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Patient-derived organoids as a platform for modeling a patient's response to chemoradiotherapy in esophageal cancer.
Karakasheva, TA, Gabre, JT, Sachdeva, UM, Cruz-Acuña, R, Lin, EW, DeMarshall, M, Falk, GW, Ginsberg, GG, Yang, Z, Kim, MM, et al
Scientific reports. 2021;(1):21304
Abstract
3D patient-derived organoids (PDOs) have been utilized to evaluate potential therapies for patients with different cancers. However, the use of PDOs created from treatment-naive patient biopsies for prediction of clinical outcomes in patients with esophageal cancer has not yet been reported. Herein we describe a pilot prospective observational study with the goal of determining whether esophageal cancer PDOs created from treatment naive patients can model or predict clinical outcomes. Endoscopic biopsies of treatment-naive patients at a single tertiary care center were used to generate esophageal cancer PDOs, which were treated with standard-of-care chemotherapy, gamma-irradiation, and newer non-standard approaches, such as proton beam therapy or two small molecule inhibitors. Clinical outcomes of patients following neoadjuvant treatment were compared to their in vitro PDO responses, demonstrating the PDO's ability to mirror clinical response, suggesting the value of PDOs in prediction of clinical response to new therapeutic approaches. Future prospective clinical trials should test the use of pre-treatment PDOs to identify specific, targeted therapies for individual patients with esophageal adenocarcinoma.
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Association between thiamine decrease and neuropsychiatric symptoms in gastrointestinal and hematological cancer patients receiving chemotherapy.
Iimura, Y, Kurokawa, T, Andoh, S, Kanemoto, Y, Kawamata, T, Yazawa, K, Sato, A, Yokoyama, K, Imai, Y, Tsurita, G, et al
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2021;:111929
Abstract
BACKGROUND Clinical evidence of thiamine-related neuropsychiatric symptoms, including the initial stage, is limited because serum thiamine levels tend to be evaluated only for patients who develop severe neuropsychiatric symptoms suspected to be related to severe thiamine deficiency. This study aimed to evaluate the relationship between thiamine decline and neuropsychiatric symptoms, including initial symptoms, and the effect of chemotherapy on serum thiamine levels in gastrointestinal and hematological cancer patients receiving chemotherapy. METHOD We retrospectively identified 87 patients who were diagnosed with gastrointestinal and hematological cancers at our hospital. We evaluated the risk factors associated with neuropsychiatric symptoms, including initial symptoms (neuropsychiatric symptoms), the relationship between the presence of neuropsychiatric symptoms and serum thiamine levels, and changes in serum thiamine levels after chemotherapy. RESULTS Logistic regression analysis identified thiamine decline as a significant factor associated with neuropsychiatric symptoms (p < 0.001, odds ratio = 0.040, 95% confidence interval [CI]: 0.010-0.163). The Mann-Whitney U test showed that patients with neuropsychiatric symptoms had significantly lower serum thiamine levels (19.5 ± 5.4 ng/mL, n = 39) than patients without neuropsychiatric symptoms (31.9 ± 14.2 ng/mL, n = 48) (p = 0.001). In hematological cancer patients, serum thiamine levels gradually declined after chemotherapy, with the lowest levels at 5-8 weeks (23.5 ± 7.6 ng/mL, P = 0.035 vs. 0 weeks, Wilcoxon rank sum test). CONCLUSION Our study showed that a decrease in serum thiamine levels can be a risk factor for neuropsychiatric symptoms, and chemotherapy can lead to a decrease in serum thiamine levels.
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Sorafenib as a second-line treatment in metastatic renal cell carcinoma in Mexico: a prospective cohort study.
Martín-Aguilar, AE, Núñez-López, H, Ramirez-Sandoval, JC
BMC cancer. 2021;(1):16
Abstract
BACKGROUND Sequential inhibition of the vascular endothelial growth factor (VEGF) pathway with sorafenib could be useful for patients with metastatic renal cell carcinoma (RCC). Our aim was to determine the activity and tolerability of sorafenib as a second-line therapy in advanced RCC initially treated with a different VEGF-tyrosine kinase inhibitor (TKI). METHODS A prospective observational cohort in Mexico (2012-2019). We included 132 subjects with metastatic RCC and who had progression despite treatment with sunitinib. The primary end-point was time to disease progression as evaluated every 12-16 weeks. RESULTS The mean age of the cohort was 59 years (interquartile range [IQR] 50-72), 96 (73%) were men, and 48 (36%) had a favorable prognosis according to the IMDC (International Metastatic RCC Database Consortium) prognostic model. The median progression-free survival (PFS) and overall-survival after the introduction of sorafenib treatment was 8.6 months (95% confidence interval [CI]: 6.7-10.5) and 40 months (95% CI: 34.5-45.4) respectively. The median overall survival from RCC diagnosis to death was 71 months (95% CI: 58.2-83.8). On multivariable analyses, age > 65 years was associated with a longer PFS (HR 0.51; 95% CI: 0.31-0.86; p = 0.018). The median PFS in subjects aged > 65 years was longer compared to subjects ≤65 years (14.0 [95% CI: 9.2-18.8] vs. 7.2 months [95% CI: 5.3-9.1]; p = 0.012). Adverse events grade ≥ 3 associated with sorafenib occurred in 38 (29%) patients. CONCLUSION Sequential inhibition of VEGF with sorafenib as a second-line treatment may benefit patients with metastatic RCC, especially in subjects > 65 years old.
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Lactobacillus Kefiri LKF01 (Kefibios®) for Prevention of Diarrhoea in Cancer Patients Treated with Chemotherapy: A Prospective Study.
Ghidini, M, Nicoletti, M, Ratti, M, Tomasello, G, Lonati, V, Ghilardi, M, Parati, MC, Borgonovo, K, Cabiddu, M, Petrelli, F
Nutrients. 2021;(2)
Abstract
Diarrhoea is one of the main side effects that cancer patients face. The literature showsthat the incidence of chemotherapy (CT)-induced diarrhoea (grade 3-4) in treated patients is in the range of 10-20%, particularly after 5-fluorouracil (5-FU) bolus or some combination therapies of irinotecan and fluoropyrimidines. The aim of the present study was to evaluate the clinical effectiveness of Lactobacillus kefiri LKF01 (Kefibios®) in the prevention or treatment of CT-related diarrhoea in the cancer population. We conducted a prospective observational study. Patients enrolled were adults treated for at least four months with 5-FU-based CT. Kefibios® was administered to patients every day. The primary outcome was the evaluation of the incidence of grade 3-4 CT-induced diarrhoea. We included 76 patients in the final analysis. A 6.6% incidence of high-grade diarrhoea was found in the evaluated population (4.7% of patients treated with 5-FU-based therapy and 8.5% of patients treated with capecitabine-based CT). The overall incidence of high-grade diarrhoea observed was higher in the 1st and 2nd cycles (3.9%), with a subsequent sharp reduction from the 3rd cycle (1.3%) and negativisation from the 5th cycle. Lactobacillus kefiri LKF01 (Kefibios®) is safe and effective in preventing severe diarrhoea in cancer patients receiving 5-FU or capecitabine-based treatment.
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Prognostic and predictive factors of eribulin in patients with heavily pre-treated metastatic breast cancer.
Chen, PH, Yeh, DC, Tung, HH, Lin, CY
Medicine. 2021;(47):e27859
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Abstract
A predictive marker for efficacy of eribulin administered as different lines of treatment in metastatic breast cancer (MBC) has not been identified. We aimed to determine the predictive factors for efficacy of eribulin administered as different lines of treatment in MBC patients.This restrospective cohort study included 49 heavily pre-treated MBC patients who received either eribulin monotherapy or combination therapy with eribulin and anti-Her2 therapy. Associations between clinical response of eribulin-based treatment, time-to-treatment failure (TTF), and possible predictive markers were investigated.Patients' median age was 55 years; 65% were ER+; 43% were HER2+; and 16% were triple-negative. Median TTF was 5.23 months and longer in non-visceral metastases patients. Eastern Cooperative Oncology Group (ECOG) status was 0-1; eribulin as ≥2nd-line treatment; eribulin combined with dual blockades; lymphocyte-monocyte ratio (LMR) ≥3; and monocyte-lymphocyte ratio (MLR) <0.4. In patients with eribulin as >3rd-line treatment, univariate analysis showed that ECOG status was 0-1, and LMR ≥3 and MLR <0.4 were associated with a low risk of TTF. Multivariate analysis showed that ECOG status 0-1 was an independent protective factor. Leukopenia and neutropenia were the most common manageable adverse events.ECOG status is an independent predictor for TTF, while LMR and MLR may have an interactive effect with other biomarkers (e.g., ECOG status) to predict response in MBC patients receiving eribulin as ≥2nd-line treatment.
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Effectiveness of Combined Treatment with Traditional Chinese Medicine and Western Medicine on the Prognosis of Patients with Breast Cancer.
Lee, YC, Chen, YH, Huang, YC, Lee, YF, Tsai, MY
Journal of alternative and complementary medicine (New York, N.Y.). 2020;(9):833-840
Abstract
Objective: Traditional Chinese Medicine (TCM) can be used to balance the body's immunity and tumor development during different stages of cancer treatment. Recently, TCM has been an important part of the health care system for breast cancer in Taiwan. This study was conducted as a prospective observation of the prognosis of Western medicine and combined treatment of TCM and Western medicine. Methods: Between April 2014 and March 2015, eligible participants were treated with Western medicine (n = 16) or TCM plus Western medicine (n = 29). The TCM treatment for patients followed the principles of a breast cancer protocol that had been developed in the Integrative Cancer Center. The outcome measures included quality of life, frequency of symptom distress, and clinical safety, and were measured with the Functional Assessment of Cancer Therapy-General (FACT-G), the Common Terminology Criteria for Adverse Events (CTCAE) Scale, and laboratory examinations, respectively. Data on these measures were collected at baseline and at 3 months after treatment initiation. Survival was estimated by Kaplan-Meier curves. Results: The two treatment groups did not differ significantly at baseline in terms of demographic information, FACT-G score, or frequency of symptom distress, except for fatigue, sleep disturbance, and mucositis. Most laboratory examinations did not differ significantly between the two groups, but higher red blood cell counts and lower liver function were found with the combined treatment than with Western medicine alone (p < 0.05). The mean overall survival rates were 25.5 months for the combined group and 22.7 months for the Western medicine group (p = 0.037). Conclusion: The results of this study suggest that combining Western and TCM therapy may have a favorable effect on the prognosis of breast cancer patients. Chinese herbal medicine is worth studying in a future larger cohort with a control group. It also warrants verification as a preventive intervention.
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Utility of neutrophil-to-lymphocyte ratio to identify long-term survivors among HCC patients treated with sorafenib.
Casadei-Gardini, A, Dadduzio, V, Rovesti, G, Cabibbo, G, Vukotic, R, Rizzato, MD, Orsi, G, Rossi, M, Guarneri, V, Lonardi, S, et al
Medicine. 2020;(22):e19958
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Sorafenib is the first multikinase inhibitor demonstrating a survival benefit for patients suffering from advanced hepatocellular carcinoma (HCC). However, 1 issue remains open: what is the factor able to predict which patients will be long survivors?In the present study, we harnessed the potential of conditional survival, aiming at estimating the probability that a patient receiving sorafenib survives for more than 3 years.The present multicentric study was conducted on a cohort of 438 HCC patients. The primary end point was conditional overall survival. Kaplan-Meier survival analysis was used to calculate conditional overall survival probabilities at 3 years.The 3-year conditional survival of patients without disease progression highlights that NLR and ECOG are the factors that most accurately predict the probability of long survival. The 3-year conditional survival of patients with disease progression showed a medium effect size for HCV status, alpha-fetoprotein and NLR at all time-points. Macro-vascular portal vein invasion, extra hepatic disease, and BCLC we have a large effect size at 6 months and a medium effect size at 12 and 24 months.Our findings support the use of baseline NLR for the identification of patients with a higher probability of long-survival. NLR should be used as a stratification factor in the forthcoming clinical trials on the drugs for the advanced HCC now in pipeline.
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Patient factors associated with discrepancies between patient-reported and clinician-documented peripheral neuropathy in women with breast cancer receiving paclitaxel: A pilot study.
Salgado, TM, Liu, J, Reed, HL, Quinn, CS, Syverson, JG, Le-Rademacher, J, Lopez, CL, Beutler, AS, Loprinzi, CL, Vangipuram, K, et al
Breast (Edinburgh, Scotland). 2020;:21-28
Abstract
PURPOSE Discrepancies between clinicians' assessment of chemotherapy-induced peripheral neuropathy (CIPN) and patient-reported outcomes (PRO) have been described, though the underlying reasons are unknown. Our objective was to identify potential patient-specific factors associated with under-describing of CIPN to clinicians in women with non-metastatic breast cancer treated with paclitaxel. METHODS Patients enrolled in an observational study (n = 60) completed weekly CIPN PRO using the EORTC CIPN20. Clinician-documented CIPN using the NCI CTCAE were abstracted from the electronic medical record and paired with CIPN20 data at weeks 7 and 10. Patients were classified as under-describers if their CIPN20 was above the 80th percentile of the CIPN20 distribution for that CTCAE grade from an independent clinical trial (N08CA). Demographics, Assessment of Survivor Concerns (ASC), Trust in Oncologist Scale (TiOS), and health literacy assessment were collected post-treatment via survey. Repeated measures cumulative logistic regression models were used to identify factors associated with under-describing CIPN. RESULTS Forty-two women completed the survey (response rate 70%). Three and 9 patients were categorized as under-describers at weeks 7 and 10, respectively. Women who were not working (OR = 9.00, 95%CI 1.06-76.15), had lower income (OR = 7.04, 95%CI 1.5-32.99), and displayed higher trust in their oncologist's competence (OR = 1.29, 95%CI 1.03-1.62 for a 0.1-unit increase in score) were more likely to under-describe CIPN symptoms. CONCLUSIONS This preliminary study identified non-working status, low income and trust in oncologist's competence as potential factors influencing under-description of CIPN to the clinical team. Further work is needed to clarify these relationships and test additional factors.
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Real-life activity of eribulin mesylate among metastatic breast cancer patients in the multicenter national observational ESME program.
Jacot, W, Heudel, PE, Fraisse, J, Gourgou, S, Guiu, S, Dalenc, F, Pistilli, B, Campone, M, Levy, C, Debled, M, et al
International journal of cancer. 2019;(12):3359-3369
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Abstract
Eribulin mesylate (EM) was recently approved for metastatic breast cancer (MBC) chemotherapy (CT) in late lines by the FDA, with debated results in second line. We evaluated outcomes in breast cancer patients receiving EM as second, third and fourth line in a national real-life cohort of 16,703 consecutive MBC patients initiating their first metastatic therapeutic line between 2008 and 2014. Primary and secondary objectives were overall survival (OS) and progression-free survival (PFS). An imbalance was seen for HER2+ tumors and concomitant anti-HER2 targeted therapies use, we thus performed a subanalysis in HER2- patients. PFS and OS were significantly better in EM patients in third and fourth lines, compared to "Other chemotherapies" patients (PFS: 4.14 vs. 3.02 months, p = 0.0010; 3.61 vs. 2.53 months, p = 0.0102, third and fourth-line; OS: 11.27 vs. 7.65 months, p = 0.0001; 10.91 vs. 5.95 months, p < 0.0001, third and fourth-line). No significant difference was reported in second-line (PFS: 5.06 vs. 4.14 months, p = 0.1171; OS: 13.99 vs. 11.66 months, p = 0.151). Among HER2- patients, a significant difference was seen for all lines, including 2nd-line (PFS: 4.57 vs. 3.91 months, p = 0.0379; OS: 14.98 vs. 10.51 months, p = 0.0113). In this large real-world database, HER2-negative MBC patients receiving EM in second or later CT line presented significantly better PFS and OS. This difference disappeared in second line in the overall population, probably because of the imbalance in HER2-targeted treatments use. Our results mirror those of the published randomized trials. The effect of anti-HER2 therapies addition in this setting still needs to be defined.
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The performance of three oncogeriatric screening tools - G8, optimised G8 and CARG - in predicting chemotherapy-related toxicity in older patients with cancer. A prospective clinical study.
Kotzerke, D, Moritz, F, Mantovani, L, Hambsch, P, Hering, K, Kuhnt, T, Yahiaoui-Doktor, M, Forstmeyer, D, Lordick, F, Knödler, M
Journal of geriatric oncology. 2019;(6):937-943
Abstract
BACKGROUND Older patients are vulnerable to chemotherapy-related toxicity (CRT). Therefore we evaluated screening tools in their power to predict CRT. METHODS Patients with cancer aged ≥65 years completed three screening questionnaires (G8, optimised G8 and Cancer and Ageing Research Group (CARG). Additionally, Comprehensive geriatric assessment (CGA) for verification of supportive care needs was undertaken on patients with impaired G8 scores. During chemotherapy treatment patients were assessed, capturing grade 0-5 CRT as defined by NCI CTCAE 4. RESULTS 104 patients with non-haematological cancers were included at three study sites. Median age was 73 years (range 65-85). Onco-geriatric screening detected 74% as impaired using G8 and optimised G8 questionnaires and 86% using CARG screening. Grade 3-5 toxicity affected 64.4% of all patients. G8 (OR 0.3 95% CI [0.1;1.0]) and optimised G8 (OR 0.4 95% CI [0.1; 1.5]) did not reliably predict CRT, whereas screening with CARG demonstrated a strong prediction of severe CRT: OR 4.2, 95% CI [1.1, 15.9]. CGA was undertaken on 66 patients, revealing deficiencies in nutritional (83%) and functional-status (54%) and occurrence of relevant comorbidity (53%). CONCLUSION The CARG tool could be useful for predicting CRT. CGA showed clinically relevant supportive care needs in patients with a positive G8 screening.