Treatment Schedule Research Articles

Community oncology preparedness and perceptions of challenges in care with HER2/HER3 therapy for NSCLC.

e21010 Background: The rapid pace of advances in molecular testing and targeted treatment for non-small cell lung cancer (NSCLC) can make it difficult to stay up to date with new developments. Accelerating the integration of practice-changing data requires clarification of actionable vs non-actionable mutations, relevance for therapeutic decisions, and treatment options for patients. To address this need further an educational program was designed in 2023. Methods: A one-hour online, video-based program was designed for clinicians and their teams and hosted on OMedLive from February 2023. Knowledge and competence questions were administered pre-, and immediate post-activity. and the intersection of patient and clinician perspectives, including behavioral impact, and qualitative insights. Behavioral impact, perception, and practice pattern questions were also assessed immediately post-activity. Results: More than 1,700 participants have engaged in the educational program to date. Of the participants in the clinician program, 94% were physicians and 93% noted their specialty as oncology with 67% identifying as treaters seeing an average of 8 patients with NSCLC on a monthly basis. Low baseline (8% - 40%) knowledge and competence was observed for awareness of NGS-based approaches to detect ERBB2 mutations, trial eligibility criteria and outcomes, time to onset of drug-related toxicities, and ability to identify patients who would benefit from clinical trials with HER3 investigational therapies. Only 28% were confident in their ability to appropriately test for HER2 mutational status and 47% likely to incorporate testing for HER2 expression level or amplification prior to the selection of targeted therapy. The greatest challenges in managing patients with HER2-mutated NSCLC was identified as managing side effects (33%), affordability of therapy for patients (27%), and adherence to treatment schedules (17%). Conclusions: The outcomes of this educational program demonstrate a need for greater alignment and education among pathology and oncology team members on HER2 testing for patients with NSCLC. Additional education is needed relevant to investigational HER3 therapeutics, the appropriate patient to receive these therapies, and the potential application within the current treatment landscape. As these agents deepen their impact in the NSCLC landscape, it is important to prepare teams for timely management of adverse events.

Travel-associated carbon emissions of patients receiving cancer treatment from an urban safety net hospital.

e13812 Background: Climate change is one of the grand challenges of the 21st century. The U.S. currently emits 11% of the annual global greenhouse gases, and 8-10% of its emissions result from the healthcare industry. Studies on the contribution of patients' commute for cancer treatment to healthcare-associated CO2 emissions remain limited. This study aims to determine the CO2 emissions of patients’ commute for cancer treatment among patients with malignancies at an urban safety net hospital. Methods: We conducted a retrospective study of patients seen at an oncology clinic from July 1, 2022 - June 30, 2023. Demographic data, data on visit diagnosis and indication (e.g., laboratory, infusion, or follow-up visits), and patients' home addresses were collected from the EMR. Distance between patients’ homes and the hospital was calculated using a Google Map API and a macro for distance. Total CO2 emissions from patients’ travel in miles were estimated at 400 grams of CO2 per mile based on the Environmental Protection Agency’s estimate of the average CO2 emissions for a passenger vehicle. The primary outcome was CO2 emissions from patients’ round-trip travel. The total estimated CO2 emissions were converted to equivalents of coal burned, smartphones charged, and gallons of gasoline used based on the EPA equivalencies calculator. Results: Of the 8,235 visits, 5,095 (61.8%) were follow-up/laboratory visits, and 3,137 (38.1%) were chemotherapy infusion visits. Of the 1,080 patients who attended the clinic, the mean age was 63.8 years, 700 (64.8%) were males, 379 (35.1%) were females, 525 (48.6%) were black or African American, 139 (12.9%) were whites. Breast cancer was the most common diagnosis, with 423 (39.2%) of patients. Each patient traveled an average of 9.6 miles round trip (Range = 0.7-298.6 miles) to receive cancer care. An estimated 1,520 grams of CO2 was emitted for each patient’s visit. A total of 79,582 round trip miles was made in 8,235 visits, which corresponds to 31,832 kg of CO2 emissions, equivalent to 35,658 pounds of coal burned, 1,462 propane cylinders used for a home, or 3,872,250 smartphones charged. Conclusions: Cancer care is associated with significant CO2 emissions. Efforts to decrease the overall carbon footprint of cancer treatment through adoption of telemedicine and alternative treatment schedules, are needed to reduce the effect of cancer treatment on the climate. [Table: see text]

Fertility-Preserving Treatments and Patient- and Parental Satisfaction on Fertility Counseling in a Cohort of Newly Diagnosed Boys and Girls with Childhood Hodgkin Lymphoma.

The purpose of this study is to evaluate the use of fertility-preserving (FP) treatments and fertility counseling that was offered in a cohort of newly diagnosed children with classical Hodgkin lymphoma (cHL). In this observational study, boys and girls with cHL aged ≤ 18 years with scheduled treatment according to the EuroNet-PHL-C2 protocol were recruited from 18 sites (5 countries), between January 2017 and September 2021. In 2023, a subset of Dutch participants (aged ≥ 12 years at time of diagnosis) and parents/guardians were surveyed regarding fertility counseling. A total of 101 boys and 104 girls were included. Most post-pubertal boys opted for semen cryopreservation pre-treatment (85% of expected). Invasive FP treatments were occasionally chosen for patients at a relatively low risk of fertility based on scheduled alkylating agent exposure (4/5 testicular biopsy, 4/4 oocyte, and 11/11 ovarian tissue cryopreservation). A total of 17 post-menarchal girls (20%) received GnRH-analogue co-treatment. Furthermore, 33/84 parents and 26/63 patients responded to the questionnaire. Most reported receiving fertility counseling (97%/89%). Statements regarding the timing and content of counseling were generally positive. Parents and patients considered fertility counseling important (94%/87% (strongly agreed) and most expressed concerns about (their child's) fertility (at diagnosis 69%/46%, at present: 59%/42%). Systematic fertility counseling is crucial for all pediatric cHL patients and their families. FP treatment should be considered depending on the anticipated risk and patient factors. We encourage the development of a decision aid for FP in pediatric oncology.

Effect of adaptive control of cooling rate on microstructure and mechanical properties of laser additively manufactured Inconel 718 thin walls

Ni-alloy Inconel 718 (IN718) is finding ever-increasing applications in various industries like aviation and aerospace. IN718 is a precipitation-strengthened alloy which derives its strength mainly from the intermetallic phases, γ” (Ni3Nb) along with the γ’ (Ni3(Al, Ti)) phase which can be precipitated using standard heat treatment schedules. However, the consummation of Nb in Laves phase formation during solidification tends to deteriorate the strength of the material. During laser additive manufacturing (LAM) by directed energy deposition (DED), the cooling rate variation along the build direction causes variations in the microstructure, properties and Laves phase distribution. The study aims to minimize the heterogeneities along the build direction by monitoring and controlling the cooling rate during DED of IN718. The feedback control system involves the use of two pyrometers in tandem with a leading pyrometer measuring the molten pool temperature and a trailing pyrometer measuring the temperature at a distance behind the molten pool. Two sets of thin walls of 120 layers were fabricated with one set being of constant process parameters without feedback control and the other set being of adaptive-controlled process parameters. The adaptive control was aimed at maintaining the cooling rates above a desired limit by changing the process parameters, namely the laser scan speed and the powder feed rate. The Laves phase morphology, which affects the strength of the deposited part deleteriously was finer and more discrete in the adaptive-controlled walls which led to their easier dissolution during heat treatment. This in turn helped in the precipitation of more amount of strengthening phases during heat treatment which led to better mechanical properties. The characterizations of the two sets of walls reflected the superior part quality of the adaptive-controlled wall in terms of homogeneity of microstructure, enhanced microhardness and tensile strength, thereby validating the importance of adaptive control of cooling rate in ensuring better quality in LAM parts.

The Lebanese percreta group: A retrospective cohort study of both radical and conservative management outcomes of abnormally invasive placenta.

The aim of the present study was to illustrate the outcomes of abnormally invasive placenta (AIP) cases managed in three leading centers in Lebanon. We conducted a retrospective multicenter cohort study. Patients managed conservatively (cesarean delivery with successful placental separation) or radically (cesarean hysterectomy) were included in the study. Data included patient characteristics, surgical outcomes (blood loss, operative time, transfusion, partial bladder resection), maternal outcomes (death, length of stay, ICU admission, postoperative hemoglobin level) and neonatal outcomes (Apgar score, neonatal weight, admission to neonatal intensive care unit, neonatal death). The study included 189 patients. In the radical treatment subgroup (141/189), patients were para 3 and delivered at 34 4/7 weeks in average, bled 1.5 L and were transfused with three packed red blood cells, with operative time averaging 160 min. A total of 36% were admitted to the ICU and patients stayed on average for 1 week despite partial bladder resection in 19% of cases. Unscheduled radical delivery occurred at a lower gestational age, was associated with more blood loss, higher rate and volume of transfusion, and risk of maternal and neonatal death. In addition, patients delivered in an unscheduled fashion experienced higher rates of partial bladder resection and longer interventions. In the conservative treatment subgroup, on average patients were para 2 and delivered at 36 weeks, bled 800 mL on average with low rates of transfusion (35%) and ICU admission (22.9%). With regard to neonatal outcomes, the average neonatal birth weight was 2.4 kg in the radical subgroup and 2.5 kg in the conservative subgroup. Neonatal death occurred in 5.4% of cases requiring radical management while it occurred in 2% of patients treated conservatively. Through their multidisciplinary approach, the three centers demonstrated that management of AIP in Lebanon has led to excellent outcomes with no maternal mortality occurring in scheduled radical treatment. By comparison of the three leading centers, pitfalls in each center were identified and addressed.

Weekly ultra-hypofractionated radiotherapy in localised prostate cancer

BackgroundModerately hypofractionated radiotherapy regimens or stereotactic body radiotherapy (SBRT) are standard of care for localised prostate cancer. However, some patients are unable or unwilling to travel daily to the radiotherapy department and do not have access to, or are not candidates for, SBRT. For many years, The Royal Marsden Hospital NHS Foundation Trust has offered a weekly ultra-hypofractionated radiotherapy regimen to the prostate (36 Gy in 6 weekly fractions) to patients unable/unwilling to travel daily. MethodsThe current study is a retrospective analysis of all patients with non-metastatic localised prostate cancer receiving this treatment schedule from 2010 to 2015. ResultsA total of 140 patients were included in the analysis, of whom 86 % presented with high risk disease, with 31 % having Gleason Grade Group 4 or 5 disease and 48 % T3 disease or higher. All patients received hormone treatment, and there was often a long interval between start of hormone treatment and start of radiotherapy (median of 11 months), with 34 % of all patients having progressed to non-metastatic castrate-resistant disease prior to start of radiotherapy. Median follow-up was 52 months. Median progression-free survival (PFS) and overall survival (OS) for the whole group was 70 months and 72 months, respectively. PFS and OS in patients with hormone-sensitive disease at time of radiotherapy was not reached and 75 months, respectively; and in patients with castrate-resistant disease at time of radiotherapy it was 20 months and 61 months, respectively. ConclusionOur data shows that a weekly ultra-hypofractionated radiotherapy regimen for prostate cancer could be an option in those patients for whom daily treatment or SBRT is not an option.

Real-world outcomes of newly diagnosed AML treated with venetoclax and azacitidine or low-dose cytarabine in the UK NHS

AbstractVenetoclax with azacitidine is the standard of care for patients with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy; however, uncertainties remain regarding the treatment schedule, accurate prognostication, and outcomes for patients treated outside clinical trials. The option of venetoclax with low-dose cytarabine (LDAC) is also available; however, it is not clear for which patients it may be a useful alternative. Here, we report a large real-world cohort of 654 patients treated in 53 UK hospitals with either venetoclax and azacitidine (n = 587) or LDAC (n = 67). The median age was 73 years, and 59% had de novo AML. Most patients received 100 mg of venetoclax with an azole antifungal. In cycle 1, patients spent a median of 14 days in the hospital, and 85% required red cell transfusion, 59% platelet transfusion, and 63% required IV antibiotics. Supportive care requirements significantly reduced after the first cycle. Patients receiving venetoclax-azacitidine had a complete remission (CR)/CR with incomplete hematological recovery rate of 67%, day 30 and day 60 mortality of 5% and 8%, respectively, and median overall survival of 13.6 months. Mutations in NPM1, RUNX1, STAG2, and IDH2 were associated with improved survival, whereas age, secondary and therapy-related AML, +8, MECOM rearrangements, complex karyotype, ASXL1, and KIT mutations were associated with poorer survival. Prognostic systems derived specifically for patients treated with venetoclax-azacitidine performed better than the European LeukemiaNet and Medical Research Council classifications; however, improved risk classifications are still required. In the 149 patients with NPM1 mutated AML, outcomes were similar for those treated with venetoclax-azacitidine and venetoclax-LDAC.

Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a high mortality neoplasm which usually appears on a cirrhotic liver. The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis. Notwithstanding the current deployment of treatments with curative intent (liver resection/local ablation and liver transplantation) in early and intermediate stages, a high rate of HCC recurrence persists, underscoring a pivotal clinical challenge. Emergent systemic therapies (ST), particularly immunotherapy, have demonstrate promising outcomes in terms of increase overall survival, but they are currently bound to the advanced stage of HCC. This review provides a comprehensive analysis of the literature, encompassing studies up to March 10, 2024, evaluating the impact of novel ST in the early and intermediate HCC stages, specially focusing on the findings of neoadjuvant and adjuvant regimens, aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent. We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent. Finally, we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

To modulate or to skip: De-escalating PARP inhibitor maintenance therapy in ovarian cancer using adaptive therapy

Toxicity and emerging drug resistance pose important challenges in poly-adenosine ribose polymerase inhibitor (PARPi) maintenance therapy of ovarian cancer. We propose that adaptive therapy, which dynamically reduces treatment based on the tumor dynamics, might alleviate both issues. Utilizing invitro time-lapse microscopy and stepwise model selection, we calibrate and validate a differential equation mathematical model, which we leverage to test different plausible adaptive treatment schedules. Our model indicates that adjusting the dosage, rather than skipping treatments, is more effective at reducing drug use while maintaining efficacy due to a delay in cell kill and a diminishing dose-response relationship. Invivo pilot experiments confirm this conclusion. Although our focus is toxicity mitigation, reducing drug use may also delay resistance. This study enhances our understanding of PARPi treatment scheduling and illustrates the first steps in developing adaptive therapies for new treatment settings. A record of this paper's transparent peer review process is included in the supplemental information.

Periodic colonization of Trichogramma japonicum for bio-control of yellow stem borer (Scirpophaga incertulas) in summer low-land rice (Oryza sativa)

Yellow stem borer [Scirpophaga incertulas (Walker)], is a major pest of low-land rice (Oryza sativa L.), causing 30–40% yield losses. The use of biological control agents to suppress yellow stem borer (YSB) population and damage across Asia includes inundative releases of the egg parasitoid, Trichogramma japonicum Ashmead. However, information on the time and number of parasitoids’ releases are lacking to control YSB in summer low-land rice. Therefore, an experiment was conducted during summer seasons of 2018 and 2019 at ICAR-National Institute of Biotic Stress Management, Raipur, Chhattisgarh to standardize the time and number of T. japonicum releases for effective biocontrol of YSB. Experiment consisted of 3 different treatment schedules, viz. T1, Four releases of T. japonicum at weekly intervals on the 7th, 14th, 21st, 28th days after planting (DAT); T2, Four releases of T. japonicum at weekly intervals on the 14th, 21st, 28th, 35th DAT; T3, Four releases of T. japonicum at weekly intervals on the 21st, 28th, 35th, 42nd DAT; and T4, Control (no release of wasps). Significant reduction of YSB-induced damage symptoms was observed in the treatment schedule (T2) consisting of four releases of T. japonicum (@50,000 wasps/ha/release) at weekly intervals on the 14th, 21st, 28th, 35th DAT of rice which significantly reduced the dead heart (9.1%, 45.83% reduction over control) and the white ear (1.8%, 47.05% reduction over control), as compared to untreated control plots (T4) (16.8% dead heart, 3.4% white ear) in summer 2018. Similarly, in summer 2019, the reduction in dead heart and white ear by the treatment (T2) was 43.35% and 46.15% over control, respectively. The significant reduction of YSB-induced damages corresponded with the increased grain yield in (T2) from 2018–19 i.e. 12.74–20.18% across the seasons. The results suggest that the (T2) augmentative releases provided ecologically viable bio-control of YSB during the summer seasons in low-land rice.

Muscle-invasive bladder cancer in elderly and frail people: Is hypofractionated radiotherapy a feasible approach when no other local options are available?

The study aims to report the feasibility and safety of palliative hypofractionated radiotherapy targeting macroscopic bladder tumors in a monocentric cohort of frail and elderly bladder cancer patients not eligible for curative treatments. Patients who underwent hypofractionated radiotherapy to the gross disease or to the tumor bed after transurethral resection of bladder tumor from 2017 to 2021 at the European Institute of Oncology IRCCS, were retrospectively considered. Schedules of treatment were 30 and 25 Gy in 5 fractions (both every other day, and consecutive days). Treatment response was evaluated with radiological investigation and/or cystoscopy. Toxicity assessment was carried out according to RTOG/EORTC v2.0 criteria. A total of 16 patients were included in the study, of these 11 received hypofractionated radiotherapy on the macroscopic target volume and five on the tumor bed after transurethral resection of bladder tumor. No grade (G) >2 acute toxicities were described after treatment for both groups. Only one patient in the group receiving radiotherapy on the macroscopic disease reported G4 GU late toxicity. Ten patients had available follow-up status (median FU time 18 months), of them six had complete response, one had stable disease, and three had progression of disease. The overall response rate and disease control rate were 60% and 70%, respectively. Our preliminary data demonstrate that palliative hypofractionated radiotherapy for bladder cancer in a frail and elderly population is technically feasible, with an acceptable toxicity profile. These outcomes emphasize the potential of this approach in a non-radical setting and could help to provide more solid indications in this underrepresented setting of patients.

Femoral to abdomen tunneling at the bedside for medium/long term venous access.

Femoral to abdomen tunneling of small-bore central venous catheters is a bedside technique for patients with contraindications to a thoracic approach, or as an alternative to a lower extremity catheter exit site. A femoral to abdomen tunneling technique was implemented for patients receiving medium and long-term intravenous treatments with contraindications to the thoracic venous approach or as an alternative to a lower extremity catheter exit site. All venous access devices were inserted with ultrasound guidance under local anesthesia, and catheter tip placement assessed by post procedural radiography. In this case series, from January 2020 to January 2023, a total of eight FTA-tunneled venous access devices were inserted. There were seven ambulatory patients and one bedbound patient. The median length of the subcutaneous tunnel was 20 cm, ranging from 15 to 27 cm. The median length of the intravenous catheter to the terminal tip was 31 cm, ranging from 23 to 40 cm. Tip location was confirmed by post-procedural abdominal radiograph. The catheter tip locations were interpreted to be at the level of T8-T9 (2), T12 (1), L4 (2), L2 (2), L1(1).No insertion or post insertion related complication was reported. Six patients completed the scheduled intravenous treatment. One patient was unable to be tracked due to transfer to an outside facility. One catheter initially demonstrated to be coiled over the left common iliac vessel was repositioned using a high flow flush technique. There was one reported catheter dislodgment by the nurse providing care and maintenance. The overall implant days were 961, with a median dwell time of 125 days ranging from 20 to 399 days. Femoral to abdomen tunneling provides an alternative exit site useful in select patients with complex intravenous access. The data of this small retrospective review suggests this a safe and minimally invasive bedside procedure.

Machine-learning and mechanistic modeling of metastatic breast cancer after neoadjuvant treatment.

Clinical trials involving systemic neoadjuvant treatments in breast cancer aim to shrink tumors before surgery while simultaneously allowing for controlled evaluation of biomarkers, toxicity, and suppression of distant (occult) metastatic disease. Yet neoadjuvant clinical trials are rarely preceded by preclinical testing involving neoadjuvant treatment, surgery, and post-surgery monitoring of the disease. Here we used a mouse model of spontaneous metastasis occurring after surgical removal of orthotopically implanted primary tumors to develop a predictive mathematical model of neoadjuvant treatment response to sunitinib, a receptor tyrosine kinase inhibitor (RTKI). Treatment outcomes were used to validate a novel mathematical kinetics-pharmacodynamics model predictive of perioperative disease progression. Longitudinal measurements of presurgical primary tumor size and postsurgical metastatic burden were compiled using 128 mice receiving variable neoadjuvant treatment doses and schedules (released publicly at https://zenodo.org/records/10607753). A non-linear mixed-effects modeling approach quantified inter-animal variabilities in metastatic dynamics and survival, and machine-learning algorithms were applied to investigate the significance of several biomarkers at resection as predictors of individual kinetics. Biomarkers included circulating tumor- and immune-based cells (circulating tumor cells and myeloid-derived suppressor cells) as well as immunohistochemical tumor proteins (CD31 and Ki67). Our computational simulations show that neoadjuvant RTKI treatment inhibits primary tumor growth but has little efficacy in preventing (micro)-metastatic disease progression after surgery and treatment cessation. Machine learning algorithms that included support vector machines, random forests, and artificial neural networks, confirmed a lack of definitive biomarkers, which shows the value of preclinical modeling studies to identify potential failures that should be avoided clinically.

Influence of cooling rate during the heat treatment process on the precipitates and ductility behavior of inconel 718 superalloy fabricated by selective laser melting

IN718 superalloy by elective laser melting (SLM) has shown great application prospects in the aerospace engine key parts. Different phases are precipitated during the SLM forming process. Although the Laves phase could be dissolved in dendrites by heat treatment, the specific evolution of the second phase particles is still unclear. In this work, the influences of solution and aging heat treatment, as well as cooling rate on the precipitates and ductility behavior of IN718 superalloy fabricated by SLM were systematically investigated. The medium temperature (980 °C) solution treatment regimes included three different colling rates and the control group only underwent aging treatment were studied. The results indicated that high temperature solid solution treatment effectively improved compositional segregation and significantly enhanced homogeneity of microstructure. The reduce of cooling rate at 980 °C was beneficial to the extension time and increased the number of δ phase precipitation. An appropriate number of δ phase improves the notch sensitivity and nails grain boundaries. In addition, the complex dislocations and second phase particles retards the migration of slip dislocations during ductility deformation process, which enhances the strength of SLM-ed IN718. The yield strength of specimens increases from 680 MPa to 1205 MPa. The microhardness is greatly improved as compared with as-deposited IN718, and the highest microhardness reaches 485 HV. The results provide a technical support and reference for formulating the heat treatment schedule of IN718 prepared by SLM.

Abstract PO1-22-04: Cosmetic results of the breast in patients treated with Five Fraction Accelerated Partial Breast Irradiation for early stage breast cancer: retrospective review comparing Daily versus Every Other Day Treatment

Abstract Introduction: Breast cosmesis results using Accelerated Partial Breast Irradiation (APBI) with IMRT external beam in 5 fractions (6Gy x 5 fractions) has been reported as good to excellent in the literature. This retrospective review compares breast cosmesis in patients treated with Daily versus Every Other Day APBI in the community practice setting. Methods: The patient electronic medical records (EMR) were used to identify APBI patients treated at the community cancer center with the 6Gy x 5 fraction regimen. Harvard breast cosmesis four point scale results (poor, fair, good, excellent results) were extracted for each treated APBI patient from clinical notes in the EMR to rate breast cosmesis. For many patients in this review, provider reporting of cosmesis in the EMR overlapped good and excellent categories and so a “good to excellent” score was assigned. Therefore, a three point scale was utilized in statistical analysis (poor-1, fair-2, good to excellent-3). Results: There were 62 patients treated with APBI at a single institution with greater than 6 months follow up (18 patients treated daily and 44 patients treated every other day). Median follow up was 12 months (range 6- 32 months). Of all patients treated there were 0 with poor cosmesis, 3 with fair (1 every other day treatment, 2 every day treatment), 59 with good to excellent cosmesis. Univariate logistical regression analysis revealed no significant difference between daily and every other day treatment (p=0.457) Conclusion: With careful patient selection, quality planning and treatment delivery, good to excellent cosmesis is achievable in the great majority of patients undergoing breast APBI (6Gy x 5 fractions) using IMRT in the community radiation oncology clinic with either daily or every other day treatment. More study is needed, but in this review cosmetic differences seem to be minimal between daily and every other day treatment schedules. Citation Format: Alex Goss, Ellaine Haroz, Anna Voltura, Jennifer McGrath, Olivia Sloan, Matthew Jackson, Savvas Morris, Bryan Goss. Cosmetic results of the breast in patients treated with Five Fraction Accelerated Partial Breast Irradiation for early stage breast cancer: retrospective review comparing Daily versus Every Other Day Treatment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-22-04.

Abstract PO1-07-05: Preliminary Evaluation in Breast Cancer of PointCheck: a Noninvasive AI-Based Neutropenia Monitoring Device

Abstract Background Febrile neutropenia (FN) is a common complication that can arise in breast cancer patients receiving myelosuppressive chemotherapy and increases the risk of fatal infections. Despite better preventive strategies there are between 140,000 to 200,000 FN-related hospitalizations yearly. Quick detection and awareness of grade III neutropenia (Absolute Neutrophil Count [ANC] < 1,000/µL) or greater can be critical to managing FN and treatment scheduling and dosing in patients with breast cancer. The current gold standard for neutropenia detection is a peripheral blood collection that requires patients to come into the clinic. PointCheck™ is a novel, noninvasive technology that can monitor for grade III neutropenia or greater and enable prompt detection in the home by acquiring microscopy videos of superficial capillaries through the nailfold skin and analyzing those videos with computer vision AI algorithms. To evaluate the usability, diagnostic performance, and preliminary clinical utility of PointCheck™ on FN detection we conducted a multi-center observational usability and diagnostic study. Methods The present study included an overall cohort of 175 diverse cancer patients, with 70 breast cancer patients. The primary endpoint was to achieve a score over 80.8 on a standardized System Usability Scale (SUS). Secondary endpoint was achievement of diagnostic performance with an area under the curve (AUC) above 0.80. We also performed an exploratory analysis on the device's clinical utility. Eligible participants were introduced to the device, watched a tutorial video and were given a user manual. They used the device autonomously under the supervision of the clinical team. Usability data was collected using the SUS, the scoring system that has a scale between 0-100. PointCheck™ measurements were analyzed using AI algorithms and compared to same-day Complete Blood Counts (CBCs) collected within 90 minutes of the measurement to assess accuracy in classifying patients as grade III neutropenic or greater (< 1,000/µL), or non-grade III neutropenic (≥1,000/µL). In the exploratory clinical utility analysis, clinicians provided narrative insights by completing a Likert survey assessing how PointCheck™ would support or impact their clinical decisions. Results 81.4% of breast cancer patients scored above 80.8 on the SUS scale across all sites, with a mean SUS score of 87.7 (SD=13.2). Furthermore, the AI-based PointCheck™ classifier accurately discriminated neutropenia patients with an AUC = 0.90 in the overall cohort. In the exploratory analysis, a majority of clinicians (65.2%) agreed that the device could have helped better evaluate their patients (Table 1). Whereas almost 3 out of 4 clinicians (72.4%), described that the use of PointCheck™ could have avoided preparing a chemotherapy infusion if the patient was not ready due to grade III neutropenia or greater. Conclusions The present study showed that there is a high perception of usability of PointCheck™, indicating an above average user experience and falling within the top 10% of systems. Furthermore, we found that PointCheck™ can accurately detect grade III neutropenia or greater in a large cohort of patients including breast cancer patients. Application of PointCheck™ to clinical practice as a monitoring system can contribute to the early detection of FN and antineoplastic therapy management. Table 1: Clinical Utility Survey Results Citation Format: Juan Garcia-Mosquera, Manuel Alva, Toshiaki Iwase, Ganimete Lamaj, Pablo Tolosa, Rodrigo Sánchez-Bayona, José Pelaez-Escobar, Alberto Pablo-Trinidad, Ryan Benasutti, Aurélien Bourquard, Ian Butterworth, Alvaro Sánchez-Ferro, Carlos Castro-González, José Manuel Pérez-García, Alejandro Martínez-Bueno, Eva Ciruelos, Azadeh Nasrazadani. Preliminary Evaluation in Breast Cancer of PointCheck: a Noninvasive AI-Based Neutropenia Monitoring Device [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-07-05.

Abstract PO1-03-02: Impact of Body Mass Index (BMI) on the efficacy of different adjuvant chemotherapy schedules in patients with breast cancer: analysis from the randomized phase III GIM2 trial

Abstract Background: The long-term results of the Italian randomized phase III GIM2 study showed that, in women with node-positive breast cancer (BC), dose-dense (DD) chemotherapy significantly improved both disease-free survival (DFS) and overall survival (OS) compared with standard-interval (SI) chemotherapy. Obesity has been identified as an independent poor prognostic factor in patients with BC, with a potential negative impact on the efficacy and toxicity of systemic therapies. Nevertheless, the specific influence of body mass index (BMI) on the efficacy of different adjuvant chemotherapy schedules (DD or SI) remains a subject of debate. This analysis aimed to investigate this hypothesis in patients enrolled in the GIM2 trial. Methods: GIM2 was a randomized multicentric phase III trial that compared different chemotherapy schedule (DD vs SI) and regimen (FEC-P vs EC-P) in 2091 node-positive early breast cancer patients. BMI (kg/m2) was categorized as follows: < 18.5 (underweight), 18.5 to < 25 (lean), 25 to < 30 (overweight), and ≥ 30 (obese). The primary endpoint was to assess association between BMI and DFS and OS. Survival estimates were compared using the Kaplan-Meier method and log-rank test. Univariate and multivariable Cox proportional hazard models, adjusted for relevant prognostic factors, were used. Results: A total of 1925 patients were included in the present analysis, of whom 31.6% (n=632) were overweight and 19.3% (n=386) obese. Median age was 52 years. Overweight-obesity condition was significantly associated with postmenopausal status, greater representation of T2-T4 tumors with N > 2 in both patients in the DD and SI arm. After a median follow-up of 15.0 years (IQR 8.4-16.3), compared to patients with normal BMI, those who were overweight or obese at diagnosis had a higher risk of experiencing a DFS event (Hazard Ratio [HR] 1.11 95% CI 0.94-1.31 and HR 1.37 95%CI 1.14-1.65, respectively, p=0.003) and OS event (HR 1.11 95% CI 0.89-1.38 and HR 1.59 95%CI 1.26-2.01, respectively, p=0.0003). No significant interaction was found between BMI and treatment schedule in terms of DFS (p for interaction=0.56) nor OS (p for interaction=0.19). At the multivariate analysis, in the DD arm, adjusted HR (aHR) for DFS and for OS were 1.01 (95% CI 0.75- 1.35) and 1.04 (95% CI 0.72-1.52) for obese vs. normal BMI groups, and 0.88 (95% CI 0.68- 1.15) and 0.77 (95%CI 0.54-1.10) for overweight vs. normal BMI groups, respectively. In the SI arm, aHRs for DFS and OS were 1.24 (95% CI 0.94- 1.63) and 1.35 (95%CI 0.96- 1.90) for obese vs. normal BMI groups, and 1.04 (95%CI 0.82- 1.33) and 1.01 (95% CI 0.74-1.40) for overweight vs. normal BMI groups, respectively. Similar results were observed when considering hormone receptor-positive and negative BC separately. Conclusion: In the GIM2 trial, BMI was prognostic but not predictive of different benefit to adjuvant chemotherapy. In high-risk patients, DD schedule should be considered the preferred schedule irrespective of BMI. Citation Format: Francesca Poggio, Eva Blondeaux, Marco Tagliamento, Marta Perachino, Simone Nardin, Benedetta Conte, Sabino De Placido, Mario Giuliano, Valeria Forestieri, Michelino De Laurentiis, Adriano Gravina, Giancarlo Bisagni, Anita Rimanti, Anna Turletti, Cecilia Nisticò, Angela Vaccaro, Francesco Cognetti, Alessandra Fabi, Simona Gasparro, Ornella Garrone, Ylenia Urracci, Maria Grazia Alicicco, Mauro Mansutti, Paola Poletti, Pierpaolo Correale, Claudia Bighin, Fabio Puglisi, Filippo Montemurro, Giuseppe Colantuoni, Luca Boni, Matteo Lambertini, Lucia Del Mastro. Impact of Body Mass Index (BMI) on the efficacy of different adjuvant chemotherapy schedules in patients with breast cancer: analysis from the randomized phase III GIM2 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-03-02.

Abstract PO3-05-12: Randomized Phase 2 of Bria-IMT, an Allogenic Human Cell Line with Antigen Presenting Activity, in Heavily Pretreated Metastatic Breast Cancer

Abstract Introduction Despite progress in MBC, too many continue to succumb due to treatment resistance or intolerance. SV-BR-1-GM is an allogenic human breast cancer cell line with antigen presenting cell activity designed to overcome the immune-suppressive tumor microenvironment while being acceptable to extensively pretreated contemporary MBC patients. We report interim exploratory analysis of the ongoing RCT of the Bria-IMT regimens. Methods An interim exploratory analysis using preliminary partially available evaluable data of the ongoing prospective, randomized phase 2 (NCT03328026; 2018-present) of Bria-IMT (irradiated SV-BR-1-GM) with a PD-1check point inhibitor (CPI) every 3 weeks (25 patients dosed to date). Both regimens include cyclophosphamide 300 mg/m2 48-72 hours prior to intradermal Bria-IMT (~20 x 106 cells) followed by interferon-alpha at the inoculation sites 2 days later. The control arm used the original sequence with simultaneous start of Bria-IMT and CPI in cycle 1. The experimental arm started CPI in cycle 2 after the 2nd inoculation. Candida skin test was performed before cycle 1 to determine anergy status while delayed-type hypersensitivity skin test (DTH), defined as >5mm erythema & induration, was done at every cycle by intradermal injection of a small test dose of Bria-IMT prior to full dose inoculation. Results Median age: 58 (range 37-81); median prior therapies: 8 lines (range 4-18); 89% were grade 2/3 (n=18); 68% hormone receptor positive; 61% HER2 negative, 33% HER2 low, and 6% HER2 high; 33% triple negative. Overall, 53% of subjects had a clinical benefit as best response by BICR, PI or target lesion measurement. The two treatment arms were similar with a trend showing longer median durations on therapy (mDOT) of 3.7 mo in the experimental delayed CPI arm compared with mDOT = 2.9 for original sequence control arm. 47% of patients were anergic to candida. Among all anergic subjects, the mDOT was 3.5 compared to 2.5 mo for non-anergic patients. However, among anergic subjects, the alternative treatment arm had a lower risk of treatment discontinuation (improved HR) with mDOT of 3.7 compared to the 3.3 mo mDOT of the original treatment. 50% of anergic subjects eventually developed DTH to SV-BR-1-GM. mDOT was 4.0 mo for DTH+ pts vs 3.0 mo for those who did not mount DTH. Median OS was not yet reached; mean OS was higher in non-anergic vs anergic pts. Among those who developed an inoculation site reaction to Bria-IMT, OS was greater than for those who did not. Time on the Bria-IMT regimen exceeded the time on penultimate treatment in 22% of subjects while 33% of subjects with prior CPI use exceeded last therapy. AEs were mild with 28% of subjects (n=7) having > grade 3 events. The most common grade 3+ AE was lipase increase (n=3). One subject with encouraging changes in peripheral blood tumor markers and CTCs completed a PET study using Zr-89 crefmirlimab berdoxam, a zirconium-89 labelled truncated antibody specific to human CD8α (CD8 Immuno-PET) and demonstrated increased uptake in some metastatic lesions and draining lymph nodes. Updated results will be provided at the meeting. Conclusion Sequencing of CPI with Bria-IMT is associated with differential clinical outcome trends but not statistically significant in this interim preliminary exploratory analysis regardless of prior CPI use. Bria-IMT is immunogenic with clinical benefit demonstrated for both treatment schedules among patients with inducible DTH reactions. Patients who develop an immune response to Bria-IMT had an increase in OS compared to those who did not. The nodal localization of CD8+ cells on PET may indicate a systemic activation of CD8 positive lymphoid cells. It also provides support that the Bria-IMT + CPI combination immune-based therapy can result in an increase of CD8+ tumor infiltrating lymphocytes in breast cancer metastatic sites. These preliminary results will be evaluated in the ongoing randomized phase 3 pivotal registrational trial. Citation Format: Carmen Calfa, Chaitali Nangia, Minal Barve, John Knecht, Jarrod Holmes, Kendrith Roland, Ralph Boccia, Frances Valdes-Albini, Zach Gostout, Mingjin Chang, William Williams, Charles Wiseman, Bonnie Guerin, Shaker Dakhil, Giuseppe Del Priore, Saranya Chumsri. Randomized Phase 2 of Bria-IMT, an Allogenic Human Cell Line with Antigen Presenting Activity, in Heavily Pretreated Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-12.

Simple predictors for the completion of scheduled gemcitabine‑cisplatin regimens based on real‑world urothelial cancer data.

Gemcitabine plus cisplatin (GC) is the standard first line of chemotherapy for urothelial carcinoma. However, it is often difficult to complete scheduled GC therapy because of real-world adverse events. Therefore, the reasons behind delays, scheduled cancelations and determined predictive factors for completing scheduled GC therapy were retrospectively analyzed. Patients diagnosed with locally advanced or metastatic urothelial carcinoma from 2009 to 2020 received a 4-week GC therapy schedule in Oita University Hospital. Information was retrospectively extracted from medical records and all cycles were divided into two groups: One wherein all treatments were administered and completed on schedule and the other wherein treatment was either delayed or canceled in during the treatment schedule. Predictive factors were then statistically extracted between the two groups. In total, 70 patients received 201 cycles of a 4-week scheduled GC therapy. Of the 201 cycles, a total of 68 (33.8%) completed all scheduled treatments, while 133 (66.1%) did not complete the treatment as scheduled. In the group where administration was not completed on schedule, the factors of male, ureteral cancer, lower stage, <90% of gemcitabine and cisplatin dosage, solitary kidney, high creatinine level, low estimated glomerular filtration rate level, low platelet count and high alkaline phosphatase level at the initiation of each cycle were more significant. Additionally, the lowest anticancer drug percentage administration was on day 15. From these results, predictive factors for patients with various backgrounds who completed the scheduled 4-week GC therapy based on real-world data were identified. This information can be useful for clinical physicians when deciding the course of treatment.

SINGLE-PILL, TRIPLE ANTIHYPERTENSIVE THERAPY IN RURAL SUB-SAHARAN AFRICA: PRELIMINARY EXPERIENCE

Objective: Arterial hypertension is worldwide the leading modifiable cardiovascular risk factor. Beside life-style changes, strong evidence supports the efficacy of pharmacological treatment in reducing the complications of hypertension. International guidelines have recommended single-pill, low-dose combinations as initial treatment strategy. We investigated whether management of hypertension through this approach is feasible and effective in a rural sub-Saharan Africa setting. Design and method: Diagnosis of hypertension was established over three sets of blood pressure measurements: during a community-based, house-to-house screening in 2020 and in 2022, and at the hypertension outpatient clinic. Blood pressure measurements were performed according to the ESH recommendations by trained personnel, using a validated, oscillometric device OMRON M7 IT-HEM-7322-E. In 98 individuals diagnosed to have arterial hypertension, once-daily, single-pill combination of olmesartan, amlodipine, and hydrochlorothiazide was prescribed at a dose suitable to their blood pressure values and clinical characteristics. They were instructed on its administration and potential side effects and encouraged towards lifestyle modifications. Treatment regimen was adjusted, if needed, at each outpatient clinic visit scheduled after 4, 8, 12, and 16 weeks Results: 79 patients (aged 61 [53-70] years; median and interquartile range) strictly adhered to the treatment schedule, while overall 19 individuals dropped-out (aged 70 [65-80] years) because of different reasons. About 20% were tobacco smokers and nearly all consumed alcohol. Blood pressure was &lt;140/90 mm Hg after 4 weeks in 44 (56%), after 8 weeks in 62 (78%), after 12 weeks in 69 (87%), and after 16 weeks in 74 (94%) participants. Excellent tolerance was widely reported. Conclusions: Management of hypertension with once-daily, single-pill combination of olmesartan, amlodipine, and hydrochlorothiazide as initial treatment was feasible and effective also in a rural sub-Saharan setting, with very high rate of hypertension control in patients adherent to treatment. Our results provide real life evidence in favor of extensive implementation of single-pill combination therapy also in low- and middle-income countries where local Health Care Systems should include recommendation on their usage in national guidelines and should make them available also in rural and remote areas at low or no cost as reliable first-line treatment strategy