tbuckley/cabot-search huggingface dataset:
Importance of androgen receptor (AR) to estrogen receptor ratio in breast cancer patients during endocrine therapy determined on circulating epithelial tumor cells (CETCs) in breast cancer patients.
Authors: Monika Pizon, Dorothea Schott, Daniel Lux, Ulrich Pachamnn, Katharina Pachmann
Journal: Journal of Clinical Oncology (2018)

e24031 Background: The androgen receptor (AR) is expressed in the majority of breast cancers and across the three main breast cancer subtypes. Despite the high frequency of AR expression in breast cancer its role is complex, dependent on the hormonal milieu, and remains controversial. On one hand AR seems to be a good prognostic marker in ER+tumors probably due to more differentiated state. On the other hand it is known that AR signaling and AR are involved in resistance to ER-directed endocrine therapies, in particular, the high AR:ER ratio. The aim of the current study was to investigate the frequency of AR and ER positive CETCs in breast cancer patients. Methods: The number of vital CETCs was determined from blood of 66 patients suffering from breast cancer and the expression of AR and ER on these cells were investigated using the maintrac method. Results: AR expressing CETCs were detected in 100% of breast cancer patients. Patients with advanced disease had statistically more CETCs as compared to patients in early stage of disease. The fraction of AR positive CETCs was significantly higher than the fraction of ER positive CETCs (90% vs. 50.0%; p < 0.001). Patients with lymph node metastasis had less AR positive CETCs as compared to patients with negative lymph node status. AR:ER ratio on CETCs was higher in patients during tamoxifen therapy compared to patients without endocrine therapy (2.2 vs 1.3, p < 0.05). Interestingly, treatment with aromatase inhibitor had no influence on AR:ER ratio. Conclusions: Breast cancer patients have detectable CETCs with a high frequency of AR regardless of stage of disease. AR to ER ratio may influence breast cancer response to endocrine therapy, especially with tamoxifen. It is crucial to identify biomarkers that would enable the selection of patients who might benefit from combination treatment with ER and AR inhibitors.
Some patients who achieved CR due to accelerator+brake therapy that was performed in the form of activated autologous lymphocytes with the concomitant use of low-dose immune checkpoint inhibitors.
Authors: Yoshinobu Abe, Yoshiyuki Aikawa
Journal: Journal of Clinical Oncology (2017)

e14561 Background: Otsuka et al. from Kyoto University reported in Oncoimmunology (October 24, 2016) that a group responding to Opdivo showed an increase in the number of “Type-9 helper T (Th9) cells”, which are a type of lymphocyte. On the basis of this clinical study, in September 2015, our clinic introduced immunotherapy that is performed in the form of activated autologous lymphocytes with the concomitant use of low-dose Opdivo and Yervoy. This therapy was named Accelerator+Brake therapy, and obtained a registered trademark in Japan. Methods: Accelerator+Brake therapy was performed for 359 patients between September 2015 and September 2016. These patients had lung cancer (n = 84), breast cancer (n = 45), colorectal cancer (n = 32), etc. The therapy was also performed for patients with sarcoma, which is a rare type of cancer. The patients underwent 5 courses of Accelerator+Brake therapy with 2-week intervals (overall treatment period: two and a half months), and the numbers of NK and T cells increased to approximately two billion through culture activation. In every course, Opdivo and Yervoy were administered at doses of 20 and 10-25 mg, respectively. Although not all patients have been followed up on a long-term basis, we encountered some patients who achieved CR after one or two courses. Results: I present 6 cases of CR. First case is 65 y.o. male, renal pelvis cancer has spread to his mediastinal lymph nodes. Second case is 57 y.o. male, intrahepatic cholangiocarcinoma has spread to his bilateral lungs. Third case is 64 y.o. female, breast cancer has spread to her lumbar vertebra. 4 th case is 53 y.o. male, renal cancer has spread to his lung. 5 th case is 55 y.o. female, breast cancer has spread to her lung. Last case is 39 y.o. male, renal cancer has spread to his pleural lesion. All 6 cases result in CR. I also present several cases of PR. Conclusions: Activated autologous lymphocytes with the concomitant use of low-dose Opdivo and Yervoy named Accelerator+Brake therapy is may become a breakthrough treatment to solid cancer.
Characteristics and outcomes of acute myeloid leukemia (AML) with extramedullary disease (EMD).
Authors: Fevzi Firat Yalniz, Jorge E. Cortes, Gautam Borthakur, Guillermo Garcia-Manero, Tapan M. Kadia, Marina Konopleva, Courtney Denton Dinardo, Naval Guastad Daver, William G. Wierda, Srdan Verstovsek, Naveen Pemmaraju, Zeev Estrov, Farhad Ravandi, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2018)

7039 Background: EMD has been reported in 2.5-30% of AML patients (pts). The association with modern cytogenetic and molecular features and their prognostic value have not been fully explored. Methods: We reviewed medical records of all AML pts treated at MDACC from 8/12 to 1/2018. Results: Among 2388 pts, 88 (4%) had EMD; 30 were newly diagnosed. The sites involved were skin (n = 14), central nervous system (CNS) (n = 6), musculoskeletal (n = 4), nodal (n = 4) and intestinal (n = 2). 27/30 (90%) had concomitant marrow disease. Most relevant characteristics are in Table. Cytogenetics (CG) were not different between EMD and non-EMD pts (p = 0.1). Compared to non-EMD pts, pts with EMD had more KIT mutations (p = 0.003) but not FLT3-ITD, NPM1, RAS or IDH. The median overall survival (mOS) was shorter (6.1 vs 18.4 months; p = 0.004) in pts with EMD. On univariate analysis, the presence of any EMD (p = 0.02), skin involvement (p = 0.04) but not CNS (p = 0.9) was associated with shorter OS. There was no OS difference between KIT-mutated and wild-type EMD pts (p = 0.5). Of the 58 relapsed EMD (28 in 1st relapse and 30 in ≥2nd relapse), 13 had isolated EMD, 45 had concurrent marrow disease and 18 had prior SCT. The common sites involved were CNS (n = 32; 23 had isolated and 9 had ≥ 2 sites), skin (n = 11) and musculoskeletal (n = 6). Compared to non-EMD pts, there was no difference in CG and molecular characteristics. On univariate analysis, the mOS was not significantly different in pts with relapsed EMD compared to non-EMD pts (5.8 vs 5.9 months; p = 0.3), whether in first relapse (p = 0.3) or ≥2nd relapse (p = 0.5). Conclusions: AML with EMD carries a poor prognosis. The role of genetic and molecular markers warrants further investigation especially for treatment planning and clinical follow-up post remission. Non-EMD n = 2300 EMD at relapse n = 58 EMD upon AML diagnosis n = 30 p Age 64 (17-95) 56 (20-78) 59 (23-81) 0.08 Male 1322 (57) 31 (53) 24 (80) 0.04 WBC x 109/L 4.1 (0.1-479) 5.8 (0.6-142) 12 (1.8-186) < 0.001 IDH1 340 (16) 5 (12) 2 (8) 0.2 IDH2 300 (14) 5 (12) 4 (15) 0.5 RAS 254 (12) 6 (12) 6 (21) 0.1 KIT 339 (16) 7 (17) 10 (37) 0.01 FLT3ITD 542 (25) 9 (17) 5 (17) 0.3 NPM1 317 (15) 10 (20) 5 (18) 0.7 CG 0.1 Favorable 107 (5) 3 (5) 4 (14) Intermediate 1226 (63) 38 (69) 19 (65) Adverse 620 (32) 14 (26) 6 (21)
Outcome of mismatch repair deficient metastatic colorectal cancer (CRC): The Mayo Clinic Experience.
Authors: Zhaohui Jin, Cristobal T. Sanhueza, Benny Johnson, Thomas C. Smyrk, David W. Larson, David M. Nagorney, Joleen Marie Hubbard, Axel Grothey
Journal: Journal of Clinical Oncology (2017)

e15030 Background: Deficiencies in the DNA mismatch repair (dMMR) system cause errors during DNA replication, which in turn give rise to microsatellite instability (MSI-H). MSI-H in mCRC is rare and its prognostic and predictive impact on outcome is unclear. This cohort study aims to investigate the prognostic and predictive value of MSI-H in metastatic CRC prior to the immune therapy era. Methods: 75 MSI-H mCRC patients (pts) and 75 matched (age, gender, disease sidedness, metachronous) MSS mCRC pts were identified from 1268 mCRC who had MSI/MMR test results at Mayo Clinic Rochester between 1/1992 and 7/2016. A retrospective review was conducted by using data from electronic medical records (EMR). Statistical analyses utilized Kaplan-Meier method, Log-rank test, and Cox proportional hazards models. Results: In the MSI-H group, there were 39 male (52%) and 36 female (48%) pts. Median age at metastatic disease diagnosis was 54.7 years. 35 patients presented with stage IV CRC. Primary tumors location: 38 right side, 11 transverse colon, 15 left side, 11 rectum. The MSS group was well matched (3 mismatches for gender and 1 mismatch for metachronous metastatic disease). Median overall survivals (OS) were 28.1 and 37.4 months for MSI-H and MSS pts, respectively ( p= 0.098). 98.7% MSS pts and 94.7% MSI-H pts had Fluoropyrimidine-based chemotherapy for metastatic disease and there was no median OS difference between these two groups (37.4 vs. 32.3 months p= 0.91). 43 MSI-H and 39 MSS pts had metastasectomy including ablation ( p= 0.51) with longer median OS (82.0 and 69.9 months, p= 0.90) compared to pts without metastasectomy (13.9 and 19.7 months, p= 0.15). Age &lt; 65, metastasectomy, asymptomatic metastatic lesions, BRAF wild type, and multiple metastasectomy were associated with better survival in univariate analysis. Only metastasectomy remained statistically significant in multivariate analysis ( p&lt; 0.0001). Conclusions: MSI-H mCRC do not appear to have improved prognosis compared with MSS cancers, in fact, there is a trend toward inferior outcome. In both groups, metastasectomy including multiple metastasectomy should be considered to optimize OS.
Decision dissonance/alignment scale to promote patient-centered decisions about urinary diversion with cystectomy for bladder cancer.
Authors: Scott Michael Gilbert, Michael C Leo, Christopher Wendel, Robert S. Krouse, Marcia Grant, Kim N. Danforth, Marilyn L. Kwan, Teresa Harrison, Joanna E Bulkley, Carmit K. McMullen
Journal: Journal of Clinical Oncology (2017)

e16010 Background: The choice of urinary diversion (UD) with cystectomy is an opportunity to provide preference-driven care. We adapted a decision dissonance scale to measure concordance of patient goals with choice of ileal conduit (IC) vs. neobladder (NB) UD. Methods: With patient and clinician input, we identified 6 IC- and 4 NB-aligned goals, each rated on an 11-point scale (0 = not at all important to 10 = very important). Kaiser Permanente members rated the importance of these goals in a comprehensive survey mailed 6 months post-op (71% response rate (269/381)). Excluding respondents (n=93) with contraindications to NB and missing data on goals, we examined structural validity with principal axis factor analysis and convergent validity using correlations with other decision-making measures. Results: Items aligned to IC vs. NB factored separately as hypothesized (Table 1). NB patients prioritized (p&lt;.05) NB-aligned goals (M=8.8, SD=1.8) over NB-dissonant goals (M=4.3, SD=2.4). IC patients’ alignment (M=5.4, SD=2.7) and dissonance (M=5.6, SD=2.1) ratings were similar. Dissonance was negatively correlated with informed decision-making (r=-.27) and satisfaction with care (r=-.21), and positively correlated with decision regret (r=.28) (each p&lt;.01), but not correlated with shared decision making or decision style preference. Alignment was not significantly correlated with decision-making measures. Conclusions: Our measure distinguished patient values that could guide shared decision-making about UD choice. Patients who chose a NB had strong preferences for maintaining body integrity and function. [Table: see text]
Calcium channel blockers use and overall survival in pancreatic cancer patients receiving gemcitabine.
Authors: Leszek Kraj, Andrzej Śliwczyński, Joanna Krawczyk-Lipiec, Krzysztof Woźniak, Anna Waszczuk-Gajda, Sebastian Rybski, Lucjan Wyrwicz
Journal: Journal of Clinical Oncology (2017)

e15756 Background: Preclinical studies have shown that calcium channel blockers (CCB) may potentiate anticancer effect of chemotherapy via intra-cellular drug accumulation. Gemcitabine-based chemotherapy is commonly used in pancreatic cancer (PC) patients. The aim of this study was to determine whether CCB may affect overall survival (OS) in PC patients receiving gemcitabine-based chemotherapy. Methods: The retrospective cohort of PC patients treated with gemcitabine between 2007 and 2016 was identified in the Polish National Health Fund databases. Electronic records of prescriptions were searched to identify in this cohort patients receiving CCB (amlodipine, nitrendipine, felodipine, lacidipine). The primary endpoint was OS and it was determined by Kaplan-Meier methods and compared by the log-rank test. Results: In total 4628 PC patients treated with gemcitabine (median OS 7.7 months; 95% CI: 7.4-7.9) were identified. Among these 380 patients were prescribed any CCB. There was a significant difference (p &lt; 0.001) in median OS between patients prescribed CCB (n = 380; OS 9.3 months; 95% CI: 7.8-11.0) and those who did not (n = 4214; OS 7.6 months; 95% CI: 7.3-7.8) with hazard ratio for death 0.70 (95% CI: 0.62-0.79). Notably, the survival curves tended to flatten in CCB group, with 24% of patients alive at 2 years (95% CI: 20-29%) and 15% alive at 5 years (95% CI: 11-19%), compared with 11% (95% CI: 10-12%) and 4% (95% CI: 4-5%) in controls respectively. Conclusions: The use of CCB in PC patients receiving gemcitabine-based chemotherapy was associated with improved OS. Further validation is needed to evaluate effectiveness of CCB-gemcitabine combinations in the management of PC.
Feasibility of Implementing the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events in a Multicenter Trial: NCCTG N1048
Authors: Ethan Basch, Amylou C. Dueck, Lauren J. Rogak, Sandra A. Mitchell, Lori M. Minasian, Andrea M. Denicoff, Jennifer K. Wind, Mary C. Shaw, Narre Heon, Qian Shi, Brenda Ginos, Garth D. Nelson, Jeffrey P. Meyers, George J. Chang, Harvey J. Mamon, Martin R. Weiser, Tatjana Kolevska, Bryce B. Reeve, Deborah Watkins Bruner, Deborah Schrag
Journal: Journal of Clinical Oncology (2018)

Purpose The US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed to enable patient reporting of symptomatic adverse events in oncology clinical research. This study was designed to assess the feasibility and resource requirements associated with implementing PRO-CTCAE in a multicenter trial. Methods Patients with locally advanced rectal cancer enrolled in the National Cancer Institute–sponsored North Central Cancer Treatment Group (Alliance) Preoperative Radiation or Selective Preoperative Radiation and Evaluation before Chemotherapy and Total Mesorectal Excision trial were asked to self-report 30 PRO-CTCAE items weekly from home during preoperative therapy, and every 6 months after surgery, via either the Web or an automated telephone system. If participants did not self-report within 3 days, a central coordinator called them to complete the items. Compliance was defined as the proportion of participants who completed PRO-CTCAE assessments at expected time points. Results The prespecified PRO-CTCAE analysis was conducted after the 500th patient completed the 6-month follow-up (median age, 56 years; 33% female; 12% nonwhite; 43% high school education or less; 5% Spanish speaking), across 165 sites. PRO-CTCAE was reported by participants at 4,491 of 4,882 expected preoperative time points (92.0% compliance), of which 3,771 (77.2%) were self-reported by participants and 720 (14.7%) were collected via central coordinator backup. Compliance at 6-month post-treatment follow-up was 333 of 468 (71.2%), with 122 (26.1%) via backup. Site research associates spent a median of 15 minutes on PRO-CTCAE work for each patient visit. Work by a central coordinator required a 50% time commitment. Conclusion Home-based reporting of PRO-CTCAE in a multicenter trial is feasible, with high patient compliance and low site administrative requirements. PRO-CTCAE data capture is improved through centralized backup calls.
Examining patients’ medical and psychosocial experiences following detection of a <i>CDH1</i> variant with multiplex genetic testing.
Authors: Jada Hamilton, Jessica M. Long, Amanda C. Brandt, Jamie Brower, Heather Symecko, Erin E. Salo-Mullen, Stephanie Christian, Fergus Couch, Judy Ellen Garber, Kenneth Offit, Mark E. Robson, Susan M. Domchek
Journal: Journal of Clinical Oncology (2018)

1583 Background: Germline CDH1 mutations are associated with hereditary diffuse gastric cancer and lobular breast cancer. We conducted a cross-sectional, self-report survey to understand genetic testing experiences, medical management, and psychosocial adaptation among patients with a CDH1 variant. Methods: We recruited participants from the Prospective Registry of Multiplex Testing (PROMPT), an online genetic registry. We invited individuals with a CDH1 variant to complete a survey of validated and investigator-designed items. We computed descriptive statistics, and used t tests and chi-square tests to compare responses of individuals with pathogenic variants (PV) or variants of uncertain significance (VUS). Results: Data were available from 55 individuals (96% female, 89% white, 75% college graduate, age 32-78) with a CDH1 PV (n = 16; 3 with a family history of gastric cancer) or VUS (n = 39; 12 with a family history of gastric cancer). Overall, 82% had received genetic counseling, 73% felt sufficiently informed when they had genetic testing, and participants reported low decisional regret about testing (M±SD= 12.6±20.1 on 0-100 scale); no differences were observed based on CDH1 variant type. Those with VUS were less satisfied with healthcare providers’ knowledge about their CDH1 result than were those with PV (p= .02). Those with PV were more likely than those with VUS to have received a recommendation for prophylactic gastrectomy (44% vs 0%, p< .001). Only 2 participants, both with PV, had a prophylactic gastrectomy. Those with VUS had less knowledge about CDH1 than those with PV (63% vs 93% correct knowledge; p <.001); yet, participants had similar perceptions of cancer risks (ps > .05). Those with PV reported greater testing-related distress (p <.001) and worry about genetic discrimination (p= .05); there were no differences between groups on other emotional outcomes including testing-related uncertainty, positive experiences, or quality of life (ps > .05). Conclusions: Many patients reported being well informed and satisfied with their CDH1 genetic testing decision; yet, patients with VUS and PV each have unique informational and emotional needs warranting additional support.
Novel mechanism of platinum resistance: Rapid selection of pre-existing BRCA1-proficient tumor cells during neoadjuvant chemotherapy (NACT) for ovarian cancer (OC) in BRCA1 germ-line mutation carriers
Authors: E. Imyanitov, E. Savonevich, A. Ivantsov, T. Gorodnova, E. Preobrazhenskaya, M. Kleshchov, E.S. Kuligina, A. Sokolenko
Journal: Annals of Oncology (2018)

Background: Cancers arising in BRCA1 mutation carriers are highly sensitive to cisplatin due to somatic inactivation of the wild-type BRCA1 allele. Accordingly, BRCA1-driven OCs usually respond well to NACT and therefore almost always undergo complete cytoreduction. However, despite this seemingly effective treatment and continuation of platinum therapy in the adjuvant setting, almost all BRCA1-associated OCs inevitably relapse. Methods: We compared BRCA1 LOH status in paired OC samples before and after NACT. Results: BRCA1 LOH was detected in 19/28 chemonaive OCs. Surprisingly, heterozygous status was restored in 13/19 (68%) samples after median of 3 cycles of NACT. The analysis of linked SNPs demonstrated that the restoration of BRCA1 proficiency is not due to the second mutation in the BRCA1 gene, but due to selection of pre-existing BRCA1-proficient cells. Furthermore, the persistence of isolated BRCA1-heterozygous cells in the chemonaïve OCs was confirmed by FISH analysis. Absence of BRCA1 LOH in post-NACT samples could not be explained by errors in tumor microdissection, as residual cancer tissues still retained TP53 mutation. Relapsed OC tissues were analyzed in 4 patients, who experienced the restoration of BRCA1 heterozygosity during NACT; the return to the BRCA1-deficient state during platinum-free interval was observed in 3 of these cases. Conclusions: 1) Loss of the remaining BRCA1 allele is not the first molecular event in the pathogenesis of BRCA1-associated cancers: it is likely to occur only after TP53 gene inactivation. 2) BRCA1-driven chemonaive cancers still contain a fraction of BRCA1-proficient cells even if they demonstrate LOH in a gross tumor mass. Therefore, drugs targeting BRCA1 deficiency are unlikely to be curative if applied alone. 3) The ratio between BRCA1-deficient and -proficient cells undergoes rapid changes during platinum therapy and platinum-free intervals. 4) Continuation of platinum therapy in the adjuvant setting for the tumors with restored BRCA1 status does not have a biologic rationale. 5) Intratumoral interactions between BRCA1-deficient and -proficient cells deserve further investigation. Legal entity responsible for the study: N.N. Petrov Institute of Oncology. Funding: Russian Science Foundation (grant number 14-25-00111). Disclosure: All authors have declared no conflicts of interest.