Background
Sarcopenia is known to be related to an increased risk of chemotherapy toxicity and to a poor prognosis in patients with malignancy. We assessed the prognostic role of sarcopenia in ...patients with diffuse large B‐cell lymphoma (DLBCL).
Methods
In total, 187 consecutive patients with DLBCL treated with induction rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R‐CHOP) immunochemotherapy were reviewed. Sarcopenia was defined as the lowest sex‐specific quartile of the skeletal muscle index, calculated by dividing the pectoralis muscle area by the height. Clinical outcomes were compared between the sarcopenic and non‐sarcopenic groups. A nomogram was constructed from the Cox regression model for overall survival (OS).
Results
Treatment‐related mortality (21.7 vs. 5.0%, P = 0.002) and early discontinuation of treatment (32.6 vs. 14.9%, P = 0.008) were more common in the sarcopenic group than in the non‐sarcopenic group. The 5 year progression‐free survival (PFS) rates were 35.3% in the sarcopenic group and 65.8% in the non‐sarcopenic group (P < 0.001). The 5 year OS rates were 37.3% in the sarcopenic group and 68.1% in the non‐sarcopenic group (P < 0.001). Sarcopenia and the five variables of the International Prognostic Index (IPI) were independent prognostic factors in a multivariate analysis for PFS and OS and were used to construct the nomogram. The calibration plot showed good agreement between the nomogram predictions and actual observations. The c index of the nomogram (0.80) was higher than those of other prognostic indices (IPI, 0.77, P = 0.009; revised‐IPI, 0.74, P < 0.001; National Comprehensive Cancer Network‐IPI, 0.77, P = 0.062).
Conclusions
Sarcopenia is associated with intolerance to standard R‐CHOP chemotherapy as well as a poor prognosis. Moreover, sarcopenia itself can be included in prognostic models in DLBCL.
In this study, we aimed to evaluate the anticancer effect of benzimidazole derivatives on triple-negative breast cancer (TNBC) and investigate its underlying mechanism of action. Several types of ...cancer and normal breast cells including MDA-MB-231, radiotherapy-resistant (RT-R) MDA-MB-231, and allograft mice were treated with six benzimidazole derivatives including mebendazole (MBZ). Cells were analyzed for viability, colony formation, scratch wound healing, Matrigel invasion, cell cycle, tubulin polymerization, and protein expression by using Western blotting. In mice, liver and kidney toxicity, changes in body weight and tumor volume, and incidence of lung metastasis were analyzed. Our study showed that MBZ significantly induced DNA damage, cell cycle arrest, and downregulation of cancer stem cell markers CD44 and OCT3/4, and cancer progression-related ESM-1 protein expression in TNBC and RT-R-TNBC cells. In conclusion, MBZ has the potential to be an effective anticancer agent that can overcome treatment resistance in TNBC.
Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), significantly reduces mortality and morbidity in patients with chronic heart failure with a reduced ejection fraction ...(HFrEF). However, a considerable number of patients treated with sacubitril/valsartan experience hypotension, oliguria, progressive azotemia, and renal failure as adverse events. These issues have been linked to significant gaps in the usage and dosing of guideline-directed medical therapy with ARNI in patients with HFrEF. We herein report a relevant case of pathologically proven acute tubular necrosis after the first dose of sacubitril/valsartan, highlighting the importance of optimizing the medical therapy in an outpatient with HFrEF.
Local radiotherapy (RT) is important to manage metastatic triple-negative breast cancer (TNBC). Although RT primarily reduces cancer cells locally, this control can be enhanced by triggering the ...immune system via immunotherapy. RT and immunotherapy may lead to an improved systemic effect, known as the abscopal effect. Here, we analyzed the antitumor effect of combination therapy using RT with an anti-programmed cell death-1 (PD-1) antibody in primary tumors, using poorly immunogenic metastatic mouse mammary carcinoma 4T1 model. Mice were injected subcutaneously into both flanks with 4T1 cells, and treatment was initiated 12 days later. Mice were randomly assigned to three treatment groups: (1) control (no treatment with RT or immune checkpoint inhibitor (ICI)), (2) RT alone, and (3) RT+ICI. The same RT dose was prescribed in both RT-alone and RT+ICI groups as 10Gy/fx in two fractions and delivered to only one of the two tumor burdens injected at both sides of flanks. In the RT+ICI group, 200 µg fixed dose of PD-1 antibody was intraperitoneally administered concurrently with RT. The RT and ICI combination markedly reduced tumor cell growth not only in the irradiated site but also in non-irradiated sites, a typical characteristic of the abscopal effect. This was observed only in radiation-sensitive cancer cells. Lung metastasis development was lower in RT-irradiated groups (RT-only and RT+ICI groups) than in the non-irradiated group, regardless of the radiation sensitivity of tumor cells. However, there was no additive effect of ICI on RT to control lung metastasis, as was already known regarding the abscopal effect. The combination of local RT with anti-PD-1 blockade could be a promising treatment strategy against metastatic TNBC. Further research is required to integrate our results into a clinical setting.
Background
To assess whether the rotation of dexamethasone to methylprednisolone decreases the intensity of dexamethasone‐induced hiccup (DIH) in cancer patients treated with chemotherapy.
Materials ...and Methods
Adult patients who experienced DIH within 3 days after the administration of dexamethasone as an antiemetic were screened. Eligible patients were randomly assigned to receive dexamethasone (n = 33) or methylprednisolone (n = 32) as an antiemetic (randomization phase). In the next cycle of chemotherapy, the dexamethasone group received methylprednisolone and vice versa in the methylprednisolone group (crossover phase). The primary endpoint was the difference in hiccup intensity as measured using the numeric rating scale (NRS) between two groups.
Results
No female patients were enrolled, although the study did not exclude them. At the randomization phase, hiccup frequency was 28/33 (84.8%) in the dexamethasone group versus 20/32 (62.5%) in the methylprednisolone group (p = .04). Intensity of hiccup was significantly higher in the dexamethasone group than that in the methylprednisolone group (mean NRS, 3.5 vs. 1.4, p < .001). At the crossover phase, hiccup intensity was further decreased after the rotation of dexamethasone to methylprednisolone in the dexamethasone group (mean NRS, 3.5 to 0.9, p < .001), while it was increased by rotating methylprednisolone to dexamethasone in the methylprednisolone group (mean NRS, 1.4 to 3.3, p = .025). There were no differences in emesis intensity between the two groups at either the randomization or crossover phases. Clinicaltrials.gov identifier: NCT01974024.
Conclusion
Dexamethasone‐induced hiccup is a male‐predominant phenomenon that can be ameliorated by rotating dexamethasone to methylprednisolone without compromising the antiemetic efficacy.
Implications for Practice
In this randomized, multicenter, phase III trial, hiccup intensity was significantly lower when the antiemetic corticosteroid was rotated from dexamethasone to methylprednisolone without a change in emesis intensity than that when dexamethasone was maintained. At the crossover phase, hiccup intensity was increased again if dexamethasone was readministered instead of methylprednisolone. The present study demonstrated that dexamethasone‐induced hiccup can be improved by rotating from dexamethasone to methylprednisolone without compromising its antiemetic efficacy.
摘要
背景.在接受化疗的癌症患者中评估将地塞米松更换为甲泼尼龙是否可以降低地塞米松诱发的呃逆（DIH）的强度。
材料与方法.筛选了接受地塞米松（止吐药）后3天内发生DIH的成年患者。入选患者被随机分配接受止吐药地塞米松（n = 33）或甲泼尼龙（n = 32）（随机化阶段）。在下一个化疗周期中, 地塞米松组接受了甲泼尼龙给药, 而甲泼尼龙组接受了地塞米松给药（交叉治疗阶段）。主要终点是使用数字评定量表（NRS）测定的两组间呃逆强度的差异。
结果.尽管这项研究并未将女性排除在外, 但也没有入组女性患者。在随机化阶段, 地塞米松组的呃逆发生率为28/33（84.8％）, 甲泼尼龙组为20/32（62.5％）（p=0.04）。地塞米松组的呃逆强度明显高于甲泼尼龙组（两组的平均NRS分别为3.5和1.4, p<0.001）。在交叉治疗阶段, 将地塞米松组的地塞米松更换为甲泼尼龙后, 呃逆强度进一步降低（平均NRS为3.5至0.9, p<0.001）, 将甲泼尼龙组中的甲泼尼龙更换为地塞米松后呃逆强度增加（平均NRS为1.4至3.3, p=0.025）。随机分组或交叉治疗阶段两组间的呕吐强度均无差异。Clinicaltrials.gov编号：NCT01974024。
结论.地塞米松诱发的呃逆主要见于男性, 但该症状可以通过将地塞米松更换为甲泼尼龙得到改善, 而不会影响止吐效果。
Dexamethasone is an established agent for the prevention of chemotherapy‐induced nausea/vomiting; however, even a short course of dexamethasone can cause many adverse effects, such as insomnia, indigestion, weight gain, acne, and hiccupping. Although often regarded trivial, persistent hiccups can cause depression, insomnia, and malnutrition. The objective of this study was to determine whether the rotation of corticosteroids affects the incidence and intensity of dexamethasone‐induced hiccup without compromising the antiemetic efficacy.
Objectives
To identify the factors that predict the progression of radiological radiation pneumonitis (RP) to symptomatic RP, and to evaluate the usefulness of the neutrophil‐lymphocyte ratio (NLR) ...as a marker of RP severity and prognosis in stage III non‐small cell lung cancer (NSCLC) patients treated with definitive concurrent chemoradiotherapy (CCRT).
Materials and Methods
We retrospectively reviewed 61 patients treated between January 2010 and December 2015. Patients' demographic characteristics, clinical data, laboratory findings and treatment parameters were analyzed to determine the predictive factors associated with progression from radiological RP to symptomatic RP.
Results
Forty‐seven patients (77%) exhibited radiological RP at a median of 78 days after radiation therapy (RT) completion, and 15 (32%) of these patients developed symptomatic RP. The interval between RT completion and radiological RP presentation was shorter in patients who progressed to symptomatic RP (P = .001); progression was highly probable if this latency period was ≤2 months (P = .002). Stage and RT technique correlated with symptomatic RP development (P = .046 and P = .046, respectively). Among dosimetric factors, a V20 (defined as the lung volume receiving ≥20 Gy) of >30% was the most significant predictor of symptomatic RP (P = .001). The NLR and C‐reactive protein level at radiological RP were higher in patients who developed symptomatic RP (P = .067 and P = .012, respectively). On multivariate analysis, a V20 >30% and an NLR at radiological RP >6 were associated with symptomatic RP development.
Conclusion
The NLR at radiological RP is a useful biomarker for predicting symptomatic RP development after CCRT in stage III NSCLC patients.
Background
The optimal treatment strategy for biliary tract cancer (BTC) after curative‐intent resection remains controversial. The purpose of this study was to evaluate the efficacy of ...fluoropyrimidine‐based adjuvant chemotherapy for BTC patients undergoing microscopically margin‐negative (R0) resection.
Methods
We retrospectively analyzed the clinical data of BTC patients who underwent curative‐intent R0 resection. Patients were eligible if they received either fluoropyrimidine‐based adjuvant chemotherapy or observation after R0 resection.
Results
A total of 153 patients were included. In the entire patient cohort, no significant differences were observed in 5‐year overall survival (OS) rates (48.4% vs. 39.6%, P = 0.439) or 3‐year recurrence‐free survival (RFS) rates (49.1% vs. 39.5%, P = 0.299) between patients who received fluoropyrimidine‐based adjuvant chemotherapy or observation. However, for patients with stages II and III BTC, chemotherapy significantly improved 5‐year OS rate (52.4% vs. 35.6%, P = 0.002) and 3‐year RFS rate (55.5% vs. 39.1%, P = 0.021) compared with observation.
Conclusion
Fluoropyrimidine‐based adjuvant chemotherapy may prolong the survival of patients with stages II and III BTC after R0 resection.
T790M mutation is most common resistant mechanism to epidermal growth factor receptor gene (EGFR) tyrosin kinase inhibitor (TKI). Several third-generation EGFR-mutant selective TKI, such as AZD9291 ...(AstraZeneca), Rociletinib (Clovis), or HM61713 (Hanmi) have been developed. Acquired resistant C797S mutation was known to be one of the resistance mechanisms of AZD9291, which has not been reported for HM61713 yet. This is the first case report of C797S mutation as resistance mechanism of HM61713.
Sarcopenia is defined as loss of skeletal muscle mass and strength. This can lead to adverse clinical outcomes in patients with advanced cancer. The lymphocyte-to-monocyte ratio (LMR), a converted ...inflammatory response, is associated with poor prognosis in patients with malignancies. Herein, we examined the prognostic influence of sarcopenia status assessed by pectoralis muscle area (PMA), inflammatory status calculated by LMR, and its association with disease-free survival (DFS) in a cohort of women diagnosed with nonmetastatic breast cancer. A total of 293 patients with nonmetastatic breast cancer who underwent primary mass resection and radiotherapy between January 2011 and December 2017 were enrolled. The cross-sectional area of the muscle (cm2) at PMA was measured using computed tomography before radiation therapy. Baseline monocyte and lymphocyte counts were obtained from the complete blood count to calculate the LMR. Most of the patients (248/293, 84.6%) underwent breast conservation surgery. Lymph node involvement at diagnosis (hazard ratio HR, 5.08; P < .001), low LMR (HR, 2.79; P = .007), and low PMA (HR, 3.80; P < .001) were independent poor prognostic factors in multivariate analysis. The mean DFS of sarcopenic and nonsarcopenic patients was 89.8 months and 118.8 months, respectively (P < .001). Sarcopenic patients with low LMR showed the worst outcomes, whereas nonsarcopenic patients with high LMR showed the best outcomes. Low PMA and low LMR were independent poor prognostic factors for DFS in patients with nonmetastatic breast cancer.
Purpose
Sarcopenia is suggested to be associated with cancer-related inflammation. We assessed the clinical outcome of small cell lung cancer (SCLC) patients according to sarcopenia and the ...neutrophil-to-lymphocyte ratio (NLR).
Methods
A total of 117 male SCLC patients treated with first-line chemo- or chemoradiotherapy were assessed based on a retrospective chart review. The mass of the pectoralis muscle was measured by computed tomography and normalized to height. Patients with the lowest quartile of muscle mass were considered to have sarcopenia. Patients were classified into four groups according to their sarcopenia and NLR statuses: sarcopenia/high NLR, sarcopenia/low NLR, non-sarcopenia/high NLR, and non-sarcopenia/low NLR.
Results
Sarcopenic patients had lower progression-free survival (PFS) than did non-sarcopenic patients (median 6.0 vs. 7.5 months,
p
= 0.009), but the difference in overall survival (OS) was not statistically significant (median 10.5 vs. 13.5 months,
p
= 0.052). However, the OS of sarcopenic patients with high NLR was significantly lower than that in all other groups (median 3.2 vs. 16.0 vs. 12.5 vs. 13.7 months, respectively,
p
< 0.001), as was PFS (median 3.2 vs. 7.7 vs. 7.6 vs. 7.1 months, respectively,
p
< 0.001). On multivariate analysis, sarcopenia with high NLR was an independent prognostic factor for shorter PFS and OS. Early discontinuation of treatment (20.0 vs. 10.3 %) and treatment-related mortality (50.0 vs. 8.4 %) occurred more frequently in these patients than in the other groups (
p
< 0.001).
Conclusions
In SCLC, sarcopenic male patients with high NLR have a poor prognosis and do not tolerate standard treatment. Intensive supportive care is needed in these patients.
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