Central Cancer Registry Research Articles

Comparative Trends in the Distribution of Prostate Cancer Stage at Diagnosis in the Department of Defense Cancer Registry and the Surveillance, Epidemiology, and End Results Data, 2004-2014.

It has been demonstrated that there was an increase in later-stage prostate cancer (PCa) at diagnosis after the U.S. Preventive Services Task Force recommended against prostate-specific antigen screening for prostate cancer. However, the cancer characteristics at diagnosis within the equal-access Military Health System (MHS) during the period have not been described. In this study, we compared PCa stage at diagnosis and its trends between the military health care system and the general public and further compared the trends in tumor stage by race. This study was based on nonidentifiable data from the U.S. Department of Defense's Central Cancer Registry (CCR) and the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. Patients diagnosed between 2004 and 2014 were included. The distributions of PCa stage at diagnosis over time were compared between the 2 populations. Comparisons were further conducted for White and Black patients, respectively. Among the 11,895 patients in the CCR and 544,142 patients in SEER, the majority of patients were diagnosed with stage I or II prostate cancer. However, the CCR had a larger proportion of early-stage tumors (stages I and II combined) with 84.3% vs. 80.0% of SEER patients. The proportion of late-stage tumors (stages III and IV combined) increased over time from 2008 for both populations and the proportion of early-stage tumors decreased for the general population. In terms of temporal distributions by race, the trends were the same between White and Black groups in the general population. In the MHS, the trends in the White patients were similar to those in the general population, but in the Black patients, the percentages of stages I and II at diagnosis continued to increase and those of stages III and IV decreased, differing from those in the general population. The MHS consistently diagnosed PCa at an earlier stage than the U.S. general population across all time periods evaluated in this study. Although similar trends were observed for White patients between both populations, the proportion of stages I and II at diagnosis increased from 2012 among Black patients in the MHS, which stands in sharp contrast to trends in the U.S. general population. Although the differences between the two populations may be associated with various factors, differences in accessibility to care and thus the use of prostate-specific antigen testing might play an important role.

Evaluation of concordance between blood-based and matched tissue molecular testing in a regional cancer center.

e15062 Background: Next-generation sequencing (NGS) to identify cancer-associated mutations together with an increasing array of targeted drugs with FDA approval allows for matching patients with more effective therapies. Tumor tissue molecular profiling is most often used to identify actionable biomarkers. Blood-based tests to sequence cell-free circulating tumor DNA (ctDNA) are a less invasive approach. Both methods have high specificity and sensitivity and provide insights into actionable biomarkers; however, little is known about how these NGS tests compare when used for the same patient. This study assessed the concordance of paired ctDNA and solid tumor profiling in patients treated in our regional cancer center. Methods: We retrospectively reviewed ctDNA and matching tumor sequencing data test results from CLIA/CAP laboratories between June 2018, and October 2023. The average testing turnaround time was 12.9 days for solid tumor sequencing and 7.7 days for ctDNA testing. We analyzed genomic variants, gene fusions, and microsatellite status in these patient results. The NGS tests for ctDNA included 83 relevant genes which reported single nucleotide variants, small insertions and deletions, splice variants, and limited copy number alterations and gene fusions. The NGS tests for tumor testing were performed on Formalin-Fixed Paraffin Embedded tissue samples using either a 592 relevant gene panel or whole exome sequencing, and either an RNA-based targeted capture panel of 52 genes or RNA whole transcriptome sequencing. Concordance is defined as both ctDNA and tumor testing reporting the same alterations, whereas discordant reports are defined as each reporting different alterations that didn’t overlap between ctDNA and tumor sequencing. Results: A total of 186 patients had both ctDNA and solid tumor sequencing tests done. Cancer types included pancreatic cancer (n = 42), breast cancer (n = 29), lung cancer (n = 28), colorectal cancer (n = 14), and others (n = 73). We observed concordance between tests in 76 (41%) patients in identifying the same genomic alterations. In 103 (55%) patients, we found discordant genomic findings (in the remaining 7 (4%) patients, there were no alterations detected (ND)). Among 103 patients for whom we found discordant findings between the tests, 41 (40%) showed genomic alterations only from the ctDNA test, 46 (45%) had results only from solid tumor profiling, and 16 (15%) had abnormal gene findings from both solid tumor and ctDNA testing but the results did not overlap. Conclusions: Our retrospective analysis comparing sequencing of ctDNA and tumor tissue demonstrated about 40% concordance in genomic findings. Our study indicates that these tests may be complementary. If one accepts a degree of discordance, then testing of ctDNA may be used to identify actionable genomic alterations in the setting of inaccessible or inadequate tumor samples for sequencing.

Assessment of breast cancer optimal care timeframes in a regional and rural real-world setting: A regional cancer centre experience in Australia.

e12614 Background: The Breast Cancer Optimal Care Pathway (Cancer Australia) is a national patient-centred guideline that seeks to standardise the management pathway for breast cancer patients and spans from early diagnosis through to survivorship. The guideline provides suggested optimal management-based timeframes including the time from general practitioner (GP) referral to specialist review (<2 weeks), time from specialist review to completion of investigations and multidisciplinary discussion (MDT) (<2 weeks), time to initiation of neoadjuvant therapy from MDT (<4 weeks) and time to surgery following completion of neoadjuvant therapy (<6 weeks). Methods: Retrospective data was obtained for patients undergoing neoadjuvant systemic therapy for newly diagnosed breast cancer between 2021 and 2023 at a regional tertiary cancer centre in Australia (Townsville University Hospital). Data included baseline patient demographics, tumour characteristics, staging, key optimal care pathway timepoints, treatment regimen and outcomes. Median and interquartile range were calculated for key timepoints. Results: Overall, 53 patients (100% female) were identified for inclusion. 10% of patients identified as Indigenous (n=5), 36% lived rurally (n=19) and 13% were treated using a tele-chemotherapy model (n=7). Receptor status was triple-negative in 20 patients (38%), hormone-positive in 17 patients (32%) and HER2-positive in 16 patients (30%). 15% of patients had stage I disease (n=8), 58% had stage II disease (n=31), 21% had stage III disease (n=11), while 6% of patients had oligometastatic stage IV disease at diagnosis (n=3). 24 patients (50%) were seen by a specialist within 2 weeks of GP referral (median: 15 days; IQR 9-19). 46 patients (87%) had a definitive management plan formulated at MDT within 2 weeks of specialist review (median: 5 days; IQR 4-9), with delays most commonly due to pending investigations (n=5; 9%). 48 patients (91%) proceeded with neoadjuvant therapy within 4 weeks of MDT (median: 14 days; IQR 11-22), with delays most commonly due to concurrent infections including COVID. 90% of patients (n=46) were ultimately commenced on neoadjuvant treatment within the 8-week optimal care timeframe from initial GP referral (median: 34 days; IQR 27-47). In comparison to patients living locally, patients residing in rural areas were less likely to achieve this target (79% v 97%, p=0.05). 83% of patients (n=43) underwent surgery within 6-weeks of completion of neoadjuvant treatment (median: 30 days; IQR 27-34). Conclusions: The neoadjuvant breast cancer optimal care timeframes were feasible to achieve in a regional and rural setting. However, further targeted research is needed to improve adherence to optimal care standards for patients from rural areas, such as the timeframe from initial referral to completion of investigations and MDT.

Improving symptom screening rates for patients with head and neck cancer.

e23246 Background: Effective symptom management in cancer care relies on regular and accurate reporting using validated patient-reported outcome measures (PROMs), such as the Edmonton Symptom Assessment System (ESAS). The ESAS measures nine common cancer symptoms, rating them on a scale from 0 to 10 to improve monitoring and communication regarding patient symptoms and prevent adverse outcomes such as emergency department visits. There is a need to enhance completion rates to ensure that head and neck cancer (HNC) symptoms are effectively addressed. High completion rates provide valuable data for cancer centers and clinicians to intervene early and support patients through their cancer journey. This makes it an important target for quality improvement (QI) with wide-ranging implications for patient outcomes and care quality. Our objectives were to: Investigate underlying reasons for poor ESAS completion rates. Lay the groundwork for strategic interventions aimed at bolstering symptom screening among HNC patients. Methods: This was a QI project targeting the HNC patient population at a regional cancer centre (RCC). Our approach included stakeholder engagement meetings alongside the expertise of QI specialists. Comprehensive data collection was conducted to analyze symptom screening rates and identify potential barriers to ESAS completion. We tracked ESAS completion on weekly HNC clinic days from 2022-2023 via manual and automated chart abstraction. Patient, staff, and volunteer interviews, along with direct clinic observations, provided data for Ishikawa diagrams, facilitating a root cause analysis. Results: We identified a marked decline in ESAS completion rates, steadily decreasing from an average of 29.4% during the 2022-2023 fiscal year to an average of 7.6% between April-November 2023, with rates dropping as low as 3.3% in September 2023. Root cause analysis pinpointed several barriers to ESAS completion, including the transition from paper-based assessments used during the pandemic to electronic formats, low patient awareness of the purpose of symptom screening, perceived lack of value in screening by patients and staff, and the absence of direct guidance from staff in helping patients complete their ESAS. Variable communication practices and inconsistencies in registration staff directing patients to kiosks was also observed. Improving infrastructure and support for volunteer services was identified as a potential solution, which may optimize their effectiveness in symptom screening roles. Conclusions: The project has laid the foundation for targeted QI interventions aimed at improving ESAS screening adherence. By addressing the identified barriers, this work endeavors to re-engage patients in active symptom reporting and to integrate this critical aspect of care into the daily routine of the outpatient hospital setting, thereby enhancing the overall management of HNC symptoms.

The CROWN study: Cardiac outcomes with near-complete estrogen deprivation.

TPS12146 Background: Treatment for premenopausal women with high/intermediate risk hormone receptor (HR)-positive breast cancer (BC) includes the concurrent use of ovarian function suppression (OFS) and an aromatase inhibitor (AI) to induce near-complete estrogen deprivation (NCED). The long-term cardiovascular (CV) sequela for women treated with NCED is unknown. Premature menopause in non-cancer populations is associated with CV morbidity. Given the overall CV injury associated with BC treatment and the future life-years of these women, the CV impact of NCED warrants further study. The CROWN study uses sophisticated imaging assessments of cardiac dysfunction and biomarker and demographic correlates to understand the evolution of CV injury with the goal of developing tools to assess and mitigate CV risk. Methods: This is an NIH funded prospective cohort study conducted at 3 regional NCI-supported Cancer Centers (Duke University, Wake Forest University and Virginia Commonwealth University) that includes premenopausal women, age ≤ 55, with Stage I-III BC following completion of planned chemotherapy, surgery and radiation with an ECOG 0-2. HR-positive BC patients are receiving an AI and OFS. Women with HR-negative BC are included as comparators. CV imaging and biomarkers will be obtained at baseline, 1 year and 2 years (Table). These assessments include serial cardiac magnetic resonance (CMR) and coronary computed tomography angiography (CCTA) imaging as well as laboratory measurements, including exploratory biomarkers. The primary objective is to determine the 24-month difference in stress myocardial blood flow as measured by adenosine CMR imaging in both groups. Correlation of CMR imaging with CCTA detail of coronary plaque changes is planned. The relevance of pre-existing risk factors on study outcomes, including an emphasis on race and dynamic change in modifiable and treatment related risk factors will also be assessed. We plan to enroll 90 women,65 in the NCED group and 25 in the HR-negative group, allowing for a 10% drop out rate. The first primary statistical analyses will include testing hypotheses between group (NCED vs HR-negative) and within group (longitudinal changes within the NCED group). Secondary analyses involve developing predictive equations to determine if patient demographics, clinical parameters and serum biomarkers are associated with CV changes over time. We have currently enrolled 34 women (31 NCED and 3 HR-negative). 2 out of 3 patients entering the 2nd year of the study have returned for their year 1 imaging. Retention will be a key component of this study as analysis of the primary and secondary endpoints are dependent on completion of imaging. Clinical trial information: NCT05309655 . [Table: see text]

Time to treatment initiation: An assessment of trends in delays in patients with lung cancer across Missouri.

11186 Background: Lung cancer is a major health challenge globally. Missouri's incidence rate of 68.1% exceeds the national rate of 54.0% indicating a significant disease burden. It is the 2nd most common malignancy in men and women in the state. Timely treatment can significantly improve while delays can worsen outcomes. The Institute of Medicine strongly recommends efforts promoting timely care in lung cancer. The RAND Cooperation suggests treatment should begin within 6 weeks after diagnosis. These priorities align with the Healthy People 2030 Initiative which aims to reduce lung cancer incidence and mortality through enhanced screening and early treatment. The U.S. National Committee on Health Care identified a goal of 60% of lung cancer patients receiving treatment within 30-days of diagnosis. Our primary objective was to assess delays in treatment initiation post-diagnosis and to investigate Missouri’s adherence to treatment delay guidelines in lung cancer patients. Methods: Study population included adults (age>18) with a diagnosis of Lung Cancer, identified using ICD-10 codes C50.0-C50.9. Records were retrieved from the Missouri Cancer Registry and Research Center database for the years 2012-2022. Data for 2022 had a completion rate of 90%, all others had at least 95% completeness. We used the RAND guidelines 42-day treatment delay rule and the Missouri Cancer Action Plan's (MCAP) 30 day treatment delay metric as our benchmarks. Treatment delay was determined by subtracting the Date of Initial Diagnosis from the Date of First Course Treatment. Records with missing or incomplete dates were excluded. Data processing and analyses were performed using Python 3.11. Results: Of the 68,293 adult lung cancer patients in the database, 7,882 were excluded due to missing or incomplete data. Among the eligible 60,411 patients, 89.5% were Caucasian, median age was 69 (range 18-105), gender distribution was nearly equal with males accounting for 51.3% of the total. Average time from diagnosis to treatment was 36.8 days, with a median of 27 days. About 31.2% of patients had a gap over 42 days from diagnosis to first treatment. This delay has risen from 26.3% in 2012 to 42.6% in 2022, marking a 16.3% increase. In terms of adherence to the MCAP’s 30 day treatment delay metric, 45.6% of patients experienced more than a 30-day gap between diagnosis and treatment. The trend shows an increase in delays, from 40.4% in 2012 to 58.1% in 2022, reflecting a 17.7% rise. Conclusions: Despite the declining incidence rate of lung cancer in Missouri over the years, our analysis revealed a surprising increase in treatment initiation delays over the years. The average time from diagnosis to treatment and the percentage of patients experiencing delays exceed the RAND guideline and the MCAP's treatment delay metric and with a rising trend from 2012 to 2022. Further analysis into factors causing delay in treatment initiation is needed and being planned.

Patterns and risk factors of immune-related adverse events in a real-world cohort with lung cancer receiving immunotherapy.

12130 Background: Immune checkpoint inhibitors (ICIs) have emerged as a core pillar of lung cancer (LC) therapy, but ICIs are commonly associated with a spectrum of immune-related adverse effects (irAEs). The real-world patterns and risk factors of irAEs in LC remain uncertain. Methods: Patients with LC newly started on ICIs between 10/01/2018 and 09/30/2021 were retrospectively collected from the Tufts Medical Center cancer registry and pharmacy records. irAEs occurring within 12 months after initiation of ICIs were identified. Univariable logistic regression was used to assess the risk factors of irAEs. Those with p-value<0.20 were included in multivariable logistic regression analysis (MVA), along with clinically relevant factors. Results: Of 125 LC adult patients (median age: 70 years, 68 males), 104 had non-small cell lung cancer (NSCLC), 123 had advanced stages, and 16 had preexisting autoimmune diseases (ADs). Six patients were treated with dual-agent ICIs. Pembrolizumab was the most often used single agent (67.2%). In total 50 irAEs occurred in 39 patients. The most common irAEs were endocrinopathies (34%), pneumonitis (20%), dermatitis (14%), and gastrointestinal toxicity (14%) with the median onset time of 148, 136, 19, and 68 days, respectively. 70% of irAEs were grade 1 or 2. 44% of irAEs were treated with immunosuppression, 38% were referred to specialist care, and 30% required hospitalizations. 56% of irAEs resolved within 12 months and 67.9 % of those were rechallenged with ICIs. In exploratory univariable analyses among all the patients, age, small cell lung cancer (SCLC), PDL1 positivity (TPS≥1%), concurrent NSAIDs use, and radiation therapy had p< 0.2. In MVA, SCLC remained significantly associated with irAEs (OR=4.14, 95% CI [1.50, 12.09], p=0.007). Among NSCLC subset (N=104), age, PDL1 positivity, concurrent NSAIDs, and acetaminophen use had p<0.2. Age (OR=0.94, 95% CI [0.883, 0.990], p=0.026) and PDL1 positivity (OR=3.17, 95% CI [1.12, 9.87], p=0.036) remained significant in MVA (Table). Conclusions: Our study described the real-world patterns of irAEs in LC patients. SCLC was found to be an independent risk factor of irAEs in our cohort. In NSCLC, younger age and PDL1 positivity were associated with irAEs occurrence. Future studies are required to validate these findings in larger samples. [Table: see text]

Risk factors for positive margin in breast conservation surgery for localized breast cancer.

e12539 Background: Breast cancer is an evolving global concern due to its increasingly high morbidity and mortality rates. This is, in part, due to health care disparities in breast cancer patients that have been a problem for screening, diagnosis, and treatment. Breast-conservation surgery (BCS) is defined as the removal of breast tumor tissue surrounded by a margin of normal tissue and includes lumpectomy, partial mastectomy, wide excision, and segmental mastectomy. Negative margins post-BCS are necessary to avoid any breast cancer recurrence. A negative margin is defined as no gross or microscopic disease, also known as no tumor on ink. Positive margins are associated with patients who may have to undergo re-excisions with larger margins or total mastectomy, exposing patients to greater morbidity and delaying the start of adjuvant therapy. Methods: This was a retrospective cohort study designed to examine factors associated with positive margins (PM) in breast cancer patients undergoing breast-conserving surgery. The Charleston Area Medical Center cancer registry was queried from 2009-2022 for females diagnosed with invasive breast cancer who had surgery for localized disease (TxN0M0), excluding those with previous malignancies. Data were analyzed with SAS 9.4 using student’s t-test for continuous variables, Chi-square or Fisher’s exact for categorical variables, and multivariate analysis to identify factors predictive of positive margins. Results: In total, 1133 female patients with mean age of 64±11 met inclusion criteria. The positive margin group (PMG) made up 10.2% of the population while the negative margin group (NMG) was 89.8%. The PMG had significantly (p < .0001) larger tumors than the NMG, 19.7±12 and 13.8±9, respectively. Multifocal tumors made up 18% of the PMG compared to 4.4% of the NMG (p < .0001). Invasive lobular carcinoma made up 20% of the PMG compared to 7.2% of the NMG (p = .003). Recurrence was significantly (p = .030) higher in the PMG compared to the NMG, 7.4% and 3.2%, respectively; however, 5-year survival showed no difference. Regression modeling showed that multifocal tumors were 4.4 times (95% CI: 2.4-8; p < .0001) more likely to be associated with PM, lobular carcinoma was 2.8 times (95% CI: 1.6-4.8; p = .0003) more likely to be associated with PM, and stage II patients were 2.4 times (95% CI: 1.5-3.7; p = .0002) more likely to have PM. Conclusions: Univariately, tumor size, multifocality, lobular carcinoma, stage II, and local/distant recurrence were all associated with positive margins. This finding was re-demonstrated with respect to multifocality, lobular carcinoma, and stage II following multivariate analysis. The results of this study may help to guide surgeons and oncologists in the management of localized, invasive breast cancer, especially in emphasizing the importance of timely follow-up in patients at higher risk and in the education of patients regarding their care.

Geographic disparities in brachytherapy accessibility for cervical cancer.

1577 Background: While brachytherapy stands as a crucial component of the treatment for locally advanced cervical cancer, the issue of geographic disparities in brachytherapy accessibility has become a noteworthy public health concern in South Korea. Moreover, the specific factors contributing to these disparities have not been clearly elucidated. In light of this, we conducted a nationwide ecologic study to comprehensively investigate the socioeconomic factors associated with brachytherapy accessibility. Methods: A total of 2,998 patients newly diagnosed with cervical cancer in 2020 were identified through the Korea Central Cancer Registry (KCCR). Across 17 administrative districts in South Korea, 32 brachytherapy facilities were available. To capture unique socioeconomic factors for each region, including the number of Korean Medicaid (K-Medicaid), Medicare (K-Medicare) beneficiaries, marriage immigrants, registered foreigners, and total residents, data were obtained from the Korean Statistical Information Service (KOSIS). Notably, K-Medicaid and K-Medicare represent governmental medical insurance assistance for patients in poverty and those aged over 65, respectively. The brachytherapy accessibility rate (BAR) was defined as the number of brachytherapy procedures divided by new cervical cancer cases. Additionally, each district's socioeconomic factor was normalized by the number of residents. Univariate and multivariate logistic regression analyses were conducted to explore the relationships between BAR and socioeconomic factors. Results: The capital city and its adjoining metropolitan area accounted for 46.9% of the total brachytherapy facilities, with Seoul having 25% (8 out of 32) and Gyeonggi having 21.9% (7 out of 32). Conversely, three non-metropolitan regions had no brachytherapy facilities. In the multivariate logistic regression analysis, the brachytherapy accessibility rate (BAR) demonstrated an inverse association with both the number of K-Medicare beneficiaries and the total immigrant population (Odds ratios of 0.66 and -2.85, respectively). Conclusions: To the best of our knowledge, this is the inaugural study highlighting the robust associations between older age and foreign residency status with reduced accessibility to brachytherapy. The observed inaccessibility to brachytherapy has the potential to impede the delivery of standard care, consequently leading to a poorer prognosis for vulnerable populations. Future research endeavors and targeted social interventions will be imperative to rectify geographic disparities in brachytherapy accessibility and ensure equitable healthcare outcomes.

Long term follow up of monoclonal gammopathy of undetermined significance (MGUS) in US Veterans: Racial differences and associations with other malignancies.

7573 Background: Monoclonal gammopathy of undetermined significance (MGUS) is associated with lymphoid malignancies such as lymphoma and myeloma, but the association with other malignancies has not been described in the US veteran population. Methods: Veterans diagnosed with MGUS from 1991-2023 were identified from the US Veteran Affairs Central Cancer Registry (VACCR). Age at the diagnosis of MGUS was divided into four categories of <60, 60-69, 70-79, 80+. Variables collected included demographic factors and the diagnosis of other cancers. Differences were analyzed using the Chi Square test. Results: There were 3975 veterans who met the criteria. Most patients were male (96.7%) with a median age at diagnosis of MGUS of 70.5 (IQR 65.4-76.0). Almost 1/3 of patients were Black and were diagnosed with MGUS at a younger age compared to White veterans (Table, p<0.0001). Over the 32-year period included in this study, 2/3 of patients remained with a diagnosis of MGUS (62.3%) alone whereas 29.4% had 1 additional malignancy diagnosed and 8.3% had 2 or more additional malignancies. Black veterans with MGUS were more likely to have additional malignancies than white patients (41.4% vs 35.9%, p=0.016). MGUS was diagnosed prior to other cancers in 52% of patients and afterward in 48%. The most common cancers diagnosed in patients with MGUS were prostate (31%), lymphomas (13%), GI (12.5%), lung (12.0%), and skin (6.8%). CLL (3.4%), LPL (3.0%). Among lymphomas, CLL (3.4%) and LPL (3.0%) were most common. Of note, multiple myeloma or plasmacytoma was diagnosed in 6.5% of patients. The proportion of patients with MGUS and additional malignancies was comparable in the 4 age cohorts (p=0.072), indicating that younger patients with MGUS were as likely to be diagnosed with additional malignancies as older patients. Conclusions: In US veterans, nearly 1/3 of those diagnosed with MGUS were Black. These patients were younger when diagnosed with MGUS and were more likely to develop additional malignancies compared to White veterans. Over the 32 years of this study, a considerable proportion of veterans with MGUS developed various solid tumors. Further investigation is warranted to understand the racial, genetic, and other factors that may be contributing to the development of cancers in patients with MGUS. [Table: see text]

Clinical differences and management trends of localized breast cancer in the advanced geriatric population.

e12543 Background: Breast cancer remains the most common cancer diagnosis in women and, with the aging Baby Boomer population, is poised to represent an even larger volume of oncologic care in the United States over the coming decades. Combined with limited evidence-based guidelines for geriatric patients, particularly those above the age of 80, there exists the potential for unnecessary morbidity and mortality. This study aims to shed light on the characteristics of this population, including disparities, with an aim to identify subsets of patients who may benefit from more aggressive treatment. Methods: This was a retrospective cohort study to examine key clinical differences between the advanced geriatric breast cancer population (≥80 years) and those of younger age, comparing comorbidities, tumor characteristics, and management trends. The Charleston Area Medical Center cancer registry was queried from 2009-2022 for females diagnosed with invasive breast cancer who had surgery for localized disease, excluding those with previous malignancies. Data were analyzed with SAS 9.4 using student’s t-test for continuous variables, Chi-square or Fisher’s exact for categorical variables, and 5-year survival rates attained via Cox regression models. Results: The analysis involved 1041 female patients, divided into two age groups: 969 who were < 80 years old and 72 who were ≥80 years old at time of breast cancer diagnosis. The ≥80 group had significantly more individuals with hypertension, 83.3% v 63.7% (p < .001), osteoporosis, 26.8% v 9.5% (p < .001), cardiac arrhythmia, 18.1% v 7.3% (p = .001), and CVA, 11.1% v 4.5% (p = .014), than the < 80 group. Looking at overall trend, tumor grade was significantly (p = .040) lower in the ≥80 group than the < 80 group, G1 34.7% v 24.9%, G2 44.4% v 45.4%, G3 20.8% v 29.7%, respectively. Her2neu positivity was significantly (p = .010) lower in the ≥80 group at 0.0% compared to the < 80 group at 8.4%. There was no difference in the rate of endocrine therapy between the two groups (p = 0.320). Only 26.4% of the ≥80 group received radiotherapy compared to 79.0% of the < 80 group (p < .001). None of the ≥80 group received chemotherapy compared to 22.5% of the < 80 group (p < .001). Overall, 5-year survival for those < 80 and ≥80 was 92% and 84%, respectively (p < .001). Conclusions: In summary, patients 80 years of age or older were more likely to have hypertension, osteoporosis, cardiac arrhythmia, and history of CVA. Regarding tumor characteristics, both grade and Her2neu positivity were significantly higher in the < 80 group. There was no difference in the administration of endocrine therapy. Radiotherapy and chemotherapy, however, were used at significantly lower rates in the advanced geriatric population, likely in adherence with current NCCN guidelines for adjuvant therapy in patients ≥70. Further investigation may help to elucidate subgroups amenable to more aggressive adjuvant therapies.

Automating the detection of treatment progression in patients with lung cancer using large language models.

e13620 Background: Accurate assessment of treatment response is fundamental to advancing cancer patient care, particularly in lung cancer, where treatment modalities are diverse and complex. The extraction of treatment response, particularly disease progression information, from Electronic Health Records (EHRs) is essential for several reasons: It facilitates generation of real-world evidence from real-world data, enables personalized treatment planning, and contributes to a broader understanding of cancer therapeutics. However, much of treatment response information is documented in free-text EHR notes and traditional methods of extracting such information from notes are labor-intensive, error-prone, and inefficient, presenting significant barriers to timely and accurate real-world evidence studies. The advancement of Natural Language Processing (NLP) technologies, especially Large Language Models (LLMs), presents a transformative opportunity to automate the extraction of treatment responses. Methods: We used a cohort of 1,953 primary lung cancer patients identified from UPMC Hillman Cancer Center cancer registry and retrieved ~113,000 clinical notes from UPMC clinical data warehouse. We focused on extracting disease progression information, following the RECIST guidelines which define progression as an increase in tumor size or cancer markers after therapy. We selected ~50 notes to perform manual annotations by an experienced oncologist and created a gold standard dataset to validate the NLP models. We fine-tuned a state-of-the-art open-source LLM named LLAMA-2 and compared against a traditional rule-based NLP system for the automated extraction of disease progression from notes. The process of fine-tuning involved adjusting the model's parameters specifically to improve its ability to recognize and classify instances of disease progression. Results: Our analysis demonstrated a significant enhancement in performance with the LLM compared to the traditional rule-based NLP system. LLM exhibited a remarkable increase in sensitivity by ~37%, indicating its superior ability to accurately identify disease progression. Additionally, the model maintained high specificity and PPV, achieving scores nearly comparable to the rule-based system but with a notable improvement in the F1-score by ~14%. Conclusions: Our research highlights the transformative potential of LLM-based NLP algorithms in automating the extraction of treatment responses from free-text EHRs. This methodology not only provides a scalable and efficient mechanism for processing large volumes of clinical text but also significantly enhances the accuracy of lung cancer treatment response assessments. [Table: see text]

Healthcare spending after a cancer diagnosis among working-aged adults.

11071 Background: The cost of cancer care has increased dramatically over the past decades, increasing the financial burden on patients. However, current estimates of healthcare spending and out-of-pocket burden rely heavily on data from older populations, which may not reflect contemporary treatment patterns in working-aged adults given the rise in use of novel therapies and increased incidence at younger ages. Methods: We used the 2012-2021 Colorado Central Cancer Registry linked to the All-Payer Claims Database to identify adults aged 22-63 newly diagnosed with cancer. We examined median health plan payments and out-of-pocket spending across the most common insurance and cancer types in six months after diagnosis. Results: Among 20,460 individuals newly diagnosed with cancer, the median total spending in the six months after diagnosis was $60,123 for those insured by private fee-for-service (FFS) plans and $26,326 for those insured by Medicaid. The majority of spending was for medical care. Among individuals insured by private FFS plans, those with lymphoma had the highest total median spending at $125,892, followed by lung ($99,823), breast ($87,121), leukemia ($86,776), and colorectal cancer ($76,273). Although total spending was markedly lower among those insured by Medicaid, individuals with leukemia ($52,591) and lymphoma ($46,787) experienced the highest median spending. Out-of-pocket spending was substantially higher for the privately insured ($3,751 or approximately $625/month) across all cancer types, and highest for lymphomas ($4,262), breast ($4,706) and colorectal ($4,216) cancers. Conclusions: Total healthcare spending after a cancer diagnosis is significant in the working-aged population and creates a substantial out-of-pocket burden, even among those privately insured. [Table: see text]

Cervical cancer screening in 48000 females over two decades: Feasibility and success of community-based screening in Kerala, India.

10550 Background: Cervical Cancer is still significant cause of mortality and morbidity among females in India. Various methods of cancer screening are currently practiced for cervical cancer prevention including human papilloma virus (HPV) screening, pap smear, visual inspection with Lugol’s iodine (VILI), visual inspection with acetic acid (VIA) etc. The success of any cancer screening method is based on the feasibility of large-scale implementation at community level and the scientific validity of the screening test. VIA/VILI has been proven to prevent mortality in cervical cancer. This study is based on analysis of prospectively maintained database of community based cervical cancer screening using VIA/VILI in northern Kerala from 2002 to 2020. Methods: Retrospective analysis of prospective database of cervical cancer screening from 2002 to 2020 done by Malabar Cancer Care Society in Kerala, a non-governmental organization with support from governmental bodies like ISRO. Data was collected into excel sheets and were rechecked. The data on demography, type of screening, detection of precancerous and cancerous lesions was analyzed. Descriptive statistics were used to analyze the data using SPSS Version 20.0. Results: A total of 48008 individuals were screened over 18 years. 55% were premenopausal. 33% were fully asymptomatic and remaining 66% had white discharge per vaginum (25%), bleeding per vaginum (14%) or combination of symptoms (25%). 18% had abnormal per speculum findings (bleeds on touch, discharge etc.) 86% had unhealthy cervix.26% (12650) had VIA/VILI and 74% (35658) had pap smear. The pap smear findings were normal (41%), atrophic (17%), inflammatory (40%) and 2% had pre-cancerous/ cancerous changes. Of these lesions, 46% were HSIL, 36% were LSIL, 5% ASUS and 13% were squamous cell carcinoma (52 cases). Screen positive rate was 325 (0.005%) out of 48008. Treatment of precancerous lesions was by Cryotherapy (54%), LEEP (10%) and Surgery (36%). Treatment of invasive carcinoma was by surgery (91%) and radiation (85%). Referral to regional cancer center was done in 26% patients. The screen positive rate shows decreasing trend over the last two decades. Conclusions: Cervical Cancer screening in large scale in low resource setting is feasible in India by both pap smear and VIA/VILI with community based interventions led by NGO with support from governmental bodies. This model can be considered ideal for India and other low middle income countries with logistic difficulties for large scale HPV based screening.

Immunotherapy toxicity prediction in patients with melanoma using machine learning algorithms.

e21567 Background: Immune checkpoint inhibitor (ICI) related toxicity is common in melanoma patients, but identifying who will experience toxicity can be challenging. Precision medicine tools that accurately predict ICI toxicity could improve patient outcomes. This study aimed to use Machine Learning (ML) to predict ICI toxicity in patients with melanoma. Methods: 384 datasets were available for patients started on immunotherapy between 2014-2023 in a single, large regional cancer center in Kent, U.K. Raw data was preprocessed using a standard scaling function and one hot encoding, followed by SMOTE to balance the imbalanced classes. Six ML algorithms were developed using 80% of the training data, tested on 20% of validation data and used the Grid Search Cross-Validation technique for hyperparameter optimization. Shapley Additive Explanations (SHAP) explainable artificial intelligence was used to interpret the toxicity prediction model to improve the interpretation and transparency of the decision boundary. Results: Of the 384 patients, 112 patients (29%) had completely resected disease and then had adjuvant treatment while 272 (71%) were unresectable or had metastatic disease and had palliative treatment intent. In the metastatic setting, the commonest immunotherapy regimen was Pembrolizumab (155, 57%), followed by Ipilimumab/Nivolumab (85, 31%). The commonest regimen in the adjuvant setting was Pembrolizumab (86, 77%). 95 patients (25%) experienced ICI-related toxicity. The number of patients with Grades 1-4 toxicity was 2 ,4, 18 and 4 respectively, the remaining had unspecified toxicity grades. The commonest class of toxicity (CTCAE v5) was gastrointestinal (36, 38%), followed by endocrine (20, 21%) and skin (19, 20%). Linear Regression and Gaussian Naïve Bayes predicted toxicity with the most accuracy, 92% (Table 1). The model showed that increasing age, female gender and not receiving Nivolumab predicted toxicity. Regardless of the regimen or treatment intent, our ML model could also predict immunotherapy response with 90% accuracy. Conclusions: These ML algorithms used clinically available data to predict ICI toxicity accurately. Key predictors of toxicity included increasing age, female gender and not receiving Nivolumab in the setting of both adjuvant and palliative intent. Future work will aim to externally validate these models in other centers. We will also explore if models could be trained for use in patients treated with nivolumab in combination with new anti-LAG-3(relatlimab). [Table: see text]

Optimizing clinical research in a regional cancer center network: A survey-based approach.

e13560 Background: Conducting clinical research (CR) within regional care networks (RCNs) of comprehensive cancer centers presents unique challenges. This study aimed to identify and address such barriers at Memorial Sloan Kettering Cancer Center's (MSKCC) RCN, encompassing six sites across New York and New Jersey. Methods: A survey was conducted among medical oncologists at the RCN sites (February 2022-February 2023) to assess their perspectives on research-related challenges. The 23-question survey included multiple-choice, open-ended, and ranking questions regarding protocol availability, consenting processes, staffing support, and more. Results: 92/108 (85%) medical oncologists completed the survey, revealing three key challenges: 1. Limited protocol availability: Only 47% of the time was there a suitable trial available in the RCN for patients interested in clinical trials. Notably, 50% of attendings referred over 5 patients out of the RCN to MSKCC Main Campus for trial enrollment. Identified barriers to opening desired protocols (n=23 in total) included closed to accrual, pending amendments, and sponsor approval issues. 2. Inadequate investigator representation: 278 protocols lacked RCN physicians listed as consenting providers hindering potential patient participation. 3. Insufficient research staff including clinical trial nurses and administrative staff. Only 33% were satisfied with the research support, and 67% of physicians identified lack of clinical research support staff as the biggest barrier to accrual. 58% reported delays of more than one week in screening eligible patients due to insufficient support. Following these observations, interventions were implemented. Thirteen of the 23 studies were opened to accrual, all RCN physicians were added to the 278 protocols, and an analysis of staffing needs increased clinical trial nursing and administrative staff. Therapeutic and non-therapeutic accruals in the Department of Medicine rose by 10.5%, and total research visits increased by 21.4% compared to the previous year. Conclusions: This survey-based approach identified and addressed key barriers to CR within MSKCC's RCN, and in turn, increased research activity was noted. These findings offer a potential roadmap for optimizing research in similar networks by enhancing protocol accessibility, addressing staffing needs, and fostering collaboration. Further investigations are ongoing to address challenges in other clinical departments.

HIPEC application potential in the treatment of extensive carcinomatosis in ovarian cancer (retrospective study)

Background. The high prevalence of advanced forms of cancer currently requires new treatment approaches. Only modern high-tech surgical procedures can provide means for improving the results of treatment.The aim. To study the results of treatment of patients with ovarian cancer with symptoms of peritoneal carcinomatosis using the HIPEC (Hyperthermic IntraPEritoneal Chemotherapy) method.Materials and methods. The study was conducted in Irkutsk Regional Cancer Center and included 88 patients. They were divided into 2 groups: group 1 – primary cytoreductive surgery (CRS) with the HIPEC method (41 patients); group 2 – primary cytoreductive surgery (47 patients). The most important criterion was the peritoneal cancer index (PCI). If the PCI was ≤ 14, we chose cytoreductive surgery with or without HIPEC.Results. PCI analysis showed differences in its values between the study groups (CRS – 10.17 ± 0.952; CRS + HIPEC – 12.93 ± 0.744; p = 0.002). There was an increase in length of stay in patients who underwent major surgeries in combination with HIPEC (21.8 ± 0.9 days versus 14.5 ± 0.6 days in the CRS group; p = 0.001). The CRS + HIPEC group had a longer duration of surgery (394.88 ± 19.935 min vs. 172.98 ± 11.514 min in the CRS group; p = 0.001). There was an increase in the overall percentage of postoperative complications in the CRS + HIPEC group – up to 26.8 % without statistically significant differences with the CRS group – 8.5 % (p = 0.082). The median time of relapse onset in the CRS + HIPEC group was 26 ± 4.3 months, while in the CRS group it was 18 ± 2.6 months.Conclusion. Using HIPEC method has proven its significance in increasing diseasefree survival.

The Association of Ethnicity and Oncologic Outcomes for Oral Cavity Squamous Cell Carcinoma (OSCC).

(1) Background: To compare oncologic outcomes of South Asian (SA) patients treated for oral squamous cell carcinoma (OSCC) to the general population. (2) Methods: Adult patients who underwent surgical resection of OSCC +/- adjuvant treatment between 2009 and 2022 (N = 697) at a regional cancer centre in Canada were included. SA patients, identified using a validated method, were compared to non-SA patients. Kaplan-Meier methods were used to compare the primary outcomes, disease-specific survival (DSS) and recurrence-free survival (RFS) across baseline univariate characteristics, including betel nut consumption. Median follow-up time was 36.4 months. Cox proportional hazard models were used to identify independent predictors of survival with significance set at p < 0.05. (3) Results: SA patients (9% of cohort, N = 64) were significantly younger and had lower rates of smoking and alcohol consumption compared to non-SA patients (p < 0.05). SA patients had a two-fold higher risk of recurrence and significantly worse disease-specific survival, even after adjusting for stage and high-risk features [RFS: HR 2.01 (1.28-3.14), DSS: HR 1.79 (1.12-2.88)]. The consumption of betel nut was not associated with outcomes. (4) Conclusions: SA patients had significantly worse oncologic outcomes, even after controlling for known predictors of poor prognosis. These findings are novel and can inform personalized treatment decisions and influence public health policies when managing patients with different ethnic backgrounds.

High-grade neuroendocrine head and neck cancer: Case series and review of the literature

BackgroundHigh-grade neuroendocrine cancers (NEC) of the head and neck (HN) are rare and aggressive, accounting for ≤1 % of all HN cancers, with a 5-year overall survival (OS) of ≤20 %. This case series examines clinical characteristics, treatments, and outcomes of patients diagnosed at a regional UK HN cancer centre over the last 23 years. MethodsA retrospective review of medical records was conducted for all patients diagnosed with NEC HN from 1st January 2000 until 1st March 2023 at Velindre Cancer Centre. ResultsDuring the study period, 19 cases of NEC HN were identified, primarily affecting males (n = 15, 79 %). Median age of 67 years (range: 44–86). At diagnosis, 32 % of patients (n = 6) were smokers. The most common primary tumour sites were larynx (n = 5, 26.3 %) and sinonasal (n = 5, 26.3 %). Most patients presented with advanced loco-regional disease or distant metastasis, with stage IVA (n = 6, 32 %) and stage IVC (n = 6, 32 %) being the most common. The key pathology marker was synaptophysin, present in 100 % of the tested patients (n = 15). In the study, of the 12 patients with non-metastatic disease, 10 received a combination of treatments that included radiotherapy (RT). Some of these patients also received chemotherapy (CT) at the same time as their radiotherapy. Surgery alone was used in two patients with stage II disease. Seven subjects had complete responses, and one achieved a partial response. Among the seven metastatic patients, three received CT, and one underwent palliative RT, all achieving a partial response. In all cases, the CT used was carboplatin and etoposide. After a median follow-up of 11 months (range: 1–96), the median OS was 27 months for the overall population, 51 months for those treated radically, and three months for metastatic patients with palliative treatment. The 1-year OS for all patients was 54.3 %, the 2-year OS was 46.5 %, and the 5-year OS was 23.3 %. Among patients treated radically, these rates were 65.3 %, 52.2 %, and 26.1 %, respectively. For patients treated palliatively, the 1-year OS was 33.3 %. ConclusionThis case series contributes preliminary observations on the characteristics and management of non-metastatic NEC HN, suggesting potential benefits from multimodality treatment strategies. Given the small cohort size, these observations should be interpreted cautiously and seen as a foundation for further research.

Older age, CNS leukaemic involvement and induction tumour lysis increases the risk of methotrexate (MTX)-induced neurotoxicity in childhood acute lymphoblastic leukaemia/lymphoma: Experience from a tertiary care centre in South India.

Methotrexate (MTX), although an indispensable part of contemporary treatment protocols for childhood acute lymphoblastic leukaemia (ALL)/lymphomas (LBL) in improving outcomes, can lead to serious neurotoxicity with long-term consequences. The aetiopathogenesis, predisposing factors and treatment for MTX-induced neurotoxicity are not yet well defined. The aim of our study was to detect the incidence, risk factors and to assess the overall outcomes of MTX-induced neurotoxicity among large cohort of paediatric ALL/LBL patients treated on a uniform protocol. We conducted retrospective audit of medical records of 622 consecutive children (≤14 years) diagnosed with ALL and LBL between January 2018 and December 2022 and treated on modified BFM-95 protocol at the Department of Pediatric Oncology, Regional Cancer Centre, Thiruvananthapuram. Risk factors predisposing to MTX-induced neurotoxicity were identified using binary logistic regression analysis. Forty-three children were diagnosed with MTX-induced neurotoxicity with an incidence rate of 6.9%. More than two-thirds of them had high-grade MTX-induced neurotoxicity CTCAE v5.0 with a median age of 9 years (range: 9 months to 14 years). Almost half of them developed MTX neurotoxicity during Protocol M followed by Phase-Ib consolidation (15%). Majority of these patients (84%, 36/43) were challenged again with MTX, with 11% (4/36) developing recurrence. Fifteen per cent had persistent neurological deficits at last follow-up. Univariate analysis found older age (age > 5 years) (p < 0.001), T-cell phenotype (p = 0.040), tumour lysis syndrome during induction (p < 0.001), baseline renal problems prior to MTX exposure (p < 0.001) and CNS leukaemic involvement (p < 0.003) to be significantly associated with MTX neurotoxicity. On multivariate analysis, older age (>5 years), tumour lysis during induction and CNS leukaemia retained statistical significance (p < 0.05). Methotrexate-induced neurotoxicity during paediatric acute lymphoblastic leukaemia/lymphoma therapy is a transient phenomenon in majority and re-challenge with MTX is generally safe. Older age children who develop tumour lysis during induction and CNS leukaemic involvement are at increased risk for MTX-induced neurotoxicity during ALL/LBL treatment.