Second Malignant Neoplasms Research Articles

Obesity and risk for liver disease: a two-sample Mendelian randomisation study.

The associations between obesity and liver diseases are complex and diverse. To explore the causal relationships between obesity and liver diseases, we applied two-sample Mendelian randomisation (MR) and multivariable MR analysis. The data of exposures (BMI and WHRadjBMI) and outcomes (liver diseases and liver function biomarker) were obtained from the open genome-wide association study database. A two-sample MR study revealed that the genetically predicted BMI and WHRadjBMI were associated with non-alcoholic fatty liver disease, liver fibrosis and autoimmune hepatitis. Obesity was not associated with primary biliary cholangitis, liver failure, liver cell carcinoma, viral hepatitis and secondary malignant neoplasm of liver. A higher WHRadjBMI was associated with higher levels of biomarkers of lipid accumulation and metabolic disorders. These findings indicated independent causal roles of obesity in non-alcoholic fatty liver disease, liver fibrosis and impaired liver metabolic function rather than in viral or autoimmune liver disease.

Using machine learning methods to investigate the impact of age on the causes of death in patients with early intrahepatic cholangiocarcinoma who underwent surgery.

The impact of age on the causes of death (CODs) in patients with early-stage intrahepatic cholangiocarcinoma (ICC) who had undergone surgery was analyzed in this study. A total of 1555 patients (885 in the older group and 670 in the younger group) were included in this study. Before and after applying inverse probability of treatment weighting (IPTW), the different CODs in the 2 groups were further investigated. Additionally, 7 different machine learning models were used as predictive tools to identify key variables, aiming to evaluate the therapeutic outcome in early ICC patients undergoing surgery. Before (5.92 vs. 4.08years, P < 0.001) and after (6.00 vs. 4.08years, P < 0.001) IPTW, the younger group consistently showed longer overall survival (OS) compared with the older group. Before IPTW, there were no significant differences in cholangiocarcinoma-related deaths (CRDs, P = 0.7) and secondary malignant neoplasms (SMNs, P = 0.78) between the 2 groups. However, the younger group had a lower cumulative incidence of cardiovascular disease (CVD, P = 0.006) and other causes (P < 0.001) compared with the older group. After IPTW, there were no differences between the 2 groups in CRDs (P = 0.2), SMNs (P = 0.7), and CVD (P = 0.1). However, the younger group had a lower cumulative incidence of other CODs compared with the older group (P < 0.001). The random forest (RF) model showed the highest C-index of 0.703. Time-dependent variable importance bar plots showed that age was the most important factor affecting the 2-, 4-, and 6-year survival, followed by stage and size. Our study confirmed that younger patients have longer OS compared with older patients. Further analysis of the CODs indicated that older patients are more likely to die from CVDs. The RF model demonstrated the best predictive performance and identified age as the most important factor affecting OS in early ICC patients undergoing surgery.

The impact of clinically relevant health conditions on psychosocial outcomes in survivors of childhood cancer: results of the DCCSS-LATER study.

Investigate the association between presence, number and type of clinically relevant health conditions and a range of psychosocial outcomes (emotional, social, cognitive, physical) in survivors of childhood cancer (CCS). CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed between 1963-2001, attained age ≥ 18, diagnosed < 18, ≥ 5years since diagnosis) completed a questionnaire on health conditions (2013-2014), and questionnaires on psychosocial outcomes (2017-2020): Hospital Anxiety and Depression Scale, Short form 36, TNO-AZL Questionnaire for Adult Health-Related Quality of Life, and the Self-Rating Scale for Post-Traumatic Stress Disorder. Associations among health conditions and psychosocial outcomes were assessed with regression analysis, adjusting for attained age, sex, and time since diagnosis, and adjusting for multiple testing (p < 0.004). A total of 1437 CCS, mean age 36.3years, 51.1% female, ≥ 15years since diagnosis, completed questionnaires on health and psychosocial outcomes. CCS with a clinically relevant health condition, and those with more conditions had worse emotional, social, and physical outcomes; regression coefficients were small to moderate. CCS with gastro-intestinal conditions, endocrine, nervous systems, eye, or ear conditions, and especially those with secondary malignant neoplasms, reported worse psychosocial functioning; regression coefficients were small/moderate to large. Health care professionals should be aware of the increased risk for psychosocial problems among CCS with health conditions, especially for survivors with secondary malignant neoplasms, gastro-intestinal, endocrine, nervous system, eye, and ear conditions. CCS may benefit from psychological interventions to develop coping strategies to manage health conditions and psychosocial consequences of the cancer trajectory.

QOL-42. ANALYSIS OF LATE EVENTS AFTER RADIATION THERAPY FOR PRIMARY PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND Late events after radiation therapy for primary brain tumors consist of secondary malignant neoplasms (SMN) and tumor recurrences. The incidence and biology of late events are not very well described. Therefore, we aimed to identify late events in our institutional cohort and describe their biology. METHODS A retrospective chart review of all irradiated pediatric brain tumor patients treated between 2000 and 2015 at our institution was performed to obtain demographics and clinical data of late events. Late events were defined as intracranial intraaxial SMN or tumor recurrence occurring later than 3 years after radiation therapy. A whole-genome methylation array was employed to identify the methylation class of the late event. RESULTS In the observed period, 267 patients received some form of cranial radiotherapy for primary brain tumor; high-grade glioma (HGG, n=66), medulloblastoma (n=74), ependymoma (n=50), germ-cell tumors (GCT, n=22), low-grade glioma (LGG, n=24), and other diagnoses (n=31). Out of the 174 patients who were alive and without an event after 3 years from the radiation therapy, 30 developed late events (16.8%), and 27 of them were histologically verified. Verified late events consisted of 8 SMNs (29.6%) and 19 primary tumor recurrences. SMNs were mainly radiation-induced gliomas (RIG, n=7) and one atypical teratoid/rhabdoid tumor (ATRT) after craniopharyngioma. All RIG tumors clustered with the “pediatricHGG_RTK1” methylation class. Tumor recurrences consisted of medulloblastomas (Group 4 and Wnt), ependymomas (PFA and ST_ZFTA), GCTs, gliomas (one NF1-associated HGG, one H3-altered thalamic glioma, one diffuse astrocytoma with BRAF-V600E mutation), and craniopharyngiomas. The overall survival rate 5 years after a late event was 39.7%, with a worse survival rate for SMN patients (14.3%) compared to those with recurrences (44.9%) (p=0.05). CONCLUSIONS Late events affected 16.8% of long-term survivors. Strikingly, SMNs represented almost 30% of late events and were associated with a very poor prognosis.

Relative risk of second malignant neoplasms highest among young adult cancer patients - a population-based registry study in Finland.

The objective of this study was to explore the incidence of second malignant neoplasms (SMNs) among adult cancer patients in Finland diagnosed with their first primary cancer (FPC) in 1992-2021. The study used data from the population-based Finnish Cancer Registry (FCR). Risk estimates were calculated using the standardised incidence ratio (SIR), the ratio of observed second cancers compared to the expected numbers assuming the same cancer incidence as the corresponding sex-age-calendar year -split of the general population. A total of 573,379 FPCs were diagnosed during 1992-2021. During the follow-up, 60,464 SMNs were diagnosed. Male cancer patients had neither a decreased nor an increased risk (SIR 1.00 [95% CI, 0.99-1.01]) and female patients had an 8% increased risk (SIR 1.08 [95% CI, 1.06-1.09]) of developing any SMN compared to a FPC in the general population. The highest SIR of any SMN was observed in patients aged 20-39 -years at FPC diagnosis, and the SIR decreased by increasing age at diagnosis. Patients with lymphoid and haematopoietic tissue neoplasms, cancers of the mouth and pharynx, endocrine glands, respiratory and intrathoracic organs, skin, and urinary organs had the highest SIRs, while patients with cancers of the male genital organs and the female breast had the lowest SIRs. Elevated SIRs were observed in cancer patients diagnosed at an early age and for FPCs known to be in large part attributable to lifestyle factors, which highlights the importance of monitoring and encouraging lifestyle changes.

Second neoplasms in patients with hereditary retinoblastoma.

10620 Background: Patients with hereditary retinoblastoma have an increased risk of developing second tumors during adolescence and adulthood. The incidence of second malignant neoplasms (SMNs) is a concern, since SMNs are the leading cause of death in these patients. This risk is increased in patients who have received external radiation therapy as part of treatment but is also increased in non-radiated patients. Increased sarcoma and melanoma risks after hereditary retinoblastoma are well established. Methods: We present a cohort of patients with hereditary retinoblastoma assessed in our multidisciplinary pediatric and adult genetic predisposition cancer unit (UPGeCI) from September 2018 to December 2023. During this period, 62 patients with retinoblastoma were attended, all with RB1 gene mutation. Of these, 84% of patients had bilateral retinoblastoma, and 16% had unilateral retinoblastoma. They ranged in age from 6 months to 55 years (median 13 years). 18 patients (29%) were treated with external beam radiation therapy. Clinical follow-up and orbital magnetic resonance imaging were performed every two years. Results: Six cases of SMNs were detected in 5 patients (9.3%), all soft tissue sarcomas. The mortality rate was 60% (3/5 patients). Four patients (80%) had received external radiotherapy as part of the treatment of retinoblastoma. Three patients presented 3 sarcomas in the facial region within the irradiated area, of which one was an osteosarcoma and the other two leiomyosarcomas. Two of them presented in adulthood, and one at 9 years old. One of the patients died, the other two are living disease-free. The fourth patient who had received external radiotherapy presented with osteosarcoma of the femur at 15 years of age. She died of septic shock. The patient who had not received external radiotherapy presented with osteosarcoma of the tibia at 6 years of age and later with osteosarcoma of the contralateral femur at 10 years of age. She died of progression. Conclusions: There is an increased risk of SMNs in patients with hereditary retinoblastoma, mainly soft tissue sarcomas, with high mortality. This risk increases if they have received external radiation therapy. Therefore, screening for SMNs is essential for of follow-up in patients with heritable retinoblastoma.

Long term sequelae of testicular cancer and treatment: A point prevalence observational study.

e17015 Background: Testicular cancer (TC) is a highly curable solid organ tumour, which usually occurs in the early years of life. Recent studies have observed an increase in the incidence of TC coupled with improvement in cure rates all around the world, especially in Western Europe and North America. Consequently, we have a growing population living in the survivorship phase. Many researchers have highlighted the late complications in TC survivors, linked with the different treatment modalities used for treatment. In this study, we aim to determine the point prevalence of morbidity and mortality in TC survivors at a tertiary care cancer centre in Ireland. Methods: Participants were assessed in a purpose built survivorship clinic and informed consent was obtained. All participants were 18 years or more of age at the time of assessment with a histologically confirmed diagnosis of testicular cancer over 5 years ago. Assessments included a thorough symptom review, clinical examination, blood tests and other investigations (e.g., X-ray, ECG) if required. Results: A total of 81 patients were recruited in the study from March 2023 to January 2024, with a median follow up of more than a 10 years (129 months). Chemotherapy had been given to 85% of patients and radiotherapy to 5%. All except one patient underwent orchiectomy while RPLND was performed in 17% of patients. There were 3 deaths in the survivorship phase, all related to second malignant neoplasms (SMNs). Hyperlipidaemia was the most common condition found in 55% of TC survivors, followed by raised gonadotropins (47%), low testosterone (34%) and hypertension (40%). Other conditions prevalent in our cohort were hearing impairment (26%), abnormal high glucose (8%) and renal impairment(7%). The majority of these co-morbidities were previously undiagnosed before assessment in our survivorship clinic, including 2 cases of coronary artery disease. Over 70% of hypogonadism, hyperlipidaemia, hypertension, renal impairment and high abnormal glucose were initially diagnosed in our clinic. Conclusions: Results from our study are comparable to the studies conducted in other cancer centres across Europe and the US. Second malignant neoplasms remain the major cause of mortality in this cohort but many modifiable risk factors can be diagnosed early and potentially treated to prevent morbidity. Our data strongly supports the need for specialised survivorship clinics to improve the prognosis and quality of life in TC survivors. [Table: see text]

Risk and impacts of drug-induced liver injury (DILI) due to immune-checkpoint inhibitors (ICI) on overall survival in patients with newly diagnosed cancer: A retrospective cohort study.

12049 Background: The risk and impact of drug-induced liver injury (DILI) due to ICI treatment on newly diagnosed cancer patients have not been fully investigated. This study aims to assess the incidence and impact of ICI related DILI on overall survival. Methods: We included patients with newly diagnosed cancer treated with ICIs between 01/2012 and 12/2020 at the Ohio State University Comprehensive Cancer Center. DILI was defined using ICD-9 and ICD-10 codes for abnormal results of liver function, acute hepatitis, drug-induced liver injury, or toxic liver disease. History of Liver Disease (HLD) before ICI infusion was defined using ICD-9 and ICD-10 codes for any liver disease, including primary and secondary liver malignant neoplasms. To examine the causal effects of ICI-related DILI, patients who developed hepatocellular carcinoma or metastatic liver disease were excluded. Kaplan Meier method was used to estimate DILI risk post-ICI infusion in patients with and without HLD. Crude and Adjusted Cox proportional models were used to examine the association between DILI, modeled as time-dependent, and overall survival. Results: A total of 2,816 patients were included in the study, with a median age of 62 years, 58% male, and 90% white non-Hispanics. An estimated 11% of patients developed DILI during follow-up. The median (interquartile range) follow-up time from ICI infusion to DILI was 8.7 (3.0–20.1) months. The overall risk of DILI was 25.3%, which was significantly higher in patients with HLD than in those without HLD (17.8% vs. 30.8%, Log-Rank P &lt;0.001). The median (interquartile range) survival time was 10.4 (3.7–22.7) months. During follow-up, a total of 1390 (49.4%) patients died. DILI was significantly associated with a higher risk of all-cause mortality in all regression models. The crude risk of all-cause mortality was 40% higher in patients with DILI than in those without DILI [HR: 1.40; 95% CI: 1.15–1.70]. In the fully adjusted models, DILI was associated with a 63% higher risk of all-cause mortality [adjusted HR: 1.63; 95% CI: 1.34–1.99]. DILI's effects on the overall survival risk remained significant when we further adjusted for HLD status [HR: 1.57; 95% CI: 1.29–1.93]. Conclusions: The findings from this retrospective cohort study highlight the significant risk and detrimental impact of DILI on overall survival in patients treated with ICIs. Notably, the incidence of DILI was significantly higher among patients with HLD, underscoring the elevated vulnerability of this subgroup. Furthermore, DILI was a significant predictor of increased all-cause mortality regardless of HLD status. These results underscore the need for vigilant monitoring and management of liver function in patients receiving ICIs, particularly in those with pre-existing liver conditions, to mitigate the risk of DILI and improve survival outcomes.

Prognostic significance of real-world (RW) recurrence patterns after resection or ablation of early-stage hepatocellular carcinoma (HCC): Insights from the US Medicare population.

e16241 Background: The prognosis after curative-intent resection or ablation of early-stage HCC remains poor, largely due to high rates of recurrence. We aimed to characterize real-world recurrence patterns and determine whether the timing of recurrence was associated with overall survival (OS). Methods: Patients (pts) with early-stage HCC who underwent resection and/or ablation were identified from the SEER-Medicare database (2010-2019). Pts who received liver transplant were excluded. A proxy for recurrence was defined as the receipt of new HCC treatments (surgery, locoregional therapy, systemic therapy) or a secondary malignant neoplasm claim (excluding liver). Pseudo-recurrence dates were assigned to pts without recurrence to match the distribution of time between initial resection/ablation and recurrence in the recurrence cohort, to avoid immortal time bias. Early vs late recurrence was defined as occurring within 1 year vs after 1 year of initial resection/ablation. Primary outcome was OS as measured both from the time of recurrence/pseudo-recurrence and initial resection/ablation. Results: 1,146 eligible pts with early-stage HCC were identified. 63% were male, mean age was 74 yrs, and initial therapy was resection (39%), ablation (50%), or both (11%). 736 (64%) experienced recurrence. Among them, 53% received ablation, 37% surgery, and 11% received both. Median OS from recurrence or pseudo-recurrence was 22 months (mo) vs 67 mo (p &lt; 0.001) for pts with vs without recurrence, respectively. When measured from resection/ablation date, median OS was 39 mo vs 83 mo (p &lt; 0.001). After adjusting for relevant demographic and clinico-pathologic factors, including type of index therapy, in a multivariable Cox regression model, recurrence remained significantly associated with an increased risk of death (hazard ratio [HR]: 2.24; 95% CI: 1.85-2.71; p &lt; 0.001). Among pts who recurred, 380 (52%) had early recurrence and 356 (48%) had late recurrence. Median OS from recurrence was 17 mo vs 30 mo (p &lt; 0.001) for early vs late recurrence, respectively, and 23 mo vs 63 mo when measured from resection/ablation The adjusted HR for the risk of death associated with early recurrence was 1.39 (95% CI: 1.14-1.68; p &lt; 0.001) compared to late recurrence. Other significant prognostic factors associated with reduced OS included larger tumor size ( &gt; = 5cm), greater extent of disease, and poor differentiation (grade III and above). Conclusions: In this study among US Medicare pts, early recurrence within one year after curative-intent treatment of early-stage HCC was significantly associated with decreased OS compared to pts who recur later or without recurrence. This highlights the need for developing and utilizing effective adjuvant therapy regimens to delay or avoid recurrence.

Impact of lung biomarker testing on out-of-pocket costs for metastatic non-small cell lung cancer.

11087 Background: Biomarker testing in metastatic non-small lung cancer (NSCLC) is critical for appropriate selection of therapy options. Claims-based datasets offer real-world information on the use and cost of biomarker testing across the United States. Methods: We used de-identified administrative claims data from Optum’s Clinformatics Data Mart Database (CDM) from 2013 to 2021 to assess for trends in biomarker testing. Eligible patients were adults with two or more lung cancer diagnosis codes and with two or more claims of a secondary malignant neoplasm. Patients were excluded if they had another primary cancer or did not have continuous insurance coverage twelve months prior and six months after diagnosis. We assessed claims-based out-of-pocket (OOP) costs associated with testing and treatment. Descriptive statistics were used to assess biomarker testing rates, and multivariable analyses (MVA) were performed to assess factors associated with testing. Results: A total of 4377 patients with metastatic NSCLC were eligible (mean age 60 years (SD: 8.33 years), 49.6% female, 76.7% former smokers). Testing rates within two months of diagnosis increased from 58.15% in 2013 to 69.96% in 2021. On MVA, biomarker testing was associated with younger age, being non-smokers, living in Mountain geographic region, or having point-of-service insurance plans. Biomarker testing was associated with a median OOP cost of $98 (IQR: $43.87-$306.58). Patients who underwent biomarker testing had a median total OOP cost of all services within 6 months of diagnosis of $3560.20 (IQR: $1538.37-$6199.44) compared to $1979.58 (IQR: $725.75-$4003.06) for those who did not undergo biomarker testing. Conclusions: Using claims data, we find that 70% of patients with metastatic NSCLC undergo biomarker testing within two months of diagnosis with metastatic disease. Most patients undergo biomarker testing early in their treatment course (0-60 days), suggesting that testing is appropriately being obtained early on in their treatment course, but this testing is associated with substantially higher overall OOP costs to patients.

Tandem High-Dose Chemotherapy Increases the Risk of Secondary Malignant Neoplasm in Pediatric Solid Tumors.

This study aimed to investigate the incidence and risk factors for secondary malignant neoplasms (SMN) in pediatric solid tumors, focusing on the effects of tandem high-dose chemotherapy (HDCT). Patients (aged < 19 years) diagnosed with or treated for pediatric solid tumors between 1994 and 2014 were retrospectively analyzed. The cumulative incidence of SMN was estimated using competing risk methods by considering death as a competing risk. A total of 1,435 patients (413 with brain tumors and 1,022 with extracranial solid tumors) were enrolled. Seventy-one patients developed 74 SMNs, with a 10-year and 20-year cumulative incidence of 2.680±0.002% and 10.193±0.024%, respectively. The types of SMN included carcinoma in 28 (37.8%), sarcoma in 24 (32.4%), and hematologic malignancy in 15 (20.3%) cases. Osteosarcoma and thyroid carcinoma were the most frequently diagnosed tumors. Multivariate analysis showed that radiotherapy (RT) > 2, 340 cGy, and tandem HDCT were significant risk factors for SMN development. The SMN types varied according to the primary tumor type; carcinoma was the most frequent SMN in brain tumors and neuroblastoma, whereas hematologic malignancy and sarcomas developed more frequently in patients with sarcoma and retinoblastoma, respectively. The cumulative incidence of SMN in pediatric patients with solid tumors was considerably high, especially in patients who underwent tandem HDCT or in those who received RT > 2,340 cGy. Therefore, the treatment intensity should be optimized based on individual risk assessment and the long-term follow-up of pediatric cancer survivors.

Second malignant neoplasms within 5 years from first primary diagnosis in pediatric oncology patients in Canada: a population-based retrospective cohort study.

From the advancement of treatment of pediatric cancer diagnosis, the five-year survival rate has increased significantly. However, the adverse consequence of improved survival rate is the second malignant neoplasm. Although previous studies provided information on the incidence and risk of SMN in long term survivors of childhood cancer, there is still scarce information known for short term (< 5 years) prognosis. This study aims to assess the incidence, characteristics, management, and outcome of children who develop SMN malignancies within 5 years of diagnosis of their initial cancer. This is a retrospective cohort study of early Second Malignant Neoplasms (SMN) in pediatric oncology patients. The Cancer in Young People - Canada (CYP-C) national pediatric cancer registry was used and reviewed pediatric patients diagnosed with their first cancer from 2000-2015. A total of 20,272 pediatric patients with a diagnosis of a first malignancy were analyzed. Of them, 0.7% were diagnosed with a SMN within the first 5 years following their first cancer diagnosis. Development of a SMN impacted survival, shown by an inferior survival rate in the SMN cohort (79.1%) after three years compared to that of the non-SMN cohort (89.7%). Several possible risk factors have been identified in the study including the use of epipodophyllotoxins, exposure to radiation, and hematopoietic stem cell 169 transplant. This is the first national study assessing the incidence, 170 characteristics, risk factors and outcome of early SMN in Canadian children 171 from age 0-15 from 2000-2015.

Phenome-wide association study of ovarian cancer identifies common comorbidities and reveals shared genetics with complex diseases and biomarkers.

Ovarian cancer (OC) is commonly diagnosed among older women who have comorbidities. This hypothesis-free phenome-wide association study (PheWAS) aimed to identify comorbidities associated with OC, as well as traits that share a genetic architecture with OC. We used data from 181,203 white British female UK Biobank participants and analysed OC and OC subtype-specific genetic risk scores (OC-GRS) for an association with 889 diseases and 43 other traits. We conducted PheWAS and colocalization analyses for individual variants to identify evidence for shared genetic architecture. The OC-GRS was associated with 10 diseases, and the clear cell OC-GRS was associated with five diseases at the FDR threshold (p = 5.6 × 10-4 ). Mendelian randomizaiton analysis (MR) provided robust evidence for the association of OC with higher risk of "secondary malignant neoplasm of digestive systems" (OR 1.64, 95% CI 1.33, 2.02), "ascites" (1.48, 95% CI 1.17, 1.86), "chronic airway obstruction" (1.17, 95% CI 1.07, 1.29), and "abnormal findings on examination of the lung" (1.51, 95% CI 1.22, 1.87). Analyses of lung spirometry measures provided further support for compromised respiratory function. PheWAS on individual OC variants identified five genetic variants associated with other diseases, and seven variants associated with biomarkers (all, p ≤ 4.5 × 10-8 ). Colocalization analysis identified rs4449583 (from TERT locus) as the shared causal variant for OC and seborrheic keratosis. OC is associated with digestive and respiratory comorbidities. Several variants affecting OC risk were associated with other diseases and biomarkers, with this study identifying a novel genetic locus shared between OC and skin conditions.

Intraoperative Options to Stimulate the Reparative Liver Regeneration in the Experiment

Background. Primary and secondary malignant neoplasms and liver damage affect more than 500 million people worldwide; one million of these people die annually. Secondary malignant neoplasms of the liver occur in every fourth cancer patient, 60% of them require liver resection. As reported, post-resection liver failure occurs in 32–60% of cases. Thus, at the current stage of medicine development, the search for novel options to stimulate reparative liver regeneration remains a challenging issue in surgery.The aim of the study was to stimulate post-resection liver regeneration by intraoperative intrahepatic and intraperitoneal administration of cyanocobalamin and ademetionine in an experiment.Materials and methods. This research is a prospective randomized study carried out at the Research Institute of Experimental Biology and Medicine, N.N. Burdenko Voronezh State Medical University (VSMU), Ministry of Health of the Russian Federation. Experiments involved 192 mature male Wistar rats, who underwent conventional liver resection (CLR) equal approximately to 70% of the initial liver volume, according to the approach proposed by G. Higgins and R. Anderson. The effect of intraperitoneal administration of ademetionine and cyanocobalamin on post-resection liver regeneration was investigated in the first block of the study. The effect of intraoperative intrahepatic injections and intrahepatic administration of drugs on post-resection liver regeneration was tested in the second block of the study. The combined use of ademetionine and cyanocobalamin and their effect on post-resection liver regeneration was studied in the third block of the study. Physical examination and laboratory findings were used to assess reparative processes. The data were processed statistically using the STATGRAPHICS Centurion 18 software package, version 18.1.12 (Statgraphics Technologies, Inc., USA). The analysis of variance (ANOVA) was applied to compare mean values for eight different group.Results. The study detected that intraperitoneal administration of ademetionine helps to normalize the general condition and biochemical parameters in 77.78% of animals. Intraperitoneal administration of cyanocobalamin does not have a significant effect on biochemical parameters, including oxidative stress. Intrahepatic administration of cyanocobalamin helps to increase the reparative liver potential, results in decreased rates of cytolysis and cholestasis syndromes, restoration of carbohydrate and fat metabolism, and increased expression of growth factors. Intrahepatic administration of ademetionine leads to decreased regenerative liver potentials, disruption of its functional activity, and decreasd protective antioxidant properties.Conclusion. Thus, the optimal intraoperative option to stimulate reparative liver regeneration in the experiment is the intrahepatic administration of cyanocobalamin supplemented by intraperitoneal administration of ademetionine. In 7 days after liver resection, this helps normalize biochemical parameters, relieves oxidative stress, and increases IL-1β and TGF-β1. In 14 days after resection, the abovementioned events lead to restoration of 95.04% of the initial liver weight, if compared with intraperitoneal administration of cyanocobalamin and ademetionine (p0,05).

Therapy-Related Acute Myeloid Leukemia After Chemotherapy For Osteosarcoma: Report of 2 Cases and Review of The Literature

Abstract Introduction/Objective Therapy-related acute myeloid leukemia (t-AML) and myelodysplastic syndrome (t-MDS) are rare but well-established late complications of chemotherapeutic agents or radiation therapy used to treat various malignancies. Many cases of t-AML/t-MDS have been described secondary to Hodgkin, non-Hodgkin lymphoma, and other solid tumors. However, only a few cases of t-AML and t-MDS have been reported following osteosarcoma treatment. We describe two patients diagnosed with osteosarcoma who developed t-AML after receiving multiple chemotherapeutic agents. Methods/Case Report A 12-year-old male with Li-Fraumeni syndrome was diagnosed with osteosarcoma of the left ilium and sacrum with pulmonary metastases. Despite multiple lines of chemoradiation therapy including doxorubicin and ifosfamide, tumor progressed at the primary tumor site. The patient subsequently presented with altered mental status and pancytopenia. Bone marrow biopsy demonstrated AML. He died despite supportive care. A 14-year-old female was diagnosed with left tibial osteosarcoma with bony and pulmonary metastases. She was treated on standard osteosarcoma chemotherapy including doxorubicin, cisplatin, methotrexate, ifosfamide and etoposide, surgery, and radiation. 1 year following therapy, she had local recurrence of osteosarcoma without progression despite not starting chemotherapy. However, 3 years later, she developed pancytopenia, and immature white blood cells were identified on peripheral smear. Bone marrow biopsy revealed AML-M7. Despite supportive care and zoledronic acid, she ultimately died from sepsis and disseminated intravascular coagulation. Results (if a Case Study enter NA) NA Conclusion With improved therapy and survival for osteosarcoma patients, these patients should be monitored for secondary malignancies. T-AML is rare following osteosarcoma treatment, but outcome remains poor, despite treatment. Underlying Li-Fraumeni syndrome may influence the risk of development of secondary malignant neoplasms. Literature review of types and prognosis of t-AML following osteosarcoma will be reviewed and compared to our cases, including related genetic predisposing factors and chemotherapeutic agents. Our second patient is the first reported case of AML-M7 secondary to osteosarcoma treatment.

Incidence and associated factors of developing second pelvic malignant neoplasms among prostate cancer patients treated with radiotherapy.

To identify risk factors of secondary pelvic malignant neoplasms (SPMNs) among prostate cancer (PCa) patients treated with radiotherapy. Simultaneously, population-based data were used to validate the high risk of SPMNs in PCa patients with radiotherapy. We identified male patients diagnosed with PCa (localized and regional) as the first primary cancer and pelvic malignant neoplasm (including bladder and rectal cancer) as secondary cancer from Surveillance, Epidemiology, and End Results database (1975-2020). An external validation cohort was obtained from the First Affiliated Hospital of Nanchang University. The Fine-Gray competing risk regression and Poisson regression were utilized to evaluate the risk of SPMNs development. Poisson regression was also performed to calculate the standardized incidence ratio (SIR). The Kaplan-Meier method was used to assess the overall survival (OS) of patients with SPMNs. 89397 PCa patients treated with radiotherapy were enrolled. We identified associated factors of SPMNs, including age at diagnosis, race, year of diagnosis, marital status, radiation strategy and latency. In the multivariable competing risk regression model and Poisson regression model, a significantly higher risk of SPMNs development was observed in patients over 50 years(P<0.05), white patients(P<0.001), unmarried patients and treated with brachytherapy combined with external beam radiotherapy or brachytherapy(P<0.05). Patients treated with radiotherapy had a higher bladder and rectal cancer incidence than the general population. Patients who developed SPMNs showed poorer OS. We identified several risk factors associated with SPMNs and confirmed a relatively higher incidence of bladder and rectal cancer among PCa patients with radiotherapy. These results help tailor treatment and surveillance strategies.

Application of cryogenic technologies in complicated cases of surgical treatment of colorectal cancer liver metastases. Case report

Surgical resection is a standard treatment strategy for both primary and secondary malignant liver neoplasms. Liver transplantation is considered the most effective treatment method for colorectal cancer liver metastasis. Palliative debulking liver resection is one of the optimal alternative procedures for patients ineligible for a liver transplant, as it improves overall survival. Resectability rates depend on the functional efficiency of the remaining portion of the liver, which can be improved by increasing the future liver remnant. The application of cryogenic technologies for the ablation of a residual tumour invading the intraparenchymal segments of the major hepatic vessel may have advantages in cases where it is impossible to expand the scope of the surgical intervention due to the insufficiency of the future liver remnant and/or the presence of severe concomitant pathology.&#x0D; Objective — to present a case report of cryogenic technology application in complicated cases of surgical treatment of patients with colorectal cancer liver metastases.&#x0D; Case report. The case report presents an experience of cryoablation of the metastasis tissue with invasion into the intraparenchymal portal branch of Sg III, which was revealed during the I stage of the split in situ/ligation of the portal vein (ALPPS) liver resection. Cryoablation was performed by the application method with a single cryocycle and spontaneous thawing. Device — Cryo‑Pulse (Ukraine). Cryoagent — liquid nitrogen (T ‑180...‑196°С). Exposure time was 3 min. The specific complications associated with cryoablation were not observed.&#x0D; Conclusions. The application of cryogenic technologies for combined debulking surgical treatment of malignant focal liver lesions may be a safe treatment option in cases of residual tumour invasion into portal vein branches. The study is still ongoing.

Risk of Second Tumors in Retinoblastoma Survivors after Ionizing Radiation: A Review.

Retinoblastoma (RB) is the most common ocular neoplasm in children, whose development depends on two mutational events that occur in both alleles of the retinoblastoma susceptibility gene (RB1). Regarding the nature of these mutational events, RB can be classified as hereditary if the first event is a germline mutation and the second one is a somatic mutation in retina cells or nonhereditary if both mutational events occur in somatic cells. Although the rate of survival of RB is significantly elevated, the incidence of second malignant neoplasms (SMNs) is a concern, since SMNs are the main cause of death in these patients. Effectively, RB patients present a higher risk of SMN incidence compared to other oncology patients. Furthermore, evidence confirms that hereditary RB survivors are at a higher risk for SMNs than nonhereditary RB survivors. Over the decades, some studies have been performed to better understand this subject, evaluating the risk of the development of SMNs in RB patients. Furthermore, this risk seems to increase with the use of ionizing radiation in some therapeutic approaches commonly used in the treatment of RB. This review aims to clarify the effect of ionizing radiation in RB patients and to understand the association between the risk of SMN incidence in patients that underwent radiation therapy, especially in hereditary RB individuals.

Real-world tolerability of front-line brigatinib in patients with anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) with and without brain metastases in the United States.

535 Background: Brigatinib, a next-generation ALK tyrosine kinase inhibitor (TKI), is approved for treatment in patients with ALK+ NSCLC with a dosing schedule of 180 mg/day after a 7-day lead-in at 90 mg/day. Brigatinib has been shown through clinical trials to have improved intracranial efficacy compared to crizotinib. There is limited information regarding the real-world tolerability of brigatinib in patients with brain metastases (BM). Our study aims to assess treatment tolerability via dose reduction rates and adherence in patients treated with front-line (FL) brigatinib and stratified by evidence of BM. Methods: This retrospective cohort study utilized the IQVIA open-source pharmacy and medical claims databases. Adults (≥18 years) with ≥1 claim for brigatinib between 22 May 2020 and 31 December 2022 with no prior claims for brigatinib or other ALK-TKI therapies were identified from the pharmacy claims database and followed until the earliest of dose reduction, treatment discontinuation, or end of follow-up. Average daily dose (ADD) was calculated as the product of pill strength and quantity of pills dispensed divided by day supply. Dose reduction was defined as ≥30 days of treatment with ADD &lt; 180 mg/day. Time to dose reduction from 180 mg/day and probability of continued therapy at ≥180 mg/day were assessed by Kaplan-Meier analysis. Adherence was defined using medication possession ratio (MPR) and calculated as the total day supply divided by the number of days from the first claim date to the last supply date of FL brigatinib. BM was defined as having ≥1 claim in the medical claims database with a diagnosis code for secondary malignant neoplasm of the brain. Results: Overall 126 patients treated with FL brigatinib were identified (median age: 57.5; 57.1% female). Median (min-max) follow-up time was 11.7 (1.0-30.7) months; 114 (90.5%) patients reached a dose of 180 mg/day, and among these 27 (23.7%) had evidence of BM. Of patients who reached a dose of 180 mg/day, 14.8% of those with BM and 18.4% with no BM (p=0.779) had a dose reduction. The probability of remaining on therapy at 180 mg/day was 86.2% at 3, 6 and 9 months and 71.8% at 12 months in patients with BM. In patients with no BM, the probabilities of remaining on therapy at a dose of 180 mg/day at 3, 6, 9 and 12 months were 89.1%, 82.6%, 70.8% and 67.1%, respectively (P=.761). Adherence was high irrespective of BM with 81.5% of patients with BM and 94.3% those without BM having MPR &gt; 80%. Results in the overall FL brigatinib sample (with and without BM) were similar. Conclusions: Real-world data suggest that FL brigatinib is well tolerated regardless of brain metastasis status. Most FL brigatinib patients in the study achieved and maintained a daily dose of 180 mg. Dose reductions and probability of remaining on therapy were similar for patients with or without brain metastases.

Features of the Course of Radioinduced Breast Cancer. Clinical Observation

Introduction. Hodgkin’s lymphoma is most commonly reported in the young age of 20 to 40 years. Radiation therapy remained the first-choice option before the advent of modern chemotherapy agents. Thereafter, the risk of radioinduced breast cancer after radiotherapy with total radiation dose of 38 Gy or more increased 4.5-fold.Materials and methods. The presented clinical case demonstrates aggressive breast cancer that developed 43 years after radiation therapy for Hodgkin's lymphoma.Results and discussion. In the 1990s, chemotherapy regimens for Hodgkin’s lymphoma were not effective enough to control the disease, therefore, radiotherapy was an indispensable measure. Secondary radioinduced tumors take the second place (26 %) in the structure of mortality from Hodgkin’s lymphoma. The emergence of new, more effective chemotherapy regimens reduced the risk of secondary tumors and, in particular, breast cancer.Conclusion. At present, up to 75 % of patients with Hodgkin’s lymphoma can be cured using modern methods of chemotherapy and radiation therapy. In follow-up care, it is necessary to consider the high risk of secondary malignant neoplasms, especially lung and breast cancer.