Barry Smith an sich

Festschrift in Honor of Barry Smith on the occasion of his 65th Birthday. Published as issue 4:4 of the journal Cosmos + Taxis: Studies in Emergent Order and Organization. Includes contributions by Wolfgang Grassl, Nicola Guarino, John T. Kearns, Rudolf Lüthe, Luc Schneider, Peter Simons, Wojciech Żełaniec, and Jan Woleński

A Framework for Semantic Similarity Measures to enhance Knowledge Graph Quality

Precisely determining similarity values among real-world entities becomes a building block for data driven tasks, e.g., ranking, relation discovery or integration. Semantic Web and Linked Data initiatives have promoted the publication of large semi-structured datasets in form of knowledge graphs. Knowledge graphs encode semantics that describes resources in terms of several aspects or resource characteristics, e.g., neighbors, class hierarchies or attributes. Existing similarity measures take into account these aspects in isolation, which may prevent them from delivering accurate similarity values. In this thesis, the relevant resource characteristics to determine accurately similarity values are identified and considered in a cumulative way in a framework of four similarity measures. Additionally, the impact of considering these resource characteristics during the computation of similarity values is analyzed in three data-driven tasks for the enhancement of knowledge graph quality. First, according to the identified resource characteristics, new similarity measures able to combine two or more of them are described. In total four similarity measures are presented in an evolutionary order. While the first three similarity measures, OnSim, IC-OnSim and GADES, combine the resource characteristics according to a human defined aggregation function, the last one, GARUM, makes use of a machine learning regression approach to determine the relevance of each resource characteristic during the computation of the similarity. Second, the suitability of each measure for real-time applications is studied by means of a theoretical and an empirical comparison. The theoretical comparison consists on a study of the worst case computational complexity of each similarity measure. The empirical comparison is based on the execution times of the different similarity measures in two third-party benchmarks involving the comparison of semantically annotated entities. Ultimately, the impact of the described similarity measures is shown in three data-driven tasks for the enhancement of knowledge graph quality: relation discovery, dataset integration and evolution analysis of annotation datasets. Empirical results show that relation discovery and dataset integration tasks obtain better results when considering semantics encoded in semantic similarity measures. Further, using semantic similarity measures in the evolution analysis tasks allows for defining new informative metrics able to give an overview of the evolution of the whole annotation set, instead of the individual annotations like state-of-the-art evolution analysis frameworks

Assessing Oral Intake Outcomes in Head and Neck Cancer Patients Treated with Definitive Radiation with or Without Chemotherapy

Background: Head and neck cancer treatment modalities can significantly impact functional outcomes of patients, especially oral intake (Brizel, et al N Engl J Med 1998; Kamal, et al Support Care Cancer 2019). Radiation therapy in particular has been associated with posttreatment xerostomia and dysphagia (Adelstein, et al J Clin Oncol 2003; Hutcheson, et al Cancer 2013) which can affect quality of life and impair weight gain, contributing to worse long-term outcomes (Payakachat, et al Head Neck, 2013). Early speech-language pathology intervention has shown to be effective in improving these functional outcomes in this population (Greco, et al Int J Radiat Oncol Biol Phys 2018). Objectives: The purpose of this study is to evaluate oral intake outcomes of patients undergoing definitive radiation therapy with or without chemotherapy for head and neck squamous cell carcinoma. Methods: A cohort of patients with stage III or IV squamous cell carcinoma of the oropharynx, larynx, and hypopharynx treated with definitive radiation therapy with or without chemotherapy were extracted from system database. Patients with evidence of distant metastases were excluded. Swallow function was assessed both pre- and post-treatment (within four months of treatment initiation or conclusion) with the Functional Oral Intake Scale (FOIS) (Crary et al, Arch Phys Med Rehabil, 2005) as measured by a Speech-Language Pathologist (SLP) involved in the patient\u27s care. Body mass index (BMI) was evaluated within four months of treatment initiation and one year after treatment completion. The use of enteral feeding at one-year post-treatment was also assessed. Data was analyzed with descriptive statistical methods, Wilcoxon sign rank tests, and [chi]2d tests. Results: The sample included 152 patients. Table 1 highlights patient baseline characteristics, tumor location, and treatment. FOIS scores decreased from pre-treatment to post-treatment, with 75% of patients having a FOIS of 7 at pre-treatment compared with only 13.8% at the post-treatment time point (Table 1). Median BMI also decreased from pre-treatment to one-year post-treatment (Table 2). At one-year post-treatment, 23.7% patients (n=33) required enteral feeding. Conclusions: Definitive radiation therapy with or without chemotherapy in the treatment of head and neck cancer is associated with impaired oral intake. Treatment is also associated with decreases in BMI and longer use of enteral feeding, which may reflect sequelae of impaired oral intake. These factors have a negative impact on quality of life and can lead to long-term morbidity. Integrative treatment plans would therefore benefit from speech-language pathology interventions throughout the treatment process

Assessing Oral Intake Outcomes in Head and Neck Cancer Patients Treated with Definitive Radiation with or Without Chemotherapy

Background: Head and neck cancer treatment modalities can significantly impact functional outcomes of patients, especially oral intake (Brizel, et al N Engl J Med 1998; Kamal, et al Support Care Cancer 2019). Radiation therapy in particular has been associated with posttreatment xerostomia and dysphagia (Adelstein, et al J Clin Oncol 2003; Hutcheson, et al Cancer 2013) which can affect quality of life and impair weight gain, contributing to worse long-term outcomes (Payakachat, et al Head Neck, 2013). Early speech-language pathology intervention has shown to be effective in improving these functional outcomes in this population (Greco, et al Int J Radiat Oncol Biol Phys 2018). Objectives: The purpose of this study is to evaluate oral intake outcomes of patients undergoing definitive radiation therapy with or without chemotherapy for head and neck squamous cell carcinoma. Methods: A cohort of patients with stage III or IV squamous cell carcinoma of the oropharynx, larynx, and hypopharynx treated with definitive radiation therapy with or without chemotherapy were extracted from system database. Patients with evidence of distant metastases were excluded. Swallow function was assessed both pre- and post-treatment (within four months of treatment initiation or conclusion) with the Functional Oral Intake Scale (FOIS) (Crary et al, Arch Phys Med Rehabil, 2005) as measured by a Speech-Language Pathologist (SLP) involved in the patient\u27s care. Body mass index (BMI) was evaluated within four months of treatment initiation and one year after treatment completion. The use of enteral feeding at one-year post-treatment was also assessed. Data was analyzed with descriptive statistical methods, Wilcoxon sign rank tests, and [chi]2d tests. Results: The sample included 152 patients. Table 1 highlights patient baseline characteristics, tumor location, and treatment. FOIS scores decreased from pre-treatment to post-treatment, with 75% of patients having a FOIS of 7 at pre-treatment compared with only 13.8% at the post-treatment time point (Table 1). Median BMI also decreased from pre-treatment to one-year post-treatment (Table 2). At one-year post-treatment, 23.7% patients (n=33) required enteral feeding. Conclusions: Definitive radiation therapy with or without chemotherapy in the treatment of head and neck cancer is associated with impaired oral intake. Treatment is also associated with decreases in BMI and longer use of enteral feeding, which may reflect sequelae of impaired oral intake. These factors have a negative impact on quality of life and can lead to long-term morbidity. Integrative treatment plans would therefore benefit from speech-language pathology interventions throughout the treatment process

Outcomes of MR-guided Stereotactic Body Radiotherapy (SBRT) or yttrium-90 Transarterial Radioembolization for Hepatocellular Carcinoma Treated at an Urban Liver Transplant Center

Background: There are overlapping indications for both stereotactic body radiotherapy (SBRT) and yttrium-90 (Y90) trans-arterial radioembolization as locoregional treatments for hepatocellular cancer, though most centers preferentially use one modality over the other. MR-guided radiation allows both effective on-table localization and integrated motion management as compared with many traditional linear accelerators, allowing SBRT to be done more easily. Y90 radioembolization has been a well-established modality to deliver highly conformal dose due to the localization of the microspheres to the vascular supply of a tumor. We looked at patient characteristics and treatment outcomes for patients receiving MR-guided SBRT or Y90 at an urban transplant center. Objectives: To compare patient characteristics and treatment outcomes of MR-guided SBRT with Y90 transarterial radioembolization in a liver transplant center. Methods: This retrospective single-institution study analyzed patients with HCC treated with SBRT or Y90 from August 2017 to September 2020. To select a patient population eligible for either treatment modality, any Y90 procedures for lesions \u3e 10 cm or for treatment volumes \u3e 1000 cc were omitted from the cohort. A total of 239 patients were included in the analysis, receiving a total of 98 courses of SBRT and 187 courses of Y90 treatment. Local control (LC), freedom from liver progression (FFLP), and overall survival (OS) rates were measured from treatment completion date to death date or last follow-up. All outcomes were censored at time of loss to follow-up; LC and FFLP were censored at time of liver transplant if applicable. Cox regression models were used for survival, with significant factors on the univariate analysis further analyzed with a multivariate model. Results: Median time to follow-up was 11 months (0-44 mo). The mean size of lesions treated with SBRT were smaller than those treated with Y90 (2.7 cm vs 4.3 cm, P\u3c0.01). The groups of patients differed in liver disease characteristics, with SBRT patients having fewer Child-Pugh A disease (62% vs 80%, P\u3c0.01), more having received locoregional treatments to the liver in the past (81% v 35%, P\u3c0.01), and more disease in previously treated liver (57% vs 25%, P\u3c0.01). Dose of radiation for SBRT was 45-50 Gy administered in 5 fractions; dose of Y90 radiation to tumor was prescribed to a median of 235.2 Gy (range 55.8-512.3 Gy). There was a higher rate of one year LC in the SBRT cohort (77% vs 57%, P\u3c0.01), while median FFLP (9 mo vs 8 mo, P=NS) and median OS were not significantly different (24 mo vs 21 mo, P=NS). Multivariate analysis revealed size of largest lesion (P\u3c0.01) was correlated with decreased local control; a 1 cm increase in tumor size was associated with a 25% increased risk of local failure. Subsequent transplant (P\u3c0.01) was the remaining significant factor. Treatment modality did not remain an independent predictor of LC. Predictors of OS in multivariate analysis included age (P=0.01), prior liver treatments (HR 2.86, P\u3c0.01), size of largest lesion (P\u3c0.01), Child-Pugh stage (P\u3c0.01), portal vein thrombosis (HR 1.6, P=0.04), and subsequent liver transplant (HR 0.08, P\u3c0.01). Conclusions: These findings support the effectiveness of both MR-guided SBRT and Y90 transarterial radioembolization in locoregional management of HCC at a single institution despite clear differences in the patient cohorts. Though survival outcomes were comparable, local control differences favored the cohort treated by SBRT, in large part due to differences in tumor size. This data supports further investigation in a randomized study between SBRT and Y90

Surgery After Neoadjuvant Stereotactic MRI Guided Adaptive Radiation in Pancreatic Cancer: Multi-institutional Toxicity and Survival Outcomes

Background: Favorable toxicity and survival outcomes after dose escalated stereotactic MR guided adaptive radiation therapy (SMART) have been recently published for locally advanced (LA) and borderline resectable (BR) pancreatic cancer. Perioperative morbidity and mortality are not well understood after ablative radiation therapy, which may temper enthusiasm for offering surgery. Objectives: The purpose of this study was to investigate survival and toxicity in resected pancreas cancer patients after neoadjuvant ablative SMART. Methods: In this IRB approved analysis, we retrospectively reviewed 33 consecutive patients with resectable, BR, and LA pancreatic cancer based on NCCN 2.2021 staging criteria who were treated at 2 institutions from 2017-2020 with neoadjuvant SMART 50 Gy in 5 fractions on a 0.35T MR Linac and later underwent definitive surgical resection. Overall survival (OS) and locoregional control (LRC) were evaluated by Kaplan-Meier method. Results: Median follow up was 22.4 months from diagnosis and 17.8 months from last day of RT. Most had BR (55%), otherwise initially resectable (33%) or LA (12%) pancreatic cancer. Median duration of induction chemotherapy was 3.5 (SD 1.6) months with most common regimens being FOLFIRINOX (74%), gemcitabine/abraxane (24%) and FOLFOX (3%). Performance status was ECOG 0, 1, 2 in 16 (48.5%), 12 (36.4%), and 5 (15.2%), respectively. Whipple was performed in 27 (82%) of patients, distal pancreatectomy in 4 (12%), and total pancreatectomy in 2 (6%). The median duration from SMART completion to surgery was 6.9 weeks (4.7-44.1). R0 resections were achieved in 28 (84.8%) of patients with the rest being R1, all in BR patients. Vascular resection/reconstruction was performed of the portal vein (PV) in 8 (24.2%) patients, SMV in 4 (12%), SMA in 1 (3%), and common hepatic artery in 2 (6%). Vascular resection/reconstruction was performed in all LA patients. Median OS, 1-year OS, and 2-year OS from diagnosis were 29.6 months, 93.8%, 81.5%, respectively. Median OS from RT was not yet reached; 1-year OS was 90.9%. LRC at 1 and 2 years was 97% and 93%, respectively. Radiation related acute and late grade 3+ gastrointestinal toxicity was seen in 2 (6%) and 2 (6%) patients. Post-op mortality at 30 and 90 days was seen 2 (6%) and 3 (9%) of patients with 1 death from GI bleed attributed to surgery and 1 death from hepatic ischemia related to PV resection. Conclusions: To the best of our knowledge, this is the first report suggesting that surgery for pancreas cancer after dose escalated 5-fraction SMART is feasible. Further clarification is needed with respect to ideal patient selection and timing for surgery, the safety of arterial versus venous resection/reconstruction, and histopathologic response after delivery of ablative versus non-ablative radiation dose

Evaluating Quality of Life and Functional Outcomes in Salvage Surgery for Head and Neck Cancer

Background: Unique challenges surround treatment for residual or recurrent head and neck squamous cell carcinoma (HNSCC). Of the limited treatment options for residual or recurrent HNSCC, salvage surgery is often the best option. However, salvage surgery can result in significant morbidity, affecting both quality of life (QoL) and functional outcomes. Few studies have examined QoL outcomes following salvage surgery in the setting of HNSCC. Objectives: To analyze head and neck related quality of life and functional outcomes in patients with head and neck cancer who underwent salvage surgery. Methods: In this IRB approved study, FACT-HN Version 4 was administered pre-operatively and 6 months post-operatively to patients undergoing salvage surgery for HNSCC between November 4, 2014 and April 27, 2020. Retrospective cohort analysis was performed on this population with major outcome being postoperative QoL score. Functional outcomes included postoperative tracheostomy and feeding tube status. QoL outcomes were compared with paired t-tests. Univariate logistic regression was used to determine characteristics associated with presence of permanent tracheostomy and feeding tube, defined as presence greater than 30 days. Results: Overall, 25 patients undergoing salvage surgery for HNSCC were included in this analysis. Primary tumor sites were larynx/hypopharynx (44.0%), oral cavity (24.0%), oropharynx (20.0%), salivary (4.0%), skin (4.0%), and unknown primary (4.0%). Salvage surgeries consisted of total laryngectomy (36.0%), definitive neck dissection (24.0%), mandibulectomy (16.0%), parotidectomy (8.0%), with total laryngectomy/total glossectomy, radical tonsillectomy, TORS base of tongue excision, and transoral laser laryngeal excision all comprising 4% of cases. Total QoL scores were not significantly different preoperatively to postoperatively (mean 108.7, 95% CI=97.7 to 119.7 vs. 103.8, 95% CI: 93.1 to 114.5; P=0.436, with maximum total score of 148). Patients with lower preoperative Emotional Well-Being (EWB) subscores demonstrated significantly worse EWB subscores postoperatively (postoperative mean: 17.0, 95% CI: 14.5 to 19.4 vs. 21.7, 95% CI: 20.0 to 23.4; P=0.002). Of patients who underwent tracheostomy tube placement, 53.8% (N=7/13) remained tracheostomy dependent long-term (\u3e30 d). Of patients who underwent feeding tube placement, 81.0% (N=17/21) remained feeding tube dependent long-term (\u3e30 d). Tracheostomy and feeding tubes remained in place with median durations of 3.02 months (range 0.16 to 20.55) and 10.13 months (range 0 to 24.89), respectively. All patients with T3/4 disease undergoing salvage surgery required long-term feeding tube (N=6). Conclusions: This study provides important information about quality of life and functional outcomes for patients undergoing salvage surgery for HNSCC. There is a high rate of long-term tracheostomy and feeding tube dependence following salvage surgery. While no difference was found in head and neck related quality of life total score and sub-scores at 6 months postoperatively, general emotional well-being preoperatively was most associated with general emotional well-being postoperatively. This information should be taken into consideration when counseling and managing patients with residual or recurrent HNSCC

Racial Differences in Treatments and Toxicity in Non-Small Cell Lung Cancer Patients Treated with Thoracic Radiation Therapy

Background: Racial disparities are of particular concern for lung cancer patients given historical differences in surgery rates for African-American lung cancer patients that resulted in lower overall survival and higher recurrence rates compared with rates in White patients. Objectives: The overall objective of this study was to examine racial differences in thoracic radiation therapy (RT) treatments and toxicities in a large cohort of patients from a multi-institutional consortium database of non-small cell lung cancer (NSCLC) patients. Methods: A large multi-institutional statewide prospectively collected patient-level database of locally advanced (stage II or III) NSCLC patients who received thoracic RT from March 2012 to November 2019 was analyzed to assess the associations between race and treatment and toxicity variables. Race (White or African-American) was defined by patient self-report or if not available then by the electronic medical record system classification. Race categories other than White or African-American comprised a small minority of patients and were excluded from this analysis. Patient-reported toxicity was determined by validated tools including the Functional Assessment of Cancer Therapy-Lung (FACT-L) quality of life instrument. Provider-reported toxicity was determined by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Uni-variable and multi-variable regression models were then fitted to assess relationships between primary outcomes by race and indicators of high-quality treatment and secondary analysis of symptoms. Spearman rank correlation coefficients were calculated between provider reported toxicity and similar patient reported outcomes for each race category. Results: A total of 1441 patients from 24 institutions with mean age of 68 years (range 38-94) were evaluated; 226 patients were African-American, of whom 61% were treated at three facilities. Race was not significantly associated with RT treatment approach, use of concurrent chemotherapy, or the dose to the planning target volume (PTV) or organs at risk including the heart and lungs. However, there was increased patient-reported general pain in African-American patients (compared with White patients) at several time points including pre-RT (22% (vs 15%), P=0.02) and at the end of RT (30% (vs 17%), P=0.001). African-American patients were significantly less likely to have provider-reported grade 2+ radiation pneumonitis (odds ratio (OR) 0.36, P=0.03), despite similar levels of patient-reported respiratory toxicities such as cough and shortness of breath and even after controlling for known patient and treatment-related factors. Correlation coefficients between provider- and patient-reported toxicities were generally similar across race categories. Conclusions: In this large multi-institutional observational study, we reassuringly found no evidence of differences in radiation treatment or chemotherapy approaches by race, in contrast to historical differences by race in surgical care that led to worse survival and outcomes in minority race patients. However, we did unexpectedly find that African-American race was associated with lower odds of provider-reported grade 2+ radiation pneumonitis despite similar patient-reported toxicities of shortness of breath and cough. There are several possibilities for this finding including that pneumonitis is a multifactorial diagnosis that relies on clinical as well as radiologic information and clinical information alone may be insufficient. The Spearman correlation analysis also revealed stronger correlations between patient- and provider-reported toxicities in White patients compared with African-American patients, particularly for trouble swallowing/esophagitis. These findings together for pneumonitis and esophagitis discouragingly suggest possible under-recognition of symptoms in black patients. Further investigation is now warranted to better understand how these findings impact the care of racially diverse lung cancer patients

The Influence of Dosimetric Parameters on Quality of Life for Early Stage Non-small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy

Background: Lung stereotactic body radiotherapy (SBRT) has become a standard treatment option for early stage non-small cell lung cancer (NSCLC) patients who are medically inoperable. The influence of radiation dose/volume parameters on quality of life is not known. Our hypothesis is that clinically meaningful declines in quality of life over time will be associated with increased radiation lung dose/volume parameters. Objectives: To investigate clinical toxicity and quality of life (QOL) outcomes of stage I NSCLC patients after SBRT as a function of radiation dose/volume parameters. Methods: In this IRB-approved study, 55 stage I NSCLC patients who received SBRT (12 Gy x 4) and completed QOL forms were analyzed. Clinical symptoms and QOL were measured at baseline and at 3, 6, 12, 18, 24, and 36 months post-SBRT. Clinical toxicity was graded using the common terminology criteria for adverse effects (CTCAE v4.0). Quality of life was followed using the validated Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI) instrument. Dosimetric parameters, including the mean lung radiation dose (MLD), and the volume of normal lung receiving \u3e 5, 10, 13 or 20 Gy (V5, V10, V13, and V20) were measured from the radiation treatment plan. Student\u27s t-test and Pearson correlation analyses were used to examine the relationships between radiation lung metrics and clinically meaningful changes in QOL and/or clinical toxicities. Kaplan-Meier method was used to estimate rates of local control (LC), disease free survival (DFS), and overall survival (OS). Results: With a median follow-up of 24 months, the 3 year LC, DFS, and OS were 93%, 65% and 84%, respectively, with 5.5% grade 3 toxicity and no grade 4 or 5 toxicities. Clinically meaningful declines in patient reported QOL (FACT-TOI, lung cancer subscale, physical well-being, and/or functional well-being) post-treatment significantly correlated with increased dosimetric parameters, such as V10, V13, and V20. Conclusions: While lung SBRT is associated with excellent LC and minimal clinical toxicity for early stage NSCLC, clinically meaningful declines in QOL significantly correlated with increasing lung dose/volume parameters. This suggests that further improvements in the techniques of lung SBRT have the potential to further enhance patients\u27 QOL following this treatment