tbuckley/cabot-search huggingface dataset:
A phase I, open label, dose escalation and cohort expansion study to evaluate the safety and immune response to autologous dendritic cells (DC) transduced with AdGMCA9 (DC-AdGMCAIX) in patients with mRCC.
Authors: Fairooz F. Kabbinavar, Nazy Zomorodian, Arie S. Belldegrun, Steven G. Wong, Adrian Bot, Thinle Chodon, Begonya Comin-Anduix, Phuong Nguyen, Faraz Khan, Matthew Rettig, Allan J. Pantuck
Journal: Journal of Clinical Oncology (2014)

490 Background: Carbonic anhydrase IX (CAIX) is an attractive target for the development of a RCC specific vaccine. We developed a fusion gene construct, GM-CSF + CAIX, transduced by a replication deficient adenovirus into autologous dendritic cells (DC) that are injected in patients with mRCC. This is a ph1 study of cancer vaccine against CAIX gene expressed on RCC tumors. Methods: A recombinant adenovirus encoding the GMCSF-CAIX fusion gene (AdGMCAIX) was produced per GMP in collaboration with the NCI RAID program. The final product is produced in an in-house GMP cell processing facility using DCs cultured ex vivo from patients’ PBMC's and engineered with AdGMCAIX prior to intradermal injection. The transduced DCs are expected to stimulate an antigen specific immune response against CAIX expressing RCC, leading to a potential anti-tumor effect. Dose escalation in 3 dose cohorts (5 X 10 6 , 15 X 10 6 , and 50 X 10 6 cells/administration) follows the std 3+3 ph1 design with an expansion cohort. DC-AdGMCAIX is given intradermally Q 2 weeks X 3 doses. The primary aim is safety of DC-AdGMCAIX injections. Secondary aims are to evaluate immune responses &amp; the antitumor effects per RECIST 1.1. Pts with clear cell mRCC with ECOG 0-1 &amp; measurable disease &amp; adequate organ function were enrolled. Results: Six pts with clear cell mRCC are enrolled. Four pts received all 3 planned vaccine doses and the fifth pt only the 1st dose. No SAE’s were seen to date. One pt had chills that lasted several minutes and transient Gr1 leucopenia. One pt has worsening of pre-existing proteinuria, though unclear if related to the vaccine. One pt has PD &amp; the other two have SD on D85 scans. Tumor bx shows intra-tumoral infiltration by T cells. Conclusions: These early data show that autologous DC transduced by Ad-GMCAIX vector can be safely given to mRCC patients without any acute SAE’s noted at the doses tested so far. The study will complete its 3 rd cohort &amp; expansion cohort enrollment. This data support the further development of Ad-GMCAIX vaccine strategies either alone or in combination with approved therapies. Funding: Supported by NCI RAID Initiative NSC 740833 and Kite Pharma.
Robotic radiosurgery for the treatment of one to three brain metastases: A pragmatic application of cost-benefit analysis using willingness to pay.
Authors: Jeffrey Noah Greenspoon, Waseem Sharieff, Anthony Whitton, Timothy Joseph Whelan, Jim R. Wright, Jonathan Sussman, Amiram Gafni
Journal: Journal of Clinical Oncology (2012)

17 Background: With the emergence of radiosurgery as a new radiotheraputic technique, health care decision makers are required to incorporate community need, cost and patient preferences when allocating radiosurgery resources. Conventional patient utility measures would not reflect short term preferences and would therefore not inform decision makers when allocating radiosurgery treatment units. The goal of this article is to demonstrate the feasibility of cost-benefit analysis to elicit the yearly net monetary benefit of robotic radiosurgery. Methods: To calculate the yearly incremental cost of robotic radiosurgery as compared to fixed-gantry radiosurgery we used direct local cost data. We assumed a standard 10 year replacement and 5% amortization rate. Decision boards summarizing the clinical scenario of brain metastases and the difference between robotic and fixed-gantry radiosurgery in terms of immobilization, comfort and treatment time were then presented to a sample of 18 participants. Participants who preferred robotic radiosurgery were randomly assigned to either a low ($1) or high ($5) starting point taxation based willingness-to-pay algorithm. Results: The yearly incremental cost of providing robotic radiosurgery was $99,177. The mean community yearly willingness-to pay for robotic radiosurgery was $2,300,000, p=0.03. The calculated yearly net societal benefit for robotic radiosurgery was $2,200,823. Among participants who preferred robotic radiosurgery there was no evidence of starting point bias, p=0.8. Conclusions: We have shown through this pilot study that it is feasible to perform cost-benefit analysis to evaluate new technologies in Radiation Oncology. Cost-benefit analysis offers an analytic method to evaluate local preferences and provide accountability when allocating limited healthcare resources.
Variations in Y chromosome-related genes and clinical outcome in metastatic colorectal cancer.
Authors: Stefan Stremitzer, Sebastian Stintzing, Volker Heinemann, Wu Zhang, Dongyun Yang, Yan Ning, Yu Sunakawa, Ana Sebio, Shinichi Yamauchi, Satoshi Matsusaka, Anish Parekh, Angela Mendez, Rita Elkhoueiry, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2015)

634 Background: Males have a higher cancer risk and worse clinical outcome in metastatic colorectal cancer compared to females, which has been related to loss of Y chromosome. In this study, we investigated single nucleotide polymorphisms (SNPs) in Y chromosome-related genes and their association with clinical outcome in patients from the FIRE-3 study (NCT00433927). Methods: Three SNPs (FOXL2 rs11924939 C&gt;T, DMRT1 rs755383 T&gt;C and DMRT1 rs3739583 A&gt;T) were investigated in genomic DNA isolated from tissue samples of 295 patients (KRAS exon 2 wild-type) from the bevacizumab-arm of the FIRE-3 study. The median age of 195 (66.6%) male and 98 (33.4%) female patients was 65 months (range 27-76). Seventy-four (25.6%) patients had right-sided tumors and 215 (74.4%) had left-sided tumors. Results: The C/C genotype of DMRT1 rs755383 T&gt;C was associated with significantly longer progression-free survival (PFS) in univariable (C/C 14.3 months, T/T or T/C 10.0 months, hazard ratio (HR) 0.58; P=0.033) and in multivariable Cox regression analysis adjusted for baseline characteristics (HR 0.63; P=0.026). This difference was confirmed in male patients (C/C 15.9 months, T/T or T/C 10.1 months, HR 0.58; P=0.038 and HR 0.53; P=0.023) and patients with left-sided tumors (C/C 14.6 months, T/T or T/C 10.4 months, univariable HR 0.61; P=0.044 and multivariable HR 0.60; P=0.046). The T/T genotype of FOXL2rs11924939 C&gt;T was associated with longer PFS in patients with right-sided tumors (T/T 13.4 months, C/C or C/T 7.8 months, univariable HR 0.47; P=0.043 and multivariable HR 0.30; P=0.031) and shorter PFS in left-sided tumors (T/T 6.9 months, C/C or C/T 11.3 months, univariable HR 1.83; P=0.017 and multivariable HR 1.99; P=0.009). Conclusions: In this study, we demonstrated for the first time that SNPs in Y chromosome-related genes are associated with outcome in metastatic colorectal cancer in a gender- and location-specific way. These results highlight the value of the SNPs as potential biomarkers.
Quality of end-of-life care: Are blood cancers different?
Authors: Oreofe Olukemi Odejide, Diana Salas Coronado, Corey D. Watts, Alexi A. Wright, Gregory Alan Abel
Journal: Journal of Clinical Oncology (2014)

195 Background: Hematologic cancers have been associated with aggressive cancer-directed care near death and underutilization of hospice and palliative care services. We sought to explore hematologic oncologists’ perspectives and decision-making processes regarding end-of-life (EOL) care. Methods: Between September 2013 and January 2014, 20 hematologic oncologists from the Dana-Farber/Harvard Cancer Center participated in four focus groups regarding EOL care for leukemia, lymphoma, multiple myeloma and hematopoietic stem-cell transplantation. Focus groups employed a semi-structured format with open-ended questions, and were followed by thematic analysis. Results: Many participants felt that identifying the EOL phase for patients with hematologic cancers was challenging due to the continuing potential for cure despite advanced disease and the often rapid pace of decline near death. This difficulty was reported to result in later initiation of EOL care. Barriers to high-quality EOL care were multi-factorial, including unrealistic expectations from patients and physicians, long-term patient-physician relationships resulting in difficulty conducting EOL discussions, and inadequacy of existing home-based EOL services. Participants also expressed concern that some EOL quality measures developed for solid tumors may be unacceptable for patients with blood cancers given their unique needs at the EOL (see Table). Conclusions: Our analysis suggests that hematologic oncologists need better clinical markers of when to initiate EOL care.In addition, current quality measures may be inappropriate for identifying overly-aggressive care for patients with blood cancers. Further research is needed to develop effective interventions to improve EOL care for this patient population. [Table: see text]
Outcomes of stereotactic body radiotherapy in patients with clinical stage I non-small cell lung cancer who are fit to undergo surgery.
Authors: S. Senan, N. E. Verstegen, C. J. Haasbeek, B. J. Slotman, F. J. Lagerwaard
Journal: Journal of Clinical Oncology (2011)

7051 Background: Approximately 23% of all NSCLC cases in the Netherlands currently undergo a surgical resection. As an increasing number of fit patients have elected to undergo stereotactic body radiotherapy (SBRT) in recent years, we studied outcomes after SBRT in potentially operable stage I NSCLC. Methods: In a single institutional prospective database collected since 2003, 25% of lung SBRT cases (n=177 pts) were found to be potentially operable when the following pts were excluded (1) double lung tumors or other concurrent malignancy, (2) prior high dose radiotherapy/pneumonectomy, (3) COPD GOLD 3-4 (d)WHO score ≥3 (e) co-morbidity precluding surgery. Pts consisted of 101 males and 76 females; median age 76 years; 60% staged as T1 and 40% T2. Median Charlson comorbidity score was 2 (0-5). Patients with no histological diagnosis for a FDG-PET-positive new or growing lesion with CT features of malignancy were accepted as surgical publications report a <4% incidence of benign disease when similar patients undergo surgery in The Netherlands. An SBRT dose of 60 Gy was delivered using a risk-adapted scheme in 3, 5 or 8 once-daily fractions, depending on tumor size and location. Follow-up chest CT scans were obtained at 3, 6 and 12 months, and yearly thereafter. Results: Median follow-up was 32 months; median overall survival (OS) was 61.5 months with 1-, 3- and 5-year survivals of 94.7%, 84.7% and 51.3%, respectively. OS at 3 years in pts with (n=59) and without (n=118) histological diagnosis did not differ significantly (96% versus 81%, respectively, p=0.39). Post-SBRT 30-day mortality was 0%, whereas the predicted 30-day mortality for a lobectomy derived using the Thoracoscore predictive model (Falcoz '07) would have been 2.6%. Local control rates at 1 and 3 years were 98% and 93%, respectively. Regional and distant failure rates at 3 years were each 9.7%. Toxicity was mild with grade ≥3 radiation pneumonitis and rib fractures in 2% and 3%, respectively. Conclusions: Despite a median age of 76 years, potentially operable pts who undergo primary SBRT have a median OS exceeding 5 years. This finding supports ongoing randomized clinical trials that compare surgery and SBRT in operable stage I NSCLC.
Population-based mammography screening program in Latvia: Results of the first round.
Authors: A. Hegmane, J. Eglitis
Journal: Journal of Clinical Oncology (2011)

e11038 Background: The incidence of breast cancer is increasing in Latvia as well as the mortality, mainly due to the high rate of advanced stage disease at the time of diagnosis. Mammography (MG) screening programme was initiated to diagnose breast cancer in earlier stages when treatment results are better. Methods: Population-based mammography screening programme in Latvia was launched in January 2009. The program offers a biennial mammography screening to women aged between 50 and 69. Screening is decentralised, 25 radiology units are involved in MG screening programme. Double reading of mammograms is mandatory according to the national policy. Results: Selection of the target population for MG screening was based on population register of Latvia. 286,785 women were invited to have screening MG from January 2009 to December 2010. 57,340 (20%) screening MG had been done. Participation varied from 17.3% to 22.7% in different regions of Latvia; however the avarage participation rate was low. The results (BIRADS categories) are shown in the table. BIRADS 3 as a final result was assigned in 9850 (17.18%) cases, it varied among the radiology units (6-62%). Conclusions: It is necessary to improve participation rate by public awareness on mammography screening benefits. Mammography quality control system should be established, the second reading of the mammograms must be done by radiologists in a central breast unit to reduce the rate of BIRADS 3 category as a final result. Lack of the quality assurance and monitoring system, no exchange of the data with the Cancer Registry are limitations for effective implementation of the MG screening programme in Latvia. BIRADS category No. of examinations % 1 16,566 28.9 2 30,155 52.59 3 9,850 17.18 4 687 1.19 5 82 0.14
Unresectable hepatocellular carcinoma: Is radio-embolization an alternative for chemo-embolization?
Authors: Laila Lobo, Danny Yakoub, Omar Picado, Caroline Ripat, Fiorella Pendola, Rishika Sharma, Shree Venkat, Raphael Yechieli
Journal: Journal of Clinical Oncology (2016)

323 Background: Transarterial Radio-embolization (TARE) has emerged as a newer regional technique to Transarterial Chemo-embolization (TACE) for treatment of unresectable hepatocellular carcinoma (HCC). The aim of this study is to evaluate clinical outcomes of both techniques. Methods: Online search for studies comparing TARE to TACE from 2005 to present was performed. Primary outcome was overall survival rate for up to 4 years. Secondary outcomes included post-treatment complications and treatment response. Quality of included studies was evaluated by STROBE criteria. Relative Risk (RR) and 95% Confidence Intervals (CI) were calculated from pooled data. Results: The search strategy yielded 172 studies, 5 met our selection criteria and included 653 patients undergoing embolization for unresectable HCC. Of these patients, 284 underwent TACE and 269 underwent TARE. Median age was 63 and 64 years for TACE and TARE, respectively. Meta-analysis showed no statistically significant difference in survival for up to 4 years between the two groups (HR = 1.06; 95% CI: 0.81-1.46, p = 0.567). TACE required at least one day of hospital stay compared to TARE which was mostly an outpatient procedure. TACE had more post-treatment pain than TARE (RR = 1.96, 95% CI: 1.40-2.75, p &lt; 0.01), but less subjective fatigue (RR = 0.62, 95% CI: 0.48-0.80, p &lt; 0.01). There was no difference between the two groups in the incidence of post-treatment nausea, vomiting, fever or other complications. In addition, there was no difference in partial or complete response rates between the two groups. Conclusions: TARE appears to be a safe alternative treatment to TACE with similar complication profile and survival rates. Larger prospective randomized trials, focusing on patient-reported quality-of-life are required to consolidate these results, and to evaluate cost vs benefit for both techniques.
Online video support group pilot: Connecting young women diagnosed with breast cancer.
Authors: Nicole Anne Taylor, Michelle Esser, Lori Atkinson, Medha Sutliff, Christina Stephens, Jean Rowe, Mary Ajango
Journal: Journal of Clinical Oncology (2015)

113 Background: Young Survival Coalition (YSC) is the premier global organization dedicated to the critical issues unique to young women and breast cancer. Young breast cancer survivors (YBCS) have a strong desire to connect in-person with other young survivors although location, timing of meetings and illness can deter in-person meetings. YSC sought to create a programmatic initiative where YBCS can connect online through video to “see” and support each other as well as reduce a sense of isolation. Methods: YSC initiated an 8 month online video support group pilot, with six groups meeting monthly. Two groups focused on specific populations: under age 30; and YBCS with metastatic breast cancer. A YSC staff person provided technology support at the start of each meeting. A paid facilitator or a peer volunteer led each meeting. A variety of technology platforms were tested, with “GoToMeeting” being the most reliable and the most commonly used. Results: Approximately 29 YBCS participated regularly across the six groups. Post-meeting and post-pilot evaluations were strongly positive. Eighty percent felt their concerns were addressed during the meetings and being able to “see” other YBCS helped to build community and add to the support received. The top reason for participating in the support group was to connect with other YBCS (70%). The topics of most interest were sex and intimacy and anxiety (tied) followed by discussion of side effects. A little over half of the respondents (54%) reported wanting a facilitator to lead the groups instead of a peer. Seventy-three percent said they would participate in online video support groups again if offered. A text message reminder of the upcoming support group meeting, received a day prior to the meeting, was preferred over email. Conclusions: YSC’s online video support group program is a viable and innovative method of connecting YBCS, by providing the opportunity to give and receive support in the comfort of their own home. This pilot provided YSC the information needed to move into a second stage of program implementation and evaluation.
Comparison of Cyclophosphamide/Total Body Irradiation (Cy/TBI) and Etoposide/Total Body Irradiation (Etop/TBI) Conditioned Allogeneic Stem Cell Transplant (alloHSCT) for Adult Acute Lymphoblastic Leukaemia (ALL), Data from an Australian Tertiary Care Centre
Authors: Anish Puliyayil Nair, Shaun Fleming, Sharon Avery, David J. Curtis, Sushrut S. Patil, Patricia A. Walker, Andrew Wei, Jenny Muirhead, Andrew Spencer
Journal: Blood (2015)
RADAR assessment of quality of reporting of serious adverse drug reactions (sADRs) to an Institutional Review Board (IRB) for 14 clinical trials with imatinib mesylate
Authors: C. L. Bennett, J. L. Lagman, J. M. McKoy, D. M. Courtney, S. M. Belknap, A. O. Sartor, B. Djulbegovic, D. P. West
Journal: Journal of Clinical Oncology (2008)

6588 Background: Although sADR reporting to IRBs is intended to be an important part of safety efforts, the quality of these reports has not been adequately studied. We evaluated completeness of standard sADR reporting to an IRB versus information for the same sADRs abstracted from primary data sources on structured case report forms at a comprehensive cancer center (CCC). Methods: Subjects participated in 14 phase I- III clinical trials with imatinib at 1 of 3 NCI-designated CCCs. Completeness of reports (using CTCAE-3 criteria), causality assessments (using the Naranjo instrument) for 2 sADRs known to be drug-associated (edema/pulmonary edema) and 2 sADRs not known to be drug-associated (bone fractures/infections), incidence, and prevalence rates were measured. Results: Of 115 sADRs from 177 subjects, overall completeness was 2.4-fold greater for information in structured case report forms versus standard IRB forms (95.0% versus 40.3%, p<0.05). Information supporting causality assessments was recorded 3.5-fold more often in primary data sources versus standard IRB forms (93% versus 26%, p<0.05). Estimated incidence (per patient-year) and prevalence rates (per patient) for each of the 4 sADRs based on IRB reports were a median of 0.6% and 2.0%, respectively; versus medians of 1.1% and 2.3% when primary data sources were reviewed. Total sADR incidence and prevalence rates were 5.9% and 11.9% based on IRB record reviews and twice as great when primary data sources were reviewed (12.1% and 24.3%). Conclusions: Structured sADR reports from source documents were more detailed and contained more causality information than standard IRB reports. Use of dynamic, collaborative, pro-active, and structured reporting systems may improve IRB reporting and patient safety. No significant financial relationships to disclose.
Clinical deployment of automatic treatment planning for pancreas SBRT patients.
Authors: Joseph A. Moore, Wuyang Yang, Kim Evans, Avani Satish Dholakia, Albert Koong, Daniel Tandel Chang, Karyn A. Goodman, Joseph M. Herman, Todd R. McNutt
Journal: Journal of Clinical Oncology (2014)

219 Background: To clinically utilize an SQL relational database of prior treated patients to generate objectives for future treatment plans. A database approach allows for more rapid planning by starting with a better initial solution and improves safety by providing good known achievable dose values for the initial optimization. The use of a database allows for trending of dose, structure and toxicity data. Methods: A database of fifty-three patients from three institutions is populated with dose and structure data via an automatic script within the treatment planning system. For each new patient, overlap volume histograms (OVHs) are generated to describe the relationship between targets and critical structures. To aid in database consistency, a renaming interface is used which maps known alternative structure names to common names in the database. To ensure all required structures are present, the user is prompted with the names of missing structures. This interface allows selection of machine, energy and commonly used beam sets. The database is queried for all prior patients with the same or closer relationship between the target and each critical structure. The dose objectives reported are the lowest achievable dose from all patients as difficult or harder to plan as determined by OVH. Queried dose objectives are automatically loaded into the treatment planning system and optimized. A protocol quality tool is developed to quickly assess how well plans adhere to specified protocols. Results: Twenty-seven SBRT patients have been planned and clinically approved using the automatic planning tool and future patients continue to be added to the database. OVH computation required approximately 2 minutes, while typical plan optimization required 2.5 minutes. If auto-planned patients require even one fewer optimization to achieve an acceptable plan, total planning time is reduced. Safety is improved by reducing the number of protocol violations from 35% to 6% for one objective. Conclusions: Automatic treatment planning allows for rapid planning while reducing normal tissue dose to known achievable values. The continued addition of patients to the database allows for improvement of the automatically selected planning objectives.