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BackgroundThe programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) axis plays a central role in suppressing antitumor immunity; axis dysregulation can be used by cancer cells to evade the immune system. Tislelizumab, an investigational monoclonal antibody with high affinity and binding specificity for PD-1, was engineered to minimize binding to FcγR on macrophages to limit antibody-dependent phagocytosis, a potential mechanism of resistance to anti-PD-1 therapy. The aim of this phase IA/IB study was to investigate the safety/tolerability, antitumor effects and optimal dose and schedule of tislelizumab in patients with advanced solid tumors.MethodsPatients (aged ≥18 years) enrolled in phase IA received intravenous tislelizumab 0.5, 2, 5 or 10 mg/kg every 2 weeks; 2 or 5 mg/kg administered every 2 weeks or every 3 weeks; or 200 mg every 3 weeks; patients in phase IB received 5 mg/kg every 3 weeks. Primary objectives were to assess tislelizumab’s safety/tolerability profile by adverse event (AE) monitoring and antitumor activity using RECIST V.1.1. PD-L1 expression was assessed retrospectively with the VENTANA PD-L1 (SP263) Assay.ResultsBetween May 2015 and October 2017, 451 patients (n=116, IA; n=335, IB) were enrolled. Fatigue (28%), nausea (25%) and decreased appetite (20%) were the most commonly reported AEs. Most AEs were grade 1–2 severity; anemia (4.9%) was the most common grade 3–4 AE. Treatment-related AEs led to discontinuation in 5.3% of patients. Grade 5 AEs were reported in 14 patients; 2 were considered related to tislelizumab. Pneumonitis (2%) and colitis (1%) were the most common serious tislelizumab-related AEs. As of May 2019, 18% of patients achieved a confirmed objective response in phase IA and 12% in phase IB; median follow-up duration was 13.6 and 7.6 months, respectively. Pharmacokinetics, safety and antitumor activity obtained from both phase IA and IB determined the tislelizumab recommended dose; ultimately, tislelizumab 200 mg intravenous every 3 weeks was the dose and schedule recommended to be taken into subsequent clinical trials.ConclusionsTislelizumab monotherapy demonstrated an acceptable safety/tolerability profile. Durable responses were observed in heavily pretreated patients with advanced solid tumors, supporting the evaluation of tislelizumab 200 mg every 3 weeks, as monotherapy and in combination therapy, for the treatment of solid tumors and hematological malignancies.Trial registration number NCT02407990.

BackgroundNutritional counseling is frequently overlooked in cancer patients with normal nutritional status. This study aimed to evaluate the impact of nutritional counseling in head and neck cancer (HNC) patients with normal nutritional status prior to concurrent chemoradiotherapy (CCRT).MethodsA total of 243 patients with pretreatment normal nutritional status and locally advanced HNC receiving concurrent chemoradiotherapy (CCRT) at three medical centers were enrolled. All patients were retrospectively allocated into the early (≤ 2 weeks, n = 105, 43.2%), late (> 2 weeks, n = 102, 42.0%), and no nutritional counseling groups (n = 36, 14.8%) according to the time interval between the date of CCRT initiation and the first date of nutritional counseling for comparison.ResultsThe 1-year overall survival rates were 95.0%, 87.5%, and 81.3% in the early, late, and no nutritional counseling groups (p = 0.035), respectively. The median body weight changes at end of CCRT were − 4.8% (range, − 13.3 to 8.7%), − 5.6% (range, − 21.9 to 5.6%), and − 8.6% (range, − 20.3 to 2.4%) in patients in the early, late, and no nutritional counseling groups, respectively. The early termination of chemotherapy rates and the incompletion rates of planned radiotherapy were 1.9% and 1.9%, 2.9%, and 2.0%, 13.9%, and 19.4% in patients in the early, late, and no nutritional counseling groups, respectively.ConclusionsOur findings strongly suggest that while some HNC patients may have pretreatment normal nutritional status, early nutritional counseling is nevertheless essential for the improvement of treatment tolerance and survival outcome.

BackgroundConcurrent chemoradiotherapy (CCRT) treatment incompletion is a known negative prognosticator for patients with head and neck cancer (HNC). Malnutrition is a common phenomenon which leads to treatment interruption in patients with HNC. We aimed to compare the performance of three nutritional tools in predicting treatment incompletion in patients with HNC undergoing definitive CCRT.Material and methodsThree nutritional assessment tools, Mini Nutritional Assessment-Short Form (MNA-SF), Malnutritional Universal Screening Tool (MUST), and Nutritional Risk Screening 2002 (NRS-2002), were prospectively assessed prior to CCRT for HNC patients. Patients were stratified into either normal nutrition or malnourished groups using different nutrition tools. Treatment incompletion and treatment-related toxicities associated with CCRT were recorded.ResultsA total of 461 patients were included in the study; malnourished rates ranged from 31.0 to 51.0%. The CCRT incompletion rates were 4.9–6.3% and 14.5–18.2% for normal nutrition patients and malnourished patients, respectively. The tools had significant correlations with each other (Pearson correlation 0.801–0.837, p<0.001 for all) and accurately predicted the incompletion of CCRT. MNA-SF had the highest performance in predicting treatment-related toxicity, including emergency room visits, need for hospitalization, any grade III or higher hematological adverse events, and critical body weight loss, compared to the other tools.ConclusionsMNA-SF, MUST, and NRS2002 were all shown to be competent tools for prediction of treatment incompletion and treatment-related toxicity in HNC patients undergoing CCRT. We suggest implementing nutritional assessment prior to treatment to improve the rate of treatment completion and to reduce treatment-related toxicity in HNC patients.

We probed the associations of preoperative modified geriatric nutritional risk index (mGNRI) values with prognosis in patients receiving surgery for oral cavity squamous cell carcinoma (OCSCC). This retrospective study analyzed the clinical data of 333 patients with OCSCC and undergoing surgery between 2008 and 2017. The preoperative mGNRI was calculated using the following formula: (14.89/C-reactive protein level) + 41.7 × (actual body weight/ideal body weight). We executed receiver operating characteristic curve analyses to derive the optimal mGNRI cutoff and employed Kaplan–Meier survival curves and Cox proportional hazard model to probe the associations of the mGNRI with overall survival (OS) and disease-free survival (DFS). The optimal mGNRI cutoff was derived to be 73.3. We noted the 5-year OS and DFS rates to be significantly higher in the high-mGNRI group than in the low-mGNRI group (both p  < 0.001). A preoperative mGNRI below 73.3 was independently associated with unfavorable DFS and OS. A mGNRI-based nomogram was constructed to provide accurate OS predictions (concordance index, 0.781). Hence, preoperative mGNRI is a valuable and cost-effective prognostic biomarker in patients with OCSCC. Our nomogram facilitates the practical use of mGNRI and offers individualized predictions of OS.

Background Whether the prevalence of frailty and its clinical significance are relevant to treatment outcomes in younger (aged < 65 years) cancer patients remains uncertain. This study aimed to evaluate the impact of frailty on treatment outcomes in younger cancer patients with head and neck and esophageal malignancy. Material and methods This multicenter prospective study recruited 502 patients with locally advanced head and neck and esophageal cancer during 2016–2017 in Taiwan, aged 20–64 years who received curative-intent concurrent chemoradiotherapy (CCRT) as first-line antitumor treatment. Baseline frailty assessment using geriatric assessment (GA) was performed for each patient within 7 days before CCRT initiation. Results Frailty was observed in 169 (33.7%) of 502 middle-aged patients. Frail patients had significantly higher incidences of chemotherapy incompletion (16.6% versus 3.3%, P < .001) and radiotherapy incompletion (16.6% versus 3.6%, P < .001) than fit patients. During CCRT, frail patients had a significantly higher percentage of hospitalizations (42.0% versus 24.6%, P < .001) and a trend toward a higher percentage of emergency room visits (37.9% versus 30.0%, P = .08) than fit patients. Frail patients more likely had a significantly higher incidence of grade ≥ 3 adverse events than fit patients during CCRT. The 1-year survival rate was 68.7% and 85.2% (hazard ratio 2.56, 95% confidence interval 1.80–3.63, P < .001) for frail and fit patients, respectively. Conclusions This study demonstrated the significance of pretreatment frailty on treatment tolerance, treatment-related toxicity, and survival outcome in younger patients with head and neck and esophageal cancer undergoing CCRT. While GA is commonly targeted toward the older population, frailty assessment by GA may also be utilized in younger patients for decision-making guidance and prognosis prediction.

Background/Aim: Restriction of mouth opening (RMO) is a common manifestation of head and neck cancer (HNC) and a poor prognostic factor following concurrent chemoradiotherapy (CCRT) of patients. This study aimed to explore whether the Mallampati score, a visual assessment of the distance from the tongue base to the roof of the mouth, can be used as a surrogate for RMO in predicting treatment outcomes in patients with HNC undergoing CCRT. Patients and Methods: A total of 461 consecutive patients who received definitive CCRT for the treatment of locally advanced HNC between August 2016 and December 2017 at Chang Gung Memorial Hospital in Taiwan (Linkou, Keelung, and Kaohsiung branches) were enrolled in this prospective study. Patients were allocated by the pre-treatment Mallampati score of 1 or 2 (n=24) vs. 3 or 4 (n=207) to compare treatment compliance and treatment-related complications. Results: Patients in the Mallampati score of 3 or 4 group had a higher prevalence of betel quid chewing, oral cavity and oropharynx cancers, advanced tumor stage, poorer performance status, and were more likely to receive platinum monotherapy during CCRT. Patients in the Mallampati score of 3 or 4 group had a 2.08-fold (p=0.002) hazard ratio (HR) for overall survival compared to those in the score of 1 or 2 group in the univariate analysis, the difference remained significant in multivariate analysis (adjusted HR=1.61; 95% CI=1.02-2.61; p=0.047). Patients in the Mallampati score 3 or 4 group had a 2.36-fold (95% CI=1.07-5.19; p=0.033) increased likelihood of incomplete chemotherapy, 2.44-fold (95% CI=1.17-5.06; p=0.017) increased likelihood of incomplete radiotherapy, and 1.84-fold (95% CI=1.18-2.87; p=0.007) risk of unexpected hospitalization compared to those with a Mallampati score of 1 or 2 in multivariate analysis. Conclusion: Patients with HNC with higher pre-treatment Mallampati scores had poorer survival outcomes and were at a higher risk of treatment incompletion and treatment-related toxicities when undergoing CCRT. Our results support the utility of Mallampati score as a surrogate for measuring RMO to predict survival outcomes, treatment compliance, and safety profiles in patients with HNC undergoing CCRT.

BackgroundNo gold standard of nutritional assessment is established among patients with head and neck cancer (HNC) receiving concurrent chemoradiotherapy (CCRT). This study aimed to evaluate the clinical significance of pre-treatment nutritional status using the Mini Nutritional Assessment-short form (MNA-SF) among HNC patients receiving CCRT.MethodsA total of 461 consecutive patients with newly diagnosed HNC treated with definitive CCRT at three medical institutes were prospectively enrolled. Nutritional status was assessed using MNA-SF within 7 days before CCRT initiation. Patients were classified as having normal nutrition, at risk of malnutrition, and malnourished groups according to MNA-SF for comparison.ResultsThe 1-year overall survival rates were 89.8%, 76.8%, and 67.7% in the normal nutrition, at risk of malnutrition, and malnourished groups, respectively. Patients with normal nutrition had significantly lower rates of uncompleted radiotherapy and chemotherapy (4.5% and 4.1%, respectively) compared with patients at risk for malnutrition (14.1% and 11.5%, respectively) and those malnourished (11.1% and 11.1%, respectively). Patients with normal nutrition had significantly lower treatment-related complication rates regarding emergency room visits, hospital admission, and need for tubal feeding than those with at risk of malnutrition and malnourished. Patients with normal nutrition had significantly fewer severe hematologic toxicities (p = 0.044) and severe non-hematologic toxicities (p = 0.012) of CCRT than those malnourished.ConclusionPre-CCRT nutritional status identifies HNC patients vulnerable to treatment interruption and treatment complications. We suggest that nutritional assessment with MNA-SF should be incorporated in pre-CCRT evaluation for all HNC patients.

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Studies in Caucasians have shown that values of hematological indices could be affected by a wide variety of factors. However, parallel work in other ethnical populations, particularly from the Asia-Pacific region, is lacking. Therefore, we designed this study to explore the association between clinical/laboratory parameters and hemogram levels. Adult individuals who came to our hospital for health exams were screened. Information on demographics and laboratory profiles was obtained. We analyzed the impacts of these parameters on the variation of hemogram. Overall, 26,497 adults were included in the current analysis after excluding those with abnormal hemogram. Multivariate regression analysis showed increasing age and male gender negatively affected the number of platelets, whereas a higher serum apolipoprotein B level was associated with an elevated platelet count. Gender and serum albumin level were the major determinants of variation in hemoglobin level. A modestly increased white cell count was seen in men as well as individuals with elevated apolipoprotein B levels, but it was inversely correlated with changes in age and serum albumin levels. Conversely, some variables, although statistically significantly associated with the hematological indices, only provided a trivial explanation for the heterogeneity observed. We further established predictive models for the approximate estimation of hematological indices in healthy adults. Our data indicate that age, gender, and serum levels of apolipoprotein B and albumin affect hematological indices in various ways. We also demonstrate that variation in hemogram could be successfully predicted by a number of clinical and laboratory parameters.

Current evidence suggests that radiotherapy (RT) provides excellent locoregional control and survival rates, exceeding 90% at five years for stage I glottic cancer, particularly when hypo-fractionated regimens are employed. However, outcomes for stage II disease are less favorable, even with modifications to fractionation. In this retrospective study, we analyzed oncological outcomes in a cohort of 121 patients with T2N0M0 glottic cancer in an effort to identify the most effective treatment modality. Our findings indicate that concurrent chemoradiotherapy (CCRT) is the most effective treatment for this patient population. Specifically, the 5-year and 10-year locoregional control rates for patients receiving CCRT were 88.5% and 83.2%, respectively, compared to 72.8% and 69.6% for those treated with definitive RT alone (adjusted hazard ratio: 0.30, 95% confidence interval 0.12–0.76, p = 0.011). Notably, the most significant treatment effects were observed in patients with subglottic extension and vocal cord mobility impairment, which are established poor prognostic indicators for glottic cancer. Conclusion: CCRT improves local control, recurrence-free survival, and overall survival in T2N0M0 glottic cancer, albeit with high toxicity.