tbuckley/cabot-search huggingface dataset:
A multicenter phase II trial of docetaxel, cisplatin and cetuximab (TPE) followed by cetuximab concurrent with radiotherapy in patients with local advanced squamous cell carcinoma of the head and neck (ECRIPS study).
Authors: Sadamoto Zenda, Yosuke Ota, Naomi Kiyota, Susumu Okano, Masato Fujii, Morimasa Kitamura, Shunji Takahashi, Tsutomu Ueda, Nobuya Monden, Takeharu Yamanaka, Makoto Tahara
Journal: Journal of Clinical Oncology (2017)

6071 Background: Induction chemotherapy is a treatment option for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, Docetaxel, Cisplatin, and 5-FU (TPF) followed by Cisplatin with radiotherapy is currently not recommended due to toxicity concerns. The aim of this phase II study was to assess the feasibility of Docetaxel, Cisplatin, and Cetuximab (TPE) followed by Cetuximab with concurrent radiotherapy for LA-SCCHN. Methods: Patients were eligible if they had histologically proven SCC of oropharynx, hypopharynx or larynx, a PS of 0-1, adequate organ function, and no distant metastasis. Induction chemotherapy consisted of Cisplatin 75mg/m 2 and Docetaxel 75mg/m 2 on day1 and the induction regimen was repeated every 3 weeks up to a total of 3 courses. Cetuximab was administered at an initial dose of 400mg/m 2 followed by 250mg/m 2 weekly until the end of radiotherapy. Radiotherapy (70Gy/35fr/7w) was started after last administration of Docetaxel. Primary endpoint was the rate of treatment completion. The planned sample size was 55 with one-sided alpha of 0.025 and the power of more than 90% based on the expected and threshold treatment completion rates of 65% and 40%. Results: Between August 2013 and October 2015, 54 patients with a median age of 58 years were eligible and had the study treatment. There were 50 males, hypopharynx/oropharynx/larynx cancer of 28/19/7 cases, and 48 Stage IV disease. Response rate at induction chemotherapy was 72% while that after radiotherapy was 76% . Of 54 patients, 50 (93%) received &gt; 2 courses of induction chemotherapy, and 41 (76%) had the full dose of radiotherapy. The rate of treatment completion was thus 76% (95%CI, 62–87%). The frequency of grade 3-4 neutropenia, febrile neutropenia, and allergy/infusion reaction was 93%, 39%, and 11%, respectively. One treatment-related death was observed. Conclusions: Induction TPE followed by Cetuximab with concurrent radiotherapy was feasible with a promising efficacy. A phase III study to evaluate this treatment strategy is warranted. Clinical trial information: UMIN000009928.
JAG1 overexpression contributes to Notch1 signaling and the migration of HTLV-1-transformed ATL cells
Authors: Marcia Bellon, Ramona Moles, Hassiba Chaib-Mezrag, Joanna Pancewicz, Christophe Nicot
Journal: Journal of Hematology & Oncology (2018)

HTLV-1 is a retrovirus that infects over 20 million people worldwide and is responsible for the hematopoietic malignancy adult T cell leukemia (ATL). We previously demonstrated that Notch is constitutively activated in ATL cells. Activating genetic mutations were found in Notch; however, Notch signaling was also activated in the absence of genetic mutations suggesting the existence of other mechanisms. We analyzed the expression of Notch receptor ligands in HTLV-I-transformed cells, ATL patient-derived cell lines, and fresh uncultured ATL samples by RT-PCR, FACS, and immunohistochemistry. We then investigated viral and cellular molecular mechanisms regulating expression of JAG1. Finally, using shRNA knock-down and neutralizing antibodies, we investigated the function of JAG1 in ATL cells. Here, we report the overexpression of the Notch ligand, JAG1, in freshly uncultured ATL patient samples compared to normal PBMCs. We found that in ATL cells, JAG1 overexpression relies upon the viral protein Tax and cellular miR-124a, STAT3, and NFATc1. Interestingly, our data show that blockade of JAG1 signaling dampens Notch1 downstream signaling and limits cell migration of transformed ATL cells. Our results suggest that targeting JAG1 can block Notch1 activation in HTLV-I-transformed cells and represents a new target for immunotherapy in ATL patients.
Symptom burden in hospitalized patients with curable and incurable cancers.
Authors: Lauren Waldman, Richard Newcomb, Ryan David Nipp, Ephraim P. Hochberg, Vicki Jackson, Joseph Greer, David P. Ryan, Jennifer S. Temel, Areej El-Jawahri
Journal: Journal of Clinical Oncology (2018)

190 Background: Inpatient supportive care interventions are targeted to patients with advanced solid tumors due to perceived higher symptom burden. Yet, few studies have characterized symptom prevalence in hospitalized patients with curable cancers. We aimed to describe and compare symptom burden and palliative care utilization in hospitalized patients with curable and incurable cancers to determine the allocation of such supportive care resources. Methods: We conducted a single center study of 1549 patients (238 curable hematologic, 239 curable solid, 123 incurable hematologic, 949 incurable solid cancers) who experienced an unplanned hospitalization between 9/14 - 4/17. On admission, we assessed patients’ physical symptoms (Edmonton Symptom Assessment System) and psychological distress (Patient Health Questionnaire - 4 and Primary Care PTSD Screen). Results: The median number of moderate to severe symptoms reported by patients with curable hematologic, curable solid, incurable hematologic, and incurable solid cancers were 5 [3-6], 5 [3-7], 5 [4-6], and 6 [4-7], respectively. Most patients reported moderate to severe fatigue (83.6%, 82.9%, 81.3%, 86.9%). Table 1 depicts rates of psychological distress. In adjusted analyses patients with incurable solid cancers reported higher symptom burden (β = 7.6, p &lt; 0.01), depression (β = 0.4, p = 0.01), and anxiety (β = 0.3, p = 0.03) symptoms, but no difference in PTSD symptoms. Among patients in top quartile of symptom burden, palliative care was consulted in 16.2%, 7.9%, 23.8%, and 49.6% (p &lt; 0.01) of patients with curable hematologic, curable solid, incurable hematologic, and incurable solid cancers, respectively. Conclusions: Hospitalized patients with solid and hematologic cancers experience substantial physical and psychological symptoms regardless of the curability of their illness. Palliative care is rarely consulted for highly symptomatic patients with curable cancers. Inpatient supportive care interventions should target the needs of all highly symptomatic patients with cancer. [Table: see text]
Risk tolerance and attitudes toward chemotherapy: Who chooses palliative treatment when cure is possible?
Authors: Thomas William LeBlanc, Karen Scherr, Annabel Wang, Monica Lemmon, Peter A. Ubel
Journal: Journal of Clinical Oncology (2017)

10054 Background: Many patients with acute myeloid leukemia (AML) face a difficult choice about whether to receive palliative chemotherapy or high-dose, potentially-curative chemotherapy that poses a risk of early death. How people weigh these factors in decision-making is unknown. We hypothesized that the possibility of cure primarily drives decision-making, regardless of treatment risk. Methods: We designed an electronic survey describing two treatment paths: (1) high-dose chemotherapy with possibility of cure but a 10% risk of early death, and (2) palliative chemotherapy with no chance of cure but no risk of early death. We recruited respondents via Amazon MTurk and presented 7 scenarios in random order, varying only the likelihood of cure associated with high-dose chemotherapy. Subjects rated their preferred treatment on a 4-point Likert scale. We assessed numeracy and attitudes toward chemotherapy using validated scales, and employed attention checks for quality assurance. Results: 100 subjects completed the survey (median age 30.5; 52 female, 85 Caucasian). 46 (46%) had at least a bachelor’s degree and numeracy was generally high (median 4.75 out of 6). Respondents’ preferences for intensive chemotherapy varied with likelihood of cure, however some displayed a fixed preference for either curative or palliative treatment throughout, regardless of benefit level. For example, given a 50% likelihood of cure 20 respondents (20%) still preferred palliative therapy; similarly, with only a 1% likelihood of cure 28 respondents (28%) still preferred high-dose chemotherapy. In a multivariable model, preference for palliative chemotherapy was significantly predicted by subjects’ scores on the attitudes toward chemotherapy scale (p &lt; 0.001), controlling for age, education, and numeracy. Conclusions: Contrary to our hypothesis, a significant proportion of subjects preferred palliative chemotherapy, even in scenarios where high-dose chemotherapy confers a high likelihood of cure. Pre-existing attitudes toward chemotherapy appear to drive patients’ decision-making, even when treatments are potentially curative. This finding may have significant implications for risk communication in oncology.
Survival outcomes by HPV status in non-oropharyngeal head and neck cancers: A propensity score matched analysis of population level data.
Authors: Sibo Tian, Jeffrey M. Switchenko, Jaymin Jhaveri, Richard John Cassidy, Matthew Jeffrey Ferris, Robert H. Press, Neil T Pfister, Mihir Patel, Nabil F. Saba, Mark William McDonald, Kristin Ann Higgins, David S. Yu, Walter John Curran, Theresa Wicklin Gillespie, Jonathan Jay Beitler
Journal: Journal of Clinical Oncology (2018)

6005 Background: The impact of HPV status in non-oropharynx (OPX) cancers is unclear. Limited sample sizes, and unadjusted comparisons have confounded interpretation. Our goal was to evaluate the prognostic value of HPV status in non-OPX cancers using an administrative database. Methods: The National Cancer Data Base was queried to capture patients diagnosed between 2010-2013 with invasive cancers of OPX, hypopharynx (HPX), larynx (LX), and oral cavity (OC). HPV positivity was defined by high-risk subtypes, i.e. 16 & 18. Patients with HPV status, survival outcomes and non-metastatic disease were analyzed. Survival was estimated using the Kaplan-Meier method, and log-rank tests were used to compare distributions. Propensity matched methods were utilized by reweighting patients using the inverse probability of treatment weighting (IPTW) approach; included variables were: age, sex, Charlson-Deyo score, treatment with surgery, chemotherapy, radiotherapy, group stage, and subsite where appropriate. Analyses were stratified by AJCC 7th edition stage I-II vs III-IVB. Results: A total of 27,954 patients were included: 1,140 cases of HPX, 5,074 cases of LX, 4,540 cases of OC, and 17,200 cases of OPX. The proportion of HPV positive cases were: 20.9% in HPX, 14.2% in LX, 12.2% in OC, and 67.5% in OPX. HPV positivity was associated with superior overall survival (OS) in multiple non-OPX groups. In HPX, actuarial OS by HPV status were at 2-yr 75.9% vs 59.6%; at 5-yr 60.2% vs 33.6% (HPV+ vs HPV-); survival was significant with IPTW (HR 0.56, p < 0.001). HPV-positivity was associated with superior OS for stage III-IVB LX cancer; OS at 2-yr was 75.3% vs 66.2% (IPTW HR 0.81, p = 0.029). HPV status was not prognostic overall in OC. HPV status in stage III-IVB OC patients trended towards significance (IPTW HR 0.82, p = 0.059); OS at 2-yr was 64.9% vs 59.1%. Survival outcomes by HPV status in OPX were: stage I-II IPTW HR 0.45 (p < 0.001); stage III-IVB HR 0.42, (p < 0.001). Conclusions: HPV positivity was associated with improved survival in HPX, locally-advanced LX, and potentially locally-advanced OC patients. These finding, if prospectively validated, may have implications for future risk stratification.
Outcomes with chemotherapy for metastatic non-small cell lung cancer (mNSCLC) in patients previously treated with immune checkpoint inhibitors (CPI).
Authors: Radowan Elnair, Guy vin Chang, Steven Francis Powell, Christopher Joseph Sumey, Jonathan Scott Bleeker
Journal: Journal of Clinical Oncology (2018)

e21119 Background: For mNSCLC patients, CPI are used as second line therapy after progression on first line chemotherapy or as first line therapy for a subset of patients. Recent retrospective studies suggest higher response rates and longer progression free survival (PFS) with chemotherapy in patients pretreated with CPI for mNSCLC as compared to historical data. We assessed the response to chemotherapy after CPI and potential response predictors. Methods: We performed a retrospective review of patients with mNSCLC who received at least one line of chemotherapy following discontinuation of CPI from July 2015 through January 2018 at our integrated community-based health system. PFS for first line of therapy following discontinuation of CPI (PFS-1), and overall survival (OS) following discontinuation of CPI were recorded as endpoints. Patient demographics, tumor histology, receipt of radiation therapy, prior chemotherapies received, and PD-1/PD-L1 expression status were reviewed. RECIST v1.1 was used to determine progression. Given the small sample size we considered a p value of 0.1 for significance. Results: A total of 36 patients met eligibility criteria; 50% were male. Median age at the time of receiving CPI was 69 years (range 37-86), with a median of one line of chemotherapy prior to CPI (range 0-5) and one line of chemotherapy following discontinuation of CPI (range 1-3). The median for PFS-1 was 4.8 months (range 0.9-21.7). 27 out of 35 evaluable patients (77.1%) remained alive at a median follow-up of 11.7 months (range 3.0-24.4). Receipt of radiation therapy in the metastatic setting was associated with improved PFS-1 (p = 0.06). PD-1/PD-L1 expression did not correlate with a longer PFS-1 (p = 0.96). PFS on CPI was not significantly related to PFS-1 (p = 0.57) or to OS (p = 0.99). Conclusions: The PFS and OS data from this cohort compares favorably with historical data for patients treated in the second line and beyond for mNSCLC, suggesting that patients previously treated with CPI may have improved outcomes compared to those who are CPI naïve. These effects appear independent of the PD-1/PD-L1 expression status or PFS on CPI.
Impact of clostridium difficile infection on short-term outcomes in hospitalized patients with hematologic malignancies: A national sample.
Authors: Kahee A. Mohammed, Eric Adjei Boakye, Jiajing Chen, Nosayaba Osazuwa-Peters, Martin W. Schoen, Leslie J. Hinyard, Kevin A Palka
Journal: Journal of Clinical Oncology (2018)

e18711 Background: Patients with hematologic malignancies are susceptible to clostridium difficile infection (CDI) given their exposure to chemotherapy and subsequent development of neutropenia. This study aimed to evaluate the incidence of CDI and its impact on in-hospital mortality, length of hospital stay, and health care utilization among patients with hematologic malignancies. Methods: Data from Nationwide Inpatient Sample (2008–2013) were analyzed to identify hospitalized patients (aged ≥18 years) with hematologic malignancies (n = 518,648). Weighted, multivariate hierarchical logistic regression analyses were performed to adjust for patient and hospital level variation in outcomes. Results: The incidence of CDI was higher among patients with acute myeloid leukemia (AML) (5.0%) followed by acute lymphocytic leukemia (ALL) (3.7%) and chronic myeloid leukemia (CML) (3.1%). In the adjusted models, patients with CDI had higher odds of in-hospital mortality [chronic lymphocytic leukemia (CLL) (OR = 1.4, 95% CI = 1.2–1.6), CML (OR = 1.3, 95% CI = 1.1–1.7), and multiple myeloma (MM) (OR = 1.4, 95% CI = 1.2–1.6)]. Patients with CDI were three times more likely to have a prolonged hospital stay and have double the total hospital charges compared to those without CDI (Table). Conclusions: The incidence of CDI is high among hospitalized patients with acute leukemias and is associated with a greater length of stay and higher hospital charges. Given the burden associated with CDI, efforts should aim at prompt and accurate diagnosis, and early treatment. Total Patients Clostridium Difficile Infection Incidence In-hospital Mortality aOR (95% CI) Prolonged Hospital Stay aOR (95% CI) Average Total Hospital Charges: CDI vs no CDI CLL 99,110 2.5% 1.4 (1.2–1.6) 3.6 (3.2–4.2) $80,695 vs $46,290 CML 28,071 3.1% 1.3 (1.1–1.7) 3.2(2.6–3.9) $117,7272 vs $57,128 AML 82,100 5.0% 1.0 (0.9–1.2) 3.2 (2.9–3.4) $232,231 vs $108,475 ALL 58,338 3.7% 1.1 (0.9–1.5) 2.6 (2.2–3.0) $187,354 vs $73,612 MM 116,751 2.9% 1.4 (1.2–1.6) 3.5 (3.2–3.9) $107,313 vs $55,808 Non-Hodgkin 45,727 2.7% 1.1 (0.9–1.5) 3.7 (3.1–4.4) $126,608 vs $60,720 Hodgkin 33,551 2.0% 1.2 (0.9–1.7) 3.6 (2.9–4.5) $128,576 vs $54,649
Survival advantage for hepatectomy with or without hemicolectomy in colorectal liver metastases.
Authors: Dalia A. Mobarek, Jiwon Chang, Scott L. DuVall, Steven H. Krasnow
Journal: Journal of Clinical Oncology (2016)

e15014 Background: Surgical resection of Colorectal Liver Metastases offers the greatest chance of long-term survival. We aimed to study survival in patients presenting with hepatic metastasis at the outset and rates of surgical intervention in the Veterans Health Administration. Methods: The Veterans Affairs Central Cancer Registry and VA Informatics & Computing Infrastructure were queried and linked to retrospectively analyze stage IV CLM from 10/01/2004-12/31/2012. Cohort construction and analyses were performed utilizing SQL Server, SAS software, version 9.4 (SAS Institute Inc., Cary, NC) and Microsoft Excel. Event-free survival curves and hazard ratios were estimated using Kaplan-Meier analyses and Cox proportional hazards regression. Results: We identified 1245 subjects, across 118 Veterans Affairs Medical Centers nationwide, who met the inclusion criteria. Of the 56% (n = 698) of subjects who received surgery, hepatectomy was performed in 3% (n = 23), combined hemicolectomy and hepatectomy in 7% (n = 52), and hemicolectomy alone in 89% (n = 623). Median overall survival for subjects receiving hepatectomy, combined hemicolectomy and hepatectomy, or hemicolectomy alone, as their first surgical intervention, was 49.77, 30.11, and 16.04 months. The 3- year and 5-year survival was 64% and 37% for hepatectomy, 29% and 18% for combined hemicolectomy and hepatectomy, and 20% and 8% for hemicolectomy (p < 0.0001). When controlling for sex, Charlson Comorbidity Index, preoperative chemotherapy, BMI, and age at first surgery, subjects receiving hemicolectomy are 3.290 times more likely to experience death at any time after surgery than patients receiving hepatectomy (HR = 3.29, p = 0.0007, 95% CI 1.65 – 6.55). There was no significant difference in mortality between subjects receiving combined hemicolectomy with hepatectomy and those with hepatectomy (HR = 1.98, p = 0.072, CI 0.94 – 4.17). Conclusions: Patients receiving hepatectomy with or without hemicolectomy had a significant survival advantage over patient’s receiving hemicolectomy alone. This should be further examined in prospective studies as this may increase the survival of patients with stage IV colorectal cancer irrespective of hemicolectomy.
A Roadmap for Value‐Based Payment Models Among Patients With Cirrhosis
Authors: Michael L. Volk, Jessica Mellinger, Meena B. Bansal, Ziad F. Gellad, Mark McClellan, Fasiha Kanwal
Journal: Hepatology (2018)

Healthcare reimbursement is shifting from fee‐for‐service to fee‐for‐value. Cirrhosis, which costs the U.S. healthcare system as much as heart failure, is a prime target for value‐based care. This article describes models in which physician groups or health systems are paid for improving quality and lowering costs for a given population of patients with cirrhosis. If done correctly, we believe that such frameworks, once adopted, could help reduce burnout by freeing physicians of the burden of checking boxes in the electronic medical record so that they can devote their energies to managing populations. Conclusion : Value‐based payment models for cirrhosis have the potential to benefit patients, physicians, and healthcare insurers.
Cancer is not a risk factor for bullous pemphigoid: 10‐year population‐based cohort study
Authors: C.T. Chen, H.Y. Hu, Y.T. Chang, C.P. Li, C.Y. Wu
Journal: British Journal of Dermatology (2018)

BackgroundBullous pemphigoid (BP) is the most common autoimmune bullous disease. Whether there is an increased risk for subsequent BP among patients with cancer is still unclear.
Genetic landscape of soft-tissue sarcomas: Moving toward personalized medicine.
Authors: Antoine Italiano, Emmanuel Khalifa, Yec'han Laizet, Maud Toulmonde, Sophie Cousin, Carlo Lucchesi
Journal: Journal of Clinical Oncology (2017)

11002 Background: Patients with advanced soft-tissue sarcomas have a very poor outcome with a median overall survival of less than 18 months. Identification of molecular abnormalities for which targeted therapies are available or can be developed is critical for improving their outcomes. Methods: We have analyzed the mutational and copy number profiles of patients with sarcoma sequenced through the AACR Project GENIE Consortium in order to identify the proportion of cases bearing actionable mutation. Results: 587 patients (pts) were included in the study (295 males). 331 pts (56%) had complex genomics sarcomas, 144 (25%) translocation-related sarcomas and 112 (19%) others sarcomas (inactivating mutation, simple amplicon). The five most frequent histology were: Leiomyosarcoma (n = 112; 19.1%); Undifferentiated Pleomorphic Sarcomas (n = 74, 12.6%), dedifferentiated liposarcoma (n = 55, 9.4 %), angiosarcoma (n = 43, 7.3%), synovial sarcoma (n = 38, 6.5%). 430 pts (73%) had at least one mutation. The ten most frequently mutated genes were: TP53 (34.7%); ATRX (9.1%), RB1 (8.4%), KMT2D (5.8%), NF1 (5.3%), ATM (5.1%), PI3KCA (4.9%), ERBB4 (4.2%), PTEN (4%), and ARID1A (3.7%). 504 patients (85.9%) presented at least one copy number alteration. The 5 five most frequently amplified genes were: MDM2 (20%), CDK4 (16.7%), GLI1, MAP2KA, and TERT (3.2% for each gene), and the most frequently deleted were RB1 (12.7%), CDKN2A (10.3%), CDKN2B (9.7%), TP53(9.5%), PTEN (8.5). 92.5% of pts had at least one targetable mutation, copy number alteration and/or fusion gene ( Leiomyosarcoma n = 100/17%, UPS n = 74/12%, dedifferentiated diposarcoma n = 54/9%, angiosarcoma n = 41/7%, synovial Sarcoma n = 36/6%), with incidences reported that will be reported in details at the meeting. Conclusions: This is the first large report of genomic landscape including mutation and copy number profiling through NGS of soft-tissue sarcomas. Our results indicate a significant proportion of actionable mutations and represent a rationale for the MULTISARC study: the first study implementing Exome Seq and RNA Seq for clinical decision making in patients with advanced STS. The design of this study supported by the French government and launched in 09/2017 will be presented at the meeting.