tbuckley/cabot-search huggingface dataset:
Short-course radiation followed by mFOLFOX-6 plus avelumab for locally advanced rectal adenocarcinoma.
Authors: Ali Shamseddine, Youssef Zeidan, Ibrahim Moustafa Khalifeh, Joseph Gergi Kattan, Rim Turfa, Deborah Mukherji, Sally Naji Temraz, Faek Jamali, Yasser Hani Shaib, Assaad Soweid, Samer Deeba, Malek Kreidieh, Ziad zuheir El Husseini, Maya Charafeddine, Monita Al Darazi, Fady B. Geara
Journal: Journal of Clinical Oncology (2020)

139 Background: Total neoadjuvant treatment (TNT) for locally advanced rectal cancer is becoming an accepted approach over the last few years with increasing pathologic complete response (pCR) and compliance of patients for chemotherapy in comparison with the current standard of care i.e., fluoropyrimidine based chemoradiation followed by surgery and adjuvant chemotherapy. Sequential use checkpoint inhibitors after radiation therapy (RT) has demonstrated synergistic effect in vivo leading to decrease in size of irradiated and non-irradiated secondary tumors outside the radiation field (abscopal effect). Methods: This is an investigator initiated; open-label, single-arm multicenter phase II study, adopting Simon’s two-stage aiming at evaluating the pCR rate and safety of using short-course radiation therapy (25 Grays in 5 fractions), followed by 6 cycles of mFOLFOX-6 plus Avelumab (anti PDL1), then total mesorectal excision(TME) in patients with locally-advanced, potentially resectable rectal adenocarcinoma. Results: 13 out of 44 patients were accrued from 20, July till 28, Dec 2018 in the first stage of the study (30% from total sample size). They all met the inclusion criteria and received full protocol treatment. 12 out of the 13 completed TME. 1 of the 13 had progression of disease, so surgery was aborted and patient was dropped out the study. The sample consisted of 9 (69%) males and 4 (31%) females with median age of 62 (33.0, 73.0) years. The first interim analysis revealed 3 patients (25%) achieved pCR (tumor regression grade: TRG = 0) out of 12 as compared to the historical control group with pCR of 16%. For the rest of the patients, 3 (25%) had major pathologic response rate (pRR) with TRG = 1 (&lt; 10% viable cells is tumor bed).In total, 6 out of 12 patients (50%) had major pathologic response rate. As for safety, no serious adverse events of grade 3 and 4 were reported. Conclusions: Based on the first interim analysis results, incorporation of Avelumab and short course radiotherapy is tolerable in patients with locally advanced rectal cancer treated with TNT. The study will resume recruitment to reach the target accrual. Clinical trial information: NCT03503630.
Role of Wnt5a in suppressing invasiveness of hepatocellular carcinoma via epithelial mesenchymal transition.
Authors: Kazuki Wakizaka, Toshiya Kamiyama, Tatsuya Orimo, Shingo Shimada, Akihisa Nagatsu, Yoh Asahi, Yuzuru Sakamoto, Hirofumi Kamachi, Tomoko Mitsuhashi, Akinobu Taketomi
Journal: Journal of Clinical Oncology (2020)

573 Background: Wnt signaling pathway includes canonical pathway and non-canonical pathway. Wnt/β-Catenin pathway as canonical pathway is associated with the development of hepatocellular carcinoma (HCC). On the other hand, the association between aberrant activation of non-canonical pathway activated by Wnt5a and tumor progression of HCC is not well-known. We investigated the significance of the expression of Wnt5a in HCC. Methods: Immunohistochemical staining of Wnt5a was performed on the specimen of 243 patients who underwent hepatic resection for HCC. We investigated whether the expression of Wnt5a correlated with the clinicopathological factors, survival, and recurrence in HCC patients. The expression of Wnt5a in human HCC cell lines HLE, HLF, HepG2 and Huh7 was investigated by western blotting. The effects of overexpression or knockdown of Wnt5a on cell lines were evaluated by proliferation assay and invasion assay and changes in epithelial mesenchymal transition (EMT) related molecules were studied by western blotting. Results: The Wnt5a expression was positive in 63 patients (25.9%) and negative in 180 patients (74.1%). The Wnt5a negative was significantly associated with poorly differentiation (P = 0.003) and vascular invasion positive (P = 0.046). By univariate analysis, Wnt5a negative (P = 0.020) was identified as a significant prognostic factor of OS. Multivariate analysis of OS showed that Wnt5a negative (HR 1.895, 95% CI 1.053-3.409, P = 0.033) was identified as an independent prognostic factor. In the HCC cell lines, the Wnt5a expression was lower in HLE and HLF than in HepG2 and Huh7. Knockdown of Wnt5a by shRNA increased the proliferation and invasiveness in Huh7 with high expression of Wnt5a. As a result, the expression of E-cadherin decreased. In HLF with low expression of Wnt5a, overexpression of Wnt5a inhibited the invasiveness and the expression of vimentin decreased. Conclusions: Wnt5a negative was associated with poorly differentiation and vascular invasion, and was independent poor prognostic factor in HCC patients. Wnt5a may be a tumor suppressor involved in EMT mediated changes of invasiveness.
Immune adverse events (irAEs) with adjuvant ipilimumab in melanoma, use of hormone replacement and immunosuppressants, and association with outcome: E1609 study analysis.
Authors: Ahmad A. Tarhini, Sandra J. Lee, Ni Kang, F. Stephen Hodi, Uma N. M. Rao, Gary Irvin Cohen, Lawrence E. Flaherty, Teresa M. Petrella, Vernon K. Sondak, John M. Kirkwood
Journal: Journal of Clinical Oncology (2020)

60 Background: E1609 evaluated adjuvant ipilimumab at 3 mg/kg (ipi3) and 10 mg/kg (ipi10) versus high-dose interferon-α (HDI). In-depth analysis of irAEs and the use of immunosuppressants and hormone replacement may provide important lessons for management and future research. Methods: E1609 enrolled 1670 adult pts with resected cutaneous melanoma (AJCC7 IIIB, IIIC, M1a, M1b); Table. We investigated the characteristics of irAEs, corticosteroid, immunosuppressant and hormone use on the ipi arms and association with outcome. Stratified log-rank test was used and since most irAEs were observed within 3 months of initiating ipi, a 3-month landmark adjustment analysis was conducted. Results: The rates of corticosteroid, immunosuppressant and hormone use by treatment are summarized in Table and none had a significant association with RFS or OS. Significant association between occurrence of grade 1-4 irAEs (vs. no AE) and RFS was observed [5-year RFS: 0.49, 95% CI: (0.45, 0.52) compared to 0.41, 95% CI: (0.31, 0.50); landmark p=0.010]. Occurrence of grade 1-2 irAEs appeared to have a stronger association with RFS [5-years RFS: 0.52, 95% CI: (0.47, 0.56) compared to 0.41, 95% CI: (0.31,0.50) with no AE; p=0.006] and a trend towards improved OS [5-year OS: 0.75, 95%CI:( 0.71, 0.79) compared to 0.67, 95% CI: (0.56, 0.75) with no AE; p=0.064]. Among specific irAEs, rash was most significantly associated with RFS (p = 0.004 and 0.002) and OS (p = 0.007 and 0.003) for grade 1-4 and grade 1-2, respectively, followed by endocrinopathies, and weaker associations seen with other AEs. Conclusions: Adjuvant therapy with ipi is associated with significant irAEs that appear to be related to the immune mechanism of action. Corticosteroids and immunosuppressants were not shown to negatively affect the clinical outcomes. Predictors of irAE risk and understanding the underlying mechanisms are a major gap and are currently actively being investigated. Clinical trial information: NCT01274338. [Table: see text]
Morbidity associated to advanced gastric cancer and its impact on overall survival.
Authors: Mónica Isabel Meneses Medina, Ana Karen Valenzuela, Jorge Humberto Hernandez-Felix, Haydee Cristina Verduzco-Aguirre, Vanessa Rosas Camargo, Edwin Ulises Cortez Dominguez, Luis Guillermo Anaya Sánchez, Alejandro Noguez-Ramos, Fidel David Huitzil Melendez
Journal: Journal of Clinical Oncology (2020)

327 Background: Advanced gastric cancer (GC) is a disease with high morbidity and poor prognosis. We hypothesize that different sites of metastasis have different impact in terms of symptoms and complications. We sought to evaluate if site specific morbidity in our patients impacted treatment and survival. Methods: Medical records from patients with advanced GC treated from Jan 2005 to Dec 2015 were retrospectively reviewed. Morbidity was defined as having any symptom by metastases in a specific site. OS was estimated by Kaplan Meier method and compared by Log-rank test. P value &lt; 0.05 was considered significant. Results: We included 180 consecutive patients, median age at diagnosis was 56 years (21-90), 55% were women. Most common sites of metastases were: peritoneum 76.1%, non-regional lymph nodes 38.9%, liver 22.8%, lung 26.7%, bone 9.4% and ovary 12.8%. Regarding morbidity, at diagnosis 68% of patients presented morbidity by the primary tumor: obstruction 56%, bleeding 27%, obstruction and bleeding 3%, other 14%. Disease by peritoneum caused morbidity in 30%, by lung in 8%, by ovarian in 4.4%, by lymph nodes in 3.3%, and by other sites in 5.6% of patients. OS in the global cohort was: 3.53 months (2.2 to 4.8), nevertheless by univariate analysis we found that OS was affected by morbidity at some sites as it is show in table. More patients with peritoneal morbidity could not receive treatment vs those without peritoneal morbidity (p = 0.042). Conclusions: We found that morbidity in peritoneum, lung and ovary adversely affected prognosis of patients with advanced GC. Moreover, peritoneal morbidity preclude patients from receiving oncological treatment. [Table: see text]
Final results of multicenter phase Ib/ II study of biweekly trifluridine/tipiracil with bevacizumab combination for patients with mCRC refractory to standard therapies (BiTS study).
Authors: Masato Nakamura, Hironaga Satake, Koji Oba, Masahito Kotaka, Yoshinori Kagawa, Hisateru Yasui, Takanori Watanabe, Toshihiko Matsumoto, Takayuki Kii, Tetsuji Terazawa, Akitaka Makiyama, Nao Takano, Mitsuru Yokota, Yoshihiro Okita, Koreatsu Matoba, Hiroko Hasegawa, Akihito Tsuji, Naoki Nagata, Junichi Sakamoto, Takeshi Kato
Journal: Journal of Clinical Oncology (2020)

121 Background: We have conducted the multicenter, phase Ib/II study to assess the activity and safety of biweekly Trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) combination for pts with metastatic colorectal cancer (mCRC) who were refractory or intolerant to standard therapies, and the primary endpoint of investigator assessed progression-free survival rate at 16 weeks (16w-PFS) was met [Kotaka M, ASCO-GI 2018]. We show longer follow-up data from this prospective study. Methods: Patients with unresectable mCRC; refractory or intolerant to standard chemotherapies were enrolled. Phase Ib part is designed to determine the recommended phase II dose (RP2D), and the treatment was determined as biweekly FTD/TPI (70mg/m2/day on day 1-5, every 2 weeks) with BEV (5mg/kg, every 2 weeks). The primary endpoint in phase II part was a 16w-PFS with a hypothesis of 15% considered unacceptable and 38.7% deemed promising. Given a one-sided α of 0.025 and statistical power of 90%, a minimum of 40 pts were required for phase II part. This trial registered in University Hospital Medical Information Network, number UMIN000029198. Results: From October 2017 to January 2018, totally 46 pts were enrolled. Nine patients (20.5 %) received regorafenib before enrollment. Of the 44 eligible pts, 16w-PFS rate was 40.9 %. With a median follow up of 15.36 months (range, 2.79-16.93), median PFS was 4.29 months (95% CI: 2.54 to 5.83), median TTF was 4.16 months (95% CI: 2.39 to 5.82), and median OS was 10.86 months (95% CI:8.32 to 13.68), respectively. Disease control rate was 59.1 % (95%CI: 43.3 to 73.7 %). Patients received the study treatment for a median of 6.5 cycles (range, 1 to 24). The median relative dose intensity of FTD/TPI and BEV was 80.9% (range: 44.0 to 100%), 81.5% (range: 50.0 to 100%), respectively. Common grade 3 or higher adverse events were hypertension (40.9%), neutropenia (11.4 %) and leucopenia (11.4 %). Conclusions: An update analysis confirmed that biweekly FTD/TPI plus BEV showed promising anti-tumor effect with acceptable less toxicities, and might be one of the treatment options for patients with heavily treated mCRC. Clinical trial information: UMIN000029198.
2019 update: EULAR RA management recommendations, efficacy and safety systematic literature reviews
Authors: Peter Nash
Journal: Annals of the Rheumatic Diseases (2020)

> ‘The main aim of evidence-based treatment recommendations and guidelines are to translate findings from health research into clinical practice. When implemented successfully these should improve quality of care and lead to improved health outcomes.’1 

This issue of the journal contains the latest update of the European League Against Rheumatism, Rheumatoid Arthrits (EULAR RA) management recommendations as well as the efficacy and safety systematic literature reviews representing an enormous amount of work by a dedicated team. As we enter a new decade, it is timely to consider the utility and worth of this extensive endeavour.

RA management guidelines have been popular for the last two and a half decades and have recently undergone meta-analysis.2 EULAR committee defined in 2004 the standard operating procedures required to tackle such a task.3 

A number of aspects need highlighting.

These are ‘recommendations’ and not ‘guidelines’—the latter having medicolegal implications particularly as much of the advice is based on expert opinion in the absence of appropriate clinical trials and further the level of agreement while high is rarely unanimous. The …
An Action Plan for Environmentally Sustainable Cancer Care
Authors: Andrew Hantel, Gregory A. Abel
Journal: JAMA Oncology (2020)

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Relevance of real-time teletransmission of physical activity, sleep, and circadian rhythms from gastrointestinal cancer (GIC) patients (pts) during daily routine (IDEAs, IRAS 233972).
Authors: Francis Levi, Sandra Komarzynski, Qi Huang, Teresa Young, Yeng Ang, Claire Fuller, Julia Brettschneider, Barbel Finkenstadt-Rand, Joanna Fursse, David-Pollard White, Pasquale Innominato
Journal: Journal of Clinical Oncology (2020)

801 Background: The relative amount of activity and rest over the 24-hours, as measured by the dichotomy index I &lt; O from actimetry records, is an independent predictor of overall survival and quality of life, and an early warning signal for emergency hospitalisation. The IDEAs study aimed to determine the sleep, physical and circadian pathologies in pts during their daily routine at home, which could lower I &lt; O and be modifiable through personalised interventions. Methods: The rest-activity and surface temperature patterns were monitored in real time using a tele-transmitting chest sensor and a GPRS-platform for one week in 25 pts, with a WHO performance status of 0-1 and metastatic GIC (colorectal, 56%). Each pt completed questionnaires including Chronotype, HADS, and Pittsburgh Sleep Index, filled a precise diary of daily activities, meals and sleep times, and the MD Anderson Symptoms Inventory daily. I &lt; O counts the In-bed activity bouts per min that are below the median activity Out-of-bed. Other pt-specific circadian parameters were estimated with spectral analyses and Hidden Markov models (HMM). I &lt; O predictors were identified through correlation and regression analyses. Results: A poor I &lt; O was found for 13 pts (52%). Self-reported scores for sleep quality or physical fitness showed no significant differences according to I &lt; O. Yet HMM-modelled rest-activity revealed that pts with poor I &lt; O had lower activity out-of-bed (median activity counts per minute, 110 vs 52, p = 0.001) and fractionated sleep (probability of remaining at rest when asleep, 94% vs 90%, p = 0.01). Poor I &lt; O was significantly associated with an abnormal circadian rhythm in chest surface temperature, that was either wrongly timed or suppressed, for 83% of the pts as compared to 25% of those with a good I &lt; O (p = 0.012). Conclusions: Nearly half of the pts displayed altered circadian rest-activity rhythm, with poor sleep and low daytime activity. In most of them, the circadian rhythm in body temperature, which critically regulates sleep, was abnormal. Exploration and specific treatment of sleep and circadian disorders are warranted for improving outcomes in cancer pts. Clinical trial information: 233972.
Novel therapeutic avenues for cholangiocarcinoma treatment: A meta-analysis.
Authors: Nabeal Aljabban, Jihad Aljabban, Merve Gurakar, Kamal Khorfan, Saad A. Syed, Adam Gayar, Hajra Khan, Dexter Hadley, Behnam Saberi
Journal: Journal of Clinical Oncology (2020)

584 Background: Cholangiocarcinoma (CCA) is a rare cancer of the bile ducts but has been increasing in incidence. The mainstay of treatment of CCA is resection or chemoradiation for more advanced disease, with immunotherapy being an evolving field in treatment. A better understanding of CCA pathogenesis will pave new avenues for treatment. Methods: We employed our STARGEO platform to conduct a meta-analysis of public data from NCBI's Gene Expression Omnibus. We performed meta-analysis with 259 CCA tumor samples against 16 normal intrahepatic duct samples as a control. We then analyzed the signature in Ingenuity Pathway Analysis. Results: Our analysis revealed FXR/RXR and LXR/RXR activation as top canonical pathways. Top upstream regulators identified included HNF1A (with predicted inhibition) and ERBB2 (with predicted activation). The most upregulated genes included several extracellular matrix proteins implicated in cancer including COL1A1, LAMC2 (correlated with poor prognosis in CCA), KRT17 (a keratin implicated in various malignancies but not well described in CCA), and LAMB3 (exerts tumorigenesis through PI3k/Akt signaling). Additionally, we found stark upregulation of the immunophillin FKPBP1A, which is involved in mTOR activation. We also noted upregulation of ubiquitin-associated gene UBASH3B, which inhibits endocytosis in EGFR and has been described in breast cancer but not CCA. From our investigation of immune checkpoint inhibitors, we found upregulation of classically described inhibitors such as CTLA4, TIGIT, and BTLA. In addition, we found upregulation of SIGLEC7, which has been recently shown to suppress immune function by binding to terminal sialic acid on glycans on the surface of immune cells. Conclusions: Our analysis highlights the possible role of ERBB2 and several extracellular genes in the pathogenesis of CCA. We also identify the role of genes not previously described in CCA such as FKBP1A and UBASH3B. Lastly, our results promote the promise of immunotherapy in CCA treatment.
Impact of immunotherapy on quality of life in patients with house dust mite allergic rhinitis
Authors: Daniel Pedregal‐Mallo, Esteban Pacheco, Juan Pablo Rodrigo, Jose Luis Llorente, Cesar Alvarez‐Marcos
Journal: Allergy (2020)

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Standards, Guidelines, and Quality Measures for Successful Specialty Palliative Care Integration Into Oncology: Current Approaches and Future Directions
Authors: Arif H. Kamal, Claudia Bausewein, David J. Casarett, David C. Currow, Deborah J. Dudgeon, Irene J. Higginson
Journal: Journal of Clinical Oncology (2020)

Although robust evidence demonstrates that specialty palliative care integrated into oncology care improves patient and health system outcomes, few clinicians are familiar with the standards, guidelines, and quality measures related to integration. These types of guidance outline principles of best practice and provide a framework for assessing the fidelity of their implementation. Significant advances in the understanding of effective methods and procedures to guide integration of specialty palliative care into oncology have led to a proliferation of guidance documents around the world, with several areas of commonality but also some key differences. Commonalities originate from a shared vision for integration; differences arise from diverse roles of palliative care specialists within cancer care globally. In this review we discuss three of the most cited standards/guidelines, as well as quality measures related to integrated palliative and oncology care. We also recommend changes to the quality measurement framework for palliative care and a new way to match palliative care services to patients with advanced cancer on the basis of care complexity and patient needs, irrespective of prognosis.