tbuckley/cabot-search huggingface dataset:
A phase III study comparing trastuzumab emtansine with trastuzumab, pertuzumab, and docetaxel in elderly patients with advanced stage HER2-positive breast cancer: (JCOG1607 HERB TEA study).
Authors: Akihiko Shimomura, Kenji Tamura, Tomonori Mizutani, Taro Shibata, Fumikata Hara, Tomomi Fujisawa, Naoki Niikura, Takashi Hojo, Chizuko Kanbayashi, Shigehira Saji, Norikazu Masuda, Masataka Sawaki, Naohito Yamamoto, Fumio Nagashima, Tadahiko Shien, Hiroji Iwata
Journal: Journal of Clinical Oncology (2019)

TPS1100 Background: Systemic chemotherapy with anti-HER2 therapy is the standard of care for HER2-positive advanced breast cancer. Patient outcomes have improved remarkably with the use of novel anti-HER2 drugs, including trastuzumab (H), pertuzumab (P), and trastuzumab emtansine (T-DM1). The combination treatment comprising H, P, and docetaxel (D) (HPD) is highly recommended as the 1st-line treatment for patients with HER2-positive advanced breast cancer. In contrast, for elderly patients over 65 years of age, this regimen seems to be intolerable mentally and physically, and impairs their quality of life. A new standard treatment with less toxicity and non-inferior efficacy for elderly patients is needed. Methods: We have planned a randomized, multicenter, open-label, phase III trial to confirm the non-inferiority of T-DM1 compared to HPD in terms of overall survival (OS) in elderly patients with HER2-positive advanced breast cancer. The eligibility criteria are as follows: 1) histologically proven metastatic breast cancer, 2) age 65-74 years with a performance status (PS) score 0-2, or 75-79 years with a PS score 0-1, 3) HER2 overexpression or amplification confirmed in primary or metastatic tissues, and 4) no anti-HER2 therapy with chemotherapy for breast cancer, excluding (neo) adjuvant therapy. Patients are randomized to receive either HPD (H 6 mg/kg, P 420 mg/body, and D 60 mg/m 2 ) or T-DM1 3.6 mg/kg every 3 weeks. The dose up of D (75 mg/m 2 ) after the second cycle is defined based on the data regarding safety during the first cycle. The primary endpoint is OS. The secondary endpoints are progression-free survival, response rate, adverse events, breast cancer-related death, and deterioration of activities of daily living. The trial is designed to achieve 70% power to confirm non-inferiority of T-DM1 to HPD at a one-sided alpha of 5% with a non-inferiority margin of 1.3 in terms of hazard ratio. With a median OS of 30 months in both arms, 6 years of accrual, and 5 years of follow up, the planned sample size is 330. The trial began in January 2018 and nineteen patients have been enrolled as of January 2019. Clinical trial information: UMIN000030783.
Circulating tumor DNA-based mutational landscape of advanced colorectal cancer.
Authors: Fang Yan, Wei Gao, Lifei Zhu, Wenzhuan Xie, Chan Gao, Jing Zhao, Mengli Huang, Shangli Cai, Yi Zhong
Journal: Journal of Clinical Oncology (2019)

e15034 Background: Alterations in oncogenic driver genes are extensively tested to guide anticancer treatment in colorectal cancer (CRC). As the repertoire of therapeutic targets continue to grow, we are interested to interrogate the possibility of resorting to circulating tumor DNA (ctDNA) where tissue samples are not readily available. Methods: Targeted next generation sequencing (NGS) was performed on ctDNA obtained from patients with advanced CRC using a 150-gene panel. Mutational profiles of ctDNA were compared with those detected in tissue samples from the 3D Medicine database as well as The Cancer Genome Atlas (TCGA) database. Genomic aberrations such as single nucleotide variations (SNVs), insertions/deletions, copy number variations, gene rearrangement and fusions were analyzed. Results: Notably, 244 of 256 samples (95.3%) were ctDNA-positive, as indicated by a maximum somatic allele frequency (MSAF) of &gt; 0%. At least one reportable genomic alteration was detected in 96.5% of all cases, with an average of 8.12 mutations per case. The most frequently mutated genes were TP53 (47%), APC (42%), KRAS (32%) in ctDNA. A similar trend was also observed for SNVs, where TP53 (46.9% vs. 77.6% vs. 53.8%), APC (41.8% vs. 66.0% vs. 73.0%), and KRAS (30.5% vs. 48.4% vs. 43.5%) had the highest mutation frequencies across three data sets (ctDNA, tissues and the TCGA database). The SNV profiles of therapeutically relevant genes for CRC were also largely consistent between ctDNA and the tissue samples included in the 3D Medicine database: BRAF (7.0% vs. 8.7%), KRAS (30.5% vs. 48.4%), NRAS (2.7 vs. 3.1%), ERBB2 (5.1% vs. 5.2%), MLH1 (0.8% vs. 2.9%), MSH2 (2.7% vs. 3.1%), and MSH6 (3.1% vs. 3.7%). Patients harboring copy number gains had a significantly higher level of MSAF than those free of gene amplifications (p &lt; 0.0001). Conclusions: Mutational landscape of ctDNA in general correlated with that detected in prior tissue samples as well as the TCGA database, supporting a role for ctDNA testing as a complementary approach to tissue testing in CRC.
Tumor stroma proportion to predict platinum chemoresistance in primary ovarian carcinomas: A prospective study.
Authors: Emil Lou, Rachel Isaksson Vogel, Spencer Hoostal, Aaron Grad, Minnu Monu, Tomasz Lukaszewski, Jaai Deshpande, Michael Linden, Molly Klein, Deanna Gek Koon Teoh, Melissa Ann Geller
Journal: Journal of Clinical Oncology (2019)

5581 Background: Platinum chemotherapy resistance occurs in approximately 25% of patients with ovarian carcinoma and represents a major barrier to effective care of this patient population. To date there are no effective nor validate predictive biomarkers of chemoresistance of ovarian carcinomas. We performed a prospective trial designed to enroll patients with ovarian masses suspicious for ovarian cancer, with the goal of identifying tumor-based predictive biomarkers of platinum resistance. Methods: 60 women were enrolled on the study. Tumor specimens were collected from 49 of these women with newly diagnosed pelvic masses, of which 29 were found to have histopathologically proven primary ovarian carcinoma. Of these primary malignant cases, 24 had specimens accessible for assessment of tumor-stroma proportion and data available regarding chemosensitive vs chemoresistance status via review of the medical record using a UMN IRB-approved protocol. Tumor slices were stained with H&amp;E and also for antibodies against two microRNAs (29b and 199a) differentially expressed in ovarian cancer cell lines. Tumor-stroma proportions were assessed by two experienced pathologists blinded to chemoresistance status, with &lt;50% stroma scored as low proportion, &gt;50% scored as high proportion. Results: The average age of assessed patients with malignant tumors was 62. 87.5% had high-grade epithelial carcinomas. Baseline median CA-125 was 416 (range 32-2782). 80% of ovarian cancer patients with chemoresistance had tumor stroma proportions &gt;50%; 73.7% of cancer patients with chemosensitive tumors had proportions &lt;50% (p-value: 0.047). Expression of miR29b or 199a did not significantly correlate with chemoresistance. Conclusions: Tumor-stroma proportion is a useful predictive biomarker of platinum chemoresistance. If validated in larger datasets, it would be a relatively inexpensive and helpful tool for tailoring treatment strategies and clinical decision-making in women with ovarian cancer.
Electronic but overly eclectic: Disciplined EHR data management is needed to automate MIPS reporting.
Authors: Anna E. Schorer, Jacob Koskimaki, Robert S. Miller, Wendy S. Rubinstein, Elmer Victor Bernstam, John C. Krauss, Richard Moldwin, Neeta K. Venepalli, James Lin Chen
Journal: Journal of Clinical Oncology (2019)

e18074 Background: Physician reimbursement for care delivered to Medicare beneficiaries fundamentally changed with the 2015 MACRA legislation, requiring eligible clinicians to report quality measures in the Merit-Based Incentive Payment System (MIPS). To determine whether structured data in electronic health records (EHRs) were adequate to report MIPS results, EHR data ingested by ASCO’s CancerLinQ (CLQ) was analyzed. Methods: Nineteen MIPS measures specified for medical oncology, including 8 shared by other specialties, were retrieved from qpp.cms.gov and systematically evaluated to determine data elements necessary to satisfy each measure. The existence of corresponding data fields and completion of these fields with clinical data was analyzed according to EHR implementation in de-identified and aggregated CLQ data. Results: Five clinician informaticists reviewed the 19 oncology MIPS measures, and identified a consensus list of 52 discrete EHR data elements (DEs) that would be needed. CLQ-processed data from 4 commercial EHR systems implemented at 47 CLQ practices found structured data fields for 84% (43 of 52) of the DE, but fewer than half (46%) of these fields were ever populated and only 32% (17 of 52) of DE were recorded for &gt; 20% of cases. Only 3-5 of 19 MIPS measures could be reliably reported based on data element availability by most practices in this sample set. There were minimal differences between the EHRs ability to encode MIPS DE. Elements most likely to be encoded were those for registration (birthdate, gender), billing (diagnosis, meds), vital signs and smoking status, while those seldom or never encoded related to care plans (tobacco, alcohol, pain management). Other DE rarely encoded were patient events occurring outside the oncology practice (receipt/completion of consultations, dates of hospice enrollment and death), which would be dependent on data exchange between work units and practice entities or, more likely, re-entry by oncology practices. Conclusions: Only a minority of DE required to satisfy MIPS criteria are available as discrete data fields in current EHRs, limiting automated reporting efforts. Improved data quality and completeness is needed to satisfy mandated reporting.
Exo-circRNAs: a new paradigm for anticancer therapy
Authors: Hetian Bai, Kexin Lei, Fei Huang, Zhou Jiang, Xikun Zhou
Journal: Molecular Cancer (2019)

CircRNAs, as new members of long noncoding RNAs, have been the focus of recent investigation. CircRNAs feature a closed continuous loop structure without 5'-3' polarity or a poly A tail. Many studies have reported the potential application of circRNAs in the clinic as new biomarkers and therapeutic targets in different diseases, especially for cancer. Additionally, the exosomes are important vehicles in cell-to-cell communication. And exo-circRNAs are circRNAs in exosomes which can be detected to provide additional evidence for conventional diagnostic methods and can be applied to suppress the malignant progress in cancer. In this review, we describe the biogenesis, characteristics, and functions of circRNAs and exosomes. Specifically, we present a comprehensive update of the promising role of exo-circRNAs in anticancer therapy.
Reduced blood product utilization via implementation of an anemia clinic and consult service in a large health system hospital: Focus on cardiovascular patients.
Authors: Reid Christian Bowers, Sandra Tomany Korman, Michael A. Thompson, Manish Krishna Pant, Sherjeel Sana, Federico Augusto Sanchez
Journal: Journal of Clinical Oncology (2019)

e18014 Background: As part of a system wide implementation of Patient Blood Management (PBM), an Anemia Clinic program was implemented at St. Luke’s Medical Center, Advocate Aurora Health in Milwaukee, WI. Methods: September 2016 the Anemia Clinic started accepting referrals for management of non-cancer anemia, predominantly pre-operative cardiovascular surgery (CVS) Pts. Hgb thresholds were &lt; 13 g/dL in men and &lt; 12 g/dL in women. Non-anemia cytopenias triggered Hematology referral. All Pts were screened for iron, B12, folate, and reticulocyte. Nutrient deficiency received appropriate supplementation. Pts with CKD or chronic disease were eligible to receive erythropoiesis stimulating agents. Results: PBM implementation 2015-2018 resulted in a drop in packed red blood cell (PRBC) usage during a surgical episode (Table). Of 508 CVS Pts pre-operatively anemic in 2018, 155 were referred to the Anemia Clinic and 353 were not. There was not a statistical difference between the referred and the non-referred for percentage of Pts who received PRBCs (65.4% vs. 70.3% Chi-Square p = 0.31). Of preoperatively anemic Pts who were transfused in 2018 an average of 2.23 PRBCs were used in the referred group vs. an average of 2.35 PRBCs in those in the not referred group (Poisson Means p = 0.49). Length of stay (LOS) in the referred group was a median 10d ( P 25 = 7d, P 75 = 15d) vs LOS in the non-referred group was a median 11d ( P 25 = 7d, P 75 = 20d). LOS analyses of observed-to-expected (O/E) ratios used the Premier Healthcare Providers Alliance Database (PHD) which contains data on approximately 45% of US hospital discharges.. For 2018 through Nov. the referred group was observed to have LOS m geo = 10.19 days vs LOS m geo = 11.72 days (N = 141, O/E 0.87). The not referred group was observed to have a LOS m geo = 12.45 days vs. an LOS m geo = 10.65 days (N = 311, O/E 1.17). Conclusions: Referral to the Anemia Clinic as part of a broader program of PBM was associated with shorter LOS and a decrease in PRBC use. Implementation of PBM at our institution decreased PRBC use even in patients not referred to anemia clinic due to systematization of best practices. Implementation of our methods as the initial approach to general anemia referrals may increase access and efficiencies in the systemization and treatment of hematologic malignancies. [Table: see text]
Evaluation of long term survival in pretreated metastatic colorectal cancer patients undergoing GOLFIG chemoimmunotherapy regimen.
Authors: Pierpaolo Correale, Rocco Giannicola, NIcoletta Staropoli, Domenico Ciliberto, Domenico Azzarello, Giovanni Tripepi, Rita Maria Agostino, Alessandra Strangio, Maria Altomonte, Antonio Nesci, Guido Francini, Pierpaolo Pastina, Pierfrancesco Tassone, Luigi Pirtoli, Nadia Caporlingua, Antonia Consuelo Falzea, Pierosandro Tagliaferri
Journal: Journal of Clinical Oncology (2019)

e15057 Background: In the last few years, there has been a renewed interest on the potential use of immunotherapy alone or combined to chemotherapy (CHT) for mCRC patients. GOLFIG regimen (biweekly Gemcitabine+FOLFOX and IL2 and GM-CSF) was designed to enhance immunomodulating effects of selected cytotoxic drugs by combining them with cytokines able to promote priming and effector phases of the immune-response. This regimen has been tested in two different phase II and III clinical trials in mCRC patients, whose successful results have been published. Here we present the results a retrospective analyses including all the patients treated in a period of 16 years. Methods: This is a multi-institutional retrospective study including 179 mCRC patients (106 men, 73 women). They received a median of 12 courses of GOLFIG regimen (treated between June 2002 and November 2018). K-RAS mutational status has also been evaluated in 74 pts (41 wild type and 33 mutated); as for sidedness 112 pts had a left disease and 67 pts right disease; 71 pts received only one previous CHT line and 100 more than two lines. PFS and OS were evaluated by Kaplan-Meier curves and Cox-regression analyses in different subgroups (RAS mutational status, sidedness, previous CHT lines) to estimate their effect on survival endpoints. Results: We recorded a mean PFS and OS of 15,28 [95%CI:10,36-20,20] and 24,61 [95%CI:19,07-30,14] months, respectively, with no difference in efficacy outcomes observed among the different subgroups (one vs. more than one previous CHT lines; left vs. right primary side; k-ras status mutated vs. wt). Finally, we recorded a 2, 5 and 10 year OS-rate, in 42, 17 and 14 percent of the patients, respectively. The occurrence of self-limiting autoimmunity was confirmed as highly predictive of longer survival. Conclusions: These results confirm that GOLFIG regimen has strong efficacy in mCRC pts and may represent a reliable option in pretreated setting without evident effect of known prognostic variants. Such data offer a strong basis for future clinical trials in mCRC patients, where GOLFIG may represent a scaffold for combinatory immunotherapy approaches with immune-checkpoint blocking drugs.
Characterization of Lynch syndrome (LS) associated cancers in patients with immune dysfunction.
Authors: Shahla Bari, Xia Wang, Taiwo Ajose, Jameel Muzaffar
Journal: Journal of Clinical Oncology (2019)

1532 Background: LS is caused by a germline mutation in one of several DNA mismatch repair (MMR) genes: MLH1, MSH2, MSH6 or PMS2. Inappropriate immune responses as seen in chronic inflammatory conditions as well as immunodeficiency states confer increased risk of developing cancer. This aim of this study was to evaluate the effect of immune dysfunction on the characteristics of LS associated cancers. Methods: This was a retrospective analysis of LS patients and carriers at two institutions listed above. We evaluated mutational profiles, immune status, age of onset of first and subsequent cancers in this cohort. Results: 106 patients with mutations consistent with LS were included. 72 patients had at least one cancer while 34 were carriers. 44% patients were Caucasian female, 18% white males, 14% African American males, 11% African American females and 10% Hispanic females. Colon cancer (CRC) was the most common cancer (44%) and PMS2 was the most common mutation, noted in 35 patients (33%). Of the 72 patients with LS associated cancer, 18 patients were either immunosuppressed or had an autoimmune condition. Of the 10 patients who had an autoimmune condition ,7 had multiple cancers. Of the 9 patients who were immunosuppressed, 5 had multiple cancers. Out of a total of 18 out of 72 patients who had multiple cancers, 12 (66%) had either an autoimmune condition or were immunosuppressed. CRC was the index cancer in 42% and breast in 33% of patients with multiple cancers. Patients with MSH2 were most likely to have an immune related condition (32%) and accounted for 41% of patients with multiple cancers. The median age of first cancer in this group was 46 years while it was 48.5 years in the population without immune dysfunction (p = 0.2). There was a high prevalence of breast cancer (24%) as a LS associated cancer in our study population. 66% of the patients with PMS2 mutation had breast cancer with a median age of onset of 48 years (62 years for sporadic cancer). Conclusions: Our study is the first to look at the effect of immune dysfunction in LS patients. Immune dysfunction was associated with a higher rate of multiple cancers and was more commonly associated with the MSH2 mutation. It also highlights importance of aggressive screening for breast cancer in LS patients (especially with PMS2 mutation).
Progression free survival and time to local failure after radiosurgery of pleural metastases in twenty-two patients with thymomas.
Authors: Giulia Pasquini, Antonio Chella, Claudia Menichelli, Marco Lucchi, Maria Grazia Fabrini, Michelangelo Maestri, Roberta Ricciardi, Sabrina Cappelli, Iacopo Petrini, Anna de Rosa, Melania Guida, Maurizio Lucchesi
Journal: Journal of Clinical Oncology (2019)

8565 Background: Thymomas but not thymic carcinomas can benefit of cytoreductive surgery even if a complete resection is not achievable. Surgical resection of pleural metastases, the most common site of progression, can be performed in selected patients. We evaluated the outcome of stereotactic body radiation therapy (SBRT) for treatment of pleural metastases in patients’ not eligible for surgery. Methods: We retrospectively identified 22 patients treated with SBRT for pleural metastases between 2004 and 2019. According to RECIST criteria, time to local failure and progression free survival (PFS) were calculated using Kaplan-Meier estimation. Results: Twelve of the 22 patients were male. The median age was 40 years (range 29-73). There were 1 A, 3 AB, 3 B1, 3 B2, 3 B2/B3 and 9 B3 thymomas. The Masaoka stage at diagnosis was IIA in 2, IIB in 7, III in 5, IVA in 7 and IVB in 1 patient. Pleural metastases and primary tumor were synchronous in 8 patients. Thymectomy was performed in 21 patients. Seven patients received pre-operative chemotherapy and 12 post-operative radiotherapy. One patient received chemotherapy and radiotherapy after a macroscopically incomplete thymectomy. Five patients had a single pleural metastatic site and 17 presented multiple localizations. Sixteen patients received SBRT on multiple sites of pleural metastases. At the time of the analysis a patient received SBRT exclusively on one of 3 pleural metastases. The median dose of radiation was 30Gy (range 25-40) given in 3 fractions. Ten patients experienced a progression of treated lesions with a median time to local failure of 25.5 months (95%CI 20.9-30.1). The median PFS was 20.4 months (95%CI 10.7-30). There were not significant differences in PFS between patients diagnosed with synchronous and metachronous metastases (p=0.477), across those treated with chemotherapy or naive (p=0.189) and between those who received or not a previous surgical resection of the pleural metastases (p=0.871). Conclusions: SBRT of pleural metastases is feasible and offer an interesting local control of diseases. The impact of this treatment on patients’ survival is hardly predictable because of the heterogenous clinical behavior of thymomas.