tbuckley/cabot-search huggingface dataset:
Quality-of-care implications of improving physician communication through a Web-based tool (Teamwork).
Authors: Alex Pimenta Silva, Vanessa Dybal Bertoni, Therese M. Mulvey, Carlos Sampaio
Journal: Journal of Clinical Oncology (2012)

310 Background: Our practice is a community-based multidisciplinary oncology-hematology outpatient clinic located in Northeastern Brazil serving a population of three million. Hospitalizations are frequent events for treatment of complications and for palliative care. Patients are distributed in several different units across five hospitals. A team of oncologists, hematologists and other clinicians is organized in daily shifts for ambulatory consults and hospital visits. The group meets every Monday morning in rounds for case discussion and planning. The number of patients, physicians and hospitals involved poses a communication challenge. Methods: In order to improve communication and quality of care, we created a internet application (Teamwork) which provides a patient table sorted by hospital, room number, assistant physician, last visiting doctor, diagnosis and treatment plan. This information is easily accessible from any internet connected computer, tablet or smartphone with a friendly graphic interface. The doctor who admits or consults with the patient is responsible for daily updates. All the multidisciplinary teams may consult and add information. Results: Data from our program between March 2011 and June 2012 demonstrated that on average 7 physicians visited a mean of 21.8 patients daily in 5 different hospitals. With the use of the online application (Teamwork) improvements in quality of care were noticed, including: 1) Admitted patient information was rapidly available for the team, anywhere; 2) Doctors could immediately identify the physician responsible for the most recent visit, improving communication, optimizing time and reducing uneccessary phone calls to make decisions; 3) Doctors out of town could obtain updated information about their patients and contribute to their care; 4) Statistical information was readily available, providing data for improvement of team organization. Conclusions: The use of a simple online database, easily accessible and updatable represents a major step forward in the quality of care as measured by enhanced communication among providers, making it possible to assist patients in several hospitals, in a large city, with minimal communication stress.
Surveillance and treatment expenditures of stage I testis cancer
Authors: H. Yu, R. A. Madison, C. S. Saigal
Journal: Journal of Clinical Oncology (2008)

6599 Background: The economic impact of treatment choice for men with stage I testis cancer has primarily been examined via modeling at referral centers. Actual expenditures in the community are unknown. We evaluated expenditures for surveillance, retroperitoneal lymph node dissection (RPLND) and radiation therapy (XRT) in a population of privately insured men. Methods: Using a claims database, we identified men who had radical orchiectomy for testis cancer from 2002 to 2007. Stage I men were identified as having primary RPLND or XRT if they occurred within 4 months of orchiectomy and were not preceded by chemotherapy. Surveillance patients were defined as men without RPLND, XRT, or chemotherapy within 4 months of orchiectomy. We identified claims related to testis cancer and calculated annual expenditures per patient, including treatment, follow up, and treatment for recurrences. We compared follow up test expenditures to expenditures predicted using National Comprehensive Cancer Network guidelines. Results: 405, 98, and 541 patients had surveillance, RPLND and XRT, respectively, with mean follow up of 23, 24, and 23 mo. Cumulative 5-year expenditures were greatest for RPLND and lowest for XRT. Most expenditures were incurred during in year 1. Physician and hospital services comprised the majority of expenditures. Overall expenditures in years 2–5 were highest in men on surveillance. Follow up test expenditures were much lower than projected. Conclusions: Long- term expenditures for stage I testis cancer are lowest after XRT. Expenditures for surveillance are between XRT and RPLND, even though no active treatment occurs at the initiation of this strategy. Follow up testing in these patients do not account for the bulk of expenditures. This suggests that surveillance patients are incurring more expenses related to physician and hospital services, including treatment for recurrences. These data also emphasize that actual expenditures for this disease may vary from projected models due to high rates of non-compliance with follow up protocols. Stage I Testis Cancer Follow-Up Expenditures Total Treatment Expenditures (5- Year) 5-Year Expenditures (follow-up tests only) NCCN-based Projection of 5-Year Follow-Up Test Expenditures * Surveillance $95,578 $9,207 Surveillance For Seminoma $17,512 Surveillance for NSGCT $21,942 RPLND $116,633 $10,994 $12,104 XRT $84,387 $6,081 $12,150 * Expenditures projected based on follow up guidlines recommended by the NCCN. Claims data are unable to distinguish seminomas from NSGCTs in surveillance patients, therefore compliance with both seminoma and NSGCT guidelines are calculated. No significant financial relationships to disclose.
Prognostic factors and outcome analysis of soft tissue sarcomas of the head and neck region.
Authors: N. R. Khanna, A. Patil, N. A. Jambhekar, A. K. Dcruz, D. Chaukar, P. S. Pai, S. Gupta, G. Bahl, M. A. Muckaden, S. Laskar
Journal: Journal of Clinical Oncology (2010)

e16008 Background: Soft tissue sarcomas account for less than 1% of all head and neck malignancies. These tumors depict great heterogeneity in clinical features, prognostic factors and outcome. This study evaluates the prognostic factors influencing outcome amongst patients treated with a multimodality approach. Methods: Medical records of 60 eligible patients treated at Tata Memorial Hospital from 1995-2004 were evaluated. The prognostic factors evaluated were age, gender, subsite, tumor size, grade, surgical margins, bone involvement, tumor depth, and treatment parameters. Results: Of the 60 patients, 53 were males and 12 females (mean age 36 years, range 1 to 78years). Majority presented with painless mass (44/70; 73%). Half of the patients presented with primary tumors (31/60; 50%). Patients with metastatic disease at presentation were not included in the analysis. Neck was the commonest site of involvement (40%), followed by skin and scalp (23%), cheek (8%), pharyngeal region (8%), paranasal sinuses (7%), and larynx 3%. Spindle cell sarcoma (NOS) was the commonest histology (50%). Fifty nine (98%) patients underwent radical surgery as the primary treatment and 35 (49%) received post operative radiotherapy. Seven patients (12%) received chemotherapy. After a median follow up of 34 months, local control (LC), disease free survival (DFS) and overall survival (OS) for the entire cohort was 59%, 57% and 62% respectively at 5 years. Patients receiving adjuvant radiotherapy had a significant improvement in 5 year LC (24% to 78%; p=0.000), DFS (18% to 80%; p=0.000), and OS (28% to 84%; p = 0.000). None of the other prognostic factors were significant in terms of OS. None of the patients developed grade III/IV acute or late treatment induced toxicities. Conclusions: Head and neck soft tissue sarcomas are best treated with a multimodality approach. Post operative adjuvant radiation therapy results in improvement of LC, DFS, and OS. No significant financial relationships to disclose.
Identifying cancer mutations in neuroendocrine prostate cancer (NEPC) through massively parallel DNA sequencing of formalin-fixed paraffin-embedded (FFPE) tissue.
Authors: Himisha Beltran, Kyung Park, Scott T. Tagawa, Roman Yelensky, Doron Lipson, Garrett Frampton, Philip J Stephens, Maureen T. Cronin, David M. Nanus, Juan Miguel Mosquera, Mark A. Rubin
Journal: Journal of Clinical Oncology (2012)

110 Background: NEPC is an aggressive and lethal variant of prostate cancer that most commonly arises from existing prostate adenocarcinoma (PCA). Little is known about the underlying biology of NEPC, as metastases are rarely biopsied. The purpose of this study is to determine the spectrum of somatic mutations in NEPC by using a novel DNA sequencing platform and to evaluate for targetable molecular alterations. Methods: 44 NEPC and mixed NEPC/PCA were evaluated and 77 high density foci of NEPC, PCA, and benign areas were selected for DNA extraction. Massively parallel sequencing via HiSeq2000 was performed using indexed seq libraries constructed by adapter ligation followed by hybridization with optimized capture probes. Data was processed using publicly available and newly validated software tools to make mutation assignments for base alterations, indels, and CNAs in 182 cancer associated genes and common sites of rearrangement for 15 genes. Results: 5/8 biopsies and 62/65 (overall 93%) of prostate foci yielded sufficient DNA (&gt;50 ng) for analysis from 40m of FFPE tissue. Average median sequence coverage was 934x. TMPRSS2-ERG fusion was present in 28% of NEPC. Recurrent homozygous deletions involving PTEN and RB1 were seen, and 1 tumor with BRCA2 loss. Several high confidence non-synonymous mutations were identified including TP53 (40%), CTNNB1 (12%), and less frequently mutations involving PTEN, PIK3CA, AR, as well as other novel mutations/fusions. There was high concordance between NEPC and PCA foci in mixed tumors, as well as between primary tumor and metastases. High confidence lesions were validated with exome sequencing and FISH. Conclusions: This study shows feasibility of an in-depth DNA analysis using FFPE tissue, and even biopsy material. Comprehensive genome sequencing has nominated novel biologic pathways and provides insight into disease progression from PCA to NEPC, as well as potential new drug targets for a tumor that is currently lethal. This is a useful and comprehensive sequencing tool to evaluate tumors such as NEPC and other metastatic tumors, where obtaining tissue is challenging.
The impact of neoadjuvant chemotherapy and surgery on quality of life (QL) in patients with early stage NSCLC: A prospective analysis of the GINEST project
Authors: R. J. Gralla, M. J. Edelman, F. C. Detterbeck, T. M. Jahan, D. M. Loesch, S. A. Limentani, R. Govindan, C. K. Obasaju, L. P. Bloss, M. A. Socinski
Journal: Journal of Clinical Oncology (2005)

8092 Background: The assessment of the impact of combined modality therapy on QL has rarely been prospectively analyzed. Modest but significant survival gains reported with both neoadjuvant and adjuvant approaches must be viewed in terms of added risks and toxicities associated with multi-modality treatment. Validated QL instruments are available, such as the LCSS (Lung Cancer Symptom Scale), used in this study. Methods: This analysis compares patient-determined QL ratings from baseline (prior to neoadjuvant chemotherapy) with those 6 months post-op. All patients had clinical Stage I or II NSCLC, and participated in one of the two similar randomized protocols of the GINEST Project to receive pre-operatively: three 21-day cycles of gemcitabine plus carboplatin or paclitaxel in the first trial, or gemcitabine plus carboplatin or cisplatin in the second. Patients completed the LCSS at baseline, before each subsequent cycle of chemotherapy, immediately pre-op, and every 3 months post-op. Results: Full QL data over the 9 month evaluation period are available in this ongoing study on 33 patients: M/F = 48%/52%; median: age = 63, PS = 0, complete resections =94%. Pathologic staging: Stage I - 76%, Stage II - 15% Stage III - 9%. Surgical procedure: pneumonectomy = 12%, bilobectomy = 15%, lobectomy = 73%. At 6 mos post-op, 78% of patients rated their QL as stable or improved (95% CI: 64% - 92%). A subgroup (7 of 33 pts) reported worsening of QL (≥ 1 decile), with a mean decrease of 44% in these patients. In this subgroup, an average of 5 of the 9 LCSS parameters also declined; no single symptom was associated with the QL decline. Worsening QL appeared more likely in pts having more than a lobectomy or Stage III extent. It did not appear to correlate with the chemotherapy regimen or baseline QL score. Conclusions: In this evaluation of early stage NSCLC pts 6 months post-op, given neoadjuvant gemcitabine-containing chemotherapy, most pts (78%) reported improved or stable QL. Prospective QL assessments are feasible to carry out in combined modality trials and add information essential for evaluating risk, benefit, and long-term implications. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Lilly Oncology, Bristol-Myers Squibb Eli Lilly Eli Lilly and Company- Advisory Board, Lilly Oncology, Bristol-Myers Squibb, Pfizer, AztraZeneca, Aventis, Amgen Eli Lilly, Aventis, Genentech, Lilly Oncology, Lilly Underwriters US Trial 02099 in breast cancer, Bristol-Myers Squibb, Pfizer, AztraZeneca, Aventis, Amgen Lilly Oncology, Bristol-Myers Squibb
Does panitumumab have a clinical benefit in cetuximab-refractory KRAS wild-type metastatic colorectal cancer?
Authors: Toshiyasu Watanabe, Eiji Shinozaki, Sho Kijima, Yoshihito Ohhara, Yasutoshi Kuboki, Koichi Takagi, Masato Ozaka, Mariko Ogura, Yoshinori Kikuchi, Mitsukuni Suenaga, Keisho Chin, Satoshi Matsusaka, Junichi Koike, Kimihiko Funahashi, Yoshihisa Urita, Nobuyuki Mizunuma, Kiyohiko Hatake, Hironori Kaneko, Motonobu Sugimoto
Journal: Journal of Clinical Oncology (2012)

654 Background: Panitumumab and cetuximab can be used in metastatic colorectal cancer (mCRC) and these drugs are IgG2 fully human and IgG1 chimeric (mouse/human) monoclonal antibody against the epidermal growth hactor receptor (EGFR) respectively. The efficacy of panitumumab as a salvage chemotherapy after cetuximab-based chemotherapy failure is not clarified. Methods: This study aimed to evaluate the panitumumab efficacy to KRAS wild-type mCRC patients who failed cetuximab-based chemotherapy. Response, progression-free survival (PFS) and serum tumor marker level (CEA and CA19-9), were assesed. We studied response by days from last cetuximab-based chemotherapy to panitumumab induction (C-P days). Results: 22 patients (11 men, 11 women, median age 54 years m4 0-78 n) were enrolled. All of thease patients were cetuximab-based chemotherapy refractory KRAS wild-type mCRC. After progression, they received panitumumab monotherapy (6 mg/kg every 2 weeks).The best response was SD 10/22 (45.5%), PD 11/22 (50%) and NE 1/22 (4.5%). Overall median PFS was 90 days (13 to 182). The patients C-P days less than 30 days were 15 patients(5:SD, 10:PD). The patients more than 79 days were 7 patient(5:SD, 1:PD, 1:NE). Serum tumor marker level was decreased more than 50% patients. Conclusions: This study suggested that it might be limited as possibility of clinical benefit with panitumumab administration after cetuximab failure.
Efficient precise knockin with a double cut HDR donor after CRISPR/Cas9-mediated double-stranded DNA cleavage
Authors: Jian-Ping Zhang, Xiao-Lan Li, Guo-Hua Li, Wanqiu Chen, Cameron Arakaki, Gary D. Botimer, David Baylink, Lu Zhang, Wei Wen, Ya-Wen Fu, Jing Xu, Noah Chun, Weiping Yuan, Tao Cheng, Xiao-Bing Zhang
Journal: Genome biology (2017)

Precise genome editing via homology-directed repair (HDR) after double-stranded DNA (dsDNA) cleavage facilitates functional genomic research and holds promise for gene therapy. However, HDR efficiency remains low in some cell types, including some of great research and clinical interest, such as human induced pluripotent stem cells (iPSCs).Here, we show that a double cut HDR donor, which is flanked by single guide RNA (sgRNA)-PAM sequences and is released after CRISPR/Cas9 cleavage, increases HDR efficiency by twofold to fivefold relative to circular plasmid donors at one genomic locus in 293 T cells and two distinct genomic loci in iPSCs. We find that a 600 bp homology in both arms leads to high-level genome knockin, with 97-100% of the donor insertion events being mediated by HDR. The combined use of CCND1, a cyclin that functions in G1/S transition, and nocodazole, a G2/M phase synchronizer, doubles HDR efficiency to up to 30% in iPSCs.Taken together, these findings provide guidance for the design of HDR donor vectors and the selection of HDR-enhancing factors for applications in genome research and precision medicine.
The natural human monoclonal IgM antibody LM-1 inhibits human lung cancer growth in vitro and in vivo
Authors: S. Brändlein, F. Hensel, E. Wozniak, H.-K. Müller-Hermelink, H. P. Vollmers
Journal: Journal of Clinical Oncology (2005)

7347 Background: Lung cancer is a major cause of mortality worldwide and the overall survival rate has not improved significantly in the past 20 years. Of the more than 150,000 new cases of lung cancer diagnosed in Europe every year, less than 10% of patients can be cured and enjoy long-term survival. Methods: Antibody-based targeted therapy offers a new alternative to conventional radiation and chemotherapy. The human monoclonal IgM antibody LM-1 was isolated from a lung cancer patient by using the conventional human hybridoma technology (trioma technique). Results: Sequencing of the antibodies variable regions revealed that the antibody hasn’t undergone affinity maturation and is therefore a component of the innate immunity to cancer. It binds to a N-linked carbohydrate residue on a membrane molecule of about 70 kDa that is specifically expressed on malignant cells. LM-1 reacts with a series of different tumors but shows no binding to normal tissue. Furthermore the antibody LM-1 induces apoptosis in vitro on different tumor cell lines. We show here that the human natural IgM antibody LM-1 also inhibits human lung tumor growth in vivo. Conclusions: These data support the observation that natural pentameric IgM antibodies, based on their high specificty and effectivity, can be used for targeted therapy. No significant financial relationships to disclose.
Perioperative outcomes following composite resections for colorectal cancer with liver metastases: Can we do better?
Authors: Jane Yuet Ching Hui, Tianyu Li, Eric A. Ross, Nestor F. Esnaola
Journal: Journal of Clinical Oncology (2016)

412 Background: Curative resection for synchronous colorectal cancer and liver metastases (CRC/LM) can be performed simultaneously as composite resections or in isolation as staged resections. Composite resections expedite care and may be more cost-effective, but there is persistent controversy regarding their safety. This study aimed to identify potentially modifiable differences in adverse perioperative outcomes after composite versus (vs) isolated resection for CRC/LM. Methods: All patients (pts) with CRC/LM in the American College of Surgeons-National Surgical Quality Improvement Program Participant Use File who underwent elective colon, rectal, and/or liver resections from 2005 to 2013 were identified. Patient/procedure characteristics and perioperative outcomes were compared in pts who had isolated colon or rectal resection (CR or RR), isolated liver resection (LR), or composite colon/liver or rectal/liver resection (CLR or RLR) using chi square or Wilcoxon tests. Multiple logistic regression models were used to determine the independent effect of resection type on outcomes. Results: 13,523 pts underwent CR (3,601; 26.6%), RR (2,018; 14.9%), LR (7,002; 51.8%), CLR (513; 3.8%), or RLR (389; 2.9%). In colon cancer pts, the 30-day (30-d) rate of death/serious complication (DSC) was significantly higher after CLR (33.7%) than after CR (22.0%; adjusted odds ratio [aOR] 0.41, 95% confidence interval [95% CI], 0.33 to 0.52) or LR (13.9%; aOR 0.33; 95% CI, 0.27 to 0.41). Similarly, in rectal cancer pts, the 30-d rate of DSC was significantly higher after RLR (24.7%) than after RR (21.5%; aOR 0.66; 95% CI, 0.50 to 0.88) or LR (13.9%; aOR 0.47; 95% CI, 0.36 to 0.62). Differences in adverse outcomes following composite resections were not due to mortality, but to higher rates of pulmonary/infectious complications and returns to the operating room. Conclusions: Composite resections for CRC/LM are associated with higher rates of DSC, particularly in colon cancer pts. Aggressive targeted strategies to prevent pulmonary and infectious complications could significantly improve outcomes in pts undergoing composite resections for synchronous CRC/LM.
Evaluation of HER-2/neu expression in clinically localized prostate cancer
Authors: G. Burkadze, G. Turashvili, V. Pachkoria
Journal: Journal of Clinical Oncology (2005)

4768 Background: The overexpression of HER-2/neu oncoprotein is found in 20–30% of patients with breast carcinoma and is an adverse prognostic factor. HER-2/neu overexpression has been reported to occur in up to 60% of patients with prostate carcinoma and may serve a possible new target for anti-tumour therapy. However, no conclusive studies have related oncogene activation with the development of prostatic neoplasia. Reported rates of HER-2/neu overexpression in patients with prostate carcinoma vary greatly. Methods: In order to determine the immunohistochemical expression of HER-2/neu protein in clinically localized prostate cancers and to compare immunohistochemical results and clinical prognostic factors, we have studied archival formalin-fixed, paraffin-embedded radical prostatectomy specimens. The HercepTest (DakoCytomation) was used to assess HER-2/neu expression. The level of HER-2/neu expression was evaluated on a scale from 0 (no staining) to 3+ according to the published guidelines. Fluorescent in situ hybridization for gene amplification was performed on all specimens. Results: Out of 114 cases 77 specimens (67,5%) had no staining, 15 (13,2%) specimens had 1+ staining, 14 (12,3%) specimens had 2+ staining and 8 (7%) specimens has 3+ staining. There was an association between the level of HER-2/neu expression and tumor stage (P = 0.03) as well as Gleason grade (P = 0.02), but none of the specimens had HER-2/neu gene amplification. This study demonstrates that more than a third of all clinically localized prostate cancers express HER-2/neu oncoprotein via immunohistochemistry using HercepTest on archival material of clinically localized prostate cancer. Conclusions: Although HER-2/neu oncoprotein expression was detected, no positive case demonstrated gene amplification. HER-2/neu oncoprotein expression does not appear to be a prognostic marker for prostate cancer on archival specimens. No significant financial relationships to disclose.