tbuckley/cabot-search huggingface dataset:
Decision-making in breast cancer risk reduction: Results from a nested qualitative study from NRG Oncology/NSABP protocol DMP-1.
Authors: Sarah B Blakeslee, Patricia A. Parker, Christine M Gunn, Hanna Bandos, Therese Bartholomew Bevers, Tracy Ann Battaglia, Angela Fagerlin, Worta J. McCaskill-Stevens, Christine Holmberg
Journal: Journal of Clinical Oncology (2015)

e17569 Background: Tamoxifen and raloxifene are two selective receptor modulators (SERMs) that have been shown to reduce the risk of developing breast cancer in women at increased risk of the disease. Both drugs are infrequently used in the general U.S. population. Methods: To understand what influences decision-making on SERM use for risk reduction, clinical counselling sessions were recorded (N=30). The video-taped women and health care provider (HCP) were interviewed to discuss their decision-making process and the video recordings. Comparative case analysis was used. The study is based on narrative theory. Results: Of the 30 women, 18 (60%) discussed having a first or second degree relative with breast cancer and 16 (53%) talked about having had a diagnosis of “atypical cells” after a breast biopsy. Of the 30 women, 11 (37%) decided to take a SERM, 10 of whom had had a diagnosis of “atypical cells in the breast,” and four of whom discussed having had a first- or second-degree relative with breast cancer. All 11 who decided to take a SERM made their decision during the consultation session and had a strong recommendation from the HCP to have SERM therapy. The reasoning of those who decided to take a SERM was related to “feeling at risk” and wanting to reduce the risk. In addition, patients reported a sense of “proximity” that arose from having close friends or family experience breast cancer, “familiarity” with the idea of taking medicines for disease prevention, and knowing of potential side-effects from others who had taken the medication. Also, familiarity with tamoxifen as a well-known cancer drug was discussed. Of those who decided not to take a SERM, one woman with a diagnosis of atypical cells decided to have a prophylactic mastectomy. All others (19/30, 63%) agreed to close follow-up. Conclusions: Overall, the decision-making process of taking a SERM or not seems to be influenced by a sense of concern about one’s risk factors, a familiarity with the drug and potential side effects, and counseling by the provider. SUPPORT: U10CA37377, -69974, -180868, -180822; -189867. Clinical trial information: NCT01399359.
Management of isolated local failures following stereotactic body radiation therapy for low to intermediate risk prostate cancer.
Authors: Nicolette Drescher, Nima Aghdam, Malika Danner, Marilyn Ayoob, Thomas M. Yung, Siyuan Lei, Brian Timothy Collins, Jonathan Lischalk, Anatoly Dritschilo, Simeng Suy, Deepak Kumar, John J. Lynch, Sean P. Collins
Journal: Journal of Clinical Oncology (2019)

66 Background: SBRT is a safe and effective treatment option for patients with low to intermediate risk prostate cancer (PCa). SBRT delivers high biologically effective doses resulting in very low PSA nadirs. Strategies to diagnose and confirm salvageable isolated local failures (ILF) are needed. This study aims to examine the incidence and approach to management of ILF after SBRT in a large single institution cohort. Methods: All patients with low or intermediate risk PCa treated with SBRT at our institution were eligible for this study. Treatment was delivered using the robotic SBRT with doses of 35-36.25 Gy in five fractions. ILF were diagnosed using mpMRI and/or biopsy prompted by PSA rise after achieving long-term nadir. Choice of salvage therapy and post-salvage PSA were ascertained on follow up. Results: Between December, 2008 to August, 2018, 998 men with low to intermediate risk prostate cancer were eligible for analysis. Twenty patients (low risk, n = 4; intermediate risk, n = 16) were found to have ILF on either MRI (n = 15) and/or biopsy (n = 17). Three patients with MRI-identified ILF elected active surveillance in lieu of biopsy. Median pre-treatment PSA was 7.5 ng/ml. Median time to diagnosis of ILF was 72 months (37-96 months) with median PSA at the time of ILF of 2.3 ng/ml (1.1-10 ng/ml). Median PSA doubling time was 17 months (5-22 months). Thirteen patients with biopsy proven ILF proceeded with salvage therapy (cryotherapy n = 12, HIFU n = 1). Of 12 patients who underwent cryotherapy, 8 had a post-treatment PSA of &lt; 0.1ng/ml, two patient’s results were unavailable, one patient had a PSA nadir of 0.7 ng/ml and one patient had yet to undergo post-salvage PSA test at the time of this report. Conclusions: The incidence of ILF is rare in our series. Diagnosis and management of ILF post-SBRT continues to evolve in the era of successful salvage therapy. Our report suggests an important role for early utilization of MRI and confirmatory biopsy at relatively low PSA levels and long PSA doubling time. Additionally, undetectable PSA post-salvage therapy supports early treatment after identifying ILF. Larger trials are needed for refinement of patient selection and most appropriate salvage modality.
Results of stereotactic body radiotherapy (SBRT) for management of primary and secondary hepatic tumors: Analysis of early outcomes.
Authors: Eman ElAlfy, Pierre-Yves Bondiau, Yousri A. Rostom, Karen Benezery, Jerome Doyen
Journal: Journal of Clinical Oncology (2015)

e15160 Background: To evaluate survival and local control (LC) with use of robotic SBRT with real time tumor tracking in the treatment of primary and secondary hepatic tumors. Methods: Between March 2007 and December 2012; 59 patients (pts) (76 lesions) with 48 Hepatic metastases (HM) mostly from primary GIT, 8 Hepatocellular Carcinoma (HCC), 3 Cholangiocarcinoma (CC) with mean age of 67 years(yrs); treated with SBRT (cyberknife system). Margin for HCC, CC was 5 mm for CTV and 3 mm for PTV, no margin used for HM. Median dose was 47.61 Gy to PTV in 3 fractions and 136 beams prescribed to 80 % isodose line. Results: Treatment was well tolerated with minimal grade 1, 2 and only 2 % grade 3 toxicity. All pts; Overall survival (OS) was 81.4% at 1 yr and 53.3% at 2 yrs, Disease free survival (DFS) was 64.6% at 1 yr and 40.7% at 2 yrs, LC was 75% at 1 yr and 54.1% at 2 yrs. HCC; OS was 41.7% at both 1 and 2 yrs, all pts had progression before 1 yr, LC was 75% at both 1 and 2 yrs. HM; OS was 83.6% at 1 yr and 57% at 2 yrs, DFS was 69.5% at 1 yr and 46.1% at 2 yrs, LC was 76.3% at 1 yr and 57.9% at 2 yrs. CC; OS was 100% at 1 yr and 50% at 2 yrs, both DFS and LC were 50% at 1 yr and 0% at 2 yrs. Factors influencing better OS; type of lesion, age < 65 yrs (p = 0.033), small PTV volume (p = 0.002). Factors influencing DFS; dose of 45 Gy (p = 0.001), dose per fraction of 15 Gy (p = 0.001), coverage > 95% for PTV (p = 0.001). Factors associated with better for LC were: type of lesion, dose to PTV (p = 0.037), coverage > 95% for PTV (p = 0.001). Conclusions: Age < 65 yrs, Good Performance Status, small volume of tumor, total dose, dose per fraction, coverage > 95% for target volume are good prognostic factors for survival and LC.
Early predicting factor for biochemical failure for patients with intermediate and high-risk prostate cancer treated by definitive radiotherapy.
Authors: Hye Jin Kang, Chul Seung Kay, MI NA Yu
Journal: Journal of Clinical Oncology (2019)

52 Background: The prostate-specific antigen nadir (nPSA), a strong prognostic factor for prostate cancer, does not occur until several years after definitive radiotherapy. Our aim was to assess an early predictive factor for biochemical failure (BCF) in patients with intermediate- and high-risk prostate cancer treated with definitive radiotherapy. Methods: Between 2007 and 2017, 97 patients with localized prostate cancer underwent radiotherapy at two institutions. We used a pelvic lymph node involvement risk of 15% as the cutoff value, calculated using the Roach formula, to decide whether to deliver prostate and seminal vesicle only radiotherapy (PORT) or whole-pelvis radiotherapy (WPRT). Twenty-seven patients (27.8%) underwent PORT with the prostate receiving 45 Gy (4.5 Gy per fraction) and the other 70 patients (72.2%) underwent WPRT with the prostate receiving 72 Gy (2.4 Gy per fraction). The median equivalent dose in 2 Gy fractions to the prostate was 80.3 Gy based on the assumption that the α/β ratio is 1.5 Gy. Sixty-two patients (63.9%) were treated with androgen deprivation therapy (ADT). Results: The median follow-up time was 40 (range, 10 to 133) months. The 4-year BCF-free survival (BCFS) rate was 87.0%. In the univariate analysis, the nPSA, the nPSA within 12 months (nPSA12), and ADT use were significant predictive factors for BCF. nPSA ( p = 0.003) and ADT use ( p = 0.041), but not nPSA12 ( p = 0.485), were independent predictive factors for BCF in the multivariate analysis. However, there was a strong correlation between nPSA and nPSA12 in this study ( r = 0.854, p &lt; 0.001). The receiver operating characteristic curve identified 0.47 ng/ml as the optimal cutoff value of nPSA12 for predicting BCF. The 4-year BCFS rate in patients with nPSA12 &lt; 0.47 ng/ml was 100% in contrast to 71.3% in patients with nPSA12 ≥ 0.47 ng/ml. Conclusions: The nPSA12 has a strong correlation with nPSA and is a considerable predictor of BCF. Therefore, the treatment outcome can be predicted early using nPSA12. Furthermore, ADT can significantly reduce BCF in patients with intermediate- and high-risk prostate cancer.
Effect of Timing of Monoclonal Antibody Therapy on the Time to Next Treatment and Response Rate in Heavily Pre-Treated Patients with Myeloma Who Separately Received Both Daratumumab and Elotuzumab-Based Regimens
Authors: Melody R. Becnel, M Laura Rubin, Ranjit Nair, Elisabet E. Manasanch, Hans C. Lee, Krina K. Patel, Swaminathan P Iyer, Sheeba K. Thomas, Donna M. Weber, Robert Z. Orlowski
Journal: Blood (2018)
Development and validation of a DNA methylation panel for the prediction of outcome in node-positive penile squamous cell carcinoma after lymphadenectomy.
Authors: Yao Zhu, Weijie Gu, Fangning Wan, Beihe Wang, Yu Wei, Dingwei Ye
Journal: Journal of Clinical Oncology (2019)

513 Background: Node-positive penile squamous cell carcinoma is lethal disease with heterogenous outcome after lymphadenectomy. Molecular prognostic factor are poorly tested in this population to individualize treatment. The aim of this study was to develop and validate the prognostic value of a DNA methylation panel in node-positive penile cancer after lymphadenectomy. Methods: Patients with node-positive penile squamous cell carcinoma, and received inguinal or ilioinguinal lymphadenectomy were eligible. The prognostic marker study had 3-stage design: first, discovery set of 23 frozen tissues was used to generate candidate CpG sites associated with overall survival; second, development set of 68 formalin-fixed and paraffin-embedded (FFPE) samples was used to construct a multivariable methylation panel for outcome stratification; third, validation set of 69 FFPE specimens from multi-center database was used to independently validate the performance of the prognostic marker. The study was approved by local ethnic committee. The primary endpoint was overall survival. The prognostic value of the DNA methylation panel value was evaluated by hazard ratio (HR), concordance index (C-index) and clinical benefit. Results: At discovery stage, 11 CpG sites were significantly associated with overall survival. In development set, we constructed a 3-CpGs-based prognostic panel for survival prediction. The HR of the panel (dichotomized using median cutoff) was 6.5 in multivariate analyses (p &lt; 0.001). Addition of methylation panel significantly improved the C-index of N stage from 0.64 to 0.75 (incremental C = 0.11, p &lt; 0.001). In the validation set, the methylation panel showed a HR of 7.8 in multivariate analyses. Addition of the molecular marker significantly improved the C-index of N stage from 0.69 to 0.78 (incremental C = 0.09, p &lt; 0.001). The main limitation was retrospective design. Conclusions: We developed and validated a methylation prognostic panel for node-positive penile cancer. The prognostic maker showed remarkable improvement in risk stratification, and need further evaluation in prospective setting.
Abstract P006: Association of Multimorbidity With Cardiovascular Endpoints in Elderly Patients With Atrial Fibrillation
Authors: J’Neka S Claxton, Alanna M Chamberlain, Pamela L Lutsey, Lin Y Chen, Richard F MacLehose, Lindsay G Bengtson, Alvaro Alonso
Journal: Circulation (2019)

Introduction: The prevalence of atrial fibrillation (AF) and multimorbidity increase with age; however, the burden imposed by concurrent conditions on outcomes is unknown. Therefore, we aimed to determine the effect of the number and type of comorbid conditions on outcomes in elderly individuals with incident AF. Methods: Patients with non-valvular AF 75 years and older were identified in the MarketScan Medicare Supplemental database from 2007-2015. Fourteen chronic conditions, defined by two occurrences of a diagnostic code from inpatient and outpatient claims prior to or at the time of AF diagnosis, were obtained and classified into two categories: cardiovascular (CV) or non-CV (listed in Table footnote). We used Cox regression to estimate the associations of the number and type of conditions with stroke, severe bleeding, and heart failure hospitalizations (HF). Results: Among 275,617 patients with AF (mean age 83 years, 51% women), 90% had at least one or more additional chronic conditions. The mean (SD) number of conditions per participant was 1.8 (0.9) for CV conditions and 2.1 (1.2) for non-CV conditions. Over a mean follow-up of 23 months, 7,814 strokes, 13,622 severe bleeds, and 19,252 HF events occurred. After adjustment for age, sex, the number of conditions in the other comorbidity group, an increase of one CV condition was associated with greater risk of stroke, severe bleeding, and HF (Table). In contrast, an increase in one non-CV condition was associated with a lower risk of stroke, and a small increase in bleeding and HF risk (Table). After further adjustments for frailty and medications, the strength of the associations within each group decreased across outcomes. Conclusion: CV conditions in AF patients 75 years and older are more strongly associated with stroke, HF, and bleeding than non-CV conditions. This underscores the effect of CV conditions on CV outcomes in a population in which multimorbidity is most common and health care management and delivery is complex.
A pilot study to test the feasibility of histological characterisation of asthma–COPD overlap
Authors: Eleni Papakonstantinou, Spasenjia Savic, Aline Siebeneichler, Werner Strobel, Paul W. Jones, Michael Tamm, Daiana Stolz
Journal: European Respiratory Journal (2019)

<b>This pilot study suggests that specific histopathological findings, such as thickening of reticular basement membrane in COPD patients, may reveal an overlapping COPD–asthma phenotype with higher response to ICS/LABA</b>http://bit.ly/2Lb5sAW
Phase I/II dose-escalation trial of fractionated dose <sup>177</sup>Lu-J591 plus <sup>177</sup>Lu-PSMA-617 for metastatic castration-resistant prostate cancer (mCRPC).
Authors: Scott T. Tagawa, Muhammad Junaid Niaz, Joseph Osborne, Shankar Vallabhajosula, Himisha Beltran, Lauren Christine Harshman, David M. Nanus, Ana M. Molina, Bishoy Morris Faltas, Amy Hackett, Lauren Gracey, Jyothi Sreekumar, John Babich, Karla V. Ballman, Neil Harrison Bander
Journal: Journal of Clinical Oncology (2019)

TPS339 Background: PC is a radiosensitive disease. PSMA is selectively overexpressed in advanced PC with upregulation by androgen receptor (AR) pathway dysregulation; limited expression exists in other organs. Prior studies of beta-emitting radiolabeled anti-PSMA antibody J591 demonstrated accurate targeting, efficacy with dose-response effect, and safety with predictable dose-limiting myelosuppression. Recent prospective trials have shown efficacy and safety of 177 Lu-PSMA-617 in mCRPC. Studies demonstrate different binding sites of J591 and PSMA-617 and co-administration leads to non-competitive additive binding and delivery of payloads to PSMA+ cells. As the pharmacokinetics and biodistribution of the 2 agents is mostly non-overlapping (other than tumor) and given our prior dose-response data, we hypothesize that delivery of the combination will yield higher tumor delivery with less off-target toxicity (i.e. better responses without increased toxicity). Methods: Men with progressive mCRPC following at least 1 potent AR-targeted agent (e.g. abi/enza) and docetaxel (or unfit/refuse chemo) with metastatic disease on CT/MRI or bone scan without limit of # prior therapies (excluding bone-targeted beta-emitting radioisotopes) provided adequate organ function will be enrolled. Pre-treatment 88 Ga-PSMA-11 will be performed, but results are not used for eligibility. Treatment includes fractionated 177 Lu-J591 at a fixed moderate dose with escalating doses of 177 Lu-PSMA-617 (7.4 – 18.5 GBq per cycle, fractionated D1 and D15) in a 3+3 dose-escalation study. Dose-limiting toxicity (DLT) is defined as attributable grade &gt; 3 heme toxicity or grade &gt; 2 non-heme toxicity. Following determination of recommended phase 2 dose (RP2D), the phase 2 portion will enroll in a 2-stage design. Primary endpoints: DLT and RP2D (ph 1) and PSA decline proportion (ph 2). Secondary endpoints include toxicity, radiographic response, PFS, rPFS, OS, CTC count changes. Correlatives include baseline/follow up PSMA imaging, whole body distribution of 177 Lu, tissue and circulating genomic assessment, immunologic assessment, and patient reported outcomes (FACT-P and BPI-SF). Clinical trial information: NCT03545165.
Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies
Authors: Yi-Zhou Jiang, Ding Ma, Chen Suo, Jinxiu Shi, Mengzhu Xue, Xin Hu, Yi Xiao, Ke-Da Yu, Yi-Rong Liu, Ying Yu, Yuanting Zheng, Xiangnan Li, Chenhui Zhang, Pengchen Hu, Jing Zhang, Qi Hua, Jiyang Zhang, Wanwan Hou, Luyao Ren, Ding Bao, Bingying Li, Jingcheng Yang, Ling Yao, Wen-Jia Zuo, Shen Zhao, Yue Gong, Yi-Xing Ren, Ya-Xin Zhao, Yun-Song Yang, Zhenmin Niu, Zhi-Gang Cao, Daniel G. Stover, Claire Verschraegen, Virginia Kaklamani, Anneleen Daemen, John R. Benson, Kazuaki Takabe, Fan Bai, Da-Qiang Li, Peng Wang, Leming Shi, Wei Huang, Zhi-Ming Shao
Journal: Cancer Cell (2019)
Quantification of Non-Hodgkin Lymphoma Disease Burden Using FDG PET-CT Helps Predict the Severity of Cytokine Release Syndrome
Authors: Jiasheng Wang, Yongxian Hu, Yanlei Zhang, Guoqing Wei, Huijun Xu, Wenjun Wu, Shaohui Liu, Kangyan Wang, Zhenxing Guo, Alex Hongsheng Chang, Kui Zhao, He Huang
Journal: Blood (2018)
The role of architectural patterns and cytologic features in the prognosis of clear cell renal cell carcinoma.
Authors: Qi Cai, Alana Christie, Qinbo Zhou, Ellen Araj, Jeffrey A Cadeddu, Vitaly Margulis, Nirmish Singla, Satwik Rajaram, Ivan Pedrosa, Dinesh Rakheja, Renee McKay, James Brugarolas, Payal Kapur
Journal: Journal of Clinical Oncology (2019)

632 Background: Clear cell renal cell carcinoma (ccRCC) exhibits a spectrum of clinical behavior and intratumoral heterogeneity histologically. Pathologic grading for ccRCC is primarily based on nucleolar size. Sarcomatoid and rhabdoid changes are known to be associated with aggressive behavior, the significance of the histopathologic heterogeneity occurring in ccRCC remains largely unknown. We evaluated the prognostic role of architectural patterns and cytologic features in ccRCC. Methods: We identified sequential ccRCC cases at our institution between 2006 and 2015 for which follow-up information was available beyond 1.5 years, excepting those who died sooner. Architectural patterns and cytologic features were predefined and quantitated in nephrectomy specimen slides, which were reviewed by an experienced GU pathologist. Nine novel architectural patterns and ten cytologic features were correlated with disease-free survival (DFS) and overall survival (OS). Kaplan-Meier curves were generated to visualize survival distributions. Results: 549 cases met selection criteria and were comprehensively reviewed including 16 grade 1 (2.9%), 278 grade 2 (50.6%), 201 grade 3 (36.6%) and 54 grade 4 (9.8%). Pathologic tumor stage distribution included 63.9% pT1 (n = 351), 6.0% pT2 (n = 33), 27.5% pT3 (n = 151), and 2.6% pT4 (n = 14). Microcystic, tubular, bleeding follicles, and small compact nest patterns (n = 309), were associated with better DFS and OS. In contrast, large nests, thick trabecular, solid sheet, alveolar or papillary/pseudopapillary patterns (n = 240) were associated with worse DFS and OS (p &lt; 0.0001). In addition to multinucleated giant cells, and sarcomatoid and rhabdoid changes, cytologic features including large intracytoplasmic eosinophilic inclusions, voluminous cytoplasm, cytoplasmic spindling, a giant nucleus with perinuclear halo, and a wrinkled nucleus with perinuclear halo were associated with worse DFS and OS (p &lt; 0.0004). Conclusions: Architectural patterns and cytologic features observed in ccRCC predict tumor behavior and are associated with clinical prognosis. Evaluation of histopathologic heterogeneity may shed light on tumor biology and complement prognostic models.
How KEAP1 Deletion in Single Cell Mitigates Sickle Cell Pathology
Authors: Nadine Keleku Lukwete, Mikiko Suzuki, Harit Panda, Akihito Otsuki, Fumiki Katsuoka, Ritsumi Saitou, Daisuke Saigusa, Akira Uruno, Masayuki Yamamoto
Journal: Blood (2018)
Allelic ratio of <i>KRAS</i> mutations in pancreatic ductal adenocarcinoma.
Authors: Jochen K Lennerz, Albrecht Stenzinger
Journal: Journal of Clinical Oncology (2015)

4023 Background: Traditional sequencing studies of KRAS in pancreatic ductal adenocarcinoma (PDAC) delineated a mutation frequency of ~75% and that KRAS mutant tumors are associated with shorter overall survival. Recently highly-sensitive next-generation sequencing technologies have delineated that the KRAS mutation frequency in PDAC is ~93% indicative of a fraction of cases missed by traditional sequencing approaches. Here, we explored whether PDAC with KRAS mutations at low-allelic ratios carry prognostic differences. Methods: We employed the PDAC dataset (n = 142) from the International genome consortium (ICGC) initially reported by Biankin et al., 2012. We accounted for tumor purity by calculating the corrected allelic ratio ( = allelic ratio/cellularity). Overall survival differences using a corrected allelic ratio cutoff of 10% were calculated employing Kaplan-Meier, log-rank, and Cox proportional hazard regression analysis (HR). Results: Accounting for tumor purity, we identified 115 cases (80.9%) with allelic ratios of mutant KRAS ≥ 10% while the remainder (n = 27 cases, 19.1%) harbored either mutant alleles below 10% (n = 17) or wild-type KRAS (n = 10). Allelic ratios span the full range from wild-type to > 100% mutant KRAS. The lower as well as the upper end of this spectrum suggest heterogeneity within the cancer cell population (clonality) or variations in DNA content (ploidy), respectively. The subset with low-allelic ratios ( < 10%) of mutant KRAS had shorter overall survival (14.5 months) when compared to those with high-allelic ratios (20.3 months; HR 1.68 CI:0.9-3.13). While this difference did not reach statistical significance (P= 0.10), several prior studies employing thresholds around 10% (cutoff determined by sensitivity of the sequencing technology) have shown that the presence of a KRAS mutation is a marker of poor prognosis. Conclusions: KRAS is not simply mutated or wild-type in PDAC – it has actually never been. While over 90% of PDAC carry mutated KRAS alleles, the impact on PDAC biology may vary with the tumor-specific allelic ratio and dosage of mutated KRAS. Therefore, we propose that the tumor-specific allelic ratio of somatically mutated genes should become part of a comprehensive molecular diagnostic report.