Delivery of adjuvant chemotherapy (AC) to veterans with resected colon cancer

Patients with incomplete administration of AC for colon cancer (CC) likely experience inferior survival while oxaliplatin- and capecitabine-containing AC may not improve survival for older patients. The influence on AC completion of age, other baseline patient characteristics, or regimen characteristics is unknown. We evaluated the association of baseline characteristics and planned AC regimen with AC delivery in resected CC patients

Leading with an Intercultural Mindset: Leadership Development Programs for International Students

This mixed methods study explored co-curricular student leadership development programs that included intercultural learning and were designed for international students studying at higher education institutions in the United States. The study aimed to better understand: (a) common program characteristics; (b) program administrator perceptions; and (c) the international student experience. Data was collected in a two-phase explanatory sequential design, involving surveys and semi-structured interviews. Six main content areas across all programs were identified: (a) diversity, equity, and inclusion (DEI); (b) global engagement; (c) intercultural learning; (d) leadership development; (e) personal and professional development; and (f) supporting the international community. Administrators generally perceived leadership programs as positively contributing to the international student experience, citing an increase in student sense of belonging, self-confidence, and motivation to seek out other leadership opportunities. International student respondents corroborated the administrators’ perspectives, unanimously indicating that the program contributed to their sense of belonging. Students also noted increased self-confidence and gains in leadership, intercultural, and interpersonal knowledge and skills. Findings highlight the value of co-curricular programs to the international student experience, particularly in cultivating a sense of belonging. In order to better support international students, campuses should dedicate resources to support these types of programs

Ruthenium polypyridyl complexes and their modes of interaction with DNA : is there a correlation between these interactions and the antitumor activity of the compounds?

Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy) L1L2](2-n)?, and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}2{l-H2N(CH2)6NH2}]4?. The ligand tpy is 2,20:60,200-terpyridine and the ligand L1 is a bidentate ligand, namely, apy (2,20-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L2 is a labile monodentate ligand, being Cl-, H2O, or CH3CN. All six species containing a labile L2 were found to be able to coordinate to the DNA model base 9-ethylguanine by 1H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure–activity relationships that might be used to guide optimization of the activity of agents of this class of compounds

A large microRNA cluster on chromosome 19 is a transcriptional hallmark of WHO type A and AB thymomas

BACKGROUND: Thymomas are one of the most rarely diagnosed malignancies. To better understand its biology and to identify therapeutic targets, we performed next-generation RNA sequencing. METHODS: The RNA was sequenced from 13 thymic malignancies and 3 normal thymus glands. Validation of microRNA expression was performed on a separate set of 35 thymic malignancies. For cell-based studies, a thymoma cell line was used. RESULTS: Hierarchical clustering revealed 100% concordance between gene expression clusters and WHO subtype. A substantial differentiator was a large microRNA cluster on chr19q13.42 that was significantly overexpressed in all A and AB tumours and whose expression was virtually absent in the other thymomas and normal tissues. Overexpression of this microRNA cluster activates the PI3K/AKT/mTOR pathway. Treatment of a thymoma AB cell line with a panel of PI3K/AKT/mTOR inhibitors resulted in marked reduction of cell viability. CONCLUSIONS: A large microRNA cluster on chr19q13.42 is a transcriptional hallmark of type A and AB thymomas. Furthermore, this cluster activates the PI3K pathway, suggesting the possible exploration of PI3K inhibitors in patients with these subtypes of tumour. This work has led to the initiation of a phase II clinical trial of PI3K inhibition in relapsed or refractory thymomas (http://clinicaltrials.gov/ct2/show/NCT02220855)

Long-Term Outcomes in Stage II/III Thymic Epithelial Tumor Patients Treated with Post- Operative Radiotherapy

Thymic epithelial tumors (TETs) are rare malignancies that originate in the anterior mediastinum. Unlike other tumors of the chest, TETs recur most often in the pleura. The primary treatment of early stage TETs is surgical resection, with the role of adjuvant chemotherapy/radiotherapy controversial. Mixed results have been reported as to whether postoperative radiotherapy (PORT) decreases tumor recurrence or time to recurrence, but PORT can cause short-term and long-term toxicity. Therefore, assessing the benefit of PORT is important. For the present retrospective study, we created a database of stage II/III TET patients seen at Simon Cancer Center from 2000-2023 to examine long-term outcomes. Of the 214 stage II/III TET patients that underwent surgery in the database, 67 patients treated with PORT were isolated. Subsequently, 67 patients who did not receive PORT were matched to the PORT population based on similarities in histology, surgical margins, and chemotherapy received. Local vs. distant tumor recurrence, long-term complications, and overall survival were then compared. The PORT population had the following histologic distribution: 3 Type A, 3 Type AB, 47 Type B1/B2/B3, and 14 carcinoma; for the non-PORT population: 8 Type A, 13 Type AB, 36 Type B1/B2/B3, and 10 carcinoma. There were 16 stage IIA, 6 stage IIB, and 45 stage III patients in the PORT population, and 17 stage IIA, 9 stage IIB, and 41 stage III patients in the non-PORT population. The PORT population had 57 recurrences, whereas the non-PORT population had 20 recurrences (p=1.02 x 10-9). The PORT population had 5 deaths and 50 instances of long-term complications, while the non-PORT population had 3 deaths and 25 instances of long-term complications. Overall, these data do not support the routine usage of PORT in resected Stage II/III TET. Further analysis in larger data sets are warranted

Fortified breakfast cereal consumed daily for 12 wk leads to a significant improvement in micronutrient intake and micronutrient status in adolescent girls: a randomised controlled trial

Background: Poor micronutrient status is reported among adolescents across Europe and USA. This may be related to the well-documented decline in the regular consumption of breakfast by this group. The regular consumption of a breakfast cereal offers a possible means to improve micronutrient status; fortified cereal is likely to have enhanced benefit. A study was conducted to determine the efficacy of the regular consumption of a fortified cereal with milk, compared with unfortified cereal, consumed either as a breakfast or a supper, in improving micronutrient intake and micronutrient status of adolescent girls. Methods: A randomised, double-blind, placebo-controlled intervention trial was conducted in girls recruited at ages 16–19 years, from schools and colleges in Sheffield, UK. Girls were randomised to receive 50 g fortified or unfortified cereal, with 150 ml semi-skimmed milk, daily, for 12 weeks, as a breakfast or as a supper. Dietary intake was estimated using a 4-d food diary and blood collected for the assessment of nutritional status. Within-group changes were tested using a paired sample t test; two-way ANOVA was used to analyse effects of the intervention, with cereal type and time of consumption as factors, correcting for baseline values. The analysis was conducted on 71 girls who completed the study. Results: Consumption of unfortified cereal elicited an increase in the intake of vitamins B1, B2 and B6; consumption of fortified cereal elicited increases in vitamins B1, B2, B6, B12, folate and iron (P < 0.001) and of vitamin D (P = 0.007), all increases were significantly greater than for unfortified cereal. Consumption of the fortified cereal also led to a significant improvement in biomarkers of status for vitamins B2, B12, folate and of iron, compared with girls receiving the unfortified cereal, and maintained vitamin D status, in contrast with the girls receiving the unfortified cereal (P < 0.001). Conclusions: The daily consumption of cereal with milk for 12 weeks by adolescent girls, increased intakes of micronutrients. The consumption of fortified cereal elicited greater increases than for unfortified cereal and improved biomarkers of micronutrient status. The findings justify strategies to encourage the consumption of fortified cereal with milk by adolescents, either as a breakfast or a supper

Trends in Thymic Epithelial Tumor Patients with Comorbid Autoimmune Disease

Thymic epithelial tumors (TETs) are rare malignancies originating from the thymus in the anterior mediastinum. TETs include thymic carcinoma and thymoma. Approximately 30-40% of thymomas have associated autoimmune paraneoplastic disorders, the most common being myasthenia gravis. A broad range of other paraneoplastic syndromes have also been reported. Currently, little is known about demographic or histological trends in thymoma patients with comorbid autoimmune disease. In this single institution retrospective chart review, we assessed the distribution of thymoma-associated paraneoplastic syndromes at the IU Simon Cancer Center (IUSCC) to identify trends within demographic and histological features. We created a database of IUSCC patients seen from 2000-2023 and identified 170 subjects with biopsy-proven malignant TET and associated autoimmune disease. Data was exported to excel and R for analysis. Factors analyzed included: age at diagnosis, sex assigned at birth, BMI, WHO (World Health Organization) classification, and Masaoka staging. Overall survival was also compared to matched controls without paraneoplastic syndrome. A total of 37 different paraneoplastic syndromes were identified in association with thymoma in IUSCC patients. The most prevalent was Myasthenia Gravis (110 patients), followed by Hypothyroidism (21 patients, 5 confirmed as Hashimoto’s thyroiditis), Good Syndrome (19 patients), and Pure Red Cell Aplasia (15 patients). Significant findings included: 36.4% of patients with paraneoplastic comorbidity had &gt;1 paraneoplastic syndrome, 51.8% presented with Stage IV disease, and 40.4% had WHO Type B2 tumor pathology, with Type B3 being second most common (25%). No significant demographic associations were identified. 10-year survival of TET patients with paraneoplastic syndromes was not significantly different from those without (p= 0.721). These results indicate potential associations between thymoma staging and grading and development of paraneoplastic disease. Further analysis with a larger data set is warranted. Serum and blood test analysis may also elucidate reasons behind the development of paraneoplastic disease in thymoma patients.&nbsp

Late gastrointestinal tissue effects after hypofractionated radiation therapy of the pancreas

Background To consolidate literature reports of serious late gastrointestinal toxicities after hypofractionated radiation treatment of pancreatic cancer and attempt to derive normal tissue complication probability (NTCP) parameters using the Lyman-Kutcher-Burman model. Methods Published reports of late grade 3 or greater gastrointestinal toxicity after hypofractionated treatment of pancreatic cancer were reviewed. The biologically equivalent dose in 1.8 Gy fractions was calculated using the EQD model. NTCP parameters were calculated using the LKB model assuming 1–5 % of the normal tissue volume was exposed to the prescription dose with α/β ratios of 3 or 4. Results A total of 16 human studies were examined encompassing a total of 1160 patients. Toxicities consisted of ulcers, hemorrhages, obstructions, strictures, and perforations. Non-hemorrhagic and non-perforated ulcers occurred at a rate of 9.1 % and were the most commonly reported toxicity. Derived NTCP parameter ranges were as follows: n = 0.38–0.63, m = 0.48–0.49, and TD50 = 35–95 Gy. Regression analysis showed that among various study characteristics, dose was the only significant predictor of toxicity. Conclusions Published gastrointestinal toxicity reports after hypofractionated radiotherapy for pancreatic cancer were compiled. Median dose was predictive of late grade ≥ 3 gastrointestinal toxicity. Preliminary NTCP parameters were derived for multiple volume constraints

Evaluation of Chemotherapeutic Outcomes for Thymic Carcinoma Patients

Background and Hypothesis:Thymic Epithelial Tumors are uncommon tumors of the anterior mediastinum composed ofthymomas and thymic carcinomas (TC). TC’s are known to have worse disease outcomes andlower rates of survival in comparison to thymomas and are suspected to have lower responserates to chemotherapy as well. As these tumors are rare, little data exists assessing the trueefficacy of chemotherapeutic regimens for TC patients. Due to this lack of data, and that theIndiana University Health Simon Cancer Center treats a high percentage of TET patients, adatabase of these patients covering a variety different disease characteristics and treatmentshas been established. We hypothesize, upon evaluation of this database, response rates toanthracycline based regimens (PAC) will be superior to non-anthracycline based regimens (i.e.,PE, Carbo/Taxol) for TC patients. Methods:In this project, a collection of patients seen by Dr. Patrick Loehrer and/or Dr. Kenneth Keslerwas acquired, and a database was created using these patients in RedCap. Once established,we evaluated patient medical records in Cerner and entered data related to diseasecharacteristics and treatments. These patients were then analyzed accordingly to evaluatechemotherapy response rates. Results:The database yielded 123 instances of chemotherapy treatment for TC. Of which, the mostpopular treatments were PAC and Carbo/Taxol. The data suggests that PAC generates a higherresponse rate (65.5%) than other therapies (Carbo/Taxol: 27.6%, PE: 58.3%, etc.). Therefore,there is evidence that anthracycline based regimens may be more effective at generatingresponse rates in comparison to non-anthracycline based regimens. Conclusion and Potential Impact:This project will help elucidate the effectiveness of recommended systemic therapies for thymiccarcinoma patients from one of the largest TET databases constructed. Ultimately, we hope thatwith clarity of the effectiveness of treatment, this can serve as a reliable reference for evidencebasedmedicine for the care of TC patients

Prediagnostic adult body mass index change and esophageal adenocarcinoma survival

Background: We examined whether body mass index (BMI) changes in adulthood, prior to disease onset, are associated with overall survival among esophageal adenocarcinoma patients. Methods: We included 285 histologically confirmed patients with a complete baseline BMI questionnaire. Using extended Cox regression models, we obtained adjusted hazard ratios (HRs) for the associations between overall survival and BMI at diagnosis, BMI 6 months before diagnosis, self-reported average adult BMI, and ΔBMI (BMI 6 months before diagnosis minus average adult BMI), categorized into tertiles 25 and <35 kg/m2 was associated with better overall survival. Compared to patients with stable BMI in adulthood, patients who gained BMI throughout adulthood had 1.68 times the all-cause hazard of death (95% CI: 1.17-2.43; P <.01), independent of diagnosis BMI and percent weight loss 6 months before diagnosis. Compared to patients with average adult BMI < 27.5 who maintained stable adult BMI, patients with average adult BMI ≥ 27.5 kg/m2 who gained BMI had the worst survival (HR = 3.05; 95% CI 1.62-5.72; P <.01). Conclusion: Body mass index gain in adulthood is associated with poor overall survival, and maintaining a normal body weight throughout adulthood is associated with the best overall survival among esophageal adenocarcinoma patients, independent of BMI at diagnosis