To provide recommendations for appropriate cytotoxic chemotherapy dosing for obese adult patients with cancer.
The American Society of Clinical Oncology convened a Panel of experts in medical and ...gynecologic oncology, clinical pharmacology, pharmacokinetics and pharmacogenetics, and biostatistics and a patient representative. MEDLINE searches identified studies published in English between 1996 and 2010, and a systematic review of the literature was conducted. A majority of studies involved breast, ovarian, colon, and lung cancers. This guideline does not address dosing for novel targeted agents.
Practice pattern studies demonstrate that up to 40% of obese patients receive limited chemotherapy doses that are not based on actual body weight. Concerns about toxicity or overdosing in obese patients with cancer, based on the use of actual body weight, are unfounded.
The Panel recommends that full weight-based cytotoxic chemotherapy doses be used to treat obese patients with cancer, particularly when the goal of treatment is cure. There is no evidence that short- or long-term toxicity is increased among obese patients receiving full weight-based doses. Most data indicate that myelosuppression is the same or less pronounced among the obese than the non-obese who are administered full weight-based doses. Clinicians should respond to all treatment-related toxicities in obese patients in the same ways they do for non-obese patients. The use of fixed-dose chemotherapy is rarely justified, but the Panel does recommend fixed dosing for a few select agents. The Panel recommends further research into the role of pharmacokinetics and pharmacogenetics to guide appropriate dosing of obese patients with cancer.
Cancer-related cognitive impairment (CRCI) is often related to chemotherapy. Increased chronic inflammation is believed to play a key role in the development of CRCI related to chemotherapy but ...studies assessing this hypothesis specifically in patients receiving chemotherapy are rare.
We assessed several cognitive domains using the Cambridge Neuropsychological Test Automated Battery (CANTAB) in twenty-two breast cancer patients currently receiving chemotherapy. We also measured inflammatory cytokine and receptor (MCP-1, TNF-α, sTNFRI, sTNFRII) concentrations in patient sera using Luminex assays. These concentrations were log-transformed to obtain a normal distribution. Associations between log-transformed cytokines and cognition were evaluated using Pearson correlations and linear regression, taking into account relevant covariates.
Increased concentrations of sTNFRI and sTNFRII were associated with poorer performance on the CANTAB Delayed Matching to Sample (DMS, tests visual memory). Increasing sTNFRI levels were negatively correlated with DMS percent correct (r=−0.47, p=0.029) and DMS percent correct after a 12 second (s) delay (r=−0.65, p=0.001). Increasing levels of sTNFRII negatively correlated with DMS percent correct after 12s delay (r=−0.57, p=0.006). After controlling for relevant demographic (i.e. age, education) and clinical variables (i.e. disease stage, regimen type), we found that increased sTNFRI remained significantly related to decline on the DMS at the 12s delay (p=0.018).
This preliminary study shows a significant association between higher sTNFRI and lower scores on the short-term visual memory delayed match to sample test in breast cancer patients receiving chemotherapy, supporting the hypothesis that sTNFRI is involved in CRCI.
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•First study to examine association between inflammation and CRCI during chemotherapy treatment.•Assessed TNF-α, IL-6, IL-8, sTNFR1, sTNFR2, and IL6R in relation to multiple cognitive domains.•Increasing sTNFRI concentrations are associated with worse short-term visual memory.•This association remained after adjustment for age, education, stage, & anthracycline exposure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Objective To determine whether concurrent use of GnRH agonists with chemotherapy preserves ovarian function in women with breast cancer who did not use tamoxifen. Design Systematic review and ...meta-analysis. Setting University-based hospitals. Patient(s) Premenopausal women with breast cancer treated with chemotherapy who did not receive tamoxifen. Intervention(s) Randomization to concurrent GnRH agonists with chemotherapy or chemotherapy alone. Main Outcome Measure(s) Odds ratio (OR) of resumption of menses 1 year or more after chemotherapy. Result(s) Searches were conducted in PubMed, Scopus, Cochrane Trials Register, and the National Research Register through March 2014, and all randomized trials that reported resumption of menses 1 year or more after GnRH agonist with chemotherapy or chemotherapy alone among women with breast cancer who did not receive tamoxifen were included. Four studies were analyzed in the meta-analysis and included 252 patients (GnRH agonist with chemotherapy, n = 131; chemotherapy alone, n = 121). There was no significant difference in the rate of return of menses between the two groups (OR, 1.47; 95% confidence interval 0.60–3.62). Heterogeneity among the trials was not significant ( I2 = 16.6%). Conclusion(s) Concurrent GnRH agonists with chemotherapy may not preserve ovarian function in women with breast cancer. Furthermore, randomized data are limited regarding fertility after concurrent use of GnRH agonists with chemotherapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cancer-related fatigue is a common, burdensome symptom of cancer and a side-effect of chemotherapy. While a Mediterranean Diet (MedDiet) promotes energy metabolism and overall health, its effects on ...cancer-related fatigue remain unknown. In a randomized controlled trial, we evaluated a rigorous MedDiet intervention for feasibility and safety as well as preliminary effects on cancer-related fatigue and metabolism compared to usual care. Participants had stage I−III cancer and at least six weeks of chemotherapy scheduled. After baseline assessments, randomization occurred 2:1, MedDiet:usual care. Measures were collected at baseline, week 4, and week 8 including MedDiet adherence (score 0−14), dietary intake, and blood-based metabolic measures. Mitochondrial respiration from freshly isolated T cells was measured at baseline and four weeks. Participants (n = 33) were 51.0 ± 14.6 years old, 94% were female, and 91% were being treated for breast cancer. The study was feasible, with 100% completing the study and >70% increasing their MedDiet adherence at four and eight weeks compared to baseline. Overall, the MedDiet intervention vs. usual care had a small-moderate effect on change in fatigue at weeks 4 and 8 (ES = 0.31, 0.25, respectively). For those with a baseline MedDiet score <5 (n = 21), the MedDiet intervention had a moderate-large effect of 0.67 and 0.48 at weeks 4 and 8, respectively. The MedDiet did not affect blood-based lipids, though it had a beneficial effect on fructosamine (ES = −0.55). Fatigue was associated with mitochondrial dysfunction including lower basal respiration, maximal respiration, and spare capacity (p < 0.05 for FACIT-F fatigue subscale and BFI, usual fatigue). In conclusion, the MedDiet was feasible and attenuated cancer-related fatigue among patients undergoing chemotherapy, especially those with lower MedDiet scores at baseline.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Multigene genomic profiling has become the standard of care in the clinical risk-assessment and risk-stratification of ER
, HER2
breast cancer (BC) patients, with Oncotype DX
(ODX) emerging as the ...genomic profile test with the most support from the international community. The current state of the health care economy demands that cost-efficiency and access to testing must be considered when evaluating the clinical utility of multigene profile tests such as ODX. Several studies have suggested that certain lower risk patients can be identified more cost-efficiently than simply reflexing all ER
, HER2
BC patients to ODX testing. The Magee equations
use standard histopathologic data in a set of multivariable models to estimate the ODX recurrence score. Our group published the first outcome data in 2019 on the Magee equations
, using a modification of the Magee equations
combined with an algorithmic approach-the Rochester Modified Magee algorithm (RoMMa). There has since been limited published outcome data on the Magee equations
. We present additional outcome data, with considerations of the TAILORx risk-stratification recommendations.
355 patients with an ODX recurrence score, and at least five years of follow-up or a BC recurrence were included in the study. All patients received either Tamoxifen or an aromatase inhibitor. None of the patients received adjuvant systemic chemotherapy.
There was no significant difference in the risk of recurrence in similar risk categories (very low risk, low risk, and high risk) between the average Modified Magee score and ODX recurrence score with the chi-square test of independence (
> 0.05) or log-rank test (
> 0.05). Using the RoMMa, we estimate that at least 17% of individuals can safely avoid ODX testing.
Our study further reinforces that BC patients can be confidently stratified into lower and higher-risk recurrence groups using the Magee equations
. The RoMMa can be helpful in the initial clinical risk-assessment and risk-stratification of BC patients, providing increased opportunities for cost savings in the health care system, and for clinical risk-assessment and risk-stratification in less-developed geographies where multigene testing might not be available.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The skyrocketing cost of health‐care demands that we question when to use multigene assay testing in the planning of treatment for breast cancer patients. A previously published algorithmic model ...gave recommendations for which cases to send out for Oncotype DX® (ODX) testing. This study is a multi‐institutional validation of that algorithmic model in 620 additional estrogen receptor positive breast cancer cases, with outcome data on 310 cases, named in this study as the Rochester Modified Magee algorithm (RoMMa). RoMMa correctly predicted 85% (140/164) and 100% (17/17) of cases to have a low‐ or high‐risk ODX recurrence score, respectively, consistent with the original publication. Applying our own risk stratification criteria, in patients who received appropriate hormonal therapy, only one of the 45 (2.0%) patients classified as low risk by our original algorithm have been associated with a breast cancer recurrence over 5‐10 years of follow‐up. Eight of 116 (7.0%) patients classified as low risk by ODX have been associated with a breast cancer recurrence with up to 11 years of follow‐up. In addition, 524 of 537 (98%) cases from our total population (n = 903) with an average modified Magee score ≤18 had an ODX recurrence score <26. Patients with an average modified Magee score ≤18 or >30 may not need to be sent out for ODX testing. By avoiding these cases sending out for ODX testing, the potential cost savings to the health‐care system in 2018 are estimated to have been over $100,000,000.
We have developed an algorithmic approach using immunohistochemistry and clinical data to help predict patients at a lower and higher risk for breast cancer recurrence. We estimate that by avoiding sending out certain cases for Oncotype DX testing, the potential cost savings to the health‐care system in 2018 would have been over $100,000,000.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Male patients with breast cancer (BrC) have increased risk of developing 2nd-primary BrC (2nd-BrC). Given the relative rarity of male BrC, population-based registries are needed to analyze overall ...survival (OS) outcomes for these patients.
Using the Surveillance, Epidemiology and End Results registry of patients diagnosed from 1975 to 2016, a cohort study of men whose only malignancy was BrC (BrCO; n = 6,475), and men who developed 2nd-BrC after initial BrC diagnosis (BrC-2; n = 85) was performed. The standardized incidence ratio (SIR) of 2nd-BrC, Kaplan-Meier OS and multivariable Cox regression modelling were performed.
The SIR for 2nd-BrC was 32.95 (95%CI:23.85–44.38,p < 0.05). The majority (88%) of 2nd-BrC for BrC-2 were contralateral from 1st-BrC; suggesting the unlikeliness of miscoding local recurrences as 2nd-BrC for most patients. There was no statistically significant difference between rates of hormone (reported in 44%) or HER-2 (reported in 33%) receptor status between BrC-O and BrC-2, albeit with limited data. The 2nd-BrC for BrC-2 was significantly more likely to be localized or distant stage (rather than regional) than BrC-O. Median OS was 103 months (95% CI: 99, 108) for BrC-O and 62 months (95% CI 49, 128 after 2nd-BrC. When sub-grouped by BrC stage, and when analyzed by Cox regression, there was no significant difference in OS between BrC-O and BrC-2.
Patients with male BrC are at significantly increased risk of 2nd BrC, but they can expect similar post-BrC prognosis (versus those without 2nd-BrC), after adjusting for patient demographics and tumor characteristics known to affect OS.
None.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Myelodysplastic syndromes (MDS) are among the most frequent hematologic malignancies. Patients have a short survival and often progress to acute myeloid leukemia. The diagnosis of MDS can be ...difficult; there is a paucity of molecular markers, and the pathophysiology is largely unknown. Therefore, we conducted a multicenter study investigating whether serum proteome profiling may serve as a noninvasive platform to discover novel molecular markers for MDS. We generated serum proteome profiles from 218 individuals by MS and identified a profile that distinguishes MDS from non-MDS cytopenias in a learning sample set. This profile was validated by testing its ability to predict MDS in a first independent validation set and a second, prospectively collected, independent validation set run 5 months apart. Accuracy was 80.5% in the first and 79.0% in the second validation set. Peptide mass fingerprinting and quadrupole TOF MS identified two differential proteins: CXC chemokine ligands 4 (CXCL4) and 7 (CXCL7), both of which had significantly decreased serum levels in MDS, as confirmed with independent antibody assays. Western blot analyses of platelet lysates for these two platelet-derived molecules revealed a lack of CXCL4 and CXCL7 in MDS. Subtype analyses revealed that these two proteins have decreased serum levels in advanced MDS, suggesting the possibility of a concerted disturbance of transcription or translation of these chemokines in advanced MDS.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Abstract Context Previous research has shown that the effectiveness of acupressure bands in reducing chemotherapy-related nausea is related to patients' expectations of efficacy. Objective To test ...whether an informational manipulation designed to increase expectation of efficacy regarding acupressure bands would enhance their effectiveness. Methods We conducted an exploratory, four-arm, randomized clinical trial in breast cancer patients about to begin chemotherapy. All patients received acupressure bands and a relaxation CD. This report focuses on Arm 1(expectancy-neutral informational handout and CD) compared with Arm 4 (expectancy-enhancing handout and CD). Randomization was stratified according to the patient's level of certainty that she would have treatment-induced nausea (two levels: high and low). Experience of nausea and use of antiemetics were assessed with a five-day diary. Results Our expectancy-enhancing manipulation resulted in improved control of nausea in the 26 patients with high nausea expectancies but lessened control of nausea in 27 patients having low nausea expectancies. This interaction effect (between expected nausea and intervention effectiveness) approached statistical significance for our analysis of average nausea ( P = 0.084) and reached statistical significance for our analysis of peak nausea ( P = 0.030). Patients receiving the expectancy-enhancing manipulation took fewer antiemetic pills outside the clinic (meanenhanced = 12.6; meanneutral = 18.5, P = 0.003). Conclusion This exploratory intervention reduced antiemetic use overall and also reduced nausea in patients who had high levels of expected nausea. Interestingly, it increased nausea in patients who had low expectancies for nausea. Confirmatory research is warranted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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