Abstract Background: First-line treatment for chronic lymphoid leukemia (CLL) has shifted from chemoimmunotherapy to targeted therapies, including Bruton's tyrosine kinase inhibitors (BTKis) and BCL-2 inhibitors. Acalabrutinib is a next-generation BTKi administered continuously, while venetoclax plus obinutuzumab is a time-limited regimen. Both are guideline-endorsed frontline therapies, yet direct real-world comparisons are lacking. Methods: We performed a retrospective cohort analysis using the TriNetX Research Network, a global federated health data platform covering over 150 healthcare organizations. Adult patients (≥18 years) with CLL who initiated first-line treatment with acalabrutinib or venetoclax plus obinutuzumab between January 1, 2015, and April 15, 2025, were identified. Patients with TP53 mutations or incomplete baseline data were excluded. The primary endpoint was time to next treatment (TTNT); secondary outcomes included overall survival (OS), subgroup analyses of TTNT, and treatment-related adverse events. Propensity score matching (1:1) using age, sex, race, hemoglobin, platelet count, LDH, β2-microglobulin, and eGFR was performed to reduce confounding. Kaplan–Meier curves were used to estimate survival outcomes, and Cox proportional hazards models were used to calculate HRs. Results: Among 115,624 CLL patients without TP53 mutations, 30,603 received first-line treatment during the study period. Of these, 2,097 received acalabrutinib and 682 received venetoclax plus obinutuzumab. Prior to matching, patients in the acalabrutinib group were older, while those in the venetoclax group exhibited more advanced disease and greater renal impairment. After 1:1 propensity score matching, 669 patient pairs were analyzed, with balanced demographic and clinical characteristics. Median follow-up was 23.4 months in the acalabrutinib group and 20.5 months in the venetoclax–obinutuzumab group. At analysis, 37.4% of patients on acalabrutinib and 22.1% on venetoclax–obinutuzumab had initiated subsequent therapy. Median TTNT was 47.7 months for acalabrutinib and not reached for venetoclax–obinutuzumab (HR 1.84; 95% CI, 1.50–2.26; p < 0.0001). The estimated 4-year TTNT rates were 49.1% and 63.6%, respectively. Median OS was not reached for either group. The 4-year OS estimates were 81.7% for acalabrutinib and 88.4% for venetoclax–obinutuzumab (HR 1.84; 95% CI, 1.28–2.65; p = 0.0009). Subgroup analyses consistently favored venetoclax plus obinutuzumab across predefined clinical strata, including age, sex, Rai stage, and renal function. Differences were not statistically significant in patients with atrial fibrillation, diabetes, or cerebrovascular disease. Safety: Cytopenias were the most frequently reported adverse events. Compared to acalabrutinib, venetoclax plus obinutuzumab was associated with higher rates of neutropenia (any grade: 54.3% vs. 33.3%, p < 0.001; grade 3/4: 35.2% vs. 20.2%, p < 0.001), thrombocytopenia (any grade: 45.9% vs. 31.9%, p = 0.003; grade 3/4: 15.1% vs. 10.6%, p = 0.022), and febrile neutropenia (7.1% vs. 3.4%, p = 0.003). Tumor lysis syndrome was more frequent in the venetoclax group (6.3% vs. 2.3%, p < 0.001). COVID-19 infection was also higher in this group (13.1% vs. 9.4%, p = 0.037). The rate of atrial fibrillation was 9.4% in the acalabrutinib group but did not significantly differ between regimens. Conclusion: In this large, real-world matched cohort study of TP53 wild-type CLL patients, venetoclax plus obinutuzumab was associated with significantly longer TTNT and higher 4-year OS compared to acalabrutinib. Although venetoclax-based treatment was linked to higher incidences of neutropenia, infections, and tumor lysis syndrome, these events were generally manageable with appropriate supportive care.
Bortezomib is a proteasome inhibitor that eradicates multiple myeloma (MM) cells by accumulating toxic misfolded proteins. However, the emergence of bortezomib resistance remains a significant challenge in MM treatment. An aggresome is a subcellular structure enclosed by vimentin that forms when cells are treated with proteasome inhibitors. Aggresomes sequester misfolded proteins bound and transported by HDAC6 and dynein before they are degraded by autophagy, thereby potentially increasing the efficacy of bortezomib in MM treatment. To this end, we screened anticancer drugs for their potential to block aggresome formation and synergize bortezomib-induced MM cell death. The results showed that doxorubicin synergized bortezomib-mediated cytotoxicity and impaired bortezomib-induced aggresome formation in U266B1 cells. Mechanistic studies revealed that doxorubicin downregulated aggresome-promoting factors such as vimentin, HDAC6, and dynein, while enhancing pro-apoptotic pathways by inducing ER stress in bortezomib-treated U266B1 cells. Remarkably, doxorubicin did not potentiate cell death triggered by proteasome inhibitors that do not stimulate aggresome formation, and the combined treatment of bortezomib and doxorubicin failed to generate synergistic cell death in multiple myeloma cell lines lacking aggresome formation activity. These data demonstrate that doxorubicin synergizes bortezomib-induced cell death by blocking aggresome formation. Our studies suggest the therapeutic potential of combining bortezomib and doxorubicin in the treatment of MM.
The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trials such as FOWARC (J Clin Oncol 2019; 37: 3223-3233), NCT04165772 (N Engl J Med 2022; 386: 2363-2376), and PROSPECT (N Engl J Med 2023; 389: 322-334). In this review, we comprehensively assess these pivotal trials and offer additional insights into the evolving role of pelvic radiation in contemporary oncology.
Pomalidomide is one of the immunomodulatory drugs (IMiDs) used for multiple myeloma (MM) treatment. However, the exact molecular mechanism of pomalidomide in MM therapy remains unclear. The current study demonstrated that pomalidomide treatment inhibited MM cell proliferation and induced cell death via ferroptosis. This phenomenon could be reversed by ferrostatin-1, a ferroptosis inhibitor. Additionally, pomalidomide induced ferroptosis by increasing lipid peroxidation, reactive oxygen species (ROS), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) expression. Furthermore, it blocked the conversion of GSH to GSSG and inhibited glutathione hydroperoxidase 4 (GPX4) expression. In vivo experiments demonstrated that pomalidomide significantly reduced the growth of subcutaneous MM tumors in mice, as evidenced by decreased tumor weight and volume. The molecular mechanisms observed in the mice model corroborated the findings from in vitro experiments. Collectively, these results enhance our understanding of the potential mechanisms of pomalidomide in MM therapy.
Background/Aim: The effect of pelvic neoadjuvant radiotherapy (nRT) for stage M1a rectal adenocarcinoma patients treated with systemic therapy followed by proctectomy and metastasectomy was scarcely investigated in the literatures. Patients and Methods: The eligible rectal cancer patients diagnosed between 2011-2019 were identified via the Taiwan Cancer Registry. In the primary analysis, we used propensity score weighting to balance observable potential confounders and compared the hazard ratio (HR) of death for the nRT group vs. without RT group. We also compared the incidence of rectal cancer mortality (IRCM) and performed various supplementary analyses. Results: Our primary analyses included 145 patients. nRT was associated with improved OS (HR=0.51, p=0.01). The numerical trends remained similar for IRCM and in supplementary analyses. Conclusion: nRT was associated with improved OS in our study population.
BACKGROUND/AIM:The role of neoadjuvant radiotherapy in the management of patients with locally advanced rectal cancer (LARC) who have undergone neoadjuvant systemic therapy has been the subject of recent debate.PATIENTS AND METHODS:We identified eligible rectal cancer patients diagnosed between 2011 and 2020 using data from the Taiwan Cancer Registry. In our primary analysis, we applied propensity score weighting (PSW) to balance observable potential confounders. We then compared the hazard ratio (HR) of death the neoadjuvant concurrent chemoradiotherapy (nCCRT) group and the neoadjuvant chemotherapy without radiotherapy (nCT) group. Additionally, we conducted a comprehensive assessment of other outcomes and performed various supplementary analyses.RESULTS:The primary analysis included 2,298 patients. The overall survival did not exhibit statistically significant differences, with a PSW-adjusted HR of 0.72 (95% confidence interval=0.33-1.56, p=0.40) when comparing the nCCRT group to the nCT group. These findings were consistent with those of other long-term outcomes and supplementary analyses.CONCLUSION:In patients with LARC who have undergone neoadjuvant systemic therapy, the addition of radiotherapy did not yield statistically significant differences in long-term clinical outcomes.
Background: The influence of the breast as the primary site on the outcome of diffuse large B-cell lymphoma (DLBCL) and further changes in therapeutic strategies remain unclear. We aimed to compare the outcomes between primary breast and non-breast DLBCL and analyze the genetic profiles of some of the study cohorts using next-generation sequencing. Methods: This matched-pair study reviewed the medical records of 19 patients with stage I and II primary breast DLBCL diagnosed between January 2005 and December 2021 on the basis of the Wiseman and Liao criteria, and we used 1:4 propensity score matching to identify patients with non-breast DLBCL as the control group. The overall response rate, progression-free survival (PFS), and overall survival (OS) were the outcome measures. Results: Patients with primary breast and non-breast DLBCL had a 5-year PFS of 72.6% and 86.9%, respectively ( P = .206). These 2 groups also had comparable 5-year OS (86.9% vs 87.8%; P = .772). The breast as the primary site was not associated with inferior PFS (hazard ratio [HR]: 2.14; 95% CI: 0.66-6.96; P = .206) and OS (HR: 1.26; 95% CI: 0.27-5.93; P = .772). Conclusion: Patients with primary breast DLBCL and those with non-breast DLBCL had comparable PFS and OS under rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens. Further investigations of the mutation profile, its clinical impact, potential central nervous system relapse, and prognosis of primary breast DLBCL are required.
Introduction The “7+3” regimen is widely recognized as the established standard induction therapy for newly diagnosed acute myeloid leukemia (AML), exhibiting a complete remission (CR) rate of 70%. However, the prognosis for patients who do not achieve CR following induction remains discouraging. Leukemia stem cells (LSCs) are recognized as major contributors to chemoresistance in AML. Hence, it is crucial to identify potential targets within LSCs that can overcome chemoresistance. Patients and methods This prospective study involved 20 consecutive de novo AML patients who underwent “7+3” induction therapy. These patients were divided into CR (n=15) and non-CR (n=5) groups. By employing single-cell RNA sequencing (scRNA-seq), we meticulously examined the cellular states of bone marrow mononuclear cells from AML patients at the time of diagnosis and identified LSCs among these cells. The genetic profiles of the LSCs were subsequently compared between the CR and non-CR groups and further validated using independent cohorts. Results The non-CR AML patients exhibited a significant increase in the proportion of immature cells during hematopoiesis within the AML cell populations. Moreover, we found that expressions of MPO and TRH within LSCs were significantly higher in the CR than non-CR groups, which were further validated by independent cohorts. Furthermore, patients with higher expression of TRH and MPO demonstrated substantially improved relapse-free survival (p = 0.009 for TRH; p = 0.002 for MPO) and overall survival (p < 0.001 for TRH; p = 0.002 for MPO). The dysregulation of the OXPHOS pathway, along with altered interferon alpha and gamma responses, disrupted cholesterol homeostasis, and aberrant MYC activity, may contribute as underlying mechanisms for the observed association between MPO or TRH and chemotherapy response. Conclusions MPO and TRH in LSCs may increase chemosensitivity in AML and serve as chemoresponse biomarkers, offering potential benefits in guiding induction strategies for newly diagnosed AML patients
Algae are low photosynthetic autotrophs, which are widely used in bio-energy and agricultural fertilizer fields, and this can greatly reduce carbon emissions in agricultural production. Therefore, the automatic cultivation and detection of algae cells in algae farms are of great significance to agricultural automation. In this paper, an automatic temperature-controlled low-cost lab-on-chip small and intelligent algae culture AIoT system was proposed, and lensless microfluidic system is used for image acquisition to realize portable real-time tracking and analysis of algae cell culture. In order to realize the low cost and the miniaturization of the equipment, an automatic temperature control method based on the sensor chip for heating and controlling the medium flow for cooling was designed. Compared with the traditional complex temperature control equipment, heating and cooling system in this method is quite simple, greatly reducing the cost of temperature control systems. In addition, a Winograd optimization algorithm based on the neural network algorithm is proposed. Hardware implementation is optimized by the algorithm, which largely reduces the computational complexity, circuit area, and power consumption of the neural network, and a circuit structure was also designed for this algorithm. The experiment showed that this method can well complete the Scenedesmus quadricauda culture and analysis, and the process time consumption is reduced to 55.56%. When the precision is int8, the circuit area and power consumption were reduced by 3.19% and 11.09% respectively. Finally, a multi-channel terminal culture and sensor nodes AIoT wireless network connection of S. quadricauda culture acquisition prototype system was realized, which promoted the development of intellectualization and lab-on-chip in the algae farm.
Albumin–bilirubin (ALBI) grade is an objective and reproducible model for evaluating overall survival (OS) in patients with hepatocellular carcinoma (HCC). However, the original ALBI grade was established for patients with Child–Pugh classes A–C. HCC patients with Child–Pugh class C or poor performance status (Barcelona Clinic Liver Cancer (BCLC) stage D) usually receive hospice care. Thus, optimized cutoffs for the ALBI grade for stratifying OS in HCC patients receiving anticancer therapy are pertinent for accurate prognostication. This study retrospectively enrolled 2116 patients with BCLC stages A–C HCC after the exclusion of those ineligible for receiving anticancer therapy. The modified ALBI (mALBI) grades were: an ALBI score ≤−3.02 for mALBI grade 1, an ALBI score >−3.02 to ≤−2.08 for mALBI grade 2, and an ALBI score >−2.08 for mALBI grade 3. The original ALBI and mALBI grades were independent predictors of OS in all the enrolled patients and those receiving transarterial chemoembolization. In patients receiving curative therapy (radiofrequency ablation and surgical resection), the mALBI grade (grade 2 vs. 1 and grade 3 vs. 2) was an independent predictor of OS. Original ALBI grade 2 vs. 1 was an independent predictor of OS but not ALBI grade 3 vs. 2. The mALBI model can differentiate between patients with early, intermediate, or advanced HCC who received anticancer therapy into three prognostic groups. External validation of the proposed mALBI grade is warranted.
As an important indicator of water pollution, algae are highly sensitive to changes in their environment and respond to a wide range of pollutants, they provide an early caution signal of worsening ecological condition. In this article, a kind of portable microfluidic lensless depth neural network algae monitor is proposed. The lensless algae image acquisition module, algae segmentation and classification circuit, and touch panel were integrated into the equipment. Therefore, the equipment can collect and analyze algae automatically in wild water body without laboratory. In order to miniaturize the equipment and reduce the cost, lensless microfluidic channel sampling is adopted. In addition, a dual asymmetric quantization algorithm and circuit structure are proposed for the implementation of deep neural network hardware. Finally, the prototype system construction was completed. Compared with the current analysis equipment, the equipment size and hardware cost are greatly reduced, and the accuracy reduction is kept in a small range, which makes a better compromise between the accuracy, hardware cost and circuit power consumption. The performance of the equipment fully meets the needs of the current portable algae monitor equipment, and the cost is greatly reduced compared with the current equipment. The accuracy of the equipment achieves 94.27%, the size achieves 11 * 11 * 17.5cm. These advances in portability and cost are conducive to promoting the transformation of water algae analysis based on artificial intelligence from large servers in the laboratory to portable algae analysis equipment, and promoting the rapid early analysis of water monitoring.
Cells are the fundamental unit of life activities, and the basis of studying life phenomena. It is very important to observe the growth state of yeast cells for exploring the law of life movement, diagnosis and treatment of diseases, drug screening and so on. This study proposes a kind of intelligent low-cost portable cell culture platform using the microfluidic channel and the special machine learning circuit. The platform can independently complete the whole work of living cell culture and monitoring. For realizing the reusable and low-power deep learning circuit, a complement optimization neural network algorithm for hardware optimization and corresponding multi-clock-domain reusable multi-level precision neural network accelerator circuit were proposed, which can reduce the circuit area and power of convolution operation in all precisions by average 18.11% and 23.5% respectively. Besides, a dynamic multi-level precision control method based on the battery level is proposed to dynamically adjust the precision of machine learning operation, in order to balance the working time and segmentation accuracy of the culture platform. In addition, a microcolumns-based three-port input microfluidic structure was designed for better yeast culture effect. The experiment showed that the culture platform can realize yeast cell culture and achieve almost the same segmentation accuracy as the large biological laboratory with low-power and low-cost. Compared with the previous work, the cost of mass production was reduced by 88.95%, and the equipment volume was 27.1% smaller. At the same time, it can achieve the best balance of working time and working accuracy under the condition of limited power of equipment according to the needs of users.
BACKGROUND:Randomized controlled trials had demonstrated local therapy, such as radiotherapy, can improve outcomes of patients with lung cancer with oligometastatic disease (OMD). However, the definition of OMD is not uniform and the European Society for Radiotherapy and Oncology (ESTRO) and European Organisation for Research and Treatment of Cancer (EORTC) proposed a new classification in 2020 comprising nine subtypes. Therefore, we aimed to investigate the prognostic significance of this European classification for patients with lung OMD treated with definitive radical radiotherapy.PATIENTS AND METHODS:We identified eligible patients via an in-house database. Patient, disease, and treatment characteristics, as well as outcomes, were obtained via chart review plus peer review. Overall and progression-free survival were estimated via the Kaplan-Meier method. Log-rank test was used in univariate analysis and Cox regression in multivariable analyses to investigate the prognostic significance of the subtypes of OMD.RESULTS:We identified 35 eligible patients with six different OMD subtypes treated from 2011 to 2019. After a median follow-up of 23 (range=2-88) months, the median progression-free and overall survival were 11 and 38 months, respectively. The prognosis for patients with the subtype 'induced oligoprogression' was statistically worse than for those without in both univariate (p=0.02) and multivariate (adjusted hazard ratio for death=4.8, 95% confidence interval=1.4-16.2, p=0.01) analyses.CONCLUSION:We found the subtype with induced oligoprogression in the European classification to be associated with worse survival. Further studies are needed to confirm our finding.
Background: As growing evidence links gut microbiota with the therapeutic efficacy and side effects of anti-hyperglycemic drugs, this article aims to provide a systematic review of the reciprocal interactions between anti-hyperglycemic drugs and gut microbiota taxa, which underlie the effect of the gut microbiome on diabetic control via bug-host interactions. Method: We followed the PRISMA requirements to perform a systematic review on human vs. animal gut microbiota data in PubMed, SCOPUS, and EMBASE databases, and used Cochrane, ROBIN-I, and SYRCLE tools to assess potential bias risks. The outcomes of assessment were trends on gut microbiota taxa, diversity, and associations with metabolic control (e.g., glucose, lipid) following anti-hyperglycemic treatment. Results: Of 2,804 citations, 64 studies (17/humans; 47/mice) were included. In human studies, seven were randomized trials using metformin or acarbose in obese, pre-diabetes, and type 2 diabetes (T2D) patients. Treatment of pre-diabetes and newly diagnosed T2D patients with metformin or acarbose was associated with decreases in genus of Bacteroides, accompanied by increases in both Bifidobacterium and Lactobacillus. Additionally, T2D patients receiving metformin showed increases in various taxa of the order Enterobacteriales and the species Akkermansia muciniphila. Of seven studies with significant differences in beta-diversity, the incremental specific taxa were associated with the improvement of glucose and lipid profiles. In mice, the effects of metformin on A. muciniphila were similar, but an inverse association with Bacteroides was reported. Animal studies on other anti-hyperglycemic drugs, however, showed substantial variations in results. Conclusions: The changes in specific taxa and β-diversity of gut microbiota were associated with metformin and acarbose in humans while pertinent information for other anti-hyperglycemic drugs could only be obtained in rodent studies. Further human studies on anti-hyperglycemic drugs other than metformin and acarbose are needed to explore gut microbiota's role in their therapeutic efficacies and side effects.
This paper presents a CNN accelerator structure for lensless microfluidic acquisition of biological image processing. We propose a low power optimized convolution circuit which utilized the sparse characteristics of lensless cell image acquisition system. And a reconfigurable dual-register group structure is also developed for improving the CNN processing efficiency. The CNN accelerator structure can accelerate various cell image analysis algorithm, including image edge segmentation and super-resolution reconstruction. The circuit is implemented with UMC 110nm process, the circuit area is 2.66 mm(2) and the maximal frequency is 300 MHz.
This paper proposes a microfluidic lensless-sensing mobile blood-acquisition and analysis system. For a better tradeoff between accuracy and hardware cost, an integer-only quantization algorithm is proposed. Compared with floating-point inference, the proposed quantization algorithm makes a tradeoff that enables miniaturization while maintaining high accuracy. The quantization algorithm allows the convolutional neural network (CNN) inference to be carried out using integer arithmetic and facilitates hardware implementation with area and power savings. A dual configuration register group structure is also proposed to reduce the interval idle time between every neural network layer in order to improve the CNN processing efficiency. We designed a CNN accelerator architecture for the integer-only quantization algorithm and the dual configuration register group and implemented them in field-programmable gate arrays (FPGA). A microfluidic chip and mobile lensless sensing cell image acquisition device were also developed, then combined with the CNN accelerator to build the mobile lensless microfluidic blood image-acquisition and analysis prototype system. We applied the cell segmentation and cell classification CNN in the system and the classification accuracy reached 98.44%. Compared with the floating-point method, the accuracy dropped by only 0.56%, but the area decreased by 45%. When the system is implemented with the maximum frequency of 100 MHz in the FPGA, a classification speed of 17.9 frames per second (fps) can be obtained. The results show that the quantized CNN microfluidic lensless-sensing blood-acquisition and analysis system fully meets the needs of current portable medical devices, and is conducive to promoting the transformation of artificial intelligence (AI)-based blood cell acquisition and analysis work from large servers to portable cell analysis devices, facilitating rapid early analysis of diseases.
Abstract Introduction: Background: Chemotherapy with a fluoropyrimidine with or without a platinum is currently the standard care for metastatic gastric cancer (GC). Randomized trials have established the role of either a taxane- or an irinotecan-containing regimen as second line chemotherapy. However, medical insurance systems don't permit the reimbursement of both taxane and irinotecan in some countries, including Taiwan. Patients who fail the first line chemotherapy in Taiwan usually receive a regimen containing a fluoropyrimidine / platinum different from the prior regimen, or a self-paid regimen containing paclitaxel, docetaxel or irinotecan. The impact of selecting an identical vs. a class switch chemotherapy on the outcomes of patients is not known. Procedures: The medical records of patients who were diagnosed with metastatic gastric adenocarcinoma from 2008 to 2012 and had received a second line chemotherapy after a first line regimen of fluoropyrimidine (5-fluorouracil, UFT, capecitabine or S-1), and/or platinum (cisplatin, carboplatin or oxaliplatin) were retrospectively obtained from two medical centers in Taiwan. In a second line situation, we defined an identical regimen as a regimen containing another fluoropyrimidine with or without a platinum; and a class switch regimen as a regimen containing paclitaxel, docetaxel or irinotecan. The characteristic and clinical outcomes of the two groups of patients were compared. Kaplan-Meier curves were used to demonstrate the progression free survival (PFS) and overall survival (OS) function of each treatment group. All reported p values were two-sided with the alpha set at a significance of 0.05. Findings: A total of 201 patients met the study criteria. Patients in the identical regimen group were older (p=0.001) and were less likely to stop first line treatment due to disease progression (PD; p=0.026) compared to the class switch group. Although the response rates (CR+PR) were similar (7.8% vs. 8.3%), toxicity occurred more frequently in identical group than in class switch group by 5%. The survival outcomes measures for the identical regimen group and class switch group included 9 and 6.8 weeks (p=0.949) median PFS since second line treatment, 16 and 12 weeks (p=0.585) median OS since second line treatment, and 48 and 58 weeks (p=0.457) median OS since disease diagnosis, respectively. Conclusions: Patients receiving an identical chemotherapy after failure of a fluoropyrimidine with/without a platinum regimen have similar PFS and OS compared to patients receiving a class switch chemotherapy for GC. A higher percentage of PD as the reason to stop first line therapy was noted in patients receiving a class switch chemotherapy and might influence the assessment of a class switch regimen. Further prospective clinical trials are needed to clarify this potential confounding factor. Citation Format: Li-Yuan Bai, Yung-Chia Kuo, Jen-Shi Chen, Wen-Chi Chou, Chang-Fang Chiu, Yu-Min Liao. Class switch or identical regimen as a second-line chemotherapy for patients with metastatic gastric adenocarcinoma: A retrospective analysis of two medical centers in Taiwan [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1640.
Context. Undertreatment of cancer pain among outpatient cancer patients needs to be addressed to enhance care and improve patients' quality of life (QoL).Objectives. This prospective, cross-sectional, patient-focused study aimed to explore the prevalence of pain and undertreatment of cancer pain in outpatients in Taiwan.Methods. A total of 2652 non-selected outpatients with cancer and aged 20 years or older from 16 medical centers across Taiwan were included in this survey. All patients completed a questionnaire based on the Brief Pain Inventory. Pain management index (PMI) was used to evaluate the adequacy of pain management. Possible clinical variables of patients with positive PMI were examined by univariate and multivariate logistic regressions.Results. A total of 1659 (62.6%) outpatients had experienced some degree of pain; among these, 32.4% had negative PMI. Patients with a negative PMI score had significantly poor outcomes of QoL and a significantly higher tendency toward dissatisfaction with pain control by the physician and with the prescribed analgesic drugs. Female gender, primary tumor from breast, nonecancer-related cause of pain, and hospital locations from north Taiwan were independent variables that predicated patients with undertreatment of cancer pain. Most importantly, a forward trend of undertreatment of pain among patients who presented with lower prevalent rate of pain was observed.Conclusion. One-third of Taiwanese outpatients experienced pain because of undertreatment. Awareness of the prevalence of undertreatment of cancer pain and identification of the vulnerable subjects may assist in enhancing patient care and improving patient's QoL. (C) 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.
Abstract Conventional cytogenetics can categorize patients with acute myeloid leukemia (AML) into favorable, intermediate, and unfavorable‐risk groups; however, patients with intermediate‐risk cytogenetics represent the major population with variable outcomes. Because molecular profiling can assist with AML prognosis and next‐generation sequencing allows simultaneous sequencing of many target genes, we analyzed 260 genes in 112 patients with de novo AML who received standard treatment. Multivariate analysis showed that karyotypes and mutation status of TET2, PHF6, KIT, and NPM1mutation/FLT3‐ internal tandem duplication (ITD)negative were independent prognostic factors for the entire cohort. Among patients with intermediate‐risk cytogenetics, patients with mutations in CEBPAdouble mutation, IDH2, and NPM1 in the absence of FLT3‐ITD were associated with improved Overall survival (OS), similar to those with favorable‐risk cytogenetics; patients with mutations in TET2, RUNX1, ASXL1, and DNMT3A were associated with reduced OS, similar to those with unfavorable‐risk cytogenetics. We concluded that integration of cytogenetic and molecular profiling improves prognostic stratification of patients into three groups with more distinct prognoses (P < 0.001) and significantly reduces the number of patients classified as intermediate risk. In addition, our study demonstrates that next‐generation sequencing (NGS)‐based multi‐gene sequencing is clinically applicable in establishing an accurate risk stratification system for guiding therapeutic decisions.
e16139 Background: The benefit of adjuvant chemotherapy (AC) for upper tract urothelial cancer (UTUC) is controversial. Pathologic characteristics such as lymphovascular invasion (LVI) and squamous differentiation (SD) are prognostic and may help decision-making in selecting patients who need adjuvant chemotherapy. We evaluated the impact of pathologic characteristics on the efficacy of adjuvant chemotherapy in UTUC Methods: We retrospectively reviewed records on 200 consecutive patients with UTUC (pathologic stage II, III, and non-metastasis IV) treated with radical nephroureterectomy between January 2004 and September 2014 and obtained free surgical margins. Adjuvant chemotherapy of gemcitabine and cisplatin was given. Overall survival (OS), recurrence-free survival, local-regional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were estimated using the Kaplan-Meier method. The values of prognostic factors were evaluated by Cox regression analysis. Results: The median follow up is 19.5 months. LVI was found in 74 (37.0%) patients and SD in 57 patients (28.5%). AC was administered in 60 (30%) patients. Multivariate analysis showed LVI, SD and AC were independent prognostic factors in terms of OS and DMFS but not in LRFS. For patients with LVI, AC improved OS and DMFS, but the benefit of AC was not observed in patients without LVI. In contrast, there was no improvement of OS and DMFS in patients with squamous differentiation when AC was administered, but AC significantly improved OS and DMFS in patients without squamous differentiation. Conclusions: Lymphovascular invasion and squamous differentiation had differential impact on the efficacy of adjuvant chemotherapy in UTUC. The design of chemotherapy for UTUC should consider pathologic characteristics. OS (%) P DMFS (%) P With LVI (with vs without AC) 83.3 vs 21 < 0.001 85.1 vs 32.4 < 0.001 Without LVI (with vs without AC) 65.2 vs 63.2 0.832 77.8 vs 82.4 0.692 With SD (with vs without AC) 44.9 vs 39.3 0.268 67.6 vs 49.3 0.250 Without SD (with vs without AC) 85.9 vs 55.7 0.005 86.7 vs 72.6 0.039