Oncologic Evaluation Research Articles

Long term survival and outcomes in patients with paraneoplastic neurologic syndromes.

It is unknown whether delay in diagnosis affects morbidity reportedly in paraneoplastic syndromes (PNS). We aimed to explore various aspects of PNS, including prevalence, clinical characteristics, diagnostic criteria, and treatment outcomes. We studied n-PNS diagnosis between 2016 to 2023, and included only patients with positive onconeural antibodies, who developed cancer, and exhibited a recognizable PNS phenotype. We identified 12 patients with positive Abs and co-occurring cancer, most prevalent PNS antibodies included anti-GAD65, anti-Recoverin and anti-Yo. The most common phenotypes were limbic encephalitis (n=5, 42%) and encephalomyelitis (n=4,33%). Cancer preceded neurological presentation in 6 cases. Among the 6 patients who initially presented with n-PNS, median time from neurological presentation to oncologic diagnosis was 73 days, as five of them (83%) were diagnosed with cancer during oncological evaluation prompted by the PNS diagnosis or suspicion. Lymphoma was the most frequent cancer (n=3, 25%), followed by lung cancer (n=2, 17%), and ovarian cancer (n=2, 17%). Among patients who received immunotherapy as n-PNS treatment (n=9, 75%), steroids were a part of the management at 78% (n=7). Another immunotherapy used included plasmapheresis (n=5, 55%) and steroid sparing immunosuppressant (n=2, 29%). Four (33%) patients had short term therapeutic benefit with improvement or stabilization at mRS ≤ 4. Median Disability-adjusted life years (DALYs), as disease burden value, was 13 years. Death occurred in 9 of the 12 patients, with most cases deaths attributed to cancer progression. Compering to the expected median survival by type and stage of tumor, from 9 deceased patients, 56% (n=5) died younger than expected. Median survival was 410 days (range 29-2738 days), and 152 days since the appearance of n-PNS (range 8-1434 days). There were no differences in survival between patients who initially presented with n-PNS versus cancer (p=0.39). In up to 8 years of follow up, there was no difference in mortality among patients who presented initially n-PNS. There was a significant decline in the quality of life, most face substantial disability and functional impairment long term.

Évaluation de la réponse thérapeutique en imagerie morphologique des tumeurs solides (RECIST) : historique, application et adaptation des critères aux thérapies innovantes

The evaluation of therapeutic response in morphological imaging of solid tumors is based primarily on the RECIST criteria (Response Evaluation Criteria in Solid Tumours) established in 2000 and revised in 2009 to version RECIST 1.1. These criteria enable the efficacy of anti-cancer treatments to be analyzed on the basis of the measurement of tumor lesions by computed tomography (CT) or magnetic resonance imaging (MRI). The choice of target and non-target lesions is crucial for establishing a baseline examination prior to treatment, in order to monitor disease progression. Results are classified into 4 categories: partial response, complete response, stable disease and progressive disease. With the emergence of immunotherapy, adaptations to the criteria were necessary, leading to the creation of iRECIST in 2017, which takes into account the phenomenon of pseudoprogression. In addition, other limitations of the RECIST 1.1 criteria have been identified, notably their inability to assess functional changes in tumors, leading to the development of alternative criteria such as mRECIST and CHOI for specific types of cancer. These developments underline the importance of accurate and appropriate treatment evaluation in oncology.

Abstract B006: Qualitative research study on the use of minimal residual disease as an intermediate endpoint in multiple myeloma clinical trials in Saudi Arabia

Abstract Introduction: The U.S. Food and Drug Administration has recently considered minimal residual disease (MRD) as an acceptable accelerated approval endpoint in multiple myeloma (MM). Meta-analysis studies have shown the clinical benefit of MRD negativity in certain hematological cancers such as MM. Objectives: This qualitative research study, with a unique focus on the Saudi context, aims to assess the opinions and experiences of hematology and oncology specialists and consultants in Saudi Arabia. The study is particularly interested in their views on the use of MRD as an intermediate endpoint in early-phase clinical trials for fast-track drug approval by the Saudi Food and Drug Authority in the context of multiple myeloma. This includes assessing the use of MRD in both newly diagnosed and relapsed/refractory MM. The secondary objective is to gather information about the feasibility and availability of sensitive MRD detection methods in real-world medical practice and clinical trials in Saudi Arabia. Study Design: The study will involve interviewing 30 registered male or female physicians specialized in hematology and oncology in Saudi Arabia. The physicians will be included in the study using purposive sampling methods. The study will collect the physicians’ opinions and experiences about MRD. The interviews will be conducted through a single focus group and several face-to- face interviews or performed online, using ZOOM. Participants should have more than one year of experience post-residency or post-fellowship training. The predetermined set of semi- structured questions will cover topics such as the definition of MRD, its clinical and research significance, MRD detection thresholds, duration of MRD negativity, and its correlation with other clinical endpoints, such as progression-free survival and overall survival. The interviews will be conducted by scientific oncology and hematology evaluation experts at the Saudi Food and Drug Authority, who play a crucial role in this study. The study will consist of 5–10 semi- structured one-to-one interviews and focused group discussions of as few as four participants. Before starting any interview, participants will complete consent forms, including the study’s goals and who will conduct the study. Qualitative data will be prepared and analyzed by an expert in data analysis, ensuring the highest research standards. The results will be presented using descriptive and interpretive methods. Citation Format: Albandari A Alnasser, Tariq H Alqurayshah. Qualitative research study on the use of minimal residual disease as an intermediate endpoint in multiple myeloma clinical trials in Saudi Arabia [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B006.

Abstract B007: A qualitative research study on hematology and oncology consultants’ experiences and opinions on using minimal residual disease (MRD) as a fast-track approval endpoint in early-phase clinical trials in multiple myeloma in Saudi Arabia

Abstract Introduction: The U.S. Food and Drug Administration recently considered the minimal residual disease (MRD) as an acceptable accelerated approval endpoint in multiple myeloma (MM). The data from the meta-analysis studies established the clinical benefit of MRD negativity in certain hematological cancers such as MM. Objectives: The primary objective of this qualitative research study is to assess hematology and oncology consultants’ opinions and experiences on the adequacy of using minimal residual disease (MRD) as an intermediate endpoint in early- phase clinical trials in multiple myeloma (MM) for fast-track approval of drugs and biological products in the Saudi Food and Drug Authority. That may include using MRD in MM in both settings: newly diagnosed and relapsed/refractory MM. The secondary objective is to gather information about the feasibility and availability of sensitive methods for detecting MRD in the context of real-world medical practice and clinical trials in Saudi Arabia. Study Design: The study design is a qualitative approach to interviewing 30 registered male, or female physicians specialized in hematology and oncology in Saudi Arabia. The interviews will be conducted in two ways: a single focus group and several face-to-face interviews. The participants should have more than 1 year of experience post-fellowship training. The participants will be invited for an interview via email or phone. A predetermined set of semi-structured questions is to be asked in the same order to each participant. The topic of questions will include the definition of MRD, clinical and research significance of MRD, MRD detection thresholds (e.g., 10^-5 vs. 10^-6), duration of MRD negativity at the complete response, correlation with other clinical endpoints such as progression-free survival (PFS) and overall survival (OS). The interviews will be conducted by scientific oncology and hematology evaluation experts at the Saudi Food and Drug Authority who have considerable experience in engaging in personal discussion. This qualitative study has about 5–10 semi-structured one-to-one interviews of hematology and oncology consultants performed at a convenient time for each doctor. Moreover, the discussions in focus groups can be as small as four participants. Qualitative data will be prepared and analyzed by an expert in data analysis. Citation Format: Tariq Hassan Alqurayshah, Albandari Alnasser, Tariq Alqurayshah. A qualitative research study on hematology and oncology consultants’ experiences and opinions on using minimal residual disease (MRD) as a fast-track approval endpoint in early-phase clinical trials in multiple myeloma in Saudi Arabia [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B007.

Cardiotoxicity following thoracic radiotherapy for lung cancer.

Radiotherapy is the standard of care treatment for unresectable NSCLC, combined with concurrent chemotherapy and adjuvant immunotherapy. Despite technological advances in radiotherapy planning and delivery, the risk of damage to surrounding thoracic tissues remains high. Cardiac problems, including arrhythmia, heart failure and ischaemic events, occur in 20% of patients with lung cancer who undergo radiotherapy. As survival rates improve incrementally for this cohort, minimising the cardiovascular morbidity of RT is increasingly important. Problematically, the reporting of cardiac endpoints has been poor in thoracic radiotherapy clinical trials, and retrospective studies have been limited by the lack of standardisation of nomenclature and endpoints. How baseline cardiovascular profile and cardiac substructure radiation dose distribution impact the risk of cardiotoxicity is incompletely understood. As Thoracic Oncology departments seek to expand the indications for radiotherapy, and as the patient cohort becomes older and more comorbid, there is a pressing need for cardiotoxicity to be comprehensively characterised with sophisticated oncology, physics and cardio-oncology evaluations. This review synthesises the evidence base for cardiotoxicity in conventional radiotherapy, focusing on lung cancer, including current data, unmet clinical needs, and future scientific directions.

PDOC-09 EVALUATION OF HEALTH SERVICE DELAYS FOR CHILDREN WITH CENTRAL NERVOUS SYSTEM TUMORS AT BUGANDO REFERRAL HOSPITAL MWANZA, TANZANIA

Abstract OBJECTIVE Rapid diagnosis and treatment initiation is crucial for children with central nervous system tumors (CNS). Despite advancement in diagnostic modalities, health service delays persist in many LMICs. The current study evaluates the diagnostic and treatment delays experienced by children presenting to a zonal referral hospital in Mwanza Tanzania, with the goal of identifying breakpoints that can be addressed to improve quality of care through a multidisciplinary approach. METHODS All children age <18yrs with a diagnosis of a CNS tumor from 2020-2023 were included in the analysis. Data was extracted from hospital electronic medical system and clinical files and included demographics, diagnosis, and dates at first presentation to the hospital, diagnosis, surgical intervention, oncology presentation and treatment initiation. Treatment initiation included either surgical resection, chemotherapy or radiotherapy. RESULTS A total of 50 patients were included in the evaluation, with average age of 6.4yrs and equal M: F representation. Most of the cases (80%, n=40) were primary CNS tumors, with 20% metastatic disease. Low grade Glioma (LGG) and high-grade Glioma (HGG) tumors were similarly distributed (n=19, n=21). Among those who had a tumor resection, 56% (n=18) were completed before initial oncology evaluation. Delays were frequently experienced, with the average time from presentation to neurosurgery evaluation of 166 days, time to diagnosis of 121 days, time to oncology evaluation of 139 days, and time to treatment initiation of 127 days. 1yr overall survival for LGG was 67% (n=12/18) and 36% (n=8/22) for HGG, with a treatment abandonment rate of 38% overall (n=19/50). CONCLUSIONS There is significant delay in accessing services for patients presenting with CNS tumors. A multidisciplinary approach and social support of children with CNS tumor is necessary to facilitate early diagnosis and timely treatment to improve quality of care and leads to a higher survival rate.

Application of cell-free DNA fungal polymerase chain reaction for invasive fungal disease evaluation in pediatric oncology and stem cell transplant patients.

Molecular diagnostics may enable early, noninvasive detection of invasive fungal disease (IFD) in immunocompromised patients. Cell-free deoxyribonucleic acid (cfDNA) fungal polymerase chain reaction (PCR) assays were recently incorporated into institutional prolonged febrile neutropenia pathways. We aimed to evaluate the performance of plasma cfDNA PCR panels (mold and Candida panels) in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients with clinical concern for IFD. This single-center, observational study assessed plasma cfDNA fungal PCR performance for noninvasive IFD detection in hospitalized pediatric oncology and HSCT patients. The primary outcome was IFD diagnosis per published consensus definitions within 1month. Positive and negative agreement between plasma cfDNA fungal PCR and consensus definitions were calculated. We also described test turnaround time and patient survival. From October 2021 to 2022, 54 patients underwent 60 evaluations with 11 proven/probable IFD cases. Comparing plasma cfDNA fungal PCRs to consensus definitions for proven/probable IFD, there was 73% positive agreement and 96% negative agreement. Two proven/probable cases with negative PCRs were caused by organisms not included on either panel. Median time to cfDNA fungal PCR result was 35hours (interquartile range: 19-69) in eight proven/probable cases detected by cfDNA fungal PCR. There were 17 deaths among 54 patients, and IFD contributed to 45% of deaths in patients with proven/probable IFD. Plasma cfDNA fungal PCRs detected relevant molds or yeast in most cases classified as proven/probable IFD. However, this targeted approach missed some cases. More studies are required to determine optimal utilization of molecular diagnostics in pediatric patients.

Multi-Institutional Study of Referral Patterns for Gynecologic Oncology Consultation.

Evaluation by a gynecologic oncologist (GO) is associated with improved clinical outcomes for patients with gynecologic cancers, yet little is known about health care factors that influence patients' referrals to GO. Medical records of 50 consecutive new patients seen in GO clinics at each of six referral centers across the United States were reviewed. Patient and disease characteristics were collected along with referral indication, evaluation and referral dates, diagnostic procedures, provider specialties, and zone improvement plan (ZIP) code of up to three referring providers per patient. The primary outcome was interval between first evaluation and referral. Univariate associations were evaluated with Chi-square and Wilcoxon rank-sum tests and multivariable associations with negative binomial regression models. Secondary outcome was prolonged time to GO referral, defined as greater than the 75th percentile. Logistic regression was used for multivariable modeling. Three hundred patient records were analyzed. The median time from first health care encounter to referral was 15 days (IQR, 5-43). The mean distance from residence to GO was 39.8 miles (standard deviation, 53.8). Seventy-one percent of GO referrals were initiated by obstetrician-gynecologists, 9% by family physicians, and 6% internists. Presentation-to-referral interval was 76% shorter for patients evaluated by an emergency medicine clinician (exp(Beta), 0.24; 95% CI, 0.11 to 0.53; P < .001). Public insurance was associated with 1.47 times longer time to referral compared with private insurance (exp(Beta), 1.47; 95% CI, 1.05 to 2.04; P = .001). Residents of nonmetropolitan ZIP codes were less likely to have prolonged time to referral (odds ratio [OR], 0.288; P = .017). Distance from residence to GO (per 10 miles) increased the likelihood of prolonged time to referral (OR, 1.10; P = .010). Interventions are needed to improve recognition and referral of patients for gynecologic oncology evaluation. Community outreach and engagement with obstetrician-gynecologists should be prioritized to improve times to referral.

Validation, adaptation and application of a multi‐criteria decision analysis‐based framework for chemotherapeutic agents in Egypt

AbstractHealth technology assessment is a systematic, transparent, robust, and unbiased assessment of healthcare technology that links evidence and decisions. Healthcare decisions usually require trading‐off, and using a structured approach, such as multi‐criteria decision analysis (MCDA), could improve decision quality. This study aimed to adapt an MCDA‐based framework for oncological drug evaluation in an Egyptian clinical setting to explore the perspectives of different stakeholders. The 10th edition of the Evidence and Value: Impact on decision making framework was translated, validated, adapted, and applied to explore key differences between the priorities of different stakeholders for coverage decisions in the oncology field in Egypt. A direct rating scale or hierarchical point allocation was used to elicit criteria weights. Normalized weights were calculated and compared using the preset cut‐off value of 0.008. Understandability, willingness to use the adopted weighting techniques, and cognitive burden were assessed and compared. Ninety participants completed the criteria‐weighting interview for the adapted tool. The elicited criteria weights differed between the two adopted weighting techniques when comparing stakeholders' priorities using the preset cut‐off (0.008). However, there was no significant difference in the weighting technique understandability, future use willingness, and cognitive burden parameters on categorization by either the weighting technique or stakeholder group. This study provides a specially tailored, straightforward procedure for Egyptian stakeholders to evaluate oncologic drugs in a standardized manner by combining various inputs. It also highlights the main variations across Egyptian stakeholder preferences.

Aberrant origin of the left vertebral artery: clinical case and scientific literature

The variants in the origin of the trunks of the aortic arch are very heterogeneous. Among them, it is worth highlighting the variants that involve the origin of the vertebral artery and more specifically the left vertebral artery. We present the case of a 62-year-old patient in whom an aberrant vertebral artery was incidentally described in a computed tomography for oncological evaluation. This anatomical variant is asymptomatic in up to 5% of cases and can give rise to clinical problems of a vascular nature.

Swept-source optical coherence tomography angiography findings in a case of primary vitreoretinal lymphoma over a three-year follow-up

BackgroundVitreoretinal lymphoma (VRL) still represents a diagnostic challenge for retinal specialists. Early diagnosis and treatment are critical for a better prognosis. Several diagnostic tools have proven helpful in the identification of VRL abnormalities. However, swept-source OCT angiography (SS-OCT-A) findings and their long-term follow-up are yet to be explored.Case presentationa 42-year-old man presented with blurred vision in his left eye for 2 weeks. He denied any systemic symptoms. A multimodal imaging examination was performed, raising the clinical suspicion of VRL and guiding the ensuing diagnostic procedures. The patient underwent treatment and at the last FU visit three years later, no disease signs were present on fundus examination, nor on oncologic evaluation. Some novel SS-OCT-A features were identified, and uncommonly reported findings were examined over a long-term follow-up. At baseline multiple hyperreflective alterations were detected on the enface outer retina slabs and choriocapillary analysis revealed low reflectance areas in the foveal and parafoveal areas. One month after the first presentation, multiple hyperreflective retinal lesions in a vertical shape were detected on OCT which appeared on midretinal slabs of enface SS-OCT-A as hyperreflective spots mainly located near second-order retinal vessels. These alterations remarkably reduced after treatment.ConclusionSS-OCT-A may be a useful imaging technique in the detection of VRL, providing ophthalmologists additional findings that assist the diagnosis and follow-up of this disease. This may prove useful for a more timely and precise diagnosis, prompt therapy, and treatment response monitoring. The original aspects found in this case may provide grounds for future studies, ultimately fostering a better understanding of the disease.

Use of 18F-fluoro-2-deoxy-d-glucose (18F-FDG) PET/CT for lymph node assessment before radical cystectomy in bladder cancer patients.

To assess the diagnostic performance of 18F-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomograpy (PET)/computed tomography (CT) in nodal staging before radical cystectomy (RC) and pelvic lymph node dissection (PLND) for bladder cancer (BCa). This analysis was based on a cohort of 199 BCa patients undergoing RC and bilateral PLND between 2015 and 2022. Neoadjuvant chemotherapy (NAC) or immunotherapy (NAI) was administered after oncological evaluation. All patients received preoperative 18F-FDG PET/CT to assess extravesical disease. Point estimates for true negative, false negative, false positive, true positive, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of conventional imaging and PET/CT were calculated. Subgroup analysis in patients receiving neoadjuvant treatment was performed. At preoperative evaluation, 30 patients (15.1%) had 48 suspicious nodal spots on 18F-FDG PET/CT. At RC and bilateral PLND, a total of 4871 lymph nodes (LNs) were removed with 237 node metastases corresponding to 126 different regions. Pathological node metastases were found in 17/30 (57%) vs 39/169 patients (23%) with suspicious vs negative preoperative 18F-FDG PET/CT, respectively (sensitivity = 0.30, specificity = 0.91, PPV = 0.57, NPV = 0.77, accuracy = 0.74). On per-region analysis including 1367 nodal regions, LN involvement was found in 19/48 (39%) vs 105/1319 (8%) suspicious vs negative regions at PET/CT, respectively (sensitivity = 0.15, specificity = 0.98, PPV = 0.40, NPV = 0.92, ACC = 0.90). Similar results were observed for patients receiving NAC (n = 44, 32.1%) and NAI (n = 93, 67.9% [per-patient: sensitivity = 0.36, specificity = 0.91, PPV = 0.59, NPV = 0.80, accuracy = 0.77; per-region: sensitivity = 0.12, specificity = 0.98, PPV = 0.32, NPV = 0.93, ACC = 0.91]). Study limitations include its retrospective design and limited patient numbers. In eight out of 10 patients with negative preoperative 18F-FDG PET/CT, pN0 disease was confirmed at final pathology. No differences were found based on NAC vs NAI treatment. These findings suggest that 18F-FDG PET/CT could play a role in the preoperative evaluation of nodal metastases in BCa patients, although its cost-effectiveness is uncertain.

Chronic hepatitis B and occult infection in chemotherapy patients - evaluation in oncology and hemato-oncology settings: The CHOICE study.

Reactivation of hepatitis B virus (HBV) infection is a well-known risk that can occur spontaneously or following immunosuppressive therapies, including cancer chemotherapy. HBV reactivation can cause significant morbidity and even mortality, which are preventable if at-risk individuals are identified through screening and started on antiviral prophylaxis. To determine the prevalence of chronic HBV (CHB) and occult HBV infection (OBI) among oncology and hematology-oncology patients undergoing chemotherapy. In this observational study, the prevalence of CHB and OBI was assessed among patients receiving chemotherapy. Serological markers of HBV infection [hepatitis B surface antigen (HBsAg)/anti-hepatitis B core antigen (HBc)] were evaluated for all patients. HBV DNA levels were assessed in those who tested negative for HBsAg but positive for total anti-HBc. The prevalence of CHB in the study cohort was determined to be 2.3% [95% confidence interval (95%CI): 1.0-4.2]. Additionally, the prevalence of OBI among the study participants was found to be 0.8% (95%CI: 0.2-2.3). The findings of this study highlight the importance of screening for hepatitis B infection in oncology and hematology-oncology patients undergoing chemotherapy. Identifying individuals with CHB and OBI is crucial for implementing appropriate antiviral prophylaxis to prevent the reactivation of HBV infection, which can lead to increased morbidity and mortality.

Abstract 7432: Improving FAIRness of computational approaches for cancer: The computational resources for cancer research portal

Abstract The Computational Resources for Cancer Research website is a public portal supported by NCI that democratizes access to available computational resources for the cancer research community. In supporting an emerging FAIR (Findable, Accessible, Interoperable, Reusable) data science ecosystem inclusive of software, models and data, the goals of the portal are to serve cancer data scientists by increasing understanding, access, and adoption of computational resources for cancer research, and to foster new collaborative research projects. Initially populated with resources developed in NCI supported collaborations with the US Department of Energy, the portal is serving as a unified reference and resource for computational resources developed broadly by the cancer community. These collaborative projects include CANDLE (the Cancer Distributed Learning Environment), IMPROVE (Innovative Methods and data for PRedictive Oncology model Validation and Evaluation), ADMIRRAL (AI Driven Multi-scale Investigation of Ras-Raf Activation Lifecycle), MOSSAIC (Model Outcomes using Surveillance Data and Scalable AI for Cancer) and ATOM (Accelerating Therapeutics for Opportunities in Medicine). The resources include software, models, and datasets as well as descriptive use cases and references to tutorials associated with many of the described resources. The portal also integrates content from the Predictive Oncology Model and Data Clearinghouse (modac.cancer.gov) which can be accessed through REST APIs. Ongoing development of the portal is driven by community insights and contributions including input from an interdisciplinary advisory committee, working groups, early users, and preliminary feedback received at AACR 2023. The portal will also support community contributions of computational resources. In addition, the portal highlights computational approaches in emerging and challenging areas, such as digital twins for cancer. The portal will enable the cancer research community to learn about new computational research methods through use cases and educational material, access cancer related software, datasets, and AI models, engage with peers and cross-disciplinary researchers at different career levels through an interactive forum, explore emerging areas, such as computational imaging, community-based standards for data management, predictive radiation oncology, and digital twin technologies, learn about in industry and community events, conferences, and workshops, and create new collaborative research projects. The presentation will deliver insights into key resources offered through the Computational Resources for Cancer Research Portal, how the portal will help the cancer research community identify and adopt computational resources of interest, and how researchers can join and participate in this growing community. Citation Format: Eric Stahlberg, Lynn Borkon, Ruth Frost, Sara Jones, Amar Khalsa, Lauren Lewis, Emily Greenspan, Sunita Menon. Improving FAIRness of computational approaches for cancer: The computational resources for cancer research portal [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7432.

Combined surgical and chemotherapy treatment for invasive primary urethral cancer: a case presentation

BackgroundThe European Association of Urology (EAU) defines primary urethral carcinoma (PUC) as a carcinoma that arises in the urethra without a previous diagnosis of carcinoma elsewhere in the urinary system. It is considered as a rare cancer, accounting for less than 1% of all malignant tumors and 5% of malignant tumors of the urinary system. The difficulty in diagnosis and its rarity can lead to delayed diagnosis and decreased survival. We think that a case report to be made in the literature for this rare disease with no consensus on treatment will contribute to disease management.Case presentationIn this article, we describe the diagnosis and treatment process of a 75-year-old patient who was diagnosed with primary urethral cancer and had urethral discharge and difficulty in urination. The biopsy result from the suspected hyperemic area in the urethra in cystourethroscopy was primary urethral cancer. Urethrectomy followed by urethroplasty was performed on the patient's 2-cm primary urethral cancerous tissue. In the postoperative first month, an F-18 FDG whole-body PET scan for oncological evaluation showed increased pathological F-18 FDG uptake in the periphery of the mass in the penile urethra and indistinguishable boundaries from the prostatic urethra. After this, adjuvant gemcitabine and carboplatin therapy was planned by the oncology team.ConclusionsBased on our outcome in this case, we believe that chemotherapy combined with surgery increases the chance of successful treatment in locally advanced urethral cancer.

Gallbladder Cancer Incidentally Found at Cholecystectomy: Perioperative Risk Factors.

Risk factors of gallbladder cancer (GBC) are not well-defined resulting in greater than 60% of GBCs being diagnosed incidentally following cholecystectomy performed for presumed benign indications. As most localized GBCs require more extensive oncologic surgery beyond cholecystectomy, this study aims to examine factors associated with incidentally found GBC to improve preoperative and intraoperative diagnoses. The American College of Surgeons National Surgical Quality Improvement Program Database from 2007 to 2017 was used to identify cholecystectomies performed with and without a final diagnosis of GBC. Univariate and multivariable logistic regressions were used to compare demographic, intraoperative, and postoperative characteristics among those with and without a diagnosis of GBC. The incidence of GBC was observed to be 0.11% (441/403,443). Preoperative factors associated with risk of GBC included age > 60 (OR 6.51, p < .001), female sex (OR 1.75, p < .001), history of weight loss (2.58, p < .001), and elevated preoperative alkaline phosphatase level (OR 1.67, p = .001). Open approach was associated with 7 times increased risk of GBC compared to laparoscopic approach (OR 7.33, p < .001). In addition to preoperative factors and surgical approach, longer mean operative times (127min vs 70.7min, p < .001) were significantly associated with increased risk of GBC compared to benign final pathology. This study demonstrates that those with incidentally discovered GBC at cholecystectomy are unique from those undergoing cholecystectomy for benign indications. By identifying predictors of GBC, surgeons can choose high risk individuals for pre-operative oncologic evaluation and consider better tools for identifying GBC such as intraoperative frozen pathology.

Endoscopy in the Diagnosis and Management of Gastrointestinal Neuroendocrine Tumors

Abstract Gastrointestinal neuroendocrine tumors (GI NETs) are considered rare neoplasms that arise from enterochromaffin cells which form a part of the neuroendocrine cell system present throughout the GI tract. Although considered a rare tumor, its prevalence has increased significantly in recent years owing to the increase in the number of endoscopic evaluations, advanced imaging modalities, and greater detection of the entity by pathologists. The role of an endoscopist remains pivotal in diagnosing and managing GI NETs, ranging from tumor detection, sampling, characterization, and staging which forms the basis of oncological evaluation, particularly of those involving the stomach, duodenum, and colorectum. Endoscopic therapy can provide curative resection of tumors and surveillance scopies in a minimally invasive fashion owing to lesser patient morbidity. Our review aims to provide an overview of the role of the gastroenterologist in diagnosing and managing GI NETs.

HTA310 Evolution of French Economic Opinions Published By the Economic Evaluation and Public Health (CEESP) in Oncology

HTA310 Evolution of French Economic Opinions Published By the Economic Evaluation and Public Health (CEESP) in Oncology

A mechanistically novel peptide agonist of the IL-7 receptor that addresses limitations of IL-7 cytokine therapy.

Interleukin (IL)-7 is broadly active on T-cell populations, and modified versions have been clinically evaluated for a variety of therapeutic applications, including cancer, lymphopenia, and infectious diseases; and found to be relatively well-tolerated and biologically active. Here we describe novel IL-7R agonists that are unrelated in structure to IL-7, bind to the receptor subunits differently from IL-7, but closely emulate IL-7 biology. The small size, low structural complexity, and the natural amino acid composition of the pharmacologically active peptide MDK1472 allows facile incorporation into protein structures, such as the IgG2-Fc fusion MDK-703. This molecule possesses properties potentially better suited to therapeutic applications than native IL-7 or its derivatives. We compared these compounds with IL-7 for immune cell selectivity, induction of IL-7R signaling, receptor-mediated internalization, proliferation, and generation of immune cell phenotypes in human and non-human primate (NHP) peripheral blood cells in vitro; and found them to be similar in biological activity to IL-7. In cynomolgus macaques, MDK-703 exhibits a circulating half-life of 46 hr and produces sustained T-cell expansion characteristic of IL-7 treatment. In the huCD34+-engrafted NSG mouse model of the human immune system, MDK-703 induces an immune cell profile very similar to that generated by IL-7-derived compounds; including the pronounced expansion of memory T-cells, particularly the population of stem-like memory T-cells (Tscm) which may be important for anti-tumor activities reported with IL-7 treatment. Clinical administration of IL-7 and modified variants has been reported to induce anti-drug antibodies (ADAs), including IL-7 neutralizing antibodies. The novel peptide agonist reported here scores very low in predicted immunogenicity, and because the peptide lacks sequence similarity with IL-7, the problematic immunogenic neutralization of endogenous cytokine should not occur. The properties we report here implicate MDK-703 as a candidate for clinical evaluation in oncology, anti-viral and other infectious disease, vaccine enhancement, and treatment of lymphopenia.

A Prospective Study of Machine Learning-Assisted Radiotherapy Planning for Patients Receiving 54 Gy to the Brain

Radiotherapy (RT) planning is presently a semi-manual, iterative, labor-intensive process which may result in unnecessary variation in plan quality. To improve treatment plan quality and decrease RT planning time, we conducted a prospective, blinded study to compare machine learning-assisted planning with conventional manual planning for patients receiving 54 Gy in 30 fractions for a primary brain tumor. From January 31, 2022 to January 10, 2023, 40 patients receiving 54 Gy for primary CNS tumors were prospectively enrolled (median age 50 years, range 4-78 years). Patients underwent standard CT/MR simulation and target/OAR delineation by the treating radiation oncologist. Each patient had one ML plan and 1-2 manual RT plans created by different planners. The reviewing oncologist was blinded to planning method by removing optimization and IMRT/VMAT beam arrangement details from all plans, which were then rated based on clinical acceptability, target coverage, OAR sparing, conformity, and dose-fall off. One preferred plan was chosen and used for clinical treatment. A total of 115 plans for 40 patients were evaluated: 40 ML plans (35% of all plans), and 75 manual plans (65% of all plans; 5 and 35 patients had 1 and 2 manual plans created, respectively). ML plans required a mean planning time of 65 min as compared to 107 min for manual plans, with a mean time savings of 41 min per patient (paired t-test p = 0.002). 97% of ML plans (95% confidence interval [CI] 85-100) and 96% of manual plans (95% CI 87-99) were designated clinically acceptable by the treating radiation oncologist. While ML-assisted plans represented 35% of plans evaluated, they were chosen as preferred for clinical treatment in 43% of cases (17/40, 95% CI 29-58, p = 0.32). Median doses to the brain (10.8 Gy vs. 11.3 Gy, Wilcoxon rank-sum p = 0.012) and brain minus PTV (9.2 Gy vs 10.0 Gy, Wilcoxon rank-sum p = 0.009) were lower with ML planning versus manual planning, respectively. Doses to other structures, including hippocampi, cochlea, pituitary and hypothalamus were not statistically different. In this prospective study with blinded oncologist evaluation, ML-assisted RT planning for primary CNS tumors was faster than manual planning, and produced a very high rate of acceptable plans with similar or superior OAR sparing. Future work will be undertaken to iteratively refine the ML model using the preferred cases from this study.