tbuckley/cabot-search huggingface dataset:
Effect of irreversible electroporation (IRE) combined with chemotherapy (C) on survival in locally advanced pancreatic cancer (LAPC) patients (pts).
Authors: Michalis Karamouzis, Dimitrios Oikonomou, Nikolaos Dimitrokallis, Demetris Papamichael, Pantelis Kountourakis, George Astras, Demetrios Moris, Spyridon Davakis, Alexandros Papalampros, Athanasios S Petrou, Evangelos Felekouras
Journal: Journal of Clinical Oncology (2019)

e15723 Background: LAPC represents 40% of PC pts. IRE is a non-thermal ablative technique that can be used in inoperable pts and safely combined with C. Methods: From 2015 to 2018 laparotomic IRE was performed in a total of 34 LAPC pts. The median age was 64.7yrs (range, 46-81yrs) and 15 (44%) were males. The median tumor size was 3.9cm (range, 2-5.2cm) with the majority of tumors located at pancreatic head (26 pts, 76%), followed by body (6 pts, 18%) and tail of pancreas (2 pts, 6%). Induction C was applied in 27 out of 34 pts and in case of disease control IRE was done, while in 7 pts IRE was done without prior C. In the majority of pts C after IRE was also given. Results: Induction C was applied in 27 out to 34 pts (80%) [FOLFIRINOX in 16 pts, nab-paclitaxel-gemcitabine (AG) in 11 pts]. After the completion of 3 cycles of C tumor evaluation showed partial response (PR) in 20 pts and stable disease (SD) in 7 pts. All pts were treated with IRE and 50% of them had a preoperative biliary stent, while 3 pts had metallic stent that was removed before IRE. No IRE-related deaths occurred. Two major complications grade III were reported: pancreatic fistula grade A in 7 pts and 2 pts diagnosed with delayed gastric emptying. There was also one minor complication (wound infection) in 3 pts (9%). Up to 31/12/2018, the median overall survival (OS) of all pts was 24.2 months (mos) (range, 6-36 mos) and median progression free survival (PFS) was 14.6 mos (range, 3-24 mos). The median OS of the pts treated with C-IRE-C was 22.5 mos (range, 13-36 mos) and median PFS 16.9 mos (range, 3-24 mos), while in pts treated with IRE-C only was 15 mos (6-22 mos) and 10.9 mos (range, 5-16 mos), respectively. The group treated with FOLFIRINOX-IRE-C showed median OS 22.5 mos (range, 15-36 mos) and median PFS 17.1 mos (range, 3-24 mos), while the group treated with AG-IRE-C had median OS 19 mos (range, 13-36 mos) and median PFS 15.8 mos (range, 7-24 mos). After IRE, 24 pts (71%) continued with adjuvant C, either FOLFIRINOX 5 pts (15%) or G-based regimen 18 pts (46%) until disease progression or unacceptable toxicity, while 12 pts (35%) have more than 24 mos OS and 3 pts (9%) have reached 36 mos OS and are still alive. Conclusions: The combination of C with IRE is safe and results in survival increase of LAPC pts. Pts treated with the sequence FOLFIRINOX-IRE-C seems to benefit the most.
A joint model of tumor size dynamics and survival with new lesions in EGFR mutation-positive non-small cell lung cancer patients with treatment of gefitinib or carboplatin and paclitaxel.
Authors: James Dunyak, Hong Yan, Nidal Al-Huniti
Journal: Journal of Clinical Oncology (2019)

e20697 Background: Tumor dynamics have been serving as significant predictors in diagnosis, staging, prognosis and treatment of patients with non-small cell lung cancer (NSCLC). The purpose of this study is to propose a joint model that links the longitudinal tumor burden to progression free survival (PFS) with the appearance of new lesion in a population of NSCLC patients with gefitinib treatment or Carboplatin/Paclitaxel. Methods: The model was extended to the estimation of new lesion based on a previously developed tumor size and survival joint model. The derivative of the tumor loads and the probability of new lesions served as biomarkers in the survival submodel. Parameters were estimated from the posterior distribution in a Bayesian framework and numerical study was realized with R and STAN. A total of 434 NSCLC patients with EGFR mutation positive treated with gefitinib or chemotherapy (carboplatin+paclitaxel) from IPASS (‘NCT00322452’) were used to construct the model. Predictions were performed on the IFUM study (‘NCT01203917’) with 102 EGFR mutation positive NSCLC patients. Results: The model performed well in PFS prediction in both within-sample and out-of-sample estimations. Further improvement of model specifications is necessary since the tumor load developing rate and appearance of new-lesion negatively impacted survival predictions. About 90% accuracy was realized by the joint model when recapitulating the outcomes from the response evaluation criteria in solid tumors (RECIST). The appearance of new lesion contributed less than tumor size in accommodating drug effect when comparing progression-specific hazards. Conclusions: This Bayesian joint model well recapitulated the outcomes from the RECIST with sequentially updated tumor size that linked to survival predictions. New insights of relative predictive values were provided by the joint model regarding the components of RESICT.
Efficacy and safety profile of sunitinib as a first line treatment for advanced/metastatic clear-cell renal cell carcinoma: Pooled analysis of randomized controlled trials.
Authors: Tarek Haykal, Varun Samji, Yazan Zayed, Ragheed Al-Dulaimi, Inderdeep Gakhal, Areeg Bala, Jason Sotzen, Ranine Ghamrawi, Khalil Katato, Rizwan Danish
Journal: Journal of Clinical Oncology (2019)

e16067 Background: Metastatic clear-cell renal cell carcinoma (RCC) is largely incurable, and its treatment remains challenging. Sunitinib, a tyrosine kinase inhibitor, is one of the current standard-of-care options for treatment-naïve patients with metastatic RCC. Despite the proven efficacy of Sunitinib, prolonged treatment with some tyrosine kinase inhibitors (TKIs) has been associated with significant adverse events (AEs). Therefore, we aimed to calculate the exact efficacy in addition to the prevalence of all AEs of Sunitinib in a pooled analysis from all available randomized controlled trials (RCTs). Methods: A comprehensive electronic database search was conducted for all RCTs comparing the clinical outcomes and adverse events of Sunitinib versus all other available treatments for treatment-naïve advanced/metastatic clear-cell renal cell carcinoma. We then calculated the pooled outcomes and prevalence of the most common reported side effects of Sunitinib. All statistical analyses were performed using R Statistical Software v3.4.0 (R Foundation, Vienna, Austria). Results: We included 8 RCTs, with a total of 4106 patients. The mean age was62, with 66.44% males.The efficacy of Sunitinib was reported as 3 main outcomes: Median progression free survival at 10.73 [7.76, 13.7] months, median overall survival at 23.28 [16.74, 29.81] months and the estimated objective response rate at 25[13, 37] %. Any grade AEs were reported in 72% of patients with the following frequencies: fatigue 44%, diarrhea 38%, nausea 31%, hand-foot syndrome 30%, hypertension 27%, dysgeusia 25%, hypothyroidism25%, constipation 20%, stomatitis 20%, inflammation of the mucosa 18%, dyspepsia 16%, vomiting 14%, rash 12%, asthenia 11%, and epistaxis10%.Grade 3&amp;4 (severe) AEs were reported in 52% of patients with the following frequencies: hypertension 9%, fatigue 8%, hand-foot syndrome 5%, asthenia 5%, diarrhea 4%, and inflammation of the mucosa 2%. Conclusions: Despite Sunitinib being one of the current standard treatments for patients with metastatic/advanced clear-cell RCC, with well-described efficacy, its safety profile is still concerning with a significant prevalence of reported grade 3-4 AEs of 52% of the treated patients in the included RCTs. These findings underscore the importance of the emergence of newer drugs and treatment plans for patients with metastatic RCC, not only to achieve similar or better clinical outcomes but also to decrease the percentage of grade 3-4 AEs.
B7-H3 expression by immunohistochemistry as a negative prognostic biomarker in colorectal carcinoma (CRC) in a racially diverse population.
Authors: Meghan Kaumaya, Wei Zhang, Kevin Kuan, Sorab Gupta, Shaomin Hu, Devika Rao, Kim Ohaegbulam, Richard Hwang, Qiang Liu, Xingxing Zang, Sanjay Goel, Radhashree Maitra
Journal: Journal of Clinical Oncology (2019)

e15127 Background: In CRC, utility of immunotherapy (IT) remains limited to persons with microsatellite instability–high (MSI-H) status. Immunotyping of CRC patients is critical towards further establishing IT's potential. Both incidence and survival rates for CRC in the United States vary between races due to multiple factors including genetic heterogeneity. In this study, we have profiled tumor samples in a racially diverse population for the expression of four different members of the B7 family of immune check point regulators. Methods: Tissue microarray (TMA) was generated from 208 CRC patients. Formalin fixed paraffin embedded (FFPE) tissues were utilized for immunohistochemistry (IHC) post- antigen retrieval. Antibodies specific for IHC staining were used for B7-H3 (D9M2L), PD-L1(E1L3N), B7-H4/B7x(D1M81) and HHLA2(566.1). Each specimen was scored for percent staining of tumor tissue (4 quartile groups) and for intensity (1-4x), and then an overall score (1-16) was calculated. The clinical outcome of interest was overall survival (OS), measured as time from diagnosis of metastatic cancer to death. Analysis for differences in OS was by log rank test, while differences between mean staining was by t test. Race was designated as non-Hispanic white (NHW, n = 41), non-Hispanic black (NHB, n = 84), Hispanic (n = 75), and others (8). Results: B7-H3 protein expression showed strong cytoplasmic distribution. NHB patients had a mean lower expression than NHW patients (0.19 vs 0.41, p = 0.02). Correspondingly, NHB patients had a worse OS than NHW patients (606 vs 759 days). No discernible differences were found in Hispanic patients. PD-L1 showed membranous distribution with 17% expression without significant difference among patients of different racial origin. HHLA2 was more widely expressed with about 35% staining but without statistical significance. B7-H4/B7x failed to show any expression. Conclusions: Expression of B7H3 varies among patients with differential racial backgrounds. It has the potential to be a prognostic biomarker and may be a reason for worse outcome among NHB patients in our population. Other B7 immune checkpoint markers failed to show clinical relevance.
How will the cost of biosimilars affect patients’ willingness to receive them?
Authors: R Donald Harvey, Megan McGrath, John W. Cook, Margie D Dixon, Rebecca D. Pentz
Journal: Journal of Clinical Oncology (2019)

e18338 Background: The cost of oncology care is increasing. The NIH projects that the oncology drug market will reach $111.9 billion by 2020. Studies show that oncology patients experience considerable financial burden, regardless of insurance status and in general believe that oncology medications are too expensive. However, there is some evidence outside of oncology that suggests patients may not trust generics or cheaper medications. Therefore, there is a need to assess oncology patients’ views of a biosimilars and their potential to reduce costs. Methods: We surveyed a convenience sample of 79 oncology patients in clinics and the infusion center. The survey consisted of five questions on cost and patient participation in decision making. Results: Of 79 patients approached, 75 (95%) completed the survey. Fifty (66%) believed that expensive medications do not work better than less costly ones for the same disease; yet only 30 of those 50 (60%) and 44% overall (33/75) would prefer that their doctor prescribe them the cheaper version of their anti-cancer medication. Of the 20 respondents who believed that expensive drugs do not work better but still wanted the more expensive drugs for themselves, 8 believed cancer was too serious of an illness to take any chances with a cheaper medication, 5 wanted the most expensive that insurance would cover and 2 wanted the best possible medication. 90.67% respondents (68/75) wanted to know if their physician was prescribing a cheaper version of their drug. Conclusions: Our results show that, overall, oncology patients agree that cheaper medications work as well as more expensive ones, but there are definite concerns among some patients that drug price may be a proxy for quality, particularly in cancer. Overcoming these negative perceptions among patients will be important if optimal cost savings are going to be realized with expanded biosimilar use.
Response rate to chemotherapy after disease progression with anti-PD-1/PD-L1 in metastatic cancer.
Authors: Munaf Al-Kadhimi, Thomas A. Hensing, Daniel H. Shevrin, Britt Erika Hanson, Nicholas Paul Campbell, Bruce Brockstein
Journal: Journal of Clinical Oncology (2019)

e14088 Background: The checkpoint inhibitor (CPI) immunotherapy class of drugs is redefining how we treat cancer. The US FDA has approved CPI drugs as 1st, 2nd or salvage line after progression on conventional chemotherapy (CTX) for multiple cancers including melanoma, lung, bladder and other cancers. However, many questions remain regarding optimal treatment post-progression. Indeed, it has been noted that the patterns of response and relapse to CPI agents are quite different from those of standard cytotoxic agents and that response to CTX AFTER CPI may be different than in the de novo setting. The purpose of this retrospective analysis is to evaluate the activity (response rate (RR), response duration (DOR) and progression free survival (PFS)) of subsequent CTX after disease progression following treatment with CPI. Methods: In this analysis, patients (pts) were enrolled under an IRB approved waiver of consent. We identified pts treated with CPI agents between Jan, 2011 and Dec, 2018 at a multi-site community cancer program who received subsequent CTX as a result of disease progression (PD). We assessed the RECIST RR to subsequent therapy, DOR from onset of response, and PFS from the onset of post CPI CTX, identifying index lesions from the most recent pre-treatment anatomic scan. Results: A total of 47 cases satisfying the above criteria were found; 31 NSCLC, 8 melanoma, 1 SCLC, 1 GEJ, 1 gastric, 2 head/neck, 1 large cell neuroendocrine tumor, 2 bladder cancer. 25 pts had PD as best response to post-CPI CTX. 9 pts (19%) achieved a partial response (PR) with a median DOR of 99 days. 22 pts achieved a PR or stable disease (SD) for a clinical benefit (CB) rate of 47%. The median duration of CB was 92 days. Of the 9 patients who achieved PR, 5/6 had achieved response to CTX prior to CPI . The median PFS for the entire cohort was 97 days. Conclusions: While an expected RR could not be calculated in this heterogenous group of pts, the number and degree of responses suggests CPI possible “priming” that may enhance response to CTX. Post-CPI CTX may be of value and in this retrospective study of a heterogenous group of pts, responses may be more frequent than expected. A larger further study is warranted.
Spatial and temporal heterogeneity of PD-L1 and its impact on benefit from immune checkpoint blockade in non-small cell lung cancer (NSCLC).
Authors: Lingzhi Hong, Seyedeh Dibaj, Marcelo Vailati Negrao, Alexandre Reuben, Emily Roarty, Waree Rinsurongkawong, Jeff Lewis, Don Lynn Gibbons, Boris Sepesi, Vassiliki Papadimitrakopoulou, Bonnie S. Glisson, George R. Blumenschein, Phillip Andrew Futreal, Ignacio Ivan Wistuba, Jack A. Roth, Stephen Swisher, John Heymach, George R. Simon, J. Jack Lee, Jianjun Zhang
Journal: Journal of Clinical Oncology (2019)

9017 Background: Temporal and spatial heterogeneity of PD-L1 has been reported. However, its impact on clinical benefit from immune checkpoint inhibitor (ICI) has not been clearly defined. Methods: We queried the MD Anderson Lung Cancer GEMINI database and compared PD-L1 expression (tumor proportion score by immunohistochemistry using FDA-approved antibodies) in NSCLC specimens from different organs at different time points. We assessed the predictive value of PD-L1 for benefit from ICIs in patients with metastatic NSCLC. Results: In 1398 NSCLC patients, PD-L1 level was significantly associated with biopsy sites (p = 0.007). Adrenal and liver metastases had the highest PD-L1 level and positive rate (by 1% or 50% cutoff) while PD-L1 was the lowest in bone and brain biopsies. In addition, PD-L1 was significantly higher in fresh tissues (PD-L1 staining at &lt; 90 days after biopsy) than archival tissues (PD-L1 staining at &gt; 90 days after biopsy), in squamous cell carcinoma than adenocarcinoma, in EGFR wild-type ( WT ) than EGFR mutant, in MET amplified than MET WT , and in STK11 WT than mutant (p &lt; 0.01). Among 112 patients with longitudinal specimens tested, 55 (49%) had major changes with PD-L1 at different time points falling into different clinically relevant categories ( &lt; 1%, 1-49%, &gt; 50%). ICIs were associated with significant decrease in PD-L1 level compared to treatment-naïve counterparts (p = 0.019). Furthermore, 398 patients with EGFR/ALK WT metastatic NSCLC who received ICIs were divided into three groups based on biopsy sites including lung (n = 252); lymph node (LN, n = 85) and distant metastasis (n = 61). Higher PD-L1 level in biopsies from lung or distant metastasis was associated with significantly higher response rate, disease control rate and significantly longer progression free survival and overall survival using either 1% or 50% cutoff. However, the PD-L1 expression from LN biopsies was not associated with either response or survival in this cohort of patients. These findings remained constant in multivariate analyses. Conclusions: PD-L1 expression varies substantially across different anatomic sites and changes during clinical courses. PD-L1 in LN biopsies may not be reliable to predict clinical benefit for ICIs in NSCLC. Repeat biopsy and PD-L1 staining should be considered if only remote tissues, particularly, LN biopsies are available.
Risk of anxiety and depression in breast cancer survivors compared to women who have never had cancer: A population-based cohort study in the United Kingdom.
Authors: Helena Carreira, Rachael Williams, Garth Funston, Susannah Jane Stanway, Krishnan Bhaskaran
Journal: Journal of Clinical Oncology (2019)

1564 Background: Breast cancer survivors are the largest group of cancer survivors in the United Kingdom (UK). Having had a breast cancer diagnosis may adversely affect the patient’s mental health. We aimed to estimate the long-term risk of anxiety and depression in women with history of breast cancer compared to those who have never had cancer. Methods: We conducted a matched population-based cohort study, using data from the Clinical Practice Research Datalink (CPRD) GOLD primary care database. The exposed cohort included all adult women diagnosed with breast cancer between 1987 and 2018; the unexposed group included women with no cancer history, matched to exposed women in a 4:1 ratio on primary care practice and age. Cox regression models stratified on matched set were used to estimate hazard ratios of the association between breast cancer survivorship and anxiety and depression. Results: 59,972 women (mean 62 years; standard deviation (SD) 14.0) had history of breast cancer. The median follow-up time was 3.0 years (SD 4.4), which amounted to 256,186 person-years under observation. The comparison group included 240,387 women followed up over 3.5 years (SD 4.5) (1,163,819 person-years). The incidence of anxiety in breast cancer survivors was 0.08 (95% confidence interval (95%) 0.07-0.08) per 1000 person-years, and the incidence of depression was 70 (95%CI 68-71) per 1000 person-years. The risks of both depression and anxiety were raised in breast cancer survivors compared with controls, and this appeared to be driven by the first 3 years following diagnosis (Table). Conclusions: Breast cancer survivors in the UK had significantly higher risk anxiety and depression diagnosed in primary care for three years following diagnosis than women who never had cancer. Risk of anxiety and depression in breast cancer survivors compared to women who did not have cancer by time since diagnosis. [Table: see text]
Impact of body composition on outcomes from anti-programmed death-1 (PD-1) treatment.
Authors: Arissa Young, Henry T. Quach, Elizabeth J. Davis, Javid Moslehi, Grant R. Williams, Douglas Buckner Johnson
Journal: Journal of Clinical Oncology (2019)

9516 Background: Obesity is associated with improved outcomes in melanoma patients (pts) treated with PD-1, whereas low muscle mass, known as sarcopenia, has been associated with poor outcomes in many cancers. We sought to assess the impact of body composition on PD-1 outcomes. Methods: We analyzed pre-treatment CT scans at the L3 slice using Slice-o-matic software (Tomovision V. 5.0) to determine skeletal muscle, visceral adipose, and subcutaneous adipose tissue parameters for 104 pts with metastatic melanoma who received PD-1 monotherapy. We assessed sarcopenia using skeletal muscle index (SMI=skeletal muscle area/m 2 ). We also quantified total adipose tissue index (TATI), and skeletal muscle gauge (SMG = SMI x skeletal muscle density [SMD]). We stratified pts into high/low groups using previously published cutoffs and assessed toxicity (tox), progression-free and overall survival (PFS/OS), and response rate (RR) by group. Results: Sarcopenia (low SMI) was negatively associated with any tox (39% vs. 60%, p=0.04) but not OS, PFS, or RR. Adiposity (TATI) was not associated with outcomes. By contrast, SMG was significantly associated with OS (median 35.5 vs. 16.0m, p=0.01 for high vs. low SMG). Interestingly, when incorporating TATI with SMG, we found that high SMG/high TATI pts (high muscle/high fat) have superior clinical outcomes (Table). Notably, low SMG/high TATI pts (low muscle/high fat) had seemingly the worst outcomes. Conclusions: We found that high SMG, a measure incorporating muscle area and density, was associated with improved OS in PD1 treated pts. Further, pts with high adiposity and high SMG had superior outcomes, potentially identifying the population responsible for the favorable effect of obesity in these pts. Validation and combination treated cohorts will be presented. [Table: see text]