tbuckley/cabot-search huggingface dataset:
FOLFIRINOX combined to targeted therapy according RAS status for colorectal cancer patients with liver metastases initially non-resectable: A phase II randomized Study—Prodige 14 – ACCORD 21 (METHEP-2), a unicancer GI trial.
Authors: Marc Ychou, Michel Rivoire, Simon Thezenas, Rosine Guimbaud, Francois Ghiringhelli, Anne Mercier-Blas, Laurent Mineur, Eric Francois, Faiza Khemissa, Driffa Moussata, Yves Becouarn, Philippe Houyau, Thomas Aparicio, Rene Adam, Marie-Pierre Galais, Franck Audemar, Eric Assenat, Trevor Stanbury, Olivier Bouche
Journal: Journal of Clinical Oncology (2016)

3512 Background: Liver metastases (LM) from colorectal cancer (CRC) are initially resectable in only 10-15% of patients (pts). The conversion to resectability following induction chemotherapy is an important strategy to increase survival. Our study was designed to determine the most appropriate chemotherapy (associated with a targeted therapy) for CRC pts with LM considered as initially unresectable. Methods: This French phase II, multicenter, prospective trial, randomized pts between bi-chemotherapy (BiCT) versus tri-chemotherapy (TriCT). The population was initially stratified by targeted therapy depending on KRAS status and then by RAS status (from 02 Dec 2013 due to the change in cetuximab's [Cet] marketing authorization): Cet for wt(K)RAS pts and bevacizumab (Bev) for mtRAS pts. The hypothesis was to increase the rate of LM resection (R0-R1) from 50% with BiCT to 70% with TriCT (bilateral α-test 5%; power 90%). Results: 256 patients were randomized in 33 sites from February 2011 till April 2015: 126 BiCT (FOLFIRI [56 pts]; FOLFOX4 [70 pts]) and 130 TriCT (FOLFIRINOX). The resection rate (R0 or R1; CI95%) of the LM was 45.2% [36; 54] for pts treated with BiCT vs 56.9% [48; 66] for TriCT (p = 0.062).The LM resection rate (R0 or R1; CI95%) was 44.7% [35; 55] for pts treated with Bev (mtRAS) vs 55.6% [47; 64] for Cet (wtRAS) (p = 0.087). At the time of data analysis, the median follow-up (CI95%) was 22.5 months [19.6;29.5] for the BiCT pts and 23.5 months [19.8; 28.8] for the TriCT pts and at analysis 78 patients had died. The median overall survival (OS) is significantly different (p = 0.048): in the TriCT Arm the median OS was not reached and is 36 months [23.5;40.6] in the BiCT Arm. The severe toxicity rate was 37.6% for BiCT vs 41.7% for TriCT (p = 0.503). 38 BiCT pts and 34 TriCT pts had surgical complications, with two deaths in each arm. Conclusions: First line FOLFIRINOX chemotherapy, in association with a targeted therapy, showed a higher rate of LM R0/R1 resections than standard BiCT (FOLFIRI or FOLFOX4) combined with the same targeted therapy, with a statistically significant difference in terms of OS. Clinical trial information: 2009-012813-22.
Two years follow-up data of multiple-line treatment in stage IV tumors from a whole exome-guided real-world study of 1,000 Chinese cancer patients.
Authors: Qiang Xu, Cheng Chen, Xiaoyu Pei, Xiuli Liu, Xiaoman Xu, Guan Wang, Xin Cai, Jinwang Wei, Angela Wu, Chun Dai
Journal: Journal of Clinical Oncology (2018)

e24282 Background: We previously reported a real-world study to apply clinical whole exome sequencing (CWES) in 1,000 cancer patients. Here we reported 2 years follow-up data in a cohort of stage IV patients with multiple lines of therapies for the potential clinical benefits of precision treatments. Methods: Whole exome of tumor/normal samples in over 1,000 cancer patients from 70 hospitals in China were sequenced. Regular follow-up was conducted each 3 months after the CWES report since the first half of 2016. Only the patients with stage IV disease who failed the previous treatment upon receiving the CWES reports were included in this cohort analysis. Results: 29 stage IV patients formed the study cohort, covering a broad tumor spectrum, including lung, colorectal, breast, pancreatic, renal, thymus, fibroblastoma, mesothelioma and hemangioendothelioma. 13/29 (45%) patients’ treatment followed the CWES reports (Group A). 16/29 (55%) patients did not follow the CWES suggestions (Group B). By Jan 2018, Group A had an average 9.1 months disease control (DC) period, with 5/13 (38%) failed this round of therapy. Whereas Group B had an average 3.6 months DC period, with 10/16 (63%) failed the treatment. The longest followed DC time in Group B was 9 months, while almost half of Group A (6/13) were beyond 9 months, ranging from 12 to 20 months. While the average number of line treatments and the types of therapies before CWES were similar in two groups (10/13 chemo, 3/13 targeted in Group A; 13/16 chemo, 3/16 targeted in Group B), CWES-beyond treatments were 100% targeted (10/13) or immuno (3/13) in Group A, versus about half were still chemo in Group B (7/16 chemo, 5/16 targeted, 3/16 targeted+chemo, 1/16 immuno). In Group B, only one patient used Keytruda without genomic support for only one-month DC. In Group A, three patients used Keytruda with genomic support, two with DC for 20 and 14 months respectively, and one with PD after 7 months. Conclusions: The current study suggested that CWES has potential to help exploring the clinical benefits in multiple line therapies among late stage tumors. Randomized clinical studies are needed to verify the validity in boarder clinical settings.
Using patients’ and oncologists’ voices to shape a communication skills trial.
Authors: Nina A. Bickell, Dena Schulman-Green, Kerin B. Adelson, Jenny J Lin, Rebeca Franco, Rachel Solomon, Cardinale B. Smith
Journal: Journal of Clinical Oncology (2016)

e18161 Background: Goals of Care (GoC) discussions, while emotionally and practically challenging for advanced cancer patients and their oncologists, can help clarify patient values and ease decision-making. However, this process is subject to oncologists’ and patients’ emotions and communication skills (CS). To maximize participation in and effectiveness of a CS trial to enable quality GoC discussion, we worked with a group of patients, oncologists & palliative care doctors trained in CS to tailor an intervention trial to patient & oncologist preferences and practice realities. Methods: With the goal of engaging physicians, obtaining their buy-in and encouraging participation, we interviewed nearly all solid tumor oncologists. We used their input to inform the study design and intervention development. Once funded, we worked with patient stakeholders via a series of interviews and meetings to develop study surveys & tailor the CS intervention and recruitment approaches. The study is being conducted at academic, community, municipal & rural hospitals (n = 4). Results: We sought initial input from oncologists about the best timing to initiate GoC discussions, and prior positive experiences with GoC discussions. Most identified the first imaging visit after initiation of first line therapy as an acceptable time to initiate GoC. Additionally, several oncologists noted incorporating useful phrases from prior meetings involving the palliative care team. We incorporated this input and shaped the intervention to occur at the post-imaging visit. We pair palliative care physicians trained as communication coaches to participate in joint visits in real practice settings. Nearly 90% of oncologists are participating in the CS trial. Patient stakeholder feedback on the CS training intervention led to including non-verbal as well as verbal cues, expanding social support measures in survey tools & adjusting timing of recruitment strategies. Conclusions: Involving patients & physicians in the development & design of a trial focusing on an emotionally charged area can increase their engagement, participation and substantively change the trial design & implementation. Clinical trial information: NCT02374255.
<i>MET</i> exon 14 mutation may not be a potential predictive biomarker in Chinese patients.
Authors: Si-yang Liu, Lan-ying Gou, Jian Su, Jin-Ji Yang, Xu-Chao Zhang, Yi-Long Wu
Journal: Journal of Clinical Oncology (2016)

e20578 Background: Recent studies have come to the conclusion that MET exon 14 mutation would define an unique subtype of NSCLC and optimize the genotype-directed therapies. Here we report our different results about the detection of MET exon 14 mutation in Chinese patients. Methods: In total, 1101 patients with lung adenocarcinoma has been screened for MET exon 14 mutation. Both NGS and sanger sequencing was used. Moreover IHC and FISH was also performed on the specimens of MET exon 14 mutational patients. Results: 826 of them were detected by NGS and 275 by sanger sequencing. A total of 10 patients have been identified with MET exon 14 mutations which accounted for only 0.91% of lung adenocarcinoma, much less than the western patients’ data of 3%. Then 6 of MET exon 14 mutational patients have been performed with IHC and FISH. All the detailed data has been presented in Table 1. Furthermore among 2 patients received crizotinib, only 1 patient combined with MET amplification experienced a partial response and PFS has been 9 months. However whether sensitivity to crizotinib in this patient was conferred by the MET exon 14 mutation or by MET amplification is still unclear. For the other one, the disease has progressed in only 1.0 month. Conclusions: MET exon skipping mutation rate is lower and may not a good predictive biomarker for c-MET inhibitor in Chinese lung adenocarcinoma patients. Clinical characteristics of patients with lung cancers harboring MET exon 14 mutation. Gender Age smoking Histology TNM stage c-MET IHC c-MET FISH Crizotinib Clinical benefit Best response PFS (month) P 1 M 60 60 ADC IV Negative Negative (ratio1:1) No NA P 2 F 41 0 ADC I Negative Negative (ratio1:1) No NA P 3 M 49 0 ADC I Negative Negative (ratio1:1) No NA P 4 M 45 20 ADC IV 100%++ Negative (ratio1:1) Yes No PD 1.0 P 5 M 76 0 ADC IV 80%++ copies>5 Yes Yes PR 9.0 P 6 F 50 0 ADC IV 70%+++ 30%++ Negative (ratio1:1) No NA
Evaluation of the quality of cancer treatment in a population of patients (pts) with metastatic colorectal cancer (mCRC) in routine clinical practice in different regions of Russia.
Authors: Mikhail Fedyanin, Shamai Aliyeva, Liubov Yu Vladimirova, Sanal Erdniev, Alexander Ivanov, Alexey Katkov, Valeriy Kulik, Evgeniya Kuzmina, Elena Matyushina, Larisa Nikitina, Rashida Orlova, Anton Yurievich Povyshev, Eduard Pshevlotskiy, Madina Ramazanova, Olga Shalofast, Elena Smirnova, Alexandra Tkachuk, Natalya Ulanova, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2017)

e18022 Background: In Russia, there are no federal screening programs for detecting early stage of colon cancer; therefore we can assess the impact of various factors that could potentially affect the mortality of pts with mCRC Methods: We conducted a survey with 13 question according treatment of pts with CRC in 17 regional comprehensive cancer centers in 14 regions of Russia, with a total population of 26.347 billion. Results of the survey were conducted by methods of descriptive statistics. Effects of factors on mortality rate in regions were analyzed by a regression model Results: Only 34% pts with stage II-III received adjuvant chemotherapy. Mutation status of KRAS gene has been evaluated only in 33% pts with mCRC. In 2013, metastasectomy was performed only 13% of pts. Only 80% of pts who needed systemic treatment received chemotherapy (CT): doublets of CT (XELOX/FOLFOX/FLOX or FOLFIRI/XELIRI/IFL) - 49%, monotherapy of fluoropyrimidines - 39% of pts, bevacizumab – in 14% and anti-EGFR antibodies - 5% pts. Only 14% of pts with mCRC was placed central vein devices. Second line CT was performed in 47% pts: doublets – in 54%, monotherapy of fluoropyrimidines - in 24% pts, bevacizumab - 13% and anti-EGFR antibody - 8%. Third-line treatment was performed in 25% of pts: anti-EGFR antibodies - in 7.5%. According to regression analysis adjuvant chemotherapy (р = 0.01), bevacizumab only in the 1 st line (р = 0.01), and installation of central venous devises (р = 0.07) and anti-EGFR antibody in the 1 st line (р = 0.1) in wtKRAS pts had independent positive effect on the mortality rate in regions. We revealed a significant reverse connection between a high mortality rate in the region and administration of fluoropyrimidine monotherapy as 1 st line treatment of metastatic disease (p = 0.01) Conclusions: The mortality with colorectal cancer is depended of complex factors that reflect the health care organization in the region, both at the stage of treatment of pts with early-stage and metastatic disease. We revealed that targeted agents are the most effective only in the 1 st line settings.
Radiation therapy for patients with extensive stage small cell lung cancer: A survey study of medical oncologists.
Authors: Jia Luo, Catherine Degnin, Yiyi Chen, Timur Mitin, Ronald John Maggiore
Journal: Journal of Clinical Oncology (2017)

e20025 Background: National guidelines recommend prophylactic cranial irradiation (PCI) and consideration for thoracic radiation therapy (TRT) for patients with extensive stage small cell lung cancer (ES-SCLC) after chemotherapy. The referral practice patterns among US medical oncologists are unknown. Methods: We developed a survey that was sent to US medical oncologists. The survey evaluated demographics, self-rated knowledge of key TRT studies and approach to radiation oncology referral for ES-SCLC patients regarding TRT and PCI. A predefined knowledge score (KN) (from 0 to 4) was used to characterize self-rated knowledge of existing Jeremic et al and CREST TRT trials with “0” being unaware of the study, “1” being some knowledge, and “2” being knowing trial details. Associations between respondent characteristics and responses were evaluated using Chi-squared or Fisher’s exact tests. Results: 316 complete responses were analyzed. Most respondents had over 10 years of experience (74%; n = 233) and have taken care of more than 10 patients with lung cancer (73%; n = 230), with those treating more patients having higher KN (p = 0.001). 76% (n = 239) of respondents recommended TRT referral after chemotherapy and were more likely to refer if a complete response at metastatic sites had been achieved (p = 0.0001). Higher KN (p = 0.003) was associated with a higher likelihood of TRT referral. 24% (n = 77) did not recommend referral; of these, 84% (n = 65) cited insufficient evidence as their rationale. 75% (n = 237) would obtain brain imaging prior to PCI referral, and 90% (n = 283) supported PCI referral in the absence of brain metastases. Conclusions: Among surveyed US medical oncologists the majority refer patients with ES-SCLC to TRT after chemotherapy. Those physicians who do not refer feel the evidence supporting TRT is insufficient. This is in line with ambiguity reflected in recent ASCO and NCCN consensus guidelines. Most physicians recommend referral for PCI consideration. Additionally, most obtain brain imaging prior to PCI referral, a practice not supported by clinical evidence. These differences in practice patterns support the need for further research to determine the role of TRT and PCI in patients with ES-SCLC.
Characteristics of proteomic patterns in patients with metastatic and non-metastatic colorectal cancer.
Authors: Dmitriy I. Vodolazhsky, Denis S. Kutilin, Leonid Kharin, Evgeniy N. Kolesnikov, Olesia A. Bogdanova, Vyacheslav A. Sustretov, Vladimir Trifanov, Oleg I. Kit
Journal: Journal of Clinical Oncology (2017)

e23007 Background: Over the past 20 years, the number of deaths from colorectal cancer (CRC) increased by 46% worldwide: every year more than 1 million people are diagnosed with this pathology. Proteomic studies using protein microarrays are a very attractive strategy for the screening of new highly specific biomarkers which can improve prognosis prediction of CRC. We performed a screening proteomic study to find new informative biomarkers for metastatic and non-metastatic colorectal cancer which can be further used in routine histochemical studies. Methods: The samples of tumor and non-tumor tissues of 20 patients with histologically confirmed adenocarcinoma of the colon were studied. Extraction, labeling and hybridization of proteins on the slide containing 224 antibodies for key cellular proteins were performed using the Panorama Antibody Microarray - Cell Signaling Kit, and the GenePix 4100A scanner was used for scanning. The data were analyzed using GenePixTMPro 6.0. Results: We revealed a significant (p &lt; 0.05) increase in expression of such proteins as C-myc, SMAD4, PCAF, Adaptin (b1 + b2), FAK Phospho (pY577), PKC g and Phospho-Pyk2 (pY579/580) by 2.1; 1.5; 1.5; 1.5; 2.7 and 1.6 times, respectively, in tumor tissue of patients with metastatic colorectal cancer compared to non-tumor colon tissues. A significant increase (p &lt; 0.05) in expression of proteins NGFR p75 (Nerve Growth Factor Receptor) by 3.8 times and Phospho-Ta (pS199 / 202) by 1.9 times was found in tumor tissue of patients with non-metastatic CRC in comparison with non-tumor colon tissue. Conclusions: The study showed changes in proteomic profile of malignant colon tissue, and proteomic profile differed significantly in tumor tissues of patients with metastatic and non-metastatic cancer. We found changes in expression of 9 proteins, differential in each group of patients (with metastatic and non-metastatic CRC). These proteins have a high potential as biomarkers for CRC prognosis prediction.
Interim analysis of survival outcomes in a prospective cohort evaluating a prognostic 31-gene expression profile (GEP) test for melanoma.
Authors: Eddy C. Hsueh, James R. DeBloom, Jonathan H. Lee, Jeffrey J. Sussman, Craig L. Slingluff, Kelly McMasters
Journal: Journal of Clinical Oncology (2017)

9573 Background: DecisionDx-Melanoma has been validated as an accurate prognosticator of cutaneous melanoma (CM) metastasis risk. The GEP test classifies CM pts as Class 1 (low risk) or Class 2 (high risk). Interim survival analysis from two clinical registry studies (NCT02355574/NCT02355587) designed to prospectively evaluate outcomes in pts for whom the GEP test was performed is described. Methods: Eleven US dermatologic and surgical centers participated in the IRB-approved protocols. Physicians enrolled CM pts who were ≥16 years old and had successful GEP test results. Endpoints of recurrence-free (RFS), distant metastasis-free (DMFS) and melanoma-specific survival (MSS) were assessed using Kaplan-Meier and Cox regression analysis. As an interim analysis at year 3 of an expected 5-year study, the critical alpha level (p-value) was 0.01. Results: At the time of data extraction, 322 pts were accrued and completed at least one follow-up visit. Median age was 58 years (range 18-87), median Breslow thickness (BT) was 1.2mm, 55% were male, 20% (58/296) were ulcerated, and 15% (36/237 biopsied) had a positive sentinel lymph node (SLN). Median follow-up time was 1.5 years for pts without a recurrence. Of 25 recurrent cases, 80% (20/25) were Class 2 and 40% (10/25) were SLN-positive. Two percent of Class 1 pts had a recurrence compared to 6% (12/201 biopsied) of SLN-negative pts. Of the SLN-negative pts who recurred, 75% (9/12) were called Class 2. Combined GEP and SLN risk prediction identified 88% (21/24) of recurrences. Kaplan-Meier event rates for each class are shown in the table. In Cox multivariate analysis, BT and GEP Class 2 were significant predictors of recurrence (p&lt;0.01 for each). Conclusions: Results of this analysis show that the GEP test provides prognostic information that complements conventional staging and significantly enhances identification of high risk CM pts, consistent with reported validation studies.The results support use of the test for guiding surveillance decisions and enrollment of CM pts in clinical trials. Clinical trial information: NCT02355574, NCT02355587. [Table: see text]
24-hour cancer clinic: An approach to same-day care.
Authors: Jonathan Thomas Kapke, Ravi Narra, Tina Curtis, Dave Atkinson, J. Douglas Rizzo, Laura C. Michaelis
Journal: Journal of Clinical Oncology (2018)

6544 Background: Managing healthcare delivery and optimizing the cost of care for cancer patients is a difficult task for healthcare systems. Cancer patients are at risk for complications of their disease and adverse effects of treatment that often require urgent medical care. The inability to access oncology specific care 24-hours a day can lead to increased use of the Emergency Department (ED), which is often associated with unnecessary diagnostic testing, high rates of hospital admission, low patient satisfaction and excessive cost. On 11/1/16, Froedtert & the Medical College of Wisconsin opened the 24-hour Cancer Clinic (24hCC). The 24hCC is staffed by oncology trained providers and offers around the clock access to patients for a variety of urgent care needs. In this study, we evaluated resource utilization, admission rates, patient satisfaction and cost for patients seen in the 24hCC compared to the ED. Methods: We analyzed de-identified data for patients seen in the 24hCC and the ED between 1/1/17 and 1/24/18 as part of a quality improvement project. Utilization was defined as the quantity of imaging, ECG and lab studies ordered. Cost was measured based on hospital charges. Patient satisfaction surveys were reviewed. Results: Prior to the 24hCC, oncology patients seeking urgent, same-day care were often directed to the ED. There were an average of 250 ED visits per month with an admission rate of 55%. During the time period analyzed, 897 patient visits were completed in the 24hCC and 1621 in the ED. There was 56%, 32% and 11% less imaging, ECG and lab utilization respectively for patients seen and discharged from the 24hCC compared to the ED. The admission rate from the 24hCC was 18% compared to 42% from the ED. The mean overall rating of care for the 24hCC was 97.5%, with a 89.7% top box score (9 or 10 on 1-10 scale). When comparing diagnostic charges in the 24hCC to the ED during the first six months of data collection, the median charge was $1554 less for discharged patients and $2269 less for admitted patients. Conclusion: Our data demonstrates that a 24-hour oncology specific clinic can provide same-day care that is associated with decreased utilization, less hospital admission, improved patient satisfaction and lower cost for selected non-emergent cancer patients.