tbuckley/cabot-search huggingface dataset:
Multispectral quantitative analysis of tumor-infiltrating lymphocyte (TIL) in triple negative breast cancer.
Authors: Tomoharu Sugie, Eiichi Sato, Minoru Miyashita, Rin Yamaguchi, Takashi Sakatani, Yuji Kozuka, Suzuko Moritani, Eiji Suzuki, Kazuhiro Kakimi, Yoshiki Mikami, Takuya Moriya
Journal: Journal of Clinical Oncology (2018)

e24123 Background: Standardized evaluation of TIL is currently based on the extent of lymphocytic infiltration into the tumor stroma for breast cancer. However, the distributions of subpopulations and immune checkpoint molecules are not well determined in the intratumor as well as the stromal area. Methods: Thirty-one surgical archives of triple negative breast cancer (TNBC) were cut in sections and the following antibodies were used for multicolor staining: DAPI (Opal 7-color kit, Perkin Elmer), anti-CK (AE1/AE3, DAKO), anti-CD8 (CD8/144B, Abcam), anti-FOXP3 (236A/E7, Abcam), PD-L1(SP142, Spring Bio). Multicolor slides were loaded onto Vectra automated multispectral microscope (PerkinElmer, Hopkinton, MA) and inForm|Advanced image analysis software was used to quantify multiple biomarkers in the single section. Results: Quantification of immune cells and check point molecule was summarized in Table. CD8, FoxP3 and PD-L1 densities and intensities in the stromal area were significant higher than those in the intratumor area (p < 0.01) and all these molecules were significantly positively correlated each other in the stroma (p < 0.01). Among them, the highest positive correlation was observed between stromal PD-L1 and stromal CD8 (r = 0.82, p < 0.01). Density of tumor PD-L1 was also associated with CD8 infiltration into tumors as well as the tumor stroma (r = 0.514; p < 0.01 and r = 0.598; p < 0.01, respectively). Infiltration of FoxP3 positive cells into the stroma was correlated with PD-L1 expression in the stromal but not the intratumor area (r = 0.4; p < 0.05 and r = 0.20; p = 0.28, respectively). Conclusions: Infiltration of CD8 T cells is associated with immuno-inhibitory ligand and regulatory cells. Expression of PD-L1 in the tumor stroma, not the intratumor area represents an actual immune reaction. Stromal PD-L1 may be a better marker for immuno-oncology therapy for TNBC. Mean (95%CI) CD8 FOXP3 PD-L1 Density (cells mm-2) Intratumor 110.9 (66.4-155.5) 25.4 (15.7-35.1) 134.2 (41.9-226.6) Stroma 367.5 (228.1-506.8) 157 (110.3-203.8) 482.9 (251.0-714.7) Intensity (int pixel-1) Intratumor 8.8 (6.9-10.6) 1.9 (1.3-2.6) 3.8 (2.5-5.2) Stroma 6.2 (4.4-8.0) 2.9 (1.8-4.1) 7.9 (4.3-11.4)
Detailed pathologic evaluation of low dose CT (LDCT) detected stage I/0 lung adenocarcinomas (ADCA).
Authors: Eric Burks, Jacob Sands, Travis B. Sullivan, Kimberly M. Rieger-Christ
Journal: Journal of Clinical Oncology (2017)

8543 Background: Although LDCT lung screening improves survival, some worry that indolent BAC-like ADCA may be over-detected/treated. Comprehensive histologic subtyping has recently been adopted to improve grading and thus risk stratification in lung ADCA. We report a detailed pathologic comparison of stage I/0 lung ADCAs detected by LDCT screening vs. incidentally discovered ADCAs stratified by NCCN risk criteria. Methods: We performed comprehensive histologic subtyping on 35 consecutive stage I/0 LDCT screen detected ADCAs in patients meeting NCCN group 1/2 high risk (HR) criteria and compared to incidentally detected stage I/0 ADCAs meeting HR (n = 41) or low-risk (LR, n = 28) criteria. Results: Screen detected and incidentally detected ADCAs from HR groups show an equally low-rate of indolent, non-invasive/minimally invasive ADCAs (9%) compared to LR patients (36%). Aggressive solid predominant ADCAs were equally more frequent in HR patients from screen and incidentally detected patients (19%) compared to LR patients (6%). The rate of angiolymphatic invasion (59%) and air space invasion (32-34%) were similarly elevated in HR screen and incidental patients compared to LR patients (39% &amp; 17% respectively). A collection of lepidic predominant (BAC-like) ADCAs associated with aggressive non-predominant cribriform and/or solid patterns, elevated mitotic rates, and high proportion of lymphatic invasion were uniquely observed in the screen-detected group (12%). Subgroup analysis of screen detected NCCN group 1 vs. 2 shows group 2 tumors exhibit histologic features which are at least as aggressive as group 1 tumors, albeit at smaller invasive sizes (1.2 cm vs. 1.5 cm) and lower stage (IA 75% vs. 61%). Conclusions: This is the first detailed pathologic comparison of LDCT screen detected vs incidentally discovered stage I/0 ADCA. Tumors from HR patients are pathologically more aggressive than LR tumors. Not all BAC-like tumors in LDCT screen detected patients should be presumed indolent given that approximately half of these bear histologic features of aggressive ADCAs while still in a lepidic predominant phase. NCCN group 2 tumors are similar to group 1 and should be further studied.
Second or none: Many patients treated for refractory differentiated thyroid cancer with small molecular kinase inhibitors do not receive a second line of therapy.
Authors: Ronda Copher, Oluwakayode Adejoro, Stacey DaCosta Byfield, Mary DuCharme, Debanjana Chatterjee, Prashant Ramesh Joshi, Avinash Desai, Mahadi Ali Baig
Journal: Journal of Clinical Oncology (2017)

e17589 Background: Describe the treatment patterns of patients initiated on NCCN-recommended small molecular kinase inhibitors (SMKIs) for radioiodine-refractory differentiated thyroid cancer (DTC) approved in the United States. Methods: A large national US claims database was used to identify adult patients diagnosed with thyroid cancer (≥2 non-DX medical claims, ≥ 30 days apart) from 1/1/2006 - 6/30/2016 (study period) with claims for SMKIs from 1/1/2010 - 5/31/2016. Continuous enrollment required participation in a commercial or Medicare Advantage health plan ≥3 months before and ≥1 month following index date (date of first pharmacy claim for SMKI). Line of therapy (LOT) periods were defined by receipt and timing of SMKIs. Patient follow up was earliest disenrollment, death or end of the study period. Patient characteristics and SMKI treatment patterns were described. Results: A total of 217 DTC patients were identified; 63% commercially insured and 37% Medicare Advantage. Almost half were male (48%); mean age was 61.2 years (standard deviation SD 12.5 years) and mean follow-up period was 499 days (SD 414 days). In the study period, 35% (n = 77) of patients had ≥2 LOTs and 18% (n = 39) had ≥3 LOTs. Mean treatment duration was 5.4 months (SD 6.7 mos) for LOT1, 4.9 months (SD 3.8 mos) for LOT2, and 4.2 months (SD 4.9 mo) for LOT3. During the full study period, the most used regimens were Sorafenib for both LOT1 (37%) and LOT2 (25%), pazopanib (18%) and sunitinib (18%) in LOT3. Also, in the study period, 33 patients had sorafenib in LOT1 of which 16 were treated with sorafenib again (48%) in LOT2. Post FDA approval in 2015, Lenvatinib became the predominant first-line regimen (47%, n = 29) during study period. Across all first line therapies, for those patients with ≥12 months of follow-up, 53% (n = 60) initiated LOT2. Conclusions: Sorafenib was the most common first line of therapy for DTC, with Lenvatinib adoption increasing as first-line therapy since the drug’s approval in 2015. Depending on the period evaluated, almost half to 2/3 of patients are not receiving a second line of treatment, efficacious and patient appropriate therapy is of importance in treating this rare cancer.
BRAF/MEK inhibition in melanoma patients with rare BRAF mutations.
Authors: Jessica Cecile Hassel, Christian Menzer, Alexander M. Menzies, Matteo S. Carlino, Georgina V. Long, Richard Kefford, Thomas K. Eigentler, Douglas Buckner Johnson, Max Schlaak, Frank Meiss, Bastian Schilling, Ralf Gutzmer, Claudia Pföhler, Friedegund Elke Meier, Lisa Zimmer, Thomas Haalck, Kai Thoms, Annette Kopp-Schneider, Alexander Enk
Journal: Journal of Clinical Oncology (2018)

9542 Background: BRAF/MEK inhibition is standard of care in patients (pts) with a BRAF V600E/K mutated melanoma. Efficacy data for pts with less frequent BRAF mutations are limited so far. Methods: 71 metastatic melanoma pts with rare activating BRAF mutations (excluding BRAF V600E/K) treated at 13 melanoma centers with either a BRAF inhibitor (i) or MEKi monotherapy or the combination were included. BRAF mutation, patient and disease characteristics, response and survival data were examined. Results: 41 (58%) pts harbored a rare BRAF V600 mutation and 30 (42%) a non V600 mutation (Table). The most frequent mutations were V600R (30 pts, 42%) and K601E (10 pts, 14%). The median age was 61 years, 75% were male. Most melanomas were of cutaneous origin (84%) and a nodular subtype (40%). At treatment start, most pts had stage IV M1c (44%) or M1d melanoma (28%) (AJCC 2017), and 40% had an elevated LDH. Most pts received combined BRAFi/MEKi (48%) or BRAFi monotherapy (45%). In the 41 pts with V600 mutations (30 = V600R, 4 = V600D) the response rate (RR) to single agent BRAFi and combination BRAFi/MEKi was 33 and 61%, respectively. Median PFS was 3.7 months and 8.2 months. In the 30 pts with non-V600 mutations (10 = K601E, 6 = L597Q/S) the RR to BRAFi was 7%, to MEKi 40% and to combination treatment 36%. Median PFS was 1.6 vs 4.8 vs 3.8 months. Conclusions: Patients with rare BRAF mutations can respond to targeted therapy. Pts with non-V600 mutations are less likely to respond to BRAFi monotherapy, but activity with MEKi alone or in combination with BRAFi appears more promising. BRAF genotype Treatment N ORR (CR + PR) Median PFS (in months) Median OS (in months) V600 Total 41 20 (49%) 7.3 16.1 BRAFi 18 6 (33%) 3.7 10.5 MEKi 0 - - - BRAFi/MEKi 23 14 (61%) 8.2 31.1 V600R Total 30 14 (50%) 6.5 14.8 BRAFi 12 3 (25%) 3.7 8.9 MEKi 0 - - - BRAFi/MEKi 18 11 (61%) 8.2 31.1 Non-V600 Total 30 7 (23%) 2.5 7.8 BRAFi 14 1 (7%) 1.6 7.6 MEKi 5 2 (40%) 4.8 6.9 BRAFi+MEKi 11 4 (36%) 3.8 8.0 K601E Total 10 1 (10%) 2.2 7.2 BRAFi 5 0 1.4 7.2 MEKi 1 0 0.4 5.2 BRAFi/MEKi 4 1 (25%) 3.8 NA* *Median not reached
Use and performance of mediastinoscopy before surgery for non-small cell lung cancer (NSCLC) in the Mid-South region of the United States (US).
Authors: Nicholas Ryan Faris, Fujin Lu, Matthew Smeltzer, Carrie Fehnel, Nibedita Chakraborty, Cheryl Houston-Harris, Raymond S Signore, Edward T Robbins, Raymond U. Osarogiagbon
Journal: Journal of Clinical Oncology (2016)

8543 Background: Reports on the use and performance of mediastinoscopy (med.) as a pre-operative invasive staging test for patients with NSCLC vary widely. We sought to evaluate med. use and performance for NSCLC patients in community level hospitals in a high incidence and mortality region of the US. Methods: We used patient-level data for 1,538 patients from 11 hospitals in 4 contiguous Dartmouth Hospital Referral regions (East Arkansas, West Tennessee, North Mississippi) who had a resected NSCLC from 2009-2013 with no neo-adjuvant therapy. We used descriptive statistics to summarize the pattern of med. use, logistic regression to compare stage distribution and Poisson regression to compare lymph node (LN) yield for patients who had a med. to those who did not. Results: Overall, 172 patients (11%) had a pre-operative med. Only 20% of patients with a clinical indication for a med. had one done. 94% of patients with no pathologic LN examination (pNX) and 84% of pathologic node positive (pN1-3) patients did not have a med. However, 20 patients (12%) had a positive finding of malignancy after med. but still went on to primary surgical resection. The median numbers of LN and LN stations examined from a med. were 2 and 1, respectively. Although there was a significant difference in LN examination for patients who had a med. and those who did not, the distribution of pathologic nodal stage was not significantly different between the two groups (Table). Conclusions: The use of mediastinoscopy as an invasive staging test is substantially lower than previous reports. Additionally, even when a med. is done, the performance is suboptimal: lymph node counts and station sampling during meds. are inappropriately low and even when done appropriately (found malignancy), some patients still went on to primary surgery. pN stage and lymph node examination rates by use of med.* Surgery without Med. n = 1366 Med. + Surgery n = 172 p value pN0 70% 63% 0.0707 pN1 12% 20% 0.0033 pN2 8% 12% 0.1421 Total N1 LNs (median (interquartile range)) 3 (1,6) 5 (2,8.5) <0.0001 Total N2 LNs 2 (0,5) 4 (2,7) <0.0001 Total N2 stations 1 (0,3) 2 (1,3) <0.0001 Total LNs 7 (3,11) 10 (6,15) <0.0001 *adjusted for patient characteristics.
A retrospective evaluation of unplanned hospital admission rates for women with ovarian cancer.
Authors: Shayan M Dioun, Eirwen Murray Miller, Joan Tymon-Rosario, Dennis Yi-Shin Kuo, Nicole Suzanne Nevadunsky
Journal: Journal of Clinical Oncology (2017)

e18129 Background: Unplanned admission following chemotherapy is a measure of quality cancer care. Large retrospective datasets have shown admission rates 10-35% in women with ovarian cancer receiving chemotherapy. It is unclear whether the Oncology Care Model is sustainable based on these admission rates. We sought to evaluate the rate and risk factors for hospital admission following chemotherapy in our racially diverse urban population. Methods: After IRB approval, all patients with epithelial ovarian cancer who received chemotherapy at our institution from 2005-2016 were identified. Charts were retrospectively reviewed for clinicopathologic data. Categorical variables were compared with chi-squared and continuous variables with the student t-test. Results: 222 evaluable patients were identified. 37 (17%) patients had unplanned admissions following initial chemotherapy. Indications for admission included neutropenic fever (9), abdominal pain (15), metabolic disturbances (2), infection (3), and other (8). The median number of days from chemotherapy to admission was 8 (IQR 7-18.5). No significant differences were seen in race, medical co-morbidities, age, or BMI in admitted patients. Stage and primary neoadjuvant chemotherapy were predictive of admission. Conclusions: Unplanned hospital admission rates following initial chemotherapy in our racially diverse patient population are consistent with previously reported rates. Though age and medical co-morbidities did not predict admission, stage and primary neoadjuvant chemotherapy were predictive of subsequent admission. The Oncology Care Model may not account for hospital admission rates of this magnitude and further investigation is needed to identify predictors of hospitalization and poor outcomes. [Table: see text]
OS2.2 Highly personalized peptide vaccination for patients with newly diagnosed glioblastoma: the GAPVAC trial
Authors: P Dietrich, W Wick, N Hilf, K Frenzel, C Gouttefangeas, M Platten, P thor Straten, U Lassen, J Rodon, V Bukur, A Admon, S H van der Burg, A von Deimling, J R Kroep, F Martinez-Ricarte, H Okada, C H Ottensmeier, B Ponsati, H S Poulsen, S Stevanovic, G Tabatabai, H Rammensee, U Sahin, H Singh-Jasuja
Journal: Neuro-Oncology (2018)

There is a need for treatment personalization as every cancer is molecularly unique. In addition glioblastoma (GB) are immunologically regarded as resistant, “cold” tumor with few targetable antigens available from mutations, thus demanding new personalized immunotherapies. So far outside Neuro-Oncology, T cells orchestrate impressive anti-tumor effects with checkpoint inhibitors, but also vaccines. The GAPVAC consortium established an immunotherapy, for which personalized selection of 2 peptide-based actively personalized vaccines (APVAC) per patient for treatment of newly diagnosed GB was based not only on whole-exome sequencing but also on human leukocyte antigen (HLA)-ligandome analyses providing insight into the actual presentation of relevant epitopes in the tumor. GAPVAC-101 (NCT02149225) enrolled 16 patients in a European phase I feasibility, safety and immunogenicity trial integrated into standard of care. For APVAC1, up to 7 peptides were selected from a trial specific warehouse based on individual biomarker data. Vaccination (i.d.) with GM-CSF and poly-ICLC in 15 patients started with the 1st adjuvant cycle of temozolomide (TMZ). For APVAC2, analyses revealed a median of 36 somatic, non-synonymous mutations in the patients’ tumors. From the 4th TMZ cycle, 11 patients received APVAC2 with usually 2 de novo antigens per patient selected according to mutation, actual or putative HLA presentation and immunogenicity. Overall 20 APVAC2 antigens incl. 14 mutated were vaccinated. Adverse events were largely reversible injection site reactions and two anaphylactic reactions and one increase in cerebral edema. Short, non-mutated APVAC1 antigens induced sustained CD8 responses with memory phenotype. Mutated APVAC2 antigens induced predominantly CD4 responses of favorable TH1 type. Median PFS and OS were 14.2 and 29 months from diagnosis, respectively, in patients that received ≥1 APVAC vaccination (N=15). Overall, GAPVAC displayed expected safety profiles and high biological activity indicating further development.
The effect of supervised, individualized exercise on cost savings during cancer treatment.
Authors: Karen Y Wonders, Malek M. Safa, Emily Jo Vannorsdall, Alejandro R. Calvo
Journal: Journal of Clinical Oncology (2018)

6605 Background: Research indicates that endurance exercise training is helpful in attenuating the deleterious effects of cancer treatments. However, nationally less than 5% of patients are ever referred to a cancer exercise program. Cost is a barrier to these programs, as they often are not reimbursable under most insurance plans. Therefore, the purpose of this investigation was to determine if exercise training during cancer treatment helped to minimize side effects and reduce health care costs. Methods: This was a retrospective, two-group study which ascertained the protective effect of an exercise-training program during cancer treatment. Medical records were reviewed to determine outcome data for length of hospital stays, hospital readmits, ER visits, treatment compliance, fatigue, and anxiety/depression related to oncology conditions. Patients were excluded if they had pre-existing conditions prior to treatment. Individuals in the exercise group (EX, n = 672) completed 12 weeks of prescribed, individualized exercise. Individuals in the sedentary group (SED, n = 728) did not participate in an exercise program during treatment. Results: Patients in the EX group had significantly lower reports of fatigue, pain, cardiac problems, depression, and anxiety than their SED group counterparts (p < 0.05). The EX group tolerated their treatment significantly better than the SED group (p < 0.05). Most notable, the EX group had a significantly lower number of ER visits, 30-day readmits, and length of stay (p < 0.05). Conclusions: These data point to a protective effect of individualized exercise that translated to improved patient outcomes and cost savings for the payer, provider, and patients, alike.
Effect of alectinib on cardiac electrophysiology: Results from intensive electrocardiogram (ECG) monitoring of alectinib phase I/II pivotal studies.
Authors: Peter N. Morcos, Katrijn Bogman, Volkmar Henschel, Carolina Sturm, Thorsten Ruf, Walter Bordogna, Sophie Golding, Ali Hassan Zeaiter, Bogdana Balas
Journal: Journal of Clinical Oncology (2016)

e20564 Background: Alectinib, a potent CNS-active ALK inhibitor, has received accelerated approval by the FDA for patients with ALK+ NSCLC who have progressed on, or are intolerant to, crizotinib. The ALK inhibitors crizotinib and ceritinib have shown concentration-dependent QTc prolongation and treatment-related bradycardia. This analysis evaluated alectinib safety in terms of electrophysiologic parameters. Methods: Intensive triplicate centrally read ECG and matched pharmacokinetic data were collected across two alectinib single-arm pivotal trials and pooled to evaluate the effect of alectinib 600 mg BID on ECG. Analysis of QTcF (Fridericia’s corrected QT interval), included corrected least squares mean changes from baseline with one-sided upper 95% confidence intervals (CI) categorical analyses, and relationship between change in QTcF and alectinib plasma concentrations using linear regression. In addition, alectinib effects on other ECG parameters were also evaluated. Results: A total of 221 patients were included in the ECG-evaluable population. Alectinib did not cause a clinically relevant change in QTcF. The maximum mean QTcF change from baseline was 5.3 ms (one-sided upper 95% CI: 7.2 ms) observed pre-dose at Week 2. The upper one-sided 95% CI was < 10 ms at all time points. The majority of patients (91%) had absolute QTcF values ≤ 450 ms. Only 1 patient ( < 1%) had a QTcF interval > 500 ms; however, this patient already displayed a raised QTcF value (485 ms) at baseline. Similarly, the majority of patients (87%) had changes from baseline of ≤ 30 ms, with only 1 patient ( < 1%) having a change of > 60 ms. There was no apparent correlation between the change in QTcF and alectinib plasma concentrations. Alectinib treatment resulted in a generally asymptomatic decrease in mean heart rate of ~11 to 13 bpm at Week 2, which was stable thereafter, consistent with other ALK inhibitors. No relevant effects were seen on other ECG parameters. Conclusions: Alectinib does not prolong the QTc interval nor cause changes in cardiac function to any clinically relevant extent, with the exception of a decrease in heart rate, which is generally asymptomatic. Clinical trial information: NCT01801111. Clinical trial information: NCT01871805.
Biology and clinical outcomes of estrogen receptor positive (ER+) early primary breast cancer (BC) in older (≥70 years) women—A study based on core needle biopsies (CNB).
Authors: Kwok-Leung Cheung, Mohammad A Albanghali, Binafsha Manzoor Syed, Andrew R. Green, Emad A. Rakha, Ian O. Ellis
Journal: Journal of Clinical Oncology (2018)

e24253 Background: BC in older women appears to have more favourable biology, when compared to their younger counterparts. Most studies use surgical excisions to profile tumour biology, which might result in bias as some older women do not undergo surgery due to frailty. Diagnostic CNB is an alternative source of tumour, available in patients who receive non-operative treatment e.g. primary endocrine therapy (PET). This study aimed to investigate tumour biology in older women with ER+ BC and correlate it with clinical outcomes, based on CNB. Methods: From a series of older women (n=1,758) with BC treated in a single institution with long-term (37+ years) follow-up, tumour biology profiling was conducted following the development of a technique to construct tissue microarrays (TMA) from CNB. Immunohistochemistry was employed to measure a panel of biomarkers (ER, PgR, Ki67, p53, EGFR, HER2, HER3, HER4, BCL2, CK5/6, CK7/8, MUC1, VEGF, PTEN, AIB1, LKB1 and BRCA1). Clustering analysis and correlation with clinical outcomes were performed for the ER+ tumours. Results: A CNB TMA technique was developed with capacity of 54 cores per block, and estimated number of obtainable sections >600. TMA blocks were constructed from 639 ER+ cases. For all patients, PgR, Ki67 and MUC1 were identified as independent prognostic factors in terms of breast cancer specific survival (BCSS). ER, PgR, BCL-2 and LKB1 were found to have independent prognostic value in terms of time to progression (TTP) among PET-treated patients. Clustering revealed 3 luminal clusters, each showing a specific pattern of ER, PgR, CK7/8 and MUC1 expression. These clusters identified sub-groups (luminal A and low ER luminal) of older women with a high chance to benefit from PET, achieving a comparable BCSS to that of surgery. For PET-treated patients, the luminal A cluster was associated with lower risk of progression and longer TTP. Conclusions: The developed CNB TMA technique demonstrates potential in tumour biology profiling. The biology identified appears to have great benefits in formulating an evidence-based therapeutic approach. Further work is underway to include the ER negative cohort.