Curable Disease Research Articles

Effects of Inflammatory Cell Death Caused by Catheter Ablation on Atrial Fibrillation.

Atrial fibrillation (AF) poses a serious healthcare burden on society due to its high morbidity and the resulting serious complications such as thrombosis and heart failure. The principle of catheter ablation is to achieve electrical isolation by linear destruction of cardiac tissue, which makes AF a curable disease. Currently, catheter ablation does not have a high long-term success rate. The current academic consensus is that inflammation and fibrosis are central mechanisms in the progression of AF. However, artificially caused inflammatory cell death by catheter ablation may have a significant impact on structural and electrical remodeling, which may affect the long-term prognosis. This review first focused on the inflammatory response induced by apoptosis, necrosis, necroptosis, pyroptosis, ferroptosis and their interaction with arrhythmia. Then, we compared the differences in cell death induced by radiofrequency ablation, cryoballoon ablation and pulsed-field ablation. Finally, we discussed the structural and electrical remodeling caused by inflammation and the association between inflammation and the recurrence of AF after catheter ablation. Collectively, pulsed-field ablation will be a revolutionary innovation with faster, safer, better tissue selectivity and less inflammatory response induced by apoptosis-dominated cell death.

Reflections on the difficulties in treating gestational syphilis: from the patient to the health system

Syphilis, an infection caused by the bacterium Treponema pallidum, is a worldwide systemic disease with a chronic course that affects only humans as its host. Transmission can occur through sexual or vertical means. Newborns of mothers with untreated syphilis or those who did not undergo proper treatment may present with either an asymptomatic or severe systemic symptoms. The aim of this study was to conduct a literature review on patient behavioral factors and public health actions that can impact the treatment of gestational syphilis. Articles published in Portuguese, available in full text in the databases Medline, Scielo, Biblioteca Virtual da Saúde (BVS), Lilacs, and PubMed, were considered. Official publications from the Ministry of Health within the same time frame were also taken into account. The results indicate that the main difficulties related to the treatment of gestational syphilis include: deficiencies and/or lack of prenatal care; a shortage of information aimed at pregnant women about the disease; limited access to the primary medication or a failure to seek it; limited adherence of partners to treatment and the use of condoms in sexual relationships. It is necessary to adjust prevention campaigns and monitoring/treatment follow-up for syphilis cases in pregnant women to reduce the negative impact on public health of a treatable and curable disease.

PREVALENCE AND RISK FACTORS ASSOCIATED WITH TUBERCULOSIS OCCURRENCE AMONG PATIENTS ATTENDING MUHIMA DISTRICT HOSPITAL, NYARUGENGE DISTRICT, RWANDA

Tuberculosis (TB) is one the serious public health problems globally and locally and killed at least eight million in 2018 (WHO, 2019). TB is a curable disease if well treated and followed. One of the most key considerations for tracking and evaluating TB prevention and control programs is the prevalence and related risk factors. The study adopted a quantitative approach and a cross-sectional retrospective design to collect data from the respondents. A systematic sampling technique was used and secondary data recorded in the laboratory were collected. Specific objectives were: to determine the prevalence of tuberculosis among patients attending Muhima District Hospital in Nyarugenge District, and to identify behavioral factors associated with TB occurrence among patients attending Muhima District Hospital in Nyarugenge District. Descriptive and analytical statistics were used to analyze the data. The total number of respondents was 2161 patients. The majority, were male 1524(70.5%) and female were 637(29.5%). For the age, those less than 9 years were 19(.9%), between 10-17 years 76(3.5%), between 18-35 years 1185(54.8%), between 36-59 years 843(39.0%), and above 60 years 38(1.8%). Those who were married were 1014(47%), singles were 977(45.2%), and widower were 57(2.6%). For employment, 883(40.9%) were unemployed, 845(39.1%) were employed, 206(9.5%) were students, and 227(10.4%) were prisoners. Based on location, 1181(54.7%) were from urban areas, and 980(45.3%) were from rural areas. The prevalence of TB was 7.2%, out of which the females were 53(34.0%) and males were 103(66.0%). The prevalence of TB among HIV patients was 32.6%. For behavior practices, drinking alcohol was found among 908(42.0%) and smokers were 186(8.6%). For all the predictors of TB occurrence, none of them was statistically associated with TB occurrence. These include demographic characteristics, behavioral factors including use of alcohol, smoking and use of tobacco products, and serology. The prevalence of TB among patients attending Muhima District was higher than the National TB prevalence estimates reported by the World Health Organization (WHO, 2019), respectively 7.2% versus 5.2%. All predictors of TB occurrence including demographic characteristics and behavioral factors none of them was associated with TB occurrence. It is worth recommending a further study to understand in-depth risk factors for TB occurrence in the era of epidemiological transition.<p> </p><p><strong> Article visualizations:</strong></p><p><img src="/-counters-/soc/0045/a.php" alt="Hit counter" /></p>

Management of Acute Promyelocytic Leukemia at Extremes of Age.

Tailored treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has revolutionized the outcome of acute promyelocytic leukemia (APL) from a uniformly fatal disease to one of the most curable malignant diseases in humans. Due to its high efficacy, ATO/ATRA is the standard first-line therapy in younger adult, non-high-risk APL patients. However, early death is still a major issue in APL, particularly in older patients. Thus, rapid diagnostics, immediate access to ATRA-based therapy, and supportive care are of utmost importance. Nevertheless, challenging situations occur, particularly in patients excluded from controlled studies with clinical knowledge mainly based on case reports and registries. Besides the treatment of newly diagnosed patients, managing toxicities and complications remains challenging. This review discusses the approach to the treatment of APL in elderly and pediatric patients.

A systematic review on machine learning and deep learning techniques in the effective diagnosis of Alzheimer’s disease

Alzheimer’s disease (AD) is a brain-related disease in which the condition of the patient gets worse with time. AD is not a curable disease by any medication. It is impossible to halt the death of brain cells, but with the help of medication, the effects of AD can be delayed. As not all MCI patients will suffer from AD, it is required to accurately diagnose whether a mild cognitive impaired (MCI) patient will convert to AD (namely MCI converter MCI-C) or not (namely MCI non-converter MCI-NC), during early diagnosis. There are two modalities, positron emission tomography (PET) and magnetic resonance image (MRI), used by a physician for the diagnosis of Alzheimer’s disease. Machine learning and deep learning perform exceptionally well in the field of computer vision where there is a requirement to extract information from high-dimensional data. Researchers use deep learning models in the field of medicine for diagnosis, prognosis, and even to predict the future health of the patient under medication. This study is a systematic review of publications using machine learning and deep learning methods for early classification of normal cognitive (NC) and Alzheimer’s disease (AD).This study is an effort to provide the details of the two most commonly used modalities PET and MRI for the identification of AD, and to evaluate the performance of both modalities while working with different classifiers.

The Coagulopathy of Acute Promyelocytic Leukemia: An Updated Review of Pathophysiology, Risk Stratification, and Clinical Management.

Acute promyelocytic leukemia (APL) has a well-established mechanism and a long-term prognosis that exceeds that of any other acute leukemia. These improving outcomes are due, in part, to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), two targeted and highly active agents in this disease. However, there remains a considerable morbidity and mortality risk in APL secondary to clinically significant hemorrhagic and/or thrombotic events. Prevention and treatment of these coagulopathic complications remain significant impediments to further progress in optimizing outcomes for patients with APL. Moreover, the relative rarity of APL hinders adequately powered randomized controlled trials for evaluating APL coagulopathy management strategies. This review draws from peer-reviewed works falling between initial descriptions of APL in 1957 and work published prior to January 2023 and provides an updated overview of the pathophysiology of hemorrhagic and thrombotic complications in APL, outlines risk stratification parameters, and compiles current clinical best practices. An improved understanding of the pathophysiologic mechanisms driving hemorrhage and thrombosis along with the completion of well-designed trials of management strategies will assist clinicians in developing interventions that mitigate these devastating complications in an otherwise largely curable disease.

Invited commentary: Tracheal cancer. A rare and deadly but potentially curable disease that also affects younger people.

Invited commentary: Tracheal cancer. A rare and deadly but potentially curable disease that also affects younger people.

Evaluation of carbohydrate and lipid metabolism dynamics in chronic HCV diabetic patients treated with direct antiviral agents

Although Hepatitis C virus (HCV) infection has become a curable disease, the aftermath of the infection remains an important aspect to be evaluated. HCV infection is well known for its extrahepatic manifestations, mostly the tight relationship between HCV, type 2 diabetes mellitus (T2DM) and dyslipidemia. Not only HCV increases the risk of T2DM, but it also affects its control in diabetic patients, increasing the risk of diabetes related complications. Furthermore, HCV hijacks the lipid metabolism resulting in abnormalities in circulating lipids which can lead to multiple complications, such as increased atherosclerotic risk and hepatic steatosis. Objectives. The aim of this study was to evaluate the dynamics of the parameters of carbohydrate and lipid metabolism in HCV-infected diabetic patients compared to non-diabetic patients after viral eradication. Material and methods. This is a prospective study conducted on 100 patients with chronic HVC infection who obtained viral clearance after interferon-free treatment. 58 patients had type 2 diabetes mellitus and 42 were non-diabetic. We evaluated serum total cholesterol, triglycerides, blood glucose and glycosylated hemoglobin in both groups at treatment initiation and 1 year after. Continuous variables were expressed as mean values ± standard deviation or median, categorical variables were represented as relative or absolute frequencies. Characteristics were compared using the Mann-Whitney method or the two-sample Student's T-test method for continuous variables, Chi-square and Fischer's test for categorical variables. A p value < 0.05 was considered statistically significant. Outcomes. The study analyzed and compared lipid and glycemic profiles of diabetic and non-diabetic HVC patients before and after viral cure. Conclusions. 1 year after treatment initiation the changes in lipid metabolism seem to persist, carbohydrate metabolism seems to remain unchanged, with no differences between diabetic and non-diabetic patients.

Abdominal tuberculosis in patients with acute abdomen: an observational single centre study

Background: Abdominal tuberculosis tends to present with nonspecific features and can be hard to diagnose. Abdominal tuberculosis can mimic a variety of other abdominal conditions and only a high degree of suspicion can help in the diagnosis, otherwise, it is likely to be missed or delayed resulting in high morbidity and mortality. Therefore, a high index of suspicion, fortified with a general degree of awareness and knowledge of this form of the disease is essential. Methods: A careful history taking, and thorough clinical examination was carried out in each case. All the patients were investigated. Some of the patients needed surgical intervention. For patients who responded favorably to conservative management and did not require surgery, diagnostic studies were carried out to confirm the presence of abdominal tuberculosis. Results: Abdominal tuberculosis constituted a significant percentage (23.6%) of all cases attending the emergency with an acute abdomen. Ultrasound and CECT can show various findings which can be suggestive of abdominal tuberculosis, but there is no significant difference in PPV of ultrasound and CECT abdomen. Colonoscopy has PPV of 55.6% in diagnosis of abdominal tuberculosis. Gene Xpert is significantly better than AFB staining in diagnosing the abdominal tuberculosis with ascitic fluid examination. Conclusions: Good clinicopathological workup in patients of abdominal tuberculosis results in earlier diagnosis and prompt management of this curable disease. Ultrasound and CECT can be suggestive of abdominal tuberculosis, but final diagnosis can be made only after histopathological examination/with gene Xpert report.

Outcome and toxicity of ifosfamide, carboplatin, and etoposide versus gemcitabine and vinorelbine regimen for pediatric patients with relapsed or refractory Hodgkin's lymphoma.

Pediatric classical Hodgkin lymphoma (CHL) is a curable disease; however, the optimal salvage regimen is unclear for relapsed/refractory (R/R) disease. This study aimed to compare response rates, toxicity, event-free survival (EFS), and overall survival (OS) of ifosfamide, carboplatin, and etoposide (ICE) with gemcitabine and vinorelbine (GV) regimen after first-line doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) in pediatric patients with R/R CHL. This is a retrospective cohort study of 132 pediatric patients with R/R CHL treated from July 2012 to December 2020 with ICE (n = 82) or GV (n = 50). The median age at relapse was 13.9 years, and 68.2% were men. Rates of complete response, partial response, and progressive disease before consolidation were 50.6%, 3.7%, and 45.7% for ICE and 28.5%, 0%, and 71.5% for GV (P = 0.011). By multivariate analysis, regimen (P = 0.002), time to relapse (P = 0.0001), and B-symptoms (P = 0.002) were independent factors to lower response rates. Hematological toxicity, electrolyte disturbance, hemorrhagic cystitis, infectious complications, and hospital admission for fever neutropenia were statistically significant higher for the ICE regimen. Treatment-related mortalities were 2.4% for ICE and 2% for GV (P = 0.86). The 3-year EFS was 39.3% ± 11.4% for ICE and 24.9% ± 12.5% for GV (P = 0.0001), while 3-year OS was 69.3% ± 10.6% and 74% ± 12.9% (P = 0.3), respectively. By multivariate analysis, regimen (P = 0.0001), time to relapse (P = 0.011), B-symptoms (P = 0.001), and leukocytosis (P = 0.007) were significant for EFS, while anemia (P = 0.008), and progressive disease on early response evaluation (P = 0.022) were significant for OS. The ICE regimen had a better overall response rate and EFS, but higher toxicity, than GV; however, OS and mortality were similar.

Some Pertinent Solutions to the Challenges Faced by the Pakistani Healthcare Systems

Health systems worldwide face various challenges. Disparities are evident among different geographic locations. There are several hurdles in providing high-quality professional education, especially in low- and Lower-Middle-Income Countries (LMICs), including insufficient basic infrastructure and a shortage of professionally trained staff. This issue presents a particular risk in LMICs that are ill-equipped to deal with complex and expensive treatments [1, 2]. Although developing and enhancing educational programs to yield more healthcare professionals is constructive, these efforts need to be accompanied by educational structuring that will provide postgraduates with the necessary competencies [3]. It is not uncommon for the patients in LMICs with a potentially curable disease to receive sub-optimal treatment because of a lack of competencies and a caring attitude. This prompts some interesting challenges around the speciality training of postgraduates. In particular, what we are trying to achieve in modern oncology training programmes? Are current examination systems an effective test of knowledge, skills, and safety to practice? And, if so, are they sufficient to prepare for independent practice? Or should training programmes incorporate non-clinical skills related to issues? Interestingly, according to World Health Organization (W.H.O.), there are six elements or system building blocks of the health system that includes (i) service delivery, (ii) health workforce, (iii) health information systems, (iv) access to essential medicines, (v) financing, and (vi) leadership/governance [4]. We believe that these elements overlap with our proposal of inclusion of non-clinical leadership skills during their early years so that they are aware of the gaps and develop a mindset to improve the healthcare system by themselves. In this paper, we propose these five concepts to be inducted into our postgraduate training that will pave the way to improve our healthcare system.

Tracheal cancer: a rare and deadly but potentially curable disease that also affects younger people.

The incidence of tracheal cancer is low, few clinicians get much experience and the awareness may be low. Recent data on the treatment and outcome are limited. The aim of the present study was to present updated, national data on the incidence, characteristics, treatment and outcome for patients with tracheal cancer. All tracheal cancers registered at the Cancer Registry of Norway in 2000-2020 were extracted. The patient and tumour characteristics age, sex, stage, histology and treatment modality (surgery and radiotherapy) were examined. Overall, median and relative survival were estimated. Cox regression models were used to identify independent prognostic factors. The 77 patients diagnosed with tracheal cancer equals a crude incidence rate and an age-standardized incidence rate of 0.075 and 0.046 per 100,000 per year respectively. The mean age was 63.8 years (range: 26-94). The numerical preponderance of men (n = 41) is not statistically significant. Eighteen patients (23.4%) were diagnosed in the localized stage. The 5-year overall survival was 31.7% [95% confidence interval (CI): 21.0-42.9], and in those treated with surgical resection or curative radiotherapy, it was 53.7% (95% CI: 26.1-75.0) and 37.8% (95% CI: 18.8-56.7), respectively. Age, histological type and treatment modality were identified as independent prognostic factors. Despite improved survival, the prognosis for patients with tracheal cancer is still poor. Few are diagnosed in the early stage and thus most are not eligible for curative treatment, mainly surgery. An increased awareness and diagnosis in the earlier stage is crucial.

Pertinence of Streptococcus anginosus group in intracerebral abscesses in the era of extended antibiotic resistance

Aims• To study the incidence of Streptococcus anginosus group (SAG) in pyogenic or community acquired intra cerebral abscess.• To understand the risk factors for the same.• To analyze the specific radiological features and clinical outcome after surgery and antibiotic therapy. MethodsThis is a retrospective observational study of case series over a period of one year. Patients diagnosed with intracerebral abscess were included in the study. Pus collected from were received in the laboratory and processed according to the standard protocols. Data regarding the clinical findings and demographics were collected from medical records. FindingsA total of 202 samples were studied. 103 were found to be pyogenic. SAG were isolated from 21 samples (20.38%) and all the isolates were sensitive to Penicillin. Age of the patients ranged from 18months to 68years. Male preponderance was noted with male to female ratio of 4:1. Otogenic infections were the most common predisposing factors and focus of infection could not be ascertained in 5 patients. All patients were treated with surgical intervention and antibiotics (Vancomycin, Amikacin and Metronidazole) for 6 weeks and recovery was remarkable. One patient succumbed to the illness. ConclusionSAG can be an aggressive pathogen with propensity for abscess formation. Chronic Suppurative Otitis Media (CSOM) is still a major cause of intracerebral abscess in developing country like India which is a benign and curable disease and should not be neglected. Injudicious use of antibiotics and negligence regarding the dose and duration of therapy from both patients and health care providers is the major cause for common infections to become more difficult to treat and succumbing to complications.

Tropical Pyomyositis in Immunocompetent Hosts Posing Diagnostic Challenges: A Case Series

Abstract Pyomyositis is an acute pyogenic infection of the muscles and tissues which results in localized pus collections and abscess formation. This entity at times becomes difficult to diagnose due to lack of specific signs and atypical or nonspecific manifestations. This condition is a mimic for a wide range of differential diagnoses due to which the patient often receives many unwarranted antibiotics. Furthermore, the deep location of the muscles makes the clinical signs in apparent leading to misdiagnosis as rarer entities such as inflammatory myositis. In the last 1 year, four such interesting cases were admitted in this tertiary care center with different clinical presentations. All these cases were healthy, immunocompetent individuals who presented to smaller hospitals with clinical presentation of muscle and joint pain with fever. The muscle groups affected were different in all these cases. All four patients were transferred to this hospital due to the diagnostic dilemma between inflammatory and infective myositis. After a thorough workup including imaging and tissue diagnostics, they were labeled pyomyositis. This further stresses the need for physicians to become acquainted with this potentially life-threatening yet curable infective disease entity. The patients were managed with antibiotics for a minimum duration of 3 weeks and a maximum duration of 8 weeks for complete recovery. Pyomyositis in immunocompetent hosts was related to factors affecting the muscles without any strenuous exercise or direct trauma. Comprehensive evaluation of the muscles is facilitated by assessment of fluorodeoxyglucose uptake on positron emission tomography–computed tomography scan. The initial therapy consisting of cephalosporin and teicoplanin was found effective in our patients. The minimum length of in-hospital treatment was 4 weeks. This series further reinforces the fact that tropical pyomyositis is not exclusive to immunocompromised persons.

ESCALATED BEACOPP X 2 + ABVD X 4 IS SUPERIOR TO ABVD X 6 IN ADVANCE STAGE CLASSICAL HODGKIN LYMPHOMA: EXPERIENCE IN A TERTIARY CENTER

Introduction: Classical Hodgkin lymphoma (cHL) is a curable disease but results in advanced stages are suboptimal when treated with standard treatment ABVD with 10%–15% of primary refractoriness and 30% of relapses, although 5 years overall survival (OS) around 88%–90%. First-line treatment with more intensive schemes such as escalated BEACOPP has improved progression-free survival (PFS) in these patients, although associating greater toxicity. However, escalated BEACOPP did not improve OS when compared to ABVD due to the efficacy of rescue treatments, but assuming a high toxic cost. We present our experience to optimize first-line treatment in advanced cHL. Methods: We retrospectively analyzed patients with advanced stage cHL (IIB-IV) treated with curative intent in our center between December 2008 and December 2022 (Table 1). In the period 2008–2011, patients were treated with ABVD x 6. During the period 2011–2022, we implemented a strategy intermediate PET guided (PET2) after escalated BEACOPP (x 2). With PET2 negative, we continued with ABVD/AVD x 4; in PET2 positive patients we continued with escalated BEACOPP x 4. Both groups received radiotherapy on bulky masses. We evaluate the efficacy of this strategy by comparing results and toxicity in the two study periods. Results: In the 2008–11 period, 21 patients received standard treatment with ABVD and during the 2011–22 period, 60 the intensified one (S). In PET2, 55 (91.6%) of patients in the intensified group achieved CR and 5 (8.4%) PR versus 5 (23.8%) CR, 14 (66.7%) PR and 2 (9.52%) refractory patients in the ABVD group. At the end of treatment, 58 patients (96.6%) achieved CR in the intensified treatment group and 15 (71.4%) in the ABVD group. There where 4 (19%) refractory patients in ABVD group versus 2 (3.3%) in the intensified group. PFS for the intensified treatment group was 90.8% at 5 years versus 57.1% for the ABVD group (p = 0.00025). OS for the intensified treatment group was 98.1% versus 85.7% for the ABVD group at 5 years (p = 0.01). The incidence of admissions for febrile neutropenia tended to be higher in the intensified group (15% vs. 4.76%, p = 0.44) and no significant differences were observed in the incidence of secondary malignancies or infertility. There were no toxic deaths in any group. Keywords: Hodkin lymphoma, PET-CT No conflicts of interests pertinent to the abstract.

Hodgkin lymphoma mortality trends in age subgroups from 1999 to 2020 in the United States.

e19515 Background: Hodgkin Lymphoma has a bimodal distribution with the first peak between ages 15-35 and the second peak being 55 years old and older. Advancements in treatment therapies have improved mortality such that Hodgkin Lymphoma is considered a curable disease. However, treatment outcomes in elderly patients are inferior to those of younger patients. In our study, we analyzed Hodgkin Lymphoma mortality from 1999 to 2020 in the United States. We investigated age-adjusted mortality rates and annual percent changes with a sub-group analysis. Methods: Using the CDC Wonder database, we examined mortality trends from 1999 to 2020 for Hodgkin Lymphoma in adults age 55 and older in the United States. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 people and stratified patients by sex, race/ethnicity, and census region. We computed the annual percentage change trends for the respective stratification using Joinpoint regression software. Additionally, a comparison group between ages 15 and 54 was added for the analysis. Results: In the United States, between 1999 and 2020 there were 24,898 deaths from Hodgkin Lymphoma in Adults 55 and older. The overall age adjusted mortality rate improved from 1.9 per 100,000 people to 1.4, with a respective APC of -2.06%. Our subgroup analysis by sex, race, and census region showed improvements circumferentially. Males consistently had higher rates of improvement than females. Most notably black patients had the lowest difference in AAMR from 1999 to 2020 (0.2), however, white patients and Hispanic patients respectively had higher AAMRs. The comparison group ages 15-54 had lower AAMR change from 1999 to 2020 by sex, race, and region. However, the respective AAMR for the age 15-54 group was significantly lower. Conclusions: Hodgkin Lymphoma has had significant age adjusted mortality rate improvements since 1999. Comparing adults 55 and older to patients 15-54 there is still a notable difference in AAMR. The greater magnitude of improvement in AAMR in older adults with Hodgkin Lymphoma may be related to the approval of agents such as brentuximab vedotin, which has improved tolerability as compared to bleomycin. Alleviating pulmonary toxicity with this novel agent may be more relevant in an older patient population with increased comorbidities. Further, research is needed to continue to identify more efficacious and less toxic therapies for older individuals with Hodgkin Lymphoma. [Table: see text]

THE LOW‐RISK EARLY‐STAGE HODGKIN LYMPHOMA PATIENTS WITH INADEQUATE RESPONSE TO CHEMOTHERAPY. THE PRELIMINARY EXPERIENCE FROM THE RAFTING TRIAL

Introduction: Early-stage Hodgkin Lymphoma (eHL) treated with a combined modality approach (CMT): chemotherapy (CT) and radiotherapy (RT) is a highly curable disease. However, for 70% of eHL patients (pts.) CT alone might be sufficient for cure. The RAFTING trial is a phase 2, multicenter, international prospective study investigating risk-adapted treatment strategy in eHL pts. We hypothesized that CT alone will be sufficient for to cure low-risk pts. Here we would like to present the clinical characteristics of low-risk pts. for whom CT was not sufficient to achieve a complete response (CR). Methods: Treatment intensity in RAFTING is tailored to two risk categories: low or high risk. Low-risk pts. are defined by low baseline metabolic tumor volume (MTV) and negative interim PET after 2 ABVD cycles. High-risk pts. were defined by high baseline MTV and/or positive iPET2. Within the low-risk group the pts. without any risk factors according to modified EORTC (mEORTC) criteria (largest nodal mass (LNM) 5–10 cm, Age > 50 yo, ESR > 50 mm/h, ≥4 nodal areas (NA)) (group 1a) are treated with 2 ABVD cycles only whereas pts. with at least 1 risk factor (group 1b)—with 4 ABVD cycles. High-risk pts. (group 3) receive “triple” therapy (4 ABVD cycles, RT and nivolumab for 12 months; RT-NIV). In case of “limited relapse” (i.e., within initially involved lymph nodes and/or up to 3 new nodal areas) pts. receive delayed RT-NIV. Results: In a per-protocol analysis, out of 77 stratified pts. in March 2023, seven pts. (9%) with low-risk disease, had inadequate response to ABVD alone (defined as achievement less than CR or early relapse (<6 months after the end of the CT): 2 pts. from group 1a and 5 pts. from group 1b. Specifically, one pt. from Group 1a had an extended and symptomatic (B symptoms) relapse, and underwent salvage therapy with ASCT and two pts. from group 1b were withdrawn due to PI decision. While 4 pts. (1 in Group 1a and 3 in Group 1b) with less than CR (2 pts.) or early relapse (2 pts.) received RT + NIV. The most frequent risk factor among 1b pts. was LNM, which was observed in 4 pts., age >50 yo—in 2 patients, and ≥4 NA—in 1 pt. More than 1 risk factor had 2 pts. In 4 cases the confirmatory biopsy was done and was positive for HL in 3 out of 4 cases. Conclusion: The frequency of inadequate response after CT alone observed in the RAFTING trial was similar to that reported by the literature. The most frequent adverse prognostic factor presented in these small pts. subset was a LNM. Keywords: combination therapies, Hodgkin lymphoma, radiation therapy No conflicts of interests pertinent to the abstract.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Classic Hodgkin lymphoma (cHL) is a highly curable disease, even in advanced stages. It is controversial whether bone involvement has a negative effect on overall- and progression-free survival in patients treated with intensive chemotherapy. cHL is characterized by a unique tumor microenvironment (TME) consisting of few, scattered neoplastic Hodgkin and Reed-Sternberg (HRS) cells, embedded in an abundant background of reactive immune and stromal cells. When cHL disseminates, the new disease sites also contain both HRS cells and TME cells. Whether cases that present with bone lesions, harbour specific TME features is unknown. We investigated protein expression in lymph node biopsies from cHL patients with and without skeletal involvement at diagnosis, using nano liquid chromatography—tandem mass spectrometry (nLC-MS/MS), to identify potential markers of skeletal disease. Methods: Protein expression patterns in pre-therapeutic formalin-fixed, paraffin-embedded lymphoma samples from 69 cHL patients diagnosed at Aarhus University Hospital, Denmark between 2009 and 2018 were analysed by nLC-MS/MS. Patients were grouped according to diagnostic 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT). FDG PET/CT scans were reviewed specifically for bone involvement. The study cohort included 50 patients with nodal cHL (n-cHL) and no skeletal involvement, and 19 patients with both skeletal and nodal disease (s-cHL). Results: We identified 2,298 proteins; comparison of the protein profiles between the s-cHL and n-cHL groups revealed 220 unique proteins significantly differentially expressed (p < 0.05) and with a fold change of at least 25%. Of these, 117 proteins were upregulated (fold change 1.25–3.94), and 103 were downregulated (fold change 0.44–0.80) in s-cHL. In hierarchal clustering based on an even higher significance threshold (p < 0.001), i.e., 25 significantly differentially expressed proteins, two clusters were observed: (i) a skeletal-group comprising 12 s-cHL and 4 n-cHL samples; and (ii) a nodal-group of 46 n-cHL and 7 s-cHL samples. Of particular interest among the differentially expressed proteins, we identified isocitrate dehydrogenase (IDH1) and WD repeat- and FYVE domain-containing protein 4 (WDFY4). This pattern of protein expression suggests disturbance in cytoplasmic NADPH production, antigen processing/presentation, and B-cell survival in cHL patients with skeletal involvement compared to those without. Conclusion: Our data show differential protein expression in cHL lymphoma tissues that correlate with the presence or absence of concomitant bone involvement at diagnosis. This indicates that certain biological pathways are affected among those presenting with disease disseminated to the skeletal system. The research was funded by: Department of Clinical Medicine, Aarhus University; Health Research Foundation of Central Denmark Region; Brødrene Hartmanns Foundation; Carl and Ellen Hertz Foundation; the Danish Lymphoma Group; Kong Christian den Tiendes Foundation; Torben and Alice Frimodts Foundation; Aase and Ejnar Danielsens Foundation; Foundation of 1870; Dagmar Marshalls Foundation; Merchant Einar Willumsen’s Memorial Foundation; Eva and Henry Frænkel’s Memorial Foundation; Master Carpenter Jørgen Holm and wife Elisa f. Hansen’s Memorial Grant. The Orbitrap Fusion Tribrid mass spectrometer was funded by A. P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til Almene Formaal. Keywords: Genomics, Epigenomics, and Other -Omics, Hodgkin lymphoma, Microenvironment No conflicts of interests pertinent to the abstract.

Abstract 61: Management of Clinically Localized Prostate Cancer: Guideline Concordance and Clinical Outcomes From Tertiary Institutions in Nigeria

Abstract Purpose: Patients with clinically localized prostate cancer have a potentially curable disease. However, there are gaps in the quality of care these patients receive in Nigeria. Granular clinical data are needed to design interventions for quality improvement. This study aims to describe guideline concordance of cancer management and its association with patient outcomes. Methods: A 3-year retrospective study of all patients with T1-T3a, N0, M0 prostate cancer at three tertiary hospitals in Nigeria was conducted. Data on clinicopathologic characteristics, D’Ámico risk group, TNM staging, treatment practices, post-treatment PSA and survival were collected. Concordance with the 2022 European Association of Urology guidelines was assessed. Primary endpoints were guideline concordance of staging and treatment, and associations between concordance and outcomes. Results: This study included 110 patients; mean age 68 years. Sixty-six patients (60%) were high-risk, 34 (31%) were intermediate-risk, and 9 (8%) were low-risk. Most patients were staged with abdominopelvic ultrasound (65%, n = 71). Guideline-concordant magnetic resonance imaging for T-staging was significantly higher in low-risk (44%, n = 4) than high-risk (12%, n = 8) patients (p = 0.041). Guideline-concordant axial imaging for N and M staging was used in 11% (n = 7) of high-risk patients. In the overall cohort, 16 patients (15%) received guideline-concordant definitive treatment with either radical prostatectomy (n = 10; 9%) or radiotherapy (n = 6; 5%), whereas 62 patients (56%) received non-concordant androgen deprivation therapy (ADT) alone and 21 (19%) received no treatment. Median time to biochemical recurrence was not significantly different between those who received surgery (18 months), radiation therapy (median not obtained), or ADT alone (11 months) (log-rank p = 0.103). After a median follow-up of 36 months, median overall survival was similar for guideline-concordant and non-concordant treatment groups (37 and 34 months, respectively; log-rank p=0.540). Conclusion: Prostate cancer staging was suboptimal across all risk groups. Only a minority of patients received radical treatment for this potentially curable disease. Our results will inform the development of tailored multifaceted interventions to improve the quality of care. Citation Format: Musliu Adetola Tolani, Muhammed Ahmed, Rufus Wale Ojewola, Christian Agbo Agbo, Shehu Salihu Umar, Ernie Kaninjing, Alan Paciorek, Rebecca DeBoer. Management of Clinically Localized Prostate Cancer: Guideline Concordance and Clinical Outcomes From Tertiary Institutions in Nigeria [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 61.

Adherence to surveillance guidelines in survivors of hodgkin lymphoma: A report from the Childhood Cancer Survivor Study (CCSS).

10047 Background: Pediatric Hodgkin lymphoma (HL) is a highly curable disease. However, survivors are at high risk for long-term complications of therapy. The impact of sociodemographic and clinical factors on adherence to late effects surveillance guidelines is unknown. Methods: The CCSS is a retrospective cohort with prospective follow-up of survivors diagnosed from 1970-1999. HL survivors enrolled in CCSS who responded to a 2017 questionnaire were included. We assessed adherence to the Children’s Oncology Group surveillance guidelines for cardiomyopathy, breast cancer, colorectal cancer, and skin cancer. Multivariate logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals (aOR [95% CI]) for sociodemographic and clinical risk factors associated with adherence. Estimates were adjusted for area deprivation index (ADI); chronic health conditions; recent (≤2 years) routine check-up, cancer center or survivorship clinic visit; and possession of a survivorship care plan (SCP). Results: 1,380 HL survivors (45.6% male; median age 43.6 years, range 21.6-65.9 years) responded, of whom 55.5% were at elevated risk for cardiac dysfunction, 71.0% for breast cancer, 83.5% for skin cancer, and 39.4% for colorectal cancer. Of those at elevated risk, 42.7%, 19.9%, 31.3% and 48.9% were adherent to the guidelines for cardiac, breast, skin, and colorectal screening, respectively. Predictors of adherence to cardiac dysfunction guidelines were male sex (aOR 1.7 [1.1-2.6]), having children (aOR 1.6 [1.1-2.4]), recent routine checkup (aOR 4.0 [1.3-13.1]), recent visit to a cancer center or survivorship clinic (aOR 6.2 [3.9-10.0]), and possession of a SCP (aOR 3.1 [1.9-5.0]). Adherence to breast cancer guidelines was higher in those who were unmarried (aOR 2.1 [1.0-4.1]), had a recent visit to a cancer center or survivorship clinic (aOR 3.7 [2.0-7.0]), and possessed a SCP (aOR 3.5 [1.5-8.3]). Adherence to skin cancer guidelines was higher in those &gt; 14 years at diagnosis (aOR 1.8 [1.3-2.4]), living in a low deprivation area (ADI 1-24.9) compared to a high deprivation area (ADI 75-100) (aOR 3.4 [1.9-5.9]), employed (aOR 1.8 [1.1-2.9]), &gt; 30 years from diagnosis (aOR 2.4 [1.6-3.6]), with a recent routine check-up (aOR 3.6 [1.1-12.5]), and recent cancer care (aOR 2.4 [1.6-3.5]). Adherence to colorectal cancer guidelines was higher in those with grade 3-4 chronic health conditions (aOR 1.9 [1.1-3.3]). Conclusions: Less than 50% of HL survivors are adherent to screening guidelines. Sociodemographic risk factors are significant predictors of non-adherence, particularly to skin cancer screening guidelines. This threatens to potentiate outcome disparities among HL survivors.