bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical evidence and benefit of special FDA designations in anti-cancer drugs.
Authors: Michaeli Daniel Tobias , Michaeli Julia Caroline , Albers Sebastian , Boch Tobias , Winterhoff Boris , Michaeli Thomas 
Published: June 2023

e13655 Background: Over the past decades, US congress enabled the US Food and Drug Administration (FDA) to facilitate and expedite drug development for serious conditions filling unmet medical needs with five special designations: orphan, fast track, accelerated approval, priority review, and breakthrough therapy. It remains unclear whether multiple designations per indication are redundant. This study analyzes cancer drugs with multiple special designations regarding their FDA approval timelines, evidence, benefit, epidemiology and price. Methods: All anti-cancer drugs and their supplemental indication approvals were identified in the Drugs@FDA database from 2000 to 2022. For each indication, clinical trial characteristics, epidemiologic, and price data were collected from FDA labels, the Global Burden of Disease Study, and Medicare & Medicaid Part B and D, respectively. The association between overall survival (OS) and progression-free survival (PFS) hazard ratios (HR) and drug indications’ number of special designations were compared in meta-analyses and meta-regressions. Results: We identified 170 anti-cancer drugs with FDA approval in 455 indications. The median time to first FDA approval was 13.8 years for drugs with zero, 7.3 years with one, 7.1 years with two, 7.8 with three, 5.8 with four, and 5.3 with five special designations (HR per additional designation: 1.27, 95%CI: 1.09-1.48, p=.002). Drug indications with more special designations were more frequently granted to rare diseases with fewer treatment options supported by smaller and shorter open-label phase 1/2 trials. OS HRs were 0.79 for indications with zero, 0.74 with one, 0.73 with two, 0.69 with three, 0.59 with four, and 0.52 with five special designations (p=.024). On average, each additional special designation was associated with lower HRs for OS (ß=-0.03, p=.002) and PFS (ß=-0.07, p<.001). Each additional special designation was associated with a 19.05% (95%CI: 4.56-35.55, p=.013) higher drug price. Conclusions: The FDA’s special designations are non-redundant. Multiple special designations are associated with faster approval times and a greater efficacy for patients with high unmet needs, while multiple special designations are associated with less robust trial evidence and higher drug prices. This study supports the strategy of special FDA designations for unmet clinical needs.
Measuring time toxicity of systemic therapies for advanced esophageal and gastric cancers.
Authors: Agrawal Neha , Thawani Rajat , Chen Emerson Yu-sheng 
Published: June 2023

e13660 Background: Immunotherapy checkpoint inhibitors have demonstrated clinical benefit in esophago-gastric cancers. Little is known regarding time spent on treatment and adverse events that patients experienced to receive their care, or time toxicity, with regards to advances in immunotherapy. Methods: Fifteen phase 3 trials of anti-PD1 and anti-PDL1 inhibitors used for esophageal and gastric cancers were selected from clinicaltrials.gov if they were published by February 2021. The published methods and protocol were reviewed to estimate the number of ‘hospital days’ based on required procedures associated with screening and treatment related care and proportion of serious and severe adverse events that served as a surrogate for time toxicity. Once hospital days were estimated for all randomized groups, they were analyzed according to immunotherapy arms, which included chemo-immunotherapy and immunotherapy-only arms, and non-immunotherapy arms, which included chemotherapy only and observation arms. Results: From the 15 trials included, there were 32 randomized groups, as 2 trials had 3 randomized groups. Six trials eventually led to FDA approval. Six were for immune checkpoint inhibitors in first line setting, and 8 were in subsequent line setting, and 1 were in adjuvant or maintenance trials. Only pembrolizumab, nivolumab, and avelumab were represented. The median estimated hospital days was 38 days (range 7-52), or 1.3 months, over one year. There was no difference comparing immunotherapy vs. immunotherapy-free arms (p = 0.5), but there was difference comparing chemotherapy vs. chemotherapy-free arms (p < .05). The median survival in the group of patients who received combination chemo-immunotherapy was 13.9 months, with time toxicity of 1.4 months. The survival and time toxicity of the chemotherapy, immunotherapy and placebo arms were 9.1 and 1.3 months, 10 and 0.9 months, and 7.5 and 0.3 months, respectively. Conclusions: While there is substantial number of days committed to cancer therapies among patients with esophageal or gastric cancer, we noticed a trend of more time toxicity in patients who received chemo-immunotherapy, vs patients who received immunotherapy alone. Given the modest improvement in survival gleaned from these trials, the magnitude of survival benefit should be weighed against the time toxicity incurred in patients.
Inter-regional differences of authorship in secondary analyses of solid malignancies.
Authors: Hamadneh Yazan , Alrawabdeh Jawad , Al Zyoud Muntaser , Odeh Nada Wael , Alzubi Marah , Al Hadidi Samer 
Published: June 2023

e13661 Background: With the increasing number of clinical trials and data availability in recent years, the number of secondary analyses had subsequently increased at a global level. However, the results of such analyses must be interpreted carefully. Our study aimed to study the differences of secondary analyses based on the country of residence of the first author. Methods: We searched OVID database for articles subgroup analyses from the year 2000 until Feb 15, 2022. post-hoc, subgroup, secondary, cancer, tumor, breast, colorectal were some of the terms used in the search. Original trials, observational and secondary analyses of cohort studies were excluded. The country of the first author was used for categorizing the articles. Results: 1491 articles were included in final analysis. The first authors of 646 articles were from North America (43.9%), 476 articles from Europe (32.4%), 258 articles from East Asia (17.6%), and 86 articles from the rest of the globe (5.9%). There was a significant increase in the number of secondary analyses from East Asia especially in the last 4 years (<.001). In addition, East Asian secondary analyses were more likely to have had medical writing assistance compared to other regions (<.001). North American contribution to secondary analyses has been decreasing over the years (<.001). European analyses and analyses from the rest of the world didn’t have a significant increase over the years. Although European publication were less likely to be funded, those that were funded had a higher chance of being funded by pharmaceutical companies in comparison to the different regions (<.001). International trials that included US and non-US participants were more likely to be funded by pharmaceutical companies, had medical writing assistance, and had a higher percentage of authors with conflicts of interest than trials that only included US participants or non-US participants (<.001). Conclusions: The results show that there was an increase in secondary analyses especially from the East Asian region and those secondary analyses of international trials are highly funded and supported by pharmaceutical companies. [Table: see text]
Use of adjuvant bisphosphonate therapy in breast cancer by Indian oncologists: An implementation science study.
Authors: Davis Sissmol , John Dr Serene Sara , Davichan Dr Anjali , Santoki Aditya , Mathew Aju 
Published: June 2023

e13667 Background: Several clinical trials, expert consensus and guidelines have recommended the use of bisphosphonates (BP) in reducing the breast cancer recurrence risk in postmenopausal women. The 2019 St. Gallen Panel voted 83.7% in favour of the routine use of bisphosphonates in postmenopausal women. Similarly, the 2022 ASCO-Ontario Health guidelines for breast cancer supports the recommendation. However, the uptake of these recommendations in routine clinical practice is poorly studied. We aimed to investigate the use of adjuvant BP therapy by Indian oncologists (implementation science study). Methods: A cross sectional survey study design was used to investigate our research question. Physicians in India who treat patients with breast cancer were presented with a clinical vignette of a young woman with postmenopausal (induced) non-metastatic high risk hormone receptor-positive breast cancer. A snowball sampling strategy was employed to avoid sampling bias. Participants were requested to state their gender, primary qualification, practice setting, number of years of practice as an oncologist and proportion of patients with breast cancer in their practice. Instead of providing the option of BP therapy, we asked an open-ended question whether they would recommend any additional therapy other than surgery, radiation, chemotherapy and anti-estrogen therapy. We asked them to write in the name or class of drug if they would prescribe an additional therapy to the patient. Results: The survey was completed by 74 Oncologists. The response rate is unknown as a snowball sampling strategy was employed. Majority of the respondents were male (74%), were non-teaching private practitioners (42%), medical oncologists (62%) with up to 10 years of experience (65%), and breast cancer patients make up to 50% of their patients (84%). Most of the oncologists responded no to our question on additional therapy (76%). Of those who responded yes, only 8 suggested BP therapy (11%). Conclusions: Despite strong evidence and guidelines, adjuvant BP therapy in high-risk early breast cancer was only recommended by very few oncologists in our survey study. Steps to bridge this gap between academic research and clinical application is urgently warranted. Implementation of clinical guidelines has to be monitored routinely which may be facilitated by provider and patient surveys. This can also assist in identifying and addressing the concerns with newer recommendations.
Knowledge and use of different breast cancer screening tools among primary care physicians: A cross-sectional study.
Authors: Camejo Natalia , Amarillo Dahiana , Bernate Moira , Burguez Florencia , Darino Eliana , Deleon Adrian , Milwa Tatiana , Barcia Maria , Krygier Gabriel David 
Published: June 2023

e13673 Background: In Uruguay, breast cancer (BC) is the leading cause of cancer incidence and mortality in women. Objective: To understand the implementation of BC screening among primary care physicians in routine clinical practice and the degree of adherence to the recommendations put forward in 2015 by the Ministry of Public Health (MPH) for the early detection of BC. Methods: This was a descriptive, cross-sectional, observational study. An anonymous survey was administered to physicians working in primary care. Results: 169 physicians were included, 89.4% (151) consider the use of screening mammography decreases mortality from BC, 54.4% (92) indicate mammography from 40 years of age and 38.5% (65) from 50 years of age. The majority (56.8%, 96) indicate mammography every 2 years in the population of women aged 50-69 years. Of the respondents, 65.7% (111) were aware of the national guidelines and 47.9% (81) followed them, while 18.9% (32) followed recommendations from other scientific bodies. Conclusions: This study showed that primary care physicians make correct use of the different BC screening tools. Active measures are needed to develop educational programs for healthcare personnel, which may enable them to disseminate knowledge and positively influence patients' attitudes.
Fertility preservation in women with cancer in Brazil: Infertility specialists' perceptions and attitudes.
Authors: Andrade Warne Pedro , Lamaita Rivia Mara , Rannige Renata Lack , Rodrigues Angelica Nogueira , silva-Filho Agnaldo Lopes 
Published: June 2023

e13676 Background: Oncofertility is a universal right and a global oncology priority. However, there is a lack of communication between infertility specialists and their clinical oncologists on topics relating to fertility preservation. The present study aims to evaluate the perceptions and attitudes of infertility specialists regarding fertility preservation in women with cancer in Brazil. Methods: An online questionnaire was sent to infertility specialists affiliated to the Brazilian Federation of Associations of Gynecology and Obstetrics (FEBRASGO, in the Portuguese acronym). Results: A total of 100 (30.9%) of 323 FEBRASGO infertility specialists responded, most located in the southern and southeastern Brazilian states. Experience in Human Reproduction ranged from one to 40 years (mean ± standard deviation: 15.5 ±10.2 years). Considering women with cancer in reproductive age in whom fertility preservation was indicated, 60.3% ±28.8% of them performed the procedure (ranging from 10 to 100%). Three main barriers to fertility preservation were appointed: cost (41%), knowledge and acceptance of medical oncologists (35%) and accessibility (9%). Most infertility specialists (58%) considered age above 40 years as the limit for fertility preservation in women with cancer. Breast and ovarian cancers, leukemia, and lymphoma were considered the most relevant types to be considered for fertility preservation, while lung, thyroid, gastric and brain. Conclusions: This is the first Brazilian study on specialists' impressions on cancer patient's access to fertility preservation. While most Brazilian cancer patients are treated in the public health system, most fertility specialists are in the private sector. Currently, the model of care is fragmented and a more integrated workflow between cancer and fertility experts is fundamental to improve fertility sparing access. Further studies are needed on the topic, also including clinical oncologists, hematologists, breast cancer specialists, and patients.
Telemedicine services in community oncology practices.
Authors: Loh Kah Poh , Wang Ying , Nightingale Chandylen L. , Parsons Susan K. , Braun-Inglis Christa M. , Gada Umang , Montes Alexander , Culakova Eva , Magnuson Allison , Yilmaz Sule , Strause Sarah , Kamen Charles Stewart , Mustian Karen Michelle , Morrow Gary R. , Mohile Supriya Gupta ,   Landscape Committee
Published: June 2023

e13678 Background: Telemedicine services have grown tremendously due to the COVID-19 pandemic. We described the use of telemedicine for research purposes at community oncology practices. Methods: We utilized results from the National Cancer Institute Community Oncology Research Program 2017 and 2022 Landscape Surveys, which were designed to understand cancer delivery research capacity in community oncology practices. We used multivariable logistic regression to examine factors associated use of telemedicine for research purpose in 2022, adjusting for region, practice ownership type, and number of oncology providers. Results: Information was available from 504 and 685 discrete practices in 2017 and 2022, respectively. These represent 210 and 259 practice groups; practice groups serving only pediatric patients were excluded. Mean numbers of oncology providers at the practice group level were 18 (IQR 5-21) and 20 (IQR 7-22) in 2017 and 2022, respectively. Over 90% of practice groups reported having outpatient electronic health records and patient portal in both years. In 2022, IT service was available onsite in 71%. In 2017, 31% of practice groups utilized telemedicine for delivery of cancer care and 15% can utilize telemedicine for research purposes. In 2022, telemedicine was used for research purposes in 73% of practice groups. Specifically, telemedicine was used for collection of patient-reported outcomes (54%), delivery of health care interventions (47%), consent (39%), conduct of qualitative interviews (32%), delivery of behavioral interventions (30%), collection of biometric data (e.g., weight, blood pressure) (14%), and collection of neurocognitive testing data (12%). One-third of all practice groups (35%) did not have internet-abled devices available for patients, 53% had them onsite, and 2% had them on site and for patients to take home. On multivariable analysis, a greater number of oncology providers was associated with greater use of telemedicine for research purposes (every 10-unit increase, AOR 1.31, 95% CI 1.04-1.64). Conclusions: From 2017 to 2022, there has been an increased use of telemedicine for research purposes, though its use varies across practices. Bigger practice groups were more likely to use telemedicine for research purpose. Cancer care delivery research that incorporates telemedicine should consider implementing site-specific and standardized resources. [Table: see text]
Telemedicine and cancer care in Syria: A promising initiative during the war and COVID-19 era.
Authors: Saifo Maher , Alali Mousa 
Published: June 2023

e13680 Background: Telemedicine (TM) is the practice of medicine using technology to deliver care to patients at their locations. One of the major difficulties that cancer patients in Syria face is the ability to frequently visit Albairouni University Cancer Center (ABUH) in Damascus. The travel-related barriers to reach ABUH have increased due to the war, unsafe road, shortage of fuel, and high travel costs. Moreover, in response to the COVID-19 pandemic in the country, healthcare providers reduced unnecessary visits. Here, we present an initiative illustrating our Syrian experience of TM in cancer care. Methods: The initiative began on 2 January 2021 to serve cancer patients near to Salamyieh (a rural area, 3-hour drive to ABUH). We satellite a clinic located near to patients’ homes, and we provide it with the necessary telecommunication infrastructure to virtually contact me at ABUH. The team, consisting of physicians and volunteers, meet patients and help me gather the history, symptoms and all relevant documents to set up and complete the care plan. Patients who need to receive treatment present to ABUH where the cancer therapies are completely free of charge. The whole services of this initiative are free including the E-consults, follow-ups, and auto transportation back and forth to ABUH. The volunteers accompany and help patients in their trips to AHBU, as many of them lost their beloved caregivers due to the war. Results: Throughout the last 2 years, we served 500 new patients. The numbers of E-consults were 920 and 800 in 2021 and 2022, respectively. Few patients were uncomfortable with it due to the lack of in-person interaction. Thus, it was a challenge to build connection and trust with patients virtually. Conclusions: Collectively, despite of the limited resources, TM initiatives have a lot to offer for patients with cancer and present a great solution to follow up with them. This experience shows that TM works especially in low-income countries, during the pandemic, and in a war-affected setting, all of which are associated with poor socioeconomic status and insecurity.
Tele-oncology implementation logic model.
Authors: Alishahi Tabriz Amir , Turner Kea , Naso Cristina , Gonzalez Brian D. , Oswald Laura B. , Nguyen Oliver , Hallanger-Johnson Julie E. , Patel Krupal , Hong Young-Rock , Powell Byron J , Spiess Philippe E. 
Published: June 2023

e13681 Background: The onset of the coronavirus disease 2019 (COVID-19) pandemic changed the landscape of oncology practice and placed tele-oncology at the center of cancer care delivery. As tele-oncology will likely remain a key part of cancer care delivery, healthcare organizations need to determine how to implement tele-oncology programs. We conducted an instrumental case study at a National Cancer Institutes -designated comprehensive cancer center that successfully implemented tele-oncology. Methods: Data were collected from three sources between June 2020–February 2022. We conducted semi-structured interviews among stakeholders directly involved in implementing and/or managing tele-oncology and surveys of administrators of the center’s tele-oncology and clinicians who used the program. Document analysis of implementation deliverables were also analyzed. Data collection and analyses were guided by the Consolidated Framework for Implementation Research, and Clinical Transformation in Technology. We used the Implementation Research Logic Model (IRLM) to develop a framework depicting determinants and key steps for implementing tele-oncology. Results: We interviewed 40 clinicians. We also invited 364 employees to complete online surveys, of which 151 (41.5%) responded. Most respondents were physicians (41.7%), nurse practitioners (26.5%), or physician assistants (26.5%). To implement tele-oncology program, three elements should be considered: (1) platform, (2) people, and (3) process. We found hospitals should: 1) adopt a safe and adaptable platform to deliver tele-oncology; 2) build a multidisciplinary tele-oncology team to provide the administrative, legal, workflow, and clinical support; 3) provide training and resources to make sure all the team members can deliver their responsibilities; 4) identify and appreciate early adopters, departments, and clinicians with successful experiences; 5) frequently evaluate the clinical and implementation outcomes; 6) secure reimbursement comparable with in-person rate and ; 7) advocate for policies that are supportive of tele-oncology in the future. Conclusions: Using IRLM we presented the tele-oncology implementation framework that can be used by hospitals around the world to implement their own tele-oncology.