Multidisciplinary Tumor Board Research Articles

Multimodal treatment for resectable neuroendocrine carcinoma of the cervix.

Non-metastatic neuroendocrine carcinoma of the cervix (NECC) is a rare and aggressive disease. Lacking prospective studies, the optimal multimodal treatment approach has not yet been clearly defined. This study aims to assess the clinical outcomes of patients with non-metastatic NECC treated with surgery and (neo)adjuvant chemotherapy, according to pathologic prognostic factors and multimodal treatments received. We retrospectively examined data from patients with non-metastatic NECC candidate to receive surgery and (neo)adjuvant chemotherapy and discussed at the European Institute of Oncology's Multidisciplinary Neuroendocrine Tumor Board, between January 2003 and December 2021. Primary endpoints were event-free survival and overall survival. A total of 27 consecutive patients were evaluated, 15 with early stage NECC and 12 with a locally advanced NECC. Eight patients received neoadjuvant and 19 adjuvant platinum-based chemotherapy; 14 received adjuvant pelvic radiotherapy, half with external-beam radiation therapy alone, and half combined with brachytherapy. No patients progressed or relapsed during (neo)adjuvant chemotherapy. The median event-free survival was 21.1 months and the median overall survival was 33.0 months. Pathological FIGO stage ≥ IIB, adjuvant external-beam radiation therapy with or without brachytherapy emerged as significant and independent prognostic factors for event-free survival. Brachytherapy was also prognostic for overall survival. Non-metastatic NECC requires a multimodal approach, mainly weighted on the FIGO stage. The addition of brachytherapy should be considered, especially in patients with locally advanced disease. Because of the scarcity of robust clinical data, treatment strategy should be discussed in multidisciplinary board, taking into account patient.

Consensus recommendations in the management of Ewing sarcoma from the National Ewing Sarcoma Tumor Board.

Ewing sarcoma (ES) is a malignant tumor of bone and soft tissue that most often occurs in adolescents and young adults. Despite an international coordinated approach, several nuances, discrepancies, and debates remain in defining the standard of care for treating ES. In this review, the authors leverage the expertise assembled by formation of the National Ewing Sarcoma Tumor Board, a multi-institution, multidisciplinary virtual tumor board that meets monthly to discuss complicated and challenging cases of ES. This report is focused on select topics that apply to the management of patients with newly diagnosed ES. The specific topics covered include indications for bone marrow aspirate and biopsy for initial evaluation compared with fluorodeoxyglucose-positron emission tomography, the role of interval compressed chemotherapy in patients aged 18years and older, the role of adding ifosfamide/etoposide to vincristine/doxorubicin/cyclophosphamide for patients with metastatic disease, the data on and role of high-dose chemotherapy with autologous stem cell transplantation, maintenance therapy, and whole-lung irradiation. The data referenced are often limited to subgroup analyses and/or compiled from multiple sources. Although not intended to replace the clinical judgement of treating physicians, the guidelines are intended to provide clarity and recommendations for the upfront management of patients with ES. PLAIN LANGUAGE SUMMARY: Ewing sarcoma is a malignant tumor of bone and soft tissue that most often occurs in adolescents and young adults. For this review, the authors used the experience of the National Ewing Sarcoma Tumor Board, a multi-institution, multidisciplinary virtual tumor board that meets monthly to discuss complicated and challenging cases of Ewing sarcoma. Although not intended to replace the clinical judgement of treating physicians, the guidelines will focus on the development of consensus statements for the upfront management of patients with Ewing sarcoma.

Guideline adherence of tumor board recommendations in lung cancer and transfer into clinical practice

PurposeEvaluating patients and treatment decisions in a multidisciplinary tumor board has led to better quality of care and longer survival in cancer patients. The aim of this study was to evaluate tumor board recommendations for thoracic oncology patients regarding guideline adherence and transferal of recommendations into clinical practice.MethodsWe evaluated tumor board recommendations of the thoracic oncology tumor board at Ludwig-Maximilians University (LMU) Hospital Munich between 2014 and 2016. We compared patient characteristics between guideline-adherent and non-guideline-adherent recommendations, as well as between transferred and non-transferred recommendations. We used multivariate logistic regression models to evaluate factors associated with guideline adherence.ResultsOver 90% of recommendations by the tumor board were either adherent to the guidelines (75.5%) or over fulfilling guidelines (15.6%). Almost 90% of recommendations were transferred to clinical practice. If a recommendation was not according to the guidelines, the reason was mostly associated with the general condition (age, Charlson comorbidity index, ECOG) of the patient or due to the patients’ request. Surprisingly, sex also had a significant influence on the guideline adherence of recommendations, with females being more likely to get recommendations not according to the guidelines.ConclusionIn conclusion, the results of this study are promising, as the guideline adherence of recommendations as well as the transferal of recommendations into clinical practice were high. In the future, a special focus should be put on fragile patients as well as female patients.

MDT-How it is important in rectal cancer.

The concept of multidisciplinary team discussion of patient's care has been a part of routine medical practice for several decades [Monson et al. in Bull Am Coll Surg 101:45-46, 2016; NHS. Improving outcomes in colorectal cancer-the manual. (Guidance on commissioning cancer services-improving outcomes). 1997.]. The idea of bringing multiple specialties and ancillary services together to help optimize patient outcomes has been implemented in several clinical arenas from burns to physical medicine and rehabilitation to oncology. In the oncology realm, multidisciplinary tumor boards (MDTs) originated as a broad-based meeting that would permit the review and discussion of cancer patients to optimize treatment strategies [Cancer Co. Optimal Resources for Cancer Care: 2020 Standards. Chicago, IL: 2019.]. Over time, as further specialization occurred and clinical treatment algorithms have become more complex, multidisciplinary tumor boards have become more disease site specific. In this article we will discuss the importance of MDTs, specifically focusing on rectal cancer MDTs including their impact on treatment planning as well as the unique interplay of clinical specialties that provide internal quality control and improvement. Additionally, we will discuss some of the potential benefits of MDTs beyond the direct impact on patient care and review some of the challenges of implementation.

Adrenal Neoplasms: Lessons from Adrenal Multidisciplinary Tumor Boards.

The radiologic diagnosis of adrenal disease can be challenging in settings of atypical presentations, mimics of benign and malignant adrenal masses, and rare adrenal anomalies. Misdiagnosis may lead to suboptimal management and adverse outcomes. Adrenal adenoma is the most common benign adrenal tumor that arises from the cortex, whereas adrenocortical carcinoma (ACC) is a rare malignant tumor of the cortex. Adrenal cyst and myelolipoma are other benign adrenal lesions and are characterized by their fluid and fat content, respectively. Pheochromocytoma is a rare neuroendocrine tumor of the adrenal medulla. Metastases to the adrenal glands are the most common malignant adrenal tumors. While many of these masses have classic imaging appearances, considerable overlap exists between benign and malignant lesions and can pose a diagnostic challenge. Atypical adrenal adenomas include those that are lipid poor; contain macroscopic fat, hemorrhage, and/or iron; are heterogeneous and/or large; and demonstrate growth. Heterogeneous adrenal adenomas may mimic ACC, metastasis, or pheochromocytoma, particularly when they are 4 cm or larger, whereas smaller versions of ACC, metastasis, and pheochromocytoma and those with washout greater than 60% may mimic adenoma. Because of its nonenhanced CT attenuation of less than or equal to 10 HU, a lipid-rich adrenal adenoma may be mimicked by a benign adrenal cyst, or it may be mimicked by a tumor with central cystic and/or necrotic change such as ACC, pheochromocytoma, or metastasis. Rare adrenal tumors such as hemangioma, ganglioneuroma, and oncocytoma also may mimic adrenal adenoma, ACC, metastasis, and pheochromocytoma. The authors describe cases of adrenal neoplasms that they have encountered in clinical practice and presented to adrenal multidisciplinary tumor boards. Key lessons to aid in diagnosis and further guide appropriate management are provided. © RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Broadening the Understanding of Mucinous Carcinoma of the Breast

Mucinous carcinoma (MC) is a rare invasive neoplasm comprising only 2% to 4% of all breast cancers,1 commonly affecting women under the sixth through eighth decades of life. Also referred to as colloid carcinoma, MC has been historically described as a circumscribed, round mass with indolent behavior occurring in older women. This is an oversimplification. The imaging appearance, biological behavior, and demographic profile of MC are variable, often correlating with histologic subtype and nuclear differentiation and in some instances mimicking benign pathologies. Broadening the understanding of MC will help radiologists establish concordance, guide clinical management, and accurately surveille cases in multidisciplinary tumor boards.

Impact of 2 years of COVID-19 pandemic on ovarian cancer treatment in IRCCS-AUSL of Reggio Emilia.

To assess compliance with the 2019 regional recommendation to centralize epithelial ovarian cancer (EOC) patients and to assess whether the COVID-19 pandemic has affected the quality of care for EOC patients. We compared data from EOC patients treated before the introduction of the 2019 regional recommendation (2018-2019) with data obtained from EOC patients treated after the regional recommendation was adopted during the first 2 years of the COVID-19 pandemic (2020-2021). Data were retrieved from the Optimal Ovarian Cancer Pathway records. R software version 4.1.2 (the R Foundation for Statistical Computing, Vienna, Austria) was used for the statistical analysis. 251 EOC patients were centralized. The number of EOC patients centralized increased from 2% to 49% despite the COVID-19 pandemic. During the COVID-19 pandemic, there was an increase in the use of neoadjuvant chemotherapy and interval debulking surgery. There was an improvement in the percentage of Stage III patients without gross residual disease following both primary and interval debulking surgery. The percentage of EOC cases discussed by the multidisciplinary tumor board (MTB) increased from 66% to 89% of cases. Despite the COVID-19 pandemic, centralization has increased and the quality of care has been preserved thanks to the MTB.

Genetic counselling referral practices for patients with pancreatic adenocarcinoma: A French retrospective multicentre observational cohort study (CAPANCOGEN)

Background/objectivesGenetic counselling (GC) is a key step in the identification of inherited germline mutations. However, the oncogenetic practices are poorly described for pancreatic adenocarcinoma (PA) in Europe. The CAPANCOGEN study aimed to describe the GC referral practices in France and assess the implementation of international guidelines in patients with PA. MethodsInformation about GC referrals with PA was collected in 13 French centres from September 2019 to October 2021. In the 5 largest centres, personal and familial histories of cancers and diseases associated with a higher risk of germline mutations were collected in 460 patients, according to international, American, European and French GC referral guidelines. Univariate and multivariate logistic regression analysis were performed to identify the factors influencing GC referral. ResultsAmong 833 patients, a total of 100 patients (12%) had an indication of GC according to local multidisciplinary tumour board meetings (MTBM). Among these patients, 41% did not undergo GC. The median time between MTBM and GC was 55 days (IQR: 14.5–112). Among 460 patients with collected personal and familial history, 31.5% were not referred to a GC despite an existing indication. In multivariate logistic regression analysis, suspected CDKN2A (p = 0.032) or BRCA mutation (p < 0.001), familial pancreatic cancer history (p < 0.001) and controlled disease with first-line platinum-based chemotherapy (p < 0.001) increased the referral rate. Conversely, older age (p = 0.002) and a locally advanced PA (p = 0.045) decreased the risk of GC referral. ConclusionsGC referral is inadequate despite valuable information in patients’ medical files.

The COVID-19 pandemic has impeded cytopathology practices and hindered cancer screening and management.

The COVID-19 pandemic has had a global impact on the environment and economy and has affected hospital administration and patient behaviour. Since human-to-human coronavirus transmission occurs via droplets and physical contact, health care professionals are particularly vulnerable to contracting COVID-19. Many cytopathology laboratories updated their workflow, established new standard biosafety protocols, and built digital pathology or telescope platforms to mitigate these risks and deal with the shortage of health care personnel. The COVID-19 pandemic also disrupted medical education-all indoor training events, including conferences, multidisciplinary tumour boards, seminars, and microscope inspections were postponed. As a result, many laboratories now use new web-based applications and platforms to maintain educational programs and multidisciplinary tumour boards. To comply with government directives, health care facilities postponed non-emergency surgeries, reduced the number of routine medical examinations, restricted visitor numbers, and scaled back cancer screening activities, resulting in a sharp decline in cytopathology diagnoses, cancer screening specimens, and molecular testing for cancer. Subsequent misses or delays in the diagnosis and treatment of cancer were not uncommon. This review aims to provide comprehensive summaries of the consequences of the COVID-19 pandemic for cytopathology, particularly in terms of cancer diagnosis, workload, human resources, and molecular testing.

Molecular testing of endometrial carcinoma in real-world clinical practice.

Molecular classification has brought significant changes in the management of endometrial cancer (EC). In this article, we aim to analyze our first experience with an implementation of molecular testing into daily clinical practice. In all newly diagnosed EC, the status of mismatch repair (MMR) and p53 proteins has been evaluated immunohistochemically as a part of the routine histopathological examination since May 2021. In tumors that do not meet clinical criteria for a low risk and those with MMR deficiency or p53 mutation, the molecular genetic testing of the POLE gene is performed as well. Recommendations for adjuvant treatment or follow-up are subsequently made based on the risk of recurrence. Genetic counselling is proposed to all patients with MMR-deficient tumors or family history of cancer. A total of 85 patients with newly diagnosed EC between May 2021 and May 2022 were enrolled in the analysis. The median age was 66 years. The results of molecular testing were as follows: 22 (26%) MMR-deficient, 8 (9%) p53-mutated and none POLE-ultramutated of those 40 tumors with performed POLE sequencing. A total of 46 (51%) patient had a low risk, 2 (2%) intermediate, 14 (16%) high-intermediate and 20 (24%) patients had a high risk of recurrence. Advanced or metastatic diseases were diagnosed in 6 (7%) patients. The median time between surgery and multidisciplinary tumor board decision was 21 days (8-36). A total of 76 (90%) patients underwent the whole treatment plan according to the recurrence risk. At the time of analysis, the results of genetic testing were available in 18 patients and revealed 4 (22%) carriers of a pathogenic variant in any of the genes associated with Lynch syndrome. Molecular testing combining immunohistochemical analyses of MMR and p53 proteins in all newly diagnosed EC patients with sequencing analysis of POLE in those with non-low-risk disease is feasible and does not prolong the time needed for treatment decision.

Validation and implementation of a mobile app decision support system for prostate cancer to improve quality of tumor boards.

Certified Cancer Centers must present all patients in multidisciplinary tumor boards (MTB), including standard cases with well-established treatment strategies. Too many standard cases can absorb much of the available time, which can be unfavorable for the discussion of complex cases. In any case, this leads to a high quantity, but not necessarily a high quality of tumor boards. Our aim was to develop a partially algorithm-driven decision support system (DSS) for smart phones to provide evidence-based recommendations for first-line therapy of common urological cancers. To assure quality, we compared each single digital decision with recommendations of an experienced MTB and obtained the concordance.1873 prostate cancer patients presented in the MTB of the urological department of the University Hospital of Cologne from 2014 to 2018 have been evaluated. Patient characteristics included age, disease stage, Gleason Score, PSA and previous therapies. The questions addressed to MTB were again answered using DSS. All blinded pairs of answers were assessed for discrepancies by independent reviewers. Overall concordance rate was 99.1% (1856/1873). Stage specific concordance rates were 97.4% (stage I), 99.2% (stage II), 100% (stage III), and 99.2% (stage IV). Quality of concordance were independent of age and risk profile. The reliability of any DSS is the key feature before implementation in clinical routine. Although our system appears to provide this safety, we are now performing cross-validation with several clinics to further increase decision quality and avoid potential clinic bias.

Sometimes It Really Is the Zebra: A Rare Case of Infantile Giant Cell Fibroblastoma

Plastic surgeons often perform surgical excision of soft tissue lesions and masses on the head and neck. In the pediatric population, these are most commonly benign lesions; however, malignant lesions must always remain on the differential. In this case report, we describe a case of a scalp giant cell fibroblastoma in infancy. Once the diagnosis was confirmed, a multidisciplinary tumor board including pediatric hematology-oncology was consulted for management recommendations. Surgical re-excision with additional 1 cm margins was performed and wound closure was accomplished without any undermining of surrounding skin and ultimately covered with a skin graft. While extremely rare, giant cell fibroblastoma is a locally aggressive soft tissue tumor that plastic surgeons may encounter in clinic practice and requires multi-disciplinary care.

Clinical utility of an international multidisciplinary virtual tumor board for fibrolamellar carcinoma.

e18624 Background: Fibrolamellar carcinoma (FLC) is a rare liver cancer with approximately 1500 new cases per year, worldwide. The lack of expertise locally often incurs significant travel for patients (pts). Virtual consults have improved access to expertise but identifying the best experts for an ultra-rare condition is difficult for pts and families and multidisciplinary tumor boards of experts offer better clinical guidance. Foundations and advocacy groups play a vital role in navigation and support for pts with rare cancers. Methods: Pts with FLC and their local treating oncologists were engaged by the FibroFighters Foundation and offered a multidisciplinary virtual tumor board (VTB) review. Each VTB included the local treating oncologist, a patient advocate, a molecular pharmacologist, and international experts in the clinical management of FLC including at least one medical oncologist, one radiation oncologist, one interventional radiologist, and one surgical oncologist. Each VTB reviewed the pts’ clinical history and relevant imaging and discussed surgical, radiological, and systemic approaches. Pts consented to the observational research protocol XCELSIOR ( NCT03793088 ) to enable longitudinal clinical summaries to be prepared and for outcomes to be annotated. Results: Between August 4th 2022 and February 9th, 2023, the VTB held a total of 71 discussions for 59 unique pts (12 discussed more than once): 12 new diagnoses, 28 relapses, 14 treatment failures, and 5 ongoing care. Median age at diagnosis of pts was 18 years (range 6-44 years). Pts were seen at 44 institutions/practices across 22 states and 4 countries (USA, Australia, Switzerland, and the Netherlands). A total of 36 unique treatment regimens were discussed, with 21 unique consensus top-ranked options delivered to treating oncologists. The most common consensus options included regimens of gemcitabine, lenvatinib, and nivolumab (13), interventional radiology (IR, 11), surgical resection (6), and a regimen of gemcitabine, oxaliplatin, and lenvatinib (6). The primary team implemented the VTB recommendations 60 times out of 71 (85%): change in systemic therapy (33), IR (11), continue current regimen (11), surgery (6), radiation oncology (2). Conclusions: This is the first demonstration of a patient-focused international multidisciplinary VTB for FLC. The high rate of recommendation adoption by local treating oncologists suggests this is a valuable service to improve patient care. Outcomes are being collected prospectively in a master observational research protocol to better define clinical utility.

Assessing current diagnostic, staging, and treatment practices in community and academic centers for individuals with stage IB-IIIA non–small-cell lung cancer (NSCLC).

e20608 Background: The five-year survival for individuals with surgically resected, early-stage NSCLC is around 50%. Recent availability of biomarker driven therapy after surgery has the promise of improved outcomes. However, deficits in the quality of diagnostic evaluation, evidence-based treatment delivery, care coordination, and biomarker testing are still barriers to optimal outcomes. Methods: In 2022, the Association of Community Cancer Centers (ACCC) conducted a survey of NSCLC providers to assess current patterns in the diagnosis and treatment of patients with early-stage (IB-IIIA) NSCLC. The survey, which was distributed to ACCC members and their associated networks, collected information about each respondent and their cancer program processes around diagnosis, treatment planning, and care delivery. We administered it Qualtrics and analyzed results with SAS 9.4. Results: We had 124 survey respondents from 33 US states. Respondents’ institutions were 60% urban, 23% suburban, and 17% rural, 53% community cancer programs, 37% academic/NCI designated cancer programs, 9% private practice. On average, initial tissue biopsy was performed by interventional radiologists in 29% of cases, interventional pulmonologist in 22%, and thoracic surgeons in 16%. In stage IIA-IIIA, on average 49% typically perform invasive mediastinal staging before surgery, 17% during surgery, and 18% do not typically perform invasive mediastinal staging. The most frequent barriers to optimal staging and diagnosis included scheduling (73%), cost (51%), tissue quality (46%), limited access to tests or procedures (42%), and missed appointments (36%). Multidisciplinary tumor board use included 31% with a general cancer tumor board, 50% with a thoracic specific tumor board, and 14% have a dedicated molecular tumor board. Tumor board meetings were weekly in 57%, 2-3 times a month in 22%, and once a month in 11%. 66% have a standard biomarker testing protocol for resected NSCLC. 51% typically order EGFR and 31% regularly order PDL1 testing for patients with resected NSCLC. The largest barriers to optimal care included: scheduling (23%), patient refusal (19%), communication breakdowns (17%), inadequate staffing (15%), and limited access to subspecialties (14%). 83% agree their center has the staff and resources to help patients navigating the health system. However, only 45% typically assign a nurse navigator to individuals with early-stage NSCLC. Palliative care service referrals were made sometimes or often in 48% of sites, while 51% refer rarely or never. Conclusions: In this broad sample of oncology practices across the US, we identified several strengths and barriers to optimal care for persons with early-stage NSCLC. Improved care coordination and standardized staging and diagnosis practices could optimize care in this dynamic treatment landscape.

Clinical utility of plasma ctDNA sequencing in metastatic urothelial carcinoma.

4576 Background: Genomic stratification may help to improve the management of patients with metastatic urothelial cancer (mUC) given the recent identification of targetable molecular alterations in this disease. However, collecting tissue samples in mUC remains challenging. We assessed the clinical utility of plasma circulating tumor DNA (ctDNA) sequencing in mUC. Methods: mUC patients were prospectively enrolled in the STING trial (NCT04932525) whereby ctDNA was profiled using the FoundationOne Liquid CDx Assay (324 genes, tumor mutational burden [TMB], microsatellite instability status). Each individual genomic report was reviewed and discussed weekly by a multidisciplinary tumor board (MTB). Actionable targets were classified by ESCAT tier leading to molecular-based treatment suggestions whenever it was possible. Results: Between January 2021 and June 2022, 140 mUC patients underwent molecular profiling. Median time to assay results was 20 days. ctDNA abundance was correlated with number of prior lines and number of metastatic sites. ctDNA analysis reproduces the somatic genomic landscape reported by previous tissue-based cohorts. Concordance for serial tumor tissue was moderate (r=0.545 CI95: [0.121-0.801], p= 0.016). At least one actionable target was detected in 63 patients (45 %) with a total of 35 actionable alterations including TMB high (≥12 mutations/Mb) (N= 39, 21.1%), FGFR3 (N= 20, 10.8%) and HRD alterations (N= 14, 7.6%). The MTB recommended a matched therapy for 63 patients (45.0%). In total, 8 patients (5.7 %) were treated with an overall response rate of 50% (95%: 15.70-84.30) and a median PFS of 5.2 months (CI95%: 4.1 - NR). FGFR3 alterations were associated with lower progression-free survival in patients treated with immunotherapy. Conclusions: Overall, our analysis demonstrates that genomic profiling with a large panel of ctDNA in mUC is a reliable and feasible approach to timely initiate genotype-matched therapies. Clinical trial information: NCT04932525 .

Socioeconomic and demographic disparities in rectal cancer treatment.

e15512 Background: Early treatment (tx) improves survival in rectal cancer (ca). We explored whether socioeconomic and demographic attributes are associated with time to tx initiation for rectal ca patients (pts) in New York's largest and most diverse healthcare system. Methods: 283 rectal ca pts were identified from three multidisciplinary tumor boards from 2019-2022. Time to tx was calculated as time from biopsy to first tx (surgery, chemotherapy, or radiation). Social work assistance was defined as an intervention by a social worker for home care, housing, or transportation assistance. Reasons for tx delay were assessed from physician and social work notes. Results: Median time to tx for all pts was 41 days. Time to tx was longer for Black/African American (BAA) (56.5 days; p &lt; 0.001) and Medicare only (46.5 days; p = 0.005) pts. No differences were seen in time to tx for all pts when stratified by first tx modality (surgery, chemotherapy, or radiation). In a univariable linear regression, BAA pts (vs Asian or White; p &lt; 0.001), Medicare only pts (vs Medicaid, Medicare with Supplemental, or Commercial Insurance; p = 0.001), and pts requesting social work assistance (p = 0.001) predicted longer time to tx. Employed pts (vs unemployed or retired; p = 0.034) predicted shorter time to tx. In a multivariable model, BAA (p = 0.013), Medicare (p = 0.022), and social work assistance (p = 0.029) predicted longer time to tx. The most common reasons identified for tx delay in BAA and Medicare pts were hospitalization during diagnosis (9%), evaluation of metastatic disease (9%), and tx hesitancy (7%). The odds ratio of being hospitalized during initial workup was 2.8 times higher for BAA than Asian or White pts (p = 0.007). Conclusions: Analysis of time to tx in rectal ca showed a notable delay for BAA pts, Medicare only pts, and pts requesting social work assistance. These findings may empower further studies to assess which factors are causal and to implement interventions that promote equity in timely tx for rectal ca pts. Reasons for tx delay were also not well documented and should be further elucidated. [Table: see text]

Prevalence of pathogenic germline variants in a cohort of patients with early onset non-small cell lung cancer (EOLUNG).

10630 Background: Patients with early onset lung cancer might be more likely to carry pathogenic (or likely-pathogenic) germline variants (PGV) in genes associated with cancer predisposition. However, germline testing is not recommended in this population. We designed this study to determine the prevalence of PGVs in patients with early onset lung cancer. Methods: This prospective, multicenter cohort study assessed PGV in patients younger than 51 years diagnosed with non-small cell lung cancer (NSCLC) in 3 sites at the Catalan Institute of Oncology between June 2018 to May 2022. Genomic DNA was sequenced using a custom-designed NGS panel covering 164 cancer-predisposing genes and results were discussed in a multidisciplinary tumor board. Results: 138 patients were included. Median age was 45.5 (28-50) years; 49% were females; 79% were ever-smokers with a median packs-year of 24 and median age of tobacco initiation of 16 years old. Most patients had non-squamous histology (88%) and had stage IV (62%) at diagnosis. Somatic oncogenic drivers were found in 74 patients (54%): EGFR 27 (20%); ALK 22 (16%); KRAS 20 (14%); RET 3 (2%); ROS1 1 (1%); BRAF V600E 1 (1%). Only 4% had past personal history of cancer and 50% had family history of cancer in a first-degree relative, being lung and breast cancer the most common tumors. Overall, 20 patients (14%) carried PGVs involving 12 genes associated with cancer predisposition: PARK2 (n=4); SBDS (n=3); NBN (n=2); ATM (n=2); TSC1 (n=2) and BLM, FANCA, MCPH1, PMS2, POLH, SDHA, RECQL4 (n=1, each). Four patients (3%) fulfilled criteria to be referred to genetic counseling clinic. There were no significant differences in clinical and molecular characteristics among patients with PGVs compared to their counterparts (Table). Conclusions: In this prospective cohort, 14% of patients with early onset NSCLC harbored germline PGVs. As clinicopathological and genomic features were not associated with PGVs, germline testing might be considered in addition to comprehensive genomic characterization of tumor tissue in young patients with NSCLC. However, only a minority of PGVs were deemed clinically actionable.[Table: see text]

Overcoming barriers to adoption of precision medicine in community oncology centers in the rural southeastern United States using novel informatics tools and academic collaborations.

e13514 Background: Comprehensive genomic profiling (CGP) is an important tool to identify actionable biomarkers and guide cancer therapy. However, patient (pt) race, socioeconomic status, and clinical setting are associated with lower access to CGP, targeted therapies, and clinical trials. To address this, we expanded a novel framework for genomic data management and clinical decision support developed at a large academic medical center to a network of affiliated community cancer centers located in rural, traditionally underserved communities. Methods: The Duke Precision Cancer Medicine Initiative (PCMI) developed a centralized database to aggregate and normalize CGP results. This database enables CGP review by a multi-disciplinary Molecular Tumor Board (MTB). PCMI established a protocol that allows the MTB to review CGP results and relevant clinical data for consented patients. This protocol opened enrollment at four DCN-affiliated cancer centers in rural North Carolina. Clinical recommendations are captured in a standard note and returned to DCN providers following each review. Our protocol also includes an anonymous survey sent to oncology providers asking about barriers to access and utilization of CGP. Results: Between Jan 2022 and Jan 2023, 62 pts were enrolled and had CGP results reviewed by the MTB; 13 pts (21.0%) were Native American and 20 (32.3%) were Black. 61 actionable genomic alterations were identified from 38 pts, including 16 (25.6%) that molecularly matched clinical trial inclusion criteria. Most DCN providers reported being comfortable ordering (14/20) CGP though fewer expressed comfort with interpretation (9/20) CGP; provider-reported barriers included cost/insurance for targeted therapies (12/20) and distance to clinical trials (14/20). Conclusions: Successful academic-community partnerships to expand access to CGP, clinical trials, and targeted therapies are feasible when supported by fit-for-purpose informatics tools and scalable workflows. Additional work is required to develop comprehensive solutions that ensure equal access to CGP and precision medicine for all patients. [Table: see text]

Comprehensive genomic profiling and individual therapeutic planning in high-risk/refractory pediatric solid tumors: A single-center real-world study.

10035 Background: Despite major improvements in the survival of pediatric cancer patients that were achieved through the intensification of chemotherapy and the perfection of supportive care in the past decades, treatment outcomes for high-risk, relapsed, and refractory solid cancers remain unsatisfactory. Accelerating the progress of pediatric oncology requires both therapeutic advances and attention to reducing the long-term cytotoxic treatment-related side effects. This could be achieved by targeting specific molecular changes that drive pediatric malignancies. Methods: From September 2016 to August 2020, a total of 192 patients with pediatric high-risk solid tumors successfully underwent comprehensive genomic profiling. Since more than thirty patients had two or more biopsies from recurrent relapses, the total number of samples examined was 295. In the cohort, there were 78 cases of central nervous system tumors, 68 sarcomas, 14 neuroblastomas, 10 lymphomas, and 22 tumors of other histology. Whole-exome sequencing was performed in all patients, fusion gene analysis in 96% of patients, whole-transcriptome profiling in 84% of patients, and CNV analysis in 63% of patients. Results: The diagnostic yield of therapeutically actionable findings was 40%, with single-nucleotide variants and small insertions/deletions being the most common actionable alteration types. In 23% of patients, a clinically relevant gene fusion was identified. The majority of the identified fusions were of diagnostic significance, and 18% of those were therapeutically targetable gene fusions involving BRAF, RAF1, ALK, FGFR1, or NTRK2. Four patients were eligible for immunotherapy based on high tumor mutational burden ( &gt; 10 mut/Mb). Lymphomas and CNS tumors showed the highest rate of patients with therapeutically actionable findings (60% and 56%, respectively), followed by neuroblastomas (36%), sarcomas (25%), and other solid tumors (23%). All results and individual treatment plans were discussed and approved at multidisciplinary molecular tumor boards. Conclusions: Precision medicine in pediatric oncology has rapidly developed over the last decade and resulted in new therapeutic options based on molecular biomarkers and increased our understanding of the complexity of pediatric malignancies. Supported by the Ministry of Health of the Czech Republic, grant nr. NU20-03-00240 and the project National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102) - Funded by the European Union - Next Generation EU.

A phase II, open-label pilot study evaluating the safety and activity of liposomal irinotecan (Nal-IRI) in combination with 5-FU and oxaliplatin (NALIRIFOX) in preoperative treatment of pancreatic adenocarcinoma: NEO-Nal-IRI study.

TPS4190 Background: Neoadjuvant treatment for potentially curable pancreatic cancer (PDAC) is increasing in acceptability, but a standard regimen has yet to be established. Multiple studies have demonstrated feasibility and effectiveness of the FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen in the perioperative setting. However, FOLFIRINOX often requires dose modifications, delays and growth factor support due to excessive toxicity which can complicate care delivery when given neoadjuvantly. Liposomal irinotecan injection (Nal-IRI) is FDA approved with a well-tolerated safety profile in relapsed, refractory metastatic PDAC. The current study aims to substitute Nal-IRI for traditional irinotecan in the standard FOLFIRINOX regimen (NALIRIFOX) and to demonstrate safe and effective neoadjuvant delivery. Methods: This phase 2, open-label, multicenter single-arm study focuses on patients (pts) with operable PDAC without metastatic disease. Other key eligibility criteria include age ≥18 years, resectability confirmed by multidisciplinary GI tumor board (resectable vs. borderline), adequate cardiac, renal, hepatic function and ECOG performance status of 0 to 1. Pts receive NEO-N-IRI regimen as per Table every 2 weeks for four months followed by disease reassessment. Pts who remain surgical candidates will undergo surgical resection within 4 to 8 weeks following last dose of therapy. The primary endpoint is to assess safety and feasibility of regimen in perioperative setting. Secondary endpoints include R0 resection rate, clinical, biochemical and radiological response rate and patient-reported quality of life during treatment as measured by the NCI validated FACT-G scale. Enrollment continues to a maximum of 28 evaluable pts to demonstrate a reduction in historical 30-day postoperative complication rate. Microbiota specimens will be collected for exploratory analysis. Clinical trial information: NCT03483038 . [Table: see text]