bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterizing genitourinary exam disruptions in women presenting to a sexual health after cancer program.
Authors: Satish Sanjana , Pon Fay , Calfa Carmen Julia , Perez Alejandra T. , Rojas Kristin E.
Published: June 2022

e24048

Background: While treatment-related sexual health sequelae are documented using validated patient-reported outcome measures, the anatomic changes associated with cancer treatment are not well described, which may lead to an underestimation of the severity of these symptoms. To fill this knowledge gap and improve the management of these anatomic disruptions, we sought to objectively report the genitourinary findings of women presenting to a sexual health after cancer program over one year. Methods: At their first visit, patients undergo a thorough history and physical with a focus on the genitourinary exam. Patient demographics, primary symptoms, and treatment history were retrospectively collected and correlated to vaginal assessment scale (VAS) scores of female cancer patients presenting to the MUSIC (Menopause, Urogenital, Sexual Health and Intimacy Clinic) Program at an NCI-designated cancer center. Results: Between 2020-2021, 104 female cis-gender women with a median age of 46 (range 19-75) at diagnosis were seen. 56% identified as Hispanic/Latinx. Mean age was 47 (19-75), and most were treated for breast (80%) or gynecologic (10%) cancer. Primary complaints included vaginal dryness (53%), painful sex (45%), low desire (36%), hot flashes (22%), problems with orgasm (5%), urinary symptoms (10%), chronic pelvic pain (4%), or a need for complex contraceptive counseling (1%). Of those where a VAS was performed (n = 89), patients were found to have mild or moderate/severe loss of rugae (78%), loss of elasticity (84%), loss of vascularity (86%), and/or dryness (88%). Alarmingly, almost half were found to have some element of vaginal stenosis on exam, either vaginal scarring/adhesions (6%), foreshortened vagina (13%), or a narrowed introitus (47%) (Table). Conclusions: In an initial consult of women seeking care for sexual health after cancer treatment, the most common concerns were vaginal dryness, painful sex, and low desire. Despite only approximately half reporting either dryness or painful sex, most were found to have genitourinary disruptions in anatomy at presentation, including vaginal stenosis. The presence of vaginal stenosis in sexual health survivors who did not undergo pelvic radiation deserves future study as these findings often present as a complete inability to have penetrative intercourse.[Table: see text]
The patient's needs before and six months after the initiation of breast cancer treatment: A prospective study in 600 breast cancer patients.
Authors: Kurir Borovcic Mateja , Mavric Zlatka , Zagar Tina , Homar Vesna , Kopcavar Gucek Nena , Skufca Smrdel Andreja Cirila , Knific Jana , Borstnar Simona , Marinko Tanja , Zadravec Zaletel Lorna , Kos Natasa , Strazisar Branka , Slapar Tatjana , Mastnak Mlakar Denis , Kovacevic Nina , Hadzic Vedran , Pelhan Bojan , Sremec Marko , Rozman Tina , Besic Nikola
Published: June 2022

e24062

Background: Our aim was to determine the frequency of health-related problems faced by breast cancer patients before and six months after the initiation of breast cancer treatment. Methods: This prospective study involved 600 female breast cancer patients (26-65 years, mean 52), who participated in the pilot study in the novel individualized integrated rehabilitation programme in 2019-2022 and were followed for at least six months. The patients completed three questionnaires (EORTC QLQ - C30, B23 and NCCN) before the initiation of cancer treatment and six months after. The patients received neoadjuvant chemotherapy in 22% of the cases, tumorectomy in 53%, mastectomy in 39%, breast reconstruction in 27%, sentinel node biopsy in 67%, lymphadenectomy in 23%, external beam radiotherapy in 73%, chemotherapy in 45%, anti-HER-2 therapy in 11% and hormonal therapy in 74% of the cases. Data on the patients’ demographics, disease extent, cancer treatment and problems reported in the questionnaires were collected and analysed using descriptive analysis. Results: The problems reported by patients before the initiation of cancer treatment and after six months are presented in Table. In 14 out of 22 parameters, the frequency of problems increased in the six months after the initiation of treatment: fatigue, insomnia, lymphedema, shoulder movement impairment, disturbing scars, heart problems, hot flashes/sweating, gynaecological problems, sexual problems, body image worries, inappropriate nutrition, pain in the shoulder or arm, alopecia and concerns about returning to work. On the other hand, the frequency of problems decreased six months after the initiation of cancer treatment in 6 out of 22 parameters. Our patients less often had depression or anxiety, were too little physically active, smoked, consumed alcohol or used food supplements than before. Conclusions: Six months after the initiation of breast cancer treatment patients have more problems than at the time before treatment.[Table: see text]
Randomized controlled trial (RCT) of symptom screening with targeted early palliative care (STEP) versus usual care in patients with advanced cancer.
Authors: Zimmermann Camilla , Pope Ashley , Hannon Breffni , Krzyzanowska Monika K. , Rodin Gary , Li Madeline , Howell Doris , Knox Jennifer J. , Leighl Natasha B. , Sridhar Srikala S. , Oza Amit M. , Prince Rebecca M. , Lheureux Stephanie , Hansen Aaron Richard , Dhani Neesha C. , Liu Geoffrey , Bedard Philippe L. , Chen Eric Xueyu , Swami Nadia , Le Lisa W
Published: June 2022

e24084

Background: To direct limited specialized palliative care resources to patients in greatest need, we developed STEP (Symptom screening with Targeted Early Palliative care). STEP entails symptom screening (ESAS-r) at each oncology clinic visit and triggered alerts (for moderate-high physical and psychological symptoms) to a nurse who calls the patient to offer a palliative care clinic (PCC) visit. We conducted a phase III RCT to assess the impact of STEP versus usual care on quality of life and other patient-reported outcomes (PROs). Methods: Adults with advanced cancer were recruited from medical oncology clinics at the Princess Margaret Cancer Centre, Toronto, Canada. Consenting patients with oncologist-assessed ECOG 0-2 and estimated survival of 6-36 months were enrolled and block randomized (stratified by tumour site and symptom severity) to STEP or usual care. Participants completed measures of quality of life (FACT-G7), depression (PHQ-9), symptom control (ESASr-CS), and satisfaction with care (FAMCARE-P16) at baseline, 2, 4 and 6 months. The primary outcome was FACT-G7 at 6 months, with a planned sample size of 261/arm. Results: From 8/2019 to 3/2020, 69 patients were enrolled: 33 randomized to STEP and 36 to usual care. The trial was then halted permanently due to the COVID-19 pandemic, owing to substantial changes to elements of STEP (shift to virtual symptom screening and palliative care) and usual care (shift to virtual oncology care). Median age was 64 years (range 25-87) and 62% (43/69) were women; study arms were balanced at baseline except gender, with more women randomized to STEP. Within the STEP arm, 20 (61%) participants triggered a nurse’s call to offer a PCC visit, of whom 13 attended the clinic at least once. All outcomes tended to be better in the STEP arm compared to usual care, particularly depression and satisfaction with care at 6 months; however, results were not statistically significant (Table). Conclusions: STEP holds promise for improving quality of life and other PROs in patients with advanced cancer and effectively directing early palliative care towards those who need it most. In response to the pandemic, an online version of STEP has been developed and a further trial is in progress. Clinical trial information: NCT03987906. [Table: see text]
Preclinical study of OQL051, a gut-restricted CDK4/6 inhibitor for chemotherapy-induced diarrhea.
Authors: Tyler Robert Claude , Zeng Wenqin , Li Wenxi , Chen Liping , Liu Shilan , Zhang Shiyi
Published: June 2022

e24085

Background: Chemotherapy-induced diarrhea (CID) is a potentially life-threatening AE (incidence 50-80% with 5FU/irinotecan). Chemotherapy dose reduction or discontinuation is often required. Cyclin-dependent kinases 4/6 (CDK4/6) regulate cell cycle G1/S transition and can induce a “pharmacological quiescence”. Transient administration of a gut-restricted CDK4/6 inhibitor, prior to chemotherapy may slow/inhibit intestinal stem/epithelial cell cycling and thus, be prophylactic for CID. Methods: OQL051 (OQL), a gut restricted CDK4/6 inhibitor, was studied in MCF7 cells treated with OQL (2x serial dilution, max 10 µM) to measure cell proliferation inhibition. Colo205 cells were treated with OQL 2x serial dilution (25 µM max) to determine the protective effect of OQL on 5-FU. Measurements were performed using Cell Titer -Glo Luminescent cell Viability and caspase 3/7 assay kits. OQL PK was studied in Balb/c mice given OQL, 50 mg/kg intra-gastrically. Blood samples were collected at pre- and 0.25, 0.5, 1, 2, 4, and 6 h post-dosing. Tissues (jejunum/colon) were collected at 0.5, 2, and 6 h after OQL (n = 3/collection). Plasma and tissues were analyzed for OQL by LC-MS. CID (5FU model) was studied in 5 groups of Balb/c mice (n = 5/grp) given OQL vehicle (OQLV) +0.9%NaCl saline (NaCl), OQLV +5FU (175 mg/kg) and OQL+5FU at 3 OQL doses (25, 50, and 100 mg/kg) orally prior to 5FU injection. CID (irinotecan) model) was studied in Balb/c mice given OQL+ Irinotecan at 2 OQL doses (25 and 50 mg/kg, n = 5/ dose) plus IP Irinotecan. OQLV or OQL were given orally prior to IP Irinotecan. Diarrhea and intestine tissue damage were analyzed to evaluate the efficacy. Results: OQL treated MCF7 cells showed conc.-dependent growth inhibition (IC50 0.81 uM). Colo205 cells treated with 5-FU (10 µM) suppressed cell proliferation (60% @ 48 h). Pre-treatment with OQL decreased 5-FU inhibition/apoptosis in a dose-dependent manner. Jejunum and colon OQL conc. were 300x > plasma (AUC 12017, 10515 vs 32 ng·h/g). OQL decreased CID (5FU) grades and protected the intestinal epithelium. On day 6 post-treatment, the OQL group had mice normal (80%) and mild intestinal damage (20%) vs. OQLV group had mice normal (20%), mild intestinal damage (20%), and severe intestinal damage (60%). In the Irinotecan model, OQL showed efficacy similar to the 5FU model. On day 7 post-treatment, OQL had 40% of mice normal and 60% with mild tissue damage (grade 1) vs. OQLV with 0% normal, 40% mild, and 60% with severe intestinal damage. Histology showed intestinal tissues /epithelial cells had less edema, inflammation, and necrosis after OQL vs. OQLV. Conclusions: An oral CDK4/6 inhibitor, OQL051, was restricted to the intestinal lining and reduced 5FU intestinal cell apoptosis, necrosis, and inflammation. In a preclinical model, prophylactically used OQL051 improved not only diarrhea but also intestine damage status which supports the potential for a prophylactic CID treatment.
The effect of aroma lymphatic tressage for lower extremity edema associated with the taxane chemotherapy in patients with breast cancer: A phase 2 clinical trial.
Authors: Kim Ju Won , Ha Yang Sun , Lee Ji Yoon , Yang Jae Hee , Lee Min Jae , Lee Eun Young , You Ji Young , Jung Seung Pil , Park Kyong Hwa
Published: June 2022

e24099

Background: Taxane-associated lower extremity edema is a distinctive adverse effect of taxane, which severely compromise patients’ quality-of-life. Aroma lymphatic tressage (ALT) has been established as a complementary technique that uses a combination of aromatherapy and hand massage to relieve distress and modulate lymphatic drainage in cancer patients. This study aimed to evaluate the symptom-relieving efficacy of a short course ALT on taxane-induced lower extremity edema. Methods: Patients treated with taxane-based chemotherapy for early or advanced stage breast cancer were screened for the study. Patients were enrolled when they presented more than CTCAE G3 of lower-extremity edema. A total of 8 sessions of ALT were applied twice a week for 4 weeks after completing taxane. The primary endpoint was to determine the leg circumference change before and after receiving ALT. Patients’ subjective degree of edema, and quality-of-life were also assessed. Results: A total of 37 patients completed all sessions of planned treatment. All of the participants were female, with the median age of 55.4-years-old. 30.8% of them were premenopausal. The median height of the patients was 157.6cm, median weight was 60.9kg, and median BMI was 1.6kg/m2. Most of the patients received docetaxel (87.2%). The baseline thigh, calf, and ankle circumferences were 56.5cm, 37.4cm, and 22.6cm, each. After 8 sessions of ALT, the median circumferences decreased to 54.7cm, 36.2cm, and 21.9cm. 23 (62.2%) participants experienced a 3% or more reduction in circumference change with a month of ALT. Patients’ subjective degree of edema decreased 56.9% for 4 weeks compared to baseline, while mean body weight decreased from 62.6kg to 61.2kg. All the differences before and after the ALT were statistically significant (p-value < 0.0001) Most of the indicators assessing patients’ quality-of-life improved during the ALT periods, especially physical subscale (from 14.8 to 19.1, p-value < 0.0001). EORTC-QLQ-C30 score also improved from 70.8 to 57.1 (p-value < 0.0001). Conclusions: To our knowledge, this is the first clinical trial to evaluate clinical efficacy of ALT on taxane-associated lower extremity edema. Patients who received ALT after taxane-based chemotherapy presented significant decline of leg circumference and improvement of QoL.
Updated FDA pooled analysis of pain medication use in trial participants with HR+, HER2-negative metastatic breast cancer treated with endocrine therapy and a CDK 4/6 inhibitor.
Authors: Gao Jennifer J , Girvin Andrew , Hodgdon Christine , Osgood Christy , Ison Gwynn , Bhatnagar Vishal , Kluetz Paul Gustav , Pazdur Richard , Amiri-Kordestani Laleh , Beaver Julia A.
Published: June 2022

e24101

Background: Pain medications (PMs) are commonly used to treat pain in patients with advanced or metastatic breast cancer (MBC). We previously reported an initial analysis of PM prescribing patterns in clinical trial participants with breast cancer receiving CDK 4/6 inhibitor (CDKI)-based treatment. We present an updated analysis here. Methods: We pooled data from 7 randomized controlled trials of CDKI + endocrine therapy (ET) in patients with HR+, HER2-negative MBC. All analyzed patients received at least 1 dose of CDKI/placebo+ET and a concomitant PM with a documented start date. Medications administered during hospitalizations were not included. We looked at PM use in all patients, patients who took PM only before or after the trial started, and those who took PM both before and during the trial. PMs were categorized as opioid (includes codeine-containing), NSAIDS, or other (i.e. bone-directed, antiepileptic, topical PMs). Results: 4200 patients enrolled across the 7 trials who received at least one dose of CDKI/placebo+ET (n = 2616 CDKI, n = 1548 placebo). Of these, 2881 took a PM at any time (n = 1774 CDKI, n = 1107 placebo). Of the 1774 patients who received CDKI+ET, 487 (27%) took at least one opioid and one NSAID at any time, 782 (44%) took at least one NSAID at any time but no opioids, 244 (14%) took at least one opioid at any time but no NSAIDs, and 261 (15%) took only PM that were not opioids or NSAIDs. Of the 1107 patients who received placebo+ET, 297 (27%) took at least one opioid and one NSAID at any time, 490 (44%) took at least one NSAID at any time but no opioids, 153 (14%) took at least one opioid at any time but no NSAIDS, and 167 (15%) took only PM that were not opioids or NSAIDs. Of the 2881 patients who took a PM at any time, 2038 patients (n = 1222 CDKI, n = 816 placebo) had documented start for their PM. Of these, 544 took PM only before the trial started (n = 334 CDKI, n = 210 placebo), 915 took a PM only during the trial (n = 551 CDKI, n = 364 placebo), and 579 took a PM both before and during the trial (n = 337 CDKI, n = 242 placebo). Overall, more patients took NSAIDs only compared to opioids only. Patient characteristics at baseline were balanced between the two arms. Conclusions: Overall, PM prescribing patterns were similar between the arms. NSAID use was higher than opiates in all groups. These findings are hypothesis generating and additional research is needed to determine the impact of PM on participants’ pain and physical function. Further research should include an understanding of the duration of PM needed in patients with MBC.
Palliative specialty care availability for adults in community oncology practices.
Authors: Statler Tiffany M. , Dressler Emily Van Meter , Klepin Heidi D. , Weaver Kathryn E. , Gabbard Jennifer
Published: June 2022

e24110

Background: The American Society of Clinical Oncology recommends integration of palliative care in patients with advanced cancer. Studies have shown the availability of palliative care services, especially in outpatient settings, varies widely across practice sites; factors associated with outpatient palliative care clinic availability remain unknown. Our study describes the presence and characteristics of palliative care resources in community oncology practices. Methods: Analyses used data from the 2015 Cancer Care Delivery Research (CCDR) Landscape Assessment of National Cancer Institute Community Oncology Research Program (NCORP) practices (funding support provided by 2UG1CA189824). Oncology practices were surveyed regarding availability of specialty providers and supportive services, including palliative care, as reported by designated CCDR leads. Descriptive statistics describe availability of providers and services, and logistic regression models identify practice characteristics associated with supportive/palliative care specialist availability. Results: 216 non-pediatric exclusive NCORP practice groups were included in analyses. Characteristics are shown in Table. A majority of practices had palliative care specialists (76%), oncology certified nurses (95%), and advance practice providers (80%); 45% had nurse navigators for oncology. 76% of practices had inpatient palliative care consultation services, but only 36% had a dedicated outpatient palliative care clinic. Multivariable analyses demonstrated practices with Medicaid and/or uninsured patient volumes > 25% (Odds Ratio (OR) = 2.5, p = 0.020), more oncology providers (OR = 1.02, p = 0.025), survivorship clinic availability (OR = 2.5, p = 0.005), and who participated in the Quality Oncology Practice Initiative (QOPI) (OR = 2.0, p = 0.039) were significantly more likely to have an outpatient palliative care clinic. Conclusions: Most community oncology practices reported having palliative care specialists, although only a third had a dedicated outpatient palliative care clinic. Newly discovered factors associated with increased odds of having an outpatient palliative care clinic can inform future efforts to expand the availability of outpatient palliative care clinics within community oncology practices.[Table: see text]
Bone-targeting agent utilization among lung cancer patients with bone metastasis in Taiwan.
Authors: Shih Jin-Yuan , Chen Tom Wei-Wu , Lin Hui-Min Diana , Yang Yea-Harn , Chen Wei-Ju , Chan K. Arnold
Published: June 2022

e24111

Background: Bone is a common metastatic site among patients with advanced lung cancer. With new treatments available to improve survival of lung cancer and in all likelihood to change the natural history of disease, the diagnosis and management of bone metastasis (BM) may be of increasing clinical relevance. This study aimed to describe the management of BM using bone targeting agents (BTA) among lung cancer patients in Taiwan. Methods: A retrospective cohort of lung cancer patients with BM from 2004 through 2016 was identified using Taiwan National Health Insurance (NHI) data and Taiwan Cancer Registry. Diagnosis codes of International Classification of Disease 9th revision (ICD-9: 198.5) and ICD-10 (C79.51 and C78.03) were used to define BM. Patients were followed from the time of BM diagnosis till death or the end of study period (2017/12/31). We ascertained demographic information and BTA use among these patients. Two classes of BTAs were included: bisphosphonates (zoledronic acid (ZA), pamidronate, and clodronate) and denosumab. Results: A total of 44,800 patients with lung cancer and incident BM diagnosis were identified during the study period. Median age at the time of BM diagnosis was 67 years (25th and 75th percentile: 57-76), with 58.2% male (n = 26,058). The annual number of lung cancer patients with incident BM increased from 2,814 in 2004 to 3,829 in 2016, while the proportion of these patients receiving any BTA during the follow-up ranged from 25.2% to 34.8% annually. Clodronate and pamidronate were the common BTA prescriptions, whereas denosumab became the most frequently prescribed BTA after reimbursement by NHI since 2015. Among patients who initiated BTA after BM diagnosis (n = 10,879), the median time from BM diagnosis to BTA initiation ranged from 31 to 152 days by initial BTA type. More than half of them received more than one dose (56.3%, n = 6,126), with median numbers of doses received as 3, 4, 6 and 6 for ZA, pamidronate, clodronate and denosumab, respectively. Conclusions: A large population of patients with lung cancer were diagnosed with BM every year. However, overall, we observed only a small proportion of eligible patients receiving a BTA and a delayed initiation of BTA, indicating suboptimal treatment for lung cancer patients with BM in Taiwan.[Table: see text]
Feasibility and acceptability of measuring psychosocial outcomes for primary brain tumor patients and caregivers in a neuro-oncology clinical setting.
Authors: Body Anjelica , Ernster Alayna , Quinones Rebecca , Deleyrolle Phuong , Tran David Dinh , Rahman Maryam , Sampson Deborah , St. Clair Jennifer , Ghiaseddin Ashley Parham , Pereira Deidre B.
Published: June 2022

e24131

Background: A primary brain tumor (PBT) is a distressing diagnosis that impacts the psychosocial well-being of patients and caregivers. Validated questionnaires are useful to assess PBT patient and caregiver psychosocial outcomes. However, it is unknown whether it is feasible to assess these outcomes in a routine clinical setting. This study evaluated the feasibility of assessing psychosocial outcomes for PBT patients and caregivers at the UF Health Neuro-Oncology clinic. Methods: 171 participants (100 PBT patients, 75 with malignant glioma; 71 caregivers) completed a battery of questionnaires to assess psychosocial outcomes during routine clinical appointments. At the end of the battery, a Participant Experience Form (PEF) assessed participant perceptions about the overall experience of completing the battery on a 7-point Likert Scale. Based on criteria from Bowen and colleagues (2009), feasibility and acceptability of assessment procedures were conceptualized and operationalized by assessing: Acceptability (80% of participants will have an average score ≥ 4 on the PEF); Practicality (average time of completion will be < 35 minutes); and Implementation (80% of participants will complete the entire battery). Descriptive statistics were used to assess these outcomes. Results: Patient and caregiver scores of feasibility and acceptability outcomes were as follows: Acceptability (Average PEF score: patients = 5.75 [ SD= 0.95]; caregivers = 5.96 [ SD= 0.83]); Practicality (Average time to complete (minutes): patients = 28.7 [ SD= 11.68]; caregivers = 26.0 [ SD= 12.01]); Implementation (% of participants that completed entire battery: patients = 88.0; caregivers = 84.5). Conclusions: The results indicate that assessing psychosocial outcomes in a routine clinical setting for PBT patients and caregivers was feasible, acceptable, and practical. Future research will use this battery to evaluate longitudinal psychosocial outcomes for this population in a clinical setting.
Exploring the characteristics of dignity loss in patients with cancer in North China.
Authors: Wang Long , Guo Qiaohong , Zuo Jing , Wang Yudong , Feng Li , Zhou Xinliang , Fan Zhisong , Zhang Xue , Han Jing , Liu Jiayin , Li Dan , Hu Xinyan , Liu Wei
Published: June 2022

e24132

Background: Patients with cancer experience different degrees of loss of dignity. Exploring the characteristics of dignity loss for patients with cancer is rare in China, but it is of great significance for patients and their families in the whole anti-cancer trajectory. Methods: Inpatients and outpatients with cancer from the Fourth Hospital of Hebei Medical University were enrolled in this study. The Patient Dignity Inventory(PDI) and EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) was used for measuring patients’ dignity loss and quality of life. Spearman’s correlation analysis was conducted to analyze the correlation factors of dignity loss, and the correlation among dignity loss, quality of life and its dimensions. Results: A total of 403 patients with cancers were included in this study. In terms of loss of dignity, 20 patients (4.96%) didn’t report loss of dignity, 295 patients (73.20%) had mild loss of dignity, 78 (19.35%) had moderate and 10(2.48%) had severe loss of dignity. The three most prevalent PDI problems of patients were “experiencing physically distressing symptoms”(146, 36.23%), “Feeling that I am a burden to others” (126，31.27%) and “worrying about future” (114, 28.29%) . Companionship(r = 0.167, P = 0.001), PS(r = 0.392, P < 0.001), diagnosis to investigation time (r = 0.107, P = 0.031), stage of disease (r = 0.279, P < 0.001), stage of treatment (r = 0.333, P < 0.001), surgery and recurrence (r = 0.158, P = 0.001), anxiety (r = 0.612, P < 0.001), depression (r = 0.603, P < 0.001), psychological distress (r = 0.453, P < 0.001), symptom burden (r = 0.421, P < 0.001) and impact on life (r = 0.450, P < 0.001) were positive correlated with loss of dignity. Age (r = -0.134, P = 0.007), occupation (r = -0.124, P = 0.013) were negative correlated with loss of dignity. Loss of dignity and quality of life are significant correlated with each other. Dignity existential distress showed moderate negative correlation with emotional function (r = -0.513, P < 0.001). Dignity symptom distress showed moderate negative correlation with emotional function (r = -0.675, P < 0.001) and social function (r = -0.515，P < 0.001). Dignity symptom distress showed moderate positive correlation with fatigue symptoms (r = 0.541, P < 0.001). Conclusions: Most cancer patients’ dignity were impaired slightly or moderately in North China. Dignity of cancer patients showed significant association with quality of life. Anxiety and depression were more consistent with dignity than other factors. Improving the quality of life and dignity of patients is vital.
Levering internet-based discussion data from gynecological cancer survivors to inform survivorship care: A mixed methods thematic analysis approach.
Authors: Adams Elizabeth , Tallman David , Haynam Marcy , Nekhlyudov Larissa , Lustberg Maryam B.
Published: June 2022

e24143

Background: Internet and social media platforms offer insight into the experience of survivorship, but the volume of narrative data is often cumbersome for thorough thematic analysis. We present a semi-automated mixed methods approach to analyze web-based discussions and demonstrate its utility on American Cancer Society (ACS) Discussion Board posts from gynecologic cancer survivors. Methods: Posts from the ACS Ovarian Cancer, Uterine Cancer, and Other Gynecological Cancer Discussion Boards were analyzed for psychosocial themes described in the Cancer Survivorship Care Framework. Quantitative analysis was facilitated by verified keywords created for each theme of interest and was completed via custom Python scripts and R packages. Qualitative analysis was expedited by theme keywords and completed on a subset of posts. Results: A total of 125,498 posts made by 6,436 gynecological cancer survivors and caregivers between July 2000 and February 2020 were evaluated. Of all posts, 23,458 were related to psychosocial aspects of survivorship and were analyzed. Quantitative analysis revealed that survivors frequently discussed the role of friends and family in care, fatigue, health insurance issues, and the effect of cancer on loved ones. The most frequently used psychosocial-related words were “family,” “hope,” and “help.” Qualitative analysis demonstrated that survivors frequently discussed coping and caregiver relationships, where survivors sought advice on topics including spousal emotional adjustment, financial toxicity, and confronting mortality. Conclusions: Online platforms offer great opportunity to learn about patient experiences of survivorship care. Candid conversations between survivors may be leveraged to inform survivorship practices and improve future survivorship initiatives. Our novel methodology expedites thematic analysis of such robust narrative data and its translation into survivorship settings.
Automated assessment of illness and treatment understanding (ITU) via the Memorial Sloan Kettering Patient Portal.
Authors: Epstein Andrew S. , Bernal Camila , Romano Danielle R. , Goldberg Jessica , Desai Anjali V. , Nelson Judith Eve
Published: June 2022

e24146

Background: Patient-reported outcome (PRO) technology offers opportunities to address research questions and unmet clinical needs of cancer patients’ ITU. We tested the feasibility of PRO assessment of ITU. Methods: With the same 5-item questionnaire (2 open- [about expectations of cancer outcome and treatment intent] and 3 validated [Weeks JC NEJM 2012] closed-ended items) administered by medical oncology nurses in clinic in a previous pilot (Shin P ASCO 2020), we used the electronic patient portal in our cancer center to elicit responses from all gastrointestinal medical oncology patients scheduled for clinic follow-up. Patients registered on the portal received this questionnaire automatically the day before the second follow-up visit and then quarterly, with a brief explanation that it applied to all patients for quality improvement. Responses were available for review in the electronic health record by all oncology team members, who were offered a 20-minute Zoom introduction to this initiative. Workflow and content of communications about prognosis, treatment intent, and goals of care stayed within clinicians’ discretion. Results: From 5/2021 through 12/2021, 5000 questionnaires were sent to 3852 patients (1-3 times per patient, quarterly), of which all but one was returned, including 3863 with open- and closed-ended responses and 1135 with closed answers only. Patients: 55% male, 83% white, median age 64 (range, 15-96). Most common cancers: colorectal (54%) and pancreatic (21%). In patients with stage data (78%), 35% had stage IV disease. In closed-ended responses, patients receiving treatment (n = 2637 questionnaires) reported that based on the most recent discussions with the oncology team, they thought the treatment was at least a little likely to cure the cancer (66%), prolong life (98%), and/or help with cancer-related problems (92%). Open-ended answers ranged in length from 0-1013 words (median, 6; IQR, 10). Conclusions: Almost all patients in this large, heterogeneous cancer center cohort participated in an automatic assessment system via electronic patient portal addressing questions about their understanding of prognosis and treatment goals. PROs, traditionally focused on symptoms, represent a promising mechanism for scaling structured assessment of patients’ understanding of the prognosis and intent of their treatment. Our future research will address: effects in other cancer types/care settings; temporal changes in sequential responses: associations with clinical factors (e.g., stage, symptoms, treatment, oncologist documentation of prognosis/treatment intent, healthcare delivery and outcomes including patient reports of the quality of clinician communication); open vs. closed-ended questions for assessing ITU; administration in-person vs. via portal; and perspectives of patients and clinicians on our assessment process.
EPIK-B5: A phase III, randomized study of alpelisib (ALP) plus fulvestrant (FUL) in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC) progressing on/after an aromatase inhibitor (AI) with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i).
Authors: De Laurentiis Michelino , Costa Luis , Gligorov Joseph , Knop Ann , Senkus-Konefka Elzbieta , García-Sáenz José A. , Schmid Peter , Heniquez Aurelia , Serra Paolo , Reising Albert , Kuemmel Sherko
Published: June 2022

TPS1109

Background: Endocrine therapy (ET) + CDK4/6i is standard of care for HR+, HER2− ABC; however, CDK4/6i resistance, in which the phosphatidylinositol-3-kinase (PI3K) pathway has a key role, remains challenging. Progression-free survival (PFS) for ≥ 2nd-line ET monotherapy post CDK4/6i is poor; prognosis may be worse in patients with a PI3KCA mutation. ALP (PI3K-α selective inhibitor and degrader) + FUL is approved by the European Medicines Agency (EMA) for HR+, HER2–, PIK3CA-mutated ABC after ET monotherapy. Outside the EMA, ALP + FUL approval includes post-CDK4/6i use. ALP + FUL has shown clinical activity and consistent safety in a small subpopulation in SOLAR-1 with prior CDK4/6i treatment (n = 9) and in BYLieve Cohort A (CDK4/6i + AI as immediate prior treatment; n = 121). The EPIK-B5 study aims to confirm the efficacy and safety of ALP + FUL in a larger population with HR+, HER2–, PIK3CA-mutated ABC with prior CDK4/6i + AI treatment. Methods: EPIK-B5 is a Phase III, randomized (1:1), double-blind, placebo-controlled study assessing the efficacy and safety of ALP (300 mg/d orally starting Cycle 1 Day 1 [C1D1]) + FUL (500 mg intramuscularly on C1D1 and C1D15, and D1 of subsequent cycles) in patients (N ≈ 234) with HR+, HER2–, PIK3CA-mutated ABC progressing on/after CDK4/6i + AI. Patients randomized to placebo + FUL can cross over to ALP + FUL after progression. Randomization is stratified by presence of lung and/or liver metastasis and prior CDK4/6i setting. Adult men or postmenopausal women with confirmed HR+, HER2–, PIK3CA-mutated ABC and ≥ 1 measurable lesion are eligible. The primary endpoint is PFS per blinded independent review committee assessment. Secondary endpoints include overall survival, overall response and clinical benefit rates, duration of and time to response, PFS by PIK3CA-mutation status in circulating tumor DNA, PFS on next-line treatment, time to definitive deterioration of ECOG status, quality of life (QoL), and safety and tolerability. Exploratory endpoints include biomarker analyses, additional QoL endpoints, and time to subsequent chemotherapy. Recruitment is ongoing, with enrollment planned over 2 years in 18 countries; completion of primary data collection is anticipated in 2026. Clinical trial information: NCT05038735; EUDRACT2021-001966-39.
Phase 1 pilot study with dose expansion of chemotherapy in combination with CD40 agonist and Flt3 ligand in metastatic triple-negative breast cancer.
Authors: Reddy Sangeetha M. , Carter Meredith , Chan Isaac , Hullings Melanie , Unni Nisha , Medina Jessica , Shakeel Shahbano , Armstrong Susan , Cade Lakeisha , Fattah Farjana J. , Ahn Chul , Fang Yisheng V. , Chen Nan , McArthur Heather L. , Sinclair Nicole , Yellin Michael Jay , O'Shaughnessy Joyce , Nanda Rita , Conzen Suzanne D. , Arteaga Carlos L.
Published: June 2022

TPS1126

Background: Only a subset of patients with metastatic triple-negative breast cancer demonstrate response to currently approved PD-1 immune checkpoint blockade, and few have durable responses. Antigen presentation defects may be a reason for this low response because deficiency of antigen-presenting DC1 dendritic cells is associated with poor anti-tumor immunity. CD40 agonists are a class of agents that activate antigen presenting cells including dendritic cells and B cells and also repolarize macrophages. Flt3 ligand is a growth factor that increases dendritic cells. In line with this, we recently demonstrated in pre-clinical models that the combination of liposomal-doxorubicin chemotherapy, a CD40 agonist, and a Flt3 ligand improves outcomes of breast cancer compared to alternate combinations. Methods: This is a single arm phase I pilot study of liposomal-doxorubicin, CDX-1140 (CD40 agonist), and CDX-301 (Flt3 ligand) combination therapy in patients with metastatic or unresectable locally advanced metastatic triple-negative breast cancer. Patients will be randomized to 3 lead-in arms (triplet therapy, doublet immunotherapy only, liposomal-doxorubicin only) prior to receiving full triplet therapy with fresh tissue biopsies before and after the lead-in treatment. CDX-301 will be discontinued after 2 cycles; liposomal-doxorubicin and CDX-1140 will be continued until disease progression or clinically limiting toxicities. Primary endpoint is determination of a recommended phase 2 dose based on treatment-related adverse events including dose-limiting toxicities. Secondary endpoints include anti-tumor immune response after triplet therapy, after immunotherapy alone, and after liposomal-doxorubicin alone; median progression-free survival, overall response rate, duration of response, and clinical benefit rate. Key eligibility criteria are unresectable stage III or stage IV triple-negative breast cancer (ER ≤10%, PR ≤10%, HER2/neu negative), 1st to 3rd line metastatic treatment setting (1st line patients need to be PD-L1 negative by 22C3 assay), measurable disease by RECIST 1.1 criteria, consent for pre-treatment and on-treatment biopsies of amenable soft tissue tumor lesions, no prior treatment with an anti-CD40 antibody or a Flt3 ligand, no anthracycline treatment in the metastatic setting, no prior progression while on anthracycline-based therapy or within 6 months of completing neoadjuvant chemotherapy, and no history of non-infectious pneumonitis or current pneumonitis. This trial will enroll up to 45 patients across multiple sites. Clinical trial information: NCT05029999.
A randomized, placebo-controlled, phase 2 trial of INBRX-109 in unresectable or metastatic conventional chondrosarcoma.
Authors: Chawla Sant P. , Wasp Garrett Thomas , Shepard Dale Randall , Blay Jean-Yves , Jones Robin Lewis , Stacchiotti Silvia , Reichardt Peter , Gelderblom Hans , Martin-Broto Javier , Eckelman Brendan , Darling Michelle , Andrianov Vasily , Conley Anthony Paul
Published: June 2022

TPS11582

Background: Chondrosarcomas (CS) are the third most common type of primary bone cancer after myeloma and osteosarcoma. Conventional CS represent 85–90% of all cases and are typically treated with surgical resection. However, there are no approved systemic treatment options for patients with unresectable or metastatic conventional CS, and outcomes remain poor. INBRX-109 is a precision-engineered, tetravalent death receptor 5 (DR5) agonist antibody designed to overcome the limitations of earlier-generation agonists and exploit the tumor-specific cell death induced by DR5 activation. DR5 is one of two pro-apoptotic receptors for the trimeric tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Early clinical activity of INBRX-109 was observed in an ongoing phase 1 trial and warrants further investigation. INBRX-109 has been granted an FDA fast-track designation for conventional CS. Methods: This is a multicenter, randomized, blinded, placebo-controlled phase 2 study in patients with unresectable or metastatic conventional CS, measurable disease by RECIST 1.1, and radiologic disease progression within 6 months prior to screening. Any number of prior lines of therapy are allowed, except for prior DR5 agonists. Patients must be ≥18 years of age and have an ECOG performance status of 0/1 and have archival or fresh tissue available. Approximately 201 patients will be randomized (2:1) to INBRX-109 (3 mg/kg intravenously, every 21 days) or placebo, stratified by histologic grade (Grade 1/2 vs 3), isocitrate dehydrogenase (IDH)1 R132/IDH2 R172 status (wildtype vs mutation), and line of systemic therapy (none vs prior). Treatment will continue until disease progression/unacceptable toxicity. Patients treated with a placebo will have the option to cross over to INBRX-109 upon disease progression. The primary endpoint is progression-free survival (PFS) by independent radiology review. Secondary endpoints are overall survival, PFS by investigator assessment, quality of life, overall response rate, duration of response, disease control rate, safety, pharmacokinetics, and immunogenicity. Adverse events will be recorded and graded by NCI CTCAE Version 5.0. Median PFS of 7.0 months is projected for INBRX-109 and 4.0 months for placebo (corresponding hazard ratio of 0.571); INBRX-109 will be declared superior if the 1-sided p-value from the stratified log-rank test is <0.025. More than 50 sites are planned across the US/Europe. The study is actively enrolling. Clinical trial information: NCT04950075.
Phase 1/2 study of devimistat in combination with hydroxychloroquine (HCQ) in patients with relapsed or refractory (R/R) clear cell sarcoma (CCS).
Authors: Agulnik Mark , Davis Elizabeth J. , Albert Catherine M. , Davis Lara E. , Pardee Timothy S. , Chugh Rashmi , Trucco Matteo M.
Published: June 2022

TPS11595

Background: CCS of the soft tissues is a rare and aggressive subtype of sarcoma that often starts in the tendons of the arms or legs. It is molecularly characterized by t(12;22)(q13;q12) translocation, resulting in EWSR1-ATF1 or EWSR1-CREB1 gene fusion. Despite reports of occasional responses to systemic therapies, currently available therapies have shown limited efficacy in advanced CCS. Therefore, there is a significant unmet medical need for more active agents in CCS. Devimistat is a stable intermediate of a lipoate analog that inhibits pyruvate dehydrogenase and α-ketoglutarate dehydrogenase enzymes of the tricarboxylic acid (TCA) cycle preferentially within the mitochondria of cancer cells. Devimistat induces autophagy in cancer cells. In a metastatic mouse model of CCS, treatment with devimistat in combination with chloroquine significantly suppressed tumor growth (Egawa et al, 2018). Based on this data, we hypothesized that inhibition of autophagy with HCQ may sensitize cancer cells to devimistat with increased efficacy and acceptable toxicity. Given its expected synergy, we have initiated a single-arm phase I/II prospective, multicenter, open-label, non-randomized study to evaluate maximally tolerated dose (MTD), safety, and efficacy of devimistat in combination with HCQ in patients with R/R CCS. Methods: In the phase 1 portion of the study, patients with R/R CCS and other fusion-positive R/R sarcomas will be enrolled and a standard 3+3 design will be followed to evaluate toxicity, MTD, and recommended phase 2 dose. There will be two patient groups based on weight, and dose escalation will be conducted separately for each group. Starting dose of HCQ will be 5mg/kg PO BID for patients < 45 kg and 200 mg PO BID for patients ≥45 kg on days 1 through 5 of every 28 days. The first dose of HCQ each day will be followed 2 hours later by 1,000 mg/m2 devimistat (for patients < 45 kg) and 2,000 mg/m2 of devimistat (for patients ≥ 45 kg) administered over 2 hours. A maximum of 36 patients will be enrolled for the phase I portion, 18 for each patient group. In the phase 2 portion of the study, only relapsed or refractory CCS patients will be enrolled, and the response rate will be determined using RECIST 1.1. In phase 2, pharmacokinetics, duration of response, clinical benefit rate, progression-free survival, overall survival, safety, and patient-reported outcomes will also be assessed. This portion of the study will utilize Simon’s admissible two-stage design with 29 patients. This study started enrolling participants in November 2021 and has dosed six patients to date. The first two dose-escalation cohorts for patients ≥45 kg have been completed without DLT and the third dose level will be opening shortly. Clinical trial information: NCT04593758.
A randomized phase III clinical trial of yoga for chemotherapy-induced peripheral neuropathy treatment.
Authors: Han Katherine , Dooley Andee , Piulson Lauren , Seluzicki Christina , Zhi Wanqing Iris , Bao Ting
Published: June 2022

TPS12146

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, painful, and debilitating side effect of many standard chemotherapy regimens. Patients with CIPN typically experience pain, paresthesia, and muscle weakness, and may exhibit significant functional decline and worsened quality of life. Our prior study showed more than half of breast cancer survivors experience persistent CIPN up to a mean duration of 5.6 years, which is associated with a doubled fall risk. Identifying nonpharmacological approaches to reduce CIPN symptoms and improve cancer survivors’ outcomes is urgently needed. Yoga is a meditative movement therapy that that includes stretching, and flexibility and balance training. Our pilot study (NCT03292328) demonstrated that yoga reduced CIPN-related symptoms, and improved quality of life and functional reach scores compared to waitlist control. We hypothesize that yoga can reduce CIPN symptoms, improve function, and reduce the risk of falls. Methods: We are conducting a three-arm randomized education and usual care-controlled trial in cancer survivors with chronic CIPN pain at Memorial Sloan Kettering Cancer Center (MSK), New York, NY. Participants in the intervention arm will receive twice-weekly one-hour Hatha yoga classes virtually or in-person taught by MSK instructors, and practice yoga at home daily for eight weeks. Participants in the education control arm will receive one-hour virtual education classes twice per week taught by an MSK mind-body therapist for eight weeks. Participants in the usual care arm will continue their usual care for CIPN for eight weeks. The primary endpoint is the Brief Pain Inventory-Short Form (BPI-SF) average pain item at weeks 8 and 24. Secondary outcomes include the Neuropathic Pain Scale (NPS), Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health outcome measure, Brief Fatigue Inventory (BFI), Insomnia Severity Index (ISI), Hospital Anxiety and Depression Scale (HADS), QLQ-CIPN-20, Functional Assessments, and quantitative sensory testing (QST) at weeks 0, 4, 8, 12, 18, and 24. Eligibility criteria included: 1) Moderate-to-severe CIPN pain, defined by a score of 4 or greater on a 0-10 numerical rating scale; 2) completion of neurotoxic chemotherapy at least three months prior; 3) no changes in anti-neuropathy medications within three months of enrollment; and 4) changes in balance and functionality. We have accrued five participants as of February 2022 with a total accrual target of 268 participants. We anticipate completing accrual in March 2025. Funding resource: NIH R01CA251470. Clinical trial information: NCT05121558.