tbuckley/cabot-search huggingface dataset:
A phase II study of bortezomib with ifosfamide and vinorelbine in pediatric patients with refractory/recurrent Hodgkin disease (HD): A Children's Oncology Group (COG) study.
Authors: T. M. Horton, R. A. Drachtman, L. Chen, T. M. Trippett, P. De Alarcon, A. R. Chen, R. P. Guillerman, K. McCarten, S. M. Hogan, C. L. Schwartz
Journal: Journal of Clinical Oncology (2010)

9537 Background: Bortezomib is a 26S proteasome inhibitor that inhibits NF-kB, which is essential for HD transformation. Bortezomib is effective for the treatment of adults with indolent lymphomas, and is well tolerated in pediatric patients with solid tumors. This phase 2 study examined the tolerability and efficacy of bortezomib with ifosfamide and vinorelbine (IV) in pediatric patients with recurrent/refractory HD. Methods: Patients received bortezomib twice weekly (1.2 mg/m2/dose, days 1, 4 and 8) with ifosfamide (3g/m2/day, days 1-4) and vinorelbine (25mg/m2/dose, days 1 and 5). Primary response was determined by CT after 2 cycles. Secondary endpoints, including 2-cycle PET response and 4-cycle CT/PET response, and CD34 stem cell mobilization, were also assessed. Results: 23 evaluable patients (10 females, 13 males), median age 16y (range 11-20y) completed a total of 77 cycles of therapy. Patients tolerated therapy well; Grade 3 and 4 toxicities included Grade 3 febrile neutropenia (2), Grade 3 nausea/vomiting (3), Grade 3 hypokalemia (7), and Grade 3 peripheral neuropathy (1) that occurred with G-CSF, but did not recur in subsequent bortezomib cycles when G-CSF was omitted. Two 2-cycle CR (as measured by CT) were reported by QARC central review. 2-cycle PET response was 11/22 (50%) for patients having a negative PET and 14/22 (64%) for patients having a negative or equivocal (SVU<5) PET. Four-cycle CT-based response rates (including those who did not continue to cycle 4 due to CR or PD after 2-3 cycles) were 11/18 (61%) by QARC review and 15/20 (75%) by site review. A CR or PR response rate by PET/CT was achieved after 2-4 cycles of bortezomib-containing therapy in 21/23 (91%) patients. This compares favorably to a 70% response rate in COG trials in patients with relapsed HD. Conclusions: Since the primary endpoint for the study was 2-cycle CR response rate by CT, the study was closed after 23 patients as per protocol interim monitoring rules. Although 2-cycle CT response was no better than in previous trials, PET data indicate that bortezomib may be effective in treatment of Hodgkin lymphoma and a randomized trial of IV vs. IV with bortezomib is warranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millennium
Comparison of p53, <i>K-ras,</i> and HER2/neu expression in nonneoplastic gall bladder epithelium and gall bladder cancer (GBC) epithelium: A pilot study.
Authors: A. D. Dwary, A. Sharma, S. D. Gupta, S. Pal, S. V. S. Deo, S. Thulkar
Journal: Journal of Clinical Oncology (2011)

e14511 Background: GBC carcinogenesis is a multi step process, involving increasing genetic disarray accumulated over a long time. In view of aggressive nature of GBC and lack of good therapeutics, there is an urgent need for identification of cancer specific cellular targets which form the basis of translational therapeutics in future. This study was undertaken to evaluate the presence of some previously described genes in GBC. Goal was Comparison of immunohistochemical demonstration of p53, K-ras and HER2/neu expression between non neoplastic GB epithelium, and GB cancer epithelium. Methods: This was a single center, pilot study. Duration was from November 2006 to July 2008. Total number of sample size planned was 40 (20 cases and 20 controls). As a first step, positive controls for all these antibodies were selected by applying antibodies. Next step was deparaffinizing.Three immunohistochemical stains were applied, which were p-53 (MS Diagnostics), HER-2/neu (MS Diagnostics) and K-ras (MS Diagnostics). Technique applied was high temperature antigen unmasking principle. Counterstaining was done with haematoxylin and sections were mounted with DPX. Nuclear staining for p53 was considered positive. For HER2/neu only membrane staining (>10%) was taken as positive. Any cytoplasmic staining for K-ras was taken as positive. Results: Numbers of cases analyzed were 18. Total numbers of controls analyzed were 20. p53 protein overexpression was seen in 9 out of 18 cases (50%) vs. 4 out of 20 in control group (20%) (p = 0.09). K-ras was expressed in 3 out of 18 cases (16.7%). None of the control group showed K-ras expression. (p=0.09).Her2/neu 3+ positivity was seen in 2 (11.1%) of cases. None of the control group showed HER2/neu 3+ positivity (p=0.99). Only two patients had co-expression of both p53 and HER2/neu. This possibly suggests their independent role in GB carcinogenesis. Conclusions: p53, Her2/neu and K-ras are more expressed in GB cancers as compared to normal GB epithelium. However further study with large sample size is required to validate these results and to suggest their clinical and prognostic significance.
Gestational diabetes and risk of incident primary cancer: A large population-based cohort study in Israel.
Authors: T. Sella, G. Chodick, M. Barchana, A. D. Heymann, A. Porath, E. Kokia, V. Shalev
Journal: Journal of Clinical Oncology (2011)

1538 Background: Gestational diabetes mellitus, a state of glucose intolerance associated with pregnancy is increasing in prevalence. Data regarding the risk associated with Gestational diabetes is sparse and conflicting. The current study was conducted to examine the risk of incident over-all and site-specific malignancies associated with a history of gestational diabetes mellitus in a historical cohort study of women in Maccabi Healthcare Services, a large health maintenance organization in Israel. Methods: All women aged 15 to 50 years who underwent 50g glucose challenge tests between March 13, 1995 and May 27, 2009, without history of malignancy, diabetes or infertility were included. Clinical and demographic parameters at index date including age, socioeconomic level, BMI and parity were collected. Diagnosis of gestational diabetes was based on the 100g oral glucose tolerance test using the standard Carpenter & Coustan criteria. The main endpoint of the study was a diagnosis of cancer obtained from the Israel Cancer Register through linkage data. Results: Among the 185,315 women who had undergone glucose challenge during the study period, 11,264 (6.1%) were diagnosed with gestational diabetes. During a total follow-up period of 1.05 million person years, 2034 incident cases of cancer were identified. GDM was associated with a hazard ratio (HR) of 7.12 (95% CI: 1.71-29.67) for pancreatic cancer and a HR of 1.69 (95% CI: 0.96-2.97) for hematological malignancies. The association between GDM and hematological malignancies was limited to women with five or more years of follow-up (HR=4.43; 1.79-10.96). Conclusions: Gestational diabetes mellitus is strongly associated with an increased long-term risk of pancreatic cancer and probably with hematologic malignancies.
Gemcitabine and oxaliplatin combination as the first-line treatment in advanced pancreatic cancer: A multicenter phase II study
Authors: K. Lee, M. Kim, Y. Kim, B. Ryoo, H. Lim, H. Song, H. Kim, M. Lee, S. Im, H. Chang, J. Cho
Journal: Journal of Clinical Oncology (2008)

15618 Background: Gemcitabine is the only drug approved for use as a single-agent therapy in advanced pancreatic carcinoma (APC). However, gemcitabine-based combination chemotherapy still has not shown promising results. Methods: Previously untreated and locally advanced and/or metastatic pancreatic adenocarcinoma patients were enrolled in this multi-center phase II study. Patients received 1,000mg/m2 gemcitabine(GEM) I.V. as a 100-minute infusionon day 1 and 100 mg/m2 oxaliplatin(OXA) I.V. as a 2-hour infusion on day 2 of a 2-week cycle. The primary endpoint of this trial was the response rate. Quality of life was assessed using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30). Results: Among 48 eligible patients included from 13 centers, 44 were evaluable. The response rate for the 44 patients was 18.2%. No complete responses (CR), 8 partial responses (PR), and 19 stable disease (SD) states were observed. Median overall survival (OS) and median time to progression (TTP) were 9.4 months(95% C.I. 6.43, -) and 5.6 months (95% C.I. 2.80–5.90), respectively. Among 44 assessable patients, 16 patients (36.4%) experienced clinical benefits. Between baseline and the end of treatment, patients showed improvement in global, functional, and symptomatic scales of the EORTC QLQ-C30. These improvement were maintained regardless of disease progression or survival time. In a total of 336 treatment cycles (median per patient, 7 range, 1–5), grade 3/4 toxicity per patient was 6.3% for neutropenia, 2.1% for thrombocytopenia, 6.3% for anemia, and 2.1% for peripheral neuropathy, with no treatment-related death. Conclusions: The combination of GEM and OXA was well-tolerated and showed promising activity in patients with APC. Based on the results of this study, further controlled investigations to confirm its efficacy are warranted. No significant financial relationships to disclose.
Real-world clinical resource utilization of metastatic prostate cancer patients in the United States: Results from two large claims databases.
Authors: M. Lafeuille, M. Senbetta, R. S. McKenzie, P. Lefebvre
Journal: Journal of Clinical Oncology (2011)

204 Background: In metastatic prostate cancer (MPC) patients, treatment options include hormonal therapies, chemotherapy, and radiotherapy. This study quantifies the real-world healthcare resource utilization of MPC patients. Methods: Health insurance claims from 40 self-insured companies across the US (Employer [E]; 01/1999-02/2009), and from the Medicare 5% ([M]; 1999-2008) databases were analyzed. Patients with a metastasis diagnosis (ICD-9: 196-199) following 2 prostate cancer diagnoses (ICD-9: 185, V10.46) within 365 days were identified. Patients with other malignant diagnoses at baseline, defined as 365 days prior to metastasis diagnosis (index date), were excluded. Patients were evaluated for baseline medical history and for chemotherapy, hormonal agents, radiation, and corticosteroids utilization during both baseline and observation periods. Hospitalization rates and prostate cancer-related procedures post index date were also reported. Results: The study population comprised 11,725 patients (E: 3,227; M: 8,498). Mean age (SD) was 72.8 (10.2) in Employer and 78.1 (7.7) in Medicare. Mean observation period (SD) was 803 (753) days in Employer and 9.2 (8.2) quarters in Medicare. During the baseline period, chemotherapy, hormonal agents, radiation therapy, and corticosteroids were administered to 5%, 52%, 9%, and 21% of Employer, and 2%, 45%, 8%, and 12% of Medicare patients respectively, whereas these interventions increased to 22%, 55%, 39%, and 46% for Employer, and to 21%, 50%, 33%, and 29% for Medicare during the observation period. A total of 66% Employer and 79% Medicare patients were hospitalized post index date. Most patients (E: 92%; M: 98%) had prostate cancer-related procedures, including prostate specific-antigen testing (E: 39%; M: 80%), computerized axial tomography scan (E: 72%; M: 81%), prostate biopsy (E: 47%; M: 54%), X-ray (E: 11%; M: 64%), bone scan (E: 56%; M: 60%), and magnetic resonance imaging scan (E: 35%; M: 37%). Conclusions: This observational study describes real-world utilization patterns in patients with advanced prostate cancer. [Table: see text]
Hyperfractionated/accelerated thoracic radiation therapy (HFXRT) increased survival compared to daily RT (QDRT) for limited small cell lung cancer (LSCLC) with Concurrent Chemotherapy (ChT)
Authors: R. Komaki, P. Allen, B. Glisson, C. Lu, F. Fossella, Z. Liao, M. Jeter, C. Stevens, J. Chang, T. Guerrero, G. Blumenschein
Journal: Journal of Clinical Oncology (2005)

7158 Background: HFXRT has not been commonly used in community practice despite better 5-yr survival compared to QDRT with concurrent cisplatin and etoposide by randomized study. Methods: CT-staged LSCLC pts treated by HFXRT or QDRT with cisplatin-based ChT between 1985–1998 were reviewed. Complete responders received prophylactic cranial irradiation (PCI). The data were analyzed by Kaplan-Meier survival function and the Log Rank test. Results: 324 pts were treated and followed from 3–156M (median 47M). Median age: 60. Male (53%), KPS 90–100 (71%), wt loss <5% (80%). Pleural effusion (PE) in 24%. 217 received QDRT: median dose 50Gy/5W. 107 received HFXRT: median dose 45Gy/3W. 168 received PCI: 108 in QD group and 60 in HFXRT group. 5 yr-OS: 25% by HFXRT vs 12% by QDRT (p=0.02). In PCI pts, 5yr OS: 32.3% by HFXRT vs 18.9% by QDRT (p=0.02). MS of 24M by HFXRT vs 18M by QDRT. Acute Gr 3 esophagitis: 21.5% by HFXRT vs 9.2% QDRT (p=0.002). Gr 3 lung fibrosis: 30.8% by HFXRT vs 12.4% by QDRT (p< 0.0001). Multivariate analysis showed factors influencing OS were PCI (p=0.001), HFXRT (p<0.0001), and PE (p<0.0001). Conclusions: This retrospective study showed that OS was improved by concurrent ChT and HFXRT compared to QDRT and application of PCI. It is important to reduce normal tissue toxicities in the future when HFXRT and concurrent ChT are applied. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca MedImmune Speakers Bureau
Understanding prostate cancer survivorship relative to co-habitation.
Authors: Darryl Mitteldorf
Journal: Journal of Clinical Oncology (2016)

253 Background: Studies suggest that married men diagnosed with prostate cancer survive longer than single men. None of the published research shows why this might be the case. Nothing is known about how treatment choice satisfaction and aspects of the psycho-social experience might differ between single and married men. Our aim was to understand if there are any differences in key indicators which might influence survivorship between single and married or partnered men. Methods: 1,762 men diagnosed with prostate cancer completed a lengthy online survey during a one month in 2014. The men were randomly selected from a national Prostate Cancer support group network. We investigated compliance and satisfaction in their treatment choices, activities of life satisfaction, spirituality and overall life sentiment. We included questions relating to the length of time between diagnosis and the survey and the size and location of the respondents community. We stratified each question by whether or not a person lived alone or was married or partnered or lived in some other communal situation. Results: There were no significant differences in diagnosis years by living status. A higher proportion of people with prostate cancer who live alone get more than 3 days per week strenuous exercise than those who live in communal situations. 20.26% of men who live alone exercised seven days, while only 14.24% of the married/partnered group exercised as much We used the CORR procedure in SAS to determine if a correlation existed between answers to specific questions and whether or not a person lived alone. Very few response patterns were correlated with being alone. No question in the survey was able to produce a correlation greater than 0.31. A feeling of loneliness was most correlated with being alone (r = 0.302). Trouble urinating (r = 0.24134) and trouble moving one’s bowels (r = 0.16904) were also mildly correlated with being single. Conclusions: Our study shows that being married, partnered or single is irrelevant to prostate cancer survivorship. Our results suggest that we have to look for reasons unrelated to personal relationships and household composition to understand why married men diagnosed with prostate cancer hold a longevity advantage over single men.
Efficacy and improved toxicity profile of once a week bortezomib (BZ) with dexamethasone (dex) in newly diagnosed multiple myeloma (NDMM) patients (pts) with older age and comorbidities: Preliminary results of an ongoing clinical study.
Authors: N. C. Munshi, S. Lee, S. Kambhampati, A. Mohiuddin, M. G. Rose, C. Behler, A. Han, Y. A. Efebera, A. Houranieh, M. T. Brophy, A. Zimelman, R. H. Prabhala, T. Grady, C. E. Klein, P. Mehta, T. G. Hayes, G. D. Roodman, A. Lichtenstein
Journal: Journal of Clinical Oncology (2011)

8074^ Background: The current BZ regimen administered twice a week for 2 weeks with one week off is effective, however is inconvenient and associated with toxicities such as neuropathy. To improve convenience and compliance, we have investigated the efficacy and safety of a weekly BZ regimen. Methods: In this phase II multi-center single-arm study BZ is administered at 1.6 mg/m2 IV weekly for 4 weeks with 1 week off with dex 40mg PO on the day of and day after BZ for upto 6 cycles in NDMM pts not considered for autologous stem cell transplant in participating Veterans Hospitals (VA) nationwide. The objective is to evaluate overall response rate (ORR) and toxicity of this regimen. Results: Currently 41 pts (median age-71; range 50-89) have been enrolled at 12 VA Hospitals. Pts had significant co-morbidities including 83% with cardiovascular problems, 44% with respiratory problems, 66% with diabetes and/or hyperlipidemia, 51% with renal dysfunction, 15% with history of cancer. All pts were on at least 5 daily medications. Of the 41 pts enrolled, 33 pts have received at least 1 cycle of therapy and were evaluable for toxicity and efficacy. With a median of 4 cycles administered, this regimen was well tolerated. One pt developed grade 3 neuropathy while 3 pts experienced grade 1 and one patient with grade 1 neuropathy at diagnosis had increased to grade 2. Dex dose was reduced in 32% while BZ dose was reduced in 10% of the pts. Additionally, grade ≥1 asthenia was observed in 51%, constipation in 42%, diarrhea in 32%, anemia in 42%, and thrombocytopenia in 34%. Four pts have died of co-morbidities which were considered unrelated or probably unrelated to the treatment with BZ. Of the pts who received at least 1 cycle of therapy, 64% pts achieved ≥PR; 15% CR/nCR and an additional 15% achieved VGPR. Including MR in the analysis, ORR was observed in 97% of the evaluable pts. On intent to treat analysis including all 41 pts, ORR was observed in 78% pts and ≥ PR in 51% pts. Conclusions: These preliminary results point to the effectiveness and tolerability of the once a week BZ regimen even in older pts with significant co-morbidities.
Correlation of kinetic analysis of <sup>18</sup>f-fluoroerythronitroimidazole PET/CT during radiotherapy with outcome in head and neck cancer.
Authors: M. Hu, J. Yu, L. Kong, Z. Fu
Journal: Journal of Clinical Oncology (2011)

5554 Background: Tumor hypoxia is considered to be important prognostic factor, as well as associatedwith an increased likelihood of local recurrence and distantmetastasis in head and neck cancer (HNC). The purpose of the study was to evaluate how changes in tumor hypoxia during radiotherapy (RT) and their impact on patient outcome, according to kinetic 18F-Fluoroerythronitroimidazole (18F-FETNIM) positron emission tomography/computed tomography (PET/CT) imaging. Methods: Twenty-one patients with HNC were enrolled in the study. Patients were treated with intensity-modulated RT (IMRT), with or without chemotherapy per standard of care based on the stage of disease. All patients underwent repeated 18F-FETNIM PET/CT prior to radiotherapy and after approximately 50Gy. 18F-FETNIM uptake was quantified by calculating maximum standard uptake value (SUVmax) and hypoxia volume (HV) of primary tumor. Both SUVmax and HV in scan of prior to radiotherapy were correlated with patient outcome. All patients were followed up every 3 months after treatment completion. The follow up time was in the range of 6-30 months (median: 23.6 months). Results: The mean SUVmax and the HV decreased significantly during radiotherapy. SUVmax decreased clearly in 19/21 patients, increased in 1 patients and unchanged in 1 patients. HV decreased clearly in all patients. SUVmax, determined prior to radiotherapy separated patients according to failure and progression free survival (PFS). The significance for SUVmax was only weak p = 0.044, whereas the HV showed a significance (p = 0.025). Conclusions: The changes in primary tumor 18F-FETNIM uptake during fractionated radiotherapy indicate radio-induced reoxygenation. Our data demonstrate the relevance of 18F-FETNIM uptake in tumor for the prognosis of patients with head and neck cancer after radiotherapy.
Endothelial CD99 supports arrest of mouse neutrophils in venules and binds to neutrophil PILRs
Authors: Debashree Goswami, Sigrid März, Yu-Tung Li, Annette Artz, Kerstin Schäfer, Ruth Seelige, Mariana Pacheco-Blanco, Ding Jing, Maria Gabriele Bixel, Masatake Araki, Kimi Araki, Ken-Ichi Yamamura, Dietmar Vestweber
Journal: Blood (2017)
The role of the radiation oncologist in goals-of-care discussions.
Authors: Lauren C. Das, Christina H. Son, Ellen Wasgatt Daily, Stacie K. Levine, Olwen Mary Hahn, Stanley L. Liauw, Daniel William Golden
Journal: Journal of Clinical Oncology (2015)

42 Background: Effective goals-of-care discussions (GOCD) are essential when counseling patients with incurable malignancies. Because radiation and medical oncologists (RO; MO) often collaborate, their respective roles in GOCD can be unclear. This study aims to explore how often MO and RO initiate GOCD, barriers to GOCD, and MO opinions of RO conducting GOCD. Methods: RO and MO at NCI-designated comprehensive cancer centers were invited to participate in an anonymous electronic survey. The survey collected demographics and opinions regarding GOCD, training in conducting GOCD, and 3 case scenarios. The participants were provided with the GOCD definition: “A goals-of care discussion defines a patient's expected prognosis, elicits his or her values and preferences, and considers these preferences in formulating a recommendation for treatment and/or supportive care.” Response formats were Yes/No, Likert, or free response. Statistical analysis was performed with chi-squared and Wilcoxon rank-sum tests. Likert scores are reported as median[interquartile range]. Results: 554 RO and 1604 MO were successfully sent survey invitations. 76 (13.7%) RO and 153 (9.5%) MO responded with complete surveys. There was no difference in the gender distribution of survey respondents for RO and MO (67% vs 59% male, p = 0.26). Practice setting was academic medical center for 93% of respondents. 91% of respondents reported seeing ≤ 10 new cancer patients a week. MO were more likely to see metastatic or incurable patients. 63% of RO and 66% of MO reported having GOCD with &gt; 50% of their patients (p = .94). MO were more comfortable conducting GOC discussions compared with RO (5[4-5] vs 4[3-5], p &lt; .01). When asked how important it was for RO to conduct GOCD, RO ratings were higher than MO (5[4-5] vs 4[3-5], p = .02). 18% of RO and 42% of MO received formal training conducting GOCD (p &lt; .01). The most common factors for initiating a GOCD were declining performance status (74%) and poor estimated life expectancy (69%). Conclusions: Although MO and RO conduct GOCD in similar frequency, MO report being more comfortable conducting GOCD and are more likely to have formal training. Compared to MO, RO rate the importance of RO conducting GOCD higher.