Baclay, J.R.M.

e16457 Background: Patients with inoperable stage II-III pancreatic cancer commonly undergo sequential stereotactic body radiation therapy (SBRT) and chemotherapy. However, there is variability in clinical outcomes, and the predictors of high-risk patients with rapid tumor progression (within 3 months) and poor overall survival (OS) despite treatment are not well characterized. We developed a radiomic (imaging-derived features) signature (RS) that predicts rapid progression. We then investigated clinical characteristics, including pathologic features and treatments received, and RS in a combined analysis to develop and validate the highest-performing model to predict OS from the time of SBRT initiation. We identified the most predictive feature from the combined model that best predicts OS. Methods: In our retrospective study, we examined a cohort of 124 stage II-III pancreatic cancer patients who underwent sequential SBRT and systemic chemotherapy and had pre-treatment pancreatic protocol computed tomography (CT) imaging. We examined 10 clinical features and extracted 900 radiomic features from each segmented tumor per patient using PyRadiomics. Dividing our cohort into training and test sets (60:40), we built a prediction model for rapid tumor progression using radiomic data on the training set (n = 74), applying a LASSO-based algorithm for feature selection and 5-fold cross-validation for parameter optimization. We validated the model performance on the held-out test set (n = 50) and generated the RS for predicting rapid progression. We examined the performance of clinical features and RS in predicting OS in univariate and multivariate Cox regression models. Results: Analysis on our cohort (57 men, 67 women; mean age 67 ± 11 years) generated a 43-feature RS that predicted rapid tumor progression (AUC 0.83, 95% CI: 0.70–0.94) in the test set. High RS was a significant predictor of mortality with hazard ratio (HR) 2.22 (95% CI: 1.32–3.73, p = 0.003) within the first year and 2.85 (95% CI: 1.35–6.03, p = 0.006) thereafter. Non-intensive chemotherapy increased only early mortality risk (HR 1.95, 95% CI: 1.08–3.53, p = 0.03), while older age was significant in later years (HR 1.80, 95% CI: 1.02–3.15, p = 0.04). Conclusions: CT-derived RS accurately predicted rapid tumor progression in stage II-III pancreatic cancer patients undergoing SBRT sequentially with chemotherapy. High RS was the strongest prognostic indicator for increased mortality risk, suggesting its utility for guiding treatment or selection for clinical trials.

Abstract Background Anal squamous cell carcinoma is a rare cancer with increased occurrence of multiple cancers before and after the anal squamous cell carcinoma diagnosis. However, there are limited data on this aspect. This multi-institutional analysis aimed to define the occurrence of malignancies before and after anal squamous cell carcinoma, time trends, and impact on survival and to identify prognostic factors. Methods Initial primary malignancy was defined as a malignancy occurring before the anal squamous cell carcinoma. Second primary malignancy was defined as a distinct primary cancer that developed after anal squamous cell carcinoma diagnosis. Retrospective multi-institutional chart review was done. Progression-free survival (PFS), overall survival, and prognostic factors were evaluated. Results A total of 647 patients with anal squamous cell carcinoma treated with curative intent were analyzed. Median age was 61.2 years with 72% as females. Of these, 150 (23.3%) patients had multiple malignancies with initial primary malignancy in 16% and second primary malignancy in 8%. Patients without prior cancer had better 5-year PFS (81.2% vs 67.2%, P = .011) and overall survival (81% vs 69%, P = .008) compared with those with prior cancer. Second primary malignancies had a statistically significant adverse impact on PFS (hazard ratio [HR] = 4.22) and overall survival (HR = 3.56). Females had better 5-year PFS (82% vs 70%, P = .016) as compared with males. The median time interval for developing anal squamous cell carcinoma (as second primary malignancy) after initial primary malignancy was 9.32 years. Conclusions Anal squamous cell carcinoma patients have an increased risk of multiple malignancies. These patients who have prior cancers have inferior outcomes. Second primary malignancy is a poor prognostic factor in patients with anal cancer. Second primary malignancy can develop years after treatment of primary anal squamous cell carcinoma.

74 Background: We identified computed tomography (CT)-derived radiomic features predictive of tumor progression within three months, then examined their ability to prognosticate overall survival (OS) along with clinical features in pancreatic cancer. We evaluated these features in patients with unresected pancreatic cancer who underwent stereotactic body radiation therapy (SBRT) in sequence with chemotherapy, but not surgery. Methods: In this retrospective study, we examined a cohort of 101 patients with stage II-III pancreatic cancer who underwent SBRT with sequential chemotherapy at a single institution (Stanford Health Care) between 1999-2020. From their pre-SBRT contrast-enhanced CT images with segmented tumors, delineating regions-of-interest, we extracted 900 radiomic (quantitative pixel-level imaging characteristic) features. In the first phase, we identified radiomic features that predicted rapid tumor progression within three months following SBRT. We divided the dataset into a training set (n = 53) for model development and a test set (n = 48) for evaluation. Using logistic regression with the Least Absolute Shrinkage and Selection Operator algorithm for feature selection and classification, we built a binary prediction model on the training set to identify patients at risk of progression within three months of SBRT. To fine-tune parameters, we performed five-fold cross-validation (CV) on the training set, repeating each set of parameters five times. We assessed model performance on the test set using the area under the curve (AUC). We selected the model with the best AUC, generating the predictive radiomic feature set. In the second phase, we conducted univariate and multivariate Cox regression analyses to assess the relationship between OS and individual clinical variables (age, sex, stage, vessel involvement, tumor location, performance status, body mass index, biological equivalent dose of radiation) and the radiomic feature set as high versus low risk. Results: Our cohort consisted of 48 men (mean age, 70 years ± 11 [SD]) and 53 women (mean age, 67 years ± 13 [SD]). From the first phase, 32 textural features comprised the radiomic feature set that best predicted rapid tumor progression, with mean AUCs of 0.852 (CV, n=53) and 0.814 (test, n=48). In the univariate Cox model, only the radiomic feature set was predictive of OS (hazard ratio, HR, 1.724, p=0.011). In the multivariate Cox model, radiomic features and age were significant predictors of OS, with HR of 1.819 (p=0.007) and 1.024 (p=0.024), respectively. Conclusions: CT-derived radiomic features predict rapid tumor progression following SBRT, confer nearly a twofold increase in mortality risk, and, along with patient age, enhance the identification of patients with stage II-III pancreatic cancer with poor OS. [Table: see text]

56 Background: We sought to identify the clinical determinants of overall survival (OS) in patients diagnosed with stage II-III pancreatic cancer not undergoing surgery. We curated a relatively homogenous cohort of patients who did not undergo surgical resection, but instead underwent chemotherapy in sequence with stereotactic body radiation therapy (SBRT) to examine the features that differentiated those with poor OS. Methods: In a retrospective study, we examined a cohort of 259 patients with stage II-III pancreatic cancer who underwent chemotherapy in sequence with SBRT without surgery at a single institution (Stanford Health Care). We conducted both univariate and multivariate Cox regression analyses to assess the relationships between OS and individual clinical and tumoral variables, including: age, sex, stage, Karnofsky performance status (KPS), body mass index, vessel involvement, tumor location, and biological equivalent dose [BED] of SBRT as potential determinants. Results: The study cohort consisted of 136 men (52.5%) and 123 women (47.5%) with a median age of 69 (range 38-94). Tumor histology was predominantly ductal adenocarcinoma (n=249, 96.1%), with tumor sites of involvement spanning: uncinate (n=35, 13.5%), head (n=160, 61.8%), body (n=59, 22.8%), and tail (n=5,1.9%). More patients had stage III (n=171, 66%) than stage II (n=88, 34%) disease, and their tumor resectability by NCCN criteria were rated as: unresectable (n=145, 56%), borderline (n=28, 10.8%), resectable (n=11, 4.2%), or unrecorded (n=75, 29%). Tumor progression was observed in local (n=71, 27.4%), regional (n=29, 11.2%), and distant (n=150, 57.9%) sites during the median follow up period of 17 months (range 15-18 months) from diagnosis and 12 months (10-13 months) from SBRT. Death (n=213, 82.2%) during this period was more common than survival (n=46, 17.8%). In univariate analyses, clinical features impacting OS included: KPS (hazard ratio [HR] 0.14, p=0.007); male sex (HR 1.44, p=0.01), pancreatic head tumors (HR 1.44, p=0.011), BED (HR 1.33, p=0.035), and age (HR 1.013, p=0.044). In the multivariate analysis, which incorporated only features significant in the univariate analyses, tumor location at the pancreatic head (HR 1.412, p=0.021) and male sex (HR 1.360, p=0.03) conferred the highest risks for poor OS, with BED bordering on significance (p=0.059) (Table). Conclusions: Among patients with stage II-III pancreatic cancer who underwent chemotherapy in sequence with SBRT, but not surgery, the most significant clinical determinants of poor OS were location of the tumor in the pancreatic head and male sex. Prioritizing additional disease monitoring and alternative therapies for this subset of patients at higher risk of poor survival may be warranted. [Table: see text]