tbuckley/cabot-search huggingface dataset:
Initial breast cancer consult: Improving satisfaction and impact on distress.
Authors: Veronica B. Decker, Olga Ivanov
Journal: Journal of Clinical Oncology (2019)

e18284 Background: Goals of this performance improvement project were to: (1) determine the impact of initial breast cancer consultation on distress and number of reported problems as measured by the NCCN Distress Thermometer and Problem List (DT and PL) questionnaire and to: (2) explore the relationship between pre-consult DT and PL scores and patients’ satisfaction with information received during the consult as measured by the EORTC QLQ-INFO25. Methods: (1) Immediately prior to, and after, initial consult with the breast cancer surgeon, 59 convenience-sampled women completed NCCN DT and PL questionnaires. (2) They then completed an EORTC QLQ-INFO25 questionnaire designed to measure information satisfaction. Participants were placed in quartile groups based on DT score and, likewise, grouped based on number of reported problems on the PL. Quartile groups were then analyzed to determine scale satisfaction with the information provided. Results: (1) Both DT and PL pre-post changes were significantly positive (DT: M = 5.4, SD = 3.0 versus M = 3.6, SD = 2.8; t-test p&lt; .000); (PL: M = 5.3, SD = 4.4 versus M = 3.7, SD = 4.3; t-test p&lt; .000). Except for the INFO25 RECLESS scale (less information desired), lower scores are better. (2a.) Generally, high distress and problems reported (i.e., scores increase), guarantees lower information satisfaction. (2b.) With one exception, the quartile range for each scale was consistently small. (2c.) Score trajectories for both DT and PL quartiles over the scales were similar. Conclusions: Although data suggests current consultation processes are significantly effective, there is room for satisfaction improvement. (2a.) Providers who continue to give the DT and PL prior to a consult, must ensure information satisfaction to pre-consult DT and PL high scorers. (2b.) Similar quartile scores for each scale suggests that individually tailoring the consultation based on pre-consult DT or PL scores alone (without satisfaction improvement efforts) may have minimal benefits. (2c.) Consult satisfaction improvement efforts should focus on the following scales: INFOCD (information on CD/tape/video); RECMORE (more information wanted); INFOTHSE (other services); INFOHELP (things you can do to help yourself get well); INFODIFP (different places of care); INFOTREAT (treatments), and; INFODIS (the disease).
Can serum IL-6 levels predict sarcopenia and poor outcome in relapsed/refractory gynecologic cancer patients?
Authors: Tomoyuki Yoshikawa, Masashi Takano, Kazuya Kudoh, Morikazu Miyamoto, Tadashi Aoyama, Hiroko Matsuura, Hiroki Ishibashi, Hideki Iwahashi, Souichirou Kakimoto, Takayoshi Asakawa, Hiroko Kouta, Sayaka Ikeda, Tsunekazu Kita, Yoshihiro Kikuchi
Journal: Journal of Clinical Oncology (2019)

2592 Background: Cancer cachexia occurs in more than half of cancer patients and can be the primary cause of death for at least 20% of all patients. Cancer cachexia also lowers quality of life in cancer survivors due to a severe loss of skeletal muscle mass. Although a multitude of cytokines have been implicated in facilitating a cachectic state, the correlation of serum IL-6 and cancer-induced muscle wasting in gynecologic cancer patients has not been elucidated. Methods: The correlation between serum level of IL-6 and skeletal muscle volume in the patients with gynecologic cancers that received multiple lines of therapy was retrospectively evaluated. We used the psoas muscle index [PMI (cm2/m2)], the psoas major muscle area at the fifth lumber level divided by the height squared, measured using digital axial CT images, for the value of skeletal muscle volume. The level of IL-6 cut-off for elevation was defined as more than 12.0 pg/mL. The comparison of the survival distributions from the day of IL-6 measuaments was made using a log-rank test. Results: A total of 74 cases were assessed for the serum IL-6 and PMI: 32 cases with Mullerian cancers, 24 cases with endometrial cancers, 13 cases with cervical cancers, and 5 patients with others. The group with elevated IL-6 were associated with the lower PMI (t-test, p = 0.0154). The patients with IL-6 elevation had significantly worse survival compared with those with normal IL-6 (1y-OS; 31% vs. 80%, p &lt; 0.0001). In 28 patients with more than two-point measurements of IL-6, the patients with the decrease to the level of IL-6 cut-off had favorable survival compared with those without the decrease (6m-OS; 100% vs. 52%, p = 0.0069). Conclusions: Serum level of IL-6 could be a sentinel biomarker for cancer-induced sarcopenia in the patients with gynecologic cancers. Additionally, IL-6 could be a biomarker to determine further continuation of aggressive chemotherapy for the patients that had received multiple lines of chemotherapy.
Mutation landscape of Chinese melanoma patients.
Authors: Fuxue Huang, Dandan Li, Xizhi Wen, Fang Wang, Xiaoshi Zhang, Xuan Lin, Shuyin Chen, Hao Liu, Han Han-Zhang, Jing Liu
Journal: Journal of Clinical Oncology (2019)

9563 Background: Treatment options for melanoma, which has the highest mutation burden among common cancers, has proliferated in the past decade. Genomic profiling has becoming essential to clinical decision making. However, limited studies have interrogated the genomic landscape of Chinese melanoma patients. We also investigated the correlation between tumor mutation burden (TMB) and clinical outcomes of immunotherapy (IO). Methods: In this study, we retrospectively surveyed the genomic profiling of primary tumors of 81 (40 males, 41 females) metastatic Chinese melanoma patients with a median age of 52, using a panel consisting of 295 cancer-related genes, spanning 2.02MB of human genome. Patients used IO as first line treatment (n = 25) were enrolled for survival analyses. Results: In this cohort, 15, 24 and 42 were acral, mucosal and cutaneous melanoma, respectively. Collectively, we identified 1,114 mutations, spanning 248 genes, with BRAF, MYC and NBN being the most frequently mutated genes, occurring in 40%, 27% and 21% of patients, respectively. Mutation spectrum varied significantly by subtypes. BRAF (57%) and LRP1B (26%) were the most frequently mutated genes in cutaneous melanoma (CM). KIT and NRAS, reported to be frequently mutated in CM, each occurred in only 12% patients in this cohort. MYC amplification was the most commonly seen mutation in acral and mucosal melanoma (MM). Other frequent mutations in MM included: NBN (38%) RUNX1T1(29%) and TP53 (29%). In acral melanoma (AM), CCND1, FGF3/19, NF1and NBN were frequently mutated. It is interesting to note that no TP53 mutation was observed in AM. AM and MM had significantly more CNVs than CM. Of the 25 patients underwent IO, our data revealed a positive correlation between TMB and PFS (p = 0.007). Such correlation also exited in each subtype. Furthermore, we derived a cutoff of 15, which can effectively distinguish clinical response. Patients with TMB &gt; 15 mut/Mb had a significantly longer PFS than patients harboring TMB &lt; 15 mut/Mb (P = 0.02). Patients with CM had a longer PFS than patients with AM or MM (p = 0.018). No correlation between PDL1 expression and PFS was observed. Conclusions: Our study revealed a distinctive mutation landscape for each subtype. Furthermore, we also revealed a positive correlation between TMB and PFS as well as a lack of correlation between PDL1 expression and PFS.
Potent targeting of B cell lymphoma and plasma cell tumors by a tetravalent, Fc-engineered antibody directed against the glycoantigen CD75s.
Authors: Katja Klausz, Amir Karimzadeh-Tabrizi, Malena Buck, Anna Otte, Steffen Krohn, Christian Kellner, Wolfram Klapper, Matthias Peipp, Martin Gramatzki
Journal: Journal of Clinical Oncology (2019)

e14004 Background: Monoclonal antibodies are established treatment options for B cell-derived malignancies, but relapse is still the major challenge. Novel target structures may open alternative avenues to develop effective antibody therapies. Here, we characterized the novel tetravalent antibody ‘EBU-141 Tetra’ and identified the glycoantigen CD75s (α-2,6-sialylated lactosamines) as suitable target structure for antibody-based therapy. CD75s was detected on most B cell lymphomas, including Burkitt’s lymphoma, FL, DLBCL, MCL, CLL, and plasma cell tumors. Classical Hodgkin lymphomas were consistently negative while reactivity on individual cases of peripheral T cell lymphoma was seen. To evaluate CD75s as a target for antibody therapy, we generated a tetravalent, Fc-engineered chEBU-141 IgG1 antibody with enhanced avidity for CD75s and potent effector functions. Methods: ‘EBU-141 Tetra’ was produced by transient transfection and purified by affinity chromatography. Direct anti-tumor effects and Fc-mediated effector functions were investigated in cell proliferation assays, by fluorescence microscopy and in 51 Cr release experiments using lymphoma and myeloma cell lines and patient-derived tumor cells. Peripheral blood mononuclear cells and monocyte-derived macrophages of healthy donors were used as human effector cells in the experiments. Results: ‘EBU-141 Tetra’ showed improved binding to CD75s on cell surface of mature B cell lymphoma as well as myeloma plasma cells compared to the conventional chimeric antibody chEBU-141 IgG1. The higher avidity for CD75s resulted in markedly improved ADCC activity of ‘EBU-141 Tetra’ against Daudi Burkitt’s lymphoma, U266 plasma cells and CLL patient-derived tumor cells with EC 50 values in the low nanomolar range. In addition, ‘EBU-141 Tetra’ demonstrated efficient phagocytosis of Burkitt’s lymphoma and myeloma cell lines. Thus, the novel tetravalent, chimeric, Fc-engineered antibody ‘EBU-141 Tetra’ efficiently recruits immune effector cells for tumor cell lysis. Conclusions: Our findings further demonstrate that highly potent IgG-like antibodies against glycan-structures can be generated from mouse IgM antibodies and may open a new therapeutic window for therapy of patients with mature B cell lymphomas and multiple myeloma.
Phase II multicenter study of antroquinonol in patients with stage IV non-small cell lung cancer who have failed at least two lines of anti-cancer therapy.
Authors: Ching-Liang Ho, David S. Ettinger, Pei-Ni Chen, Howard Cheng, Wu-Che Wen, Shang-Yin Wu, Thierry Marie Jahan, Mary J. Fidler, Bradley Walter Lash, Igor I. Rybkin, Natalie Stanton
Journal: Journal of Clinical Oncology (2019)

e20522 Background: The aim of this study was to assess the efficacy of Antroquinonol in patients with stage IV NSCLC after failure in two-lines of anti-cancer therapy. Methods: Patients with stage IV non-squamous NSCLC who have failed at 2-4 lines of anti-cancer therapy were eligible, though early stage or naïve patients may voluntarily participate. A maximum of 30 evaluable patients were to receive Antroquinonol 600mg per day, of which 15 patients were to be KRAS-positive and 15 patients KRAS negative. The primary endpoint of the study was progression-free survival from the start of treatment to week 12 with disease control rate and overall survival as key secondary endpoints. Results: There were 31 patients enrolled with evaluable population 30 patients, of which 15 patients were KRAS positive and 15 patients KRAS negative. 73% were with at least two prior chemotherapy. The median PFS of 7 patients with 2 prior chemotherapy was 22.9 weeks (95% confidence interval [CI]: 5.0, 31.1); and 11 patients with more than 2 prior chemotherapy was 11.9 weeks (95% confidence interval [CI]: 6.0, 14.1), with a 1-year PFS of 11.4%. Of 11 patients who had had more than 2 prior chemotherapy, the median OS was 47.3 weeks (95% CI: 14.1,-), with a 1-year OS of 39.3%, and the overall disease control rate was 72.7%, with 100% in KRAS negative and 50% in KRAS positive. No systemic toxicities were observed. Conclusions: The monotherapy of Antroquinonol brought up higher disease control rates and longer progression-free survival and overall survival, compared with historical data. Although KRAS negative shows much better than KRAS positive group, Antroquinonol still work well with KRAS positive patients. Clinical trial information: NCT02047344.
Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review
Authors: Barbora Peltanova, Martina Raudenska, Michal Masarik
Journal: Molecular Cancer (2019)

The tumor microenvironment (TME) is comprised of many different cell populations, such as cancer-associated fibroblasts and various infiltrating immune cells, and non-cell components of extracellular matrix. These crucial parts of the surrounding stroma can function as both positive and negative regulators of all hallmarks of cancer development, including evasion of apoptosis, induction of angiogenesis, deregulation of the energy metabolism, resistance to the immune detection and destruction, and activation of invasion and metastasis. This review represents a summary of recent studies focusing on describing these effects of microenvironment on initiation and progression of the head and neck squamous cell carcinoma, focusing on oral squamous cell carcinoma, since it is becoming clear that an investigation of differences in stromal composition of the head and neck squamous cell carcinoma microenvironment and their impact on cancer development and progression may help better understand the mechanisms behind different responses to therapy and help define possible targets for clinical intervention.
Acquired resistance to MET inhibition in MET driven NSCLC.
Authors: Richard Riedel, Carina Heydt, Andreas H. Scheel, Hannah Lea Tumbrink, Johannes Brägelmann, Roberta Castiglione, Lucia Nogova, Diana S.Y. Abdulla, Sebastian Yves Friedrich Michels, Matthias Scheffler, Rieke Nila Fischer, Sophia Koleczko, Sabine Merkelbach-Bruse, Martin Sos, Reinhard Büttner, Juergen Wolf
Journal: Journal of Clinical Oncology (2019)

9030 Background: MET mutations ( MET∆ ex14 ), amplifications or translocations can activate oncogenic signaling in lung cancer and are sensitive to MET inhibition. Acquired resistance to therapy with MET tyrosine kinase inhibitors (TKI) occurs inevitably. Methods: Between 2015 and 2018, eighteen patients with MET-driven NSCLC were treated with capmatinib or crizotinib as single agent at our site. Rebiopsy samples from five patients were analyzed by NGS and fluoreszenz-in-situ hybridization (FISH) at time of progression. Results: Of the five patients with rebiopsy samples at time of progression, two had initially a MET amplification (one patient with low-level and one patient with high-level amplification), two patients had a MET∆ ex14 and one patient had a KIF5B-MET fusion. Patient 1 (low-level MET amplification) showed a partial response to crizotinib. The rebiopsy revealed an acquired KRAS mutation as a potential mechanism of resistance. Patient 2 (high-level MET amplification) showed stable disease as best response to capmatinib and patient 3 (MET∆ ex14 ) showed a partial response to capmatinib. Both patients developed acquired HER2 amplifications. Patient 4 ( MET∆ ex14 ) showed initially a partial response to crizotinib. The rebiopsy sample revealed an acquired MET kinase domain mutation (p.D1246N). As preclinical findings suggested that D1246N confers resistance to type I MET inhibitors but remains sensitive to type II inhibitors, cabozantinib was started. A CT six weeks after therapy initiation showed progressive disease. Patient 5 ( KIF5B-MET) had a partial response to crizotinib. An acquired MET p.Y1248H mutation was found at time of progression. Therapy was changed to cabozantinib. A new CT scan is pending. Conclusions: Resistance to MET inhibition is heterogeneous with on- and off-target-mechanisms occurring. We found HER2 amplification as a potential new bypass mechanism. The MET mutation D1246N conferred resistance to type I and type II inhibitors. We describe the first case of an acquired mutation of the MET tyrosine kinase domain in a patient with an oncogenic MET fusion. Further investigations are needed to collect comprehensive data to understand resistance mechanisms in MET inhibition and to develop novel therapeutic strategies.
Prediction of occult axillary metastases in treatment-naïve patients with breast cancer: A transSENTINA analysis.
Authors: Cornelia Kolberg-Liedtke, Hans-Christian Kolberg, Ingo Bauerfeind, Tanja N. Fehm, Barbara Fleige, Annette Lebeau, Lukas Schwentner, Annette Staebler, Sibylle Loibl, Michael Untch, Thorsten Kühn
Journal: Journal of Clinical Oncology (2019)

566 Background: Prediction of occult axillary metastases through clinical / biological parameters may allow reduction of axillary staging. This is particularly important, as systemic therapies have become more efficient. We have conducted a systematic analysis among patients undergoing axillary sentinel lymph-node biopsy (SLNB) before initiation of primary systemic therapy as part of a clinical trial (SENTINA) with the goal to identify predictors of sentinel lymph node status in a well-defined patient cohort. Methods: Patients with a clinically negative axillary status who underwent SLNB as part of the prospective SENTINA trial were included. Univariate and multivariate analyses were carried out to identify clinical / pathological parameters associated with SLN status, using logistic regression models. Model performance was assessed by ROC analyses. Calculations were performed using R version 3.5.2. Results: Arms A and B of the SENTINA study contained 1022 patients. Among 805 cN0 patients, all parameters considered relevant for this analysis were available. 527 and 278 patients presented with negative and positive lymph nodes upon SLN biopsy, respectively. Univariate regression models identified largest tumor diameter (odds ratio (OR) 1.016, p-value 0.0041), tumor type (ductal vs. lobular, OR 2.004, p 0.00234), tumor grading (low vs. high, OR 0.537, p &lt; 0.001), hormone receptor (HR) status (negative vs. positive, OR 2.668, p &lt; 0.001), HER2 status (negative vs. positive, OR 1.462, p 0.0158) as being associated with SLN status with an a &lt; 0.1. Multivariate analysis resulted in tumor diameter, HR status, HER2 status and tumor type being independently associated. These parameters were combined using stepwise (backward and forward) selection into a prediction model. This model predicted SLN status with an AUC of only 0.65. Conclusions: Using data obtained as part of the SENTINA trial we were able to build a prediction model that was able to predict SLN metastases in treatment naïve cN0 patients with limited accuracy. Additional (biological) parameters, such as response to systemic therapies (i.e. axillary conversion through PST) may be more appropriate to predict presence of occult sentinel lymph node metastases among patients with breast cancer.
Bisphosphonate use in geriatric breast cancer patients on aromatase inhibitors in a rural population.
Authors: Alexander Johnson, Christian Agbisit, Kathy Robinson, Kristin Delfino, Meghna R. Desai
Journal: Journal of Clinical Oncology (2019)

e12048 Background: Aromatase inhibitors (AIs) are commonly used in treatment of ER &amp; PR + breast cancer in postmenopausal women. It is well known that AIs can lead to bone loss. Bisphosphonates have been used to counteract bone loss due to AI use. The objective of this study was to evaluate the use of bisphosphonates in elderly females above 65 years, with ER + breast cancer on AIs, in a rural setting, and to examine the effects of oral vs. IV bisphosphonates on overall survival (OS) in geriatric patients. We also examined the effects of alcohol use on bone health in this population. Methods: An institutional database of 269 patients with histologically confirmed invasive or in-situ breast cancer with age 65 or older at the time of diagnosis was reviewed in an IRB approved fashion. 176 patients were ER+ and had DEXA diagnosed osteoporosis or osteopenia.They were treated with anastrozole n = 88 (50)% or letrozole n = 88 (50%). Type of bisphosphonate treatments used ,impact of alcohol consumption &amp; data on OS were collected from the database. Results: 176 patients (65.4%) were ER+ and had DEXA diagnosed osteoporosis or osteopenia. Alendronate was used in 15 patients (8.5%), ibandronate was used in 3 patients (1.7%), risedronate was used in 1 patient (0.6%), and zoledronate was used in 44 patients (25%). IV bisphosphonates were used in 44 patients (69.8%) and oral were used in 19 patients (30.2%). Majority of patietns were on calcium + D supplementation.10% of non-alcohol users had osteopenia/osteoporosis compared to 15% of former alcohol users and 29% of current alcohol users. LogRank testing found no significant difference between survival based on bisphosphonate use . Similar statistical analysis found no significant difference between survival based between IV and oral bisphosphonates. Conclusions: Our study showed that geriatric patients with ER + breast cancer on AI therapy were adequately managed for osteopenia and osteoporosis with the use of bisphosphonates (oral and IV) in a rural setting. There was no significant effect on overall survival (OS) , with use of bisphosphonates during AI therapy. No significant difference in OS was identified for patients taking IV vs. oral bisphosphonates,but this was attributed to very small number of patients that experienced death as an event in this population. Bisphosphonates were also well tolerated, with only 1 patient noting ONJ and one patient with renal toxicity. Current and former alcohol use was found to be correlated with increased rates of osteopenia/osteoporosis in this population.