tbuckley/cabot-search huggingface dataset:
Immunogenomic signatures to predict outcome in ovarian and endometrial cancers: Potential strategies in targeting the tumor immune microenvironment to improve response to immunotherapy.
Authors: Haider Mahdi, Ying Ni
Journal: Journal of Clinical Oncology (2020)

4 Background: Ovarian and MSS endometrial cancers are characterized by immunosuppressive microenvironment (TME) and low response to immunotherapy with checkpoint inhibitors (CPI). Targeting immunosuppressive factors within TMErepresents an attractive approach to enhance response to CPI. Therefore, we sought to investigate different immunogenomic signatures and immune cells within TME and correlate them with survival. Methods: We used whole transcriptome sequencing of matched tumor-normal samples from 38 uterine serous cancer and TCGA data of ovarian (n = 374) and endometrial cancers (n = 541). Immunogenomic signatures focusing on Transforming Growth Factor (TGFβ), 18-genes IFN-γ and myeloid signatures (CD47 and B7H4 expressions) and immune cell abundance were investigated. Gene expression score was calculated by averaging the normalized and log transformed individual gene read counts. The optimized score cut off was selected to best separate the survival in the pilot cohort. Then the score was tested in TCGA RNAseq datasets. Population abundance of tissue-infiltrating immune cells were estimated using MCPcounter R package from bulk transcriptome data. Results: Higher IFN-γ and lower TGF-β signatures predicted better survival for endometrial and ovarian cancers (p &lt; 0.05). The impact of TGF-β was higher in MSI-H vs. MSS cancers (p = 0.013 vs. 0.09). High CD47 predicted poor survival in endometrial cancer. Combined IFN-γ and TGF-β signatures predicted survival in the ovarian and endometrial cohorts (p &lt; 0.001). Combined IFN-γ and CD47 expression predicted survival in endometrial cancer (p = 0.033). Analysis of immune cell abundance revealed enrichment of monocytic lineage and neutrophils but paucity of cytotoxic T-cells, NK cells, dendritic cells and B-cells. Immune cell abundance is being correlated with survival. Conclusions: Our data support the role of immunogenomic markers in predicting survival. We are evaluating these markers in predicting response to CPI in a pilot cohort. Immunogenomic markers represent the tumor microenvironment, can potentially guide rationale combination immunotherapy.
A feasibility study of microwave therapy for precancerous actinic keratosis
Authors: D.N. Jackson, F.J. Hogarth, D. Sutherland, E.M. Holmes, P.T. Donnan, C.M. Proby
Journal: British Journal of Dermatology (2020)

Actinic keratosis (AK) is a common premalignant skin lesion that can progress to cutaneous squamous cell carcinoma (cSCC). Microwave therapy is an established cancer treatment and has been used for plantar viral warts.To evaluate the efficacy and feasibility of microwave as a treatment for AK.Stage I was a dose-setting study, in which seven participants had the dielectric properties of 12 thick and 22 thin AKs assessed for optimization of the microwave dose used for treatment in Stage II. Stage II was a randomized, internally controlled trial evaluating 179 AKs in 11 patients (93 treated, 86 untreated controls) on the scalp/forehead or dorsal hand. Participants received one treatment initially and a repeat treatment to unresolved AKs at week 4. The response was assessed at six visits over 4 months. The primary outcome was partial or complete resolution of the treated AKs.A significantly higher proportion of treated AK areas responded than untreated (90% vs. 15%; P < 0·001). Thin AKs were more responsive than thick AKs. The site did not affect efficacy. Pain was severe, but brief (80% reported pain lasting 'a few seconds only'). Adverse effects were minimal (erythema, n = 6; flaking, n = 3; itch, n = 3). All participants who would chose microwave therapy over their current treatment cited the shorter discomfort period.Microwave therapy is a portable, safe and effective treatment for AK. An easy-to-deliver, acceptable therapy for AK is attractive as a prevention strategy. While these results are promising, a larger randomized controlled trial is needed against an effective comparator to confirm clinical efficacy and patient acceptability. What is already known about this topic? Actinic keratoses (AKs) are common precancerous skin lesions. Successful treatment of AK can prevent cutaneous squamous cell carcinoma (cSCC). Most topical therapies for AK require repeated application over weeks and drive local skin inflammation, leading to poor compliance. An easy-to-deliver and effective treatment for AK, suitable for use in primary care, could reduce cSCC. What does this study add? Microwave therapy is a feasible, effective treatment for AK. Ninety per cent of treated AKs showed full or partial resolution at 120 days post-treatment. Microwave therapy was painful, but the pain was short-lived (seconds) and this short discomfort period was cited as the main reason that microwave was preferred to their current treatment.
Comparative Molecular Life History of Spontaneous Canine and Human Gliomas
Authors: Samirkumar B. Amin, Kevin J. Anderson, C. Elizabeth Boudreau, Emmanuel Martinez-Ledesma, Emre Kocakavuk, Kevin C. Johnson, Floris P. Barthel, Frederick S. Varn, Cynthia Kassab, Xiaoyang Ling, Hoon Kim, Mary Barter, Ching C. Lau, Chew Yee Ngan, Margaret Chapman, Jennifer W. Koehler, James P. Long, Andrew D. Miller, C. Ryan Miller, Brian F. Porter, Daniel R. Rissi, Christina Mazcko, Amy K. LeBlanc, Peter J. Dickinson, Rebecca A. Packer, Amanda R. Taylor, John H. Rossmeisl, Kevin D. Woolard, Amy B. Heimberger, Jonathan M. Levine, Roel G.W. Verhaak
Journal: Cancer Cell (2020)

Sporadic gliomas in companion dogs provide a window on the interaction between tumorigenic mechanisms and host environment. We compared the molecular profiles of canine gliomas with those of human pediatric and adult gliomas to characterize evolutionarily conserved mammalian mutational processes in gliomagenesis. Employing whole-genome, exome, transcriptome, and methylation sequencing of 83 canine gliomas, we found alterations shared between canine and human gliomas such as the receptor tyrosine kinases, TP53 and cell-cycle pathways, and IDH1 R132. Canine gliomas showed high similarity with human pediatric gliomas per robust aneuploidy, mutational rates, relative timing of mutations, and DNA-methylation patterns. Our cross-species comparative genomic analysis provides unique insights into glioma etiology and the chronology of glioma-causing somatic alterations.
Feasibility and pathological response of TAS-118 + oxaliplatin as perioperative chemotherapy for patients with locally advanced gastric cancer (APOLLO-11).
Authors: Daisuke Takahari, Atsuo Takashima, Takako Eguchi Nakajima, Naoki Ishizuka, Manabu Ohashi, Hitoshi Katai, Shinya Mikami, Keisho Chin, Souya Nunobe, Miki Ito, Takeyuki Wada, Takashi Ogura, Takeshi Sano, Narikazu Boku, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2020)

351 Background: TAS-118 is a novel oral agent, containing S-1 and leucovorin. In the SOLAR study (NCT02322593), TAS-118 + oxaliplatin (OHP) significantly improved overall survival compared to S-1 + cisplatin for patients (pts) with advanced gastric cancer (GC). We conducted this open-label study to assess feasibility of perioperative adjuvant chemotherapy with TAS-118 + OHP in pts with locally advanced resectable GC with lymph node metastasis. (Clinical trial information: UMIN000024688). Methods: Eligible pts who had histopathologically confirmed GC with clinical T3-4N1-3M0 on image findings (14 th Japanese classification of gastric carcinoma), age 20 to 79 years, were enrolled in this study. The protocol treatment consisted of preoperative 4 courses of TAS-118 (80-120 mg/body, days 1-7) + OHP (85 mg/m 2 , day 1) every 2 weeks, and gastrectomy with D2 lymphadenectomy, followed by postoperative 12 courses of TAS-118 alone (step1) or 8 cycles of TAS-118 + OHP (step2). The primary endpoints were tolerability of preoperative chemotherapy, gastrectomy and postoperative chemotherapy with TAS-118 plus OHP. Here, we report the feasibility of preoperative chemotherapy and gastrectomy, and pathological response. Results: Between December 2016 and April 2018, 45 pts with a median age of 61 years were enrolled. The numbers of pts with T stage (cT3/4a) and those with N stage (cN1/2/3) were 13/32 and 25/17/3, respectively. The completion rate of preoperative chemotherapy and gastrectomy was 88.9% ( 95% CI 78.0-95.5) and 95.6% (95% CI 86.7-99.2). The relative dose intensity of TAS-118 and OHP was 86.0% and 90.6%. During the 4 cycles of preoperative TAS-118 + OHP, 2 pts discontinued the treatment due to adverse event (AE). Major grade 3-4 AEs were diarrhea (17.8%) and neutropenia (8.9%). R0 resection rate was as high as 95.6%. One pts experienced grade 4 postoperative bleeding, but no treatment-related death was reported. pCR was achieved in 6/45 pts (13.3%) and other 7 pts (28.9%) showed near complete regression (&lt;10 % residual tumor cells). Conclusions: Preoperative TAS-118 + OHP followed by D2 gastorectomy was well tolerated and showed promising efficacy. Clinical trial information: 000024688.
A phase II study of capecitabine plus concomitant radiation therapy followed by durvalumab (MEDI4736) as preoperative treatment in rectal cancer (PANDORA).
Authors: Stefano Tamberi, Elisa Grassi, Maria aurelia Barbera, Jody Corbelli, Giorgio Papiani, Isacco Montroni, Maria Di Bartolomeo, Stefano Cascinu, Marina Marzola, Andrea Bonetti, Giovanni Frassineti, Carmine Pinto, Chiara Zingaretti, Oriana Nanni, Chiara Carli Moretti, Ilaria Panzini, Giulio Rossi, Giampaolo Ugolini
Journal: Journal of Clinical Oncology (2020)

TPS259 Background: The standard treatment for cT3-4 N0-1 rectal cancer is preoperative chemo-radiation therapy (CT/RT). The combination of capecitabine plus long course radiotherapy (RT) is standard therapy in this setting. Pathologic Complete remission (pCR) can be considered as surrogate end point of efficacy of treatment in terms of disease free survival (DFS). Clinical complete remission (cCR) is an important endpoint for “wait and see” strategy. In the PACIFIC trial in non-small cell lung cancer the patients were treated with durvalumab maintenance after CT/RT with advantage in progression free survival. Preclinical data points heavily toward a strong synergy between RT and immune treatments. Furthermore, a systemic effect of RT is possible when enhanced by targeted immune treatments. Methods: This is a prospective phase II, open label, single arm, multi-centre study to evaluate the activity of an innovative sequence in operable rectal cancer: standard concomitant CT/RT therapy with 825 mg/m2 twice daily capecitabine every day and 5040 cGy radiotherapy for 5 days per week for 5 weeks followed by 1500 mg Q4W durvalumab for 3 administration. After 9-10 weeks from neoadjuvant therapy will be performed re-staging with CT and MRI scan. Surgery will be performed at week 10-12 from the end of CT/RT. Primary Objective: pCR rate, defined as a TRG 3-4 according to DWORAK criteria. Secondary Objectives: Safety of treatment with durvalumab; cCR rate after durvalumab treatment before surgery and DFS. cCR will be evaluated with clinical, endoscopic and radiological assessment to look for evidence of residual disease. DFS will be evaluated during a follow up of 5 years. Exploratory Objective: Biological translational analysis of tumor biomarkers will be performed on the endoscopy biopsy done at the diagnosis and on the biopsy performed after the CT/RT prior to treatment with durvavalumab. We hypothesize that the addition of durvalumab after standard CT/RT for the treatment of locally advanced rectal cancer may improve the pathological response rate and we have planned to enlist 60 patients in 7 centers with an enrollment period of 12 months, already underway. Clinical trial information: NCT04083365.
Perioperative docetaxel, oxaliplatin, and capecitabine (DOX) in resectable adenocarcinomas of lower esophagus, esophagogastric junction, and stomach.
Authors: Shaunak Valame, Dipanjan Panda, Shuaib Zaidi, Praveen Garg, Syed Asim Razvi, Manish Kumar Singhal, Pratap K. Das, Pankaj Baweja, Jayanta Patowary
Journal: Journal of Clinical Oncology (2020)

349 Background: In a real-world scenario, Fluorouracil-based triplet combination chemotherapies have limited feasibility with regards to toxicity, need for central venous access, and hospitalization. The primary objective of this study was to assess pathological tumor regression to Capecitabine-based triplet regimes, with the additional possible benefit of overcoming the aforementioned barriers. Methods: This Single-Arm, Prospective study investigated the primary outcome of histopathologic regression to perioperative Docetaxel, Oxaliplatin, and Capecitabine (DOX) combination regime in histologically confirmed resectable Esophageal, Esophagogastric Junction, and Gastric Adenocarcinomas. Three preoperative and 3 postoperative cycles of Docetaxel 60mg/m 2 plus Oxaliplatin 100mg/m 2 on Day 1, with Capecitabine 500mg/m 2 twice daily from Day 1 to Day 21 were administered, with cycles repeating every 21 days. Histopathologic regression was assessed by Modified Ryan’s Schema on surgical specimen. The study had an 80% power (two-sided significance of 0.05) to detect a 20% pathological complete response. Secondary endpoints were Overall Survival, Progression-Free Survival, and Toxicity analysis. Results: Between June 2017 to May 2019, 28 patients (median age 54.5 years [Range 33 – 82]; Male 78.6%; ECOG PS 1/2 = 42.9%/57.1%) were enrolled in the study of which 92.9% completed preoperative chemotherapy. Of the 20 patients operated upon, 100% were R0 resections. Pathological complete response was observed in 20% (4/20). Ninety percent of the operated patients completed the postoperative treatment. The most common grade ≥3 toxicities were Palmar-Plantar Erythrodysesthesia (10.7%), Fatigue (10.7%), and Diarrhoea (7.1%). Conclusions: Perioperative DOX met its primary endpoint of 20% pathologic complete regression with a favourable toxicity profile and was feasible to administer in resectable Esophageal, Esophagogastric Junction, and Gastric Adenocarcinomas. This regimen deserves further evaluation in larger phase III trials.
A hybrid of the prone and left lateral decubitus positions for thoracoscopic esophagectomy with extended LN dissection for esophageal squamous cell carcinoma.
Authors: Hirofumi Kawakubo, Shuhei Mayanagi, Satoru Matsuda, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2020)

402 Background: We first performed thoracoscopic esophagectomy (TE) as a minimally invasive procedure with the left decubitus position in 1996. In 2009 we developed a hybrid of the prone and left lateral decubitus positions for TE with extended LN dissection (Extensive-TE). The patient is fixed with the semi-prone position and we can easily change patient positions from the left lateral decubitus position to the prone position using rotation system of the operation table. The upper mediastinal procedure including lymphadenectomy along the right and left recurrent laryngeal nerve (RLN) is performed with the patient in the left lateral decubitus position, while the middle and lower mediastinal procedures are performed with the patient in the prone position with artificial pneumothorax. Methods: ESCC patients who underwent Extensive-TE between January 2009 and December 2016, were retrospectively reviewed. The patients’ background, surgical outcomes, postoperative complications and recurrence-free survival (RFS) were studied. Results: Primary tumor was located in Cervical esophagus for 2 (1%), the upper-thoracic esophagus for 28 (15%), the mid-thoracic esophagus for 104 (54%) and the lower-thoracic esophagus for 57 (30%). Thenumber of patients classified with pre-treatment clinical stage of 1/2/3/4 was 94(49%)/42(22%)/46(24%)/9(5%), respectively. Eight patients were evaluated as having cM1 disease due to supraclavicular LN metastasis. The number of patients classified with postoperative pathological stage of 0/1/2/3/4 was 5(3%)/70(37%)/48(26%)/49(27%)/19(7%), respectively. The average total operation time was 542.1 and blood loss was 274.2. The incidence of postoperative pneumonia, anastomotic leakage, chylothorax, and recurrent nerve palsy was 17%, 14%, 2%, and 7% respectively. One patient died postoperatively within 90 days after surgery. Three years RFSwith clinical stage of 1/2/3+4 was 91.5%/54.8%/51.9%, respectively. Conclusions: The magnifying effect of thoracoscopy enables us to perform more precise surgery and preserve nerve and vessels. Extensive-TEwith a hybrid position is thought to be feasible and effective methods.
肺静脈前庭部周囲アブレーション一周後のアブレーション線上に伝導ギャップを同定するための肺静脈マップ | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Miyamoto Koji, Tsuchiya Takeshi, Yamaguchi Takanori, Nagamoto Yasutsugu, Andoh Shinichi, Hayashida Kiyoshi, Tanioka Yoshito, Takahashi Naohiko
Journal: Circulation (2011)
Rapid respiratory response team - The first two years' experience
Authors: J G Williams, B Furnival, J Meek, S Furlong, G Roberts, R Smith
Journal: Thorax (2000)

Our hospital based rapid respiratory response team has previously reported its early experience of community respiratory care and its success in preventing some hospital admissions for exacerbations of chronic obstructive pulmonary disease (Thorax 1998; 53:Supp 4:A70) We wish to present our data from two years' experience which also includes data on patients with malignant disease. 341 referrals were received for 314 patients from 1.12.97 to 1.12.99. 210(61%) were from general practitioners. GP Referrals Inpatient Referrals Non- Malignant Non- Malignant Malignant Disease Malignant Disease Disease Disease Number of Referrals 175 35 98 5 Mean Age (years±SD) 72±11 66±11 70±13 69.6±10 Gender (M:F) 82:93 19:17 50:48 2:3 Median number of Visits (Range) 7 (4-121) 4 (3-42) 7 (3-56) 8 (4-38) Median number of telephone calls (Range) 3 (2-80) 3 3 (0-25) 3 (2-10) Chest readmissions while in scheme 10 (5.7%) 2 (5.6%) 0 1 (20%) Only 62 (18%) patients with non-malignant disease were readmitted with respiratory disorders after discharge from the team of which 30 patients (48%) were admitted within the first three months. The readmission rates for respiratory disease while within the scheme and post discharge compare favourably with the results of others. The popularity of the scheme with primary care teams and patients alike increases. There is a local desire to include non acute respiratory care in team's remit.
Adverse events (AEs) with maintenance olaparib in patients with a germline BRCA mutation (gBRCAm) and metastatic pancreatic cancer (mPaC): Phase III POLO trial.
Authors: Michele Reni, Hedy L. Kindler, Pascal Hammel, Eric Van Cutsem, Teresa Macarulla, Michael J. Hall, Joon Oh Park, Daniel Hochhauser, Dirk Arnold, Do-Youn Oh, Anke C. Reinacher-Schick, Giampaolo Tortora, Hana Algül, Eileen Mary O'Reilly, David McGuinness, Karen Cui, Katia Schlienger, Gershon Y. Locker, Talia Golan
Journal: Journal of Clinical Oncology (2020)

686 Background: In POLO (NCT02184195), maintenance olaparib was well tolerated and led to a significant progression-free survival benefit vs placebo in patients with a gBRCAm and mPaC whose disease had not progressed on first-line platinum-based chemotherapy (HR 0.53; 95% CI 0.35–0.82) (Golan et al. NEJM 2019). We analyzed common AEs and their management in POLO. Methods: Patients were randomized (3:2) to maintenance olaparib (tablets; 300 mg bid) or placebo until disease progression or unacceptable toxicity. AEs were graded using CTCAE v4.0. Results: Of 154 randomized patients, 151 were treated (olaparib, n=91; placebo, n=60) and included in safety analyses. Median treatment duration was 6.0 months (m) for olaparib and 3.7 m for placebo. Management of fatigue/asthenia, nausea, anemia and vomiting included supportive treatment and/or dose modification; few patients discontinued treatment due to AEs (Table). Of patients with anemia, 14 olaparib recipients received a blood transfusion while on study treatment; one olaparib recipient received epoetin beta. Conclusions: The AE profile of maintenance olaparib in patients with a gBRCAm and mPaC was consistent with that seen in other tumor types.Common AEs of fatigue/asthenia, nausea, anemia and vomiting occurred early, were manageable and led to few treatment discontinuations. Clinical trial information: NCT02184195 . [Table: see text]
Pembrolizumab (pembro) in microsatellite instability-high (MSI-H) advanced gastric/gastroesophageal junction (G/GEJ) cancer by line of therapy.
Authors: Joseph Chao, Charles S. Fuchs, Kohei Shitara, Josep Tabernero, Kei Muro, Eric Van Cutsem, Yung-Jue Bang, Ferdinando De Vita, Greg A. Landers, Chia-Jui Yen, Ian Chau, Anneli Elme, Jeeyun Lee, Mustafa Ozguroglu, Daniel V.T. Catenacci, Xiaodong Li, Chie-Schin Shih, Sukrut Shah, Pooja Bhagia, Zev A. Wainberg
Journal: Journal of Clinical Oncology (2020)

430 Background: Pembro has demonstrated promising antitumor activity in patients (pts) with advanced G/GEJ cancer with PD-L1 CPS ≥1 and CPS ≥10 irrespective of MSI-H status. Here, we examine the antitumor activity of pembro monotherapy vs chemo in pts with MSI-H, advanced G/GEJ cancer in KEYNOTE (KN)-059 (NCT02335411), KN061 (NCT02370498), and KN062 (NCT02494583). Methods: Eligible pts with advanced G/GEJ cancer with ≥2 prior therapies (KN059 cohort 1; 3L+), 1 prior therapy (KN061; 2L), or no prior therapy (KN062; 1L) were enrolled. In KN059 cohort 1, pts received pembro only. In KN061 pts were randomized to pembro or paclitaxel (chemo), and in KN062 to pembro, pembro + cisplatin+5-FU/cape (chemo), or chemo. Pts received pembro 200 mg Q3W for up to 2 y. MSI-H status was determined centrally by PCR. Endpoints included OS, PFS, ORR, and safety. Data cutoff dates were Aug 8, 2018 (KN059), Oct 26, 2017 (KN061), and Mar 26, 2019 (KN062). Results: At data cutoff, 259 pts (n = 7 [3%] MSI-H) had enrolled in KN059 cohort 1 (3L+), 592 (27 [5%] MSI-H]) in KN061 (2L), and 763 (50 [7%] MSI-H] in KN062 (1L). Median follow-up was 5.6 mo, 7.9 mo, and 11.3 mo, respectively. For the overall study populations, median OS was 5.5 mo for pembro (3L+), 6.7 mo vs 8.3 mo for pembro vs chemo (2L), and 10.6 mo vs 11.0 mo for pembro vs chemo (1L). Median PFS was 2.0 mo (3L+), 1.5 vs 4.1 mo (2L), and 2.0 vs 6.4 mo (1L). ORR was 11.6% (3L+), 11.1% vs 12.5% (2L), and 14.8% vs 37.2% (1L), with median DOR of 16.1 mo, 18.0 vs 5.5 mo, and 13.7 vs 6.8 mo. In pts with MSI-H tumors, OS and PFS were prolonged with pembro vs chemo, with higher ORR (Table). Conclusions: As with PD-L1 expressers, MSI-H status is a predictive biomarker for pembro monotherapy in advanced G/GEJ cancer irrespective of line of therapy. Clinical trial information: (KN)-059 (NCT02335411), KN061 (NCT02370498), and KN062 (NCT02494583). Merck &amp; Co., Inc., Kenilworth, NJ, USA.[Table: see text]