bluuebunny/crossref_metadata_2025 huggingface dataset:
Benefits of blood transfusions in palliative care patients with advanced cancer.
Authors: Marinho Joana Catarina Lima , Marote Sara , Silva Maria Cândida , Gonçalves Jose Ferraz
Published: June 2021

e24090

Background: Anemia is highly prevalent in patients with advanced cancer and adversely affects quality of life. There is limited data on the frequency, clinical utility and effectiveness of red blood cell transfusions (RBC), and no randomized controlled trials or clinical practice guidelines on this subject are available. The aim of this study was to evaluate clinician practices on RBC transfusion in an oncologic palliative care unit (PCU), its impact on patients’ symptoms, overall survival and to identify predictive factors for survival. Methods: Retrospective cohort study of all advanced cancer patients who had received RBC transfusions over a 3-year period, after admission to the PCU for symptomatic control, as inpatients or outpatients. All had histologically confirmed malignant tumors and were not under anti-cancer treatments. Patients’demographics, clinical and laboratory features, symptoms and mortality were reviewed. Survival analysis was estimated using the Kaplan-Meier method and Cox's regression was used for multivariate analysis. Results: We identified 179 patients with a median age of 68 years [30-93], 60% were male, with a mean Charlson comorbidity index of 8.9 (SD ±2.3). The majority had gastrointestinal (42%) and genitourinary (35%) malignancies. A total of 435 RBC units, during 301 transfusion episodes were recorded. The majority (58%) were performed as inpatients. A combination of symptoms with low haemoglobin (Hb) levels was the main reason for transfusion (80%). Asthenia/fatigue was the most frequent symptom (68%). Prior to transfusion, the majority (73%) had an ECOG-performance status (ECOG-PS) greater than 2. The mean pretransfusion Hb was 6.9 g/dL and 48% patients had an Hb above 7 g/dL. Symptomatic benefit post-transfusion was achieved in 36% of patients. A statistically significant association between ECOG-PS and symptomatic benefit was found (p = 0.005). Median overall survival post-transfusion was 41 days (IC95% 30.6-51.4). On multivariate analysis, Hb level pre-transfusion, ECOG-PS and symptomatic benefit with transfusions were significantly associated with survival. Conclusions: Transfusion practices are more liberal in palliative care, increasing iatrogenic risk, while consuming a valuable and limited resource. However, transfusion does provide symptom relief, and should be offered to advanced cancer patients with a higher level of functioning. Post-transfusion symptomatic benefit, and pre-transfusion ECOG-PS and hemoglobin levels seem to be independent predictors of survival. Further high-quality trials are needed to develop validated measures of objective functional changes to evaluate the clinical impact of transfusions and to identify patients most likely to be positively impacted by transfusion.
Immune-related acute myocarditis in patients treated with immune checkpoints inhibitors: Systematic review with individual patient-level data meta-analysis.
Authors: Rumyantsev Alexey , Israelyan Edgar , Tyulyandina Alexandra , Glazkova Elena , Sergeev Yury , Tjulandin Sergey
Published: June 2021

e24096

Background: Immune checkpoint inhibitors can sometimes lead to fatal outcomes or significant morbidity due to immune-related adverse events (IRAE). Cardiac IRAE, especially myocarditis, are among the most fatal IRAE. There are scarce of the trials addressing the optimal therapeutic approaches for patients with IR-myocarditis. Initial therapy with high-dose steroids (1000 mg of prednisolone for 3-5 days) may be beneficial for many patients with this IRAE and this approach is endorsed by NCCN guidelines. We conducted a systematic review with individual patient-level data meta-analysis of published clinical cases to assess impact of various initial therapeutic modalities and adherence to NCCN guidelines on outcomes of immune-related myocarditis, associated with checkpoint inhibitors. Methods: We searched PubMed database for all full-text articles and abstracts on the treatment of patients with cardiac-related IRAE treated with various PD-1/PD-L1 or CTLA-4 inhibitors for years between 2012 and 2020 in English. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) tool was used to ensure transparent reporting. Main study inclusion criteria were: 1) morphologically confirmed immune-related myocarditis or highly clinically suspected autoimmune myocarditis (based on Bonaca et al, 2019 criteria); 2) clear association of IRAE and administration of check-point inhibitors; 3) availability of individual patient and treatment data. Pooled analysis of outcomes and multiple logistic regression analysis were conducted. The primary outcome of this study was rate of major cardiac adverse events (MACE) due to immune-related autoimmune myocarditis according to adherence to NCCN guidelines. MACE was defined as death or persisting significant disabilities due to myocarditis (ie, chronic heart failure, rhythm abnormalities or deterioration leading to impossibility of further anticancer treatment). Results: We identified 277 articles and screened them for title and abstract. After the review process we selected 81 studies for further analysis which described treatment course for 111 patients. Overall, 26 and 85 patients were treated with high-dose and non-high dose steroids. Among patients treated high-dose steroids therapy and non-high dose steroids 10 (38.5%) and 57 (67.1%) of patients respectively experienced MACE (HR 0.185; 95% CI 0.07-0.47; p = 0.0091). Initial treatment failure was associated with high rate of morbidity; however, 9 patients were rescued with various immunosuppressive drugs (eg, tacrolimus, alemtuzumab, tocilizumab). Conclusions: Our results support use of high-dose pulse therapy as a preferred therapeutic approach for all patients with suspected or proven immune-related myocarditis.
Stereotactic body radiation therapy as palliative management for incurable thoracic malignancies.
Authors: Ahn Grace S. , Bruggeman Andrew , Qiao Edmund M. , Murphy James Don , Sandhu Ajay
Published: June 2021

e24097

Background: Radiation therapy plays an important role in symptom palliation for patients with incurable cancer. Currently limited data exists regarding the role of SBRT vs conformal radiation for the palliation of symptoms due to malignancy. We report the symptom management and local control of palliative SBRT for incurable thoracic malignancies at a single institution. Methods: We retrospectively identified patients who underwent palliative SBRT between Jan 1st, 2009 and March 26th, 2019. Patients all had thoracic tumors that were not candidates for curative radiation due to age, stage, comorbidity, and/or prior treatment. We identified courses with total doses between 25-50 Gy (median 40) and total fractions between 3-10 (median 5). Symptoms such as cough, chest pain, hemoptysis, and shortness of breath were assessed at time of consult and first follow-up between 1-6 months post treatment. We also reviewed follow-up CT imaging to evaluate for local control using RECIST criteria. Descriptive statistics were used to evaluate patients’ clinicopathologic data and symptom palliation. Local control was analyzed via Kaplan-Meier method. Results: Of the 76 patients who completed palliative SBRT to 92 total lung lesions, 45 patients reported symptoms at consult and completed 50 courses of radiation to 55 lesions. Within this symptomatic cohort, average age was 71 (range, 42-93), 32 were female (58%), and most were stage IV (n = 42, 76%). Most lesions treated were non-small cell lung cancer (n = 34, 62%) while the most common primary site of metastatic lesions was colorectal (n = 6, 11%). Additional primary sites included breast, renal, sarcoma, and others (n = 15, 27%). Of the 53 lesions treated with follow-up within 6 months, 21 (40%) showed relief of at least 1 symptom and 31 (58%) showed stable symptoms. Only 1 patient (2%) showed symptom progression. All patients with hemoptysis at presentation achieved hemostasis following SBRT. Among 48 treated lesions with follow-up CT imaging, 1 (2%) showed complete response, 28 (58%) showed partial response (PR), 15 (31%) showed stable disease (SD), and 4 (8%) showed progressive disease. With further follow-up (median 23 months), 30 of the 53 lesions with initial PR or SD demonstrated local control until death. Conclusions: There is conflicting literature regarding the ideal palliative radiation dose for thoracic tumors. SBRT has the advantage of allowing a higher biologic dose without protracted treatment courses in the setting of palliation of symptoms. Our symptomatic cohort showed good symptom palliation and long-term local control of treated lesions. Prospective studies are required to further confirm the role of palliative SBRT for symptomatic thoracic tumors.
Patterns of knowledge and use of medical cannabis among Brazilian oncologists and palliative care physicians.
Authors: Freitas Júlia Maria Mathias Pedreira de , Almeida Daniela Oliveira de , Landeiro Luciana Castro G. , Reis Tércia Vilasboas , Carmo Thomas Azevedo de , Mathias Clarissa
Published: June 2021

e24099

Background: Medical cannabis (MC) emerged as an important complementary therapy in the context of oncological diseases. In 2019, the Brazilian Health Regulatory Agency (Anvisa) approved use of MC, which can be produced in the country and sold in pharmacies under medical prescription. Previous investigations have extensively correlated MC effectiveness, over management and support of symptoms caused by the disease and/ or its treatment. However, studies evaluating knowledge and patterns of MC use in oncology patients MC are lacking. In the present study, we assessed the perception of oncologists and palliative care physicians on MC as a complementary therapy for cancer patients, and their personal experiences in clinical practice in Brazil. Methods: In October 2020 an online survey was sent via e-mail by the Brazilian Society of Clinical Oncology and the National Academy of Palliative Care for physicians with expertise in oncology and/or palliative care. Outcomes measured included knowledge and opinions about MC, prescription experience and impressions about the Brazilian legislation. Data analysis was performed with descriptive statistics, comparison tests and the Poisson regression model with robust variance, using the IBM Statistical Package for the Social Sciences software, version 25. Results: A total of 124 physician participated in the study and, of those, 58.1% were oncologists, and 82.3% believed that MC has application as a complementary therapy in cancer. In contrast, only 52.4% of the participants felt comfortable recommending its use and only 15.3% have ever prescribed MC for their patients with cancer. Further, among those who have never prescribed, 71% have already referred patients to other professionals to prescribe, and 61% indicated lack of knowledge as the main factor for not prescribing. In addition, more than half of participants claimed not knowing Brazilian legislation regarding MC use. Nausea and vomiting were mentioned by 73.4% of physicians as the major indication for MC. Conclusions: Oncologists and palliative care physicians agree with the applicability of MC use for the management of symptoms related with or caused by cancer. However, our findings infer that factors such as lack of knowledge, legislation barriers and lack of robust scientific evidence, lead to its limited use among Brazilian oncologists and palliative care physicians.
Evaluating the user-perceived benefit of a virtual lung cancer patient education and support community: LVNG With Lung Cancer.
Authors: Martin Mona L. , Bucklen Kristin , Hall Lise J. , Sandy Beth , Wonser Dann , de Renne Genevieve
Published: June 2021

e24102

Background: The accessibility and quality of network support for people living with lung cancer (PLW) and their support partners (SP) can vary. Virtual platforms provide a unique opportunity for PLW/SP peer support and disease education; the challenge is to measure impact. Methods: Our aim was to determine user-perceived benefit of the Facebook based virtual community LVNG With Lung Cancer ( https://www.facebook.com/LVNGWithLungCancerUS ). Qualitative interviews were conducted with community members aged ≥18 yrs and living with lung cancer or actively supporting someone who had lung cancer. Also, inbound community comments (Dec 2015–Oct 2016) were retrospectively analyzed and grouped by similarity of content. Results: 18 PLW and 2 SP were interviewed (N = 20, saturation of concept met within the first 10). Mean yrs since diagnosis was 2.75 (range 0.08–17). Of the total expressions of benefit (n = 513) made during the interviews, 32% focused on increased health knowledge, with most participants calling out cancer information, good health behaviors, and coping strategies as key community benefits. Social impacts of the community accounted for 28% of benefit expressions; having a forum to share experiences and having a supportive environment were most frequently cited. An additional 18% of benefit expressions revealed that the community gives members feelings of empowerment, including feeling less alone (55% of respondents) and feeling inspired to help others (40% of respondents). Benefits received from community membership led to behavioral change in many respondents: 55% asked their doctor more questions, 50% shared helpful experiences with other members, and 35% took a more active role in their healthcare. In a notable example, an SP member said the community provided her with the knowledge she needed to address her symptoms and fears with her doctor, who was hesitant to biopsy because she did not meet typical risk criteria. Her self-advocacy was successful and ultimately led to an early lung cancer diagnosis. Results from the retrospective analysis of actual postings (n = 24,336; all unique users during evaluation period: n = 12,187) reflected the themes patients offered during interviews as important reasons to participate: 63% of postings were asking for or sharing cancer information, 98% provided emotional support and/or understanding, and 84% were inspirational/optimistic. Conclusions: This dual approach of assessing real-world impact of a virtual Facebook community provided insight into the benefit that members derive and highlighted the integral role of support groups in patient-centric care. Importantly, once members’ emotional and educational needs were met, they were empowered and/or inspired to take positive actions leading to better health behaviors and increased quality of life – an outcome that may have wider applicability for diseases beyond lung cancer.
The relationships between cancer diagnosis/prognosis awareness and quality of life, anxiety, and depression in Chinese gastroesophageal cancer patients: A cross-correlation analysis.
Authors: Wang Long , Zuo Jing , Wang Yudong , Feng Li , Zhang Xue , Han Jing , Li Dan , Hu Xinyan , Liu Jiayin , Zhou Xinliang , Fan Zhisong
Published: June 2021

e24111

Background: Many gastroesophageal cancer patients in China are not made aware of their cancer diagnosis/prognosis. Explorations of the differences in depression, anxiety and quality of life between cancer patients with and without such awareness are rare. The aim of this study was to evaluate the correlation between cancer awareness status and quality of life, anxiety and depression in gastroesophageal cancer patients. Methods: Participants were gastroesophageal cancer patients recruited from a medical center in North China. The degree of awareness of their cancer diagnosis/prognosis was evaluated via interviews. Data were collected using the Self-Rating Anxiety/Depression Scale and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and were analyzed using quantitative methods. Results: The study included 157 gastroesophageal cancer patients: 31 were completely unaware of their cancer diagnosis/prognosis (19.75%); 51 were partly aware (32.48%); and 75 were fully aware (47.78%). Thirty patients (19.11%) experienced anxiety and 35 (22.9%) depression. Unawareness of the real disease status was significantly correlated with worse quality of life (cognitive functioning, social functioning and appetite loss) ( Ps < 0.05) and anxiety ( P = 0.003). Conclusions: More than 50% of gastroesophageal cancer patients were unaware their diagnosis/prognosis completely and were more likely to experience worse quality of life and anxiety. Medical staff and family members should take appropriate measures to make patients aware of their cancer diagnosis/prognosis, as awareness is valuable for improving quality of life and negative emotions, contributing to the successful overall management of gastroesophageal cancer.
Developing, implementing, and validating a social toxicity assessment tool of cancer (STAT-C).
Authors: Jazieh Abdul-Rahman , Jradi Hoda , Da'ar Omar B. , Alkaiyat Mohammad , Zafar Yousuf , Alolayan Ashwaq Aman Mohammed
Published: June 2021

e24115

Background: The social impact of cancer on patients and their family is well known. Yet, unlike with physical and financial toxicities, no validated tools are available to measure this impact. This study aimed at developing, validating, and implementing a novel social toxicity assessment tool for patients with cancer diagnosis (STAT-C). Methods: Questions were generated through multiple steps including focus groups of patients, their families, and oncology care professionals. Content validity, internal consistency, face validity and factor analysis were conducted. The questionnaire (in Arabic language) was administered to 150 patients with cancer served at King Abdulaziz Medical City, Riyadh, Saudi, Arabia. Results: STAT-C contains 14 items covering three domains: Social Relations domain (eight questions) related to relationship with parents, spouse, children, siblings, friends, members of congregation, and caregiver; Social Activities domain (two questions) measures participation in social events and leisure; and Economic Impact domain (four questions) related to standard of living, finances, and loss of job. The total possible score for each patient for the 14 items in the tool varied between -28 and +28 (Range = 56). Dividing the range by three levels of a socioeconomic toxicity yielded the length of each level, which effectively defined the categories as- Severe social toxicity (SST score: -28 to -9.3), mild social toxicity (MST: -9.2 to 9.5) and no social toxicity (NST: 9.6 to 28). Conclusions: Our study revealed that STAT-C is a valid and reliable tool in assessing the social toxicity of cancer in Arabic-speaking patients. Validating the tool in an English-speaking population is planned. The tool should enable oncology professionals to deliver better patient-centered care as a component of a holistic approach.
The SHARE study: Pilot study of a communication intervention designed to elicit advanced-stage cancer patients’ preferences and goals.
Authors: Thompson Embree , Wright Alexi A. , Keating Nancy Lynn
Published: June 2021

e24120

Background: Helping seriously-ill cancer patients identify and communicate their preferences for care can increase satisfaction, decrease anxiety and depression, and result in less intensive, hospital-based end-of-life medical care. We developed an intervention designed to elicit patients’ preferences and goals for care and share them with their family and care teams. We sought to pilot-test the feasibility and acceptability of this intervention in advanced cancer patients. Methods: We enrolled advanced-stage cancer patients and their clinicians at an academic and community oncology practice. Eligibility criteria included: patients with metastatic solid tumors and ≥2 prior lines of therapy or patients for whom oncologists indicated that they “would not be surprised” if the patient died within 6 months. Participants watched a 2.5 minute video which prompted them to think about how they define “a good day;” completed a 3-page brief questionnaire, which was shared with their care team; and were given a wallet card with question prompts. The primary outcomes were feasibility (i.e., ≥60% approach-to-consent ratio among eligible patients, ≥60% of participants rated the intervention positively) and acceptability (i.e., ≥60% of participants would recommend the intervention to patients like them). Secondary outcomes, measured pre- and post-intervention, included patient anxiety and distress, hope, quality of life, and therapeutic alliance with their care team. Results: Among 59 potentially eligible patients approached, 53 agreed to participate (90% approach-to-consent ratio). Four patients were non-evaluable because they died before study completion. Among the 49 remaining participants (mean age = 63 years, range 40-86 years), all completed the intervention. Overall, 45 of 49 patients (92%) rated their experience as excellent, very good, or good. Most participants agreed or strongly agreed that they would recommend the video (83%), brief questionnaire (88%), and wallet card (63%) to patients with cancers like theirs. However, only 34% of participants reported having an opportunity to review the questionnaire with their oncologist. There were no increases in patient anxiety or distress associated with the intervention or reductions in hope, quality of life, or therapeutic alliances with oncologists (all P > 0.05). Conclusions: A communication intervention that combined a video, questionnaire, and wallet card was both feasible and acceptable for helping advanced cancer patients identify their care preferences and goals. Future studies should examine combining this with an intervention that primes clinicians to engage in goals of care discussions with advanced-stage cancer patients. Clinical trial information: NCT03392090.
Cancer patients’ awareness about clinical research in the era of social media and “fake news”: Preliminary results from ELPIS Study.
Authors: Cagnazzo Celeste , Franchina Veronica , Toscano Giuseppe , Fagioli Franca , Franchina Tindara , Ricciardi Giuseppina Rosaria Rita , Antonuzzo Lorenzo , Di Costanzo Alessandro , Russo Antonio , Cusenza Stefania , Gori Stefania , Marchetti Fabiana , Tambaro Margherita , Piccirillo Patrizia , Nanni Oriana , Cenna Rosita , Delfanti Sara , Di Maio Massimo , Dascanio Fabio , Adamo Vincenzo
Published: June 2021

e24121

Background: Barriers for low recruitment in clinical trials have been classified based on three main sources: physician, patient, system. A primary role is played by a low patient awareness, which often leads to a lack of confidence in science and a substantial inability to estimate the benefits deriving from trial participation, aggravated by the spread of fake news. A prospective observational study was conducted to investigate the views of cancer patients on aspects of clinical research, their expectations, the level of comprehensibility of informed consent and the impact of the fake news phenomenon. Methods: From January 2018, after Ethics Committees approval, the ELPIS study was initiated in 9 Italian Medical Oncology Units. After signing the informed consent, patients were asked to complete a questionnaire, consisting of a set of multiple choice and Likert-score questions. Results: As of January 2021, 115 patients were enrolled, with a balanced sex distribution and a prevalence of subjects older than 55-years (79.8%). Regarding the previous knowledge about clinical research, the average score was 3.9 (range 1-5). The vast majority of respondents (91.3%) had already started experimental therapy and many of them constantly used internet (65.2%) and social networks (34.8%). More than half (53.9%) stated the interview with the physician was sufficient for a full understanding of informed consent. In case of doubt, the majority seeked support in the clinician (39.1%) while very few (1.7%) relied on the web. The average score attributed to doctor-patient relationship was equal to 8.89 (range 1-10). Respondents were quite confident in their ability to independently search for information on their disease, discriminate fake news and identify reliable sites (average score 3.26, 3.27, 3.09 respectively, over a range of 1-5). The scores related to the presumed ability to understand the results of a clinical study and to actively collaborate to produce research were high (average score 4.72 and 4.39 over a range of 1-5). Conclusions: Preliminary data from our research show a good level of patient awareness and a fine ability to understand information, discerning real from fake news. Continuing and implementing the training initiatives of the population in the health sector will certainly contribute to further improvement, hopefully obtaining an even greater involvement of patients in the early phases of research.
Healthcare professionals’ perspectives on unique communication and care needs for Chinese American cancer patients.
Authors: Schroeder Courtney , Ernst Emma , Vesel Tamara
Published: June 2021

e24122

Background: Effective clinician-patient discussions of cancer diagnoses and prognoses are essential to enhance health outcomes in diverse oncology populations. To provide guidance on communication preferences and needs among Chinese Americans, one of the fastest growing yet understudied ethnic groups in the United States, we explored considerations and observations from healthcare providers experienced in caring for this oncologic population. Methods: In this inductive, emergent qualitative study, we completed 20 semi-structured virtual interviews with providers from assorted healthcare disciplines with experience caring for Chinese American cancer patients in Boston’s Chinatown. Responses were systematically collected and analyzed using open and focused coding, constant comparative methods, and thematic analysis. Results: Twenty healthcare professionals with experience working with the Chinese American patients were interviewed including medical oncologists, radiation oncologists, primary care physicians, nurses, nurse practitioners, social workers, case managers, patient navigators and dietitians. Fifteen were female, 5 were male, and 11 participants self-identified as Asian. Six key themes were identified: (1) Discussing cancer diagnoses and prognoses is taboo and often avoided by Chinese Americans in family, community, and healthcare settings. (2) A cancer diagnosis may be considered a death sentence by Chinese Americans, regardless of cancer location or stage. This could be related to the meaning implied by direct translation of the word “cancer.” (3) In settings where cancer diagnoses and prognoses are discussed, Chinese American patients often prefer indirect communication approaches including use of expressions such as “tumor,” “mass,” or “illness” to avoid the use of the word “cancer.” (4) The family centered role in medical decision making for Chinese American cancer patients and the preference of some family units to protect the patient from their diagnoses present unique challenges in the context of standard care. (5) Obtaining a detailed psychosocial history is important to guide communication approaches, as patient characteristics like age, generation since immigration, and education play a foundational role in communication preferences. (6) Karma and nutritional beliefs should be considered and addressed in oncologic care, as they play a critical role in health and disease management for Chinese American cancer patients. Conclusions: Further exploration of these insights and confirmation of their accuracy by discussing directly with Chinese American patients is imperative. If these findings are corroborated through further investigation, this knowledge can be used develop educational tools and implement clinical practice changes to enhance care outcomes and communication with Chinese American cancer patients.
Stress as a predictor of tumor growth and development of metastases.
Authors: Peyser Tristen , Geller David A. , Terhorst Lauren , Antoni Michael , Vodovotz Yoram , Hausmann Leslie , Olejniczak Donna , Amin Aarshati , Kiefer Gauri J. , Hecht Carol Lynn , Miceli Jessica , Tong Albert , Johnson Jonas T. , Nilsen Marci Lee , Zandberg Dan Paul , Reyes Vincent Edgar , Steel Jennifer
Published: June 2021

e24124

Background: The aims of this study were to examine; the predictors of perceived stress; and the associations between perceived stress and tumor growth and development of metastases as well as the mediational role of inflammatory biomarkers. Methods: This study is prospective in design. A battery of questionnaires, including a sociodemographic characteristic and the Perceived Stress Scale, was collected at baseline from patients diagnosed with solid tumors at various stages of treatment. Disease progression was measured over a 12-month period. Poverty threshold was determined using the U.S. Department of Health & Human Services 2020 poverty guidelines. Computerized tomography and Magnetic Resonance Imaging scans were assessed for disease progression between baseline and 12 months using Response Evaluation Criteria in Solid Tumors. Blood was collected and serum levels of IL-2, IL-1a, IL-1b, TNF-a, IL-6, and IL-8 were assessed. The predictors of stress include sociodemographic and disease specific characteristics. Primary outcomes were tumor growth and development of metastases. Descriptive statistics, correlations, and ordinal and linear regression were performed to assess the aims. Results: Of 159 patients diagnosed with cancer, 47.8% were male, mean age was 62.97 (SD = 10.35), 89.3% were Caucasian, and 13.8% met poverty guidelines. Significant predictors of stress were age (b=-.151, p=0.029, 95% C.I.=-2.86-.016) and income below the poverty threshold (b= 5.615, p=0.007, 95% C.I.=1.596-9.635). Gender was the only sociodemographic and disease specific factor significantly associated with disease progression. After adjusting for gender, greater perceived stress was associated with tumor growth and development of metastases (p =0.029), accounting for 33.3% of the variance. Circulating cytokines were significantly related to disease progression [IL-1a, p=0.020; IL-1b, p=0.011; IL-6, p<0.001; and IL-8, p<0.001] but not stress [IL-1a, p=0.369; IL-1b p=0.292; IL-2, p=0.470; IL6 p=0.406; and IL8, p=0.401]. Conclusions: Future research should evaluate inflammation in the tumor microenvironment as well as neutrophils and tumor suppressor genes as potential mediators between stress and disease progression.
Trial in progress: A phase 1b/2 study of the PARP inhibitor niraparib in combination with trastuzumab in patients with metastatic HER2+ breast cancer (TBCRC 050).
Authors: Stringer-Reasor Erica Michelle , Li Yufeng , Witherspoon Felicia , Specht Jennifer M. , Anampa Mesias Jesus Del Santo , Nanda Rita , Dees Elizabeth Claire , Wolff Antonio C. , Krop Ian E. , Lin Nancy U , Rimawi Mothaffar F. , Yang Eddy Shih-Hsin
Published: June 2021

TPS1098

Background: Approximately 20% of breast cancers (BC) express the human epidermal growth factor receptor 2 (HER2). Although HER2-directed therapies result in improved patient outcome, resistance ultimately occurs. Poly (ADP-Ribose) polymerase (PARP) inhibitors are currently indicated in cancers that express germline mutations in the DNA repair proteins BRCA1/2 due to their synthetic lethality against the homologous recombination repair (HR) pathway. In addition to its role in DNA damage repair, PARP1 has also been implicated in other cellular functions, including co-activation of genes such as NF-κB, which regulate tumor proliferation and HER2 drug resistance. Our group identified that HER2+ BC overexpress the PARP1 and phospho-p65 protein. In HER2+ BC cells and animal models, PARP inhibitors initiated apoptosis independent of a DNA repair deficiency, via inhibition of NF-kB signaling. Key proteins (p65, IKK-α) of the NF-κB-mediated growth pathways were reduced and IκBα was increased in the presence of PARPi, implicating another oncologic pathway in which HER2+ BC cells may be dependent. Methods: The study is a phase 1b/2, multicenter, single arm clinical trial evaluating the safety and efficacy of niraparib 200 mg orally days 1-21 with trastuzumab 6 mg/kg (cycle 1 loading dose of 8 mg/kg) intravenously on day 1 of a 21-day cycle for patients with unresectable or metastatic HER2+ BC. Eligible patients include metastatic HER2+ BC, progression on at least 1 prior HER2-targeted therapy, measurable disease, ECOG PS 0-1, and LVEF ≥ 50%. Stable/treated CNS disease allowed. Prior PARPi and known germline BRCA 1/2 excluded. Forty patients will be enrolled at 7 US sites within the Translational Breast Cancer Research Consortium. The primary objectives are determining the dose-limiting toxicity (DLT) of the combination and assessing the objective response rate. The phase 1b cohort has been completed (N=6). Enrollment in phase 2 began February 2021 with a total accrual goal of 40. Gehan’s two-stage design will be used assuming the response rate is at least 24% and the response rate will be estimated with Clopper-Pearson exact method. Correlative aims include assessing blood and tissue biomarkers (e.g. PARP1, p65, phosphor-p65, let-7a miRNA, NF-kB, ctDNA, etc.) for association with clinical benefit and to predict response to therapy. Clinical trial information: NCT03368729 .
Trial in progress: Phase I/II study of radiation therapy followed by intrathecal trastuzumab/pertuzumab in the management of HER2+ breast leptomeningeal disease.
Authors: Ahmed Kamran A. , Kim Youngchul , DeJesus Michelle , Kumthekar Priya , Williams Nicole Olivia , Palmer Joshua David , Giglio Pierre , Boire Adrienne Ann , Arrington John , Sahebjam Solmaz , Rosa Marilin , Soliman Hatem Hussein , Yu Hsiang-Hsuan Michael , Han Hyo S. , Forsyth Peter A. J.
Published: June 2021

TPS1099

Background: HER2+ breast cancer patients with leptomeningeal disease (LMD) represent a poor prognosis population with a high unmet clinical need. Although a multitude of treatment options are available for the management of systemic disease, once metastases travel to the leptomeninges, patients have a lack of treatment options aside from traditional local approaches. Data from a phase I/II study reveals intrathecal (IT) trastuzumab to be well tolerated with improved overall survival (OS) compared to historical controls in HER2+ breast LMD. Radiotherapy can improve the flow of IT therapy through the cerebrospinal fluid (CSF) and provide symptomatic relief. The monoclonal antibody pertuzumab is used in conjunction with trastuzumab in the management of metastatic and localized HER2+ breast cancer. Given the role of radiotherapy in the management of LMD along with the role of pertuzumab in the management of HER2+ breast cancer, there is a strong clinical rationale to combine radiotherapy with IT trastuzumab/pertuzumab in the management of HER2+ breast LMD. Methods: The study is designed as a prospective, single-arm, nonrandomized, open-label, phase I/II trial of radiation therapy followed by IT trastuzumab/pertuzumab in the management of HER2+ breast LMD. HER2+ LMD patients identified by magnetic resonance imaging (MRI) and/or CSF cytology, ≥ 18, with a life expectancy > 8 weeks are eligible. Treatment is initiated with radiotherapy, whole brain radiotherapy and/or focal brain/spine radiation followed by IT trastuzumab/pertuzumab. Safety and feasibility will be monitored by a modified toxicity probability interval-2 (mTPI-2) design. Dose reductions of IT trastuzumab will not be allowed. Once the maximum tolerated dose of IT pertuzumab is determined, the phase II portion of the study will commence to determine OS. Secondary objectives involve defining the CSF pharmacokinetics of IT trastuzumab/pertuzumab, evaluating the response rate (leptomeningeal and parenchymal), and progression free survival (leptomeningeal and parenchymal) following IT trastuzumab/pertuzumab. In the phase 2 portion, a single-arm two-stage trial is designed using the Restricted-Kwak-and-Jung’s Method. The primary endpoint is one-year OS. An interim analysis will be performed after 20 patients are enrolled. This study is open with 1 patient enrolled at the time of submission. Clinical trial information: NCT04588545 .
BEGONIA: Phase 1b/2, open-label, platform study of the safety and efficacy of durvalumab (D) ± paclitaxel (P) with novel oncology therapies for first-line metastatic triple-negative breast cancer (mTNBC): Addition of arm 7, D + datopotamab deruxtecan (Dato-DXd; DS-1062).
Authors: Schmid Peter , Nunes Ana Tablante , Dry Hannah , Dougherty Rachel , Karwe Vatsala , Scheuring Urban J.
Published: June 2021

TPS1105

Background: Patients (pts) with mTNBC have limited treatment options and poor prognosis. The combination of immune checkpoint inhibitors with chemotherapy shows promise, but only a subset of pts with mTNBC derive benefit, highlighting the need for new combinations. BEGONIA is an ongoing Simon 2-stage, multicenter, multi-arm platform study evaluating the safety and efficacy of D, an anti–PD-L1 monoclonal antibody, with or without P, in combination with novel oncology therapies as first-line treatment for mTNBC (NCT03742102). Dato-DXd is an antibody-drug conjugate (ADC) consisting of a humanized anti-trophoblast cell surface antigen 2 (TROP2) IgG1 monoclonal antibody, a stable tetrapeptide-based cleavable linker, and a topoisomerase I inhibitor payload. Dato-DXd displayed encouraging clinical activity with a manageable safety profile in heavily pretreated pts with metastatic NSCLC in the phase 1 TROPION-PanTumor01 (NCT03401385) study. TROP2 is highly expressed on breast and other epithelial tumors, and a TROP2 ADC showed activity in heavily pretreated pts with mTNBC (Bardia, NEJM 2019). Methods: Eligible female pts are aged ≥18 years with untreated unresectable, locally advanced or mTNBC, ≥12 months since prior taxane therapy, ECOG PS 0/1, adequate organ function, and ≥1 nonirradiated measurable lesion. For Arm 7, pts are excluded if they have clinically significant corneal disease, history of interstitial lung disease/pneumonitis, underlying pulmonary disorder, or prior treatment with an ADC containing a topoisomerase I inhibitor. Arm 7 will evaluate D (1120 mg) + Dato-DXd (6 mg/kg) given intravenously every 3 weeks until disease progression or unacceptable toxicity. Part 1 of each arm includes a total of 30 pts with a safety run-in (n=6) to observe dose-limiting toxicities, identify the recommended phase 2 dose (RP2D), and detect an efficacy signal for part 1 expansion. The primary endpoint of part 1 is safety and tolerability. Secondary endpoints include investigator-assessed objective response rate (ORR), duration of response, progression-free survival (PFS), and overall survival (OS). Once the RP2D has been established for part 1, a futility analysis will be performed with an option to expand the cohort to an additional 27 pts if expansion criteria are met. The primary endpoint for part 1 is ORR. Tumors will be assessed every 6 weeks per RECIST v1.1. Kaplan-Meier analysis will be used for PFS and OS. PD-L1 and TROP2 expression will be assessed by immunohistochemistry. Enrollment is ongoing. Clinical trial information: NCT03742102 .
Investigating bacterial decolonization for the prevention of radiation dermatitis: A randomized controlled trial and quality of life assessment.
Authors: Mieczkowska Karolina , Deutsch Alana , Shinoda Kosaku , Daily Johanna , Ohri Nitin , McLellan Beth
Published: June 2021

TPS12137

Background: Radiation dermatitis (RD) can be therapy-limiting and detrimental to quality of life for cancer patients receiving radiation therapy (RT). Bacteria play an important role in many inflammatory dermatoses. In an observational clinical study, our group discovered that nasal colonization with bacteria, specifically with Staphylococcus aureus (SA), prior to RT was an independent predictor of higher-grade RD (grade ≥2). Higher-grade RD patients were also found to have more SA on the irradiated skin after treatment. If successful, bacterial decolonization could be a safe and cost-effective method to prevent RD. Methods: This is a randomized controlled trial assessing the efficacy of universal bacterial decolonization in preventing RD. Subject inclusion criteria include patients who are aged ≥ 18 years with a diagnosis of a solid tumor of the breast or head and neck with plans for fractionated RT (≥ 15 fractions) with curative intent. Based on previous studies and power analyses, we plan to recruit a total of 80 patients. Patients in the control arm will be treated according to standard of care, including daily application of emollients and gentle bathing. In addition to standard of care, patients in the intervention arm will receive a decolonization regimen consisting of intranasal mupirocin ointment used twice daily and chlorhexidine wash used daily for 5 days prior to the initiation of RT and repeated for 5 days every other week throughout RT. Study evaluations for both groups will include bacterial cultures obtained via superficial swab from the nares, irradiated skin, and contralateral non-radiated skin performed at the beginning, middle, and end of RT. Additionally, standardized photographs of the skin at the radiated site will be performed prior to and at the completion of RT, which will be graded by a dermatologist blinded to study arm. Lastly, at identical timepoints, each patient will complete the SKINDEX-16 questionnaire, a validated quality of life (QoL) assessment. The primary endpoint is development of grade ≥ 2 RD, as compared to low-grade RD (grade 0-1), during RT. The secondary endpoint includes the impact of bacterial decolonization on QoL. Pearson’s chi square or Fisher’s exact tests will be used to compare the incidence rates of higher-grade RD between the interventional arm and control arm to assess if the intervention is associated with a lower incidence rate of higher-grade RD. Paired t-tests will be used to compare the QoL score change from baseline to after RT between the two arms. Linear regression models will be used in both analyses to adjust for covariates. Clinical trial information: NCT03883828.
A study evaluating targeted therapies in participants who have advanced solid tumors with genomic alterations or protein expression patterns predictive of response (MyTACTIC).
Authors: Grothey Axel , Howland Michael , Hubbard Lloryn , Szado Tania , McDonald Anne , Darbonne Walter C. , Levy Jonathan , Borden Eucharia , Spigel David R. , Vanderwalde Ari M. , Schwartzberg Lee S.
Published: June 2021

TPS1588

Background: Cancer treatment is evolving toward a more personalized approach in which the intersection of genomics, pathology and imaging methods leads to individualized care. Furthermore, identification of novel genomic alterations and other biomarkers has the potential to lead to customized, targeted treatments. Matching specific therapies to tumor biomarkers has the potential to yield valuable clinical information. Here we present a multiarm basket trial that matches patients with a broad array of metastatic solid cancers to investigational therapies alone or in combination based on specific, targetable genomic alterations or protein expression patterns that are potentially predictive of response (MyTACTIC). Historically, such trials have been conducted at large academic medical centers rather than community centers, where most US patients with cancer receive treatment. Prioritizing community centers for this study presents an exciting opportunity to generate data from a more representative patient population. Methods: This phase II, multicenter, nonrandomized, open-label study is enrolling approximately 200 participants with advanced solid tumors that harbor alterations including mutations, fusions, amplifications and protein loss in specific biomarkers that include human epidermal growth factor receptor 2 (HER2), phosphoinositide 3-kinase (PI3K), anaplastic lymphoma kinase (ALK), proto-oncogene tyrosine-protein kinase (ROS1), protein kinase B (AKT), phosphatase and tensin homolog (PTEN), high tumor mutational burden (TMB), high microsatellite instability (MSI) and deficient mismatch repair (dMMR). Patients aged ≥18 years with positive local biomarker results from tissue or blood samples will be enrolled from community oncology centers and practices. Eligibility criteria have been broadened to allow enrollment of a diverse population of patients, including those with nonmeasurable disease, HIV or viral hepatitis infections, and to allow for previous treatment with anticancer agents in the same class. Once general and arm-specific criteria are met, patients will be assigned to 1 of 10 treatment arms to receive mono- or combination therapy with targeted agents, immunotherapy and/or chemotherapy (≤25 patients per arm). The primary objective is to evaluate confirmed objective response rate, as assessed by the investigator according to RECIST version 1.1 or RANO criteria for primary central nervous system tumors. Progression-free survival, duration of response, overall survival and safety will also be assessed. Special attention has been paid to the study design and implementation to ensure equitable access, along with flexibility to add additional baskets. Enrollment is ongoing. Clinical trial information: NCT04632992.
Combination of atezolizumab and pirfenidone in second-line and beyond NSCLC: A phase I/II study.
Authors: Komiya Takefumi , Zhang Jun , Neupane Prakash C. , Mehta Kathan , Huang Chao Hui
Published: June 2021

TPS2678

Background: Checkpoint inhibitors (CPI) targeting the PD1/PD-L1 axis significantly improved patient outcomes in stage IV non-small cell lung cancer (NSCLC). However, these patients will eventually develop resistance and progression. There is a need to identify novel treatment options. Poor response to PD-L1 antibody was correlated with increase in cancer-associated fibroblasts (CAF), which is known to interact with cytotoxic T cells (CTLs) by suppressing their function in a manner similar to regulatory T cells (Tregs). Production of cytokines by CAFs leads to impaired antitumor immunity by impairing CTL function (TGF beta) and prevent recruitment/mobilization of CTLs into tumors. These effects suggesting that CAF can be a therapeutic target in lung cancer resistant to checkpoint inhibitors. Pirfenidone (P) is approved to treat pulmonary fibrosis with anti-fibrotic effect by blocking the differentiation of fibroblasts into CAFs and suppress the production of TGF beta and TGF beta-induced signaling pathways/collagens. Atezolizumab is a humanized immunoglobulin (Ig) G1 monoclonal antibody that targets PD-L1 and inhibits the interaction between PD-L1 and its receptors, PD-1 and B7-1 (CD80), both of which function as inhibitory receptors expressed on T cells. We proposed a phase I/II trial to test the combination of atezolizumab (A) with P in patients with recurrent non-small cell lung cancer (NSCLC) after progression with CPI. The primary objective of phase I is to determine the maximum tolerated (MTD) dose of P in combination with A and assess the safety and tolerability of this combination. The secondary objective is to determine the efficacy of AP in all NSCLC participants treated in this study. Exploratory objectives include the measurement of circulating levels of TGF beta and research in expression of CAF related proteins. Methods: The initial phase I will enroll 3 patients using P at 801 mg po TID. A will be at 1200mg iv every 3 weeks. If there is ≤ 1 DLT, the study will proceed to phase II If there are 2- 3 DLT, P will be reduced to 534 mg TID. If there is ≤ 1 DLT, then this dose will proceed to phase II. If there is 2-3 DLT, then the study will be terminated. The phase II will enroll 16 patients to assess efficacy. Main inclusion criteria are patients with recurrent NSCLC after progression with first-line therapy CPI with or without chemotherapy, measurable disease, ECOG 0-2, and adequate organ function. Clinical trial information: NCT04467723.