tbuckley/cabot-search huggingface dataset:
Implementing patient-reported outcome surveys as part of routine care: Lessons from an academic radiation oncology department.
Authors: Ankit Agarwal, Kelly O'Neil, Andrea Kelly, Maureen Keaty, Colleen Whitehouse, Barbara Kalinowski, Peter F. Orio, Neil E. Martin
Journal: Journal of Clinical Oncology (2016)

97 Background: We sought to implement patient reported outcomes (PRO) surveys to measure the acute and late effects of radiation treatment at a multisite academic medical center. Methods: Over the course of 18 months we addressed survey identification and implementation hurdles. Many existing validated instruments were designed for clinical research and are not ideally suited for either routine care or for the tracking of acute toxicities of radiation therapy. A physician and a nurse champion for each disease site identified or created situation- and site-specific tools based on validated questionnaires form the literature. Our aim was for questionnaires to be no longer than 20 - 30 questions. Using iPads, we deployed an institutionally-developed survey platform integrated with scheduling within the clinic. We surveyed physicians, nurses, and residents 3 months following the implementation of PROMs to assess their general response to the initiative. Results: Thirty-seven PRO measures comprised of 640 questions were implemented for all disease sites in adult patients at 6 departmental locations treating a total of 350 patients daily. Following implementation in January of 2015, &gt; 13,000 surveys have been completed through the end of September 2015. Each question took on average approximately 14 seconds to complete and common surveys took approximately 10 minutes. Of 36 departmental provider respondents (50% response rate overall), 47% stated that they use the PROMs in their daily practice. The majority of respondents felt that the PROs were valuable (67%) and relevant (75%) either usually, most of the time or always. Only 33% felt the quality of their care was enhanced usually or most of the time while 53% felt the PROs engaged patients in a better understanding of their own care. Conclusions: We successfully implemented disease site- and context-specific PROs across a large, academic radiation oncology department. Although we have achieved widespread adoption and some subjective impression of care improvement among providers, further work is necessary to reduce barriers to their clinical use and to leverage them for systematic improvements in care.
Clinicopathologic features of gastric cancer in the elderly population.
Authors: Joo Hyun Lim, Dong Ho Lee, Cheol Min Shin, Na Yung Kim, Young Soo Park, Hyun Chae Jung, In Sung Song
Journal: Journal of Clinical Oncology (2014)

33 Background: Gastric cancer is one of the most common cancers, having great incidence among the elderly. However, little is known about gastric cancer in elderly patients. This study was designed to evaluate the specific features of gastric cancer in elderly patients. Methods: We reviewed medical records of 1107 patients who had undergone radical gastrectomy for gastric cancer between June 2005 and December 2009 retrospectively. They were divided into young age group (&lt;65, n = 676), middle age group (65 ≤ age &lt; 75, n = 332) and old age group (≥75, n = 99). To find out potential risk factors, these following factors were reviewed; symptoms, comorbidities, tumor marker levels, stages, H. pylori status, locations, Lauren type, differentiation, complications, microsatellite instability and p53 overexpression. Results: Elevated levels of CA 19-9 (5.6%, 13.4% and 14.6%, P = 0.001), advanced diseases (42.5%, 47.0% and 57.6, P = 0.014), and node metastasis (37.6%, 38.9% and 51.5%, P = 0.029) were more frequently detected in the middle and old age groups. However, no significant differences in H. pylori status (63.6%, 56.7% and 61.2%, P = 0.324) were observed among the three groups. Elderly patients had a tendency to show intestinal type in Lauren’s classification (40.7%, 58.7%, and 56.6%, P &lt; 0.001). The rate of surgery-related complications did not differ among the three groups (5.3%, 5.1%, and 8.1%, P = 0.497). Microsatellite instability (P &lt; 0.001) and p53 overexpression (P &lt; 0.001) were more frequently found among the elderly patients. Conclusions: Gastric cancer in elderly patients was related to features known for favorable prognosis except p53 overexpression, despite the more advanced stage. Surgery in the elderly was as tolerable as in young patients. We recommend looking favorably upon surgery for elderly patients with operable gastric cancers.
A Selective ORAL GLYT1 Inhibitor, Improves Anemia and RED CELL Survival in a MOUSE MODEL of Beta-Thalassemia
Authors: Carlo Brugnara, Anja Harmeier, Lucia De Franceschi, Alessandro Matte, Michael Winter, Annette Koerner, Omar Khwaja, Thomas Singer, Elisabetta Beneduce, Enrica Federti, Angela Siciliano
Journal: Blood (2016)
Autologous heat shock protein vaccine (HSPPC-96) for patients with recurrent glioblastoma (GBM): Results of a phase II multicenter clinical trial with immunological assessments.
Authors: A. Parsa, C. Crane, S. Han, V. Kivett, A. Fedoroff, N. A. Butowski, S. M. Chang, J. L. Clarke, M. S. Berger, M. McDermott, M. Aghi, C. Yanes, M. Prados, A. E. Sloan, J. N. Bruce
Journal: Journal of Clinical Oncology (2011)

2565 Background: HSPPC-96 is derived from a patient’s individual tumor and contains glycoprotein-96 (gp96) polypeptide associated with cancer-specific antigenic peptides. Methods: This ongoing single-arm multicenter Phase 2 trial is designed to evaluate overall survival (primary objective) and immunologic response (secondary objective) with HSPPC-96 in patients with first or subsequent recurrence of GBM. Prior treatment with radiotherapy and temozolomide was required. All patients underwent a >90% resection of the recurrence. Vaccine therapy was to be initiated within 5 weeks post-surgery and consisted of 25 µg HSPPC-96, given ID weekly x 4, followed by bi-weekly injections for up to 52 weeks. Results: A total of 33 patients at first recurrence (M:F = 25:8) with a median KPS of 80 were entered. A median of 6 injections (range: 1-15) were administered to the ITT population, with a requisite of 4 vaccinations for the evaluable population. The vaccine was well tolerated with no attributed serious adverse events and no related grade 3 or 4 toxicities. Injection site reaction was seen in 12 patients and fatigue was reported in 9 patients. As of Jan. 2011, the median survival (KM estimates) is 324 days for ITT population (37-877) and 333 days for evaluable population (99-877). 11 patients are still alive and being followed, including 4 beyond one year (374d, 419d, 578d, and 877 days, respectively). All patients with immunological endpoints tested to date exhibited a signiﬁcant innate immune response and all patients demonstrated CD8 T cell IFN gamma production upon restimulation with autologous gp-96; following vaccine administration. Conclusions: HSPPC-96 evokes a speciﬁc and innate immune response in patients with recurrent glioma and survival data available to date indicates HSPPC-96 vaccine provides a possible clinical beneﬁt with a favorable safety proﬁle. Collectively these results provide the impetus for Phase 3 testing against currently approved therapies for patients with recurrent glioblastoma.
Treatment-related AML and AML evolving from MDS: Similar outcomes following treatment with amonafide plus cytarabine.
Authors: M. A. Sekeres, S. L. Allen, S. R. Mohan, A. S. Lundberg, H. P. Erba
Journal: Journal of Clinical Oncology (2010)

6582 Background: Secondary AML (sAML) is a well recognized poor prognostic factor in AML. sAML is a heterogeneous group of diseases, including both AML evolving from myelodysplastic syndromes (MDS→AML) and AML following chemotherapy for another malignancy, treatment-related AML (tAML). These two subtypes of poor risk AML have similar outcomes when treated with standard anthracycline-based chemotherapy, supporting their inclusion into the same clinical category. It is unknown whether this classification is valid when using experimental antileukemic agents. We therefore examined the outcomes of MDS→AML vs. tAML, following amonafide-based therapy. Methods: Patients (pts) received amonafide 600 mg/m2/day IV days 1-5 and cytarabine 200 mg/m2/day IV CI days 1-7. PRT included hematopoietic stem cell transplant (HSCT; n = 10) or cytarabine (intermediate dose, n = 13; or high dose, n = 7). The primary endpoint was CR/CRi; secondary endpoints were safety, DOR and OS. Cytogenetic classifications used modified SWOG-ECOG criteria. CR rates were compared using logistic regression (chi-squared test), DOR and OS were compared using Kaplan-Meier estimate (log rank test). Results: 88 pts with sAML were treated. 45 (51.1%) had tAML (5 pts had MDS→AML and tAML), and 48 (53.4%) had MDS→AML. Baseline characteristics were: tAML: 12 (27%) male, age 60 yrs (23-87), 35 (78%) ECOG 0-1, 37 (86%) unfavorable cytogenetics; MDS→AML: 29 (67%) male, age 66 yrs (24-81), 37 (86%) ECOG 0-1, 15 (35%) unfavorable cytogenetics. 37 pts (42%) achieved CR+CRi. CR+CRi rate was 18/45 (40%) for tAML pts and 19/43 (44.2%) for those with MDS→AML (p = 0.69). PRT was given to 16/18 tAML pts (89%, HSCT 5, HiDAC 4, IDAC 7), and 14/19 MDS→AML pts (74%, HSCT 5, HiDAC 3, IDAC 6). Median DOR: 512 d for tAML, 164 d for MDS→AML (p = 0.03) Median OS: 209 d tAML, 183 d MDS→AML (p = 0.09). Conclusions: tAML and MDS→AML are diseases with similar outcomes in response rate and overall survival following amonafide therapy, further supporting their inclusion together into a broad category of sAML, though duration of remission appears shorter for MDS→AML. These data validate sAML as an appropriate grouping when considering treatment options for these poor-risk patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Xanthus Xanthus
Safety and antitumor activity of selinexor (KPT-330), a first-in-class, oral XPO1 selective inhibitor of nuclear export: A phase I study expanded with colon cancer cohort.
Authors: Morten Mau-Soerensen, Albiruni R. A. Razak, Amit Mahipal, Hemchandra Mahaseth, John F. Gerecitano, Sharon Shacham, Cindy Y. F. Yau, Ulrik Lassen, Anthony Frank Shields, Dilara McCauley, Jennifer Cooksey, David Shao Peng Tan, Tami Rashal, Eran Shacham, Yosef Landesman, Gregory Pond, Amit M. Oza, Michael Kauffman, Lillian Siu, Mansoor Raza Mirza
Journal: Journal of Clinical Oncology (2014)

482 Background: Tumor suppressor proteins (TSPs) are inactivated by their export from the nucleus by Exportin1 (XPO1/CRM1). The oral selective inhibitor of nuclear export selinexor (KPT-330)restores the nuclear localization and function of TSPs and shows a broad anti-tumor activity in animal models. Here we report on the treatment of a subset of patients (pts) with metastatic colorectal cancer (CRC) in a phase I trial of selinexor. Methods: Objectives were to determine the recommended phase 2 dose, evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), and tumor response (RECIST 1.1) of selinexor administered in two different schedules with 8 or 10 doses in a 28-day cycle. An expansion cohort of 15 pts with CRC was planned. Results: Twenty-seven pts with CRC were treated across eight doses (3-40 mg/m 2 ) including 15 pts in the expansion cohort (30-35 mg/m 2 ). Median age was 61 yrs and median number of prior regimens was 4. MTD of the 10-dose schedule was 30 mg/m 2 . MTD for the 8-dose schedule has not been reached. Thirteen pts experienced drug related gr 3-4 adverse events (AEs) including fatigue (n = 6), hyponatremia (n = 5), thrombocytopenia (n = 3), anorexia (n = 3), dehydration (n = 2), anemia (n = 2), hyperglycemia (n = 1), pulmonary embolism (n = 1), and hypotension (n = 1). The most common gr 1-2 drug related AEs were nausea (74 %), anorexia (67 %), fatigue (67 %), vomiting (59 %), dysgeusia (52 %), and weight loss (48 %). C max increased with dose to ≈ 1.4 µM with T ½ of 4.0 – 7.4 hrs. Significant increases (2-20x) in PD marker XPO1 mRNA in circulating leukocytes were observed at all doses. Analysis of tumor biopsies confirmed nuclear localization of TSPs and induction of apoptosis following selinexor. CEA decreased in 4 of 12 pts. One pt had a partial response at 23 mg/m 2 , 6 patients had stable disease ≥8 weeks, and 3 patients had stable disease ≥24 weeks in 25 evaluable pts Conclusions: Preliminary signals of antitumor activity in CRC pts were observed. Selinexor is generally well tolerated and prolonged drug exposure is feasible. Selinexor induces Exportin in leucocytes and apoptosis in tumor biopsies with restoration of the nuclear location of TSPs. Clinical trial information: NCT01607905.
Clinicopathologic factors associated with the development of sunitinib induced hypertension (HTN) in patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Victoria Neiman, Maya Gottfried, Hans J. Hammers, Mario A. Eisenberger, Michael Anthony Carducci, Victoria J. Sinibaldi, Eli Rosenbaum, David Sarid, Eliahu Gez, Avivit Peer, Avivit Neumann, Svetlana Kovel, Avishay Sella, Wilmosh Mermershtain, Keren Rouvinov, Raanan Berger, Daniel Kejzman
Journal: Journal of Clinical Oncology (2014)

508 Background: The VEGFR inhibitor sunitinib is a standard treatment for metastatic renal cell carcinoma (mRCC). HTN, an on-target class effect of VEGF signaling-pathway inhibitors, has been shown to correlate with clinical outcome. Studies have shown the association between genetic polymorphisms in several genes, and the development of HTN in patients treated with targeted therapies. We aimed to study the association between readily available clinicopathologic factors and the development of sunitinib induced HTN in mRCC patients. Methods: Records from mRCC patients treated with sunitinib in 9 centers across 2 countries were retrospectively reviewed. Sunitinib induced HTN was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg. Analysis of the association between clinicopathologic factors and the development of HTN was performed using logistic regression. Results: Between 2004-2013, 302 patients with mRCC were treated with sunitinib. The incidence of sunitinib induced HTN was 50% (n=152). Clinicopathologic factors included in the analysis were age (median 63), gender (67% male), HENG risk (good 22%, intermediate 59%, poor 19%), smoking status (active 21%), BMI (obese=BMI ≥30, 28%; overweight=BMI 25-29.9, 37%; normal weight= BMI &lt;25, 35%), pre-treatment HTN (58%), past nephrectomy (83%), histology (73% clear cell), &gt; 1 metastatic site (82%), metastatic site (lung 72%, liver 25%, bones 40%), pre-treatment neutrophil to lymphocyte ratio (&gt;3 in 45%), treatment line (first vs advanced), sunitinib dose reduction/treatment interruption (45%). Absence of liver metastases (OR 3.5, p=0.02), pre-treatment neutrophil to lymphocyte ratio ≤ 3 (OR 5.5, p=0.001), and BMI (overweight and normal weight vs obese, OR 2.2 and 2.3 respectively, p=0.01 both) were independently associated with the development of HTN. Conclusions: In metastatic renal cell carcinoma patients treated with sunitinib, readily available clinicopathologic factors may be used to identify patients who are prone to the development of HTN.
An orthotopic model of fallopian tube serous carcinoma.
Authors: D. Khabele, A. Y. Liu, A. J. Wilson, O. Fadare, M. A. Crispens
Journal: Journal of Clinical Oncology (2011)

e15511 Background: Recent studies suggest that some high grade serous tumors of the pelvis, including a subset of ovarian serous carcinomas, originate from the fallopian tube (FT). These serous tumors typically harbor p53 mutations. Our goal was to develop an orthotopic model of metastatic FT carcinoma with characteristic features of serous pelvic tumors. Methods: After Institutional Review Board and Animal Care and Use Committee approvals, written informed consent was obtained from a patient with suspected metastatic pelvic carcinoma. At the time of surgery, non-necrotic tumors were transplanted via intraperitoneal (IP) injection into immunocompromised mice (passage, P1). Tumors were grown, harvested and re-implanted into a second cohort of mice (P2). Finally, tumors were passaged to a larger cohort (P3). P3 mice were treated with saline (n= 8) or cisplatin, 5mg/kg (n=8), weekly for 4 weeks. After sacrifice, tumors from each passage and treatment group were excised and frozen or paraffin-embedded. Patient information was obtained from the medical record. Results: The patient underwent optimal cytoreductive surgery for metastatic serous FT carcinoma in the presence of serous tubal intraepithelial carcinoma (STIC). The FT cancer, areas of STIC and a focus of normal FT, stained positive for p53 and mib-1. The patient was in remission after 6 months of taxane/platinum chemotherapy. IP tumor propagation was readily achieved up to P3 in the mice. Similar to the patient, orthotopic tumors were identified along peritoneal and mesenteric surfaces and confirmed by hematoxylin and eosin staining, p53 and mib-1. Cisplatin-treated mice had fewer tumor implants and fewer mib-1 stained cells compared to controls (p<0.05). Conclusions: Successful in vivo propagation of an orthotopic model of pelvic serous carcinoma arising from an identifiable precursor FT lesion was achieved. Histological characteristics of the patient’s metastatic FT cancer were maintained through P3 and the response to cisplatin in the mice reflected the patient’s response to therapy. This model is currently being used as a tool to study novel therapies for the treatment of p53 signature, serous carcinomas of the pelvis.
Etoposide and estramustine in previously treated hormone-refractory prostate cancer.
Authors: I. Pavese, M. DI Palma, M. Mazzoli, E. Burattini, F. Satta
Journal: Journal of Clinical Oncology (2011)

e15036 Background: It’s well known that in patients with hormone refractory prostate cancer (HRPC) who progressed after first line chemotherapy there are not a lot of therapeutic possibilities. Androgen and androgen receptor interactions are crucial for disease development and progression. In preclinical models the topoisomerase II inhibitor etoposide interfere with androgen mediated cell growth and reduce both intracellular and secreted PSA levels. So, etoposide can be considered not only classical cytotoxic drug but even an agent that directly targets androgen receptor function. Methods: 35 patients were enrolled. All had HRPC progressed after docetaxel and mitoxantrone, first and second line treatment respectively, and were almost asymptomatic (PS 0-1). Patients received oral estramustine (10 mg/kg/die) and intravenous etoposide (100 mg/mq/die 1-3 q21) until disease progression or grade 4 toxicity development. Disease progression was defined as rising PSA over 25% from base line or appearance of new lesions on radiological evaluation. PSA level was detected at every cycle. Median number of cycles administered was 4 (range 2-8). Results: 20 patients (57%) experienced a decreased level of PSA > 50% from baseline. Overall median time to progression was 15 weeks (range 3-35). Median survival of responders was 14 months, compared with 9 months for non responders. Observed toxicities (none more than grade 3) were thrombocytopenia, anemia, nausea and diarrhea, all easily manageable. Conclusions: We conclude that estramustine and etoposide is an active and well tolerated regimen in heavily pretreated and outpatient HRPC
A metabolic phenotyping approach to understanding relationships between metabolic syndrome and breast tumor responses to chemotherapy.
Authors: J. Stebbing, A. Sharma, B. North, T. J. Athersuch, A. Zebrowski, D. Pchejetski, R. C. Coombes, J. K. Nicholson, H. C. Keun
Journal: Journal of Clinical Oncology (2011)

10544 Background: Breast cancer is associated with adverse outcomes in patients with the metabolic syndrome phenotype. We previously demonstrated using a metabolic profiling (metabonomics) approach that glucose, lactate and alanine levels were perturbed during chemotherapy and that these effects were associated with weight gain during treatment. To validate these data and study this further, we examined the relationship between serum metabolite levels and the components of metabolic syndrome with treatment outcomes in breast cancer. Methods: A total of 88 women with measurable breast cancer were studied; their serum metabolites as assessed by 1H NMR spectroscopy, blood pressure, lipids, glucose, body mass index and waist circumference were recorded and correlated with treatment response. Results: We identified metabolic syndrome in approximately half of our cohort (42 patients) and observed a significant trend (p=0.03) of increased incidence of metabolic syndrome in partial response (33.3%), stable disease (42.9%) and progressive disease groups (66.1%). Of the components of metabolic syndrome, high blood sugar predicted a poor response (p < 0.001). Logistic regression of metabonomic data demonstrated that high lactate (p=0.03) and low alanine (p=0.01), combined with high glucose (p=0.01) in the same sera, were associated with disease progression. Conclusions: Metabolic syndrome is commonly observed in women with metastatic breast cancer and these patients have poorer outcomes. These data, which support our previous findings suggest that high blood glucose as part of metabolic syndrome is associated with a poor response in breast cancer. They also validate new therapeutic approaches that focus on metabolism.
Effect of in-vivo hepatitis B viral load suppression after interferon exposure on natural killer and T-cell responsiveness
Authors: Upkar S Gill, Dimitra Peppa, Lorenzo Micco, Harsimran D Singh, Nina Le Bert, Laura Rivino, Kamini Kunasegaran, Damien Tan, Antonio Bertoletti, Mala K Maini, Patrick T F Kennedy
Journal: The Lancet (2017)