tbuckley/cabot-search huggingface dataset:
Determinants of quality of life in patients with acute myeloid leukemia.
Authors: Sarah A. Buckley, Diana Jimenez-Sahagun, Megan Othus, Roland B. Walter, Stephanie Lee
Journal: Journal of Clinical Oncology (2017)

e18528 Background: There is growing interest in quantifying quality of life (QOL) effects of acute myeloid leukemia (AML) therapy. As there are no AML-specific QOL instruments available, we conducted a cross-sectional study to elicit concepts for the development of such an instrument, the AML-QOL. Methods: Adults with AML at various time points during the course of participated in an open-ended interview and completed the FACT-G, -LEU, -BMT and the PROMIS-29 questionnaires in order to elicit concepts impacting QOL. In addition, patients were asked to quantify the degree to which each impacted their QOL on a 3-point scale (little, some, large impact). Positive concepts (i.e., sources of support) were included in the AML-QOL based on prevalence; negative concepts were included based on both prevalence and the percent of cases in which the concept had high impact on QOL. Results: Among 82 patients, commonly described positive concepts were family support (85%), maintaining a positive attitude (63%), friends or community (52%), and trust in the medical team (52%). Negative concepts with the highest prevalence and impact product are shown in the Table. After completing FACT and PROMIS, 22% of patients reported confusion with items querying functional status because of ambiguity between temporary functional restrictions (e.g., inability because of an inpatient stay) and functional limitations (e.g., inability due to weakness). Conclusions: Our interviews identified concepts most important to patients during AML therapy and allowed development of a 40-item survey that is now undergoing validation. [Table: see text]
Sequencing of ramucirumab (ram) and immune checkpoint inhibitors (ICIs) in platinum (Pt)-treated real-world patients (pts) with advanced non-small cell lung cancer (aNSCLC).
Authors: Jeffrey Melson Clarke, Cliff Molife, Rebecca Miksad, Marta Batus, Katherine B. Winfree, Anala Gossai, Victoria Jennifer Stefaniak, Rebekah Foster, Zhanglin Lin Cui, Aracelis Z. Torres, Dana Feuchtbaum, Mahesh K Tawney, Philip D. Bonomi
Journal: Journal of Clinical Oncology (2018)

e21209 Background: Ram+docetaxel & ICIs are FDA-approved for aNSCLC pts failing Pt therapy. Optimal sequencing of these regimens is unknown. The study objective was to evaluate sequence patterns and outcomes with ram used pre v post-ICI in unmatched Pt-treated aNSCLC pts in the US. Methods: aNSCLC pts who initiated ram in 2L or 3L between March 2015 - May 2017, after 1L or 2L Pt therapy with ≥ 3 months of potential follow-up, and were treated with ICIs were identified in the Flatiron Health EHR-derived database. Overall survival (OS) was indexed to start of 1L and real-world progression-free survival (rwPFS) was indexed to start of 2L or 3L ram. Unadjusted hazard ratios (HR) were calculated using Cox models. Results: Of 185 eligible pts, 57% were treated with sequences including ram & ICIs. Of these, 38% and 62% received ram pre-ICI or post-ICI, respectively. Characteristics for ram pre & post-ICI pts shown in Table. All ram post-ICI pts received ram in 3L. Ram pre-ICI pts mostly (67%) initiated ram in 2L. While not statistically significant, pts receiving ram pre-ICI (reference) had longer median OS (24.0 v 19.0 months; HR = 1.30, 95% CI: 0.78 - 2.15) than ram post-ICI pts. Median rwPFS was similar (3.87 v 3.61 months; HR = 0.97, 95% CI: 0.63 - 1.47), as was ram therapy duration (2.8 v 2.4 months, log-rank P = 0.71). Conclusions: In this real world study, ram was most often used in 3L after an ICI. A trend for longer OS was observed in pts treated with ram pre-ICI, suggesting that the sequence for ram & ICIs may be important. However, this study was not large enough to support definitive conclusions in light of limited sample size and the potential impact of baseline characteristic imbalances; thus current findings warrant further study. Characteristic (%) Ram pre-ICI (n = 40) Ram post-ICI (n = 65) Demographics Age (years) 65-74 38 32 75+ 10 17 Race White 65 77 Black 0 9 Region Northeast 38 28 Midwest 23 12 South 28 39 Practice Academic 0 9 Community 100 91 Clinical Stage at diagnosis Stage III 28 11 Stage IV 68 77 Histology Non-squamous 88 75 Squamous 10 22 ECOG status 0/1 38 51 2+ 10 15 Unknown 53 34 Negative biomarker status (among % tested) EGFR 91 (85) 98 (83) ALK 94 (80) 100 (80) PD-L1 100 (18) 57 (22)
Assessment of immune status of patients with locally advanced cancer of the upper jaw.
Authors: Marina Engibaryan, Oleg Ivanovich Kit, Yulia Ulianova, Irina Viktorovna Pustovaya, Mamuka Bauzhadze, Elena Alekseevna Nikipelova
Journal: Journal of Clinical Oncology (2016)

e17562 Background: The purpose of the study was to assess changes in some immune system parameters in patients with locally advanced cancer of the upper jaw. Methods: Parameters of cellular and humoral immunity of 50 patients (27 men, 54% and 23 women, 46%) were determined before antitumor treatment. The disease was diagnosed in 80% of the cases in patients aged 40-69 years. Results: Comparative analysis of results of immune status examinations in cancer patients and healthy people showed statistically significant decrease in T-lymphocyte content in cancer patients due to subpopulations of helpers/inductors (СD4+) (31.6±2.0 and 43.7±2.3, respectively) and increase in suppressor/cytotoxic subpopulations (CD8+) (28.4%±1.6 and 22.0%±1.9) resulting in a significant reduction in immunoregulatory index (СD4+/СD8+) (1.14%±0.08 and 1.85%±0.08) which reflected increased immunosuppression in cancer patients by the beginning of treatment. Significant increase in spontaneous proliferative activity of lymphocytes was registered in cancer patients (17.3%±0.4) compared to healthy people (15.6%±0.7). Inhibition of functional activity of lymphocytes was detected by the response to their stimulation by concanavalin A (healthy people – 30.0%±1.2, cancer patients – 21.2%±0.6) and lipopolysaccharide (healthy people – 44.2%±1.4, cancer patients – 31.9%±1.5). B-lymphocyte content in patients with cancer of the upper jaw was similar to that in healthy people (17.7%±0.5 and 17.8%±0.8). Blood serum showed normal contents of main immunoglobulin classes (IgG – 10.8 g/L±0.79, IgА – 1.85 g/L±0.27, IgМ – 1.03 g/L±0.16). Immune status parameters did not depend on histological structure of tumors. Conclusions: Thus, immune status parameters in patients with locally advanced cancer of the upper jaw before the treatment were similar to the parameters in patients with locally advanced cancer despite tumor localization or histological structure. Such studies allow predicting the changes in the immune status of patients and correct its abnormalities during the treatment.
Two placebo-controlled phase 3 studies of fostamatinib, an oral spleen tyrosine kinase (Syk) inhibitor, for the treatment of persistent/chronic immune thrombocytopenia (ITP) in adults: Analysis of platelet response by prior ITP therapies.
Authors: James B. Bussel, Donald Arnold, Nichola Cooper, Alhossain Abdallah, Michael Boxer, Darla K. Liles, Waleed Ghanima, Keith McCrae, Hany Zayed, Sandra Tong, Ben Cadieux, Anne-Marie Duliege
Journal: Journal of Clinical Oncology (2018)

e15146 Background: Syk is an important signaling molecule for autoantibody-mediated platelet [plt] destruction by macrophages in pathogenesis of ITP. In 2 identical placebo-controlled phase 3 studies, the oral Syk inhibitor fostamatinib showed a collective stable response rate (proportion of patients [pts] with plt count ≥50,000/mL at ≥4 of 6 visits w/o rescue therapy during weeks 14-24) of 18% (18/101) for fostamatinib vs 2% (1/49) for placebo (P= 0.0003). An overall response (≥1 plt count ≥50,000/mL) rate of 43% was achieved with fostamatinib, compared with 14% for placebo (P= 0.0006). Here we present responses by prior therapy and baseline plt count. Methods: We examined stable responses in pts on fostamatinib from the pooled phase 3 studies according to prior thrombopoietin-receptor agonists (TPO-RA), rituximab, splenectomy, or median baseline plt count, as well as overall responses by disease duration at study entry in the double-blind studies. Results: Pts had ITP of long disease duration (median 8.5 yrs) and median 3 (range, 1-13) prior unique ITP therapies, including 94% with corticosteroids, 47% TPO-RA, 32% rituximab, 35% splenectomy, and 44% other immunosuppressants. Median baseline plt count was 16,000/μL. Stable responses on fostamatinib were achieved in 7 of 46 (15%) with and 11 of 55 (20%) without prior TPO-RA, 4 of 34 (12%) with and 14 of 67 (21%) without prior rituximab, 6 of 34 (18%) with and 12 of 67 (18%) without prior splenectomy, and 6/47 (13%) and 12/54 (22%) with baseline plt counts < and ≥15,000/µL, respectively. Overall responses were seen across a wide range of ITP durations including those with a duration of < 3 years (52%), 3 to < 8 years (48%) and ≥8 years (36%), but with no apparent correlation with disease duration. Most adverse events on fostamatinib were mild or moderate; all resolved over time or with treatment. Conclusions: Syk inhibition with the investigational agent fostamatinib produced clinically meaningful responses in adult ITP pts, with no clear relationship found between plt response and prior ITP treatment or disease duration. Clinical trial information: NCT02076399, NCT02076412.
Physician attitudes to use of epoetin biosimilars in an established market.
Authors: Isabelle Laure Ray-Coquard, Florian Scotte, Kamel Laribi, Christian Gisselbrecht, Emna Kasdaghli, Dominique Spaeth
Journal: Journal of Clinical Oncology (2016)

e18067 Background: Epoetin biosimilars have been available in Europe since 2007 but their uptake in France is low. The SYNERGY study investigated the use of epoetin zeta (Retacrit, Hospira, a Pfizer company) in chemotherapy-induced anemia (CIA) and physicians’ choices for the use of epoetin biosimilars in clinical practice in France. Methods: This observational, longitudinal, prospective, multicenter study was conducted in France, from a representative, random sample of oncologists and hematologists. The primary aim was to assess anemia response to epoetin zeta with and without iron supplementation; secondary objectives included current practice in management of CIA and attitudes to prescribing epoetin biosimilars. The study included adults with CIA, with solid tumors, lymphoma or myeloma, eligible for treatment with epoetin zeta, followed up at 12–16 weeks. Results: Of 195 physicians who responded, most (92.1%) considered biosimilars to be identical to their reference product. Most cited cost savings (83.1%) and comparable efficacy (73.8%) as the main reasons to use biosimilars (multiple reasons could be chosen), with comparable safety less frequently cited (54.9%) and innovative treatment an infrequent reason (13.3%). The majority (70.1%) of all physicians knew the principles behind the production of epoetin biosimilars and most (82.1%) were not reluctant to prescribe them. For physicians who were reluctant to prescribe an epoetin biosimilar, barriers to prescription included issues with the principle and manufacture of biosimilars (21.2%), insufficient studies (21.2%), insufficient hindsight (24.2%), mistrust of a new and unknown therapy (24.2%); doubts of comparable efficacy (12.1%) and reluctance toward use of copies (6.1%) were less common reasons. Conclusions: Despite recent data suggesting a low uptake of biosimilar epoetins in France, the majority of oncologists and hematologists in the SYNERGY study understood the issues of biosimilar production and were willing to prescribe them. Clinical trial data demonstrating therapeutic equivalence and 6 years of post-marketing safety experience may contribute to clinicians’ willingness to use epoetin zeta. Clinical trial information: NCT02158169.
Retrospective comparison between high-dose cisplatin and less-intensive weekly cisplatin/paclitaxel concurrently with radiation for locally advanced head and neck cancer (LAHNC).
Authors: Muhammad Furqan, Muhammad Uzair Saqlain, Sarah L Mott, Ravi Patel, Douglas Earl Laux, Jun Zhang, Laith I. Abushahin, Carryn M. Anderson, John Watkins, Anthony N Snow, Wenqing Sun, Gerald H. Clamon
Journal: Journal of Clinical Oncology (2016)

e17535 Background: Concurrent high dose Cisplatin (q3 weekly) or Cetuximab with radiation have shown improvement in survival for LAHNC compared to radiation alone. No randomized study has compared Cisplatin versus Cetuximab but retrospective data favors Cisplatin albeit with significant acute and long-term toxicities. Weekly Cisplatin/paclitaxel regimen was established in 2004 however it was never compared with Cisplatin. We retrospectively examined high dose Cisplatin versus weekly Cisplatin/paclitaxel given concurrently with definitive intensity modulated radiation therapy (IMRT) for LAHNC. Methods: Charts of patients treated with definitive chemoradiation during 2000-2013 for LAHNC were reviewed. Results: During the study period, 115 patients received Cisplatin 100mg/m² (Group1) and 114 received weekly Cisplatin 20mg/m² plus paclitaxel 30mg/m² (Group 2) concurrently with IMRT at our institution. Patients in Group 2 were significantly older, had lower BMI, and smoked more heavily. Patients in both groups were similar with respect to performance status and disease stage. Patients in Group 1 had significantly higher incidence of Grade ≥ 2 neutropenia and non-hematological toxicities. Median follow-up was 49 months (range, 2-117months). No statistical difference was noted for the outcomes assessed between both groups, as summarized in the table. Two third of all patients in each group had Oropharyngeal primary and their outcomes were also not affected significantly by type of chemotherapy received. Conclusions: In this retrospective study, patients receiving definitive chemoradiation with high dose Cisplatin suffered more acute and long term toxicities and their outcomes were similar to patients receiving less intensive weekly Cisplatin/paclitaxel. Outcomes Chemotherapy Groups 2 Year Estimate (95% CI) 5 Year Estimate (95% CI) Overall Survival Cisplatin 90% (82-94%) 73% (63-81%) Cisplatin +paclitaxel 82% (73-88%) 64% (54-72%) Progression free survival Cisplatin 77% (69-84%) 67% (57-75%) Cisplatin +paclitaxel 74% (65-81%) 60% (50-68%) Locoregional Control Cisplatin 80% (71-86%) 74% (65-82%) Cisplatin +paclitaxel 75% (66-82%) 68% (58-76%)
Identifying treatment options for SCLC patients with multiplexed clinical proteomic testing.
Authors: Eunkyung An, Sook-Hee Hong, Ho Jung An, Sheeno P. Thyparambil, SHANKAR SELLAPPAN, Dongyao Yan, Yuan Tian, Fabiola Cecchi, Todd A. Hembrough, Tae Jung Kim
Journal: Journal of Clinical Oncology (2018)

8574 Background: Even with standard platinum doublet therapy, most patients with small-cell lung cancer (SCLC) survive < 1 year. For those with refractory or relapsed disease, second-line, single-agent chemotherapy is recommended. Pre-treated SCLC patients can opt for clinical trials of agents such as temozolomide, fluorouracil (5FU), and antibody-drug conjugates (ADC) targeting the proteins DLL3, CD56, or TROP2. Some of these therapies have produced responses in untreated SCLC. To assess the proportions of patients who would be likely to respond to these therapies, we profiled protein targets in clinical tumor biopsies of SCLC using quantitative mass spectrometry. Methods: Archived tumor samples from 88 SCLC patients were microdissected and solubilized for proteomic quantification of 58 therapeutically relevant biomarkers. In each sample, quantities of tumor protein were compared with pre-defined thresholds based on evidence from clinical studies or on quantification limits of proteomic assays. Prevalences and protein expression levels in SCLC were compared with those of other cancer indications analyzed in the same clinical laboratory. Results: 15 of 83 (18%) SCLC tumors had low or absent MGMT protein expression ( < 200 attomoles per microgram [amol/ug]), indicating likely response to temozolomide. 14 of 88 (15%) overexpressed TYMP protein ( > 1335 amol/ug), suggesting likely response to 5FU. Except for one patient, likely responders to temozolomide or 5FU were mutually exclusive. Prevalences of quantifiable levels of the ADC markers DLL3, TROP2, and CD56 were 43%, 49% and 97%, respectively. The SCLC tumors expressed a wide range of DLL3 protein (range: 101 – 1201 amol/ug); median expression in SCLC was 2 times higher than in pediatric neurological cancers, while median expression of TROP2 was lower in SCLC than in other indications. CD56 protein levels in SCLC were similar to other indications, but with higher prevalences in SCLC. Conclusions: In patients with SCLC, clinical proteomics identified protein targets of multiple approved and investigational therapies.
Is there a role for adjuvant radiation in T1N0 squamous cell carcinoma tongue with adverse pathological features? Factors affecting local control and the development of a scoring system.
Authors: Vijay Kumar Srinivasalu, Narayana Subramaniam, Deepak Balasubramanian, Hubert Low, Adharsh Anand, Krishnakumar Thankappan, Arun Philip, Subramania Iyer, Keechilat Pavithran
Journal: Journal of Clinical Oncology (2017)

e17565 Background: The patterns of recurrence and the prognostic factors of early tongue lesions have been previously described in literature, often grouping T1 and T2N0 tongue lesions together. Adverse pathological features (APFs) have been used to predict nodal spread, but the prognostic factors predicting local recurrences in T1N0 tongue have seldom been described. We aim to evaluate the APFs associated with poor local control and the possible need for escalation of therapy. Methods: A retrospective analysis of 144 patients of pT1N0 squamous cell carcinoma tongue, extracted from our database of 598 patients of oral cavity who underwent wide local excision with neck dissection in a single institution between 2006-2014 were included in our study. Patients who received any adjuvant therapy were excluded. Results: APFs associated with local control were least margin 5 mm (p=0.004), infiltrative margin (p=0.403), depth ≥ 4mm (p=0.136), lymphovascular invasion (p=0.301) and perineural invasion (p=0.342). We derived a scoring system assigning a score to each of these factors out of a total 10 points, based on the hazard ratio for local failure. Patients with a score ≥ 5 points had a 5-year local control rate of ≤ 60%. Conclusions: Having least margin of 5 mm was the greatest predictor of local failure. This would suggest that all patients having a margin of 5 mm need revision, however if they do not have additional APF (score ≤ 4 points), they still have good local control rates (5-year local control rate of 88%) and may be observed. Those who have margins over 5 mm with a total score ≥ 5 may still benefit from adjuvant therapy for local control. Those with margins over 5mm have improved local control rates (p=0.029). [Table: see text]
Androgen receptor (AR) activation in breast cancer (BC) liver metastases.
Authors: Corinne Ramos, Nicholas N Hoke, Tom Wilks, Maren K. Levin, Sarah Hippely, Mariaelena Pierobon, Emanuel Petricoin, Joyce O'Shaughnessy
Journal: Journal of Clinical Oncology (2017)

11619 Background: AR is expressed in the majority of BCs and its signaling may contribute to the development of BC metastases (mets). The expression pattern of AR, its phosphorylated form, p-AR S650, and correlations with other BC growth and survival pathways were evaluated in BC mets by reverse phase protein array (RPPA). Methods: RPPA was performed on 93 FFPE primary BCs and mets at a CLIA-certified laboratory. Immunostaining with 24 antibodies was directed against AR, p-AR S650, p-MET, and total and p-HER1/2/3 pathway proteins. Clinical and genomic data were obtained from pt chart review. Analysis of variance (ANOVA) was used to assess any statistically significant differences between the groups. Results: 35 tissues were primary BCs (38%); 58 were mets (62%). Sites of mets: liver (n = 41); lung (n = 8); chest wall (n = 9). Of the 41 liver mets, 2 were triple negative (TN), 32 were ER+/HER2-, and 7 were HER2+. AR expression was increased in chest wall (1.7-fold; p = 0.038) compared to primary BCs. p-AR was increased in liver (2.0-fold; p = 0.039) and chest wall (1.8-fold; p = 0.026) compared to primary BCs. ER+ liver mets especially showed strong liver-specific activation of AR along with overexpression of HER1, HER3, VEGFR, and activation of mTOR, S6 Ribo, 4EBP1, and STAT3. MEK/ERK pathway was not activated in ER+ liver mets. HER2+ liver mets had pan-HER1/2/3 activation along with MET, SRC, S6 Ribo, 4EBP1, and JAK2/STAT3. In the 2 TN liver mets, EGFR, VEGFR, mTOR, S6 Ribo, 4EBP1, and JAK2/STAT3 were activated while AR and MEK/ERK were not. The ER+ liver mets showed higher expression of p-AR (p = 0.079), p-HER3 (p = 0.002), p-HER2 (p = 0.010) and p-Jak2 (p = 0.002) compared to primary ER+ BCs whereas the HER2+ liver mets showed lower level of p-IGFR (p = 0.049) and p-MET (p = 0.010) compared to primary HER2+ BCs. Interestingly, TN chest wall mets had higher levels of AR and p-AR (p = 0.008 and 0.044 respectively) compared to TN BCs. Conclusions: ER+ liver mets have strong expression of AR and p-AR, and all liver met subtypes showed accumulation of S6 Ribo/4EBP1 and activation of JAK2/STAT3, but not the MAPK pathway. HER1/3 and HER1/2/3 were activated in ER+ and HER2+ liver mets, respectively. These data suggest that targeting AR, HER1/3, and mTOR in ER+ liver met would be of interest.
Nab-paclitaxel plus S-1 followed by S-1 maintenance therapy as a first-line strategy for advanced pancreatic adenocarcinoma.
Authors: Yan Shi, Huan Yan, Jie Li, Yao Lv, Quanli Han, Zhikuan Wang, Guanghai Dai
Journal: Journal of Clinical Oncology (2018)

4117 Background: Growing evidence support maintenance therapy (MT) offer clinical benefit in pancreatic, colorectal and lung cancers. In our phase II trial, nab-paclitaxel plus S-1 (NPS) showed encouraging objective response rate (ORR) as first-line treatment in advanced pancreatic adenocarcinoma (APAC), in which S-1 was an option as MT after NPS. Our observational study aims to evaluate the effectiveness and tolerability of strategically using S-1 as MT after NPS in APAC. Methods: Between Jan 2014 and Oct 2017, 122 patients with APAC treated with NPS were included in this observational study. In patients without progression after at least 4-cycle of NPS (nab-paclitaxel, 240mg/m2 every 3-week; S-1, 80-120 mg/d per body surface area on day 1-14 of each 21-day cycle) or treatment discontinued due to any reasons, S-1 monotherapy was allowed to be given as MT at physician’s discretion according to patients’ desire and ECOG performance status. Patients were followed up every 2 months until death. ORR, progression-free survival (PFS), overall survival (OS) and safety were measured. Results: In 8 locally advanced and 114 metastatic APACs, ORR, median PFS and OS were 49.2%, 7.5 (95%CI 6.0 to 9.0m) and 10.7 months (95%CI 8.6 to 12.8m), respectively. Total 84 patients had no progression after a median of 4 cycles of NPS (2 to 8 cycles), in which 49 had a median of 4-cycle S-1 MT (1 to 32 cycles). Median PFS and OS in patients with S-1 MT were 10.4 months (95%CI 7.9 to 12.9m) and 16.7 months (95%CI 14.5 to 18.9m) compared to 5.1 months (95%CI 4.7 to 5.5m) and 8.1 months (95%CI 6.4 to 9.8m) without S-1 MT (P < 0.001). In patients with stable disease (n = 31), mPFS and mOS in S-1 MT group were 10.4 (95%CI 6.9 to 13.9m) and 16.4 months (95%CI 13.8 to 19m) compared to 5.2 (95%CI 4.3 to 6.1m) and 8.1 (95%CI 6.7 to 9.5m) without S-1 MT (P < 0.05). Survival rates were 79.1% and 65.7% at 1 year, 61.9% and 33.4% at 2 years in patients with or without S-1 MT, respectively. S-1 MT group had a higher incidence of grade 3 or 4 leukopenia/neutropenia (20.4%) compared to 12.8% in the group without MT. Conclusions: Maintenance with S-1 after NPS was effective and well tolerated in APAC, which offered a new first-line strategy for APAC with a promising OS and PFS.