Oncological Data Research Articles

On the Nonbinary Version of the Causality Relation in the Intelligent Analysis of Oncological Data

On the Nonbinary Version of the Causality Relation in the Intelligent Analysis of Oncological Data

Transforming a Large-Scale Prostate Cancer Outcomes Dataset to the OMOP Common Data Model-Experiences from a Scientific Data Holder's Perspective.

To enhance international and joint research collaborations in prostate cancer research, data from different sources should use a common data model (CDM) that enables researchers to share their analysis scripts and merge results. The OMOP CDM maintained by OHDSI is such a data model developed for a federated data analysis with partners from different institutions that want to jointly investigate research questions using clinical care data. The German Cancer Society as the scientific lead of the Prostate Cancer Outcomes (PCO) study gathers data from prostate cancer care including routine oncological care data and survey data (incl. patient-reported outcomes) and uses a common data specification (called OncoBox Research Prostate) for this purpose. To further enhance research collaborations outside the PCO study, the purpose of this article is to describe the process of transferring the PCO study data to the internationally well-established OMOP CDM. This process was carried out together with an IT company that specialised in supporting research institutions to transfer their data to OMOP CDM. Of n = 49,692 prostate cancer cases with 318 data fields each, n = 392 had to be excluded during the OMOPing process, and n = 247 of the data fields could be mapped to OMOP CDM. The resulting PostgreSQL database with OMOPed PCO study data is now ready to use within larger research collaborations such as the EU-funded EHDEN and OPTIMA consortium.

Oncologic outcomes following transanal total mesorectal excision: the United States experience.

The benefits and short-term outcomes of transanal total mesorectal excision (taTME) for rectal cancer have been demonstrated previously, but questions remain regarding the oncologic outcomes following this challenging procedure. The purpose of this study was to analyze the oncologic outcomes following taTME at high-volume centers in the USA. This was a multicenter, retrospective observational study of 8 tertiary care centers. All consecutive taTME cases for primary rectal cancer performed between 2011 and 2020 were included. Clinical, histopathologic, and oncologic data were analyzed. Primary endpoints were rate of local recurrence, distal recurrence, 3-year disease recurrence, and 3-year overall survival. Secondary endpoints included perioperative complications and TME specimen quality. A total of 391 patients were included in the study. The median age was 57years (IQR: 49, 66), 68% of patients were male, and the median BMI was 27.4 (IQR: 24.1, 31.0). TME specimen was complete or near complete in 94.5% of cases and the rates of positive circumferential radial margin and distal resection margin were 2.0% and 0.3%, respectively. Median follow-up time was 30.7months as calculated using reverse-KM estimator (CI 28.1-33.8) and there were 9 cases (2.5%) of local recurrence not accounting for competing risk. The 3-year estimated rate of disease recurrence was 19% (CI 15-25%) and the 3-year estimated overall survival was 90% (CI 87-94%). This large multicenter study confirms the oncologic safety and perioperative benefits of taTME for rectal cancer when performed by experienced surgeons at experienced referral centers.

Patient Preferences for Benefit and Risk Associated With High Intensity Focused Ultrasound for the Ablation of Prostate Tissue in Men With Localized Prostate Cancer

IntroductionFood and Drug Administration must make decisions about emerging high intensity focused ultrasound (HIFU) devices that may lack relevant clinical oncologic data but present with known side effects. This study aims to capture patients’ perspective by quantifying their preferences regarding the available benefit and important side effects associated with HIFU for localized prostate cancer. Materials and methodsPreferences for HIFU outcomes were examined using a discrete choice experiment survey. Participants were asked to choose a preferred treatment option in 9 choice questions. Each included a pair of hypothetical treatment profiles that have similar attributes/outcomes with varying levels. Outcomes included prostate biopsy outcome and treatment-related risks of erectile dysfunction (ED) and urinary incontinence (UI). We calculated the maximum risk of side effect patients were willing to tolerate in exchange for increased benefit. Preferences were further explored via clinical and demographic data. ResultsAbout 223 subjects with a mean age of 64.8 years completed the survey. Respondents were willing to accept a 1.51%-point increase in new ED risk for a 1%-point increase in favorable biopsy outcome. They were also willing to accept a 0.93%-point increase in new UI risk for a 1%-point increase in biopsy outcome. Subjects who perceived their cancer to be more aggressive had higher risk tolerance for UI. Younger men were willing to tolerate less ED risk than older men. Respondents with greater than college level of education had a lower risk tolerance for ED or UI. ConclusionsResults may inform development and regulatory evaluation for future HIFU ablation devices by providing supplemental information from the patient perspective.

Immediate Breast Reconstruction With Latissimus Dorsi Myocutaneous Flap and Silicone Implant Followed by Adjuvant Radiotherapy for Breast Cancer.

About 30% to 50% of women with breast cancer undergo mastectomy, and approximately 50% of them will receive adjuvant radiotherapy (ART). This study evaluates the medium- and long-term impact of ART after immediate breast reconstruction (IBR) with latissimus dorsi myocutaneous (LDM) flap and silicone implants. Clinical, surgical, and oncological data were retrospectively collected and analyzed based on the medical records of 176 patients who had undergone IBR with LDM flap and silicone implants. The data showed that 7.4% of patients had a history of previous radiotherapy, 56.3% received ART, 31.8% developed capsular contracture with a mean follow-up of 58.1 months, and 14.2% of surgeries were categorized as procedures with a prolonged operating time, lasting above 1 SD of the observed mean. Those who experienced prolonged operating time (odds ratio, 4.72; 95% confidence interval, 1.72-12.93; P = 0.003) and those who received ART (odds ratio, 7.38; 95% confidence interval, 3.18-17.10; P < 0.001) were more likely to develop capsular contracture. Thirty-two patients (18%) underwent capsulectomy with implant replacement, and 7 patients (4%) had the implant removed. The mean time between IBR and reoperation was 29.1 months. Patients who received ART were 2.84 times more likely to experience reconstruction failure or undergo implant-related reoperation ( P = 0.002). The results indicated that IBR with LDM flap and silicone implant followed by ART is a safe procedure, resulting in low rates of reconstruction failure. However, ART increased the likelihood of capsular contracture development and implant-related reoperation, having a negative effect on reconstructed breasts.

Abstract PO3-23-06: Short-term clinical and patient-reported outcomes of oncoplastic breast conserving surgery and mastectomy with and without immediate breast reconstruction: The UK ANTHEM multicentre prospective cohort study

Abstract Background: Oncoplastic breast conserving surgery (OPBCS) may allow women with early breast cancer to avoid mastectomy leading to fewer complications and better quality of life. High quality comparative evidence, however, is lacking. The UK ANTHEM study (ISRCTN18238549) aimed to explore the feasibility of undertaking a large-scale multicentre study comparing the clinical and patient reported outcomes (PROs) of OPBCS as an alternative to mastectomy +/- immediate breast reconstruction (IBR) in women offered both options. Methods: Women aged 18 and over with invasive breast cancer or DCIS not suitable for standard breast conserving surgery, who were offered OPBCS as an alternative to mastectomy +/- IBR were eligible to participate in the study. Demographic, operative, oncological data were collected and the numbers of women experiencing complications at 3 months following surgery compared by procedure type. Participants completed the validated BREAST-Q at baseline and 3 months post-operatively. Questionnaires were scored according to the developers’ instructions and scores compared across timepoints by procedure group. Analysis of covariance, adjusting for baseline scores was used to explore factors influencing patient-reported outcomes after surgery. Results: 361 women from 32 UK centres participated in the study. When offered both options, the majority (n=284, 78.7%) elected to undergo OPBCS with either a therapeutic mammaplasty (TM) (n=207, 57.3%) or a chest wall perforator flap (CWPF) (n=77, 21.3%). The remaining 77 (21.3%) women chose mastectomy with (n=40, 11.1%) or without IBR (n=37, 10.3%). Women having mastectomy + IBR were significantly younger than those choosing other procedure types (p=0.002) and those choosing TM had higher BMIs (P=0.008), but there were no other differences between the groups. By 3 months post-operatively, 23.0% (n=83) women had experienced at least one complication, but there were no differences between the groups (p=0.50). The BREAST-Q was completed by 329 (91.1%) and 282 (78.1%) women at baseline and 3 months respectively. Although their scores were initially the lowest, women undergoing TMs reported clinically meaningful and statistically significant increases in ‘Satisfaction with Breasts’ (baseline 53.7 [95% confidence interval [CI] 50.4-57.0] to 3 months 68.9 [95% CI 65.5-72.2], p&amp;lt; 0.001) and ‘Psychosocial Well-being’ scores (baseline 62.1 [95% CI 59.2-65.0] to 3 months 70.4 [95% CI 66.9-73.8] p&amp;lt; 0.001) from baseline to 3 months. Women having CWPF and mastectomy +/- IBR did not report any significant changes in either ‘Satisfaction with Breasts’ or ‘Psychosocial Well-being’ scores over time. ‘Physical Well-being’ scores significantly decreased from baseline to three months in all treatment groups (p&amp;lt; 0.001) but were lowest after mastectomy only (56.5 [95% CI 47.4-65.5]) and highest in the TM group (68.6 [95% CI 65.9-71.3], p&amp;lt; 0.001). ‘Sexual Well-being’ decreased in all groups except for women having mastectomy + IBR. Adjusting for baseline, women undergoing OPBCS with TM (13.2, 95% CI 4.2-22.2, p&amp;lt; 0.001) or CWPF (11.4, 1.6-21.2, p=0.02) reported significantly higher ‘Satisfaction with Breasts’ scores at 3 months than those undergoing mastectomy. Receipt of IBR did not appear to lead to significantly higher scores compared with mastectomy alone (6.47, 95% CI -6.19 to 19.12, p=0.32). Women undergoing TM reported significantly higher ‘Psychosocial’ and ‘Physical well-being’ at 3 months compared with those having other procedure types. Experiencing a post-operative complication resulted in significant decreases in all BREAST-Q domains. Conclusions: When offered OPBCS as an alternative to mastectomy, most women choose breast conservation. This option is safe and appears to be associated with improved short-term PROs, particularly in the TM group. Further work is needed to establish the long-term outcomes of these techniques to support informed decision-making. Citation Format: Charlotte Davies, Leigh Johnson, Carmel Conefrey, Nicola Mills, Patricia Fairbrother, Chris Holcombe, Lisa Whisker, William Hollingworth, Joanna Skillman, Paul White, Douglas MacMillan, Charles Comins, Shelley Potter. Short-term clinical and patient-reported outcomes of oncoplastic breast conserving surgery and mastectomy with and without immediate breast reconstruction: The UK ANTHEM multicentre prospective cohort study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-23-06.

Abstract PO3-11-08: High Risk of Metabolic Dysfunction in Non-Obese Breast Cancer Survivors

Abstract Much literature already depicts the relationship between metabolic syndrome (MS), obesity, and breast cancer. Despite that, up to one-third of non-obese individuals may exhibit undiagnosed MS or metabolic dysfunction, posing an independent cancer risk and worse outcomes even for those with a body mass index (BMI) &amp;lt; 30kg/m². In that manner, our study aims to evaluate the metabolic profile of non-obese women with postmenopausal breast cancer compared to non-obese women without breast cancer. In this cross-sectional clinical study at the State University of São Paulo Medical School - UNESP. The study group (n=130) included women aged ≥ 45 and &amp;lt; 75 years, in amenorrhea for at least 12 months, BMI ≤ 30kg/m2, histological diagnosis of breast cancer, without metastatic disease, and without established cardiovascular disease (CVD). The control group (n=130) comprised women with all the same criteria except for breast cancer diagnosis. The groups were matched by age and menopause time in a ratio of one case to one control (1:1). We aimed to analyze their clinical, biochemical, and oncological data to establish relationships between these groups. We presented the data in tables 1 - 3. The groups showed homogeneity in age, time since menopause, BMI, waist circumference (WC), and cholesterol levels. There was a higher occurrence of MS and hypertension (HTN) among women treated for breast cancer compared to the control group (30.8% vs. 20.0% and 25.4% vs.14.6%, respectively) (p&amp;lt; 0.05). Similarly, a higher percentage of women treated for breast cancer had abnormal values for total cholesterol and glucose (56.2% vs. 43.1% and 29.2% vs. 15.4%, respectively) (p&amp;lt; 0.05). In the analysis of metabolic profile risk-adjusted for age time since menopause and BMI, women treated for breast cancer showed an increased risk for MS (OR=2.76, 95% CI 1.48-5.15), elevated glucose (OR=2.69, 95% CI 1.46-4.96), and HTN (OR=3.03, 95% CI 1.51-6.10). In the evaluation of factors influencing the metabolic profile, women with breast cancer had significantly higher mean values of WC (82.6±8.5 vs. 79.9±6.4 cm, p=0.048), systolic and diastolic blood pressure (129.2±17.1 and 77.7±8.8 mmHg vs. 118.2±15.1 and 73.6±8.8 mmHg, p=0.0002 and p=0.01, respectively), and glucose (99.7±32.5 vs. 86.6±7.6 mg/dL, p=0.0002) compared to control group. We conducted a sub-analysis among women with BMI &amp;lt; 25kg/m² from both groups. Women with breast cancer (n=64) had a higher occurrence of MS compared to women without breast cancer (n=53) (17.2% vs. 1.9%, respectively). Even though this sub-analysis did not reach the minimum number of patients with BMI &amp;lt; 25 kg/m² to achieve p value &amp;lt; 0,05, this analysis reveals a significant difference in MS incidence between the groups (p=0.007). This reinforces the hypothesis that oncological diagnosis substantially affects metabolic health, and therefore, breast cancer patients should receive special attention regarding their metabolic profile, regardless of their BMI. Conclusion: Non-obese women with breast cancer showed a higher risk of MS, HTN, and diabetes, with a worse metabolic profile than non-obese postmenopausal women without breast cancer. These findings suggest that postmenopausal women diagnosed with breast cancer, even in the absence of obesity, exhibit significant metabolic dysfunction characterized by a higher occurrence of MS and its components. The findings highlight the importance of a comprehensive assessment of metabolic health in women with breast cancer, regardless of their body mass index, to ensure appropriate and individualized care for these patients. Table 1 - Comparison of clinical and laboratory characteristics among 130 non-obese postmenopausal women with breast cancer and 130 non-obese postmenopausal women (control) (average values ± standard deviation). Table 2 - Comparison of categorized clinical and laboratory characteristics that influence the metabolic profile between 130 non-obese postmenopausal women with breast cancer and 130 non-obese postmenopausal women (control). Values expressed as number and percentage in parentheses. CA, cancer; WC, waist circumference; MS, metabolic syndrome; HDL, high-density lipoprotein, LDL, low-density lipoprotein; TG, triglycerides. *Significant difference p&amp;lt;0.05 (Chi-square Test). Table 3. Association between the presence of Metabolic Syndrome, and its clinical and laboratory components, among the 130 non-obese postmenopausal women with breast cancer and the 130 non-obese postmenopausal women (control). Values expressed as number and percentage in parentheses. CA, cancer; BP, blood pressure; WC, waist circumference; TG, triglycerides. *Odds ratio (OR) adjusted for age, menopause duration and BMI. **Significant difference if p&amp;lt;0.05 (Logistic Regression). Citation Format: Pedro Paulo Perroni Filho, Daniel Buttros, Eliana Aguiar Petri Nahas. High Risk of Metabolic Dysfunction in Non-Obese Breast Cancer Survivors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-11-08.

Abstract PO2-06-01: Validity of patient-reported data from long-term survivors of metastatic breast cancer

Abstract Background: Metastatic Breast Cancer is incurable, with 5-year survival of ~30%. The Outliers Study recruited participants with metastatic breast cancer to fill out an extensive survey to better elucidate how clinical, social, and genetic factors affect metastatic breast cancer survivorship. Patient-reported surveys can be a valuable source of data for research studies and cancer registries to further our understanding of disease, but concerns regarding the validity of patient reporting remain. Beatty et al. (2022) suggest that patients with early stage breast cancer are reliable reporters of disease recurrence (79% accuracy rate), but no study to our knowledge has evaluated the validity of reporting regarding metastases, or those who are long-term survivors. In this study, over 1000 women with metastatic breast cancer filled out an extensive survey. We compared the medical records with self-reported data on clinical history to assess concordance. Objective: To determine the validity of patient-reported data pertaining to a wide variety of oncologic information, including but not limited to primary diagnosis date, stage, hormone status, metastatic date, site, and post-metastatic chemotherapy regimens, in long term survivors of metastatic breast cancer. Methods: Patients with metastatic breast cancer were recruited for the nation-wide Outliers Study to fill out an extensive survey on their oncologic history. Of &amp;gt;1000 participants enrolled in the Outliers Study, we identified a subpopulation of those who had lived the longest with metastatic disease and named this cohort “Long Term Survivors” (LTS). We acquired either partial or complete oncologic medical records from 31 LTS in order to determine the validity of patient-reported survey responses. Table 1 describes the details of this LTS cohort (n=31). We then compared each LTS survey to the medical record to verify responses and identify any inaccuracies. We also assessed accuracy to compare those who did and did not consult their medical records while responding to the survey. Results: Of the verifiable survey responses, we identified 592 accurate responses and 5 inaccuracies, yielding a 99.2% accuracy rate of patient-reported oncologic data. The identified errors included 2 minor discrepancies in clinical detail, 2 false-negative reports and 1 false-positive report. Specifically, there were minor discrepancies regarding biopsy type (i.e. core biopsy reported instead of fine needle) and site of radiation (e.g. “chest wall” instead of T12 vertebrae). The false-negative reporters failed to report 1) a positive history for surgery distant from breast for metastatic disease and 2) a positive history of biopsy for disease distant to the breast. The false positive error was a report of “surgery on distant metastasis” for a history of bone marrow biopsy. Each error identified was made by a separate participant and we found no association between patients who were reporting from memory and patients who reported an inaccurate response. Of note, there were no inaccurate responses identified pertaining to the topics of initial diagnosis date, stage, and histologic type, breast surgical history, hormone and HER2 receptor status of initial and metastatic disease, date and site of metastatic disease, BRCA mutation status, date and regimens of chemotherapy, and date of radiation history. Conclusion: Long term survivors of metastatic breast cancer report clinical data spanning a wide range of oncologic topics with high accuracy. The majority of errors identified in patient reported survey responses were minor and suggested misunderstandings of medical nomenclature (surgery vs biopsy; core vs FNA) and anatomic specificity. The topic of biopsy was most prone to error. Notably, we found no association between errored responses and patients who reported from memory without referencing their medical records. Table 1 Citation Format: Meredith Gallagher, Mark Burkard. Validity of patient-reported data from long-term survivors of metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-06-01.

Short- and long-term morbidity after Taylor flap (oblique rectus abdominis flap) for perineal reconstruction after abdominoperineal resection: A single-center series of 140 patients

BackgroundAbdominoperineal resection (APR) leads to a substantial loss of tissue and a high rate of complications. The Taylor flap is a musculocutaneous flap used in reconstruction after APR. ObjectivesWe aimed to analyze the short and long-term morbidity of reconstruction with a Taylor flap (oblique rectus abdominis flap) after APR and to identify the risk factors for postoperative complications. MethodsWe retrospectively included all patients who had undergone APR with immediate reconstruction with a Taylor flap in our department between July 2000 and June 2018. Demographics, oncological data, treatment, and short- and long-term morbidity were reviewed. ResultsAmong the 140 patients included, we identified early minor complications in 42 patients (30%) and 14 early major complications (10%). Total necrosis of the flap requiring its removal occurred in four patients (2.8%). Eleven patients (7.9%) presented with a midline incision hernia, and seven (5%) presented with a subcostal incision hernia. No perineal hernia was found. No risk factors for the complications were identified. ConclusionThe Taylor flap is a safe procedure with few complications and limited donor site morbidity. Moreover, it prevents perineal hernias. These results confirm that the Taylor flap is a well-suited procedure for reconstruction after APR.

Radical vaginal trachelectomy: long-term oncologic and fertility outcomes in patients with early cervical cancer

ObjectiveRadical vaginal trachelectomy is a fertility-preserving treatment for patients with early cervical cancer. Despite encouraging oncologic and fertility outcomes, large studies on radical vaginal trachelectomy are lacking.MethodDemographic, histological, fertility, and...

317 Clinical Informatics for Head and Cancer Patient Management

OBJECTIVES/GOALS: The management of head and neck cancers is complicated and allows for a variety of disparate approaches from providers. However, data from several hundred or thousands of patients is necessary to decipher the optimal decisions for populations of patients. And prospective trials would take years to accrue and often are financially not possible. METHODS/STUDY POPULATION: Instead, we collated the entire electronic medical record for all patients at our institution treated for head and neck cancers. We employed a variety of clinical informatics and natural language processing to gather text data into large data frames. We found key conclusions in the diagnostic, treatment, and surveillance of our patients. RESULTS/ANTICIPATED RESULTS: First, obtaining post-operative PET/CT changes in management in over one-third of patients, highlighting the utility of optimizing diagnostic imaging. Second, using a newer silicone-based cream instead of just a moisturizer decreased the absolute risk of grade 2+ radiation dermatitis by almost 15%. Lastly, we are deploying novel autosegmentation frameworks to better understand tissue decomposition in the head and neck to identify patients in need of further nutritional support while undergoing radiation therapy. DISCUSSION/SIGNIFICANCE: Collectively, we showcase the value and opportunity of mining oncological data for the improvement of patient care.

A database for oncological research and quality assurance: implementation and first experiences with the University Clinical Cancer Registry Regensburg

Legal requirements, certification specifications, as well as the demand for real world data on cancer research and treatment led to the decision to establish the University Clinical Cancer Registry Regensburg. The first organizational step in the implementation process of this oncological data registry was the evaluation and acquisition of suitable tumor documentation and database software. For this purpose, an evaluation matrix comprising required database software criteria was designed and consented by a multidisciplinary group of experts. Next, a yearly report of the Institute for Cancer Center Certification (OnkoZert 2019) was considered to identify database software already in use. The identified systems were rated according to the established criteria matrix and other relevant aspects. Onkostar was the system considered most suited for building up an oncological data repository. In the second step, the central IT department implemented Onkostar on-premise and migrated digitally available data after an adaptation and verification process. In parallel, a uniformed process for handling emerging oncological research questions was established. For research requirements, a data analysis concept was established comprising a proposal for data extraction, procedural instructions, and statistical training materials. In the final step, the implemented software and the process for handling research requirements in practice were evaluated by using two exemplary use cases with the focus on clinic-wide analyses and currently relevant scientific topics. A 2-month test phase conducted by various user groups showed a preference for Onkostar tumor documentation software from IT-Choice, mainly because of its adjustability to support research and treatment. Newly added and migrated data can be used for certification and research purposes. This software also provides support in current tumor documentation by displaying the course of cancer disease for individual patients over time. Such oncological data registries can be a powerful tool for legally required cancer registration, the certification of medical centers, as well as for additional oncological research. Tumor databases can be helpful in projects on cancer treatment and scientific aims. The experiences made at the University Hospital Regensburg may be used as a guidance for implementing clinical databases in similar settings with interdisciplinary responsibilities.

Abstract 6425: Harnessing big data from pan-cancer concerning more than 1300 patients with immune checkpoint inhibitors identifies novel predictive biomarkers

Abstract Immune-checkpoint inhibitors (ICIs) have revolutionized cancer therapy, yet many patients face the challenges of either not benefiting or developing resistance to ICIs. Advances in genome sequencing allow the exploitation of high-dimension oncological data in the research and development of precision immuno-oncology. We conducted a comprehensive literature review involving cancer patients treated with ICIs [anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), or their combination] and collected available transcriptomic data from pretreatment biopsies along with corresponding clinical outcomes. Biomarkers for ICI response were independently investigated within each study using the logistic regression method and combined with the odds ratio (OR) for meta-analysis. A total of 210 formalin-fixed paraffin-embedded pan-cancer samples with pretreatment biopsies from the National Cancer Center retrospective cohort were collected for validation. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) were employed to validate the stable and clinically applicable utility of the genomic biomarker identified in our analysis. Across 18 studies, we identified 1106 cancer patients who received immunotherapy with pre-treatment transcriptomic data, including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), stomach adenocarcinoma (STAD), glioblastoma (GBM), and bladder urothelial carcinoma (BLCA), of which 8421 genes were available in all datasets. Meta-analysis based on a common effect model revealed that 332 genes were positively correlated with a favorable response to ICIs, and 404 genes were negatively associated with the therapeutic outcome, with all pooled OR being statistically significant (P &amp;lt;0.05). We identified a novel biomarker, ZBED2 (Zinc Finger BED-Type Containing 2), which demonstrated superior predictive value over other biomarkers for ICI efficacy (pooled OR, 0.596; 95% CI, 0.450-0.788, P =0.002). Similarly, RT-qPCR (AUC: 0.821) and IHC (AUC: 0.789) results further validated the predictive utility for ICI response in the real-world cohort of 210 cancer patients with pretreatment samples receiving ICIs. Additionally, we observed that the expression of ZBED2 was favorably associated with the overall survival of patients receiving immunotherapy (HR: 0.72). In summary, our study provides a in-depth analysis of potentially predictable biomarkers for ICIs in cancer and highlights the potential of large-scale meta-analyses in identifying stable biomarkers. ZBED2 emerges as a novel predictive biomarker for ICIs and may guide the implementation of risk-related therapeutic strategies. Citation Format: Peng Wu, Chaoqi Zhang, Ao Shen, Xuanyu Gu, Nan Sun, Jie He. Harnessing big data from pan-cancer concerning more than 1300 patients with immune checkpoint inhibitors identifies novel predictive biomarkers [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 6425.

Secukinumab is not associated with cancer recurrence or progression in patients with spondyloarthritis and history of neoplastic disease.

Secukinumab is a monoclonal antibody directed against interleukin-17 approved for the treatment of psoriasis and spondyloarthritis. The favorable oncological profile of secukinumab in patients with a history of malignancy has been shown in patients with psoriasis. However, systematic data to this regard have not been published yet for patients with spondyloarthritis. The objective of the present study was to evaluate the oncological safety of secukinumab in patients affected by this group of diseases. We performed a retrospective study in which we identified from our cohort patients with spondyloarthritis treated with secukinumab and with a history of malignancy. These patients' baseline demographic, treatment, rheumatological, and oncological data were collected. The neoplastic outcome (i.e., cancer recurrence or progression) after secukinumab start was then analyzed. Our study included 22 patients with spondyloarthritis. The most frequently reported oncological diagnosis was breast cancer (9 [41%] patients). Secukinumab was started after a median of 24months following cancer diagnosis. At this time point, all but three patients were in oncological remission. No case of cancer relapse or progression was recorded over a median follow-up of 30months. In the largest cohort reported to date to this regard, secukinumab was not associated with oncological recurrence or progression in patients with spondyloarthritis with a history of malignancy. Secukinumab may, therefore, represent a safe option in this clinical scenario.

Analyzing the Impact of Oncological Data at Different Time Points and Tumor Biomarkers on Artificial Intelligence Predictions for Five-Year Survival in Esophageal Cancer

AIM: In this study, we use Artificial Intelligence (AI), including Machine (ML) and Deep Learning (DL), to predict the long-term survival of resectable esophageal cancer (EC) patients in a high-volume surgical center. Our objective is to evaluate the predictive efficacy of AI methods for survival prognosis across different time points of oncological treatment. This involves comparing models trained with clinical data, integrating either Tumor, Node, Metastasis (TNM) classification or tumor biomarker analysis, for long-term survival predictions. METHODS: In this retrospective study, 1002 patients diagnosed with EC between 1996 and 2021 were analyzed. The original dataset comprised 55 pre- and postoperative patient characteristics and 55 immunohistochemically evaluated biomarkers following surgical intervention. To predict the five-year survival status, four AI methods (Random Forest RF, XG Boost XG, Artificial Neural Network ANN, TabNet TN) and Logistic Regression (LR) were employed. The models were trained using three predefined subsets of the training dataset as follows: (I) the baseline dataset (BL) consisting of pre-, intra-, and postoperative data, including the TNM but excluding tumor biomarkers, (II) clinical data accessible at the time of the initial diagnostic workup (primary staging dataset, PS), and (III) the PS dataset including tumor biomarkers from tissue microarrays (PS + biomarkers), excluding TNM status. We used permutation feature importance for feature selection to identify only important variables for AI-driven reduced datasets and subsequent model retraining. RESULTS: Model training on the BL dataset demonstrated similar predictive performances for all models (Accuracy, ACC: 0.73/0.74/0.76/0.75/0.73; AUC: 0.78/0.82/0.83/0.80/0.79 RF/XG/ANN/TN/LR, respectively). The predictive performance and generalizability declined when the models were trained with the PS dataset. Surprisingly, the inclusion of biomarkers in the PS dataset for model training led to improved predictions (PS dataset vs. PS dataset + biomarkers; ACC: 0.70 vs. 0.77/0.73 vs. 0.79/0.71 vs. 0.75/0.69 vs. 0.72/0.63 vs. 0.66; AUC: 0.77 vs. 0.83/0.80 vs. 0.85/0.76 vs. 0.86/0.70 vs. 0.76/0.70 vs. 0.69 RF/XG/ANN/TN/LR, respectively). The AI models outperformed LR when trained with the PS datasets. The important features shared after AI-driven feature selection in all models trained with the BL dataset included histopathological lymph node status (pN), histopathological tumor size (pT), clinical tumor size (cT), age at the time of surgery, and postoperative tracheostomy. Following training with the PS dataset with biomarkers, the important predictive features included patient age at the time of surgery, TP-53 gene mutation, Mesothelin expression, thymidine phosphorylase (TYMP) expression, NANOG homebox protein expression, and indoleamine 2,3-dioxygenase (IDO) expressed on tumor-infiltrating lymphocytes, as well as tumor-infiltrating Mast- and Natural killer cells. CONCLUSION: Different AI methods similarly predict the long-term survival status of patients with EC and outperform LR, the state-of-the-art classification model. Survival status can be predicted with similar predictive performance with patient data at an early stage of treatment when utilizing additional biomarker analysis. This suggests that individual survival predictions can be made early in cancer treatment by utilizing biomarkers, reducing the necessity for the pathological TNM status post-surgery. This study identifies important features for survival predictions that vary depending on the timing of oncological treatment.

Is Robotic Surgery the Future for Resectable Esophageal Cancer?: A Systematic Literature Review of Oncological and Clinical Outcomes

BackgroundRadical esophagectomy for resectable esophageal cancer is a major surgical intervention, associated with considerable postoperative morbidity. The introduction of robotic surgical platforms in esophagectomy may enhance advantages of minimally invasive surgery enabled by laparoscopy and thoracoscopy, including reduced postoperative pain and pulmonary complications. This systematic review aims to assess the clinical and oncological benefits of robot-assisted esophagectomy.MethodsA systematic literature search of the MEDLINE (PubMed), Embase and Cochrane databases was performed for studies published up to 1 August 2023. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols and was registered in the PROSPERO database (CRD42022370983). Clinical and oncological outcomes data were extracted following full-text review of eligible studies.ResultsA total of 113 studies (n = 14,701 patients, n = 2455 female) were included. The majority of the studies were retrospective in nature (n = 89, 79%), and cohort studies were the most common type of study design (n = 88, 79%). The median number of patients per study was 54. Sixty-three studies reported using a robotic surgical platform for both the abdominal and thoracic phases of the procedure. The weighted mean incidence of postoperative pneumonia was 11%, anastomotic leak 10%, total length of hospitalisation 15.2 days, and a resection margin clear of the tumour was achieved in 95% of cases.ConclusionsThere are numerous reported advantages of robot-assisted surgery for resectable esophageal cancer. A correlation between procedural volume and improvements in outcomes with robotic esophagectomy has also been identified. Multicentre comparative clinical studies are essential to identify the true objective benefit on outcomes compared with conventional surgical approaches before robotic surgery is accepted as standard of practice.

Is Immediate Breast Reconstruction With a Latissimus Dorsi Myocutaneous Flap Safe for Starting Adjuvant Chemotherapy in Patients With Breast Cancer?

IntroductionImmediate breast reconstruction following mastectomy reduces perceptions of mutilation and femininity issues in oncological patients, but surgical complications should not delay chemotherapy. This study evaluated postsurgical complications in patients who underwent radical breast surgery followed by immediate reconstruction with latissimus dorsi myocutaneous flaps and silicone implants, along with resulting impacts in delaying chemotherapy. Materials and MethodsThis retrospective study utilized a prospectively maintained database. Clinical, surgical, and oncological data from 196 women were collected according to the operated side. Patients were grouped according to the time elapsed between surgery and the first cycle of adjuvant chemotherapy: ≤ 60 days (group 1), 61 to 90 days (group 2), or > 90 days (group 3). ResultsA total of 198 immediate reconstructions were performed on 196 patients between August 1, 2010 and March 31, 2020; after surgery, 47.4% had minor complications and 7.1% had major complications. Ninety-six patients (48.5%) received adjuvant chemotherapy. The mean time elapsed between surgery and the first chemotherapy cycle was 65.4 days (median: 59), with 52.7% of the patients assigned to group 1, 37.4% to group 2, and 9.9% to group 3. The occurrence of major postoperative complications significantly affected the start of chemotherapy (64.0 vs. 94.5 days; P = .044). Additionally, patients with 2 or more comorbidities were more likely to experience major complications (OR: 3.35; 95% CI: 1.03-10.95; P = .045) than those with 1 or 0. ConclusionMajor postoperative complications significantly delayed initiation of adjuvant chemotherapy in oncological patients who underwent radical breast surgery followed by immediate reconstruction with a latissimus dorsi myocutaneous flap and silicone implants.

Pre-pectoral breast reconstruction with tissue expander entirely covered by acellular dermal matrix: feasibility, safety and histological features resulting from the first 64 procedures.

Reconstructive options that can be used following conservative mastectomy, skin-, nipple-sparing and skin-reducing mastectomies, allow a remarkable variety of safe methods to restore the natural shape and aesthetics of the breast mound. In case of two-stage breast reconstruction, tissue expanders (TEs) are usually placed in a subpectoral position. The purpose of this retrospective cohort study is to evaluate the feasibility and safety of two-step reconstruction with TE in pre-pectoral position covered by acellular dermal matrix (ADM). Between March 2021 and May 2023, at the Azienda Ospedaliero Universitaria Careggi, University of Florence, 55 patients with BRCA 1/2 mutations or early breast cancer underwent conservative mastectomy with immediate pre-pectoral reconstruction using TE covered with ADM, followed by a second surgery with replacement of the expander with definitive prosthesis. Demographic, oncological, and histological data along with surgical complications were recorded. A total of 64 conservative mastectomies were performed. In 2 patients (3.1%) complications were found that required reintervention and, in both cases, the TE had to be removed. Two patients developed hematoma and one patient developed seroma. Two patients showed wound dehiscence, both healed after conservative treatment and without implant exposure. No case of necrosis of the skin or nipple-areola complex has been observed, neither of capsular contracture. Capsule formed around TE was populated with cells and blood vessels and showed a thin area of synovial metaplasia. In selected cases it may be more cautious to perform a two-stage breast reconstruction after radical breast surgery by means of TEs. The placement of TEs in pre-pectoral position combines the excellent aesthetic and functional results of the pre-pectoral philosophy with a quite safer and more prudent two-step approach. Our experience reports optimistic results: the ADM covering the TE is seen successfully integrating during tissue expansion and becoming a vascularised new self-tissue. Complications rates are low and such ADM-assisted two-stage pre-pectoral reconstructive technique is a safe, practical, and reproducible method.

Influence of neoadjuvant treatment strategy on perioperative outcomes in locally advanced rectal cancer.

Neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer facilitates tumour downstaging and complete pathological response (pCR). The goal of neoadjuvant systemic chemotherapy (total neoadjuvant chemotherapy, TNT) is to further improve local and systemic control. While some patients forgo surgery, total mesorectal excision (TME) remains the standard of care. While TNT appears to be noninferior to nCRT with respect to short-term oncological outcomes few data exist on perioperative outcomes. Perioperative morbidity including anastomotic leaks is associated with a negative effect on oncological outcomes, probably due to a delay in proceeding to adjuvant therapy. Thus, we aimed to compare conversion rates, rates of sphincter-preserving surgery and anastomosis formation rates in patients undergoing rectal resection after either TNT or standard nCRT. An institutional colorectal oncology database was searched from January 2018 to July 2023. Inclusion criteria comprised patients with histologically confirmed rectal cancer who had undergone neoadjuvant therapy and TME. Exclusion criteria comprised patients with a noncolorectal primary, those operated on emergently or who had local excision only. Outcomes evaluated included rates of conversion to open, sphincter-preserving surgery, anastomosis formation and anastomotic leak. A total of 119 patients were eligible for inclusion (60 with standard nCRT, 59 with TNT). There were no differences in rates of sphincter preservation or primary anastomosis formation between the groups. However, a significant increase in conversion to open (p = 0.03) and anastomotic leak (p = 0.03) was observed in the TNT cohort. In this series TNT appears to be associated with higher rates of conversion to open surgery and higher anastomotic leak rates. While larger studies will be required to confirm these findings, these factors should be considered alongside oncological benefits when selecting treatment strategies.

Tumor characteristics associated with detectable circulating tumor DNA preoperatively in patients with renal masses suspicious for RCC.

461 Background: Understanding the specific tumor characteristics associated with detectable ctDNA in the blood of patients with renal cell carcinoma (RCC) is critical to informing future studies seeking to establish the clinical utility of such testing. We characterized pathological and clinical characteristics associated with ctDNA detected preoperatively in patients with renal masses suspicious of RCC. Methods: Using our single institution prospectively maintained database, we identified consecutive patients who underwent partial or radical nephrectomy for non-metastatic suspected RCC (stages cT1b-cT3) during 2022-2023. Included were patients who had undergone tumor-informed ctDNA testing using the commercial Signatera assay (Natera). Baseline characteristics, pathology results, imaging study results, and oncological treatment and follow-up data were collected from the electronic medical records. ctDNA results were collected through the Natera portal. Study findings were reported using descriptive statistics. A p-value of &lt;0.05 was considered statistically significant. R programming language version 4.3 was used for all statistical analyses. Results: A total of 54 patients with a median age of 63 years (IQR 51-71) were included in the study. Twenty-one (39%) were women. The median follow-up time was 4 months (range: 1-21 months). Among the 54 patients, 27 (50%) had detectable ctDNA pre-operatively Post-operative results were available for 33 patients, and 3 (9%) had detectable tDNA (of those 2 had Inferior vena cava involvement). The first patient developed metastatic disease. The two other patients are receiving adjuvant immunotherapy. Analysis of 50 patients with solely malignant RCC revealed that patients with detectable versus undetectable ctDNA were older 67 vs. 54 years (p=0.03), had a higher pathological stage (p= 0.002), larger tumors (7.2 vs. 4.7 cm, p = 0.004), and higher pathological grade (grade 3-4 vs. grade 1-2; p=0.035) (Table 1). All the patients with renal vein or inferior vena cava involvement had detectable ctDNA (n=8). Conclusions: In our cohort, preoperative ctDNA was detectable in 50% of patients with suspected clinically localized RCC. Detectable ctDNA preoperatively correlated with clinically relevant features. The ability of preoperative ctDNA to predict recurrence and survival in patients with clinically localized RCC warrants further evaluation. [Table: see text]