Notable Events Research Articles

Юридическая хроника

In the March chronicle, its authors comment on some notable legal events in the field of international law (suspension of Russia’s participation in Treaty on Measures for the Further Reduction and Limitation of Strategic Offensive Arms) and tax law (the introduction of a one-time tax on excess income for a number of companies), important changes in the law on education, and also analyse how the law can help cope with everyday life problems caused by current changes in the economic situation.

Special Report: Bipolar Disorder II—Frequently Neglected, Misdiagnosed

Special Report: Bipolar Disorder II—Frequently Neglected, Misdiagnosed

РОЛЬ ЭЛЕКТРОННОГО МАРКЕТИНГА В ПОВЫШЕНИИ КАЧЕСТВА БАНКОВСКИХ УСЛУГ

One of the most notable events and changes in the structure of the world economy at the turn between the second and third millennia was the massive spread and diversity of information and communication technologies, which made it possible to implement new rules in the field of business. Electronic marketing has become the most used means of communication in the economy, including the banking sector. Increased competition between banks has led to the adoption of the concept of quality of banking services. This quality and customer satisfaction have become important topics that ensure the viability of the banking system. The article presents the results of studying the role of electronic marketing in improving the quality of banking services.

The History of Science in the Context of the State Ideology

Mandelstam’s criticism of the Rayleigh theory of the blue color of the sky (1907) and his polemic with M. Planck (1907–1908) did not become notable events in the history of physics. However, the method of their coverage in the Soviet and in the post-Soviet physics literature is remarkable. Most of Soviet physicists and historians of physics supported Mandelstam's point of view in his criticism of both Raleigh and Planck. The situation changed only at the beginning of the 21st century: in the Russian literature the publications appeared emphasizing that in the Raleigh–Mandelstam and Planck–Mandelstam controversies Mandelstam was not right, Raleigh and Planck were closer to the truth. Which presumptions of this trend can be noted? This was patriotism of the scientific school peculiar to Mandelstam’s graduate students and the former graduate students, the patriotism connected with solidarity which helped Mandelstam’s community to survive in the Soviet totalitarian regime and in the totalitarian organization of science. This was also progressionism which was popular among academics and among men in the street. The phenomenon of common knowledge, mutual knowledge among the members of a scientific community should be taken under consideration. Common knowledge is connected with the non-thematized anonymous inclusion of the ideological terminology into scientific discourse.

Overview of Open Dataset Sessions and Benchmarking Competitions in 2022 - Part 1 (QoMEX 2022, ODS at MMSys '22)

In this Dataset Column, we present a review of some of the notable events related to open datasets and benchmarking competitions in the field of multimedia. This year's selection highlights the wide range of topics and datasets currently of interest to the community. Some of the events covered in this review include special sessions on open datasets and competitions featuring multimedia data. While this list is not exhaustive and contains an overview of about 40 datasets, it is meant to showcase the diversity of subjects and datasets explored in the field. This year's review follows similar efforts from the previous year (https://records.sigmm.org/2022/01/12/overview-of-open-dataset-sessions-and-benchmarking-competitions-in-2021/), highlighting the ongoing importance of open datasets and benchmarking competitions in advancing research and development in multimedia. The column is divided into three parts, in this one we focus on QoMEX 2022 and ODS at MMSys '22.

Overview of Open Dataset Sessions and Benchmarking Competitions in 2022 - Part 2 (MDRE at MMM 2022, ACM MM 2022)

In this Dataset Column, we present a review of some of the notable events related to open datasets and benchmarking competitions in the field of multimedia. This year's selection highlights the wide range of topics and datasets currently of interest to the community. Some of the events covered in this review include special sessions on open datasets and competitions featuring multimedia data. While this list is not exhaustive and contains an overview of about 40 datasets, it is meant to showcase the diversity of subjects and datasets explored in the field. This year's review follows similar efforts from the previous year (https://records.sigmm.org/2022/01/12/overview-of-open-dataset-sessions-and-benchmarking-competitions-in-2021/), highlighting the ongoing importance of open datasets and benchmarking competitions in advancing research and development in multimedia. The column is divided into three parts, in this one we focus on MDRE at MMM 2022 and ACM MM 2022.

Seismic hazard analysis on Solok Regency, West Sumatra to support local government development program

Solok Regency is an administrative area located in West Sumatra that is currently carrying out disaster mitigation programs. Mostly, major infrastructure such as the Solok Local Government Buildings Complex, school facilities, hospital buildings, and many dense residential buildings are scattered over this area. One notable event happened on September 30, 2009, which forced the local government to take serious prevention steps to reduce casualties and damages in the future. Furthermore, there is a need to develop a comprehensive study to analyze the seismic hazards by determining the value of Peak Ground Acceleration (PGA) at the bedrock. The analysis was carried out using the Probability Seismic Hazard Analysis (PSHA) by calculating several seismic sources towards Solok regency by a radius of 500 kilometers from the Arosuka area for a 2475-year return period. The result showed a PGA value of 1.052g on Arosuka, Solok regency, while the Openquake platform shows the range of PGA values varies from 0.576g – 1.368g. The PGA values were then visualized into a seismic hazard map using a geographic information system (GIS). In addition, these scientific results are used as basic information to estimate the seismic vulnerability to support the disaster risk reduction program in West Sumatra.

Overview of Open Dataset Sessions and Benchmarking Competitions in 2022 - Part 3 (ImageCLEF 2022, MediaEval 2022)

In this Dataset Column, we present a review of some of the notable events related to open datasets and benchmarking competitions in the field of multimedia. This year's selection highlights the wide range of topics and datasets currently of interest to the community. Some of the events covered in this review include special sessions on open datasets and competitions featuring multimedia data. While this list is not exhaustive and contains an overview of about 40 datasets, it is meant to showcase the diversity of subjects and datasets explored in the field. This year's review follows similar efforts from the previous year (https://records.sigmm.org/2022/01/12/overview-of-open-dataset-sessions-and-benchmarking-competitions-in-2021/), highlighting the ongoing importance of open datasets and benchmarking competitions in advancing research and development in multimedia. The column is divided into three parts, in this one we focus on ImageCLEF 2022 and MediaEval 2022.

Hospitality in Shanghai: The Russian Jewish Community as Hosts and Polish Jewish Refugees as Guests during WW2

This article is an exploration of three exile memoirs penned by Eastern European Jewish refugees who documented a notable world history event: during WW2, when 6 million European Jews perished in Nazis concentration and death camps, Shanghai was the city where more than 20,000 Jews were saved. Through a conceptual framework inspired by Emmanuel Levinas and Jacques Derrida, this article interprets instances of hospitality in these memoirs.

Toward consistent change detection across irregular remote sensing time series observations

The use of remote sensing in time series analysis enables wall-to-wall monitoring of the land surface and is critical for assessing and understanding land cover and land use change and for understanding the Earth system as a whole. However, variability in remote sensing observation frequency through time and across space presents challenges for producing consistent change detection results throughout the available satellite record using approaches such as the Continuous Change Detection and Classification (CCDC) change detection methodology. Here we investigate new modifications to this methodology with the goal of improving accuracy and consistency in results and increasing flexibility for operational usage and future development. The modified method (Band-First Probability, or CCD-BFP) change detection procedure works by calculating a test for each band through time before summarizing between bands. We evaluate the CCD-BFP method compared to an existing implementation of CCDC using a variety of approaches, including a validation dataset of human-interpreted locations, comparison with data from fire events, use of simulated remote sensing data, and qualitative inspection of areas of interest. We find CCD-BFP improves consistency across time and space compared to the existing implementation of CCDC, with more similarity in rates of change across Landsat swath boundaries and before and after the launch of Landsat 7. Also, we find that CCD-BFP detects more of the change events in the validation dataset while reducing the overall number of change detections, indicating that it is able to more accurately capture the most notable land surface change events.

Hydroclimate variability in the Madagascar and Southeast African summer monsoons at the Mid- to Late-Holocene transition

The 4.2 ka event at the Mid- to Late-Holocene transition is often regarded as one of the largest and best documented abrupt climate disturbances of the Holocene. The event is most clearly manifested in the Mediterranean and Middle East as a regional dry anomaly beginning abruptly at 4.26 kyr BP and extending until 3.97 kyr BP. Yet the impacts of this regional drought are often extended to other regions and sometimes globally. In particular, the nature and spatial extent of the 4.2 ka event in the tropics have not been established. Here, we present a new stalagmite stable isotope record from Anjohikely, northwest Madagascar. Growing between 5.22 and 2.00 kyr BP, stalagmite AK1 shows a hiatus between 4.31 and 3.93 kyr BP (±40 and ± 35 yrs), replicating a hiatus in another stalagmite from nearby Anjohibe, and therefore indicating a significant drying at the Mid- to Late-Holocene transition. This result is the opposite to wet conditions at the 8.2 ka event, suggesting fundamentally different forcing mechanisms. Dry conditions are also recorded in sediment cores in Lake Malawi, Lake Masoko and the Tatos Basin on Mauritius, also in the southeast African monsoon domain. However, no notable event is recorded at the northern (equatorial East Africa) and eastern (Rodrigues) peripheries of the monsoon domain, while a wet event is recorded in sediment cores at Lake Muzi and Mkhuze Delta to the south. The spatial pattern is largely consistent with the modern rainfall anomaly pattern associated a with weak Mozambique Channel Trough and a northerly austral summer Intertropical Convergence Zone position. Within age error, the observed peak climate anomalies overlap with the 4.2 ka event. However regional hydrological change consistently begins earlier than a 4.26 kyr BP event onset. Gradual hydrological change frequently begins around 4.5 kyr BP, raising doubt as to whether any coherent regional hydrological change is merely coincident with the 4.2 ka event or part of a global climatic anomaly.

PP110 An External Combined Occipital And Trigeminal Neurostimulation Device For Migraine Treatment

IntroductionMigraine is a multifactorial pathology that affects 12 percent of the world’s population. Relivion® MG (Neurolief Inc., USA) is a non-invasive self-administered device for external combined occipital and trigeminal nerve stimulation that has been recently approved for marketing in Europe and the USA. The objective of this study was to conduct an early assessment of the efficacy and safety of Relivion for the treatment of migraine episodes.MethodsRelivion was identified by the early awareness and alert system, SINTESIS- nuevas tecnologías, of the Agencia de Evaluación de Tecnologías Sanitarias at the Instituto de Salud Carlos III. An early assessment of the technology was conducted by reviewing relevant clinical studies published to 29 September 2021. The literature was identified by searching PubMed, Embase, the International Clinical Trials Registry Platform, ClinicalTrials.gov, and the Cochrane Library.ResultsTwo randomized, sham-controlled double-blind trials were found. They assessed side effects and pain relief, response rate, and pain freedom two hours after treatment. One study included 55 patients and the other (the RIME study) included 131 patients. The rate of pain relief two hours after treatment ranged from 60 to 76 percent in the treatment group and from 31 to 37 percent in the control group (p<0.01). The response rate, defined as at least 50 percent pain reduction two hours after treatment, was significantly higher in the treatment group (67 to 70% versus 32 to 42%). The percentage of patients free of pain two hours after treatment ranged from 42 to 46 percent in the treatment group, compared with 11 to 12 percent in the control group (p<0.0001). No notable adverse events were recorded.ConclusionsPreliminary results indicated that Relivion effectively and safely relieves or eliminates acute migraine pain. However, more comparative studies are needed. The use of Relivion could improve the control of symptoms and improve quality of life in patients with migraine.

A review of the novel tissue factor antibody-drug conjugate: Tisotumab vedotin.

To review and compare the pharmacology, efficacy, and safety of the novel tissue factor antibody-drug conjugate, tisotumab vedotin. Literature search was performed through PubMed MEDLINE, Google Scholar, ClinicalTrials.gov, and the Food and Drug Administration. Tisotumab vedotin, a novel tissue factor antibody-drug conjugate, was granted accelerated approval by the US FDA on 20 September 2021 for adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. Tisotumab vedotin demonstrated clinical efficacy in a number of solid tumors in innovaTV 201 and more specifically in cervical cancer in the pivotal phase 2 innovaTV 204. In the single-arm innovaTV 204 study, 101 patients with recurrent or metastatic cervical cancer received intravenous tisotumab vedotin at the recommended dose of 2 mg/kg every 3 weeks until disease progression or unacceptable toxicity. The independent review committee confirmed an objective response rate of 24% with 7% complete responses and 17% partial responses. Tisotumab vedotin is associated with several notable adverse events with data from innovaTV 204 including ocular toxicity, hemorrhage, and peripheral neuropathy. Ninety-two percent of patients experienced treatment-related adverse events with 28% experiencing an adverse event of grade 3 or higher. Metastatic cervical cancer has a high risk of relapse with few effective second-line therapeutic options. Current guidelines recommend single agent tisotumab vedotin as a possible option. Ongoing trials will further define its place in therapy.

Racial Differences in Response to Chadwick Boseman's Colorectal Cancer Death: Media Use as a Coping Tool for Parasocial Grief.

The August 2020 death of Black actor Chadwick Boseman, at age 43 from colon cancer was a notable public event. Given Boseman's popularity, particularly amongst Black audiences, and racial disparities in colorectal cancer rates, public responses to this news provided a window into potential racial differences in expressing and responding to parasocial grief, that is, grief at the loss of a public figure. Additionally, given how the movies he starred in were easily viewable by audiences stuck at home during the COVID-19 pandemic and given his popularity on digital spaces like Black Twitter, this case offers insights into how media use can help people cope with parasocial grief. We conducted a mixed-methods survey study of audience responses Boseman's death. Quantitative results reveal that Black audiences had different rates of social sharing and movie viewing than non-Black audiences, with additional insights emerging from a thematic analysis of the open-ended data.

Venetoclax Plus Decitabine for Young Adults with Newly Diagnosed ELN Adverse-Risk Acute Myeloid Leukemia: Updated Results of a Phase 2 Trial

Background: The young adults with newly diagnosed (ND) ELN adverse-risk acute myeloid leukemia (AML) fit for intensive chemotherapy (IC) have low complete remission (CR) rate and dismal outcomes compared with AML in favorable- and intermediate-risk categories. Venetoclax (VEN) combination with hypomethylating agents is a new standard of care for older and unfit AML patients (pts) and has been demonstrated to improve composite complete remission and overall survival (OS). We previously reported that VEN plus decitabine (DEC) as frontline treatment for young pts with ND ELN adverse-risk AML and demonstrated promising efficacy and safety at median follow-up of 2.7months in a phase 2 trial (Chen et al, ASH 2021). Here we present an updated analysis of efficacy and safety results in the ongoing study. Methods: This multicenter, single-arm, phase 2 trial (NCT04752527) enrolled young pts (aged between 18 and 59) with ND AML, who met the adverse risk group according to 2017 ELN risk stratification screened by fast next-generation sequencing (NGS), multiplex RT-PCR and fluorescence in situ hybridization (FISH) within 72 hours, and were eligible for standard induction chemotherapy. The study design was previously reported (Chen et al, ASH 2021). The primary outcome was composite complete remission (CRc: CR plus CR with incomplete blood count recovery [CRi] and morphologic leukemia free state [MLFS]). Secondary outcomes were OS, event-free survival (EFS) and safety. The data cut-off date was July 31, 2022. Results: Between February 12, 2021 and July 31, 2022, 286 patients aged between 18 and 59 with ND AML underwent screening. 78 pts were classified as ELN adverse-risk category by fast NGS (within 72 hours) together with multiplex RT-PCR and FISH and 42 pts were enrolled, comprising 26 males and 16 females. Median age was 39 years (range, 19-58) (Table 1). As of the cut-off date, 40 pts completed the first cycle of VEN+DEC and 37 pts completed two courses. In cycle 1, 31 (77.5% [95% CI, 61-89]) pts achieved CRc, 8 (20% [95% CI, 10-36]) pts had partial remission and 1 (2.5% [95% CI, 0-15]) had no response. 24 (77.4% [95% CI, 58-90]) of 31 pts achieving CRc had measurable residual disease (MRD) negativity assessed by multiparameter flow cytometry (MFC) with a sensitivity of 10-3-10-4(0.1%-0.01%). Pts with RUNX1 and FLT3-ITD mutations had higher CRc rates of 83.3% and 80%, respectively. Pts harboring TP53 and ASXL1 mutations achieved encouraging CRc rates of 62.5% and 75%, respectively. The CRc rates in pts with 11q23/KMT2A rearrangements and complex karyotype were 66.7% and 88.9%, respectively. The CRc and MRD negativity were achieved in 91.9% (34/37, 95% CI, 77-98) and 82.3% (28/34, 95% CI, 65-93) of the pts after the second course of treatment. 31 (73.8%) of 42 pts received allogeneic hematopoietic stem cell transplantation (HSCT), among them 26 patients achieved complete remission before HSCT, 3 received HSCT after morphologic relapse and 2 with salvaged HSCT. At median follow-up of 10.2 months (range, 0.8-17), the median OS and EFS were not reached (Figure1a, b). Estimated 12-months OS was 92.9% (95% CI, 79-98) and EFS was 71.4% (95% CI, 55-84). Among enrolled pts achieving CRc in cycle 1, median time to blood cell count recovery for absolute neutrophil count (ANC) ≥1000 cells per μL was 30 days (range, 16-NR), and for platelet count ≥50 000 platelets per μL was 20 days (range, 0-NR). Among 40 pts evaluable for safety analysis, the most common non-hematological adverse events were infections with grade 3 or worse neutropenia in 18 (45%) pts and febrile neutropenia in 11 (27.5%) pts. Notable serious adverse events were pneumonia in 5 (12.5%) pts and sepsis in 1 (2.5%). Mortality rates of 30-day and 60-day were 0%. Conclusions: VEN plus DEC was an effective, lower-intensity regimen that was well tolerated for young adults with ND ELN adverse-risk AML, producing high rates of CR and encouraging EFS and OS. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Pathogenome comparison and global phylogeny of Escherichia coli ST1485 strains

Escherichia coli ST1485 strains belong to the clinically important phylogroup F and have disseminated worldwide in humans, animals, and the environment. Here, we elucidated the pathogenome of a global collection of E. coli ST1485 isolates from diverse sources retrieved from public databases and a high-quality sequenced complete genome of colistin-resistant E. coli strain CFSAN061771 isolated from raw milk cheese which designated as a reference strain. CFSAN061771 belongs to O83:H42-ST1485 pathotype and carries a conjugative ColV plasmid, pCFSAN061771_01, combining extraintestinal virulence genes (ompt, sitA, iroN, etsC, traT, cvaC, hylF, iss, tsh, mchf, iucC, iutA) with a multidrug resistance island (blaTEM-1, aph(6)-Id, aph(3″)-Ib, sul2, dfrA14). Comparative genomic analysis revealed a high frequency of pCFSAN061771_01-like plasmids in E. coli ST1485. A notable evolutionary genetic event in E. coli ST1485 strains is the acquisition of a pCFSAN061771_02-like plasmid, which confers resistance to several antimicrobials, tellurium, and quaternary ammonium compounds. The identical virulence and antibiotic resistance profiles identified in some human and animal strains are worrisome. This is the first study to emphasize the significance of E. coli ST1485 as a global high-risk virulent and multidrug-resistant clone with zoonotic potential.

Potential lipid-lowering effects of Ulmus macrocarpa Hance extract in adults with untreated high low-density lipoprotein cholesterol concentrations: A randomized double-blind placebo-controlled trial.

Ulmus macrocarpa Hance extract (UME) has demonstrated an antilipidemic effect via upregulation of the adenosine monophosphate-activated protein kinase pathway and regulation of lipid metabolism in both laboratory and animal studies. Therefore, we examined the effects and safety of UME on plasma lipids in adults with untreated high, low-density lipoprotein cholesterol (LDL-C) concentrations. In the current double-blind placebo-controlled randomized clinical trial, 80 patients with untreated high LDL-C concentrations (130-190 mg/dl) were randomly allocated to either the "UME group" (received 500 mg UME as two capsules per day) or the "Placebo group" (received placebo containing cornstarch as two capsules per day) for 12 weeks. The primary outcome was the change in LDL-C concentration within the 12-week treatment period; secondary outcomes included changes in total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol, apolipoprotein A1, and apolipoprotein B (ApoB) concentrations. UME over 12 weeks led to a greater decrease in LDL-C, TC, and ApoB concentrations than did the placebo as follows: by 18.1 mg/dl (P < 0.001); 23.3 mg/dl (P < 0.001); 9.3 mg/dl (P = 0.018), respectively. When LDL-C, TC, and ApoB concentrations were expressed as a lsmeans percentage of the baseline concentration, they after 12 weeks of UME had greater % differences compared to the placebo as follows: by 11.9% (P < 0.001); 10.0% (P < 0.001); 8.6% (P < 0.05), respectively. However, no significant inter- and intra-group changes in liver enzyme, free fatty acid, anti-inflammatory marker, and fasting glucose concentrations were observed. None of the participants experienced notable adverse events. UME causes a significant improvement in lipid profiles in adults with untreated high LDL-C concentrations. [www.clinicaltrials.gov/], identifier [NCT03773315].

Harari’s concept of macrohistory: origins of popularity and academic status

The unprecedentedly high level of popularity of Y. N. Harari, а professor at the faculty of history of the Hebrew University in Jerusalem, and his main book trilogy, foreground the problem of interpreting and explaining the so-called Hararimania phenomenon, which has become a notable event in the academic community and popular culture of modern Western societies. The purpose of this article is the historical and philosophical reconstruction of the creative evolution of Y. N. Harari with an emphasis on identifying the fundamental meaning and status of his concept of macrohistory in this evolution (process). At the same time, the internal inconsistency of this concept is substantiated, which is largely responsible for the dual nature of its perception and assessments in the mass media and professional academic discussions. The designated goal of the article is achieved through contextual interpretation and the solution of its several basic tasks. Among them: identifying and explaining the most important stages of the professional socialisation of Y. N. Harari, as well as determining the reasons behind his transition from medieval studies to macrohistory; identifying the thematic priorities of Y. N. Harari, special attention is paid to the topic of transformation of homo sapiens into homo deus; characterising the educational role of Y. N. Harari’s concept of macrohistory, in particular, the part of it that is associated with the popularisation of modern science and its futurological potential; carrying out a contextual analysis of Y. N. Harari’s idea about a new humanistic revolution, in the process of which classical ideas about humanism and liberalism must necessarily give way to techno-humanism and the data religion. The novelty of this article is determined by the following circumstances. Though there is extensive debate about the work of Y. N. Harari this article represents one of the first attempts to implement not only a historical, but also a philosophical and conceptual reconstruction of his main ideas set forth in the famous book trilogy. Simultaneously this is one of the first articles to make the analysis of Y. N. Harari’s concept of macrohistory the main focus point. This sets us apart from most of the publications devoted to Y. N. Harari, which are usually presented in the form of short and purely descriptive literary reviews. The article presents a new aspect to consider about the creative evolution of the Israeli historian – the interpretation of the causes and origins of the significant popularity of his ideas and main publications. These include the author’s deep understanding of the specifics of mass consciousness and the way its representatives perceive popular science texts. This subtle and adequate understanding largely explains the emotional figurative language, genre originality and literary style of Y. N. Harari.

Preliminary Outcome and Quality of Life among Geriatric Head and Neck Cancer (GHNC) Patients Treated with Institutional Nimorad (Nimotuzumab-Modulated Radiotherapy) Protocol

<h3>Purpose/Objective(s)</h3> Treatment for geriatric head and neck squamous carcinomas (GHNC) remain challenging due to multiple patient and treatment related factors. We analyzed radical intent treatment for GHNC with modulated arc therapy (VMAT) and concurrent Nimotuzumab (Nim) as part of prospectively maintained database NIMORAD (Nimotuzumab-modulated radiotherapy) for early clinical outcome and toxicity. <h3>Materials/Methods</h3> 30 (M:25, F:5) patients of biopsy proven locally advanced squamous cell carcinomas staged by whole body PETCT scan (stage III-IVB) were analyzed. All were above 70 years (Range: 70-88 years) and received uniform treatment with VMAT (66-70 Gy/33 fractions) and Inj Nim 200mg weekly for 6 cycles. Cisplatin ineligibility was in terms of age>70, multiple comorbidities, deranged kidney or hearing functions. Patients more than 80 years were selected for NIMORAD only if baseline G8 screening score was 14 or more. All the cases were discussed in Institutional GHNCC (Geriatric head neck cancer clinic). Institutional comprehensive geriatric assessment was followed with G8 scoring, activities of daily living (ADL) by Katz index, nutritional scoring by subjective global assessment (SGA) and co-morbidity scoring with Charlsons comorbidity index (CCI). Primary analysis was related to survival (disease free survival, local control and overall survival) and toxicity. First surveillance PETCT was between 10-14 weeks post treatment. The toxicities were graded as per CTCAE version 3.0. Follow up was every 3 months with 2^nd surveillance PETCT 6-8 months depending on 1^st response. Statistical analyses were carried out using statistical software. <h3>Results</h3> Median follow-up, age and G8 screening score were 18 months, 77 years and 13 respectively. 83.3% patients were male and 60% had oropharyngeal primaries with 10% HPV positive. At 1^st follow up complete response (CR) at primary site was 85% on both FOL and PETCT. Till last follow up 60% had complete response, 16% had loco-regional failure and 2% distant metastases. Nine patients died till last follow up and 5 were lost to follow up. All P16 positive patients (3) had loco-regional and distant control till last follow up. The acute grade 2 mucositis and dysphagia were 70% and 90% respectively with 30% grade 3 dysphagia. Long term tube dependency rates were 10% mostly beyond 80 years. 20% had hematological grade 2 plus toxicity and 10% had skin rash due to Nim. The other notable adverse events were grade 3 trismus, osteoradionecrosis and aspiration pneumonia between 2-5%. Median Katz index was 5, SGA and CCI were higher for hospitalized patients. <h3>Conclusion</h3> This single Institution NIMORAD protocol for GHNC shows promising clinical results with no additional toxicity profile. This can be an option for improved disease control in locally advanced GHNC. Future large cohort prospective documentation with longer follow up is warranted.

CML-046 Dose Modification Dynamics of Ponatinib in Patients With Chronic-Phase Chronic Myeloid Leukemia From the PACE and OPTIC Trials

In the PACE trial (NCT01207440), patients with resistant/intolerant chronic-phase chronic myeloid leukemia (CP-CML) demonstrated lasting responses to ponatinib 45 mg once daily (QD). The OPTIC trial (NCT02467270) prospectively evaluated a response-based dose-reduction strategy to optimize the dosing schedule of ponatinib in patients with CP-CML resistant to second-generation BCR::ABL1 tyrosine kinase inhibitor (TKI) therapy or with a T315I mutation. Our objective was to analyze dosing dynamics between the 2 trials and compare efficacy and safety outcomes. In PACE, patients received an initial dose of ponatinib 45 mg QD. In OPTIC, patients were randomly assigned (1:1:1) to an initial oral dose of ponatinib 45 mg, 30 mg, or 15 mg QD. In PACE, proactive dose reductions were mandated as arterial occlusive events (AOEs) emerged as notable adverse events (AEs). In OPTIC, patients in the 45-mg and 30-mg cohorts in OPTIC achieving ≤1% BCR::ABL1IS had their doses reduced to 15 mg QD; doses were also reduced to manage AEs. Data from patients with CP-CML in PACE and from the 45-mg starting dose cohort in OPTIC were analyzed. Efficacy outcomes include ≤1% BCR::ABL1IS, progression-free survival (PFS), and overall survival (OS). Safety outcomes include treatment-emergent (TE) AEs and TE-AOE rates. A total of 364 CP-CML patients had ≥1 prior second-generation TKI or a T315I mutation and received a starting dose of ponatinib 45 mg (PACE, n=270; OPTIC, n=94). The percentages of patients with vascular disorders were 44% in PACE and 32% in OPTIC. The median follow-ups were 57 months (PACE) and 32 months (OPTIC). The ≤1% BCR::ABL1IS responses by 24 months were 52% (PACE) and 56% (OPTIC), 2-year PFS was 68% (PACE) and 80% (OPTIC), and 2-year OS was 86% (PACE) and 91% (OPTIC). Dose reductions due to AEs occurred in 82% (PACE) and 46% (OPTIC) of patients. Per 100 patient-years, exposure-adjusted TE-AOEs were 15.8 (PACE) and 7.6 (OPTIC) at 0 to <1 year. The response-based dose-reduction strategy in OPTIC resulted in comparable or better efficacy outcomes and fewer AE-related dose reductions and exposure-adjusted TE-AOEs, further demonstrating the benefit of the response-based dosing regimen used in OPTIC. This abstract is an encore from the European Hematology Association 2022 Annual Meeting.