bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electronic patient reports outcomes and symptom monitoring for hematopoietic stem cell transplantation: A PILOT study.
Authors: Jorge Thiago William Carnier , Scheinberg Phillip , Campagnaro Melina , Filho César , Cartolano Lorenzo , Singh Jean , dos Prazeres Luiz Felipe , Mota Camila , Teodoro Juliana , Delijaicov Dimitra 
Published: June 2021

e13592 Background: Patients undergoing hematopoietic stem cell transplantation (HSCT) present with various symptoms during hospitalization. The daily life routines of those undergoing HSCT change significantly before, during, and after the transplant. The utilization of technologies of digital support for oncological patients through mobile applications is a trend. WeCancer App is an electronic patient-reported outcome tool that provides on-demand multidisciplinary digital support by nurses, psychologists, and nutritionists. It also encompasses real-time remote patient monitoring, a notification center to the patient and medical staff, symptom monitoring, medication control, and a content hub with reliable medical information. Methods: This study examined whether electronic patient-reported outcomes [e-PROs]) in post-HSCT patients (6 patients included) up to 16 weeks after hospital discharge. The following were observed: number of symptoms reported, specific symptoms, toxicity after transplantation, application adherence, number of accesses, chat interactions, total hours of chat time. Patients could report common symptoms through a mobile application, for monitoring, symptom management, and follow-up with a specialized nurse, determining care based on digital support clinical protocols through online chat. The alerts made through the chat system guided the nursing team's clinical actions about online clinical management that can stratify the risk by crossing the intensity of symptoms by the ESAS scale (Manchester classification) and promoting preventive educational conduct of vigilance and risk mitigation. Results: Median follow-up for overall treatment was 16 weeks. The e-PRO completion rates were > 90% at baseline and ≥ 80% at all on-treatment assessments and adherence. In-App adherence 329 reports were made 218 (66.26%) symptoms, 66 (20.06%) wellness, 30 (9.11%) gratitude and 15 (4.6%) exercise. Of the 64 chat interactions, there were 19.25 total hours and 18.05 average minutes per patient. The chat questions and interactions reported were: 48.2% symptoms, 27.7% treatment questions, 9.6% exams, 7.2% emotional aspect, 6% nutritional aspect and 1.3% medical devices. Some monitored patients (2) had guidance on outpatient graft versus host disease (GvHD) early in its onset with success avoiding a visit to the office or emergency room. Conclusions: We show the real-life benefits of incorporating ePRO into a post HSCT strategy adjunct to the treatment center. Symptoms that would only be brought to the physician in the next appointment were communicated in real-time to the transplant team, permitting early intervention and likely to reduce transplant-related deterioration and later interventions. The results suggest that further research should be done to prove the effectiveness of the App.
Impact of the COVID-19 pandemic on clinical activity during the lockdown in North France: A single center experience.
Authors: Hammoudi Ali , Marliot Guillaume , Cucchi Margot , Mahi Naima , Pannier Diane , Leblanc Eric , Mirabel Xavier , Ceugnart Luc , Robin Yves-Marie , Lartigau Eric , Penel Nicolas 
Published: June 2021

e13594 Background: During the French COVID-19 pandemic, clinical activity for cancer care has declined and modified the management of patients in cancer institute. France has imposed two national lockdowns of the population (from March 17 to May 11 and from October 30 to December 15 2020). We evaluate the impact of the lockdown period in North France on clinical activity. Methods: We measured and compared key-indicators of clinical activity between different periods: 2019 versus 2020; before and during the first and second lockdown. Results are given as percentage of changes with 95% confidence interval (CI). Results: The comparative analysis between 2019 and 2020 showed that most clinical activities except hospitalizations (-0.0% [-0.2; +0.1%] has changed. There was a significant increase in overall treated patients (+0.4% [+0.3; +0.5], telemedicine +99.9% [+99.4; +99.7], MRI (+8.8% [+8.2; +9.5], ambulatory chemotherapy (+3.5% [+3.3; +3.8]), number of chemotherapies prepared (+2.0 [+.1.9; +2.2]) and admission in palliative care unit (+15.3%, [+10.8; +19.8]). On the contrary, a significant decrease in treated patients aged > 65 years old (-6.4% [-6.9; -5.9]), incidence rate (-3.1% [-3.6; -2.7]), multidisciplinary team meeting on patient assessment (-3.1% [-3.5;-2.5]), pathology reports (-2.9% (-3.3;-2.6]), radiotherapy (-4.6% [-4.7;-4.4]) and surgery (-6.7% [-7.4;-5.6]) were observed. In 2020, before and during the first lockdown all key-indicators declined except telemedicine (+40,400%) and admission in palliative care unit (+35.5% [+31.0-+49.7]). During the first lockdown, key-indicators decreased from -63.0% [-70.3-59.2] for outpatient visits to -5.1% [-7.0-3.8] for chemotherapy. The impact caused by the second lockdown was non-significant compared to the first one since all key-indicators has increased during the second lockdown: from +23.8% [+22.2; +25.5] for radiotherapy to +76.6% [+72.5; +79.5] for the management of new cases. Conclusions: Dramatic changes occurred in 2020 during the COVID-19-related lockdown compared to 2019. An Increase in chemotherapy treatment and admission on palliative care unit and a decrease in surgery and radiotherapy strongly suggests that the clinical activity was changed in 2020 compared to 2019. This was in line with the reduction of cancer screening in 2020. The impact of the first lockdown on clinical activities was higher compared to the second one. These observations should be investigated further in order to better understand the effects of a pandemic-related lockdown on cancer care.
National survey on access to new oncology drugs pending health technology assessment and financial arrangements.
Authors: van Waalwijk van Doorn-Khosrovani Sahar Barjesteh , Pisters-van Roy Anke , Bloemendal Haiko , Gelderblom Hans 
Published: June 2021

e13599 Background: In the Netherlands, the health insurance package usually covers cancer drugs after EMA approval and positive recommendation of the Dutch Society of Medical Oncology (NVMO). However, the government can temporarily exclude newly licensed indications with high budget impact from coverage until the national HTA-body advises on the clinical effectiveness and cost effectiveness. Based on the recommendations of the HTA-body, the government negotiates a financial arrangement with manufacturers. Because submitting value dossiers, assessments and negotiations takes time there have been concerns regarding patients’ access to these novel treatments, especially for life threatening conditions such as cancer. Due to a lack of transparency, it is not known to what extent patients are given access to ‘free of charge programmes’ (FCPs). Methods: A list of oncology drugs and indications which were temporarily excluded from reimbursement due to negotiations with the government (July 2015-Dec. 2020). We contacted all the pharmaceutical companies that were engaged in the process above, to inquire about access to their products during the HTA evaluation and negotiations. Results: In total 17 oncology drugs (46 EMA registered indications) of 11 companies were subjected to financial agreements by the government. In 41,3% (19/46) of cases, FCPs were available via individual prescriber requests in a selected number of hospitals. In all other cases such arrangements were not needed because alternative treatment options were available (15,2%; 7/46) or because treatment was not recommended by the NVMO (13,0%; 6/46). For one indication FCP was available but the treatment eventually received a negative recommendation. In 30,4% (14/46) of the cases there was immediate reimbursement in place following a positive NVMO recommendation through umbrella agreements. Such agreements cover existing indications but also all the indications that will be licensed in the future. Umbrella agreements were especially set up for immune checkpoint inhibitors that showed benefit across multiple indications. As anticipated, some patient-access programmes had already started prior to EMA approval. In 5 cases an official compassionate use programme was set up through the Dutch Medicines Evaluation Board prior to authorisation. Conclusions: Our survey indicates that all manufacturers are committed to enabling patients’ and clinicians’ early access to their products pending payers’ approval in a high income country such as the Netherlands. However, the lack of transparency regarding the hospitals offering these programmes may result in inequity in access. Besides, there is no structural data collection. Recently, the NVMO has established a platform (DRUG Access Protocol) to harmonise all compassionate use programmes and FCPs, generating real-world data and ensuring equal access for all patients.
Preclinical evaluation of novel CDK4/6 inhibitor GLR2007 in glioblastoma models.
Authors: Yin Lei , Yao Zhenglin , Wang Yue , Huang Julius , Mazuranic Michelle , Yin Ang 
Published: June 2021

e14023 Background: Glioblastoma multiforme (GBM) is characterized by a high frequency of cyclin-dependent kinase (CDK)4 and CDK6 pathway dysregulation. CDK4/6 inhibitors palbociclib and abemaciclib are approved for the treatment of breast cancer, but poor blood–brain barrier (BBB) penetration limits their efficacy in GBM. GLR2007 is a novel CDK4/6 inhibitor with potential for improved penetration across the BBB. Here, we report on the activity of GLR2007 in GBM cell lines and its anti-tumor efficacy in mouse xenograft models. Methods: Three in vitro assays were used to assess the activity of GLR2007. Inhibition of CDK4/6 enzymatic activity by GLR2007 or palbociclib was calculated, and cell cycle stages were analyzed in U87-MG cells treated with vehicle control or GLR2007 for 24 h. Cell viability was evaluated in U87-MG and U118-MG cell lines after culture for 72 h with GLR2007 or abemaciclib. In vivo evaluation of the anti-tumor efficacy of GLR2007 versus vehicle, abemaciclib, and/or palbociclib was performed in BALB/c nude mouse GBM xenograft models. Quantitative whole-body autoradiography was used to determine the distribution of [14C]GLR2007 in the tissues of Sprague Dawley rats. Results: GLR2007 potency toward CDK4 and CDK6 was 33.1 and 3.8 times that of palbociclib, respectively. At concentrations >13.72 nM, GLR2007 caused G1 arrest of U87-MG cells. GLR2007 inhibited proliferation in U87-MG cells (IC50 15.6±2.4 nM) and U118-MG cells (IC50 23.2±5.2 nM). Anti-tumor efficacy of GLR2007 versus vehicle control was observed in two mouse GBM xenograft models (Table). Studies performed in rats demonstrated the distribution of [14C]GLR2007 in whole brain tissue following a single oral dose, with total radioactivity levels in the brain exceeding those in plasma by 2.3–4.5-fold from 2–6 h after dosing. Conclusions: These preclinical studies demonstrate the potential of GLR2007 as a novel CDK4/6 inhibitor for treatment of GBM. GLR2007 showed numerically greater anti-tumor efficacy than approved CDK4/6 inhibitors in xenograft models, and evidence of substantial central nervous system penetration. [Table: see text]
Assessment of low-intensity transcranial magnetic stimulation (TMS) in treatment for high-grade glioma (HGG).
Authors: Popov Ivan A. , Kit Oleg I. , Shikhlyarova Alla I. , Frantsiyants Elena M. , Rostorguev Eduard E. , Engibaryan Marina A. , Timoshkina Natalya N. , Gusareva Marina A. , Potemkin Dmitrii S. , Stasov Vitaliy V. , Arapova Yulia Yu. , Zhukova Galina V. , Atmachidi Dmitriy P. , Nikitin Emzari S. , Kuznetsova Natalya S. , Pandova Olga V. , Khatyushin Vladislav E. 
Published: June 2021

e14027 Background: The existing modern standards of combination treatment of HGG patients do not provide recovery and a long-term favorable prognosis, and the increasong incidence of HGG determines the need for additional effective technologies for anticancer and decongestant therapy. One of such methods involves TMS, and we have reported its preliminary assessment earlier (DOI: 10.1200/JCO.2020.38.15_suppl.2545). In this study, we continued the observation to examine the survival of patients. Methods: Patients with HGG received combination treatment: stage 1 – surgical removal of tumors within visible unaltered tissues; stage 2 – radiation therapy (the Varian Novalis linear accelerator) to the bed of the removed tumor, single boost dose 2 Gy, total boost dose 60 Gy; stage 3 – multi-course chemotherapy: temozolomide 150 mg/m² on days 1-5 with a 23-day interval. Starting from the second day after surgery, patients of group 1 (n = 25) received 10 TMS sessions, and during radiotherapy – 15 TMS sessions. Patients of group 2 (n = 25) received combination treatment without TMS. 6 and 12 months after the surgery, survival of patients was assessed with the Kaplan-Meier method and the Log-Rank test. Results: After 6 months of the follow-up, the survival of patients in group 1 remained at 100%, while in the control group it decreased to 88.8±8.7%. The difference in the 1-year overall survival was even more pronounced: in group 1, it was 68.5±10.4%, exceeding the value in group 2 (52.0±7.5%.) The differences were statistically significant (Log-Rank test p = 0.001). Conclusions: The results confirm the effectiveness of accompanying TMS in the early postoperative period, as well as at the stage of radiation therapy. The undoubted effectiveness of the considered techniques makes it expedient to include this type of treatment in the combination therapy for HGG patients. The reported study was funded by RFBR, project number № 19-315-90082\19.
Concurrent chemoradiation in the management of newly diagnosed glioblastoma multiforme: Retrospective review of single center experience over a period of 10 years.
Authors: Price Louise , Ziff Charlotte , Elmasry Abdelfattah , Giridharan Selvaraj 
Published: June 2021

e14028 Background: Glioblastoma Multiforme (GBM) is the most common primary intracranial tumour of the brain. The standard of care first line management is maximum safe debulking followed by concurrent chemo radiation (Stupp et al, 2005). In spite of further recent advances, median survival still remains poor and ranges between 14 to 21 months, especially in the MGMT unmethylated group. There are no randomised trials investigating less than 6 cycles of adjuvant temozolomide (TMZ). In our study we retrospectively analyse the impact on overall survival (OS) and progression free survival (PFS) in cases where adjuvant treatment has been discontinued due to toxicity or patient’s fitness Methods: We collected data from 2007 to 2016 for a cohort of patients who underwent adjuvant treatment for GBM following histological diagnosis. The final analyses included patient’s who completed concurrent chemoradiotherapy to a dose of 60 Gray in 30 fractions and had at least one cycle of adjuvant TMZ chemotherapy Results: Of 110 patient cohorts, 57% of patients completed adjuvant chemo radiotherapy followed by 4-6 cycles of adjuvant TMZ, 43% received 3 or less cycles of TMZ. Overall PFS was 11.9 months. Those that completed 4 or more cycles of adjuvant TMZ had an improved PFS (Log rank test P-value 0.001) versus those that completed 3 or less cycles. On cox analysis the number of adjuvant cycles of TMZ significantly affects OS, P-value 0.0003. Median overall survival was 16 months for the whole group, but was 10 vs. 20 months for the two groups. On cox analysis we also identified second line chemotherapy had a significant impact on OS (cox model P-value 0.002) Conclusions: We identified patients receiving three or fewer cycles of adjuvant TMZ had poorer outcomes. Second-line chemotherapy improved outcomes at relapse regardless of redo surgery.
A first-in-human phase dose-escalation study of YH002, a recombinant humanized agonistic anti-OX40 IgG1 monoclonal antibody, in patients with advanced solid tumors.
Authors: Ganju Vinod , Cooper Adam , Wilkinson Kate , Park John J. 
Published: June 2021

e14501 Background: YH002 is a recombinant humanized IgG1 antibody that targets the human OX40 receptor. Preclinical studies have demonstrated the specificity, potency, and anti-cancer efficacy of YH002 in a comprehensive panel. The totality of nonclinical data supports progression of YH002 into clinical studies in adult patients (pts) with advanced solid tumors. Methods: This is an ongoing phase 1 dose-escalation study. Patients with advanced or metastatic refractory solid tumors received YH002 as single agent by IV administration at 0.01 to12.0 mg/kg dose levels every 21 days (Q3W), to evaluate the safety, tolerability and preliminary efficacy. An accelerated titration dose escalation design followed by a traditional 3+3 dose algorithm were utilized to assess dose-limiting toxicity (DLT) and identify MTD and/or RP2D. Tumor assessments were performed per RECIST v1.1 every 9 weeks. Results: By December 31 2020, six patients were enrolled and treated at escalating dose levels of 0.01 (n=1), 0.03 (n=1), 0.1 (n=1) and 0.3mg/kg (n=3), with tumor types including colon cancer, thymic cancer, prostate cancer, colorectal cancer, breast cancer and bladder cancer. Median treatment duration was 10.2 weeks (range 2 – 18). The median age of patients was 67 years old (range 47-78). These patients had progressed after a median of 2 prior lines of available standard therapy. As of data cutoff, no dose limiting toxicities (DLTs), no Grade (G) 3 or above adverse events (AE) or AEs leading to treatment discontinuation were reported. Drug-related adverse events (AEs) were all G1/2 events and occurred in 4 patients, including 8 G1 AEs (pneumonitis, rash, pruritus, arthralgia, myalgia, fatigue, lethargy, rash pruritic) and 3 G2 AEs (1 pneumonitis and 2 fatigue). Out of 5 patients having tumor assessment by RECIST, one pt with Thymic SCC at 0.3 mg/kg had best response of stable disease at week 9, one pt with prostate cancer at 0.1 mg/kg experienced Non-CR/Non-PD, and rest of 3 pts experienced progressive disease. Conclusions: These preliminary results demonstrate that YH002 was safe and tolerable up to 0.3mg/kg. Updated safety and antitumor activity will be presented. Clinical trial information: NCT04353102.
Side effects of extended interval dosing of checkpoint inhibitors among patients during COVID-19 pandemic at the Moncton and the Miramichi hospitals.
Authors: Abdelsalam Mahmoud , Sughayar Rana , Myers Glenn , Avileli Mrudula , Salem Maged 
Published: June 2021

e14550 Background: Since the COVID-19 pandemic started, managing cancer patients who are more vulnerable than the rest of the population has been a concern. One of the strategies to decrease cancer patient visits to the Oncology Clinic was by the use of an extended dosing schedule of immune checkpoint inhibitors. The goal of the present study is to record and describe patients’ experiences with irAEs on the modified treatment schedules. Methods: The study included cancer patients getting their treatment at the cancer care clinics at The Moncton Hospital and the Miramichi Hospital, and who switched to receiving either a modified dose of Pembrolizumab or Durvalumab. These participants were asked to complete a short survey that covered important data in their diagnosis and treatment, as well as the type of cancer diagnosed and which drug they were prescribed for treatment. Participants were also asked about the presence of any possible immune-related symptoms from a list of possible AEs since their last treatment visit, and to indicate (A) how often the symptom was experienced, and (B) how severe the symptom was. Results: Twenty-one patients filled out the questionnaire half of whom were females. Most of the patients had lung cancer and were on pembrolizumab. All the patients interviewed developed at least one new symptom after the change in the dose was introduced. The most frequent symptoms reported were itchy skin and fatigue and they were severely experienced. However, very few of the symptoms experienced required a physician consult or hospitalization. Most of the participants welcomed the change in the dose to protect them from COVID-19 and were mainly indifferent as to whether they get the low dose more frequently or the higher dose less frequently. Conclusions: This study has highlighted the frequency and severity of irAEs with the use of extended dosing schedule of immune checkpoint inhibitors. Future research should have more patients to validate this outcome and look for the causes behind the increased incidence and severity of irAEs with higher dose less frequent intervals of these immunotherapies.[Table: see text]
The mechanism of the growth inhibitory effect of paclitaxel on gefitinib-resistant non-small cell lung cancer (NSCLC) cells during the COVID-19 pandemic.
Authors: Mohiuddin Md , Kimura Hideharu , Watanabe Satoshi , Abo Miki , Sone Takashi , Saeki Keigo , Terada Nanao , Tanimura Kota , Kasahara Kazuo 
Published: June 2021

e15007 Background: Coronavirus disease 2019 (COVID-19) poses a great challenge for the treatment of cancer patients. It presents as a severe respiratory infection in aging individuals, including lung cancer patients. COVID-19 may be linked to the progression of aggressive lung cancer. In addition, the side effects of chemotherapy, such as chemotherapy resistance and the acceleration of cellular senescence, can worsen COVID-19. Given this situation, we investigated the role of paclitaxel (a chemotherapy drug) in the cell proliferation, apoptosis, and cellular senescence of gefitinib-resistant non-small-cell lung cancer (NSCLC) cells (PC9-MET) to clarify the underlying mechanisms. Methods: PC9-MET cells were treated with paclitaxel for 72 h and then evaluated by a cell viability assay, DAPI staining, Giemsa staining, apoptosis assay, a reactive oxygen species (ROS) assay, SA-β-Gal staining, a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and Western blotting. Results: Our results revealed that paclitaxel significantly reduced the viability of PC9-MET cells and induced morphological signs of apoptosis. The apoptotic effects of paclitaxel were observed by increased levels of cleaved caspase-3 (Asp 175), cleaved caspase-9 (Asp 330) and cleaved PARP (Asp 214). In addition, paclitaxel increased ROS production, leading to DNA damage. Inhibition of ROS production by N-acetylcysteine attenuates paclitaxel-induced DNA damage. Importantly, paclitaxel eliminated cellular senescence, as observed by SA-β-Gal staining. Cellular senescence elimination was associated with p53/p21 and p16/pRb signaling inactivation. Conclusions: Given these findings, paclitaxel may be a promising anticancer drug and offer a new therapeutic strategy for managing gefitinib-resistant NSCLC during the COVID-19 pandemic.