tbuckley/cabot-search huggingface dataset:
Rational use of intensity-modulated radiation therapy (IMRT) as determined by radiation oncologists in cooperation with Blue Cross Blue Shield of Massachusetts (BCBSMA).
Authors: Harvey J. Mamon, Lee Steingisser, John Fallon, Gerard Walsh, Joseph O. Jacobson
Journal: Journal of Clinical Oncology (2012)

73 Background: IMRT is a sophisticated radiation technique that allows more precise delivery than conventional external beam radiation (EBRT). Prospective randomized data indicating which patients are most likely to benefit from IMRT are limited, and the rate of IMRT utilization varies widely. Methods: BCBSMA reached out to radiation oncologists to develop a consensus regarding the use of IMRT. Initial discussions started in 2009. The process included discussions within radiation oncology departments and meetings and conference calls with BCBSMA. In April 2011 a survey was sent to radiation oncologists, followed by the formation of a Physician Advisory Council consisting of representatives of 11 large academic and private practices. The council met in June 2011 and continued to develop guidelines over a series of conference calls. Results: The BCBSMA IMRT policies went into effect on 9/1/11. No policies for the use of EBRT were created. It was agreed that IMRT is appropriate for cancers of the head and neck, prostate, and anus. For other sites, emphasis was placed on the QUANTEC recommendations regarding acceptable doses to normal tissues. To justify the use of IMRT, radiation oncologists were asked to demonstrate that conventional EBRT resulted in excess dose to normal tissues, and that IMRT could lower the doses to an acceptable range. In addition, a process was set up for peer-to-peer review to consider the application of IMRT to cases outside of the guidelines. Preliminary analysis of claims compared the case rat /1,000 BCBSMA members over a 6 month pre-IMRT policy implementation base period to a 6 month post-implementation case rate. The number of IMRT cases during the study period was decreased by 20% while the EBRT cases/1,000 members during the study period increased by 14%. During the two prior years, the IMRT cases/1,000 members for IMRT increased 20%, while the EBRT cases/1000 members decreased 3%. Conclusions: The experience in Massachusetts suggests that practicing physicians and insurers can work together to achieve a consensus regarding the appropriate application of high-technology treatments potentially impacting their rate of utilization.
Phase I/II trial of gefitinib and RAD001 (everolimus) in patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: D. T. Milton, M. G. Kris, C. G. Azzoli, J. E. Gomez, R. Heelan, L. M. Krug, W. Pao, B. Pizzo, N. A. Rizvi, V. A. Miller
Journal: Journal of Clinical Oncology (2005)

7104 Background: The mechanisms of resistance to EGFR tyrosine kinase inhibitors remain poorly understood but may be related, in part, to dysregulation of downstream apoptotic pathways, such as the PI3K/Akt/PTEN axis. In preclinical models, inhibition of the PI3K/Akt pathway restores gefitinib (Iressa™) sensitivity in resistant cell lines. mTOR is a serine/threonine kinase located downstream of Akt that regulates cellular growth and G1/S cell cycle progression. RAD001 is an orally available mTOR inhibitor that inhibits growth of cancer cell lines, including A549. We undertook this phase I/II study to characterize the safety, pharmacokinetics (PK), and antitumor activity of the combination of gefitinib and RAD001 in pts with advanced NSCLC with no prior history of EGFR-directed therapy. Methods: Phase I: 3-pt cohorts with no intrapatient escalation, at RAD001 dose levels of 5 and 10 mg daily. All pts received gefitinib 250 mg daily. PK studies were performed over a 3-week period during which pts received a single dose of RAD001 on day 1, followed by daily gefitinib on day 8, and then daily RAD001 on day 22. 6 pts will be treated at the MTD or highest RAD001 dose level prior to expanding to the phase II portion. Results: 6 pts have been enrolled to date. Patient characteristics: Female: 3; Karnofsky Performance Status median 80%; age median 62; prior chemotherapy median 2 (1–4). Toxicity (≥ Grade 2): by RAD001 dose level, 5 mg (n=3): 1 patient developed G2 stomatitis; 10 mg (n=3): 1 pt developed G2 diarrhea and G3 stomatitis, 1 pt developed G3 diarrhea, hypokalemia, and creatinine elevation, and G4 acidosis. Preliminary PK studies demonstrate AUC ratios (combination/alone) of 1.32 ± 0.46 for RAD001 and 1.15 ± 0.14 for gefitinib. Within the 5 mg dose level, a 25 pack-year smoking male pt with squamous cell carcinoma experienced a confirmed partial response; no EGFR exon 19 or 21 mutation was identified. Conclusions: 2 patients experienced dose-limiting toxicity (DLT) in the 10 mg dose level. 3 more patients will be enrolled in the RAD001 5 mg dose level prior to expanding to the phase II portion. Preliminary PK data suggests no significant interactions between the agents. Supported, in part, by Novartis. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Novartis AstraZeneca, Novartis AstraZeneca
The Unique Pattern of Somatic Imprint in Oct-4+ Very Small Embryonic Like (VSEL) Stem Cells Isolated from Adult Tissues Further Supports Both Their Epiblast/Germ Line Origin and Explains Quiescent Status: Potential Modification of Somatic Imprint as a Key to Longevity?
Authors: Dong-Myung Shin, Ewa K Zuba-Surma, Mariusz Z Ratajczak, Magdalena Kucia
Journal: Blood (2008)
Correlation of acid ceramidase (AC), a key enzyme of the sphingolipid metabolism, with prognosis in epithelial ovarian cancer.
Authors: L. C. Hanker, E. Ruckhäberle, T. Karn, U. Holtrich, R. Gaetje, N. Sänger, A. Rody, K. Engels, M. Kaufmann
Journal: Journal of Clinical Oncology (2011)

e15562 Background: Acid ceramidase (AC), a key enzyme of sphingolipid metabolism, plays an important role in cancer progression. Objective of this study was to explore the expression of AC in ovarian cancer and its relationship with prognosis. Methods: The expression of AC in n=119 ovarian cancer patients was determined by immunohistochemistry and correlated to clinical and pathological characteristics as well as survival. Results: Low AC expression was independently associated with reduced progression-free survival of 14 (CI95%: 9.20-18.8) vs. 19.6 (CI95%: 11.1-28.1) months (p=0.004) as well as reduced overall survival of 41.2 (CI95%: 30.7-51.7) months versus 58.1 (CI 95%: 34.6-81.6) months (p=0.096). In multivariate analysis AC presents as independent prognostic factor for PFS (HR 1.70; CI95%: 1.00-2.88, p=0.05) and OS (HR 1.44; CI95%: 0.80-2.62, P=0.23). Conclusions: Acid ceramidase is an independant prognostic factor in epithelial ovarian cancer. Low AC expression is associated with tumour progression in ovarian carcinoma. These results are in contrast to the concept of AC as an promoter for tumor progression, but are supported by the tumour-suppressing and proapoptotic function of the enzymatic product of AC, i.e. sphingosine (SPH) in various cancer types.
Evaluation of local control and toxicities in carcinoma cervix, treated with EBRT &amp; HDR intracavitory radiotherapy
Authors: H. U. Ghori, O. P. Singh, V. Yogi, A. P. Mathur, J. P. Sharma
Journal: Journal of Clinical Oncology (2008)

16583 Background: Carcinoma cervix is the commonest malignancy in the Indian women Most of the patients present in the advanced stage of the disease. Radiotherapy is the important primary modality of treatment. in most patient of ca. cervix. Judicious combination of external beam radiotherapy (EBRT) and Brach therapy can give maximum benefits to the pt with acceptable limit dose to the bladder and rectum. Method: We include 50 patient of ca. cervix, advanced stage with proven histopathology of sq.cell ca. Patient with normal hematological and biochemical parameters with good performance status included in this study. They were divided in two group. Pt. in group A received EBRT 46 Gy by Telecobalt to the pelvis in conventional fractionations scheduled followed by ICRT by HDR, 6 Gy/ fraction, per week upto 5 fractions. Pt. In group B received EBRT 46 Gy by Telecobalt to the pelvis in conventional fractionation. ICRT by HDR, first fraction deliverd from third week of treatment with 6Gy per fraction per week up to five fractions. Local control and toxicities analyzed. Result: Patient shows good response to the treatment. After follow up at one yr pt shows slightly better control in group B with slightly increased toxicities of rectum& bladder in group B. Conclusion: Judicious combination of EBRT & ICRT in Carcinoma Cervix gives better tumors control with acceptable toxicities. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Gandhi Medical College Government of M.P. Bhopal
Analysis of patients (pts) with chronic phase chronic myeloid leukemia (CML-CP) who develop pleural effusion on first-line dasatinib: Management and outcomes.
Authors: P. Laneuville, M. Baccarani, J. E. Cortes, A. Hochhaus, H. Kantarjian, N. P. Shah, M. B. Bradley-Garelik, C. Zhu, K. Porkka
Journal: Journal of Clinical Oncology (2011)

6605 Background: At 18 months (mos) of follow-up in the randomized phase 3 DASISION trial of dasatinib vs imatinib (IM) in newly diagnosed CML-CP, dasatinib continued to show superior efficacy and acceptable safety/tolerability (Shah et al. Blood 2010; 116: abs 206). Although fluid retention was more frequent with IM, pleural effusion was only seen with dasatinib. Here, pts with drug-related pleural effusion are analyzed retrospectively and management methods are discussed. Methods: In DASISION, pts received dasatinib 100 mg once daily (QD) or IM 400 mg QD. Pts with baseline pleural effusion were excluded. Chest x-rays were performed at baseline and after 6 mos, or more frequently if indicated clinically. Pleural effusions were graded according to CTCAE v3.0 criteria. Results: After 18 mos median treatment duration, 31/258 dasatinib-treated pts had a pleural effusion (12%; 3% grade 1, 9% grade 2, <1% grade 3). Pts with pleural effusion were older (median age 59 vs 44 yrs). In pts with (n=31) vs without (n=227) pleural effusion, Hasford risk score was intermediate in 68% vs 45% and high in 10% vs 20%, and median dasatinib dose was 93 vs 100 mg/d. Most effusions (87%) occurred beyond 8 weeks of treatment (median time to event: 33 weeks). Pleural effusions were managed by dose modification (interruption in 24 pts; reduction in 13 pts) and/or medical intervention (diuretics in 13 pts; corticosteroids in 11 pts; therapeutic thoracentesis in 3 pts). 4 pts (1.5%) discontinued therapy due to pleural effusion. To date, most effusions (84%) have not recurred. Based on consensus from an expert panel, a management algorithm will be presented. Of pts with pleural effusion, 94% and 65% achieved a complete cytogenetic response and major molecular response, respectively (vs 84% and 56% in pts with no pleural effusion). In pts with or without pleural effusion, peripheral lymphocytosis was noted in 42% vs 19%. Conclusions: At 18 mos in pts receiving first-line dasatinib in DASISION, pleural effusion was predominantly mild to moderate in severity, more commonly associated with lymphocytosis, managed by dose modification and/or medical intervention, and did not appear to impact efficacy.
Change of skeletal muscle index during the chemotherapy as a prognostic factor of survival in pancreatic cancer patients receiving palliative chemotherapy.
Authors: Younak Choi, Tae Yong Kim, Kyung-Hun Lee, Sae-Won Han, Do-Youn Oh, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2015)

363 Background: Body composition has emerged as a prognostic factor in cancer patients. We investigated whether sarcopenia at the diagnosis and progressive loss of skeletal muscle were associated with survival in pancreatic cancer (PC) patients receiving palliative chemotherapy. Methods: We retrospectively reviewed PC patients receiving palliative chemotherapy between 2003 and 2010. Skeletal muscle cross-sectional area at L3 was measured by computed tomography. Sarcopenia was defined using the previously published sex-specific cutoff points for Korean people. Loss of skeletal muscle was classified by sex-specific cutoffs from ROC curve. Results: Among 484 patients, 260 (53.7%) patients were more than sixty years old and 295 (61.0%) patients were male. Overall, 187 (38.6%) patients were sarcopenic at the diagnosis (male, &lt;49.2cm 2 /m 2 ; female, &lt;31.1 cm 2 /m 2 ). Decreased skeletal muscle index (SMI) during the chemotherapy, which was defined as a reduction by more than 0.21 for male and by more than 2.19 for female, was observed in 198 (77.3%) male patients and 61 (38.1%) female patients. Decreased body mass index (BMI) by more than 1 was observed in 149 patients (37.3%) without difference between genders. Median overall survival (OS) of whole patients was 8.4 months [95%CI 7.6-9.2]. In the multivariate analysis, sarcopenia (p=0.001), decreased SMI (p=0.003), and decreased BMI (p=0.001) was significantly poor prognostic factors for OS. When we analyzed four groups by SMI and BMI changes (maintained SMI and BMI, maintained SMI and decreased BMI, decreased SMI and maintained BMI, decreased SMI and BMI), the groups with maintained SMI had longer survival than the groups with decreased SMI regardless of BMI changes. Median OS was 11.5 months with maintained SMI and 8.1 months with decreased SMI (HR 0.534 and 1, p=0.004) in decreased BMI groups and 9.9 months with maintained SMI and 8.6 months with decreased SMI (HR 1 and 1.490, p=0.002) in maintained BMI groups, respectively. The analyses separately done by gender showed similar results. Conclusions: Decrease of SMI during chemotherapy was a significantly poor prognostic factor for survival regardless of BMI changes.
The effect of talactoferrin on overall survival in prognostically important NSCLC subsets in a randomized, placebo-controlled phase II trial.
Authors: P. M. Parikh, A. Ranade, A. K. Vaid, S. H. Advani, A. Bapna, J. Zhu, Y. Wang, P. M. Ismail, R. K. Malik
Journal: Journal of Clinical Oncology (2011)

7569 Background: Talactoferrin alfa (TLF), a novel immunomodulatory agent, has demonstrated anti-tumor activity in two randomized, placebo-controlled phase II studies in NSCLC, including a 100-patient 2nd/3rd-line monotherapy study and a 110-patient study in 1st-line in combination with chemotherapy. Both studies met their primary endpoints, with improved overall survival (OS) in the monotherapy study and improved response rate in the combination study (ASCO 2006 and 2007). Here we report the OS data of TLF in prognostically important patient subsets for patients enrolled in the monotherapy study in 2nd/3rd-line. Methods: A total of 100 patients with Stage IIIB/IV NSCLC whose disease had failed 1st or 2nd line therapy were randomized to receive oral TLF (1.5 g bid) or placebo in addition to best supportive care at 11 leading cancer centers in India. TLF or placebo was administered for a maximum of three 14-week cycles with a dosing regimen of 12 consecutive weeks followed by 2 weeks off. The primary endpoint was OS. Results: The trial met its primary endpoint with a 65% increase in OS for the TLF arm (3.7 mos for placebo, 6.1 mos for TLF; HR 0.68, 1-tailed p<0.05). TLF was well tolerated with fewer AEs compared to placebo (p<0.01). Assessment of OS across various patient subsets showed a consistent effect of TLF (Table). Apparent activity was also observed in patients with both squamous and non-squamous NSCLC histology. Conclusions: The effect of TLF on OS in this 2nd/3rd line NSCLC study was consistently also seen in various prognostically important patient subsets. These findings remain to be confirmed in the ongoing phase III FORTIS-M trial. Group Subgroup N HR (90% CI) ITT (overall population) 100 0.68 (0.47, 0.98) Sex Male 66 0.62 (0.39, 0.99) Female 34 0.97 (0.51, 1.83) Age group ≤65 yr 75 0.70 (0.45, 1.08) >65 25 0.54 (0.25, 1.18) Histology Nonsquamous 79 0.70 (0.45, 1.07) Squamous 21 0.43 (0.16, 1.13) Disease stage IIIB 25 0.61 (0.30, 1.22) IV 75 0.68 (0.44, 1.06) Line of therapy 2nd 75 0.71 (0.46, 1.00) >=3rd 25 0.58 (0.26, 1.28) ECOG PS 0 23 0.54 (0.24, 1.18) 1 77 0.70 (0.46, 1.08)
A randomized phase II study of PD 0332991, cyclin-dependent kinase (CDK) 4/6 inhibitor, in combination with letrozole for first-line treatment of patients with postmenopausal, estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer.
Authors: R. S. Finn, K. Boer, I. Lang, R. J. Parikh, R. Patel, M. Schmidt, C. T. Hagenstad, H. J. Lim, T. Pinter, D. Amadori, D. Chan, R. Dichmann, S. T. Kim, S. Randolph, D. J. Slamon, J. P. Crown
Journal: Journal of Clinical Oncology (2011)

TPS100 Background: PD 0332991 is an orally bioavailable selective inhibitor of CDK4/6 and prevents cellular DNA synthesis by prohibiting progression of the cell cycle from G1 to S phase. Preclinical evaluations suggest that reduction in CDKN2A (p16) expression and cyclin D1 (CCND1) overexpression confer susceptibility to PD 0332991 (Finn et al. Breast Cancer Res 2009;11:R77). In addition, PD 0332991 was synergistic in combination with tamoxifen in vitro in ER+ human breast cancer cell lines (Ibid.). Based on these observations, a phase I/II study (ClinicalTrials.gov ID: NCT00721409) in combination with letrozole as first-line therapy in advanced ER+ post-menopausal breast cancer was initiated. The phase I portion has been completed and the recommended phase II dose (RP2D) was determined to be PD 0332991 125 mg once daily (QD) on Schedule 3/1 (3 weeks on treatment followed by 1 week off treatment) plus letrozole 2.5 mg QD. The combination was generally well tolerated, and encouraging antitumor activity was observed (Slamon et al. ASCO 2010. Abstract 3060). Methods: The phase II portion is a two-part study. In both parts, eligible patients are randomized to receive either letrozole 2.5 mg QD plus PD 0332991 125 mg QD on Schedule 3/1 or letrozole 2.5 mg QD alone. Part 1 enrolled post-menopausal women with ER+, HER2-negative breast cancer (N=60) without biomarker selection and Part 2 is now enrolling post-menopausal women with ER+, HER2-negative breast cancer with biomarker selection (CCND1 amplification and/or loss of p16; N=150). In Part 2, tissue samples are required at screening for fluorescence in situ hybridization (FISH) analysis for CCND1 and p16 copy number changes. Patients will continue with the assigned study treatment until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint is progression-free survival, and secondary endpoints include overall survival, response rate, safety, and biomarker correlative studies. Part 1 has completed accrual with 66 patients and Part 2 is now open for accrual.
Randomized clinical trial to evaluate an e-health intervention for fear of cancer recurrence, anxiety, and depression among cancer survivors.
Authors: L. I. Wagner, J. Duffecy, K. A. Lehman, S. D. Sanford, M. Begale, E. Nawacki, D. C. Mohr
Journal: Journal of Clinical Oncology (2011)

TPS237 Background: Fear of cancer recurrence is a universal experience among survivors and for many, fear persists years after treatment completion. Psychosocial interventions to teach strategies for managing these fears would improve quality of life, yet barriers to accessing psychosocial care exist. Internet-based approaches to deliver psychosocial interventions can overcome these barriers. E-health interventions disseminate standardized intervention content using a medium that is widely accessible and relatively inexpensive. Incorporating a social networking feature may improve e-intervention adherence through facilitating peer support. The purpose of this study is to evaluate an innovative e-health intervention +/- social networking to reduce fear of recurrence, depression, and anxiety among cancer survivors. Methods: Eligibility criteria include 1) any cancer diagnosis (excluding basal or squamous cell skin cancers), 2) completed cancer treatment and in remission, with no evidence of disease or stable disease, 3) ECOG performance status 0-2, 4) at least 19 years of age, 5) no history of psychiatric hospitalization in the past 5 years and 6) not currently receiving psychosocial treatment. Participants are randomized by group into one of two conditions: e-health intervention versus e-health intervention + social networking component. The e-health intervention is an interactive website with 8 weeks of didactic material based on empirically supported cognitive behavioral strategies and tools to facilitate application of coping strategies. Optional modules teach behavioral management strategies for fatigue, pain, sleep disturbance, cognitive dysfunction and body image concerns. The social networking feature includes structured interactions with cancer survivors randomized to the same group. Outcome measures include the Concerns about Recurrence scale, Hospital Anxiety and Depression Scale, adherence to the intervention (website utilization) and EQ-5D to evaluate cost effectiveness. To date, 31 participants have been randomized: e-health intervention only (two groups, n = 8 per group), e-health + social networking (two groups, n = 6 and 9).
Genomics of Hairy Cell Leukemia
Authors: Enrico Tiacci, Valentina Pettirossi, Gianluca Schiavoni, Brunangelo Falini
Journal: Journal of Clinical Oncology (2017)

Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with unique clinicopathologic features and an initial exquisite sensitivity to chemotherapy with purine analogs; however, the disease relapses, often repeatedly. The enigmatic pathogenesis of HCL was recently clarified by the discovery of its underlying genetic cause, the BRAF-V600E kinase-activating mutation, which is somatically and clonally present in almost all patients through the entire disease spectrum and clinical course. By aberrantly activating the RAF-MEK-ERK signaling pathway, BRAF-V600E shapes key biologic features of HCL, including its specific expression signature, hairy morphology, and antiapoptotic behavior. Accompanying mutations of the KLF2 transcription factor or the CDKN1B/p27 cell cycle inhibitor are recurrent in 16% of patients with HCL and likely cooperate with BRAF-V600E in HCL pathogenesis. Conversely, BRAF-V600E is absent in other B-cell neoplasms, including mimickers of HCL that require different treatments (eg, HCL-variant and splenic marginal zone lymphoma). Thus, testing for BRAF-V600E allows for a genetics-based differential diagnosis between HCL and HCL-like tumors, even noninvasively in routine blood samples. BRAF-V600E also represents a new therapeutic target. Patients’ leukemic cells exposed ex vivo to BRAF inhibitors are spoiled of their HCL identity and then undergo apoptosis. In clinical trials of patients with HCL who have experienced multiple relapses after purine analogs or who are refractory to purine analogs, a short course of the oral BRAF inhibitor vemurafenib produced an almost 100% response rate, including complete remission rates of 35% to 42%, without myelotoxicity. To further improve on these results, it will be important to clarify the mechanisms of incomplete leukemic cell eradication by vemurafenib and to explore chemotherapy-free combinations of a BRAF inhibitor with other targeted agents (eg, a MEK inhibitor and/or an anti-CD20 monoclonal antibody).