tbuckley/cabot-search huggingface dataset:
A pilot study of intratumoral SD-101 (toll-like receptor 9 agonist), nivolumab, and radiotherapy for treatment of chemotherapy-refractory metastatic pancreatic adenocarcinoma.
Authors: Justin Chen, Jasmine Huynh, Arta Monjazeb, May Thet Cho, Edward Jae-Hoon Kim
Journal: Journal of Clinical Oncology (2020)

TPS782 Background: Pancreatic adenocarcinoma is an aggressive disease projected to be the second leading cause of cancer-related death. A majority of patients have advanced disease on diagnosis. Combination chemotherapy is first-line for advanced disease but limited by toxicity and median survival under 1 year. SD-101 is a toll-like receptor 9 agonist that is injected intratumorally to increase immunogenicity in the tumor microenvironment. Localized radiation can further enhance this via antigen release and potential abscopal effects. Immunotherapy has revolutionized care for various solid organ malignancies but not yet for pancreatic cancer. Therefore, the combination of SD-101, localized radiation, and checkpoint inhibitor is a promising therapeutic strategy for metastatic pancreatic adenocarcinoma. Methods: Six patients with chemotherapy-refractory, liver-metastatic pancreatic adenocarcinoma will be evaluated for combination SD-101, radiation, and nivolumab. SD-101 is injected intratumorally into a liver metastasis on days 1, 8, 15, 29 with optional dosing days 43 and 57. Localized radiation (6-10 Gy per fraction) to the injected lesion will be given on days 1, 3, 5, 8, and 10. Nivolumab will be given at 240 mg every 2 weeks starting day 2 until progression or unacceptable toxicity. Blood samples will be collected at baseline and at regular intervals while on treatment. Biopsies will be obtained at baseline and on day 29. Primary objectives are to evaluate safety and tolerability, defined so if ≥5 patients reach day 29 without experiencing grade ≥3 treatment-related toxicity. Secondary objectives include preliminary efficacy as defined by disease control rate, duration of response, progression-free survival, and overall survival. Exploratory objectives include objective response rate and biomarker correlatives (T-cell clonality, tumor mutational burden, tumor infiltrative immune cell subsets, and immune-related gene expression profile). Blood and biopsy specimens will be analyzed using flow cytometry, qRT-PCR, RNA sequencing, and whole exome sequencing including immunohistochemistry on biopsy specimens. Clinical trial information: NCT04050085.
乳癌における3次元心エコー検査の役割:断層心エコー,MUGAスキャン,および心臓MRIの比較
Authors: Walker Jonathan, Bhullar Navdeep, Fallah-Rad Nazanin, Lytwyn Matthew, Golian Mehrdad, Fang Tielan, R Summers Arthur, K Singal Pawan, Barac Ivan, D Kirkpatrick Iain, S Jassal Davinder
Journal: Journal of Clinical Oncology (2010)
5-hydroxymethylation signatures in plasma circulating cell-free DNA as markers for appendiceal and colorectal peritoneal metastasis.
Authors: Yaniv Berger, Xiao-Long Cui, Diana West, Marco Rivas, Phillip Hsu, Urszula Dougherty, Zifeng Deng, Enal Hindi, Oliver Eng, Marc Bissonnette, Blase N. Polite, Kiran Turaga
Journal: Journal of Clinical Oncology (2020)

195 Background: Noninvasive tests for peritoneal metastasis (PM) detection lack sensitivity. Genome-wide mapping of 5-hydroxymethylcytosine (5hmC) on nanogram quantities of peripheral plasma circulating cell-free DNA (PcfDNA) was previously shown to differentiate non-metastatic colorectal cancer from healthy subjects. We aimed to examine if patients with colorectal cancer (CRC), high grade appendiceal cancer (HGA) or low grade appendiceal cancer (LGA) with PM have distinct signatures of 5hmC in PcfDNA compared to each other and to patients matched for tumors without PM. Methods: We analyzed plasma samples from a prospectively collected tissue bank. To correlate 5hmC signatures with intraoperative findings, only patients who underwent abdominal surgery in proximity to plasma collection were selected. Key steps of PcfDNA processing included extraction from plasma, nano-hmC-Seal chemical labeling and enrichment of 5hmC-modified fragments, next-generation sequencing, and mapping to the reference human genome. DESeq2 R package was finally used to compare relative 5hmC enrichment and detect distinct 5hmC signatures according to disease histology and PM presence. Results: Plasma samples were collected between 11/2016 – 3/2019 from 46 patients with CRC (n = 21), HGA (n = 17) and LGA (n = 8). Of those, 32 (70%) had PM based on intraoperative findings (median peritoneal cancer index score = 15, range 2-39) and 14 did not have PM. Most samples (91%) were collected on the same day as surgery. An average of 24 million paired-end reads were sequenced for each sample. Four samples (8.7%) were excluded from the analysis due to low sequencing coverage or high duplication level. Unique 5hmC enrichment patterns were found to discriminate with p &lt; 0.05 between CRC PM and HGA PM (n = 616 differentially hydroxymethylated genes (DHMGs)), CRC/HGA PM and LGA PM (n = 1074 DHMGs), and CRC/HGA PM and CRC/HGA patients without PM (n = 1576 DHMGs). Conclusions: Distinct signatures of 5hmC in PcfDNA could differentiate patients with CRC/HGA/LGA PM from each other and from patients with similar tumor histologies without PM. Thus 5hmC signatures in PcfDNA might potentially serve as a sensitive marker of occult PM.
Early results of the randomized, multicenter, controlled evaluation of S-1 and oxaliplatin as neoadjuvant chemotherapy for Chinese advanced gastric cancer patients (RESONANCE Trial).
Authors: Xinxin Wang, Shuo Li, Tianyu Xie, Yixun Lu, Xin Guo, Chen Lin
Journal: Journal of Clinical Oncology (2020)

280 Background: Perioperative chemotherapy brings potential benefits to growing patients with gastric cancer based on several clinical trials including MAGIC, ACTS-GC, CLASSIC and INT-0116. However, the effect of neoadjuvant therapy before D2 gastrectomy remains pending. According to phase II clinical trials, SOX regimen as neoadjuvant chemotherapy is associated with increased rate of D2 lymph nodes dissection and R0 resection. We hypothesize that SOX regimen can improve survival of patients with gastric cancer. Methods: Through CT, EUS and laparoscopic exploration, patients with gastric cancer on the stage IIA-IIIC were included in the study and divided into 2 groups randomly. Patients in neoadjuvant group received 2-4 cycles of SOX before surgery and 4-6 cycles after surgery, while patients in no neoadjuvant group received 8 cycles after surgery. The primary endpoint was 3-y DFS and the secondary endpoint were 5-y OS, ORR, D2/R0 resection rate and side effect. Results: A total of 772 patients were enrolled in the study between September 2012 and July 2019. After neoadjuvant therapy, the downstaging was found in neoadjuvant group (261/386, 67.6%). The pathological efficiency rate and pCR rate of neoadjuvant group were 67.8% and 23.6% respectively. The R0 resection rate in neoadjuvant group was significantly higher than that in adjuvant group(73.1% vs 58.1%, p &lt; 0.05). There was no difference in terms of surgical time, blood loss, postoperative complications and hospital stay. Conclusions: SOX makes increased rate of R0 resection, acceptable adverse effect and no impression on surgeries, which suggest that perioperative chemotherapy using SOX can prolong median survival time, DFS and OS. Clinical trial information: NCT01583361.
Increased frequency of PD-1+CD57+Siglec-7- dysfunctional NK cells in patients with nonalcoholic fatty liver disease.
Authors: Yuzuru Sakamoto, Sachiyo Yoshio, Akihisa Nagatsu, Yoh Asahi, Shingo Shimada, Tatsuya Orimo, Hirofumi Kamachi, Toshiya Kamiyama, Tatsuya Kanto, Akinobu Taketomi
Journal: Journal of Clinical Oncology (2020)

589 Background: The proportion of non-alcoholic fatty liver disease (NAFLD) has been increasing as a cause of hepatocellular carcinoma (HCC) worldwide. Natural killer (NK) cells are involved in the first line of immune defense against cancer. NK cell function is regulated by activating and inhibitory NK cell receptors. However, the role of NK cells in the pathogenesis of NAFLD and NAFLD-HCC is still largely unknown. In this study, we aimed to clarify the phenotypic and functional features of NK cells in NAFLD and NAFLD-HCC patients. Methods: We performed mass cytometry (CyTOF) and flow cytometry analysis of NK cells in 33 NAFLD patients (22 chronic hepatitis (CH), 8 liver cirrhosis (LC), 3 with HCC (HCC)) and 9 healthy donors (HDs). We compared surface markers on NK cells in cancerous and non-cancerous intrahepatic lymphocytes (IHLs). We also measured NK cell function in the presence of IL-12 and IL-18. Results: The frequency of NK cells was lower in NAFLD patients compared to HDs. PD-1, CD57, ILT2 were highly expressed, and Siglec-7, NKp30, NKp46 were downregulated on NK cells from NAFLD patients, compared with those of HDs. In NAFLD patients, Siglec-7 levels on NK cells were negatively correlated with PD-1 and CD57, and positively correlated with NKp30 and NKp46. The other inhibitory markers (NKG2A, KIR3DL1 and KIRDL2/L3), activating markers (CD69 and NKG2D) and checkpoint markers (Tim-3 and TIGIT) were comparable between NAFLD patients and HDs. PD-1 and CD57 expression levels on NK cells were also significantly upregulated in NAFLD-HCC patients than those in HDs. CD57 was rarely expressed on NK cells in non-cancerous IHLs, on the other hand, highly expressed in cancerous IHLs. The IFNγ production and CD107a expression on NK cells were also decreased in NAFLD patients. PD-1 + CD57 + Siglec-7 − NK cells were observed in NAFLD patients, rarely in HDs. PD-1 + CD57 + Siglec-7 − NK cells were functionally impaired compared to other NK subsets. Conclusions: In patients with NAFLD, NK cells are reduced and functionally impaired, the reason of which may be the increased proportion of dysfunctional PD-1 + CD57 + Siglec-7 − NK subset, and dysfunctional NK cells might be related to impairment of surveillance for HCC.
The impact of pretreatment absolute lymphocyte count (pALC) and neutrophil-lymphocyte ratio (pNLR) on checkpoint inhibitors (CPIs) response rates in renal cell carcinoma (RCC) and bladder urothelial cancers (BC).
Authors: Tonjeh Mary Stella Bah, David Sommerhalder, Philip A. Haddad
Journal: Journal of Clinical Oncology (2020)

31 Background: CPIs have been established as essential components of cancer immunotherapy across multiple cancer types with proven clinical benefit, improved outcomes, and less toxicity. Studies in lung and head and neck cancers found that low ALC, a marker of immune exhaustion, was associated with poor response to CPIs and worse progression-free survival. We explored the effect of pALC and pNLR on CPI response rates in patients with RCC and BC. Methods: We retrospectively reviewed every RCC and BC patient that received CPIs at Overton Brooks VA Medical Center and LSUHSC-S between 2015 and 2019. Patients’ pALC and pNLR were calculated. The patients were divided according to pALC into 2 groups: Group A with pALC &gt; 1000 and Group B with pALC &lt; 1000. Similarly, using NLR’s established upper normal limit of 3, 2 groups were created: Group 1 with pNLR &lt; 3 and Group 2 with pNLR &gt; 3. Our primary outcome of interest was defined as the presence or absence of CPI response. Patients who attained stable disease, partial response, and complete response were categorized as responders. Those who progressed on CPIs were labeled as non-responders. The significance of the association between pALC and pNLR groups and the occurrence of any response was analyzed statistically. Results: Twenty patients (13 RCC, 7 BC) were treated with CPIs and had documented responses. Twelve patients had pALC &gt; 1000 (Group A) whereas 8 patients had pALC &lt; 1000 (Group B). Both groups were comparable with respect to age, sex, race, and types of CPIs. Group A had a significantly higher response rate (75% vs 25%, p = 0.027). As to pNLR, 10 patients had pNLR &lt; 3 (Group 1) and another 10 patients had pNLR &gt; 3 (Group 2). Patients with pNLR &gt; 3 had worse response rates to CPIs compared to those with pNLR &lt; 3 (30% vs 80%, p = 0.024). Conclusions: This is the first report from a real-world clinical setting to show a detrimental association between pALC &lt; 1000 and pNLR &gt; 3 and CPI response rates in a retrospective cohort of consecutive non-selected kidney and bladder cancer patients. This association and its clinical utility require further confirmation in a prospective larger cohort.
Impact of baseline hepatitis B viremia and management on outcomes in patients (Pts) with advanced hepatocellular carcinoma (HCC) and elevated alpha-fetoprotein (AFP): Outcomes from REACH-2.
Authors: Peter R. Galle, Masatoshi Kudo, Josep M. Llovet, Richard S. Finn, Mark Karwal, Denis Pezet, Tae-You Kim, Tsai-Sheng Yang, Vittorina Zagonel, Jiri Tomasek, Jean Marc Phelip, Yann Touchefeu, Su-Jin Koh, Guido Stirnimann, Chunxiao Wang, Kenyon Ogburn, Paolo Abada, Ryan C. Widau, Andrew X. Zhu
Journal: Journal of Clinical Oncology (2020)

569 Background: REACH (NCT01140347) and REACH-2 (NCT02435433) were global, randomized, blinded, placebo (PL)-controlled phase 3 trials of ramucirumab (RAM) in pts with advanced HCC following sorafenib. REACH-2 limited enrollment to pts with AFP ≥400 ng/mL, and met its primary OS endpoint, consistent with the prespecified REACH subgroup with baseline AFP ≥400 ng/mL. Analysis of pooled individual pt data from REACH (AFP ≥400 ng/mL) and REACH-2 showed improved OS with RAM vs PL for pts with hepatitis B virus (HBV) etiology (7.7 vs 4.5 mos; HR 0.74, 95% CI 0.55, 0.99). Here we investigate survival and liver function in REACH-2 pts with HBV etiology tested for serum HBV DNA. Methods: Pts had advanced HCC, Child-Pugh A, ECOG PS 0/1, AFP ≥400 ng/mL, prior sorafenib treatment, and were randomized (2:1) to receive RAM 8 mg/kg or PL Q2W. Pretreatment serum HBV DNA was quantified by HBV-specific PCR (Roche) by a central lab. HBV DNA &gt; 15 IU/mL were detectable (HBV DNA+), &lt; 15 IU/mL were undetectable (HBV DNA-). OS in pooled treatment arms was evaluated using Kaplan-Meier method and Cox proportional hazards model. Liver function was assessed at baseline and before each cycle with the ALBI linear predictor. Outcomes were assessed by concomitant antiviral therapy. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Results: Of 107 REACH-2 pts with HBV etiology, 106 had available PCR samples and were included in a pooled analysis (70 RAM and 36 PL pts). 48 pts were HBV DNA+ and 58 pts were HBV DNA-. HBV DNA+ pts had poorer median OS vs HBV DNA- pts (5.3 vs 10.1 mos, unstratified HR 1.45 95% CI 0.93, 2.28). HBV DNA+ pts taking concomitant antiviral therapy (n = 36) had numerically improved OS compared with those without (n = 12) (5.8 vs 4.0 mos). No difference in OS was noted for HBV DNA- pts by antiviral therapy use (n = 39 antiviral; n = 19 no antiviral) (10.2 vs 9.7 mos for yes vs no antiviral). In pts taking antiviral therapy, regardless of HBV DNA serology, liver function was improved and liver injury/failure related AEs were less frequent. Conclusions: Our data reinforce the use of antiviral therapy to improve outcomes in pts with advanced HBV-associated HCC and elevated AFP. Clinical trial information: NCT02435433.
Self-reported patient experience and quality of care among elderly patients with colon cancer.
Authors: Rebecca A Snyder, Rebecca Wardrop, Alexander Mclain, Alexander A. Parikh, Anna Cass
Journal: Journal of Clinical Oncology (2020)

33 Background: Although studies have identified demographic and clinical factors associated with quality colorectal cancer care, the association between patient-reported experience of care and quality of care is unknown. Our primary aim was to assess the relationship between patient-reported experience of care and receipt of guideline-concordant colon cancer (CC) treatment. Methods: Fee-For-Service Medicare beneficiaries with resected stage I-III CC (2003-2013) were identified in the linked SEER registry and Consumer Assessment of Healthcare Providers and Systems patient experience survey (SEER-CAHPS) dataset. Patient-reported ratings were compared based on receipt of care consistent with recommended treatment guidelines [resection of ≥ 12 lymph nodes (LN) (stage I-III) and receipt of adjuvant chemotherapy (stage III)]. Linear regression was performed to compare mean patient experience scores by receipt of guideline concordant care, adjusting for patient and hospital factors. Results: 1010 patients with stage I-III CC were identified (mean age 76.7, SE 6.9). Of these, 58.4% of stage I (n = 192/329) and 73.4% of stage II (n = 298/406) patients underwent resection of ≥ 12 LN. Among stage III patients, 76.0% (n = 209/275) underwent resection of ≥ 12 LN and 52.4% (n = 144/275) received adjuvant chemotherapy. By multivariable analysis, patient-reported ratings of health care quality, personal and specialty physicians, customer service, physician communication, getting needed care, and getting care quickly were similar among patients who received guideline-concordant treatment compared to those who did not. However, mean ratings of overall health care quality [91.3 (SE 2.0) vs. 82.4 (SE 1.7), p = 0.0004] and getting needed care [92.8 (SE 2.4) vs. 86.8 (SE 2.0), p = 0.047] were higher among stage III patients who received guideline concordant care compared to those who did not. Conclusions: Patient-reported ratings of health care quality and ability to get needed care are associated with guideline concordant cancer care among elderly patients with stage III CC. Further investigation is needed to determine if patient-reported experience correlates with other clinical measures of quality of colorectal cancer care.
Pretreatment Heterogeneous Enhancement Pattern of Hepatocellular Carcinoma May Be a Useful New Predictor of Early Response to Lenvatinib and Overall Prognosis
Authors: Yusuke Kawamura, Masahiro Kobayashi, Junichi Shindoh, Yuta Kobayashi, Kayoko Kasuya, Tomoya Sano, Shunichiro Fujiyama, Tetsuya Hosaka, Satoshi Saitoh, Hitomi Sezaki, Norio Akuta, Fumitaka Suzuki, Yoshiyuki Suzuki, Kenji Ikeda, Yasuji Arase, Masaji Hashimoto, Hiromitsu Kumada
Journal: Liver Cancer (2020)

The aim of this study was to evaluate the performance of pretreatment computed tomography (CT) enhancement of hepatocellular carcinoma (HCC) as a potential predictor of response to lenvatinib and its relevance to survival outcomes.We evaluated 51 consecutive patients who received lenvatinib treatment for unresectable HCC. On imaging analysis, pretreatment arterial/portal phase dynamic CT images were classified as follows: type 2, homogeneous enhancement pattern with increased arterial blood flow; type 3, heterogeneous enhancement pattern with a septum-like structure; and type 4, heterogeneous enhancement pattern with irregularly shaped ring structures. Treatment response was evaluated using modified Response Evaluation Criteria in Solid Tumors at 2-12 weeks after initiation of lenvatinib, and the correlations between the CT enhancement patterns and response to lenvatinib or survival outcomes were investigated.Of the 51 patients, 38 (75%) experienced an objective response (OR). ORs were significantly more common in heterogeneously enhanced HCC (types 3 and 4) than in homogeneous HCC (type 2) (83 vs. 53%, respectively; p = 0.037). Multivariate analysis revealed that pretreatment heterogeneous enhancement pattern is an independent predictor for response to lenvatinib (odds ratio, 4.75; p = 0.042). Presence of OR was associated with longer progression-free survival (PFS) (hazard ratio, 0.36; p = 0.017), and patients with oncologically aggressive type 3 and 4 tumors showed similar PFS to those harboring type 2 tumors (p = 0.455), reflecting that OR was more common in type 3 or 4 tumors compared with type 2 tumors. Although postprogression survival was extremely poor in patients with type 4 tumors (p = 0.064), overall survival after introduction of lenvatinib was not statistically different among the three groups of patients (p = 0.053).The CT enhancement pattern of HCC may predict response to lenvatinib. OR seems to occur more frequently in HCC with oncologically aggressive features and may contribute to prolonged survival through a prolonged progression-free interval, even in an oncologically poor-risk group of patients.
Outcomes of elderly patients with resectable liver metastases from colorectal cancer (CRLM): Single center experience.
Authors: Laura Mansour, Rami Mohamad Nassabein, Filip Gryspeerdt, Franck Vandenbroucke-Menu, Francine Aubin, Jean-Pierre M. Ayoub, Michel Dagenais, Real W. Lapointe, Richard Letourneau, Marylene Plasse, Andre Roy, Simon Turcotte, Mustapha Tehfe
Journal: Journal of Clinical Oncology (2020)

34 Background: Half of patients with colorectal cancer develop liver metastases during the course of their disease. Surgery is the only potentially curative option for CRLM if resectable. Treatment of patients over 70 years old is challenging mainly because of comorbidities and other geriatric syndromes. Thus, we intended to report our experience with elderly patients with resectable CRLM. Methods: After approval by the Institutional Review Board (IRB), all records from a prospectively collected database at Centre Hospitalier de l’Université de Monréal (CHUM) were retrospectively analyzed. Clinicopathological characteristics, surgery and chemotherapy treatment modalities were reviewed. RFS and OS in patients ≥ 70y were calculated using the Kaplan Meier survival curve. Results: From 2010 to 2016, 101 patients older than 70 years were identified. Safety and surgical complications were previously reported. Median age was 75 years. CRLM were synchronous in 46.5% and metachronous in 53.5%. Relapse free survival (RFS) of patients ≥ 70 years was 33.7 months. Overall survival (OS) of patients ≥70 years was comparable to those of less than 65 years old (median OS: 56 vs 62 months; p = 0.15, respectively). Hepatic relapse showed worse survival when compared to extra-liver recurrence, mOS: 44 vs 33.2 vs 29.3 months for non-hepatic, hepatic only and hepatic with other sites respectively (trend p = 0.034). Although non-statistically significant, Patients with metachronous CRLM had superior mOS compared to those with synchronous disease (58.7 vs 44.7 months; p = 0.22). Conclusions: Survival Outcomes of patients with an age ≥ 70 years were comparable to those of younger patients and what is reported in literature. Age should not be a limiting factor in the management of elderly patients with resectable CRLM. Hepatic metastatectomies +/- chemotherapy should be offered with curative intents.