National Comprehensive Cancer Network Guidelines Research Articles

Abstract PO5-08-01: Investigating the Link between APC I1307K Mutation and Breast Cancer in Arab Population

Abstract Background: Identifying asymptomatic individuals with an increased risk of hereditary breast cancer may significantly enhance early detection and prevention strategies and may inform treatment decision of patients who carry such variants. The APC I1307K missense mutation is known to be unrelated to conditions such as familial adenomatous polyposis (FAP), attenuated FAP, or gastric adenocarcinoma. However, individuals of Ashkenazi Jewish ancestry who carry this variant, have increase risk of colon cancer compared to the general population. The association of this variant with other cancer types, such as breast cancer, and in individuals of other ancestries, like Arabs, remains unknown. In this study, we investigate the potential association between APC gene (I1307K variant) and breast cancer risk. Method: Over a course of 18 months, all newly diagnosed patients with solid tumors were offered to participate in a universal germline genetic screening study, utilizing a standard 21-gene or an investigational 84-gene panel testing. A retrospective analysis was conducted on the 153 patients within the study group who carry the APCI1307K missense variant irrespective of cancer type. Patients were classified as meeting the criteria or not meeting the criteria of the National Comprehensive Cancer Network (NCCN) v.1.2020. Data were extracted from electronic medical records and our institutional cancer registry. Descriptive statistics test was employed. Results: Among the screened cancer patients (n=3400), 153 (4.5%) were tested positive for the APC I1307K missense mutation are included in this analysis. Median age at cancer diagnosis was 52 (range,19-80) years, and 99 (64.7%) were female. Breast cancer was the most common primary tumor (n=67, 43.8%) followed by colorectal (n=38, 24.8%), lung (n=7, 4.6%) and pancreatic cancer (n=6,3.9%). Among the 67 breast cancer patients included, 16 (23.9%) were not eligible for genetic testing as per the NCCN guidelines, and were tested as part of the universal genetic testing study. Among the patients with breast cancer, 53 (79.1%) had screening colonoscopy and 9 (17.0%) were found to have polyps (range, 1-3); 8 (88.9%) were low-grade dysplasia, while the other 44 (83.0%) had completely normal colonoscopy. On the other hand, among the 38 patients with colorectal cancer, 21 (55.3%) had tumors presenting as polyps, or exhibited concomitant polyps (range, 1-3), or displayed abnormalities in the background that were polypoid in nature. Notably, 24 (63.2%) of patients with colorectal cancer, have a family history of breast cancer. Conclusions: APC I1307K variant is unexpectedly common among our cohort of Arab patients. Individuals who carry this variant may face an elevated risk of developing breast cancer; potentially contributing to hereditary and familial cases, and such patients are at higher risk for colorectal cancer, too. Citation Format: Baha' Sharaf, Hira Bani Hani, Anas Zayed, Maha Barbar, Ahmad Hushki, Rashid Abdel-Razeq, Mohammad Titi, Reem Al-Halalsheh, Suleiman Mahafdah, Hikmat Abdel-Razeq. Investigating the Link between APC I1307K Mutation and Breast Cancer in Arab Population [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 PO5-08-01.

Abstract PO5-10-08: Clinical Value of Molecular Targets and Genome-Targeted Cancer Therapies Recommended by the National Comprehensive Cancer Network for Advanced Breast Cancer

Abstract Background: Genomic testing has expanded the possibilities of precision cancer medicine, particularly for advanced, treatment-resistant breast cancer cases. However, the clinical significance of most genetic alterations remains uncertain, potentially overestimating tailored therapies. The National Comprehensive Cancer Network (NCCN) guidelines are evidence-based cancer-specific recommendations used in clinical practice and that are often determinative for insurance coverage. In this study, we assessed the validity of the targets and the clinical benefit of genome-targeted cancer drugs recommended in the NCCN guidelines for metastatic breast cancer. Methods: We identified genome-targeted oncology therapies supporting advanced breast cancer recommendations in the most recent NCCN breast cancer guideline (version 4.2023). Genome-targeted drugs were defined as involving use of a genomic test in which the drug targeted a genomic alteration. We analyzed data from trials supporting advanced genome-targeted breast cancer drugs recommendations. When multiple (or overlapping) articles for the same study were identified, the most recent publication was included. We extracted key details of each trial, including trial design, blinding, phase of clinical trial and primary efficacy end points. We cross-referenced the FDA-approved indications as of 30 June 2023 with the NCCN recommendations for each drug. Strength of evidence supporting molecular targetability was evaluated using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets (ESCAT). Clinical benefit for genome-targeted oncology therapies was assessed using the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS). We considered a substantial clinical benefit as a grade of 4 or 5. Molecular targets qualifying for ESCAT category level I-A and I-B associated with substantial clinical benefit by ESMO-MCBS were rated as high-benefit genomic-targeted breast cancer treatments. Results: We identified 47 recommendations supporting 17 genome-targeted drugs, which targeted 11 driver alterations. Out of these recommendations, 29 (62%) aligned with the FDA indications. We associated 47 trials with these recommendations, most randomized (24, 51%), phase 3 (23, 49%) and open-label (42, 89%). The most common primary endpoint (22, 47%) was overall response rate, followed by progression-free survival/time to progression (21, 45%). Twenty-four trials (51%) had a I-A ESCAT targetability, 7 (15%) had a I-B targetability, 6 (13%) had a I-C targetability score and 10 (21%) were categorized as II-B. ERBB2 amplification, germline BRCA1/2 mutations, PIK3CA mutations, and ESR1 mutation were mainly classified as tier I-A based on randomized trials demonstrating the effectiveness of approved targeted therapies in patients with these alterations. By contrast, RET fusions, NTRK fusions, high-tumor mutational burden and microsatellite instability were ranked as tier I-C and somatic BRCA mutations, germline PALB2 mutations and HER-2 mutations as II-B. Six trials (14%, 6/42) supporting drug approval demonstrated substantial ESMO-MCBS clinical benefit. Overall, 6 recommendations (14%) had high-benefit genomic-based cancer treatments. Conclusions: Fewer than one-fifth of molecular-targeted cancer therapies recommended in NCCN guidelines for metastatic breast cancer demonstrated substantial patient benefits. Value frameworks like ESCAT and ESMO-MCBS can help stakeholders identify therapies with the greatest potential. Citation Format: Ariadna Tibau, Thomas J. Hwang, Jerry Avorn, Aaron Kesselheim. Clinical Value of Molecular Targets and Genome-Targeted Cancer Therapies Recommended by the National Comprehensive Cancer Network for Advanced 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 PO5-10-08.

Abstract PO5-26-01: Assessing the effect of multimodal therapy in massive fungating breast cancers without distant metastasis

Abstract Background: Massive fungating breast cancers (MFBCs), which comprise exudative, foul-smelling tumors, the size of a child’s head or involve extensive ulceration are classified as locally advanced breast cancers. The National Comprehensive Cancer Network guidelines recommend preoperative neoadjuvant chemotherapy in patients with locally advanced breast cancer without distant metastases. However, limited evidence is available regarding the successful treatment of fungating breast cancers. In clinical practice, many fungating breast cancer cases are treated as stage IV tumors. This study aimed to investigate whether multimodal therapy, including surgery for giant breast cancers, can improve survival rates and whether the survival rates are comparable to those of other stage III breast cancers. Subjects and methods: Out of 1480 cases of primary breast cancer diagnosed at our hospital between June 2012 and March 2020, 123 patients with clinical stages IIIA–IIIC were chosen for analysis. Furthermore, 29 of these patients with MFBC were selected. During multimodal therapy for selected patients with fungating breast cancer, difficulties were encountered in some patients with single-stage skin suturing and closure after standard neoadjuvant chemotherapy. These patients underwent surgery with an additional skin flap or skin grafting. Furthermore, radiation therapy was added as needed. We compared the survival rates of these patients with those of patients who received drug therapy only according to the therapeutic protocol for Stage IV. Survival rates of patients with MFBC and other stage III breast cancers were also compared. Statistical analyses were conducted using the Kaplan–Meier curve and the log-rank test. Results: Of the 29 patients with MFBC, 22 (75.9%) and seven (24.1%) were treated with multimodal and palliative therapies, respectively. The median age and follow-up period of the multimodal therapy group were 62 (range: 43–94) years and 67 (range, 32–131) months, respectively. The corresponding values for the palliative therapy group were 79 (range: 42–88) years and 31 (range: 2–96) months. All patients in the palliative treatment group were hormone receptor positive and HER2 negative, and treatment with hormone therapy was initiated. The 7-year survival rate was significantly higher in the multimodal therapy group than in the palliative treatment group (92.3% vs. 68.6%, p = 0.0317). Furthermore, the 5-year distant recurrence-free rate was higher in the multimodal treatment group (79.3% vs. 63.5%). Local recurrence did not occur in any patient in the multimodal treatment group. There was no significant difference in the 7-year survival rates between patients with MFBC and those with other stage III breast cancers (86.8% vs. 75.3%; p = 0.239). Triple-negative breast cancer accounted for 20.8% (20 96) of the other stage III breast cancers, but none of these were MFBCs. Conclusions: Clinically, MFBCs are often palliatively treated as stage IV tumors, even in the absence of distant metastasis. However, the survival rate was significantly higher in the multimodal therapy group than in the palliative treatment group. Furthermore, the survival and distant recurrence-free rates for MFBC were higher than those for other stage III breast cancers. Therefore, patients with MFBCs should be actively treated using curative treatments. Citation Format: Tamaki Tamanuki, Maki Namura, Tomoyoshi Aoyagi, Haruhito Sakata, Mika Iwai, Shinichirou Shimizu, Hiroshi Matsuzaki. Assessing the effect of multimodal therapy in massive fungating breast cancers without distant metastasis [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 PO5-26-01.

Abstract PO4-08-02: Genetic testing among patients with triple-negative breast cancer at a single health system: a quality improvement project

Abstract Background: Breast cancer is the most common type and the second leading cause of cancer-related deaths in women. Approximately 15-20% of patients have triple-negative breast cancer (TNBC) at diagnosis. TNBC is aggressive, difficult to treat, prone to relapse, and associated with an increased mortality rate. The incidence of BRCA1/2 mutation is about 20% in patients with TNBC (Hartman et al. 2012). Despite the high prevalence of germline mutations in cancer susceptibility genes among TNBC patients, many do not received genetic counseling (GC) or genetic testing (GT). National Comprehensive Cancer Network (NCCN) guidelines now recommend GT for all patients with TNBC, regardless of age, especially after the approval of Poly Adenosine diphosphate Ribose Polymerase (PARP) inhibitors for targeted therapy against BRCA1/2 mutations. The aim of this quality improvement (QI) project was to identify patients with TNBC who did not receive GT and design an intervention to understand potential barriers to receiving GC and GT. Methods: We implemented a QI project to identify previously diagnosed adult patients with TNBC (18 years and older) of any stage (early or advanced/metastatic) without prior GT or family history of genetic disorders with active follow-up at the Henry Ford health breast cancer clinic. Eligible patients diagnosed between January 2015 and January 2020 from the Syapse Learning Health Network database were included. Baseline information as well as additional data including demographics, breast cancer treatment details, and whether GT and/or GC was offered or not was obtained through electronic health record review after institutional review board committee approval. Bi-monthly meetings were held amongst breast cancer providers, genetic counselors, and nurse navigators to develop an intervention to contact the patients who did not undergo GT and/or GC. After obtaining the list of patients who did not undergo GT and/or GC despite meeting eligibility criteria, they were contacted by their primary breast cancer providers via telephone regarding their willingness to obtain GT and/or GC at this time and participate in a questionnaire-based interview to understand barriers towards the same. Results: In the 5 years, a total of 123 patients were noted to have been diagnosed with triple-negative breast cancer. Of these, 93 patients were actively being followed at the Henry Ford breast clinic at the time of the QI project. 2 of the 9 patients who underwent GT and GC were positive for BRCA1/2 mutation. Of the remaining 83 patients that did not receive GC or GT, 65 (78.3%) had no clear reason explained in the chart, 27 patients (32.5%) chose not to get tested, 23 (27.7%) were not deemed to be eligible upon initial assessment and 4 (4.8%) had pending orders placed by breast surgeons upon initial diagnosis. Unfortunately, 29 of these 83 patients were noted to have been deceased when the intervention was being designed. Remaining 54 patients were contacted by their primary breast cancer oncologists to determine their willingness in participating in the questionnaire-based interview. Conclusion: Based on the results of our QI project, we have now developed a process to contact the identified patients and renew the offer for GT and GC as well as participation in a questionnaire-based interview to understand the potential barriers to testing. We also plan to improve physician education and awareness by conducting mini sessions during our annual symposium meetings as well as grand rounds and develop a protocol for ordering GT and GC in patients with TNBC at our institution. Citation Format: Manasi Godbole, Mary Nyhuis, Travis Washburn, Joann Hirth, Haythem Ali. Genetic testing among patients with triple-negative breast cancer at a single health system: a quality improvement project [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 PO4-08-02.

Abstract PO1-09-03: Clinical Impact of Multigene Panel Testing in Patients with a Personal or Family History of Breast or Ovarian Cancer Previously Negative for BRCA1/2 Genes

Abstract Rapid developments in cancer genetics and hereditary cancer risk assessments have enabled the identification of individuals at elevated risk for hereditary malignancies to guide enhanced cancer screening and prevention efforts. Multigene panel testing has emerged as the standard approach as emphasized in the National Comprehensive Cancer Network (NCCN) guidelines. The purpose of this study was to investigate the frequency of other pathogenic mutations identified through multigene panel testing in individuals who previously tested negative for germline BRCA1/2 and assess the clinical impact of panel testing. Patients either previously diagnosed with breast cancer or with a family history of breast or ovarian cancer that had also been seen by Oncology Genetics at a single institution and tested negative for BRCA1/2 genes but had not undergone prior multigene panel testing were invited via a letter to return for an additional genetic counseling visit to discuss multigene panel testing. Patients were also able to opt-in to a survey component of the study and received an email to fill out the Multidimensional Impact of Cancer Risk Assessment (MICRA) and Cancer Worry Scale (CWS). Surveys were completed prior to the initial genetic counseling appointment and repeated after discussion of the multigene panel test results. A total 24 women met with a genetic counselor of which 22 (92%) had a personal history of breast cancer, 1 (4%) had a family history of breast cancer, and 1 (4%) had a family history of ovarian cancer. The mean age was 52.6 years (range, 42-68) and 100% of women were Caucasian. Of the 24 women, 17 (71%) completed multigene panel testing. Of the women that underwent testing, 7 (41%) had negative results, 6 (35%) had variants of unknown significance (VUS), and 4 (24%) had a pathogenic mutation identified in another gene (CDKN2A, CHEK2, and CFTR). There was no significant change in MICRA or CWS scores after multigene panel results were reviewed in the 9 patients that completed both pre- and post-genetic testing surveys. The mean/median summary MICRA scores pre- and post-counselling were 30 (SD 12.4), median 26 (min 18, max 56), and 21.2 (SD 15.4), median 21 (min 3, max 43), respectively (p=0.19, Wilcoxon signed ranks test). The mean/median summary CWS scores pre- and post-counselling were 14.3 (SD 5), median 15 (min 7, max 24), and 13.6 (SD 2.59), median 14 (min 10, max 17), respectively (p=0.53, Wilcoxon signed ranks test). Of the 4 patients with newly identified pathogenic mutations, 2 started new screening protocols and 1 underwent a prophylactic mastectomy. In conclusion, multigene panel testing identified pathogenic mutations in a subset of individuals who previously tested negative for BRCA1/2 genes leading to changes in clinical management. The completion of multigene panel testing did not lead to a significant increase in MICRA or CWS scores. Key limitations of this study include a small sample size and an all Caucasian population. Citation Format: Devon Miller, Stephanie Pritzl, Angela Tess, Jessica Gooding, Lisa Barroilhet, Lori Dubenske, Kari Wisinski. Clinical Impact of Multigene Panel Testing in Patients with a Personal or Family History of Breast or Ovarian Cancer Previously Negative for BRCA1/2 Genes [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 PO1-09-03.

Development of palliative care clinical practice guidelines and referral care pathways for primary care practitioners in Pakistan

BackgroundDespite a large burden of life-limitingillness, there exists a dearth of services of palliative care in Pakistan. International guidelines have questionable applicability in Pakistan due to the socioeconomic differences. We generated a protocol describing the process of developing comprehensive palliative care guidelines and palliative care referral pathways for primary care practitioners to adopt in Pakistan.MethodsA GRADE-ADOLOPMENT approach with modification has been employed to create guidelines for a Pakistani context. The “National Comprehensive Cancer Network Guidelines Insights: Palliative Care, Version 2.2021” was used as the source guideline. Recommendations from the source guideline were reviewed by two local palliative care specialists to either “Adopt,” “Adapt” or “Exclude”. The finalized recommendations were incorporated into the local palliative care guideline. Clinical diagnosis and referral pathways were made from the finalized guideline. Any gaps in management found in the pathways were filled by taking existing recommendations from other credible guidelines.ResultsTwenty-seven recommendations were adopted without modification. No recommendations were deemed to be adapted and 15 were excluded. The referral care pathways created were reflective of the local guideline and included elements of initial assessment, preliminary management, reassessment, and referral. 6 additional recommendations were made.ConclusionThe described clinical practice guidelines and primary care clinical referral pathways will aid to standardize palliative care provision in Pakistan. These can be used by other resource constrained settings to develop guidelines within their own local context.

Neighborhood-Level Disadvantage and Delayed Adjuvant Therapy in Head and Neck Cancer

For patients with head and neck squamous cell carcinoma (HNSCC), initiation of postoperative radiation therapy (PORT) within 6 weeks of surgery is recommended by the National Comprehensive Cancer Network Guidelines and the Commission on Cancer. Although individual-level measures of socioeconomic status are associated with receipt of timely, guideline-adherent PORT, the role of neighborhood-level disadvantage has not been examined. To characterize the association of neighborhood-level disadvantage with delays in receiving PORT. This retrospective cohort study included 681 adult patients with HNSCC undergoing curative-intent surgery and PORT from 2018 to 2020 at 4 US academic medical centers. The data were analyzed between June 21, 2023, and March 5, 2024. The primary outcome was delay in initiating guideline-adherent PORT (ie, >6 weeks after surgery). Time-to-PORT (TTP) was a secondary outcome. Census block-level Area Deprivation Index (ADI) scores were calculated and reported as national percentiles (0-100); higher scores indicate greater deprivation. The association of ADI scores with PORT delay was assessed using multivariable logistic regression adjusted for demographic, clinical, and institutional characteristics. PORT initiation across ADI score population quartiles was evaluated with cumulative incidence plots and Cox models. Among 681 patients with HNSCC undergoing surgery and PORT (mean [SD] age, 61.5 [11.2] years; 487 [71.5%] men, 194 [29.5%] women) the PORT delay rate was 60.8% (414/681) and median (IQR) TTP was 46 (40-56) days. The median (IQR) ADI score was 62.0 (44.0-83.0). Each 25-point increase in ADI score was associated with a corresponding 32% increase in the adjusted odds ratio (aOR) of PORT delay (aOR, 1.32; 95% CI, 1.07-1.63) on multivariable regression adjusted for institution, age, race and ethnicity, insurance, comorbidity, cancer subsite, stage, postoperative complications, care fragmentation, travel distance, and rurality. Increasing ADI score population quartiles were associated with increasing TTP (hazard ratio of PORT initiation, 0.71; 95% CI, 0.53-0.96; 0.59; 95% CI, 0.44-0.77; and 0.54; 95% CI, 0.41-0.72; for ADI quartiles 2, 3, and 4 vs ADI quartile 1, respectively). Increasing neighborhood-level disadvantage was independently associated with a greater likelihood of PORT delay and longer TTP in a dose-dependent manner. These findings indicate a critical need for the development of multilevel strategies to improve the equitable delivery of timely, guideline-adherent PORT.

Immune-related adverse effects: Recognition and initiation of appropriate treatment in cancer patients on immunotherapy.

Delayed or improper identification of immune-related adverse events (IRAEs) during cancer treatment can impact time to receive proper treatment. This study describes rates of IRAE recognition and appropriate treatment in adult patients with cancer at a community teaching hospital. This single-center, retrospective, cohort study evaluated rates of proper IRAE treatment in conjunction with National Comprehensive Cancer Network (NCCN) guidelines. Secondary outcomes included time from presentation to IRAE diagnosis and hospital readmissions/repeat emergency department (ED) visits following initial admission for IRAE. Retrospective chart review assessed IRAE presentation including common terminology criteria for adverse event (CTCAE) grading and treatment choices. Fifteen subjects included in this study contributed to 21 encounters with noted IRAE. Over half (52.4%) of the encounters received proper IRAE treatment (e.g. correct drug, dose, route, frequency, or therapy duration). Nearly 22% of total actionable components were improper, occurring more often in patients with colitis, pneumonitis, and hepatitis. Median time to IRAE diagnosis was approximately 3.5 days, with the longest being 24 days. There were eight all-cause rehospitalizations one year after initial IRAE presentation, with four directly IRAE-related. Most (75%) IRAE-related rehospitalizations occurred with colitis. Seven ED return visits were also noted. Many IRAEs were misdiagnosed and/or received improper treatment resulting in increased rehospitalization/return ED visit rates. The importance of medical oncology involvement (e.g. medical oncology consult at time of admission and/or notification of primary oncologist) in IRAE management in the hospital or ED was also stressed. Organizations may benefit from systematic improvements and staff education to improve patient outcomes and prevent readmissions.

Utilization and Outcomes of Multigene Panel Testing in Patients With Pancreatic Ductal Adenocarcinoma.

Guidelines recommend germline genetic testing (GT) for patients with pancreatic ductal adenocarcinoma (PDAC). This study aims to evaluate the utilization and outcomes of multigene panel GT in patients with PDAC. This retrospective, multisite study included patients with PDAC diagnosed between May 2018 and August 2020 at Mayo Clinic Arizona, Florida, and Minnesota. Discussion, uptake, and outcomes of GT were compared before (May 1, 2018-May 1, 2019) and after (August 1, 2019-August 1, 2020) the guideline update, accounting for a transition period. The study identified 533 patients with PDAC, with 321 (60.2%) preguideline and 212 (39.8%) postguideline. Patient characteristics did not differ between the preguideline and postguideline periods. GT was discussed in 34.3% (110 of 321) of preguideline and 39.6% (84 of 212) of postguideline patients (odds ratio [OR], 1.26 [95% CI, 0.88 to 1.80]) and subsequently performed in 80.9% (89 of 110) of preguideline and 75.0% (63 of 84) of postguideline patients (OR, 1.10 [95% CI, 0.75 to 1.61]). Of 152 tested patients, 26 (17.1%) had a pathogenic variant (PV), of whom 17 (11.2%; 17 of 152) were PDAC-associated. Over the entire study period, GT was more likely in younger patients (65 v 70 years; P < .001), those seen by a medical oncologist (82.9% v 69.0%; P < .001), and those surviving more than 12 months from diagnosis (70.4% v 43.4%; P < .001). Demographics and personal/family cancer history were comparable between patients with and without a PDAC PV. GT remains underutilized despite National Comprehensive Cancer Network guideline recommendations. Given the poor prognosis of PDAC and potential implications of GT, efforts to increase utilization are needed to provide surveillance and support to both patients with PDAC and at-risk family members.

Abstract LB099: Identifying actionable genomic alterations in non-small cell lung cancer through the analysis of extracellular vesicles in plasma

Abstract Lung cancer is the second most common cancer worldwide, accounting for 2.2 million new cases and 1.8 million deaths in 2020. Personalized targeted therapy based on actionable molecular markers has completely transformed the therapeutic landscape in NSCLC, which has improved considerably the overall survival. However, ~50% of NSCLC patients with tissue biopsy inaccessible or inadequate, limiting biomarker testing and access to targeted therapies. The availability of a wide range of highly effective targeted therapy options for NSCLC justifies the significance of developing non-invasive and cost-effective detection assays for guiding targeted therapy selection in NSCLC.Extracellular vesicles (EVs) are lipid-bilayer-enclosed vesicles of sub-micrometer size that are secreted by virtually all cell types. They contain hundreds of different proteins, thousands of intact RNA species, and double-stranded DNA (dsDNA) fragments that sample the entire human genome. Recent findings further corroborate the potential role of EVs in early cancer screening, cancer diagnosis, treatment selection and monitoring. In this study, we used lipid nanoprobe (LNP) for EV isolation from plasma and droplet digital PCR assay for detecting actionable genomic alternation to aid targeted therapy selection in NSCLC. Specifically, we extracted EV associated DNA/RNA from plasma first, and then we used the individual ddPCR assays for detecting KRAS mutations, EGFR mutations, and ALK fusions from isolated EVs associated nucleic acids, respectively. We identified KRAS mutations G12C/G12S/G13C/G12A/Q61H, EGFR L858R mutation and exon 19 deletion, and ALK-EML4 gene fusion variant 3 from 12 NSCLC patients that matched the mutation status obtained from patient tissue specimens. Only in 1 out 13 patients, EV mutation status did not match the mutation status from the tissue specimen. This data indicated that clinical actionable gene mutations are present in EVs associated nucleic acids isolated from plasma samples of NSCLC patients. We anticipate that this novel non-invasive EVs-based actionable genomic alterations detection test would efficiently assist physicians/oncologists in selecting optimal targeted therapies for cancer treatment, as recommended by National Comprehensive Cancer Network (NCCN) guidelines for NSCLC. Citation Format: Hongzhang He, Jadranka Milosevic, Siyang Zheng. Identifying actionable genomic alterations in non-small cell lung cancer through the analysis of extracellular vesicles in plasma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB099.

Characterization of accelerated approval status, trial endpoints and results, and recommendations in guidelines for oncology drug treatments from the National Comprehensive Cancer Network: cross sectional study

ObjectivesTo evaluate National Comprehensive Cancer Network (NCCN) guideline recommendations for oncology drug treatments that have been granted accelerated approval, and to determine whether recommendations are updated based on the results...

Methodology for Using Real-World Data From Electronic Health Records to Assess Chemotherapy Administration in Women With Breast Cancer.

Identification of patients' intended chemotherapy regimens is critical to most research questions conducted in the real-world setting of cancer care. Yet, these data are not routinely available in electronic health records (EHRs) at the specificity required to address these questions. We developed a methodology to identify patients' intended regimens from EHR data in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study. In women older than 18 years, diagnosed with primary stage I-IIIA breast cancer at Kaiser Permanente Northern California (2006-2019), we categorized participants into 24 drug combinations described in National Comprehensive Cancer Network guidelines for breast cancer treatment. Participants were categorized into 50 guideline chemotherapy administration schedules within these combinations using an iterative algorithm process, followed by chart abstraction where necessary. We also identified patients intended to receive nonguideline administration schedules within guideline drug combinations and nonguideline drug combinations. This process was adapted at Kaiser Permanente Washington using abstracted data (2004-2015). In the OBCD cohort, 13,231 women received adjuvant or neoadjuvant chemotherapy, of whom 10,213 (77%) had their intended regimen identified via the algorithm, 2,416 (18%) had their intended regimen identified via abstraction, and 602 (4.5%) could not be identified. Across guideline drug combinations, 111 nonguideline dosing schedules were used, alongside 61 nonguideline drug combinations. A number of factors were associated with requiring abstraction for regimen determination, including: decreasing neighborhood household income, earlier diagnosis year, later stage, nodal status, and human epidermal growth factor receptor 2 (HER2)+ status. We describe the challenges and approaches to operationalize complex, real-world data to identify intended chemotherapy regimens in large, observational studies. This methodology can improve efficiency of use of large-scale clinical data in real-world populations, helping answer critical questions to improve care delivery and patient outcomes.

Evaluating Radar Reflector Localisation in Targeted Axillary Dissection in Patients Undergoing Neoadjuvant Systemic Therapy for Node-Positive Early Breast Cancer: A Systematic Review and Pooled Analysis.

SAVI SCOUT® or radar reflector localisation (RRL) has proven accurate in localising non-palpable breast and axillary lesions, with minimal interference with MRI. Targeted axillary dissection (TAD), combining marked lymph node biopsy (MLNB) and sentinel lymph node biopsy (SLNB), is becoming a standard post-neoadjuvant systemic therapy (NST) for node-positive early breast cancer. Compared to SLNB alone, TAD reduces the false negative rate (FNR) to below 6%, enabling safer axillary surgery de-escalation. This systematic review evaluates RRL's performance during TAD, assessing localisation and retrieval rates, the concordance between MLNB and SLNB, and the pathological complete response (pCR) in clinically node-positive patients post-NST. Four studies (252 TAD procedures) met the inclusion criteria, with a 99.6% (95% confidence [CI]: 98.9-100) successful localisation rate, 100% retrieval rate, and 81% (95% CI: 76-86) concordance rate between SLNB and MLNB. The average duration from RRL deployment to surgery was 52 days (range:1-202). pCR was observed in 42% (95% CI: 36-48) of cases, with no significant migration or complications reported. Omitting MLNB or SLNB would have under-staged the axilla in 9.7% or 3.4% (p = 0.03) of cases, respectively, underscoring the importance of incorporating MLNB in axillary staging post-NST in initially node-positive patients in line with the updated National Comprehensive Cancer Network (NCCN) guidelines. These findings underscore the excellent efficacy of RRL in TAD for NST-treated patients with positive nodes, aiding in accurate axillary pCR identification and the safe omission of axillary dissection in strong responders.

Evaluating appropriateness of 18F-fluciclovine PET/CT relative to standard of care imaging guidelines and the impact of ADT on positivity: a prospective study in 62 Veterans Administration patients at a single institution.

According to the National Comprehensive Cancer Network Guidelines, 18F-fluciclovine PET/CT is considered appropriate after negative standard of care (SOC) imaging. To prospectively compare 18F-fluciclovine to SOC imaging, investigate whether it should be done when SOC imaging is (+), and evaluate its detection rate in patients receiving androgen deprivation therapy. We recruited 57 prostate cancer patients with biochemical recurrence with 18F-fluciclovine PET/CT and SOC imaging within 30 days. Prostate-specific antigen (PSA) level, Gleason score (GS), history of radical prostatectomy (RP), radiation therapy (RT) or hormone therapy (HT) were reviewed. The 57 patients had a median PSA of 2.6 and average GS of 7.4; 27 (47.4%) had RP, 28 (49.1%) had RT, 1 (1.75%) had HT and 1 (1.75%) observation only. 18F-fluciclovine identified disease recurrence in 45/57 patients (78.9%), including oligometastasis in 18/45 (40%). SOC imaging identified recurrent disease in 12/57 patients (21.1%) while 18F-fluciclvoine identified additional sites of disease in 11/12 (91.7%). The (+) 18F-fluciclovine studies had a median PSA 2.6 ng/ml compared to 6.0 ng/ml in the (+) SOC studies. 18F-fluciclovine was superior to SOC imaging for lesion detection, identification of oligometastasis and identification of additional sites of disease.

Abstract 3812: Treatment guideline concordance for patients with metastatic hormone-sensitive prostate cancer (mHSPC) in the United States in IRONMAN, the International Registry for Men with Advanced Prostate Cancer

Abstract Background: Treatment intensification strategies with an androgen receptor pathway inhibitor (ARPI) and/or docetaxel chemotherapy in addition to androgen deprivation therapy (ADT) are guideline recommended treatment options for patients with metastatic hormone-sensitive prostate cancer (mHSPC). Prevalence of guideline concordant care for mHSPC patients in the US and its changes over time are not well characterized. Methods: The International Registry for Men with Advanced Prostate Cancer (IRONMAN) is a prospective cohort study of patients with newly diagnosed mHSPC and castration-resistant prostate cancer (CRPC). Therapies are captured by site personnel and by directly capturing data from treating physicians via physician questionnaires (PQ). We included all US patients with mHSPC enrolled from 2018 to January 1, 2023 with a completed PQ at enrollment. We examined patient characteristics, first-line treatments for mHSPC, and guideline concordance of first-line treatments. Guideline concordance was defined as a treatment regimen listed in the first National Comprehensive Cancer Network guidelines version for the year prior to treatment. Patients enrolled in clinical trials were excluded from analysis of treatment guideline concordance. Results: Among the 636 US participants with mHSPC, physicians completed PQs for 458 participants (72%). Participants had a median age of 68 years (interquartile range 62 - 75). Three hundred eight (78%) were White, 72 (18%) were Black, 13 (3%) were other races/ethnicities: 65 did not report race. First-line treatment for mHSPC based on the PQ was most commonly ADT + ARPI (59%) followed by ADT + docetaxel (17%), ADT monotherapy (14%), ADT + first-generation antiandrogen (3%), ADT + ARPI + docetaxel (3%), and other treatments (5%). Overall, 384 (86%) participants received first-line treatment that was guideline concordant at the time of treatment. Treatment guideline concordance was highest in 2018 (99%) when ADT monotherapy was considered as guideline concordant but then decreased to 80% in 2019 and remained largely stable from 2019 to 2022 (85%). Overall, rates of guideline concordance were similar when stratified by race (88% for White patients vs 85% for Black patients), age (90% for patients &amp;lt;65 years old vs 85% for patients ≥65 years old), and treatment at a Comprehensive Cancer Center (CCC) (87% at CCC vs 86% at non-CCC). Conclusion: Among patients with mHSPC treated in the US at 38 cancer centers, proportions of guideline concordant first-line treatment were high and remained stable over time, despite changes in approved therapies. Future efforts to understand reasons for treatment decisions will be important to better understand the relatively uncommon situations in which guidelines and actually received treatments differ for patients with mHSPC. Citation Format: Hannah Dzimitrowicz McManus, Lauren Howard, Kerri-Anne Crowell, Terry Hyslop, Jake Vinson, Dana E. Rathkopf, Philip Kantoff, Lorelei A. Mucci, Daniel George, Konrad Stopsack. Treatment guideline concordance for patients with metastatic hormone-sensitive prostate cancer (mHSPC) in the United States in IRONMAN, the International Registry for Men with Advanced Prostate Cancer [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 3812.

Abstract 6122: Disparities in biomarker testing practices in patients with metastatic non-small cell lung cancer (NSCLC) in the United States (US)

Abstract Background: Molecular testing is recommended in National Comprehensive Cancer Network guidelines for nonsquamous mNSCLC patients. While testing rates have been increasing, data from other tumor types suggest possible disparities in access to and use of biomarker testing. This study investigated real-world biomarker testing characteristics stratified by demographics for the EGFR, ALK, ROS-1, BRAF, MET, RET, and PD-L1 biomarkers in US patients diagnosed with mNSCLC. Methods: This study of adults ≥18 years old with stage IV mNSCLC used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database (01/2011-04/2023). Biomarker testing rate (i.e., proportion of patients with mNSCLC with at least one biomarker test) was quantified. Unadjusted biomarker testing rates were assessed in groups of patients stratified by demographic and clinical characteristics, including age group, sex, race, insurance type, Eastern Cooperative Oncology Group (ECOG) performance status (PS), smoking status, histology, and US region. Results: In 42,037 patients with mNSCLC, 34,510 (82.1%) received at least one test. The rates for each test were: ALK: 71.6%, BRAF: 48.8%, EGFR: 74.9%, MET: 41.4%, PD-L1: 49.3%, RET: 42.3%, and ROS1: 54.2%. Yearly testing rates increased, with the most recent year suggesting that anywhere from 78.7% of patients to 88.7% of patients received a test for at least one biomarker, with PD-L1 and EGFR being the least and most frequently tested, respectively. Rates of testing varied by age group, with 87.2% of younger patients (ages 18 to &amp;lt;50) receiving a test compared to 80.8% of older patients (ages ≥80). Asian patients had the highest testing rate (91.5%) whereas Black and Hispanic/Latino patients had the lowest (80.8% and 80.6% respectively). 82.2% of White patients, the largest racial demographic in this dataset, received at least one test. Commercial health plans had a slightly higher testing rate compared to Medicare or Medicaid (87.1%, 81.6% and 81.2%, respectively). Rates decreased as ECOG PS increased; in patients with ECOG PS=0, 89.6% received a biomarker test, whereas in patients with ECOG PS=3 and ECOG PS=4, 81.1% and 76.3% received a test, respectively. Smoking status (current or former) was associated with less testing (80.7%) compared to patients with no history of smoking (91.1%), and patients with non-squamous histology were more frequently tested (88.0%) compared to squamous histology (61.2%). The differences by sex and region were marginal. Conclusion: This study provides contemporary data on real-world biomarker testing and disparities in mNSCLC in the US. Results suggest that more work can be done to evaluate and address disparity gaps in specific subsets, including Black and Hispanic patients and those with a current or former history of smoking. Citation Format: Michael J. Dennis, Devin Abrahami, Maria Cecilia Vieira, Darrin Benjumea, Marley Boyd, Anran Shao, Kirsten Duncan, John Kelton, Sandip P. Patel. Disparities in biomarker testing practices in patients with metastatic non-small cell lung cancer (NSCLC) in the United States (US) [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 6122.

Abstract 1290: Racial and ethnic representation and disparities on clinical guideline panels in oncology

Abstract Purpose: Culturally competent diverse workforce is critical to equitable and progressive cancer care. Yet, racial bias, permeates practice and research in oncology. The National Comprehensive Cancer Network (NCCN) panels recommend guidelines that determine standards for patient care in the United States (US). We investigated the extent of racial/ethnic representation/disparity amid this higher echelon of cancer leadership. Methods: We collected data from publicly available NCCN (https://www.nccn.org) guidelines (version: 1.2023-5.2023) published between 11/2022-11/2023. Six research team members extracted data. Race/ethnicity (NIH categories: White, Black, Hispanic/Latinx, Asian) was identified by advanced AI detection software tools (Namsor and Kairos, utilizing names and facial recognition to infer US race). Gender was determined using name/pronoun (if available). All information was confirmed using online databases (institutional profiles, biographical paragraphs, social media) and group consensus (in case of discrepancies). Data regarding active US physicians was obtained using Association of American Medical Colleges (AAMC) 2022 physician specialty data report. The primary objective was to determine the racial/ethnic composition of panels and association between race/ethnicity and chairs/co-chairs/vice-chairs (lead positions or leads) within panels. Descriptive statistics were used. Proportions were compared using Fisher-exact or Chi-squared test (odds-ratio [OR] and 95% confidence intervals [95%CI] were reported). Results: We reviewed 63 panels corresponding to 63 distinct disease sites. A total of 1223 unique individuals [475 (38.8%) females and 748 (61.2%) males] accounted for 2162 panel members with a median of 34 members (range: 25-42) per panel. Racial/ethnic representation was 1455 (67.3%) Whites, 570 (26.4%) Asians, 93 (4.3%) Hispanics/Latinx, and 44 (2.0%) Blacks, which was comparable to racial/ethnic makeup of active US physicians (64%, 21%, 7% and 6%, respectively). Among these 2162 member positions, 129 (6.0%) were lead positions. In these leads, racial/ethnic representation was 105 (81.4%) Whites, 5 (11.4%) Blacks, 17 (3.0%) Asians, and 2 (2.2%) Hispanics/Latinx. Notably, no significant difference was seen between proportion of female (5.2%) and male (6.4%) leads (OR: 0.80; 95%CI:0.55-1.16; P=0.26). However, the proportion of Whites in lead positions was significantly higher than Non-whites (7.2% vs. 3.4%; OR: 2.2; 95%CI: 1.4-3.5; P &amp;lt; 0.001). Conclusions: Although, overall membership of NCCN panels shows favorable racial/ethnic diversity, underrepresentation and bias appear to subsist for non-White race/ethnicity, when it comes to leadership positions within this key decision-making body that influences cancer care. Further efforts to improve this disparity within oncology is an essential step to shaping equity within the field. Citation Format: Jonathan M. Loree, Arvind Dasari, Mena Shaheed, Himanish Gothwal, Kulwinder Singh, Hewad Shaheed, Riya Mangal, Shivek Gothwal, Jason Willis, Michael J. Overman, Scott Kopetz, Kanwal Pratap Singh Raghav. Racial and ethnic representation and disparities on clinical guideline panels in oncology [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 1290.

Important Radiologic and Clinical Factors for Predicting Overall Survival in Pancreatic Adenocarcinoma Patients Who Underwent FOLFIRINOX.

To predict poor overall survival (OS) in pancreatic adenocarcinoma (PAC) who underwent FOLFIRINOX (5-fluorouracil/leucovorin/irinotecan/oxaliplatin) using clinical and computed tomography (CT) findings. A total of 189 patients with PAC who received FOLFIRINOX were retrospectively included. Two reviewers assessed CT findings and resectability based on National Comprehensive Cancer Network guidelines. They determined tumor size changes according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Delta measurements were performed. Clinical results, such as whether to perform surgery, were also investigated. A Cox proportional hazard model was used to identify significant predictors for OS. A CT-based nomogram was constructed to predict OS. Seventy-four patients (39.2%) underwent surgery. For OS, rim enhancement of PAC on baseline CT (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.10-2.77; P = 0.018), high delta tumor on baseline CT (HR, 2.46; 95% CI, 1.55-3.91; P < 0.001), progressive disease at follow-up CT (HR, 8.89; 95% CI, 2.94-26.87; P < 0.001), and without surgery (HR, 2.81; 95% CI, 1.49-5.30; P = 0.001) were important features related to poor prognosis. The nomogram showed good predictive ability for the survival. Both clinical and CT findings were useful for predicting OS after FOLFIRINOX in PAC.

Upper Tract Urothelial Cancer: Guideline of Guidelines.

Upper tract urothelial carcinoma (UTUC) is a rare disease with a potentially dismal prognosis. We systematically compared international guidelines on UTUC to analyze similitudes and differences among them. We conducted a search on MEDLINE/PubMed for guidelines related to UTUC from 2010 to the present. In addition, we manually explored the websites of urological and oncological societies and journals to identify pertinent guidelines. We also assessed recommendations from the International Bladder Cancer Network, the Canadian Urological Association, the European Society for Medical Oncology, and the International Consultation on Bladder Cancer, considering their expertise and experience in the field. Among all the sources, only the American Urologist Association (AUA), European Association of Urology (EAU), and the National Comprehensive Cancer Network (NCCN) guidelines specifically report data on diagnosis, treatment, and follow-up of UTUC. Current analysis reveals several differences between all three sources on diagnostic work-up, patient management, and follow-up. Among all, AUA and EAU guidelines show more detailed indications. Despite the growing incidence of UTUC, only AUA, EAU, and NCCN guidelines deal with this cancer. Our research depicted high variability in reporting recommendations and opinions. In this regard, we encourage further higher-quality research to gain evidence creating higher grade consensus between guidelines.

Hidradenocarcinoma: A Case Series From the Scripps Clinic With a Systematic Review of the Literature.

Hidradenocarcinoma (HAC) is a rare adnexal carcinoma. To the best of the authors' knowledge, there are no published systematic reviews on HAC. To incorporate a case series from the authors' institution and systematically integrate reported information to provide a reference tool for optimization of diagnosis and management. A comprehensive MEDLINE search was conducted from database inception to 2021 using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This yielded 225 studies with 165 cases of HAC. References of included articles were also searched. In addition, 9 patients with HAC were identified from the authors' institution over the past 10 years. The mean age of HAC presentation is 60 years with a slight male predilection (60%). The head and neck is the most commonly affected region. Over 36% of cases either presented with metastatic disease or went on to metastasize. The most common treatment type was wide local excision, followed by Mohs micrographic surgery. Early detection with accurate histologic interpretation is prudent in all cases of HAC. Wide local excision is the current first-line treatment. However, Mohs micrographic surgery offers complete marginal analysis with evidence of reduced risk of metastasis and better outcomes compared with wide local excision. Currently, there are no National Comprehensive Cancer Network guidelines for the treatment of HAC, and consensus guidelines are limited to tumor and nodal metastasis staging provided by the American Joint Committee on Cancer, eighth edition. Thus, this case series and systematic review integrates important aspects of diagnosis, workup, and management of HAC.