tbuckley/cabot-search huggingface dataset:
Pneumonectomy following induction chemoradiotherapy (CRT) in NSCLC at Fox Chase Cancer Center (FCCC): Peri-operative mortality rate is lower than expected
Authors: K. M. Brown, W. J. Scott, C. Langer, S. Feigenberg, E. King, M. Goldberg
Journal: Journal of Clinical Oncology (2006)

7107 Background: Induction CRT is used commonly prior to resection for NSCLC. Selected data cite increased operative mortality in patients (pts) requiring pneumonectomy following induction CRT (&gt; 25% in RTOG 9309). We reviewed the FCCC experience with pneumonectomy for NSCLC and compared operative outcomes in pts who had induction CRT to those who had surgery (S) as initial treatment. Methods: Retrospective review of pts undergoing pneumonectomy for NSCLC from 1993–2005. Perioperative variables were analyzed for impact on operative mortality and complications. Results: 169 pts were analyzed: 110 (65%) were male; median age was 64 (range 39–84). 39 had induction CRT; 16 had preoperative chemo only and 3 had preoperative radiation only. Overall operative mortality was 13/169 (7.7%); for CRT pts, mortality was 5/39 (12.8%) compared to 7/111 (6.3%) for S pts (p = NS). In the CRT group, one pt died from respiratory failure due to radiation pneumonitis of the remaining lung; one pt died from complications of pneumonia, and the remainder died of respiratory failure. In the S group, 3 pts died of respiratory failure, 2 died after discharge of unknown causes, and one each died of pulmonary hypertension and empyema. Complications occurred in 19/39 (48.7%) of CRT pts compared to 39/111 (35%) in S patients (p = NS). Cardiac arrhythmias and pneumonia were the most common complications in both groups. A pre-op DLCO &lt;60% predicted was associated with increased operative death (p = 0.045) and complications (p = 0.066) in the CRT group; this association was not present in the S group. There was no difference in DLCO between the groups. Age, diabetes, tobacco, laterality of surgery, and pre-op FEV1 did not predict operative complications or death in any group. Conclusions: Induction chemoradiotherapy pre-pneumonectomy is not associated with a statistically significant increase in perioperative morbidity or mortality vs those undergoing surgery alone. Mortality rate for CRT appears lower than that seen in RTOG 9309. DLCO &lt;60% is a risk factor in pts with induction CRT, but not in our pts undergoing surgery alone. No significant financial relationships to disclose.
Economic impact of progressive disease (PD) following frontline therapy in classical Hodgkin lymphoma (HL).
Authors: Christopher A. Yasenchak, Wan-Yu Tseng, Chunyang Feng, Mark Yap, Debra Rembert, Debra A. Patt
Journal: Journal of Clinical Oncology (2014)

e19538 Background: Most patients (pts) with HL are cured with conventional chemotherapy (CT) +/-radiotherapy. For pts with PD, treatment options include conventional CT, autologous transplant, and allogeneic transplant. Few studies have defined the cost of therapy for PD. This study aimed to assess the economic burden of PD among pts with HL receiving 2nd and 3rd line therapy in a large network of community-based practices in the U.S.A. Methods: This retrospective, observational cohort analysis used the electronic health record (EHR) database maintained by McKesson Specialty Health/US Oncology Network to examine adult pts with classical HL who received CT (1st, 2nd, or 3rd line) between 1 Jan 2007 and 31 Dec 2011 and met all eligibility criteria. EHRs were supplemented with chart review and with data from the Claims Data Warehouse. Costs were derived from 2007 Medicare reimbursement rates and presented descriptively. Follow up time was censored at the last entry for disease status or 8 months after the date of initiation of line of therapy (LOT). Results: Records of 291 pts with HL were examined. 112 pts had non-PD (LOT1), 114 pts received 2nd line therapy (LOT2), and 65 pts received 3rd line therapy (LOT3). In LOT2, 49 pts (43%) underwent transplant (46 auto, 3 allo). In LOT3, 13 pts (20%) underwent transplant (8 auto, 5 allo). The mean total cost (MTC) of therapy was $23,361 in LOT1, $79,960 in LOT2, and $59,470 in LOT3. MTC for transplanted pts was $158,214 in LOT2 and $194,616 in LOT3 . MTC for non-transplant pts was $20,969 in LOT2 and $25,683 in LOT3. Conclusions: These results show the cost of therapy for progressive HL is significant. The MTC of therapy is 2-3x greater in LOT2-3 than LOT1. When transplant is needed, MTC of therapy increases 7-8 fold when compared to LOT1. This is noteworthy given that 20-30% of pts with advanced stage HL relapse post-1st line therapy. Of these, ≥50% undergo salvage CT and consolidative auto transplant. Furthermore, for pts that receive salvage CT and consolidative auto transplant in 2nd line, 40% eventually relapse and require 3rd line therapy. It is possible that therapies that delay or prevent progression following front line therapy will result in significant cost savings.
Ribonucleotide reductase subunit 2 (RRM2) to predict shorter survival in resected stage I-III non-small cell lung cancer (NSCLC) patients.
Authors: Erika Rijavec, Maria Giovanna Dal Bello, Graziana Savarino, Claudio Sini, Giulia Barletta, Carlo Genova, Mauro Truini, Paolo Pronzato, Domenico Franco Merlo, Ulrich Pfeffer, Francesco Grossi
Journal: Journal of Clinical Oncology (2012)

e21065 Background: Biomarkers can help in identifying patients (pts) with early-stage NSCLC with high risk of relapse and poor prognosis. The aim of this study was to investigate the relationship between the levels of expression of 7 biomarkers, various clinicopathological characteristics and their prognostic significance. Methods: Tumor tissue from 82 radically resected stage I-III NSCLC pts were consecutively collected to investigate the mRNA expression and protein levels of the following biomarkers using quantitative reverse transcriptase real-time PCR (qRT-PCR) and immunohistochemistry (IHC) with a tissue microarray technique: excision repair cross-complementation group 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunit 1 (RRM1), RRM2, p53R2, thymidylate synthase (TS) and class III beta-tubulin (β-Tub-III). Results: On a univariate analysis, p53R2 expression was significantly higher in adenocarcinoma (ADK) compared to squamous cell carcinoma (SSC) samples (p=0.002) and in stage I compared to stage II-III (p≤0.001). ERCC1 expression was significantly higher in females compared to males (p=0.03), and β-Tub-III expression was significantly higher in ADK than in SSC (p=0.03). Pts with lower RRM2 expression survived longer than pts with higher RRM2 expression (p=0.069). The multivariate analysis confirmed RRM2 as an independent prognostic marker of shorter survival (p= 0.031). The comparison between survival curves with qRT-PCR and IHC showed similar results with a trend towards longer survival among ERCC1 negative pts, BRCA1 negative pts, p53R2 positive pts and among pts with low levels of RRM1 and RRM2, although the difference was not statistically significant with both methods. qRT-PCR and IHC have shown that β-Tub-III and TS had no significant impact on survival. Conclusions: This is the first study that identifies RRM2 expression as a negative prognostic factor in resected stage I-III NSCLC. Moreover, we have demonstrated the differential expression of p53R2 and β-Tub-III in ADK compared to SSC and higher expression of p53R2 in pts with stage I compared to stage II-III NSCLC.
Genetically Distinct Parallel Pathways in the Entopeduncular Nucleus for Limbic and Sensorimotor Output of the Basal Ganglia
Authors: Michael L. Wallace, Arpiar Saunders, Kee Wui Huang, Adrienne C. Philson, Melissa Goldman, Evan Z. Macosko, Steven A. McCarroll, Bernardo L. Sabatini
Journal: Neuron (2017)
Immunological and clinical response after vaccination therapy of pancreatic carcinoma patients with autologous, tumor-lysate pulsed dendritic cells: Results of a phase II-study
Authors: C. Bauer, M. Dauer, S. Saraj, M. Schnurr, K. Jauch, D. Rüttinger, C. Bruns, B. Emmerich, S. Endres, A. Eigler
Journal: Journal of Clinical Oncology (2007)

4579 Background: Multiple studies in the experimental and in the clinical setting have shown that vaccine therapy using dendritic cells can induce antitumor immunity. Here, we report about the results of a phase II-study using autologous, tumor-lysate pulsed dendritic cells for the treatment of patients with advanced pancreatic carcinoma. Methods: Pancreatic carcinoma patients receiving abdominal surgery were included into to the study protocol. Tumor-lysate was derived by freeze-taw-cycles from surgically derived tissue specimens. Patients were eligible for DC vaccination after recurrence of pancreatic carcinoma or in a primarily palliative situation. DC were derived from PBMC according to a six-day protocol, loaded with tumor lysate and stimulated with TNF-a and PgE2. DC were applicated intracutaneously into the groin region every other week for three cycles, then monthly. All patients received standard chemotherapy with gemcitabine concomitantly. Immune response was controlled by DTH skin testing. Samples of non adherent cells were frozen for MLR and ELISPOT assays to monitor immune response ex vivo. Main study end point was partial or complete remission. Results: Ten patients have received dendritic cell vaccination so far. Of these, one patient developed a partial remission after a four-months course of vaccination therapy. Another patient showed stable disease after having received five vaccinations. Both patients showed immunological response. The patient with stable disease had a mean of 56 IFN-γ positive spots per 50E3 DC-stimulated non adherent cells prior to vaccination. After vaccination, this number increased to 191 spots per 50E3 cells (negative control: 5; positive control: 315). Both patients are alive 13 and 7 months after the start of vaccination therapy, respectively. Conclusions: Vaccination therapy with dendritic cells can be of clinical benefit in the setting of advanced pancreatic carcinoma. Clinical responses were associated with the induction of a stable immunological response. No significant financial relationships to disclose.
SWOG 1107: Parallel (randomized) phase II evaluation of tivantinib (ARQ-197) and tivantinib in combination with erlotinib in patients (Pts) with papillary renal cell carcinoma (pRCC).
Authors: Przemyslaw Twardowski, Melissa Plets, Elizabeth R. Plimack, Neeraj Agarwal, Catherine M. Tangen, Nicholas J. Vogelzang, Ian Murchie Thompson, Primo Lara
Journal: Journal of Clinical Oncology (2015)

4523 Background: pRCC is associated with activation of MET signaling pathway and less favorable responses to VEGF inhibition than clear cell RCC. In SWOG 0317, the EGFR inhibitor erlotinib yielded a response rate (RR) of 11% and median overall survival (OS) of 27 months in pRCC pts. Tivantinib is a non-ATP competitive inhibitor of MET. In a preclinical pRCC model, combination erlotinib and tivantinib showed synergistic activity. A randomized multicenter phase II trial of tivantinib alone or with erlotinib was conducted in pts with either type I or II pRCC. Methods: Pts with histologically-confirmed advanced or metastatic pRCC and 0-1 prior systemic therapy were randomly assigned to tivantinib 360 mg BID (Arm 1) or tivantinib 360 mg BID plus erlotinib 150 mg daily (Arm 2). A RR of ≥ 30% was to be considered a promising outcome. Target accrual was 70 pts (35 per arm) with interim analysis planned after enrollment of 40 pts. Robust accrual resulted in 55 pts registered by the time of interim closure. Results: Of 55 pts enrolled, 50 were eligible: 25 in each arm. Median age was 64 years; most pts were male (68%). 33 pts (66%) had no prior systemic therapy; 6% of pts had type 1 pRCC, 42% had type 2, and 52% had no subtype assigned. The study was permanently closed at interim analysis when both arms yielded RR of 0%. Median progression free survival (PFS) was 2.0 and 5.4 months, and OS was 10.3 and 11.3 months in Arms 1 and 2 respectively. Most frequent adverse events: Arm 1- fatigue, nausea and anemia; Arm 2-rash, nausea, fatigue and diarrhea. Deep exome sequencing of archival tumor specimens is ongoing. Conclusions: Tivantinib - either alone or in combination with erlotinib has no clinical activity in pts with advanced pRCC. The addition of tivantinib to erlotinib may have reduced the latter’s previously reported efficacy (although wide confidence intervals preclude a definite conclusion); this was not predicted by preclinical modeling. Although MET remains a reasonable therapeutic target in PRCC, more careful credentialing of proposed MET inhibitors, biomarkers, and patient subsets most likely to benefit would be required. (NIH/NCI NCTN CA180888;CA180819;CA180820). Clinical trial information: NCT01688973.
Efficacy and toxicity of sunitinib in patients with metastatic renal cell carcinoma (mRCC) with severe renal impairment or on haemodialysis
Authors: D. H. Josephs, T. E. Hutson, L. M. Pickering, J. M. Larkin, T. K. Choueiri, T. V. Patel, D. F. Mcdermott, T. Powles, P. G. Harper, S. Chowdhury
Journal: Journal of Clinical Oncology (2009)

5109 Background: Sunitinib is currently a standard of care for the treatment of mRCC. Due to the inclusion criteria of clinical trials, no studies of sunitinib have enrolled patients with severe renal impairment or those undergoing haemodialysis, and thus further investigation of the effect of sunitinib in this population is required. Methods: Clinical databases were used to identify all patients with mRCC treated with sunitinib in five institutions internationally. Medical records were searched to identify only those patients with a creatinine clearance (CL cr ) of &lt;30ml/min or who had end stage renal disease (ESRD) requiring haemodialysis. Baseline characteristics, toxicity data and progression free survival (PFS) were collected. Results: 21 patients met inclusion criteria with 9 (43%) undergoing haemodialysis. Baseline characteristics include a median age of 62 years (range 44–80); 90% of patients had ECOG PS of 0 or 1; 38% of patients had &gt; 2 metastatic sites and 86% had prior nephrectomy. The estimated median PFS of this cohort was 38 weeks (range 2–120) although progression has not yet been reached in 8 (38%) patients. PR or SD was observed as best response in 17 (81%) patients. The most common treatment-related adverse events (AEs) included fatigue, diarrhoea, hand foot skin reaction (HFSR), nausea and vomiting and rash. Grade 3 treatment related AEs including fatigue, HFSR, diarrhoea and rash occurred in a total of 7 (33%) of patients. Only one patient experienced grade IV toxicity (HFSR). Conclusions: These data suggest that patients treated with sunitinib who have severe renal impairment, or ESRD on haemodialysis, have a PFS that is comparable to patients with normal renal function. In addition sunitinib appears to be reasonably well tolerated in this group of patients. These preliminary results warrant confirmation in a larger cohort of patients. [Table: see text]
Consequences of death on group process during a long-term moderated Web-based support group
Authors: D. Weber, K. Mor, R. Catane, Z. Symon
Journal: Journal of Clinical Oncology (2004)

8079 Background: The impact of death on group dynamics of web based cancer support groups is yet unexplored. Methods: Cancer-Voices of the Heart is an open online web-based support group open to all users and moderated by 2 specialist social workers. Participants were recruited by advertisement directed to all users affected by cancer. Results: Since March 2002, there have been 16,782 entries into the site, 50% of which are attributed to a nucleus of twenty participants (17 female, 3 male) frequenting the forum 5 times a week on average with a duration range of 9 - 21 months. Peak entry times were late night and weekends. Fourteen users were self reported cancer patients, two were bed ridden and six were friends or family. Issues raised included body image, sexuality and spouse relations, loss of independence, spirituality, conventional and alternative therapies. The first reported death of a forum member motivated increased traffic and confrontation with previously taboo issues of death. A virtual mourning ritual was established focused on retrieved archived materials of the deceased. Biological family, previously uninvolved, frequently visited a live cyberspace monument where mutual grief and comfort were exchanged. Expression of grief was moderated by establishment of a tree of memory where users lit candles. Death precipitated a need to physically contact group members and family of the deceased. In one case, this process unmasked an impostor who representing multiple identities, fabricated a virtual death. This revelation raised a storm of emotions and feelings of betrayal threatening group integrity . Crisis intervention focused on achievement of insight that open discussion of death and dying is valuable irrespective of the impostors' motivation. Participants were empowered in their struggle and acknowledged for their determination to continue to support each other. Conclusions: Professionally led web based support groups provide a unique counseling opportunity for dealing with issues of death and dying. Free access, unrestricted by time or place induces rapid kinetics of group dynamics posing new professional and ethical challenges for group psychotherapy. No significant financial relationships to disclose.
Intractable Epilepsy and Progressive Cognitive Decline in a Young Man
Authors: Alexander L. Cohen, Lyell K. Jones, Joseph E. Parisi, James P. Klaas
Journal: JAMA Neurology (2017)

A young man with normal neurodevelopment presented with 3 years of medically refractory, progressive epilepsy and myoclonus. Initial examination included neuroimaging, electroencephalography, and biochemical analyses, all of which were unremarkable except for mildly enlarged ventricles. Over the following year, the patient experienced rapid cognitive decline with new-onset recurrent visual hallucinations and progressive lethargy. Results of subsequent electroencephalography and brain imaging were unchanged, and a fluorodeoxyglucose F 18 positron emission tomographic scan was normal.
Incidence of catheter-related venous thromboembolism in peripherally inserted central venous catheters vs tunneled chest central venous catheters in patients with hematologic malignancies.
Authors: Thomas A. Giever, Emily R. Giever, Patrick C. Foy, Lisa Baumann-Kreuziger, Laura C. Michaelis, Karen-Sue Barker Carlson, Timothy S. Fenske, Mehdi Hamadani, William S. Rilling, Parameswaran Hari, Ehab L. Atallah
Journal: Journal of Clinical Oncology (2015)

e20684 Background: Common complications of central venous catheters (CVCs) include catheter-related venous thromboembolism (CR-VTE) and central line-associated blood stream infections (CLABSI). In an effort to decrease CR- VTE rates, in 5/2012 the Medical College of Wisconsin (MCW) HM group changed the placement of CVCs from brachiocephalic vein PICCs to tunneled chest internal jugular vein CVCs in all patients with HMs unless contraindicated. Methods: We report CR-VTE and CLABSI rates pre- and post-intervention between 1/2009-6/2013. Clinical data were collected through the electronic medical record. All comparisons were using Fisher’s exact Chi-square test. Results: From 1/2009-6/2013, 1,953 CVCs were placed in patients at MCW with HMs. The table shows the significant decrease in overall incidence of VTEs (p < 0.01) with stable incidence of CLABSIs (p = 0.15) following a change to placement of tunneled CVCs. There was no statistical difference between disease types. Conclusions: The HM group at MCW instituted a change in the placement site of CVCs as part of a continuous quality improvement project. Results demonstrate a decrease in the overall incidence of CR-VTEs and a stable rate of CLABSIs when a tunneled internal jugular CVC is preferentially utilized rather than traditional PICCs. Our data highlights that such a change is feasible and may benefit patients. Pre-Intervention Post-Intervention Median age (range) Male:Female (ratio) 56 (19-92) 772:524 (1.4:1) 57 (18-89) 379:278 (1.4:1) Diagnosis (%) Lymphoproliferative disorders Plasma cell dyscrasias AML MDS APL MPD Other 477 (37) 446 (34) 307 (24) 22 (2) 20 (2) 19 (1) 5 (< 1) 223 (34) 242 (37) 146 (22) 24 (4) 10 (2) 9 (1) 3 (< 1) Total CVCs (%) PICCs Tunneled CVCs Other CVCs 1296 882 (68.1) 29 (2.2) 385 (29.7) 657 192 (29.2) 227 (34.6) 188 (28.6) Total VTEs (% of CVCs) PICCs Tunneled CVCs Other CVCs 110 (8.5) 105 (8.1) 0 (0) 5 (0.4) 31 (4.7) 23 (3.5) 6 (0.9) 2 (0.3) Total CLABSIs (% of CVCs) PICCs Tunneled CVCs Other CVCs 34 (2.6) 25 (1.9) 1 (0.07) 8 (0.6) 10 (1.5) 2 (0.3) 7 (1.1) 1 (0.2)
The implementation of a lay care navigation service at the Stanford Cancer Institute.
Authors: Cati Brown-Johnson, Laura J Holdsworth, Eben Rosenthal, Steve Asch, Marcy Winget
Journal: Journal of Clinical Oncology (2017)

119 Background: Lay care navigators address barriers to care, provide a single point of contact in complex health systems, and help efficiently resolve non-clinical patient issues. Despite navigation program proliferation, each is crafted to fit local institutional and patient needs. In Summer 2016, Stanford Cancer Institute (SCI) launched a care navigation pilot to improve patient engagement, facilitate better access to services, and improve coordination. The Stanford Care Navigator (SCN) program was based on a framework for lay navigation from the University of Alabama at Birmingham (UAB) who consulted on this project. This study describes the evolution of the SCN model and drivers of changes as SCN was iteratively designed and implemented. Methods: Qualitative study including document review of training materials, observation of cross-functional design meetings, stakeholder interviews, and a focus group with Care Navigators. Results: In spite of common goals of reducing patient distress and improving care coordination, the resulting SCN service is quite distinct from the consulting organization. Primary factors driving design changes were differences in: clinic access, patient populations and needs (e.g., SCN language translation needs vs. UAB poverty-related barriers), and a suite of pre-existing services at SCI (e.g. referral triage). Navigators call all new patients to address common barriers (traffic, parking vs. lack of transportation in Alabama). SCN refers some service items (e.g., financial support) to existing service groups, including Social Work. Conclusions: While Stanford navigation retains elements of the UAB-originating lay navigator program, in this radically different setting, service parameters differ substantially. The model was, therefore, substantially adapted rather than simply adopted. Ongoing evaluation explores navigators’ impact on patients and staff/providers.