tbuckley/cabot-search huggingface dataset:
P01.066 Patients with EGFR amplification but without EGFRvIII expression have improved benefit compared to those with EGFRvIII expression in samples of the INTELLANCE 2/EORTC 1410 randomized phase II trial
Authors: P J French, J Kros, I de Heer, P Ansell, J Looman, E Bain, M Morfouace, T Gorlia, V Golfinopoulos, M van den Bent
Journal: Neuro-Oncology (2018)

Depatux-M is an antibody-drug-conjugate consisting of an antibody (ABT-806) bound to the toxin monomethylauristatin-F. A randomized phase II trial on EGFR-amplified recurrent glioblastomas (GBMs) showed a significant improvement (p=0.06 in the primary analysis, p=0.024 in follow-up analysis) in overall survival in the Depatux-M+TMZ arm when compared to the control arm (CCNU or TMZ). In this study, we performed targeted next generation sequencing and correlated molecular features with response to treatment in order to better identify patients that benefit from the combination. DNA and RNA was isolated from samples, collected at initial diagnosis, and selected for regions with highest tumor content. Target selection was done using the Trusight 170 gene panel (Illumina) which interrogates somatic variants and copy number, RNA levels and fusion genes in a set of known cancer genes. Variant calling was done using the Illumina Basespace sequence hub. For this trial, patients were eligible with centrally confirmed EGFR amplification, defined as EGFR/CEP 7 (centromere) ratio ≥ 2 in 15% of cells (FISH) DNA and RNA data were generated from 233 and 234 samples respectively (of the 260 study patients). High-copy gene amplification was detected in EGFR (n=202), MDM2 (n=20), MDM4 (n=22), CDK4 (n=24) and CDK6 (n=5) which correlated with high expression levels. With this assay, 17 tumors did not show EGFR copy number (cn) aberrations (cn < 2.8), a further 14 showed copy number changes consistent with trisomy (2.8< cn < 4). Most EGFR amplified tumors also had additional genetic changes in the EGFR locus including point mutations (111/202), splice variants (132/202, the most common being EGFRvIII n=96) or fusion genes (13/202). Twenty-one samples did not contain additional genetic changes and expressed only EGFRwt. Response to treatment was not correlated to EGFR gene expression or amplification levels though, since EGFR amplification was a pre-requisite for inclusion, the majority of cases expressed high levels of EGFR. Preliminary analysis in the Depatux-M +TMZ arm suggests that subjects with EGFR amplification but without EGFRvIII expression had a superior clinical benefit to those with EGFRvIII expression (median survival 14.6 v. 9.2 months, HR 0.57, P=0.04). No such association was identified in the Depatux-M or TMZ/CCNU arms where the median survival of EGFRvIII negative v positive was 7.7 v. 8.3 and 8.8 v. 7.5 months respectively. Depatux-M in combination with TMZ showed a trend towards improved OS in EGFR amplified recurrent glioblastoma. This trend may be greater for subjects with an absence of EGFRvIII expression.
Radium-223 following front-line chemotherapy for patients with non-small cell lung cancer and bone metastases.
Authors: Angela Marie Taber, David Riley, Adam J. Olszewski, Ariel E. Birnbaum, Humera Khurshid, Don Yoo, Richard Noto, Kayla Rosati, Howard Safran
Journal: Journal of Clinical Oncology (2018)

e21211 Background: Radium-223 dichloride (Ra-223) is a targeted- alpha particle emitting therapy directed at bone metastases with high-linear energy transfer at a short-range. This study investigated the safety and efficacy of Ra-223 given after front-line chemotherapy in patients with non-small cell lung cancer (NSCLC) metastatic to bone. Methods: In this prospective phase II study, patients received up to 6 injections of Ra-223 (55 kBq/kg IV) q 4 weeks as maintenance therapy if they had not progressed after front-line chemotherapy. The primary end point was the proportion of patients who experienced their first symptomatic skeletal-related event (SSE) during study treatment. The control was a historic experimental arm consisting of 257 patients (majority having NSCLC) who received zoledronic acid 4mg q 3 weeks in which approximately 40% of patients experienced a SSE. Secondary endpoints included toxicity, time to SSE, PFS and OS. Results: Five of the planned 36 patients were enrolled (study closed due to slow accrual). Median number of cycles received was 3.8 (range 2-6). One patient developed a SSE (pathologic T7 fracture) after 219 days. The four remaining patients did not experience a SSE during follow-up. Treatment-related adverse events (TRAEs) were mostly grade 1/2. Two patients experienced grade 3 TRAEs; one diarrhea and one lymphopenia. No grade 4 TRAEs were seen. PFS at 6 months was 80.0% (95%CI, 20.4 to 96.9). PFS at 12 months was 40.0% (95%CI, 5.2 to 75.3). Median PFS was 10.3 months (95%CI, 4.0 to not reached). No patients expired over the planned one year of follow-up. Genomic testing and review of results are planned. Conclusions: Ra-223 has a highly favorable safety profile in patients with NSCLC who have received front-line chemotherapy. Though this study had few patients, the PFS and OS results suggest that Radium-223 might play a potential role in the treatment of NSCLC and warrants further investigation. Clinical trial information: NCT02283749.
Prognostic value of tumour infiltrating lymphocytes in stage II colon cancer. A nationwide population-based study.
Authors: Ann Christina Eriksen, Flemming Brandt Sørensen, Jan Lindebjerg, Henrik Hager, Rene dePont Christensen, Sanne Kjaer-Frifeldt, Torben Hansen
Journal: Journal of Clinical Oncology (2018)

3580 Background: Patients with high-risk stage II colon cancer (CC) may benefit from adjuvant chemotherapy, but additional prognostic markers are needed for better treatment stratification. We investigated the prognostic value of tumour infiltrating lymphocytes (TILs) in a true population-based cohort of patients with stage II CC. Methods: A total of 573 patients were included, representing all patients operated for stage II colon cancer in Denmark in 2002. Tumour blocks representing the deepest invasive part of the primary tumour were used for analysis. CD3+ and CD8+ TILs at the invasive front were evaluated by immunohistochemistry on whole tumour sections. The invasive area was manually outlined, and Visiopharm Integrator System software was used for quantification. Data were dichotomized for comparison with clinical data. The prognostic value was investigated in Cox proportional hazard models for recurrence-free survival (RFS) and overall survival (OS). Results: Low CD3+ or CD8+ TILs were significantly associated with poor RFS and OS, (p = 0.0021 and p≤0.0009, respectively, log-rank test). In multiple Cox regression analysis low CD3+ and CD8+ TILs were associated with reduced RFS with hazard ratio (HR) 1.386 (95% CI 1.039-1.850), p = 0.026, and HR 1.394 (95% CI 1.029-1.890), p = 0.032, respectively, independent of age, T-stage, localization, perforation, and microsatellite instability (MSI). In the subgroups of patients with low CD3+ or CD8+ TILs, there were no differences in survival between patients with MSI and microsatellite stable tumours, (p = 0.821 and p = 0.907, respectively). Conclusions: Low CD3+ and CD8+ TILs in the invasive area are both related to inferior prognosis in patients with stage II CC, and we recommend either of these parameters to be considered as an additional high-risk factor.
Impact of rasburicase use in outpatient management of high uric acid.
Authors: Scott C. Howard, Alex R Cockerham, Edward Joseph Drea, Yvonne Jean Barnes, Lucio Gordan
Journal: Journal of Clinical Oncology (2018)

e19032 Background: Rasburicase is used to manage patients at risk of tumor lysis syndrome (TLS), but its use in the outpatient setting is not well known. This retrospective cohort analysis estimated the association of outpatient rasburicase use with hospital admission for hyperuricemia, a hallmark of TLS. Methods: Data from outpatients diagnosed with leukemia/lymphoma presenting with hyperuricemia following anticancer therapy were obtained from the US MedAssets hospital database for Jan 2010–Jun 2016. Patient demographics, comorbidities, total days of hospital admission following outpatient index visit, and rasburicase use were recorded. A multivariable logistic regression model was developed to evaluate the association between outpatient rasburicase use and hyperuricemia-related hospital stay, controlling for age, gender and comorbidities. Results: Data for 899 patient visits with leukemia/lymphoma-related hyperuricemia were collected from > 400 hospitals across the USA. Patients receiving rasburicase were older and more likely female, with a higher Elixhauser comorbidity score (1.9 vs. 1.4) and more urgent hospital admissions (Table). Multivariable analysis showed that patients who received rasburicase spent fewer days in hospital within 1 month (5.9 vs 7.0 days; p = 0.17), 2 months (7.7 vs 10.4 days; p = 0.02) and 3 months (9.5 vs 12.6 days; p = 0.03) of diagnosis compared with those who did not, controlling for age and comorbidity scores. Conclusions: Outpatient use of rasburicase may be associated with fewer days spent in hospital post-treatment. Future analyses will assess baseline TLS risk, ethnicity and hospital type as well as the economic burden associated with hyperuricemia sequelae and the impact of rasburicase. Demographic characteristics Rasburicase (n = 73) No rasburicase (n = 826) N % N % Age, mean (SD) 65.3 (12.5) 48.1 (27.7) Sex, male 46 63.0 544 65.9 Total hospital index visits 73 100 826 100 Cancer type Leukemia 39 53.4 440 53.3 Lymphoma 34 46.6 386 46.7 Index visit admission type Emergency1 10 13.7 22 2.7 Urgent2 10 13.7 35 4.2 Elective 52 71.2 541 65.5 Other/ unknown 1 1.4 228 27.6 1 Immediate medical intervention needed (generally admitted through ER). 2 Immediate attention needed (though not generally admitted through ER).
Locally advanced colorectal cancer: Is a second look surgery and prophylactic HIPEC warranted?
Authors: Rahul Bhamre, Jay Rashmi Anam, Manish Bhandare, Avanish Saklani
Journal: Journal of Clinical Oncology (2017)

e15056 Background: Peritoneal recurrence/carcinomatosis (PC) after curative surgery for colorectal cancer is the second most common site of recurrence and carries a poor prognosis. PC present relatively in the later stage, are difficult to detect by conventional imaging on follow up, and have limited options to treat after diagnosis. Second look surgery is the only definite option to diagnose early PC and presents an opportunity for disease control by cytoreductive surgery (CRS) and HIPEC. Multiple studies have attempted to identify clinico-pathological risk factors that predict high chances of PC. Our aim is to analyze the recurrence patterns and survival in locally advanced colorectal cancer, in an attempt to identify high risk factors for PC, which can be used as an indication for second look surgery and prophylactic HIPEC in such cases. Methods: Retrospective analysis of a prospectively maintained data of all colorectal cancer patients presenting to a tertiary cancer care referral center in India, from May 2010 to October 2015 was done. All patients who underwent surgery with curative intent and were clinico-pathological stage T4 and/or N2 M0 were included in the analysis. Results: 182 patients underwent curative resection with a clinico-pathological staging of T4 and/or N2 M0. There were 71 recurrences, out of which 30 (42.2%) were peritoneal, 7 (9.9%) were hepatic only while 34 (47.9 %) were non-hepatic systemic or multiple site. For a median follow up of 26 months, the estimated 3 year OS was 78 % while the 3 year DFS was 50.4 %. The median time to diagnosis of peritoneal recurrence was 13 months (4.7 – 55.7). The 3-year OS for patients with peritoneal recurrence was 48.6 % as against 57 % for liver only recurrence and 59.9 % for non liver systemic and multiple site recurrence, with a trend towards poorer survival for peritoneal recurrences, although non-significant (p – 0.377). Conclusions: Locally advanced colorectal cancer has a high risk of peritoneal recurrence which negatively impacts the survival. Well-designed RCTs need to be conducted to identify the high risk factors for PC and whether second look surgery and prophylactic HIPEC in such patients will improve survival with acceptable morbidity and mortality.
Parallel VENTANA IHC and RT-PCR of ALK status in non-small cell lung cancer and response to crizotinib.
Authors: Chunwei Xu, Wen-xian Wang, Meiyu Fang, Yan-ping Chen, Yu Chen, Li-hua Zhong, Fang-fang Chen, Wu Zhuang, Gen Lin, Xiao-hui Chen, Hai-peng Xu, Yun-jian Huang, Yan-Fang Guan, Xin Yi, Tangfeng Lv, Xiao-jiang Wang, Yi Shi, Xian-dong Lin, Gang Chen, Yong Song
Journal: Journal of Clinical Oncology (2017)

11623 Background: Advanced NSCLC patients who harbor (ALK) rearrangement were sensitive to crizotinib. However, not all ALK-positive patients benefit equally from crizotinib. A method for determining ALK rearrangement is RT-PCR, the Chinese FDA has approved RT-PCR to detect ALK rearrangement. In this regard, VENTANA IHC is a standard method to identify ALK protein overexpression in NSCLC. However, up to now, it is still largely unknown about the response to crizotinib for Chinese NSCLC patients having ALK overexpress detected by VENTANA IHC. To better clarify the clinical implication of VENTANA IHC to detect ALK rearrangement, we compared the curative effect and survival by the two methods in advanced NSCLC patients and analysis VENTNA IHC and RT-PCR inconsistent cases. Methods: A total of 1720 patients with NSCLC who had their ALK rearrangement detected by IHC and/or RT-PCR were included in this analysis. And we compared the efficacy and survival of patients with ALK positive detected by IHC and RT-PCR. We used next-generation sequencing (NGS) to detect patients whom two methods were not consistent. Results: 187/1720 patients were identified as ALK-positive by IHC and/or RT-PCR and 66 patient received crizotinib. We identified 172/1674 patients had ALK positive by IHC method, 41/322 patients had ALK rearrangements by RT-PCR method. And 29/276 patients with ALK positive were simultaneously analyzed by IHC and RT-PCR. The overall response rates (ORR) were 65.90% by IHC and 55.88% by RT-PCR, respectively. And the disease control rates (DCR) were 86.36% by IHC and 76.47% by RT-PCR. The median PFS of IHC was 8.5 months and RT-PCR was 9.2 months Targeted next-generation sequencing in the special type: Among 6 cases of 17 cases ALK positive patients were inconsistent by IHC and RT-PCR performed with NGS, 4 cases were identified to have EML4-ALK fusions, and 2 cases were KCL1-ALK(ND) and FBXO36-ALK (PFS 21.2 months). Conclusions: VENTANA IHC is a reliable and rapid screening tool in routine pathologic laboratories for the identification of suitable candidates for targeted therapy. It has a moderate sensitivity and a slightly higher curative effect, and some VENTANA IHC positive but RT-PCR negative cases may benefit from crizotinib.
Impact of prior therapy on efficacy and safety of oral ixazomib-lenalidomide-dexamethasone (IRd) vs placebo-Rd in patients (pts) with relapsed/refractory multiple myeloma (RRMM) in TOURMALINE-MM1.
Authors: María-Victoria Mateos, Tamas Masszi, Norbert Grzasko, Markus Hansson, Irwindeep Sandhu, Ludek Pour, Luisa Viterbo, Sharon R. Jackson, Anne-Marie Stoppa, Peter Gimsing, Mehdi Hamadani, Gabriela Borsaru, Deborah Berg, Jianchang Lin, Helgi Van De Velde, Paul G. Richardson, Philippe Moreau
Journal: Journal of Clinical Oncology (2016)

8039 Background: TOURMALINE-MM1 (NCT01564537) demonstrated improved PFS with IRd vs placebo-Rd (median 20.6 vs 14.7 mos; HR 0.74) in pts with RRMM after at least 1 prior therapy (Moreau et al, ASH 2015). Efficacy and safety of IRd vs placebo-Rd were analyzed according to prior proteasome inhibitor (PI) and prior thalidomide (thal)/lenalidomide (R) exposure. Methods: Pts were randomized 1:1 to receive IRd or placebo-Rd until disease progression or unacceptable toxicity. Pts with prior PI- and thal/R-based regimens, and pts refractory to thal, were eligible, but not pts refractory to PI- or R-based prior therapy. Results: Of 722 pts, 69% had prior PI therapy (< 1% prior carfilzomib) and 55% had prior thal/R therapy, including 45% prior thal (12% thal-refractory) and 12% prior R. Prior therapies were balanced between arms. At the primary analysis (median follow-up ~15 mos), consistent PFS benefit was seen with IRd regardless of prior PI or thal/R exposure (Table). CR+VGPR rates with IRd vs placebo-Rd appeared generally similar in PI-naïve (54% vs 37%), PI-exposed (46% vs 40%), thal/R-naïve (51% vs 44%), thal/R-exposed (45% vs 35%), R-naïve (48% vs 39%), and R-exposed (45% vs 36%) pts, but lower in thal-refractory (30% vs 27%) pts. At a 23-mos analysis, IRd safety profile was consistent regardless of prior PI or thal/R exposure; rates of grade ≥ 3 AEs with IRd vs placebo-Rd were 76% vs 66% in PI-naïve, 73% vs 70% in PI-exposed, 75% vs 71% in thal/R-naïve, and 73% vs 67% in thal/R-exposed pts. Conclusions: The benefit of IRd vs placebo-Rd appeared consistent across subgroups defined by prior PI and thal/R exposure, with a consistent safety profile with IRd. Clinical trial information: NCT01564537.Median PFS, mos. Subgroup IRd, N = 360 Placebo-Rd, N = 362 HR PI naïve (n = 110 vs 109) NE 15.7 0.75 Bortezomib (Btz) naïve (n = 112 vs 112) NE 15.9 0.75 PI exposed (n = 250 vs 253) 18.4 13.6 0.74 Btz exposed (n = 248 vs 250) 18.5 13.6 0.75 Thal/R naïve (n = 167 vs 158) 20.6 13.6 0.70 R (n = 316 vs 318) / Thal naïve (n = 203 vs 192) 20.6/20.6 13.6/13.6 0.77/0.69 Thal/R exposed (n = 193 vs 204) NE 17.5 0.74 R exposed (n = 44 vs 44) NE 17.5 0.58 Thal exposed (n = 157 vs 170) / refractory (n = 40 vs 49) NE/16.6 15.7/13.0 0.75/0.73
P05.93 Adult medulloblastoma: analysis of use of chemotherapy in clinical practice
Authors: M Mastall, N Majd, G Fuller, M Gule-Monroe, J Huse, S Khatua, G Rao, D Sandberg, J Wefel, D Yeboa, W Zaky, A Mahajan, V Puduvalli, D Suki, K Alfaro, S Weathers, R Harrison, J de Groot, M Penas-Prado
Journal: Neuro-Oncology (2018)

Adult medulloblastoma (MB) is rare, accounting for 150–300 new cases in the US annually. Given the low incidence, prospective studies are challenging, and the role of adjuvant chemotherapy in standard risk patients has been controversial. Currently, the best evidence available (Level V) supports the use of upfront chemotherapy. A recent pilot prospective study (NOA-07) proved feasibility of craniospinal irradiation with vincristine, followed by cisplatin, lomustine and vincristine; 4 cycles were feasible in most patients. However, toxicity was substantial. In clinical practice, attempts to ameliorate the intensity of the treatment regimen are common, such as substitution of cisplatin by carboplatin, or removal of vincristine. It is not known if these modifications compromise outcome, and the optimal chemotherapy regimen for adult MB patients to balance efficacy and tolerability has not been established. We analyzed patterns of use of chemotherapy retrospectively in a large single institution database of patients with adult medulloblastoma. To date, 136 patients (≥18 years at diagnosis) evaluated from January 1978 to April 2017 have been identified (additional patients are being analyzed). Median progression-free survival (mPFS), median overall survival (mOS), 5-year progression free survival (PFS-5) and 5 year-overall survival (OS-5) were estimated using the Kaplan-Meier method. Median age was 28 (18–63); female-to-male ratio 1.7:1; 69/136 (50.7%) were standard risk, and 53/136 (39.0%) were high risk (subtotal resection and/or metastasis) (indeterminate risk in 14). In patients without residual disease at initial diagnosis, 27/79 (34.2%) received chemotherapy upfront; carboplatin vs. cisplatin regimens in 8 vs. 11 patients; vincristine vs non-vincristine in 20 vs. 6 patients. The patients treated with upfront chemotherapy had significant improvement in outcome in comparison with those who did not receive upfront chemotherapy (PFS-5 of 56.6% vs. 84.2%, p=0.018 and OS-5 of 79.5% vs. 90.0%, p=0.050). There was no statistically significant difference between the survival of those who had received carboplatin vs. cisplatin (PFS-5 of 100% vs. 74.1%, p=0.197 and OS-5 of 100% vs. 85.7%, p=0.325). Addition of vincristine was not associated with improved outcome (PFS-5 92.9% vs. 55.6%, p=0.166 and OS-5 of 90.9% vs. 83.3%, p=0.090). To date, we have not found a statistically significant difference in outcome in patients without residual disease treated with carboplatin vs. cisplatin-based regimens, or between regimens containing vincristine and regimens not containing vincristine. Attenuated regimens of chemotherapy in adult medulloblastoma patients may decrease toxicity without compromising efficacy. Additional patients will be added to this cohort to further improve the accuracy of this study.
How to measure faculty clinical activity in a comprenhesive cancer center.
Authors: Rafael Alvarez-Gallego, Jesus Rodriguez-Pascual, Lisardo Ugidos, Eduardo Garcia-Rico, Cesar Munoz, Antonio Cubillo
Journal: Journal of Clinical Oncology (2017)

e18202 Background: The faculty clinical activity in a comprehensive Cancer Center is difficult to measure. Time clinical units is the most common procedure worldwide. In our group we have developed a new system based on the daily real activity of each medical oncologist of our team. Methods: We collected the daily activity from january to december 2016 of each doctor considering different values( from 1 to 4)depending on the complexity of the activity. Follow up visit of a patient (1), treatment visit (2). Clinical trial visit or Inpatient visit (3) and New Patient First visit (4). Then we added all the daily values of each medical oncologist. Results: 2016 Clinical activity growth measured by traditional time methods was consider 31,5%. When we applicated our new method it was 33,4%. The clinical activity of each Oncology Unit changed clearly when we applied our method. For example , breast cancer unit change from 25% to 20 % of the global activity, GI Unit from 47% to 50%, Lung Unit from 13% to 15% . In Genitourinary and Gynecological cancer and Prostate tumor units there are no change. This changes draw the different complexity of each Oncology Unit. It was clearly usefull to get a better information of the real clinical activity of each team and cancer center. Conclusions: This tool can be useful to unifique and compare the different complexity in the clinical activity of Medical Oncology Teams, units and hospitals allocating resources based on this new system.