Clonogenic assay and computational modeling using real cell images to study physical enhancement and cellular sensitization induced by metal nanoparticles under MV and kV X-ray irradiation.

This study was initiated due to the physically unexplainable tumor controls resulting from metal nanoparticle (MNP) experiments even under MV X-ray irradiation. A more accurate explanation of the mechanism of radiosensitization induced by MNP is warranted, considering both its physical dose enhancement and biological sensitization, as related research is lacking. Thus, we aimed to examine the intricate dynamics involved in MNP-induced radiosensitization. We conducted specifically designed clonogenic assays for the A549 lung cancer cell line with MNP irradiated by 6 MV and 300 kVp X-rays. Two types of MNP were employed: one based on iron oxide, promoting ferroptosis, and the other on gold nanoparticles known for inducing a significant dose enhancement, particularly at low-energy X-rays. We introduced the lethality enhancement factor (LEF) as the fraction in the cell killing attributed to biological sensitization. Subsequently, Monte Carlo simulations were conducted to evaluate the radial dose profiles for each MNP, corresponding to the physical enhancement. Finally, the local effect model was applied to the clonogenic assay results on real cell images. The LEF and the dose enhancement in the cytoplasm were incorporated to increase the accuracy in the average lethal events and, consequently, in the survival fraction. The results reveal an increased cell killing for both of the MNP under MV and kV X-ray irradiation. In both types of MNP, the LEF reveals a biological sensitization evident. The sensitizer enhancement ratio, derived from the calculations, exhibited only 3% and 1% relative differences compared to the conventional linear-quadratic model for gold and ferroptosis inducer nanoparticles, respectively. These findings indicate that MNPs sensitize cells via radiation through mechanisms akin to ferroptosis inducers, not exclusively relying on a physical dose enhancement. Their own contributions to survival fractions were successfully integrated into computational modeling.

Clinical Utility of Next-Generation Flow-Based Minimal Residual Disease Assessment in Patients with Multiple Myeloma.

Background: Minimal residual disease (MRD) is an important prognostic factor for evaluating a deeper treatment response in patients with multiple myeloma (MM). We evaluated the clinical utility of next-generation flow (NGF)-based MRD assessment in a heterogeneous MM patient population. Methods: Patients with suspected morphological remission after or during MM treatment were prospectively enrolled. In total, 108 bone marrow samples from 90 patients were analyzed using NGF-based MRD assessment according to the EuroFlow protocol, and progression-free survival (PFS) was evaluated according to the International Myeloma Working Group response status, cytogenetic risk, and MRD status. Results: The overall MRD-positive rate was 31.5% (34/108 samples), and MRD-positive patients showed a lower PFS than MRD-negative patients (P=0.005). MRD-positive patients showed inferior PFS than MRD-negative in patients with stringent complete remission (sCR)/complete remission (P=0.014) and high-risk cytogenetic abnormalities (P=0.016). MRD was assessed twice in 18 patients with a median interval of 12 months. Sustained MRD negativity was only observed in patients with sustained sCR, and their PFS was superior to that of patients who were not MRD-negative (P=0.035). Conclusions: Clinical application of NGF-based MRD assessment can provide valuable information for predicting disease progression in patients with MM in remission, including those with high-risk cytogenetic abnormalities.

Linguistic Validation of the US National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events in Korean.

PURPOSE: The aim of this study was to translate and linguistically validate a Korean-language version of the US National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). METHODS: All 124 PRO-CTCAE items were translated into Korean (PRO-CTCAE-Korean) using International Society for Pharmacoeconomics and Outcomes Research best practices and linguistically validated in a diverse sample of patients undergoing cancer treatment (n = 120) to determine whether the Korean translation captured the original concepts. During the cognitive interviews, participants first completed approximately 60 PRO-CTCAE-Korean questions and were then interviewed to evaluate the conceptual equivalence of the translation to the original PRO-CTCAE English-language source. Interview probes addressed comprehension, clarity, and ease of judgement. Three rounds of interviews were conducted. Items that met the a priori threshold of 10% or more of respondents with comprehension difficulties were considered for rephrasing and retesting. RESULTS: A majority of PRO-CTCAE-Korean items were well comprehended in round 1; 14 items posed comprehension difficulties for at least 10% of respondents in round 1. Four symptom terms (mouth and throat sores, feeling like nothing could cheer you up, frequent urination, and pain, swelling, redness at drug injection or intravenous insertion site) were revised and retested in rounds 2 and 3. For the other 10 symptom terms, no suitable alternative phrasing was identified, and the terms were retested in rounds 2 and 3. After rounds 2 and 3, no item presented difficulties in 20% or more of participants. CONCLUSION: PRO-CTCAE-Korean has been linguistically validated for use in Korean-speaking populations. Quantitative evaluation of this new measure to establish its measurement properties and responsiveness in Korean speakers undergoing cancer treatment is in progress.

Patient-Generated Subjective Global Assessment as a prognosis tool in patients with multiple myeloma.

OBJECTIVE: Disease-related weight loss is relatively common in patients with newly diagnosed multiple myeloma (MM), but limited data exist regarding the effects of nutritional status on survival. The aim of this study was to assess the relationship between malnutrition (as measured by Patient-Generated Subjective Global Assessment [PG-SGA]) and clinical characteristics of patients with MM, and to investigate the association between the PG-SGA score before chemotherapy and overall survival in MM patients. METHODS: Using the PG-SGA score, we retrospectively explored the effect of malnutrition on the survival of Asian patients with MM. RESULTS: We divided 216 patients with MM into three groups based on their PG-SGA scores. Of these patients 23% (n = 50) had PG-SGA scores ≥9, indicating severe malnutrition requiring specialist nutrition intervention. Body mass index and serum hemoglobin were independently associated with PG-SGA scores (P < 0.05). The median survival time was not reached in nourished patients with PG-SGA scores of 0 to 3, 58.7 mo in moderately malnourished patients with PG-SGA scores of 4 to 8, and 35 mo in severely malnourished patients with PG-SGA scores ≥9 (P = 0.001). Multivariate analysis revealed that PG-SGA scores ≥9 compared with PG-SGA scores of 0 to 3 (hazard ratio [HR], 2.347; 95% confidence interval [CI], 1.271-4.334; P = 0.006), International Staging System (ISS) stage III compared with ISS stage I (HR, 2.360; 95% CI, 1.271-4.379; P = 0.007), and autologous stem cell transplantation (HR, 0.388; 95% CI, 0.248-0.606; P < 0.001) were associated with overall survival. CONCLUSIONS: A higher PG-SGA score before chemotherapy was associated with reduced survival among patients with MM. Nutritional evaluation should be an integral part of the clinical assessment of MM patients, and the PG-SGA score would be an appropriate tool to evaluate nutritional status.

Unmet needs of non-Hodgkin lymphoma survivors in Korea: prevalence, correlates, and associations with health-related quality of life.

OBJECTIVE: We aimed to describe the prevalence and correlates of unmet needs among non-Hodgkin lymphoma (NHL) survivors in Korea and to identify their association with health-related quality of life (HRQOL). METHODS: Participants were 826 NHL survivors from three hospitals in South Korea diagnosed at least 24 months prior to participating (mean, 6.3 years; range, 2.1-20.9 years). We used self-reported questionnaires, including the Need Scale for Cancer Patients Undergoing Follow-up Care (NS-C) developed in Korea and the EORTC QLQ-C30. We defined an unmet need as a moderate to high level of unmet need in the NS-C response scale. RESULTS: Among six domains, unmet need prevalence ranged from 1.7% to 38.3%. Most commonly reported domains with unmet needs were 'treatment and prognosis' (38.3%) and 'keeping mind under control' (30.5%). The three most frequently reported individual unmet needs were 'being informed about prevention of recurrence' (50.7%), 'being informed about prevention of metastasis' (49.7%), and 'having self-confidence of overcoming cancer' (42.7%). Multivariate logistic analyses revealed that younger age, being unmarried, and low monthly income were associated with unmet needs of multiple domains. Participants with unmet needs demonstrated significantly poorer HRQOL, and the most clinically meaningful differences were found in social function and emotional function. CONCLUSIONS: Korean NHL survivors have substantial unmet needs, especially those who are younger, unmarried, and have a lower income. Initiating supportive care programs for meeting unmet needs may enhance their HRQOL. Copyright © 2016 John Wiley & Sons, Ltd.

Management of B-cell non-Hodgkin lymphoma in Asia: resource-stratified guidelines.

Treatment of B-cell non-Hodgkin lymphomas has undergone substantial developments in the past 10 years. The introduction of rituximab has greatly improved survival outcomes in patients. Clinical practice guidelines based on current evidence have been developed to provide recommendations for standard treatment approaches. However, guidelines do not take into account resource limitations in resource-poor countries. The huge disparities in economy, health-care infrastructure, and access to novel drugs between Asian countries can hinder the delivery of optimum care to patients with lymphoma in Asia. We outline guidelines appropriate to different levels of health-care resources and expertise, aiming to provide advice on diagnosis and treatment, unify interpretation of results, and allow the design of future studies in Asia. In this resource-adapted consensus, we summarise recommendations for diagnosis, staging, risk stratification, and treatment of common B-cell non-Hodgkin lymphomas in Asia.

The impact of baseline and interim PET/CT parameters on clinical outcome in patients with diffuse large B cell lymphoma.

Taking a step forward from the IPI, attention is focused on the role of 18F-FDG PET/CT as a tool for guidance in risk stratification in patients with aggressive non-Hodgkin's lymphoma (NHL). Here, we analyzed the predictive value of various PET/CT parameters in patients with DLBCL. Particularly, we were interested in patients with an IPI score of 1, 2, or 3, whose prognosis are confusing. Between Jul 2008 and Feb 2010, a total of 100 patients (including 57 patients with an IPI score of 1-3) who were treated with R-CHOP for DLBCL, and had assessable PET/CT parameters were analyzed in this study. Absolute value of SUVmax, SUVsum(sum of SUVmax) and TLGsum(SUVmean x Volumemeta) from baseline and interim PET/CT, and ΔSUVsum, ΔSUVmax, and ΔTLGsum between baseline and interim PET/CT were selected as PET/CT parameters. The median number of R-CHOP cycles was 6, and interim PET/CT was performed after 2 or 3 cycles. None of the parameters which showed percentile change between initial and interim PET/CT were associated with prognosis. Instead, absolute value of SUVsum from baseline PET/CT, and SUVmax and SUVsum from interim PET/CT were significantly relevant to PFS in all patients, and in patients with an IPI score of 1­3.