tbuckley/cabot-search huggingface dataset:
Improving end of life care with advance care planning in a rural cancer center.
Authors: Jacquelyn Barnhart, Stacy Wells, Tasha Harris, Banu Symington
Journal: Journal of Clinical Oncology (2021)

e18637 Background: We discovered four out of five Medical Oncology patients admitted to the hospital December 2019 and January 2020 were discharged to hospice and died within a week. None of those patients had advance directives. In November and December 2019, all oncology patient charts were reviewed and only 7% (12/174) had advance directives. We believe an established advance directive could have helped avoid unnecessary hospitalization, improved end of life care and reduced wasteful health care costs. This led to the question: Would process changes in a rural cancer center lead to an increase in completion and documentation of Advance Directives, thereby providing more patient goal congruent care? Methods: Data collection and process mapping was performed revealing current processes and overall barriers. This was analyzed and countermeasures were developed leading to process changes and interventions. The interventions included assigning dedicated staff to “own” the advance directives education, follow up and completion, training and certification of staff, and education of the entire Cancer Center on the new process and interventions. The new process included a standardized order set to cue a referral to the dedicated staff, standardized patient education and follow up and documentation consistencies. Results: The initial data collection revealed an advance directive completion rate of 7% in new oncology patients. Process inconsistencies and communication deficiencies, with redundant screening and no follow up, created significant barriers to advance directives. Repeat data collection after creating a position for dedicated staff to educate patients and help with advance directive completion revealed a completion and documentation rate of 6% and thus, was insufficient to lead to change. When a consistent process with formal communication to the dedicated staff was implemented, improvements were noted. Our most recent data collection revealed a 36% completion and documentation rate in advance directives. Conclusions: Lack of effective advance directive programs potentially lead to end of life care incongruent with patients’ wishes and wasteful of health care resources. An advance directive ensures that if a patient is unable to clearly communicate their wishes, these wishes are still honored. In addition, the advance directive can help avoid unnecessary hospitalizations, improve end of life care and reduce wasteful health care costs. As a rural cancer center with a limited service area, we are challenged with a small sample size. Practice will be needed to ensure consistency and efficacy of the current interventions in order to support continued improvement in completion and documentation rates of advance directives. This project will be expanded to address advance directives for all patients.
Abstract GMM-035: TARGETING SPSB1 SENSITIZES PLATINUM-RESISTANT OVARIAN CANCER CELLS TO CISPLATIN
Authors: Mi-Kyung Kim, Hyun-Jung Kim, Yun Hwan Kim, Seung Cheo Kim, Woong Ju
Journal: Clinical Cancer Research (2019)

Abstract OBJECTIVE: Emergence of chemoresistance remains a critical clinical issue responsible for treatment failure in patients with ovarian cancer. The precise mechanisms underlying the development of chemoresistance are not fully understood. In our previous study using methylomic and transcriptomic analyses, SPRY domain-containing SOCS box protein 1 (SPSB1) was found to be differentially expressed between cisplatin-sensitive and –resistant ovarian cancer cells. Here, we investigated the roles of SPSB1 as a new therapeutic target for ovarian cancer cells resistant to cisplatin. METHODS: Knockdown of SPSB1 gene was performed by transfection of SPSB1 siRNA. Ovarian cancer cell lines were cultured for 5 days and 12 days after transfection for MTT assay and colony forming assay, respectively. Protein level was analyzed by western blot analysis. Cell migration assay was performed using Boyden chamber method. RESULTS: Knockdown of SPSB1 using RNAi method dramatically inhibited cell viability and migratory capability of ovarian cancer cells. Also, SPSB1 knockdown significantly induced CDK inhibitors, p21 and p27 and inhibited anti-apoptotic Bcl-2, indicating that SPSB1 inhibition induces cell cycle arrest and apoptosis in ovarian cancer cells. CONCLUSION: Our results suggest that SPSB1 might be a potential therapeutic target for cisplatin-resistant ovarian cancer. Citation Format: Mi-Kyung Kim, Hyun-Jung Kim, Yun Hwan Kim, Seung Cheol Kim, Woong Ju. TARGETING SPSB1 SENSITIZES PLATINUM-RESISTANT OVARIAN CANCER CELLS TO CISPLATIN [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr GMM-035.
Abstract 13333: Prediction of Prognosis Using Combined Objective Nutritional Score in Acute Decompensated Heart Failure Patients With Preserved Left Ventricular Ejection Fraction: Insights From Pursuit-hfpef Registry
Authors: Makoto Abe, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Masato Kawasaki, Atsushi Kikuchi, Tsutomu Kawai, Masahiro Seo, Jun Nakamura, Kyoko Yamamoto, Kiyomi Kayama, Masatsugu Kawahira, Kazuya Tanabe, Masatake Fukunami, Yoshio Yasumura, Masaaki Uematsu, Yoshiharu Higuchi, Yusuke Nakagawa, Hisakazu Fuji, Masami Nishino, Shungo Hikoso, Daisaku Nakatani, Yasushi Sakata
Journal: Circulation (2019)

Background: The objective nutritional indices such as the Controlling Nutritional Status (CONUT) score, Geriatric Nutritional Risk Index (GNRI) and Prognostic Nutritional Index (PNI) are useful for...
Shared decision-making: summary of NICE guidance
Authors: Chris Carmona, Joseph Crutwell, Marie Burnham, Louisa Polak
Journal: BMJ (2021)

### What you need to know

Shared decision-making is widely accepted as a core feature of good healthcare. Principle 4 of the NHS constitution states that “Patients, with their families and carers, where appropriate, will be involved in and consulted on all decisions about their care and treatment.”1 Because most NHS practitioners and commissioners acknowledge that this involvement and consultation is not always offered, the National Institute for Health and Care Excellence (NICE) was asked to produce guidance about facilitating shared decision-making and embedding it in everyday practice. For the purposes of the guideline, shared decision-making was defined as “a collaborative process that involves a person and their healthcare professional working together to reach a joint decision about care.”

This article summarises the recommendations from the NICE guideline.2

NICE recommendations are based on systematic reviews of best available evidence. When minimal evidence is available, recommendations are based on the Guideline Committee’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets.

### Embedding shared decision-making at an organisational level

Shared decision-making is more likely to become standard practice in organisations when it is led from the highest levels of the organisation. This can drive systematic planning and implementation of shared decision-making across the organisation. A dual approach is needed, promoting shared decision-making to people who …
Real-world clinical practice: Toxicities of maintenance PARP inhibitors in recurrent ovarian cancer—The Royal Marsden experience.
Authors: Zohra Ali, Laura Appadu, Ellen Kitetere, Julian Wampfler, Dorothy Yang, Philippa Jupp, Angela George, Susana N. Banerjee
Journal: Journal of Clinical Oncology (2021)

e18770 Background: Maintenance therapy with PARP inhibitors (PARPi) in recurrent high grade ovarian cancer is standard of care for patients who have responded to second or subsequent lines of platinum-based chemotherapy. The increased access to PARP inhibitors (Olaparib, Niraparib and Rucaparib) has provided the opportunity to explore the real-world toxicities in routine clinical practice, toxicity management and the consequent impact on maintenance therapy outcomes. Methods: Patients with relapsed ovarian cancer that received maintenance PARP inhibitor therapy in routine clinical practice between April 2015 and April 2020 were identified. Electronic patient records were reviewed retrospectively to retrieve details of any reported toxicities (occurring at any time during therapy) and their management. Data was entered into and analysed in a Microsoft Excel spreadsheet. Results: 99 patients who received second or subsequent line maintenance PARPi therapy were included (median age 63.6 years). 36% had a germline BRCA1/2 mutation, 6% had a somatic BRCA1/2 mutation and 58% were BRCA wild-type. 69% received 2 nd line maintenance therapy; 22% and 9% received a maintenance PARP inhibitor following 3 rd or 4+ line therapy respectively. 56% had not received previous maintenance therapy; 43% had received Bevacizumab. 48% patients commenced maintenance therapy at full dose. 13% of patients experienced no toxicities. 60% of patients experienced G1-2 toxicities, with 42% experiencing &gt;2 episodes; most common toxicities were fatigue, nausea/vomiting and thrombocytopenia. 26% of patients experienced &gt;G3 toxicity, with 9% experiencing &gt;2 episodes, 4% of which were recurring toxicities; most common toxicities were hypertension, neutropenia and anaemia. 64% of patients developed toxicity within the first cycle of treatment; 39% had a dose interruption, 56% of which were &lt; 2 weeks duration. 59% patients required a dose reduction from their starting dose due to toxicities. There was no significant difference in median PFS between patients who had been dose reduced compared to those who received full starting dose (p &gt; 0.05). Conclusions: In keeping with phase III clinical trials, our real-world experience is that most PARPi toxicities are low grade and occur early in treatment. Toxicities can be effectively managed with brief dose interruptions and dose reductions, without adverse impact on survival outcomes.
Effects of baseline lactate dehydrogenase (LDH), interferon gamma (IFN-g) expression, and tumor mutational burden (TMB) on treatment response to first-line atezolizumab (A) + vemurafenib (V) and cobimetinib (C) in <i>BRAF</i><sup>V600</sup> mutation–positive advanced melanoma.
Authors: Caroline Robert, Karl D. Lewis, Paolo Antonio Ascierto, Rodrigo Ramella Munhoz, Gabriella Liszkay, Luis de la Cruz-Merino, Judit Olah, Paola Queirolo, Jacek Mackiewicz, Ivor Caro, Kalpit Shah, Harper Forbes, Haocheng Li, Christian Hertig, Yibing Yan, Edward Francis Mckenna, Ralf Gutzmer, Grant A. McArthur
Journal: Journal of Clinical Oncology (2021)

9523 Background: The phase 3 IMspire150 study showed that first-line A+V+C improved investigator-assessed PFS vs placebo (P)+V+C in BRAF V600E/K mutation–positive advanced melanoma (hazard ratio 0.78; P=.0249). Prior biomarker analyses showed that IFN-g or TMB &gt; 10 mut/Mb were associated with greater PFS benefits with A+V+C (Lewis et al. J ImmunoTher Cancer 2020;8:A188-A189). We further evaluated the association of these biomarkers with outcomes. Methods: Exploratory recursive partitioning analysis (RPA) was used to model associations between PFS and age ( &lt; 65 vs ≥65 y), Eastern Cooperative Oncology Group performance status (0 vs 1), liver metastases (yes vs no), metastatic sites (≤3 vs &gt; 3), sum of longest tumor diameters ( &lt; 44 mm vs ≥44 mm), baseline LDH (normal [n] vs elevated [e]), TMB ( &lt; 10 vs ≥10 mut/Mb), PD-L1 (negative vs positive), and IFN-g (high [h; &gt; Quartile 3; Q3] vs intermediate [ &gt; Q1 and ≤Q3] vs low [≤Q1]). Time-to-event analyses were summarized using Kaplan-Meier estimates. Results: The RPA analysis included 208/256 (81.3%) patients (pts) from the A+V+C arm of IMspire150 for whom LDH, TMB, IFN-g, and PD-L1 data were available. RPA showed that LDH was associated with PFS. In pts treated with A+V+C and n-LDH, h-IFN-g signature was associated with longer PFS and higher rates of objective response (OR) and complete response (CR) vs low/intermediate (l/i) IFN-g (2-y PFS: 59% vs 38%; ORR: 77% vs 69%; CR: 38% vs 15%, respectively); TMB ≥10 mut/Mb was associated with more favorable outcomes in pts with e-LDH (Table). In contrast, neither IFN-g nor TMB discriminated PFS outcomes in n-LDH or e-LDH pt subgroups receiving P+V+C. Pts with e-LDH and TMB &lt; 10 mut/Mb had poor PFS outcomes, with 2-y PFS rates of 9% and 3% and lower rates of OR (51% and 62%) and CR (5% and 9%) in the A+V+C and P+V+C arms, respectively. Similar trends were observed for duration of response (DOR), and for the subset of pts with BRAF V600E mutation–positive melanoma. A+V+C improved PFS vs P+V+C across all subgroups with the exception of e-LDH and TMB &lt; 10. Conclusions: IFN-g and TMB discriminated PFS benefit in pts receiving A+V+C but not for those receiving P+V+C. Durable responses were observed for pts treated with A+V+C in the n-LDH + h-IFNg subgroups.[Table: see text]
TMB and <i>BRAF</i> mutation status are independent predictive factors in stage IIIC/D/IV melanoma patients receiving adjuvant PD-1 antibodies.
Authors: Andrea Forschner, Julia Eckardt, Peter Martus, Sorin Armeanu-Ebinger, Stephan Ossowski, Irina Bonzheim, Thomas Eigentler, Teresa Maria Santos Amaral, Lukas Flatz, Claus Garbe, Christopher Schroeder
Journal: Journal of Clinical Oncology (2021)

9524 Background: High tumor mutational burden (TMB) is associated with a favorable outcome in metastatic melanoma patients treated with immune checkpoint inhibitors. However, data are limited in the adjuvant setting. As BRAF mutated patients have an alternative with targeted adjuvant therapy, it is important to identify predictive factors for relapse and recurrence-free survival (RFS) in patients receiving adjuvant PD-1 antibodies. Methods: We systematically evaluated all melanoma patients who started adjuvant PD-1 antibody therapy at our center between March 2018 and September 2019 to identify predictive factors for outcome. The median follow-up time from start of adjuvant anti-PD-1 therapy was 22 months. Tumor and normal tissue of all stage IIIC/D/IV patients and of stage IIIA/B patients with relapse were sequenced using a 700 genes panel. Predictive factors for relapse and RFS were identified using univariate and multivariate logistic and Cox regression analysis. RFS was estimated by the Kaplan-Meier method. TMB high was defined as the top 20 % of the cohort, corresponding to TMB values ≥ 20 Var/Mb. Results: A total of 165 patients were included in this study. According to AJCC 8 th the initial tumor stages at the beginning of adjuvant anti-PD-1 therapy were as follows: N = 80 stage IIIA/B (48 %), N = 85 stage IIIC/D/IV (52 %). 72/165 patients (44 %) suffered a relapse, 44/72 (61 %) with loco regional and 28/72 (39 %) with distant metastases. Sequencing results were available from 79 / 85 patients with stage IIIC/D/IV. Here we present the results of this cohort. TMB low (OR 17.46, 95%CI 4.03-75.55; p &lt; 0.0001) or absence of BRAF V600E/K mutation (OR 4.13, 95%CI 1.36-12.53; p = 0.012) were statistically significant, independent predictive factors for relapse. Also, with regard to RFS, BRAF mutation status and TMB were statistically significant and independent predictive factors. In the table below we display results for the combined variables. Patients with BRAF V600E/K mutation and TMB high had the best outcome. Conclusions: We identified TMB high as positive predictive marker in stage IIIC/D/IVmelanoma patients with adjuvant PD-1 antibody therapy. In tumors with BRAF V600E/K mutation and concurrent low TMB, adjuvant targeted therapy with BRAF- and MEK-inhibitors may be an alternative. This is also supported by the data on adjuvant dabrafenib and trametinib, which showed a greater advantage in patients with low TMB, presumably due to less tumor heterogeneity.[Table: see text]
Identification of Novel Therapeutic Targets for Fibrolamellar Carcinoma Using Patient-Derived Xenografts and Direct-from-Patient Screening
Authors: Gadi Lalazar, David Requena, Lavoisier Ramos-Espiritu, Denise Ng, Patrick D. Bhola, Ype P. de Jong, Ruisi Wang, Nicole J.C. Narayan, Bassem Shebl, Solomon Levin, Eleftherios Michailidis, Mohammad Kabbani, Koen O.A. Vercauteren, Arlene M. Hurley, Benjamin A. Farber, William J. Hammond, James A. Saltsman, Ethan M. Weinberg, J. Fraser Glickman, Barbara A. Lyons, Jessica Ellison, Erik Schadde, Martin Hertl, Jennifer L. Leiting, Mark J. Truty, Rory L. Smoot, Faith Tierney, Tomoaki Kato, Hans-Guido Wendel, Michael P. LaQuaglia, Charles M. Rice, Anthony Letai, Philip Coffino, Michael S. Torbenson, Michael V. Ortiz, Sanford M. Simon
Journal: Cancer Discovery (2021)

Abstract To repurpose therapeutics for fibrolamellar carcinoma (FLC), we developed and validated patient-derived xenografts (PDX) from surgical resections. Most agents used clinically and inhibitors of oncogenes overexpressed in FLC showed little efficacy on PDX. A high-throughput functional drug screen found primary and metastatic FLC were vulnerable to clinically available inhibitors of TOPO1 and HDAC and to napabucasin. Napabucasin's efficacy was mediated through reactive oxygen species and inhibition of translation initiation, and specific inhibition of eIF4A was effective. The sensitivity of each PDX line inversely correlated with expression of the antiapoptotic protein Bcl-xL, and inhibition of Bcl-xL synergized with other drugs. Screening directly on cells dissociated from patient resections validated these results. This demonstrates that a direct functional screen on patient tumors provides therapeutically informative data within a clinically useful time frame. Identifying these novel therapeutic targets and combination therapies is an urgent need, as effective therapeutics for FLC are currently unavailable. Significance: Therapeutics informed by genomics have not yielded effective therapies for FLC. A functional screen identified TOPO1, HDAC inhibitors, and napabucasin as efficacious and synergistic with inhibition of Bcl-xL. Validation on cells dissociated directly from patient tumors demonstrates the ability for functional precision medicine in a solid tumor. This article is highlighted in the In This Issue feature, p. 2355
Should you trust the radiologist?
Authors: Sun Mi Ha, Donal Sheehan, Ahmed Shalabi, Malcolm A West, Rajapandian Ilangovan, Morgan Moorghen, John T Jenkins, Siwan Thomas-Gibson
Journal: Gut (2021)

A colonoscopy was performed in a 65-year-old asymptomatic patient with a positive faecal immunochemical test. Their only medical history was well-controlled asthma.

The colonoscopy was performed by an experienced bowel cancer screening endoscopist. The examination found a lumen-filling lesion in the ascending colon (figure 1) just downstream to the ileocaecal valve. The lesion was hard to touch and biopsies were taken. The appearance was compatible with an eroding submucosal lesion. The endoscopist informed the patient of the likely diagnosis of cancer, and requested urgent imaging.



Figure 1 
Endoscopic view of ascending colon.



The case was discussed in the Complex Polyp …
Overall survival comparison in patients with and without brain metastases treated with osimertinib for metastatic EGFR mutation positive non-small cell lung cancer (NSCLC).
Authors: Danilo Giffoni de Mello Morais Mata, Maria Luisa Romero, Carlos Amir Carmona Gonzalez, Alia Thawer, Mark Doherty, Ines B. Menjak
Journal: Journal of Clinical Oncology (2021)

e21216 Background: With the development of Epidermal Growth factor receptor (EGFR) tyrosine kinase inhibitors such as Osimertinib, the landscape of lung cancer treatment and outcomes has changed. We aimed to describe the outcomes of patients treated with Osimertinib who have brain metastasis compared to those without brain metastases. Methods: This study involved patients diagnosed with metastatic non-small cell lung cancer (NSCLC) with EGFR mutation, from January 2010 to December 2018, who had treatment with Osimertinib at a dose of 80 mg daily. Retrospective data was collected through the electronic medical records from Sunnybrook Health Sciences Centre. Descriptive statistics were used to summarize the population characteristics. The log rank test was used to compare the survival distributions. Results: A total of 56 patients were included, the mean age at initial diagnosis was 63 years (range 27 – 85 years). Overall, 82.2% of this patient population received Osimertinib in 2 nd line setting. A total of 50% (n = 28) had brain metastasis, and14.3% (n = 8) had leptomeningeal metastasis. Of the patients with brain metastasis, 14.3% (n = 4) had brain surgery. All patients with brain metastasis received central nervous system (CNS) radiation. With respect to radiotherapy modalities, 67.9% (n = 19) of patients with brain metastasis received gamma knife radiation, 42.85% (n = 12) were treated with stereotactic radiosurgery (SRS), and whole brain radiation was given to 57.1% (n = 16). Of those with brain metastasis, equal numbers of patients, 46.4% (n = 13), had EGFR mutations with exon 19-deletion and exon 21-L858R, 7.1% (n = 2) had unknown gene location EGFR mutation. The median OS for patients without brain metastasis was 38.6 months (95% confidence interval [CI] 37.5 – 39.8 months], compared to 35.9 months (95% [CI] 28.3 – 43.5 months] for those with brain metastasis ; log Rank (Mantel-Cox) p = 0.874. The median OS for patients diagnosed with leptomeningeal metastasis was 21 months (95% [CI] 2.9 – 39.0 months); log rank (mantel-cox). When brain metastasis was examined by EGFR mutation sub-groups, the median OS for patients with EGFR-exon 19-deletion was 26.4 months (95% CI [14.3 – 38.4 months], compared to 36.8 months, 95% CI [34.3 – 39.2 months] for those with EGFR-Exon 21-L858R; log Rank (Mantel-Cox) p = 0.49. Conclusions: Although there is an equivalent prevalence of brain metastasis between the two NSCLC EGFR mutation populations, in unadjusted analyses, no difference in OS was seen between patients with brain metastases compared to those without brain metastases. However, in the small number of patients with leptomeningeal disease, survival was shorter and a larger population should be studied to further explore this finding.