tbuckley/cabot-search huggingface dataset:
Addition of immunotherapy in adjuvant setting could be a promising avenue of colorectal cancer (CRC) treatment, especially in patients with higher levels of programmed cell death ligand-1 (PD-L1) positive circulating epithelial tumor cells (CETC) after neoadjuvant chemotherapy.
Authors: Monika Pizon, Dorothea Schott, Ulrich A. Pachmann, Katharina Pachmann, Siddarth Agrawal, Tomasz Sawicki, Anil Kumar Agrawal, Jerzy Rudnicki, Piotr Ziolkowski, Marta Wozniak
Journal: Journal of Clinical Oncology (2019)

e14036 Background: CRC is the third most frequent cancer in men and second in women worldwide. Recently, immune checkpoint molecules such as PD-1/PD-L1 have been identified as a possible target for immunotherapy in CRC and are increasingly being tested in clinical trials in combination with chemotherapy. However, the role of PD-L1 expression in CRC tumor cells and its interaction with other clinicopathologic factors remains elusive. In this study, we evaluated the impact of neoadjuvant chemotherapy on the fraction of PD-L1 positive CETCs and to compare its expression to the primary tumor. Methods: CETCs were determined from the blood of 20 patients suffering from CRC in different stages of the disease. The number of CETCs and their expression of PD-L1 were investigated using the maintrac method. In parallel, PD-L1 expression and tumor infiltrating lymphocytes (TILs) were assessed by immunohistochemistry on tissue biopsies. Results: PD-L1 expression could be assessed in all patients with detectable CETCs with a median of 50%. CETCs were more frequently found to be PD-L1 positive than tissue, and no correlation was observed between tissue and CETCs PD-L1 expression. Interestingly, patients with neoadjuvant chemotherapy had more positive PD-L1 CETCs compared to patients without chemotherapy (mean 66,7 vs. 35,2 p &lt; 0.05), but the total number of CETCs was significantly lower in the neoadjuvant group. Also, patients with mucinous adenocarcinoma had more PD-L1 positive CETCs compared to other histological subtypes. The number of TILs was higher in patients with lymph node metastasis and larger tumors. TILs count did not differ in patients with and without neoadjuvant chemotherapy. Conclusions: Assessment of PD-L1 expression in CETCs is feasible, and CETCs are more often positive than in tissue. PD-L1 expression on CETCs was higher in patients who received neoadjuvant chemotherapy. Further studies are necessary to validate these findings.
End-of-life care and prognosis of elderly patients with advanced cancer in palliative care unit.
Authors: Shuji Hiramoto, Tomoko Tamaki, Hori Tetsuo, Ayako Kikuchi, Akira Yoshioka, Toshihiko Kirishima
Journal: Journal of Clinical Oncology (2019)

e23011 Background: Prognosis of end-of-life characteristics, which are indicators of palliative care, especially in elderly cancer patients, remains unclear. Methods: We retrospectively analyzed 510 patients who died of advanced cancer at our hospital from August 2011 to August 2016. The patients were divided into two groups: elderly patients (over 80 years old, N = 140) and non-elderly patients (under 80 years old, N = 370). The number of patients (306 male and 204 female) with gastro-esophageal, biliary-pancreatic, colorectal, lung, breast, urological, gynecological, hepatocellular, and other cancers were 114, 98, 82, 84, 25, 36, 20 and 51, respectively. The primary endpoint of the study was to analyze the relationship of end-of-life symptoms, treatment, and chemotherapy with age. The secondary endpoint was to identify the prognostic factors in elderly patients with advanced cancer at the end-of-life. Results: ECOG Performance Status of 0.1 was recorded for 12 patients and 2-4 for 498 patients. The prevalence rate of cancer pain in elderly patients was 19.3%, which was significantly lower than that in non-elderly patients (31.4%). Fatigue in elderly patients was 27.9%, which was significantly lower than that in non-elderly patients (37.6%). Continuous deep sedation usage in elderly patients was 12.9%, which was significantly lower than that in non-elderly patients (28.9%). The mean opioid dose in elderly patients was 23.3mg/day, which was significantly lower than that that in non-elderly patients (43.8mg/day). The rate of more than one line of chemotherapy for elderly patients was 44.4%, which was lower than that for non-elderly patients (65.4%). The rate of use of more than one type of cytotoxic agent in the last regimen for elderly patients was 13.3%, which was lower than that for non-elderly patients (30.8%). Consciousness level was recognized as a significant prognostic factor (HR 1.714, p = 0.048) using multivariate analysis of prognosis in elderly patients at the end-of-life. Conclusions: End-of-life symptoms and the intensity of end-of-life treatment, including chemotherapy, were lesser in elderly patients as compared to non-elderly patients. Consciousness level was a significant prognostic factor in elderly patients at the end-of-life.
Real-world duration of maintenance therapy in 2nd-line and later ovarian cancer (OC).
Authors: David Garofalo, Ebru Aydin, Monica Labrador, Jennifer Webster, Joseph Donaldson, Prateesh Varughese, Helen Smith, Melissa Hagan, Ash Malik, Jeffrey A. Scott
Journal: Journal of Clinical Oncology (2019)

e17103 Background: Recurrent OC patients may benefit from maintenance therapy, with the goal of inducing a lasting remission or extending the time interval before progression without any deleterious impact on quality of life 1 . This analysis, based on real world data sourced from US community oncology practices, was designed to compare the time to next treatment of available maintenance treatment options in recurrent OC. Methods: This analysis utilized the Integra Data Exchange (DTX) database, a deidentified data source from community oncology practice systems (EMR, claims). This retrospective study included 3,629 OC patients with at least two visits between 7/16/16 and 4/16/18. 1,767 patients started at least one 2 nd line or later line of therapy and 577 of these patients had at least one line of maintenance treatment. Maintenance options were monotherapy PARP inhibitors, Bevacizumab, or non-platinum-chemotherapy. Patients who did not receive maintenance were categorized as observation. Time to next treatment (start of maintenance to start of next line of therapy) was compared through ANOVA and paired T-test analyses. Results: A statistically significant difference was seen in time to next treatment between PARPi (n = 151) and bevacizumab maintenance (n = 212) (p = &lt; 0.0125) and between PARPi and cytotoxic maintenance (n = 163) (p = &lt; 0.0001). Bevacizumab and PARPi maintenance had significantly longer duration when compared to observation (n = 1,626) (p = &lt; 0.0001). Cytotoxic maintenance duration was not significantly different than observation (p = 0.93). Conclusions: Our real world analysis found that there was a statistically significant increase in time to subsequent lines of therapy when certain maintenance treatment (PARPi, Bevacizumab) is utilized following 2 nd line and later treatment in OC. Further, between available maintenance options, PARPi had the longest time to next treatment when compared to other maintenance options.[Table: see text]
SAT0533 MRI ASSESSMENT OF HIP JOINTS INVOLVEMENT IN EARLY AXIAL SPONDYLOARTHRITIS PATIENTS
Authors: Ekaterina Agafonova, Tatiana Dubinina, Daria Rumiantceva, Anastasiya Demina, Shandor Erdes
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Based on available data from epidemiological studies in Russia different degree of hip involvement was found in 46% of ankylosing spondylitis (AS) patients, but only 7% of all cases resulted in total hip replacement procedures. <h3>Objectives</h3> To compare the ultrasound (US) manifestations of hip arthritis (coxitis) with the results of magnetic resonance imaging (MRI) of the hip joints (HJ) in patients with early axial spondyloarthritis (AxSpa). <h3>Methods</h3> We examined 39 patients (mean age 28 ± 5.92 years) with a diagnosis of AxSpa (ASAS criteria 2009), with prescription inflammatory back pain no more than 5 years; age &lt;45 years with US of coxitis. The median duration of the disease was 21 [3-60] months. BASDAI 4.0 ± 2.0, BASFI 2.0 [0.4; 3.5]. All patients underwent clinical, radiological, ultrasound, and MRI scans of HJ. For ultrasound coxitis was considered an increase in cervical-capsular distance (CCD) more than 7 mm. Coxitis is found in 27 men and 12 women. The CCD median was 7.5 [7.0; 8.2] mm. <h3>Results</h3> All patients in addition to ultrasound signs of coxitis had MRI signs of inflammation of the HJ. Pain in the HJ was determined in 33 (85%) patients. The relationship between the level of pain and the amount of effusion in HJ was not detected. RCC significantly correlated with laboratory parameters of disease activity, such as ESR (r = 0.34) p &lt;0.05 and CRP (r = 0.3), p &lt;0.05. X-ray examination revealed radiological changes in 7 patients (BASRI hip II-III). The following inflammatory changes (IC) were identified in the study population using MRI: synovitis was established in 36 (92%) patients, bone marrow edema (BME) – in 1 (3%), and combination of synovitis with BME was observed in 2 patients (5%). <h3>Conclusion</h3> Ultrasound allows you to detect changes in H in the early stages of the disease. It is possible to use ultrasound as a screening method to determine the presence of synovitis in the TBS. MRI HJ with AxSpa, allows to determine whether the patient has inflammatory changes, including in the absence of radiological changes in these joints. In 15% of cases, coxitis is asymptomatic at early stages, which requires a thorough examination of patients with AxSpa. In addition to clinical and radiological examination, all patients were subjected to MRI with T1 and STIR modes. <h3>Disclosure of Interests</h3> Ekaterina Agafonova: None declared, Tatiana Dubinina: None declared, Daria Rumiantceva: None declared, Anastasiya Demina: None declared, Shandor Erdes Consultant for: Development of studies concepts., Speakers bureau: Educational meetings organized or supported by companies.
Impact of large-scale nationwide genomic screening project for small cell lung cancer (LC-SCRUM-Japan).
Authors: Naoki Furuya, Shigeki Umemura, Hibiki Udagawa, Tadasuke Shimokawaji, Takashi Seto, Haruko Daga, Kosuke Tsuruno, Masato Shingyoji, Satoshi Hara, Haruyasu Murakami, Hiroshi Yokouchi, Shingo Matsumoto, Koichi Goto
Journal: Journal of Clinical Oncology (2019)

8559 Background: A variety of genetic analyses have been performed in small cell lung cancer (SCLC), however the clinical relevance of them remains unclear. We prospectively analyzed clinical samples of small-cell lung cancer using a nationwide genomic screening project (LC-SCRUM-Japan). Methods: Submitted tumor samples were subjected to a next-generation sequencing (NGS) system, Oncomine™ Comprehensive Assay, enabling the simultaneous analysis of 143 (ver.1) or 161 (ver.3) cancer-related genes. Results: From July 2015 to January 2019, 707 SCLC patients had been enrolled. The median age was 68 years. 77% were male and 94% were smokers. Among 588 samples completed analysis, we identified high prevalence of inactivating TP53/RB1 mutations in 426 (72%) /194 (33%) of cases, respectively. MYC/MYCL1/MYCN amplifications were detected in 21 (4%) /30 (5%) /9 (2%) of cases, respectively. This NGS analysis also showed that 32 (5%) of cases had well-known genetic alterations in receptor tyrosine kinase genes: 9 EGFR mutations, 9 KRAS mutations and 14 FGFR1 copy number gains. Mutations in the PI3K pathway were detected in 44 (7%) of the tumors. Among them, 8 cases enrolled in the investigator-initiated phase II study of gedatolisib (UMIN 000020585). Survival data was available in 463 patients receiving platinum-based chemotherapy. Multivariate analysis revealed that the presence of PIK3CA mutation (HR; 2.56; 95% CI 1.19 – 5.52; p = 0.016) and MYCN amplification (HR; 4.36; 95% CI 1.91 – 9.97; p &lt; 0.001) were significantly associated with unfavorable survival. The frequency of amplifications in MYC family genes was higher in the samples obtained ≥ 90 days after the first-line platinum-based chemotherapy (18.1%) than in those &lt; 90 days (8.1%, p = 0.01), suggesting MYC family amplification as one of the resistance mechanisms. Conclusions: This large-scale nationwide screening system is helpful for identifying therapeutically relevant genetic alterations, prognostic prediction, and exploring resistance mechanism in SCLC. Updated screening results will be presented at the 2019 ASCO Annual Meeting. Clinical trial information: UMIN000018656.
Impact of serum vitamin D on the response and the prognosis in breast cancer patients treated with neoadjuvant chemotherapy.
Authors: Eriko Tokunaga, Takanobu Masuda, Hideki Ijichi, Chinami Koga, Wakako Tajiri, Junko Tanaka, Yoshiaki Nakamura, Kenichi Taguchi, Masahiro Okamoto
Journal: Journal of Clinical Oncology (2019)

e12088 Background: Neoadjuvant chemotherapy (NAC) is one of the standard therapeutic strategies for operable early breast cancer (BC). A relationship between chemotherapy response and the prognosis has been suggested, especially in HER2+ or triple negative breast cancer (TNBC). Recently, the impact of vitamin D (VD) on pathological complete response (pCR) after NAC has been reported, however, there are no data regarding the relationship between VD level and the efficacy of NAC in Japanese BC patients. Methods: This study included 236 patients with BC at clinical stage I-III, who were treated with anthracycline and taxane-based NAC. HER2-directed therapies were used for HER2+ tumors. Serum 25, hydroxyl VD levels were evaluated using by ELISAusing blood samples obtained before NAC. VD deficiency was defined as &lt;20 ng/ml. Results: Pathological complete response (pCR) was obtained in 52 patients (22.0%). The pCR rate was significantly higher in the patients with HER2+ or TNBC compared with hormone receptor (HR)+/HER2-tumors (p&lt;0.0001). Median VD level was 10.7 ng/ml, and only 7 patients (3.0%) had a VD level ≥20 ng/ml. These results show that most Japanese women are deficient for VD. VD levels increase with age, and the VD levels are significantly higher in postmenopausal patients than in the premenopausal patients (p=0.0029). Patients were dichotomized into VD-low and -high groups at the median value (10.7 ng/ml). Serum VD was not associated with pCR in the all cohort, however, pCR rate was higher in VD-high group in premenopausal patients, especially in the patients withHER2+ or TNBC (p=0.0328). High VD was significantly associated with better prognosis in terms of relapse-free survival (p=0.0327) and distant metastasis-free survival (p=0.0051). This association was observed both in pre- and post-menopausal patients, especially in the patients with HER2+ or TNBC. Conclusions: High VD levels were associated with high pCR rate in premenopausal patients with HER2+ or TNBC. High VD levels were also associated with better prognosis operable BC patients treated with NAC, although VD levels of most Japanese BC patients were lower than the cut-off value.
Incidence of FGFR-TACC gene fusions in Chinese non-small cell lung cancer (NSCLC): A multicenter study.
Authors: Xiuyu Cai, Chunwei Xu, Wen xian Wang, Quxia Zhang, Yu Chen, Yong Fang, Hong Wang, You-cai Zhu, Wu Zhuang, Yun-jian Huang, Yinbin Zhang, Liping Wang, Yafei Wang, Meifang Chen, Dongyong Yang, Shangli Cai, Meiyu Fang, Gang Chen, Tangfeng Lv, Yong Song
Journal: Journal of Clinical Oncology (2019)

e13001 Background: Fibroblast growth factor receptors (FGFR) are transmembrane kinase proteins with growing importance in non-small cell lung cancer (NSCLC) biology given the frequency of molecular alterations and vast interface with multiple other signaling pathways. Furthermore, numerous FGFR inhibitors in clinical development demonstrate the expanding therapeutic relevance of this pathway. The aim of this study was to evaluate the prevalence of FGFR-TACC fusions in Chinese NSCLC populations, which had not been reported earlier, and to describe targeting potential in Chinese NSCLC populations. Methods: A multicenter study in China was initiated from February 2014, and NSCLC patients have been enrolled as of December 2018. Capture-based comprehensive genomic profiling was performed on 2743 NSCLC FFPE samples sequenced to a mean coverage depth of &gt; 650X for up to 381 cancer-related genes. Genomic alterations (GA) included short variant (SV) base subs and insertions/deletions, copy number alterations, and rearrangements/fusions. Tumor mutational burden (TMB; mut/Mb) was calculated on up to 1.2 Mb of sequenced DNA. Results: Of this entire cohort, just 16 (0.58%) patients were identified with FGFR-TACC fusions, including FGFR1-TACC 1 fusion (1), FGFR2-TACC2 fusion (3) and FGFR3-TACC3 fusion (12). Median patient age was 57 (range 36-84 years). Of the FGFR-TACC fusion NSCLC patients, 56.25% were detected in female patients. Biopsies were obtained from primary lung tumor (31.25%) and metastatic sites (68.75%). Overall TMB in the FGFR-TACC fusion was low (median 3.6 mut/Mb), although two cases (12.50%) had &gt; 20 mut/Mb. Of the FGFR-TACC fusion NSCLC patients, two cases (12.50%) featured EGFR SV alterations. Conclusions: FGFR-TACC fusions occur in a subset of patients with NSCLC. Such patients should be considered for clinical trials featuring FGFR inhibitors (AZD4547). Moreover, NGS can provide information for targeted therapy. For NSCLC patients to benefit from more personalized cancer treatment, clinical therapy should improve with clinical diagnostics through multi-gene assays to determine the actual clinical benefits.
Trends in opioid use in patients undergoing primary surgery for cervical cancer.
Authors: Katherine Tucker, Laura Farnan, Jeannette T Bensen, Irene Doherty, Paola A. Gehrig
Journal: Journal of Clinical Oncology (2019)

e17014 Background: In response to the opioid epidemic, restrictions on prescribing opioids for pain management may result in unintended consequences for patients with cancer-related pain. Factors that place women at higher risk for opioid misuse include age, insurance status, tobacco use and a diagnosis of cervical cancer. Our objective was to describe describe patterns of opioid use and prescribing practices over time. Methods: We performed a retrospective study of patients diagnosed with cervix cancer enrolled in our institution’s Health Registry/Cancer Survivorship Cohort from 5/2010-3/2017. The dataset included demographics, clinicopathologic data, reported opioid use (prior, during and after treatment) and prescription history from the EMR after IRB approval. This preliminary analysis included frequencies, cross-tabulations, and measures of distributional characteristics. Results: Of the 122 patients identified, 94 had surgery. Mean age at diagnosis was 44.7 yrs and BMI was 29.13. Eighteen (19.1%) patients had an opioid use history. Given changes in EMR documentation in 2014, 37 were excluded as assessment of opioid use and prescriptions was limited to only MD documentation. While there was no pre-defined protocol change, post-operative opioid prescribing practices changed in late 2014. From 5/2014-11/2014, 17 patients underwent surgery with 88% receiving prescriptions for 40 tablets of an opioid. From 12/2014-12/2016, 40 patients underwent surgery with 27.5% receiving prescriptions for 40 tablets of an opioid and 65% receiving 20-30 tablets. Prior to 12/2014, 1/16 patients (6.3%) required additional opioids postoperatively with no documented complication compared to 9/40 patients (22.5%) after 12/2014. In this group, most frequent prescriptions were coming from the patient’s gynecologic oncologist and/or a primary care provider. Conclusions: We saw a small increase in additional opioids after the routine number prescribed declined. However, this comprised a minority of patients. Monitoring of the opioid needs and use among women with cervix cancer will aid in the development of clinically-tailored guidelines to replace the current reactionary restrictions on treatment for all patients.
Prognostic index for patients with relapsed or refractory acute myeloid leukemia who underwent hematopoietic cell transplantation: a KSGCT multicenter analysis
Authors: Takayoshi Tachibana, Junya Kanda, Takuma Ishizaki, Yuho Najima, Masatsugu Tanaka, Noriko Doki, Shin-ichiro Fujiwara, Shun-ichi Kimura, Makoto Onizuka, Satoshi Takahashi, Takeshi Saito, Takehiko Mori, Shin Fujisawa, Emiko Sakaida, Kenji Matsumoto, Nobuyuki Aotsuka, Moritaka Goto, Reiko Watanabe, Katsuhiro Shono, Kensuke Usuki, Nobuhiro Tsukada, Heiwa Kanamori, Yoshinobu Kanda, Shinichiro Okamoto
Journal: Leukemia (2019)
Real-world data regarding the efficacy of neoadjuvant carboplatin-paclitaxel followed by dose-dense adriamycin-cyclophosphamide for triple-negative early breast cancer.
Authors: Ajay Ashok Bhojwani, Helen Flint, Benjamin James Hall, Helen Wong, Helen Innes, Joanne Cliff, Eliyaz Ahmed, Zaf Malik, Julie O'Hagen, Shaun Tolan, Allison Hall, Khizar Hayat, Douglas Errington, Farida Alam, Nicky Thorp, Susan O'Reilly, Andrea Law, Silvia Cicconi, Richard Jackson, Carlo Palmieri
Journal: Journal of Clinical Oncology (2019)

e12559 Background: Platinum based regimens in the neoadjuvant (NA) setting for triple negative breast cancer (TNBC) have resulted in a significant increase in the pathological response (pCR) rate but at the cost of worse hematological toxicities. Despite these data such NA regimens are not widely used as yet for TNBC. Currently, no real world evidence exist regarding the efficacy and toxicity of this treatment regimen. Methods: Patients treated with neoadjuvant carbo-pac-ddAC between December 2015 and May 2018 at Clatterbridge Cancer Centre NHS Foundation Trust were identified via pharmacy records. Clinical records were reviewed, and clinico-pathological information and toxicity data were recorded. Data lock was January 16, 2019. Results: 53 female patients were identified with a median age of 48 years (IQR: 40.0-55.5). At presentation: Median tumour size 29mm (IQR: 20.0-40.0), 45% (24/53) were LN +, 8% (4/53) were ER+. Of 30 patients tested for germ line susceptibility, 23% (7/30) were found to have a BRCA mutation (full details to be presented). Delivery of planned CT : 4% (2/53) discontinued early for progressive disease or patient choice; of the remaining patients there were a total of 36 deferrals and 8 dose reductions. Surgical details: Breast: 42% (22/53) mastectomy &amp; 58% (31/53) WLE, Ax management: 37% (19/51) Ax clearance &amp; 63% (32/51) sentinel node biopsy (2 patients underwent previous axillary treatment for prior BC). Of 24 patients LN+ at presentation 58% (14/24) underwent Ax clearance; of these 64% (9/14) had no Ax involvement. pCR rate (ypT0/is, N0) (cases with prior ipsilateral Ax surgery excluded) was 53% (27/51) &amp; pCR breast alone: 60% (31/52). Radiotherapy: 90% (47/52) received radiotherapy post-surgery. Outcome: At a median follow up 42.4 wks (IQR: 34.2-54.4), 6% (3/52) patients had disease recurrence resulting in 2 deaths. Conclusions: These initial real world data confirm the efficacy of NA therapy with carbo-pac-ddAC, with pCR rates consistent with literature. These results support the use of platinum based chemotherapy in the NA management of TNBC. Updated outcomes will be presented based on pCR versus no pCR; and BRCA status.