The primary objective of this research is to enhance a novel method for the eco-friendly production of trimethyl borate (TMB) from ulexite ore by utilizing carbon dioxide. Notably, CO2, a major greenhouse gas, is converted into thermodynamically stable CaCO3 following TMB synthesis. TMB, a significant organo-boron chemical, has a wide range of industrial applications. In this study, the trimethyl borate production process consists of three main steps: reaction, distillation, and pervaporation. Trimethyl borate was synthesized through the reaction of ulexite with methanol in a high-pressure reactor under a CO2 atmosphere. The obtained liquid product was subjected to distillation to produce the TMB-methanol azeotrope. Following the distillation process, the separation of TMB from the azeotrope mixture was achieved by utilizing pervaporation. The TMB-methanol azeotrope and pure TMB were characterized and confirmed by using Fourier transform infrared (FTIR) spectroscopy and gas chromatography (GC). In this research, hydroxyethyl cellulose (HEC) and polyvinylpyrrolidone (PVP) were used as the membrane materials. Blend membranes were prepared by the solution casting evaporation method. The morphologies of the membranes were characterized by FTIR spectroscopy, thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), and contact angle assessment. The pervaporation performance of all blend membranes was evaluated for the separation of the TMB-methanol azeotrope. The effects of the operating temperature, methanol feed concentration, and PVP ratios on separation performance were investigated. The results demonstrated that a TMB purity of 97.71 wt % was achieved when the PVP-HEC-2 membrane was utilized in pervaporation. In conclusion, this study introduces an innovative and environmentally friendly process for producing valuable chemicals, highlighting its potential for industrial applications.

Representativeness of Study Participants

e22591 Background: MMR protein deficient (dMMR) CRC has distinctive clinical and pathologic features that can be either sporadic or genetic. Immunohistochemistry (IHC) testing of CRC tumor tissue for absent MMR proteins and BRAF (V600E) mutation has become a routine practice in most tertiary cancer centers. We sought to examine the utilization of MMR and BRAF IHC testing and genetic consultation referrals in the diagnostic evaluation and management of CRC patients (pts) in a community hospital-based cancer center in rural central Nebraska. Methods: All pathologically confirmed CRC pts` data, diagnosed between January 2017 and December 2023 at Morrison Cancer Center, were evaluated. Data on age, gender, tumor location, stage, tumor IHC testing for MMR, BRAF (V600E) and genetic consultation referrals were collected and analyzed. The independent sample t-test, and Fisher’s exact tests were used to look at the association of patient characteristics based on the MMR status. Results: A total of 272 pts (F/M 137/135), median age 71(range:38-96), non-metastatic 215/272 (75%) and metastatic 57/272(25%) were evaluated. 205/272(75%) pts had MMR IHC testing, 86/272 (32%) had BRAF (600E) IHC testing. 42/272(15%) had dMMR and 163/272(60%) had pMMR while 67/272(25%) pts did not have MMR testing. 107/272(39%) referred for genetic consultation (GC), 33/272 (12%) followed through with GC appointment. 4/272(1.4%) were diagnosed with Lynch Syndrome. Metastatic pts were more likely to have dMMR status than non-metastatic pts [4/47 (8.5%) vs 38/158 (2.4%)], p = 0.023. More pts with dMMR status than pMMR status had BRAF mutation [22/28 (78%) vs 6/28 (21%)], p = 0.0001. GC referrals and Lynch syndrome were more likely in dMMR CRC group, p = 0.0009, and p = 0.002. Conclusions: We present a real world community hospital based cancer center data from rural central Nebraska. Utilization rates for MMR and BRAF IHC testing were 75% and 32%, respectively. Comparison of patient characteristics based on the MMR status revealed statistically significant associations in metastatic vs non-metastatic disease, positive or negative BRAF mutation, GC referral and Lynch syndrome status. Future studies comparing community based cancer center data to tertiary cancer center data would be valuable. dMMR 42/272 pMMR 163/272 P Age (Median) 76 70 Gender Female Male 22 (52%)20 (48%) 79 (49%)84 (51%) 0.7 Tumor Site Right Colon Left Colon Rectum 28 (67%)11 (26%)3 (7%) 83 (51%)46 (28%)34 (21%) 0.07 Tumor Stage Metastatic Non-metastatic 4 (10%)38 (91%) 43 (26%)120 (74%) 0.02 BRAF mutation BRAF (-) BRAF (+) 11 (33%)22 (67%) 47 (89%)6 (11%) 0.0001 GC Referral No referral 16 (49%)17 (52%) 17 (17%)81 (83%) 0.0009 Lynch syndrome Yes No 4 (16%)21 (84%) 0 (0%)87 (100%) 0.0020

Trimethyl borate (TMB) is an essential chemical for applications ranging from organic synthesis to borohydride production and requires efficient separation from methanol for optimal utilization. This study investigates the pervaporation performance of blend membranes composed of different ratios of chitosan (CS) and polyvinyl pyrrolidone (PVP) to improve the separation of TMB/methanol mixtures through pervaporation. The structural morphology, thermal properties, and crystalline nature of these membranes were comprehensively characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, contact angle measurements, scanning electron microscopy, and X-ray diffraction analysis. Pervaporation experiments were conducted by varying feed compositions, operating temperatures, and PVP ratios. The results demonstrated that increasing PVP content has a significant effect on permeation flux. The best conditions were obtained at 45 °C of operation temperature and 75

Background: The evolution of systemic therapies has improved outcomes for patients with human epidermal growth factor receptor 2 positive (HER2+) breast cancer. Nonetheless, the tolerability and safety profile of systemic therapies represent an area for further improvement. Here we report the results of a phase 2 trial evaluating a non-anthracycline, non-platinum adjuvant treatment regimen for patients following initial surgical resection. Methods: We enrolled patients with stage I or II HER2+ breast cancer who underwent upfront surgery to receive adjuvant treatment with 6 cycles of dose-dense Paclitaxel, cyclophosphamide and Trastuzumab (PC-H) every 2 weeks, followed by 13 cycles of maintenance trastuzumab every 3 weeks to complete 52 weeks of treatment (comprising 19 cycles). The primary objective was to determine the safety and feasibility of adjuvant PC-H measured by the completion rate and the frequency and the grade of adverse events, using National Cancer Institute Common Terminology Criteria. The secondary objective was to estimate relapse-free survival and overall survival. Results: Between 2010 and 2019, a total of thirty-nine patients were enrolled. Of those, 34 patients (87.18%) completed the planned treatment. Sever adverse events of grade 3 or 4 occurred in 27 patients (69.23%), including 3 patients (7.69%) with grade 3-4 decrease in ejection fraction. At median follow up of 5.6 years, all 39 patients were alive. The 5-year relapse-free survival was 94.30% (95% CI: 75.3-100). Conclusions: PC-H regimen demonstrated overall safety and efficacy, yielding high rates of relapse-free survival among patients with early stage (HER2+) breast cancer.] Citation Format: Jairam Krishnamurthy, Lina Elsayed, Elizabeth Reed, Shivani Modi, Pavan Tandra, Mehmet Copur, Kaeli Samson. Investigating the Efficacy and Safety of a Dose-Dense Paclitaxel, Cyclophosphamide with Trastuzumab in Stage I-III Human Epidermal Growth Factor Receptor 2 (HER2) Positive Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-05-05.

BACKGROUND:The evolution of systemic therapies has improved outcomes for patients with human epidermal growth factor receptor 2 positive (HER2+) breast cancer. Nonetheless, the tolerability and safety profile of systemic therapies represent an area for further improvement. Here we report the results of a phase 2 trial evaluating a nonanthracycline, nonplatinum adjuvant treatment regimen for patients following initial surgical resection. METHODS:We enrolled patients with stage I or II HER2+ breast cancer who underwent upfront surgery to receive adjuvant treatment with 6 cycles of dose-dense Paclitaxel, cyclophosphamide and Trastuzumab (PC-H) every 2 weeks, followed by 13 cycles of maintenance trastuzumab every 3 weeks to complete 52 weeks of treatment (compromising 19 cycles). The primary objective was to determine the safety and feasibility of adjuvant PC-H, measured by the completion rate frequency and the grade of adverse events, using National Cancer Institute Common Terminology Criteria. The secondary objective was to estimate relapse-free survival and overall survival. RESULTS:Between 2010 and 2019, a total of 39 patients were enrolled. Of those, 34 patients (87.18%) completed the planned treatment. Severe adverse events of grade 3 or 4 occurred in 27 patients (69.23%), including 3 patients (7.69%) with grade 3-4 decrease in ejection fraction. At median follow up of 5.6 years, all 39 patients were alive. The 5-year relapse-free survival was 94.30% (95% CI: 75.3-100). CONCLUSIONS:PC-H demonstrated overall safety and efficacy, yielding high rates of relapse-free survival among patients with early stage (HER2+) breast cancer.

AbstractPurpose:Cyclin D/CDK4/6 is critical in controlling the G1 to S checkpoint. CCND, the gene encoding cyclin D, is known to be amplified in a variety of solid tumors. Palbociclib is an oral CDK4/6 inhibitor, approved in advanced breast cancer in combination with endocrine therapy. We explored the efficacy of palbociclib in patients with nonbreast solid tumors containing an amplification in CCND1, 2, or 3.Patients and Methods:Patients with tumors containing a CCND1, 2, or 3 amplification and expression of the retinoblastoma protein were assigned to subprotocol Z1B and received palbociclib 125 mg once daily for 21 days of a 28-day cycle. Tumor response was assessed every two cycles.Results:Forty patients were assigned to subprotocol Z1B; 4 patients had outside assays identifying the CCND1, 2, or 3 amplification and were not confirmed centrally; 3 were ineligible and 2 were not treated (1 untreated patient was also ineligible), leaving 32 evaluable patients for this analysis. There were no partial responses; 12 patients (37.5%) had stable disease as best response. There were seven deaths on study, all during cycle 1 and attributable to disease progression. Median progression-free survival was 1.8 months. The most common toxicities were leukopenia (n = 21, 55%) and neutropenia (n = 19, 50%); neutropenia was the most common grade 3/4 event (n = 12, 32%).Conclusions:Palbociclib was not effective at treating nonbreast solid tumors with a CCND1, 2, or 3 amplification in this cohort. These data do not support further investigation of single-agent palbociclib in tumors with CCND1, 2, or 3 amplification.

e15141 Background: PD-L1 and TMB are the most widely used immunotherapy biomarkers to identify populations who would benefit from immunotherapy, with the higher values predicting better therapeutic efficacy. We sought to explore the occurrence and correlation of these two biomarkers in a community based cancer center patient population in rural central Nebraska. Methods: One hundred sixty consecutive cancer patients(pts) diagnosed and treated between 2018-2022 at Morrison Cancer Center were evaluated. Malignant tumor tissue specimens were analyzed for PD-L1expression and TMB (Foundation test). PD-L1 expression was classified as low ( < 1%), intermediate (1% ≥ PD-L1 < 50%), high (≥ 50%), and TMB classified as low [1–5 mutations/Megabase (muts/Mb)], intermediate (6–19 muts/Mb), high (≥ 20 muts/Mb)]. PD-L1 and TMB values were treated as continuous variables to calculate a Pearson correlation coefficient and p value. Results: Mean age at diagnosis was 64 years (range 33-89). Malignant histology diagnoses included 55 pts with lung, 18 colorectal, 12 breast, 15 unknown primary, 15 pancreas, 10 renal, 3 melanoma, 1 thyroid, 6 ovary, 5 uterus, 5 head and neck, 5 prostate, 5 biliary, and 1 vulvar. Fifty four percent (86/160) of pts had low, 33% (53/160) had intermediate, and 13% (21/160) had high PD-L1 expression score with a mean PD-L1 value of 13.8% (range 0-100). Sixty six percent (106/160) of pts had low, 30% (48/160) had intermediate, and 4% had high TMB with a mean TMB value of 5.6 muts/Mb (range 0-66). A marginal linear correlation between PD-L1 expression and TMB was observed (Pearson Correlation Coefficient = 0.172, P = 0.0270). Conclusions: PD-L1 and TMB are both important biomarkers for immunotherapy. Increasing availability and use of both PD-L1 and TMB testing in the community oncology practice beseeches the question of frequency of these two biomarkers in various cancers in the community oncology patient population as well as any association between them. The results of our study gives a glimpse of the distribution landscape of these two biomarkers for community oncology patients and suggest that PD-L1 and TMB may be independent markers with a weak association. PD-L1 and TMB may each inform use of immunotherapy by different mechanisms. [Table: see text]

In a recent Hot Topics column, Mehmet Sitki Copur, MD, FACP, et al discussed the pros and cons of patients receiving test results early through electronic medical records.

This paper proposesa novel method for CO2 capture,utilization, and sequestration (CCUS) with borax producing disodiumoctaborate tetrahydrate (Na2O & BULL;4(B2O3)& BULL;4H(2)O & EQUIV; Na2B8O13 & BULL;4H(2)O, DSOBTH) equivalent boron compoundsand sodium bicarbonate (NaHCO3). We tested the performanceof this method experimentally using aqueous ammonium (NH4 (+)) solutions in a pressurized reactor (1 L) continuouslypurged with pure (99.9%) CO2. Experimental parameters werechanged as temperature (T), 45-65 & DEG;C; solid-to-liquidratio (SLR), 0.69-0.92 g/mL; reaction time (t), 30-60 min; pressure (P), 5-30 bar;NH3 concentration (AC) 2.82-5.65 M; and steeringspeed (SS), 500 rpm. The results showed that P and T were highly influential on the performance. The best conditionsfor CO2 utilization were found as P =20 bar; T = 60 & DEG;C; SLR = 0.77 g/ml; t = 50 min; and AC = 4.76 M. Per ton of tincal, under theseconditions, produced were 0.274 ton of DSOBTH (& SIM;67% B2O3), 0.216 ton of NaHCO3 (& SIM;95% purity),0.386 ton of avoided boric acid, and 0.417 ton of avoided CO2. The total potential added value can be about $1100/ton of tincal.

For a long time, cancer survivorship has received little attention and prioritization. As survival rates continue to improve due to advances in cancer screening, early detection, and treatment, more and more individuals are living with the long-term consequences of a cancer diagnosis and treatment. There is more to life after cancer than just surviving. Following the initial intense period of diagnosis and treatment, inevitable changes in mind, body, work, relationships along with a sense of future uncertainty reign. To identify and meet the diverse needs of patients living after a cancer diagnosis, the cancer survivorship field has been established to help cancer patients not only to survive but thrive and return to health or even achieve better health and well-being than they had before their cancer was diagnosed and treated. The National Cancer Institute defines survivorship as any patient living with cancer from the time of diagnosis through the balance of his or her life. Family members, friends, and caregivers are also impacted and are, therefore, included in this definition.

Colorectal cancer (CRC) is one of the leading causes of death and comprises a considerable percentage of cases presented with metastases. Herein, we report 81 yr-old female patient who was admitted to our clinic due to persistent nausea and vomiting. She had an eight years-history of colorectal cancer, and she had undergone a right hemicolectomy and received adjuvant capecitabine treatment. An incisional hernia was palpated around the umbilicus and confirmed by abdominal CT (computed tomography). Whole-body PET (positron emission tomography) revealed FDG (fluorodeoxyglucose)-enhanced lesions in the lungs, pancreas, and small bowel, suggesting metastases. Colonoscopy did not reveal any recurrence. Biopsies obtained from the pancreas with endosonography diagnosed colorectal cancer metastasis. During hospitalisation she has been operated due to ileus and the obstructed jejunal segment was resected. Histopathological examiation confirmed intestinal metastasis of the colorectal cancer. In conclusion, pancreas and small bowel metastases are both rare phenomena individually. Ileus caused by intestinal metastasis is also exceptional. The coexistence of these rare metastases and lung metastases in CRC can be related to the unique biologic behavior of this tumor.

e12566 Background: Oncotype Dx recurrence score (RS), is a prognostic and predictive test utilized for decision making in adjuvant therapy of 0-3 node/hormone receptor positive(HR+)/ HER-2-negative early breast cancer. Ki-67 is a marker of proliferating cells and is associated with prognosis and response. Immunohistological (IHC) assessment of Ki 67 expression is less expensive and with the approval of CDK inhibitors in the high risk adjuvant setting, it is increasingly being utilized in clinical decision making. A moderate to strong correlation between Ki67 and Oncotype Dx RS has been reported in the literature. We sought to examine the relationship of Ki 67 to Oncotype Dx RS in a community-based cancer center in rural central Nebraska. Methods: Forty-three consecutive postmenopausal breast cancer patients(pts) diagnosed and treated at our community based cancer center between 2020-2021 with T1–2 N0-1 M0, HR+, HER-2-negative disease were evaluated for histological type, tumor size, Nottingham grade, HR levels, Ki 67 expression (low < 10%, intermediate 10 ≥ Ki67 < 25 high ≥ 25), and Oncotype Dx RS(low <16,intermediate 16⩽RS<26), high ⩾26). Ki 67 and Oncotype Dx RS were treated as continuous variables to calculate a Pearson correlation coefficient. Results: Mean age at diagnosis was 59.4 years (range 48-89). Mean tumor diameter was 15.6 mm. 78.9% were intermediate histologic grade and 9.7% patients had lymph node involvement. Median expression of ER and PR were 90% (5-100) and 70% (0-100), respectively. The mean Ki 67 value was 17.5 (range 5-60 %), and mean Oncotype RS was 14.4 (range 4-34). There was a positive linear correlation between Ki 67 expression and Oncotype Dx RS (Pearson Correlation Coefficient=0.49, P-value <0.001). The vast majority of high Ki 67 pts (80%) had high/intermediate Oncotype RS. All pts with low Ki 67 (100%) had low/intermediate RS. Conclusions: Our community based rural cancer center data support a linear, statistically significant, positive correlation between Ki 67 and Oncotype Dx RS in early stage 0-3 node/HR+ positive breast cancer pts. Increasing use of Ki 67 testing in different clinical settings will generate more data to better define this correlation.[Table: see text]

Various wastes being generated globally and dumped on land by mineral processing activities pose great ecological and health problems. An example is the boron mineral beneficiation solid wastes. Even greater threat is anthropogenic carbon dioxide (CO 2 ) emissions among key causes of prevalent climate change. By this work, we propose a symbiotic solution to alleviate both environmental threats through recovering valuable boron products from boron wastes (BW), while also utilizing and sequestering CO 2 stably and permanently. This article presents the results on the effect of important operation parameters for the performance of such a process within the following ranges determined by preliminary tests: temperature: 20–60°C, solid-to-liquid ratio: 0.1–0.5 g/ml, reaction time: 15–120 min, stirring speed: 300–700 rpm and particle size: 150–600 µm. CO 2 gas (99.9%) flow rate was maintained continuously at 1.57 l/min under atmospheric pressure. The important findings are (1) per ton of BW production of commercially valuable either (a) 310 kg sodium penta-borate or (b) 350 kg sodium penta-borate mixed with Na 2 CO 3 , depending on the process configuration, (c) 725 kg relatively pure CaCO 3 , a potential source for precipitated calcium carbonate (PCC) and (d) 72 kg CO 2 utilization, (2) effective parameters for CO 2 utilization, in decreasing order are temperature, solid-to-liquid ratio and time, while stirring speed and particle size are ineffective within the range investigated and (3) the optimum operating conditions as: temperature: 60 °C, solid-to liquid ratio: 0.1 g/ml, time: 90 min, stirring speed: 500 rpm and particle size: <180 µm.

•PDAC is a genetically heterogenous disease with various molecular subtypes which may explain variations in treatment response. Genetic mutations and altered molecular pathways serve as targets in therapy and may improve outcomes.•Neoadjuvant systemic therapy with or without radiation followed by evaluation for surgery is an accepted treatment approach for locally advanced disease with the goal of enabling an R0 resection to achieve improved disease-free and overall survival.•In many cancers, including pancreatic cancer, MSI is a predictive biomarker for response to immunotherapy, and a prognostic factor for survival. Treatment with neoadjuvant chemoimmunotherapy in this group of patients usually leads to pathologic complete responses.•Although rare (15%), an unusual dMMR phenotype, evidenced by discordance between IHC staining of MMR proteins and next gen sequencing, do exist. In this group of patients available data show varying responses to immunotherapy ranging from complete, to partial responses to stable disease.•We present successful treatment outcome in a locally advanced PDAC case with dMMR and germline plus somatic BRCA2 mutation treated with available chemotherapy immunotherapy and targeted therapy options.

Neoadjuvant systemic therapy is a preferred treatment approach for a number of tumor types due to many potential advantages over upfront surgery, including tumor downstaging, early treatment of micrometastatic disease, and providing an in vivo test of tumor biology. For colon cancer, current standard of care is upfront surgery followed by adjuvant systemic therapy in high-risk patients. Concerns about inaccurate radiological staging and tumor progression during preoperative treatment, as well the lack of randomized data demonstrating benefit, are among the reasons for the limited use of neoadjuvant therapy in this disease. Locally advanced colon cancer, defined as primary colon cancer with direct invasion into the adjacent structures or extensive regional lymph node involvement, is not always amenable to pathological complete resection, and when attempted it comes with high incidence of postoperative morbidity and mortality because of the required multivisceral resection. Clinical trials of neoadjuvant chemotherapy for colon cancer to date have been promising with downstaging of disease and higher rates of R0 resection. Here, we report a case of a patient with locally advanced, unresectable, mismatch repair deficient sigmoid colon cancer who was treated with neoadjuvant chemoimmunotherapy followed by surgical resection leading to a complete pathologic response after preoperative systemic chemoimmunotherapy.

Removal of boron from water is a significant issue worldwide. Boron levels in waters containing high concentrations should be kept under control. Boron removal from the industrial wastewater released from Eti Mine Boron plants was investigated by using blend and hybrid membranes in a laboratory-scale pervaporation system. Polyvinylpyrrolidone/Polyvinylidene fluoride blend membrane and Graphene oxide/Polyvinylpyrrolidone/Polyvinylidene fluoride hybrid membranes were synthesized for this process. The membranes were characterized by using scanning electron microscopy, Fourier transform infrared, X-ray diffraction and contact angle measurements. Separation performance was evaluated in terms of flux, removal ratio of boron, and boron concentration in permeate within the membrane. Membranes showed higher separation performance in industrial wastewater. The highest boron removal was obtained as 99.86% with a flux of 0.755 kg/m2h when the 8 wt% graphene oxide loaded hybrid membrane was used. This study indicates that the Polyvinylpyrrolidone and Graphene oxide addition improved the membrane features and separation performances of the pervaporation process with improved hydrophilic membrane features can be preferred as an innovative water treatment method for the removal of boron from industrial wastewater. The obtained results show that pervaporation can be readily adapted to the removal of boron species by appropriate membrane selection.

Bu çalışmada, pervaporasyon prosesi ile endüstriyel atık sudan borun uzaklaştırılması incelenmiştir. Bu işlem için Saf PVA ve Amberlit IRA 743 katkılı PVA membranlar hazırlanmıştır. SEM analizinde, saf membranlarda yoğun ve homojen bir yapı gözlenirken, katkılı membranda Amberlit IRA 743 dağılımı açıkça görülmektedir. Amberlit IRA743 ilavesinin ve çapraz bağlanmanın membranın kimyasal bağ yapısında meydana getirdiği değişimler Fourier dönüşümlü kızılötesi (FTIR) spektroskopisi ile belirlenmiştir. Membranların suya karşı ilgisi şişme testi ile belirlenirken, yüzey hidrofilikliği temas açısı ölçümleriyle araştırılmıştır. Sıcaklığın ve Amberlit IRA 743 yükleme oranının membranın ayırma performansına etkisi incelenmiştir. Sıcaklığın artması suyun akısını artırırken bor giderimine önemli bir etkisi olmamıştır. Amberlit IRA 743 miktarının artması ile suyun akısı azalırken bor giderimi artmıştır. PVA/Amberlit IRA 743 membranların endüstriyel atık sulardan bor gideriminde yüksek ayırma performansı gösterdiği ve %99’dan daha fazla oranda bor giderildiği tespit edilmiştir.