, this should be regarded with caution.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cystectomy; Gemcitabine; Muscles; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Retrospective Studies; Urinary Bladder Neoplasms
PubMed: 37932689
DOI: 10.1186/s12885-023-11572-0 -
Supportive Care in Cancer : Official... Nov 2023This study aims to systematically explore the impact of physical exercise as supportive therapy for head and neck cancer. (Review)
Review
PURPOSE
This study aims to systematically explore the impact of physical exercise as supportive therapy for head and neck cancer.
METHODS
A systematic search on PubMed/MEDLINE, Cochrane, and SPORTDiscus was conducted. Randomized controlled trials exploring the effects of a physical exercise intervention in comparison with usual care on outcomes in patients with head and neck cancer were selected. The RoB 2 tool was used to determine the study quality. The extracted data are reported as qualitative synthesis.
RESULTS
Among the 527 records examined, nine studies were included. No trials investigating exercise as prehabilitation were found, whereas eight studies involving 452 patients with head and neck cancer were conducted during anticancer treatment. Most trials did not report improvements in body mass index or body composition, while 2/4 and 3/5 investigations found a significant increase in muscle strength and cardiorespiratory fitness, respectively. Regarding the patients' reported outcomes, 4 out of 7 studies observed enhancements in some domains of quality of life, and two trials out of 3 detected an amelioration in fatigue following the exercise intervention. Analyzing the exercise programs, it seems that combining aerobic and resistance training could be more beneficial compared to a single type of full-body exercise in counteracting physical decline and controlling symptoms in the anticancer therapy phase. One trial has investigated the effect of resistance exercise on patients who had terminated the anticancer treatments, reporting significant improvements in lean mass, muscle strength, and quality of life.
CONCLUSION
Exercise may be a promising approach in patients with head and neck cancer. Future studies are needed to consolidate these results.
Topics: Humans; Quality of Life; Randomized Controlled Trials as Topic; Exercise; Head and Neck Neoplasms; Muscle Strength; Exercise Therapy
PubMed: 37924500
DOI: 10.1007/s00520-023-08126-2