tbuckley/cabot-search huggingface dataset:
Uridine triacetate as a life-saving antidote to capecitabine toxicity.
Authors: Wen Wee Ma, Thomas H. Cartwright, Bassel F. El-Rayes, James Posey, Marwan Fakih, Thomas King, Reid von Borstel, Michael K. Bamat
Journal: Journal of Clinical Oncology (2016)

e21612 Background: Uridine triacetate was approved by FDA in 2015 for adult and pediatric patients who receive an overdose of 5-fluorouracil or capecitabine or who exhibit early-onset, severe or life-threatening toxicities. Early-onset toxicities from capecitabine or 5-FU treatment are due to various metabolic causes, including DPD deficiency, and can be fatal. Uridine triacetate is an oral prodrug of uridine, a direct antagonist of 5-FU, that dilutes and competes with toxic 5-FU metabolites, particularly FUTP incorporation into RNA, reducing morbidity and mortality due to 5-FU and capecitabine. Methods: Uridine triacetate has been studied in 2 trials (173 patients) to date, including 13 who received an overdose of capecitabine or developed early-onset, severe toxicities. The Sponsor (Wellstat Therapeutics) was contacted upon recognition of an overdose or early-onset toxicity and evaluated patient eligibility. Adults (n = 6 overdose and 4 early-onset) were to receive 10 g of uridine triacetate orally every 6 hr for 20 doses. Pediatric patients (n = 3) were to receive 6.2 g/m2 orally every 6 hr for 20 doses. Uridine triacetate was to start within 96 hr following the end of capecitabine. The primary endpoint was survival at 30 days following uridine triacetate. All patients were monitored for safety. Results: All 6 adult capecitabine suicidal overdose cases (up to 28,000 mg at once) and all 3 pediatric patients who accidentally took capecitabine recovered fully within 30 days post-treatment with uridine triacetate. Both patients who presented with multiple severe post-capecitabine toxicities but initiated treatment with uridine triacetate > 96 hr died. In contrast, both patients who presented with similar multiple severe early-onset toxicities but who started uridine triacetate within the recommended 96 hr post capecitabine fully recovered. Only one AE (vomiting) was attributed to uridine triacetate. Conclusions: Uridine triacetate was a safe and effective life-saving treatment for patients following potentially lethal capecitabine overexposure or early-onset toxicities when administered within 96 hr post capecitabine dosing.
Immunotherapy awareness in the oncology patient population: An Irish hospital experience.
Authors: Umair Aleem, Cliona Grant, David James Gallagher, Sumainizah Sukor, John Kennedy, Crothur F. Kelleher, Maeve Aine Lowery, Dearbhaile M. O' Donnell, June Gleeson, Louise Glennon, Sinead Cuffe
Journal: Journal of Clinical Oncology (2018)

e15160 Background: To identify cancer patients’ awareness, experience and understanding of immunotherapy, as well as factors influencing their acceptance of treatment. Methods: This study was undertaken from October 2017-January 2018 in St. James’s Hospital. A patient questionnaire was distributed and informed consent was obtained. Results: 220/250 (88%) of patients approached participated. 129(59%)male. Majority had lung (47%),oesophageal/gastric (17%),breast (14%),ovarian (8%) or colorectal cancer (7%) 69% were aware of immunotherapy; 51% from media, 42% from oncology team. Majority believed that immunotherapy was either definitely (25%) or probably (61%) an effective type of treatment for their cancer; 14% unsure. However, a significant proportion (81%) was unsure if there was an approved immunotherapy for their cancer. Patients had high expectations of immunotherapy, believing it to be more effective (71%) or equivalent (24%) to standard chemotherapy, while none ranked it worse. Similarly, patients expected lesser (62%) or equivalent (25%) side effects compared to chemotherapy. Majority (96%) were very willing to get immunotherapy if recommended by oncology team with 93% willing to enter clinical trial to access same. Most were willing to travel to other treating centres(73%) or even abroad (24%) .However, they were less willing (56%) to pay for treatment if not funded. A significant proportion would undertake a repeat biopsy (66%) and/or extra bloods (98%) to determine their likelihood of response. Majority (75%) preferred doctor review with each visit. 88% preferred immunotherapy education at first visit; preferring both verbal and written information (96%). Majority (97%) were highly satisfied with level of information provided. Conclusions: Majority of patients have very high expectations of immunotherapy. They are willing to travel to other centres either locally or abroad and enter clinical trials to avail of this treatment, but are less willing to pay. However, we noted a lack of patient understanding as to whether immunotherapy was an approved treatment option for their cancer. Significant patients preferred doctor led clinic review which will have immense resource implications moving forward.
Concurrent nivolumab and radiotherapy to improve outcomes for patients with metastatic lung and renal cancers.
Authors: Jawaher Ansari, Ashraf Farrag Farrag, Arwa Ali, Muhammad Ali, Arif Adnan Shaukat, Khalid Hussein, Farhat Bashir, Mai Abdel Gelil, John Glaholm, Syed A. Hussain, Abdulaziz Al Hamad, Asif Ansari
Journal: Journal of Clinical Oncology (2018)

e15078 Background: Checkpoint inhibitors (CPIs) such as nivolumab have transformed the treatment paradigm for patients (pts) with metastatic non-small cell lung cancer (mNSCLC) and renal cell carcinoma (mRCC). Low response rates (20%) with CPIs has prompted novel immunotherapy combination trials. Radiotherapy (RT) causes direct tumor cell death and in addition also effectively stimulates T-cell immunity. RT is a highly cost-effective anti-cancer treatment and its combination with CPIs may herald a new potent therapeutic tool. This study reports on the efficacy and toxicity of concurrent nivolumab and RT administration. Methods: Pts with mNSCLC and mRCC receiving concurrent nivolumab and RT were assessed retrospectively for radiological response (RECIST 1.1), toxicity and symptom benefit (pain score). Results: Of the 63 pts that received nivolumab at our institution, 15 pts received concurrent RT for 32 courses; mNSCLC (n = 8), mRCC (n = 7). Median age 59 years (range 39-71); M:F ratio (4:1). Stereotactic and conformal RT was delivered to 5 and 27 sites, respectively. Most common indication for RT was oligometastatic disease progression (PD): 59%. Treatment sites included: bones (n = 13), lung (n = 7), brain (n = 5), adrenal, renal bed, skin, ethmoid and scalp. The gap between RT & nivolumab did not exceed 2 weeks for all patients. No grade 3-4 toxicities were observed; grade 2 pneumonitis noted in 2 pts. Fractionation schedules included 20Gy/5 fractions (#) (most common-47%), 48Gy/4#, 40Gy/10#, 40Gy/4#, 34Gy/4#, 30Gy/10#, 25Gy/5#, 20Gy/4#, 16Gy/4#, 22Gy/1# and 8Gy/1#. Of the 23 measurable sites, 70% had excellent response including complete response at 3 sites. Pain scores improved in 6 out of 9 sites (67%). Conclusions: The combination of nivolumab and RT appears to be well tolerated in pts with mNSCLC and mRCC with response rates exceeding published studies of nivolumab monotherapy. For patients with oligometastatic PD during nivolumab therapy, addition of RT appears to initiate a response and prolong time spent on nivolumab. Future clinical trials may better define whether RT during nivolumab treatment should be used as induction therapy, consolidative therapy or should be used for pts with oligometastatic PD.
Net survival of sarcomas according to anatomic, histology and genomic profiles in population-based cancer registries in France.
Authors: Brice Amadeo, Jean Michel Coindre, Nicolas Penel, Isabelle Laure Ray-Coquard, Karine Ligier, Patricia Delafosse, Anne-marie Bouvier, Sandrine Plouvier, Aude Lacourt, Gaëlle Coureau, Monnereau Alain, Emmanuel Desandes, Simone Mathoulin-Pélissier
Journal: Journal of Clinical Oncology (2018)

e13593 Background: Sarcomas are a group of heterogeneous and rare malignant neoplasms occurring in any anatomical site characterized by various histological subtypes. Because survival is rarely described according to histology and genomic profiles, this study aimed to provide estimates of the net survival (NS) of sarcomas using the WHO classification of soft tissue and bone published in 2013. Methods: Data were collected in 14 French population-based cancer registries covering 11% of the French population. We included all incident sarcoma patients older than 15 years of age between 2005 and 2010 followed up to 30th June 2013. Net survival rates were estimated using the Pohar-Perme method for anatomic, histology and genomic sarcoma profiles. Results: During the study period 4,406 patients with sarcomas were diagnosed. As expected, NS declined with increasing age at diagnosis. Women and men had comparable survival. According to anatomic profiles, large disparities in term of 5-year NS were observed which ranged from 48% (confidence interval –95% CI: 43-54) for woman genital tumours to 89% (95% CI: 85-94) for skin tumours. Intermediate survival were observed for soft tissue, bone and gastro-intestinal tumours, with a 5-year NS of 56% (95% CI: 54-59), 61% (95% CI: 57-66) and 70% (95% CI: 65-75), respectively. With respect to histology profiles, the same heterogeneity was observed. The 5-year NS ranged from 28% (95% CI: 19-39) for skeletal muscle tumours to 86% (95% CI: 85-94) for fibroblastic tumours. Finally, when looking at the genomic alteration profile, sarcomas with MDM2 amplification had the highest 5-year NS (76%, 95% CI: 71-81) and sarcomas with complex genomic profile the lowest (58%, 95% CI: 55-60). Tumours with undefined genomic had a NS of 44% (95% CI: 40-49). Conclusions: The present study provides for the first time NS of sarcomas using the 2013 WHO classification applied to the registry data and combining different sarcoma profiles. Large prognostic heterogeneity is reported within each sarcoma profile. The latter should be taking into account in future analyses of survival for sarcomas and in clinical trials.
Near-Apneic Ventilation Decreases Lung Injury and Fibroproliferation in an Acute Respiratory Distress Syndrome Model with Extracorporeal Membrane Oxygenation
Authors: Joaquin Araos, Leyla Alegria, Patricio Garcia, Pablo Cruces, Dagoberto Soto, Benjamín Erranz, Macarena Amthauer, Tatiana Salomon, Tania Medina, Felipe Rodriguez, Pedro Ayala, Gisella R. Borzone, Manuel Meneses, Felipe Damiani, Jaime Retamal, Rodrigo Cornejo, Guillermo Bugedo, Alejandro Bruhn
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

There is wide variability in mechanical ventilation settings during extracorporeal membrane oxygenation (ECMO) in patients with acute respiratory distress syndrome. Although lung rest is recommended to prevent further injury, there is no evidence to support it.To determine whether near-apneic ventilation decreases lung injury in a pig model of acute respiratory distress syndrome supported with ECMO.Pigs (26-36 kg; n = 24) were anesthetized and connected to mechanical ventilation. In 18 animals lung injury was induced by a double-hit consisting of repeated saline lavages followed by 2 hours of injurious ventilation. Then, animals were connected to high-flow venovenous ECMO, and randomized into three groups: 1) nonprotective (positive end-expiratory pressure [PEEP], 5 cm H2O; Vt, 10 ml/kg; respiratory rate, 20 bpm), 2) conventional-protective (PEEP, 10 cm H2O; Vt, 6 ml/kg; respiratory rate, 20 bpm), and 3) near-apneic (PEEP, 10 cm H2O; driving pressure, 10 cm H2O; respiratory rate, 5 bpm). Six other pigs were used as sham. All groups were maintained during the 24-hour study period.Minute ventilation and mechanical power were lower in the near-apneic group, but no differences were observed in oxygenation or compliance. Lung histology revealed less injury in the near-apneic group. Extensive immunohistochemical staining for myofibroblasts and procollagen III was observed in the nonprotective group, with the near-apneic group exhibiting the least alterations. Near-apneic group showed significantly less matrix metalloproteinase-2 and -9 activity. Histologic lung injury and fibroproliferation scores were positively correlated with driving pressure and mechanical power.In an acute respiratory distress syndrome model supported with ECMO, near-apneic ventilation decreased histologic lung injury and matrix metalloproteinase activity, and prevented the expression of myofibroblast markers.
Accessibility and utilization of stereotactic body radiation therapy for localized prostate cancer: An analysis of geodemographic clusters.
Authors: Nima Aghdam, Ali Arab, Deepak Kumar, Simeng Suy, Anatoly Dritschilo, John J. Lynch, Sean P. Collins, Jonathan Lischalk
Journal: Journal of Clinical Oncology (2018)

e18636 Background: Geodemographic characteristics including median income, education, ethnicity, and rural residency mediate healthcare access and disparity. SBRT offers definitive treatment with acceptable toxicity over shorter time relative to conventional radiotherapy for prostate cancer. This has important implications on reducing the treatment burden and improving radiation accessibility. In this study, we characterize the geodemographic clusters of patients who have undergone SBRT at our institution over the last decade. Methods: 1035 zip codes were derived from a quality of life database for patients treated from 2008 to 2017. The distance between each zip code to our institution was calculated using the R package Geosphere. U.S. census data for each zip code was collected for analysis. An unsupervised learning algorithm was performed to identify clusters of patients with respect to median income, racial makeup, educational level, and rural residency. Inter-cluster comparisons were performed for these features and their relation to distance traveled for treatment. Results: Patients traveled from 246 zipcodes at a median distance of 11.35 miles. The median income was $94,213, 21% are African American (AA), 6.9% live in rural areas, 87% are high school (HS) graduates. Using K-means cluster analysis, 4 zip-code groups are identified based on the aforementioned demographic features: suburban/high-income (45%), urban (30%), suburban/low-income (17%), and rural (8%). The average travel distance for treatment is 14.8, 10.8, 17.5 and 54.7 miles, respectively for each cluster (p < 0.001). Median income ($121,957) and HS graduation rate (93%) is highest in the suburban/high-income cluster. The urban and suburban/low-income clusters differ in AA residents (75% vs. 31%, p < 0.005), with similar incomes ($72,153 vs. $74,087 dollars, p = 1.0). Conclusions: Distinct geodemographic clusters are identified in this large cohort of patients. Although, a rural cluster with a significant travel distance represents an important minority, these findings suggest accessibility, as represented by travel distance and patient cluster prevalence, may be driven by income and race.
Quality of life and performance capacity in patients with breast cancer and patients with gastro-intestinal stromal tumors (GIST).
Authors: Matias Chacon, Laura Manghino, Federico Losco, Guillermo Mendez, Jorge Carlos Nadal, Reinaldo D. Chacon
Journal: Journal of Clinical Oncology (2018)

e18881 Background: Breast cancer is the most common among argentine women. In contrast, gastrointestinal stromal tumors (GIST) are infrequent neoplasms, with a similar incidence for both sexes. The objectives of this study were to evaluate the quality of life, the capacity of performance and the adjustments in the family economy that arise from the disease. Methods: Prospectively, 200 patients with breast cancer and 50 patients with GIST diagnosis were included, with or without systemic treatment, who attended the consultation at the Alexander Fleming Institute between August 2016 and August 2017. The questionnaires were administered EORTC QLQ- C30, QLQ-BR23, RNLI and a non-standardized questionnaire that included questions about patient’s social and economic context. Results: Quality of life, on functional and symptomatic scales, was lower in patients with metastatic breast cancer compared to localized breast cancer (58 versus 77.48) and metastatic GIST, which presented a score similar to its localized counterpart (77 versus 80). The reintroduction score to normal life also showed the same profile of satisfaction distribution as the overall health status, being the population with metastatic breast cancer the one with most difficulties. The disease was the major determinant for patients with metastatic breast cancer (73%) and advanced GIST (44%), causing little economic interference in GIST ( < 10%) and moderate in breast cancer (13-30%). The household economic contribution in the two models evaluated is double for patients with localized disease compared to metastatic patients. Conclusions: The present study is the first comparing quality of life scores, of reintroduction to life during cancer and economic impact of the disease in patients with breast cancer and localized and metastatic GIST. The subgroup with metastatic breast cancer presented the lowest values in quality of life and performance, as well as the highest economic impact related to the disease and treatments.
Implementation of a multidisciplinary quality improvement initiative to improve molecular testing rates in advanced non-squamous non-small cell lung cancer.
Authors: Zachary Otaibi, Rohit Rao, Matthew Bartock, Mamatha Gaddam, Samantha A Martin, Gene Grant Finley
Journal: Journal of Clinical Oncology (2017)

e18181 Background: EGFR mutations and ALK rearrangements are key therapeutic targets in nonsquamous nonsmall cell lung carcinoma (nsNSCLC). Treatment with targeted therapy has been shown to improve progression-free survival and overall survival in many cases. Current guidelines recommend testing all advanced (Stage IIIB and IV) nsNSCLC patients for these genetic aberrations. Our previous work revealed that we were not evaluating a large percentage of eligible patients. In order to improve testing rates, we conducted a series of multidisciplinary meetings aimed at direct physician education and process enhancement. Methods: Utilizing the Association of Community Cancer Centers (ACCC) molecular testing framework in conjunction with support from Pfizer, we launched a lean six sigma initiative aimed at improving our molecular profiling rates. A series of multidisciplinary meetings were conducted addressing action items outlined by the ACCC. A total of 158 advanced nsNSCLC patients were identified from our tumor registry during or shortly after the start of this initiative (2014-2015). Testing rates for EGFR and ALK were determined by individual chart review and compared to our previously published testing rates (2011-2013). Results: We found 77.9% (123/158) and 60.8% (96/158) of patients were tested for EGFR mutations and ALK rearrangements, respectively. We utilized a chi-square test of homogeneity to determine whether there was an increased EGFR and ALK testing rate post-intervention . Our EGFR testing rate increased 80.3%, from 43.2% (2011-2013) to 77.9% (2014-2015), p &lt; 0.00001, and our ALK testing rate increased 155.5%, from 23.8% (2011-2013) to 60.8% (2014-2015), p &lt; 0.00001. Conclusions: Multidisciplinary educational and process enhancement meetings improve molecular testing rates in nsNSCLC.
Hospital admissions due to immuno-oncology therapy associated toxicity: A retrospective analysis at two tertiary oncology centres.
Authors: Michael J Allen, Andrew Schmidt, Zarnie Lwin, Brett Gordon Maxwell Hughes
Journal: Journal of Clinical Oncology (2018)

e18805 Background: The use of immuno-oncology therapies (IO) is increasingly more common in the treatment of cancer. Hospital admissions secondary to immune-related adverse events (irAE) are likely to increase. We sought to determine the frequency of hospital admissions due to irAE and whether there was a delay to the recognition of IO-associated toxicity. Methods: A retrospective analysis of patients treated with IO at two tertiary hospitals in Queensland, Australia was performed. Patients who received at least one dose of IO for a non-haematological malignancy between the 1st January 2016 and 1st January 2017 were included. All subsequent hospital admissions were analysed. Results: 140 patients were included, with 78 patients (56%) requiring at least one admission. 15 (13%) admissions were as a consequence of irAE. The most common malignancies were non-small-cell lung cancer (41%) and melanoma (18%). The majority of patients were treated with a programmed cell death protein 1 inhibitor (n = 109, 78%). Those admitted were observed to be older (65.9 v 61.9 yrs; p = 0.034). Baseline characteristics were otherwise similar. The mean number of cycles administered prior to admission was 8 and 6 (p = 0.312) and the mean duration of admission was 9.3 v 8.5 days (p = 0.68) for irAE and non-irAE respectively. The most common irAE requiring admission were pneumonitis (n = 6; 40%), hepatitis (n = 3; 20%) and colitis (n = 2; 13%). Of those admitted with irAE 46.7% (n = 7) were misdiagnosed at admission and were only diagnosed upon subsequent review by an oncologist. These diagnoses were pneumonitis (n = 3), colitis (n = 2), arthritis (n = 1) and bulbar palsy (n = 1). All patients with irAE were managed with high-dose corticosteroids. 5 patients (33.3%) discontinued treatment due to irAE. No deaths resulted from irAE. Conclusions: The incidence of irAE requiring hospital admission was low. Almost half of the patients admitted due to irAE had a delayed diagnosis and subsequent delay in the administration of high-dose corticosteroids. This did not affect the length of admission or result in any mortality but suggests a need for improved cross-discipline awareness of irAE complications in order to improve quality patient care.