bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase 1b study of avelumab plus DCC-3014, a potent and selective inhibitor of colony stimulating factor 1 receptor (CSF1R), in patients with advanced high-grade sarcoma.
Authors: Rosenbaum Evan , Movva Sujana , Kelly Ciara Marie , Dickson Mark Andrew , Keohan Mary Louise , Gounder Mrinal M. , Thornton Katherine Anne , Chi Ping , Chan Jason Earl , Nacev Benjamin , Avutu Viswatej , Biniakewitz Matthew , McKennan Olivia Robin , Phelan Haley , Perez Silvia , Hwang Sinchun , Singer Samuel , Qin Li-Xuan , Tap William D. , D'Angelo Sandra P.
Published: June 2021

11549

Background: Select sarcomas are infiltrated with immunosuppressive myeloid cells. DCC-3014 is an inhibitor of the CSF1R kinase that decreases tumor infiltrating myeloid cells in preclinical models. We hypothesized that DCC-3014 combined with the anti-PDL1 inhibitor avelumab would be safe and tolerable, decrease immunosuppressive myeloid cells, and increase cytotoxic T cells. Methods: This investigator initiated, open label, single center, phase I study of DCC-3014 plus avelumab in patients (pts) with unresectable or metastatic sarcoma utilized a standard 3+3 dose escalation design. DCC-3014 was administered on days 1-3 (loading dose of 20, 30, or 50 mg) followed by oral daily maintenance (10, 14, or 20 mg) in 28-day cycles; 800 mg of IV avelumab was administered q2weeks. The primary endpoint was to determine the recommended phase 2 dose (RP2D). Secondary endpoints defined the adverse event (AE) profile and assessed clinical efficacy. Peripheral blood CD14+Lin-HLA-DRlo myeloid-derived suppressor cells (MDSCs) were measured by flow cytometry. Results: 13 pts were treated; median age was 61 (range 32 – 71), 8 were female, and median prior lines of therapy was 5 (range 2 – 10). Histologic subtypes included leiomyosarcoma (LMS, n = 7), undifferentiated pleomorphic sarcoma (2), dedifferentiated liposarcoma (LPS, 2), synovial sarcoma (1), and pleomorphic LPS (1). The Table lists treatment-related AEs (TRAEs) of any grade (G) occurring in ≥ 10% of pts and all G ≥ 3 TRAEs, sorted by frequency. All pts had at least 1 TRAE. Seven pts (54%) had a G ≥ 3 TRAE. Most TRAEs were either G ≤ 2 or expected on-target effects of CSF1R inhibition. 1 of 6 pts on the highest dose level had a dose limiting toxicity (G4 elevated AST with abdominal pain) that resolved with treatment cessation. The highest dose level was declared the RP2D. Best objective response by RECIST 1.1 was stable disease in 3 pts; 2 had LMS and were treated at the highest dose level. At baseline, the mean proportion of monocytes in peripheral blood samples with an MDSC phenotype was 12.2% (range 7.1 – 19.9). 5 of 7 pts with serial blood samples had decreased circulating MDSCs (mean decrease of 26.9% from baseline to last time point). Conclusions: DCC-3014 combined with avelumab was safe and tolerable. Study therapy decreased circulating MDSCs in select patients; T cell analyses will be reported. Study expansion at the RP2D is ongoing. Clinical trial information: NCT04242238. [Table: see text]
Health concerns in long-term survivors with ovarian cancer: Results of Expression VI–Carolin meets HANNA–Holistic Analysis of Long-term survival with Ovarian Cancer—The international NOGGO, ENGOT and GCIG survey.
Authors: Woopen Hannah , Keller Maren , Braicu Ioana , Zocholl Dario , Baum Joanna , Krabisch Petra , Boxler Tamara , Wimberger Pauline , Madroñal Catarina , Gil-Martin Marta , Bjelic-Radisic Vesna , Trpchevski Sinisha , Samartzis Eleftherios Pierre , Heinzelmann-Schwarz Viola A. , Achimaș-Cadariu Patriciu , Kubelac Paul , Vardar Mehmet Ali , Jedryka Marcin Andrzej , Vergote Ignace , Sehouli Jalid
Published: June 2021

12023

Background: So-called long-term survivors (LTS) may be cured from cancer but still experience a wide range of long-term side effects. Aim was to analyze the main concerns in long-term survival to improve follow-up care. Methods: Within the study “Carolin meets HANNA” (www.carolinmeetshanna.com) long-term survivors with ovarian cancer (LTS) were recruited since 11/2016. Long-term survival was defined as an ovarian cancer diagnosis more than five years ago. Results: Until 02/2021 1,044 long-term survivors with ovarian cancer could be recruited. Median survival time at recruitment was 11 years (range 5-43 years). More than half had been diagnosed with advanced stage ovarian cancer (58.6% FIGO III/IV). Almost half have developed recurrent disease (43.4%). 26.0% were under cancer treatment at recruitment. Health status was rated very good or good by 52.0% while 20.3% report a bad or very bad health status. Almost half of the LTS have current concerns/long-term side effects (46.1%). Main concerns are fatigue (23.9%), pain (21.6%), polyneuropathy (16.9%), gastrointestinal symptoms (16.6%) and memory problems (15.5%). 42.8% still regard themselves as cancer patients. Health status and distress did not differ between LTS 5-10 years after diagnosis and > 10 years after diagnosis (p = 0.59 and p = 0.0843 respectively). Patients with a history of recurrence and those under current treatment had a worse health status and more health concerns. LTS without recurrence reported fatigue in 18.4%, pain in 19.2%, polyneuropathy in 13.1%, gastrointestinal problems in 13.4% and memory problems in 14.4%. Fatigue, polyneuropathy, nausea and concentration problems improve with the time of survival. However, fatigue is still present in 21.1% after ten years survival time. There was no significant difference in pain between 5-10 (20.1%) and > 10 years (22.0%) survival time. In this cohort 94.2% receive regular follow-up care including CA125 testing in 77.0%, clinical examination in 54.3%, transvaginal ultrasound in 55.1%, abdominal ultrasound in 43.9%, mammogram in 50.5% and further radiological examinations such as CT scans in 53.4%. Conclusions: Follow-up care in ovarian cancer is usually delivered within the first five years after diagnosis. However, our analyses show the high frequency of health concerns in LTS despite the high frequency of follow-up care in this cohort. Therefore, specialized survivorship care should be offered beyond the typical five years of follow-up care with a focus on long-term side effects.
Prognostic understanding, hospitalization, and hospice use among older patients with advanced cancer.
Authors: Loh Kah Poh , Seplaki Christopher , Yousefi Nooraie Reza , Lund Jennifer Leigh , Epstein Ronald M. , Duberstein Paul , Flannery Marie Anne , Culakova Eva , Xu Huiwen , Klepin Heidi D. , Lin Po-Ju , Sanapala Chandrika , Watson Erin , Targia Valerie , Vogelzang Nicholas J. , Dib Elie G. , Onitilo Adedayo A. , Mustian Karen Michelle , Mohile Supriya Gupta
Published: June 2021

12037

Background: Poor prognostic understanding of curability is associated with lower hospice use in patients with advanced cancer. Little is known if this holds true for older adults specifically. In addition, prognostic understanding are variably assessed and defined in prior studies. We evaluated the associations of poor prognostic understanding and patient-oncologist discordance in both curability and survival estimates with hospitalization and hospice use in older patients with advanced cancer. Methods: We utilized data from a national geriatric assessment cluster-randomized trial (URCC 13070: PI Mohile) that recruited 541 patients aged ≥70 with incurable solid tumor or lymphoma considering any line of cancer treatment and their oncologists. At enrollment, patients and oncologists were asked about their beliefs about cancer curability (options: 100%, > 50%, 50/50, < 50%, 0%, and uncertain) and estimates of patient’s survival (options: 0-6 months, 7-12 months, 1-2 years, 2-5 years, and > 5 years). Non-0% options were considered poor understanding of curability (uncertain was removed from the analysis) and > 5 years was considered poor understanding of survival estimates. Any difference in response options was considered discordant. We used generalized estimating equations to estimate adjusted odds ratios (AOR) assessing associations of poor prognostic understanding and discordance with hospitalization and hospice use at 6 months, adjusting for covariates and practice clusters. Results: Poor prognostic understanding of curability and survival estimates occurred in 59% (206/348) and 41% (205/496) of patients, respectively. Approximately 60% (202/336) and 72% (356/492) of patient-oncologist dyads were discordant in curability and survival estimates, respectively. In the first 6 months after enrollment, 24% were hospitalized and 15% utilized hospice. Poor prognostic understanding of survival estimates was associated with lower odds of hospice use (AOR 0.30, 95% CI 0.16-0.59) (Table). Discordance in survival estimates was associated with greater odds of hospitalization (AOR 1.64, 95% CI 1.01-2.66). Conclusions: Prognostic understanding may be associated with hospitalization or hospice use depending on how patients were queried about their prognosis and whether oncologists’ estimates were considered.[Table: see text]
Pre-existing geriatric conditions in older adults with poor prognosis cancers.
Authors: Tsang Mazie , Gan Siqi , Wong Melisa L. , Walter Louise Christie , Smith Alexander K.
Published: June 2021

12044

Background: Older adults with poor prognosis cancers are more likely to experience toxicity from cancer-directed therapies. Although geriatric assessment (GA) reduces chemotherapy toxicity by detecting pre-existing conditions, GA can be difficult for oncologists to perform because of limited time and resources. We aim to determine the prevalence of pre-existing geriatric conditions that could be detected if GA were performed during routine oncology care. Methods: We used the Health and Retirement Study (HRS) linked with Medicare (1998-2016) to identify adults age >65 with poor prognosis cancers (median overall survival < 1 year). The HRS is a biennial nationally representative survey that asks about pre-existing geriatric conditions. Using the interview prior to the cancer diagnosis, we determined the presence of conditions included in GA: functional status (i.e. difficulty with climbing stairs, walking one block, getting up from a chair, bathing or showering, taking medications, and managing money), falls and injurious falls, unintentional weight loss, self-rated health, social support, mentation, advanced care planning, use of pain or sleep medications, and mobility. To identify groups with the highest prevalence of pre-existing geriatric conditions, we stratified results by age (adjusted for gender) and gender (adjusted for age). Results: Our study included 2,121 participants. At the time of cancer diagnosis, mean age was 76, 51% were female, 79% were non-Hispanic White, 26% had lung cancer, 14% had a GI cancer, and 60% had other metastatic cancers. Mean time between the HRS interview and cancer diagnosis was 12.7 months. The median overall survival of the entire cohort was 9.6 months with a 45% 1-year survival rate. The adjusted prevalence of pre-existing geriatric concerns were as follows: 65% had difficulty with climbing several flights of stairs, 27% had difficulty with walking one block, 47% had difficulty getting up from a chair after sitting down, 12% had difficulty in bathing or showering, 6% had difficulty taking medications, 11% had difficulty in managing money, 35% had a fall in the last 2 years with 12% of participants reporting injury after their fall. Those who were aged 85+, vs those aged 65-74, had higher rates of conditions indicative of cognitive impairment (e.g. 12 vs 4% had difficulty taking medications, p = 0.000, 26% vs 6% had difficulty managing money, p = 0.000) and physical impairments (e.g. 54% vs 30% had falls, respectively, p = 0.000). Rates of geriatric conditions indicative of physical impairment were higher in women vs men (e.g. 72% vs 58% had difficulty climbing stairs, p = 0.000 and 52% vs 41% had difficulty getting up from a chair, p = 0.000). Conclusions: Patients with poor prognosis cancers have high rates of pre-existing geriatric conditions that can be detected by GA. Geriatric assessments could find important impairments that could be addressed prior to cancer therapy to reduce adverse effects.
Complementary and alternative medicine use among cancer patients at two cancer centers in Brazil.
Authors: Ricardo Eliza Dalsasso , Oishi Denise , Uchiyama Angel Ayumi Tome , Marchon da Silva Catarina , Bravo Espinoza Josué , Moreira Frederico Rafael , Dos Santos Marcelo Oliveira , Riechelmann Rachel Pimenta , D'Alpino Renata D'Alpino
Published: June 2021

12060

Background: Complementary and alternative medicine (CAM) use is relatively common among cancer patients. Data regarding CAM use in Brazil is scarce. We sought to define CAM use among cancer patients and investigate factors that might influence it. Methods: We conducted a cross-sectional survey of adults diagnosed with any cancer type who came to appointments at two cancer centers in Brazil from January 2020 to January 2021. Unadjusted and adjusted analyses were conducted by using Logistic Regression models to determine the association of covariates with binary outcome. Statistical analyses were performed with SAS 9.4 (SAS Institute Inc, Cary, NC). All tests were 2-sided, and P < 0.05 was considered significant. Results: In total, 319 patients who consented to the face-to-face interview were included and all of them completed the questionnaires. Most patients (52.4%) were between 51 and 70 years-old, 59,6% were female, 85,2% were from the private service and 67% had college graduate/baccalaureate. Most cancer types were from gastrointestinal tract (31,4%), breast (20.4%), lung (12.3%) and genitourinary type. More than 85% of the participants were on any active cancer treatment. The prevalence of current CAM use was 34.2% and 50.2% of the patients did not believe CAM has anti-cancer properties. Two-thirds of the participants have never discussed about CAM with their oncologists. Only 4.1% of the respondents would abandon conventional cancer treatment in order to use just CAM. Among CAM users, 55% referred multiple therapies use. Of those therapies, spiritual surgery was the most prevalent one. There was a significant higher proportion of females reporting CAM use (p = 0,008) as well as a higher proportion of CAM use among private patients (p = 0,008). Conclusions: CAM use was common among our study population, especially spiritual surgery. Women and private patients were more prone to use CAM. Although most patients would not abandon conventional treatment, many of them have never discussed about CAM with their oncologists.
Overall and cardiac-specific mortality following serious cardiovascular events in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Bottinor Wendy , Im Cindy , Armenian Saro , Hong Borah , Howell Rebecca M. , Ness Kirsten K. , Oeffinger Kevin C. , Armstrong Gregory T. , Yasui Yutaka , Chow Eric Jessen
Published: June 2021

12073

Background: The direct impact of a major cardiovascular (CV) event on mortality among childhood cancer survivors is not well described. We hypothesized that mortality following a major CV event would be higher among survivors compared with siblings and that mortality would be influenced by primary cancer treatment. Methods: The CCSS cohort has conducted longitudinal follow-up of 25,658 survivors of childhood cancer and 5,051 siblings. All-cause and CV-cause specific mortality after a first event of heart failure (HF), coronary artery disease (CAD), or stroke occurring at least 5 years after cancer diagnosis, was estimated using the Kaplan-Meier method. The relative hazards (HR) and 95% confidence intervals (CI) between survivors and siblings as well as the influence of demographic (sex, age, race/ethnicity) and cancer treatment factors were estimated via Cox regression. Results: In total, 1780 survivors and 91 siblings experienced a serious CV event. Total deaths included 706 survivors (271 cardiac causes, 381 non-cardiac causes, 54 unknown causes) and 14 siblings. Survivors were a median age of 31.5 years (range 6.5-61.5) and 20.0 years (range 5.0-44.6) since cancer diagnosis at time of CV event. After a CV event, estimated 10- and 20-y all-cause mortality was significantly higher among survivors than siblings (Table). The HR for all-cause mortality was significantly higher among survivors than siblings after HF (HR 5.2, CI 2.1-13.0), CAD (HR 4.2, CI 2.0-9.0), and stroke (HR 4.6, CI 1.5-14.6). HF and stroke-specific mortality were not significantly increased among survivors versus siblings, in contrast to CAD-specific mortality (HR 3.5, CI 1.1-11.0). Among survivors, heart dose from radiotherapy (per 10 Gy) was associated with increased all-cause and cause-specific mortality after HF (HR 1.2, CI 1.0-1.3; HR 1.3, CI 1.0-1.7), all-cause mortality after CAD (HR 1.2, CI 1.0-1.3), and cause-specific mortality after stroke (HR 2.5, CI 1.2-4.9). Brain dose from radiotherapy was associated with increased all-cause mortality (HR 1.1, CI, 1.0-1.2, per 10 Gy) after stroke. Anthracycline dose was not associated with increased overall or cause-specific mortality risk after a CV event. Conclusions: After a CV event, mortality is higher among survivors than siblings. In survivors, mortality is primarily driven by non-cardiac causes. CAD and prior radiotherapy exposure to the heart and brain also influenced mortality.[Table: see text]
Association of cancer treatment with excess heart age among young breast cancer survivors.
Authors: Vo Jacqueline B , Rosenberg Shoshana M. , Poorvu Philip Daniel , Ruddy Kathryn Jean , Tamimi Rulla , Peppercorn Jeffrey M. , Schapira Lidia , Borges Virginia F. , Come Steven E. , Nohria Anju , Partridge Ann H.
Published: June 2021

12081

Background: Young women with breast cancer may be at increased risk for premature development of cardiovascular disease (CVD) in part due to their cancer treatment. Limited data are available on CVD risk among young breast cancer survivors. Methods: Women aged 30-40 years at diagnosis with stage 0-III breast cancer enrolled in a prospective cohort study of women diagnosed with breast cancer at ≤40 were eligible for inclusion in this analysis. Data were obtained from serial surveys and electronic medical records at breast cancer diagnosis and 5-year follow-up. We calculated “excess heart age,” which incorporates a CVD risk-based score (calculated using age, systolic blood pressure, blood pressure medication, diabetes, smoking, body mass index) to estimate the difference in years between an individual’s chronological age and their CVD-risk adjusted age. Multivariable logistic regression models (adjusting for age at diagnosis, stage, and race) were fitted to evaluate associations between treatment (radiation, endocrine therapy, anthracyclines, and trastuzumab) and having a change in excess heart age ≥2 years from baseline to 5 years. Results: Among 372 young breast cancer survivors, mean age at diagnosis was 36.6 (SD 2.89), 93% were white, and 79% were diagnosed with stage I or II breast cancer. Mean excess heart age was.32 (SD: 6.16) years at baseline, which declined to -.07 (SD 6.64) at 5-year follow-up (p=.17). At 5 years, 31% (n=114) of women experienced an increase of at least 2 years in their excess heart age since diagnosis, and their mean excess heart age was 4.34 years (range -9 to 30). In multivariable analyses, receipt of trastuzumab was associated with higher odds (OR: 1.68, 95% CI: 1.02-2.77) of experiencing an increase of ≥2 years in excess heart age between diagnosis and 5 years of follow-up. Endocrine therapy, anthracyclines, and radiation were not significantly associated with a change in excess heart age of ≥2 years at 5 years post-diagnosis. Conclusions: At 5 years post-diagnosis, approximately 1/3 of young breast cancer survivors experienced a change from baseline in their excess heart age of ≥2 years. Further research is warranted to confirm findings regarding trastuzumab and excess heart age, and potential effects on longer-term cardiac outcomes in this population. Extended follow-up of this cohort may further quantify CVD risk over time.[Table: see text]
The PROVIEW+ tool: Developing and validating a tool to predict risk of poor performance status and severe symptoms in cancer patients over time.
Authors: Seow Hsien , Sutradhar Rinku , Barbera Lisa Catherine , Tanuseputro Peter , Guthrie Dawn , Isenberg Sarina , Juergens Rosalyn A. , Myers Jeffrey A. , Brouwers Melissa C. , Tibebu Semra , Earle Craig
Published: June 2021

12095

Background: There are numerous predictive cancer tools that focus on survival. However, no tools predict risk of low performance status or severe symptoms, which are important for patient decision-making and early integration of palliative care. The aim of this study was to develop and validate a model for all cancer types that predicts the risk for having low performance status and severe symptoms. Methods: A retrospective, population-based, predictive study using linked administrative data from cancer patients from 2008-2015 in Ontario, Canada. Patients were randomly selected for model derivation (60%) and validation (40%). The derivation cohort was used to develop a multivariable logistic regression model to predict the risk of having the reported outcomes in the subsequent 6 months. Model performance was assessed using discrimination and calibration plots. The main outcome was low performance status using the Palliative Performance Scale. Secondary outcomes included severe pain, dyspnea, well-being, and depression using the Edmonton Symptom Assessment System. Outcomes were recalculated after each of 4 annual survivor marks. Results: We identified 255,494 cancer patients (57% female; median age of 64; common cancers were breast (24%) and lung (13%)). At diagnosis, the risk of having low performance status, severe pain, well-being, dyspnea, and depression in 6-months is 1%, 3%, 6%, 13% and 4%, respectively for the reference case (i.e. male, lung cancer, stage I, no symptoms). Generally these covariates increased the outcome risk by > 10% across all models: obstructive lung disease, dementia, diabetes; radiation treatment; hospital admission; high pain; depression; Palliative Performance Scale score of 60-10; issues with appetite; or homecare. Model discrimination was high across all models. Conclusions: The model accurately predicted changing cancer risk for low performance status and severe symptoms over time. Providing accurate predictions of future performance status and symptom severity can support decision-making and earlier initiation of palliative care, even alongside disease modifying therapies.
Efficacy of olanzapine combined with the standard triplet antiemetic therapy for cisplatin-based chemotherapy: A sub-analysis of a randomized, double-blind, placebo-controlled trial (J-FORCE).
Authors: Fujita Yukiyoshi , Abe Masakazu , Yamaguchi Takuhiro , Ueda Hiroki , Kitagawa Koichi , Okamura Jun , Hirano Katsuya , Sakata Yukio , Iihara Hirotoshi , Shimada Yasuhiro , Aoyama Takeshi , Shibata Kazuhiko , Hori Kensuke , Daga Haruko , Nakayama Toshiaki , Sakata Yasuhiko , Zenda Sadamoto , Hashimoto Hironobu
Published: June 2021

12098

Background: In a randomized, double-blind, placebo-controlled trial (J-FORCE), we previously reported the efficacy of olanzapine (OLZ) 5 mg plus triplet antiemetic therapy for cisplatin (CDDP)-based chemotherapy-induced nausea and vomiting (CINV) in the delayed phase (24–120 h after CDDP treatment). Here, we report the results of a pre-planned subgroup analysis of this trial (in which risk factors were used as the allocation factors). This analysis was designed to determine which patients benefit more from OLZ. Methods: Subgroup analysis was performed on complete response (CR: no emesis and no rescue medication) in the acute (within 24 h of CDDP treatment) and delayed phase and time to treatment failure (TTF: time from CDDP treatment to the first vomiting or use of rescue medication). Data from 705 patients in the efficacy analysis population (354 in the OLZ group and 351 in the placebo (PLA) group) were analyzed by sex (male/female), age (≥55 years/ < 55 years), and CDDP dose (≥70 mg/m2/ < 70 mg/m2). For CR, we calculated point estimates of differences between groups and 95% confidence intervals and performed a Mantel-Haenszel test. We used the Kaplan-Meier method for the analysis of TTF, and comparisons between groups were made using a log-rank test. Results: Delayed CR (OLZ versus PLA) and risk difference (RD) of delayed CR following OLZ treatment were significantly greater than following PLA in the following subgroups: male (83.1% versus 70.5%, RD 12.6%, p = 0.001), female (70.9% versus 56.4%, RD 14.5%, p = 0.021), age ≥55 years (78.7% versus 67.6%, RD 11.1%, p = 0.003), age < 55 years (81.0% versus 57.4%, RD 23.6%, p = 0.005), and CDDP ≥70 mg/m2 (78.8% versus 65.3%, RD 13.5%, p < 0.001). TTF of all subgroups (male/female, ≥55 years/ < 55 years, and ≥70 mg/m2/ < 70 mg/m2) was significantly longer in the OLZ group than in the PLA group (HR 0.493, p < 0.001; HR 0.612, p = 0.022; HR 0.586, p < 0.001; HR 0.401, p = 0.005; HR 0.546, p < 0.001; HR 0.543, p = 0.031, respectively). Conclusions: Our results suggest a benefit of OLZ 5 mg plus triplet therapy regardless of risk factors for CDDP-based CINV. Clinical trial information: UMIN000024676. [Table: see text]
Immune cell counts and perceived cognitive impairment before and after chemotherapy among 544 women with breast cancer.
Authors: Belcher Elizabeth , Gilmore Nikesha , Kehoe Lee , Kleckner Ian , Kleckner Amber , Gudina Abdi , Hardy Sara , Xu Huiwen , Hopkins Judith O. , Janelsins Michelle Christine
Published: June 2021

12114

Background: In a nationwide prospective study, we found that patients with breast cancer had greater perceived cognitive impairment (PCI) before and after chemotherapy compared to controls without cancer. To gain further insight into the role that inflammation plays in cognitive function, we evaluated relationships between immune cell counts and lymphocyte:monocyte ratio with PCI at pre- and post- chemotherapy. Methods: Data were collected as part of longitudinal cohort study conducted through the National Cancer Institute Community Oncology Research Program network (NCT01382082). Self-reported PCI was scored at pre-chemotherapy (0-7 days before first chemotherapy) and post-chemotherapy (0-30 days after last chemotherapy) from the PCI sub-scale of the Functional Assessment of Cancer Therapy: Cognitive Function (possible score range 0-72). Immune cell counts were measured by complete blood count with differential at pre- and post- chemotherapy. Lymphocyte:monocyte ratio (LMR) was calculated. Separate linear regression models evaluated the association of immune cell counts and LMR with 1) pre-chemotherapy PCI and 2) post-chemotherapy PCI. Models were adjusted for age, cognitive reserve (reading score), anxiety, and depression. Results: PCI and immune cell data were available for 544 patients at pre-chemotherapy and 532 at post-chemotherapy. Subjects had a mean age of 53.1 (SD=10.8). At pre-chemotherapy, higher basophil count and higher LMR were significantly associated with worse PCI (β=5.73, SE=2.37, p<0.05; β=0.047, SE=0.02, p<0.05, respectively). Higher basophil count and higher LMR were also significantly associated with worse PCI at post-chemotherapy (β=5.84, SE=2.92, p<0.05; β=1.01, SE=0.48, p<0.05). Conclusions: These data support the hypothesis that inflammation is associated with perceived cognitive function before and after chemotherapy in adults with breast cancer. Targeting inflammatory processes may be beneficial for reducing cancer-related cognitive impairment. Funding: NCI UG1CA289961, T32CA102618, R01CA231014, DP2CA195765.
Associations between patient-centered communication and quality of life in patients with ovarian cancer.
Authors: Pozzar Rachel A. , Xiong Niya , Hong Fangxin , Wright Alexi A. , Goff Barbara Ann , Tulsky James A. , Underhill-Blazey Meghan , Hammer Marilyn J. , Berry Donna Lynn
Published: June 2021

12120

Background: Patient-centered communication (PCC) occurs when clinicians respond to patients’ needs, preferences, concerns, and emotions. The National Cancer Institute (NCI) Framework for PCC in Cancer Care highlights the potential of PCC to improve health-related quality of life (HRQoL), but to date few studies have empirically examined associations between PCC and HRQoL in patients with ovarian cancer. We assessed associations between perceived PCC and HRQoL in patients with ovarian cancer. Methods: Cross-sectional, descriptive survey of English-speaking adults with ovarian cancer recruited both online and from one NCI-designated cancer center. We assessed perceived PCC with the Patient-Centered Communication in Cancer Care (PCC-Ca)-36 and HRQoL with the Functional Assessment of Cancer Therapy: General (FACT-G). We used simple linear regression to identify univariate associations between participant characteristics, PCC-Ca-36 total, FACT-G total, and FACT-G subscale (physical, social and family, emotional, and functional well-being) scores. We identified significant predictors of FACT-G total and subscale scores by entering variables associated with each outcome at p ≤ 0.25 into a multiple linear regression model and using backward elimination. Results: One hundred seventy-six participants completed the survey. In multivariable analyses, older age, working (vs. not working), no current treatment (vs. any current treatment), and greater perceived PCC were associated with better overall HRQoL. Working and no current treatment were associated with better physical well-being. Older age, not being cared for by a gynecologic oncologist (vs. being cared for by a gynecologic oncologist), and greater perceived PCC were associated with better social and family well-being. Older age, being recruited online (vs. in clinic), and greater perceived PCC were associated with better emotional well-being. Older age, working, rural residence (vs. not), no current treatment, and greater perceived PCC were associated with better functional well-being (all p ≤ 0.05). Conclusions: Greater perceived PCC was significantly associated with better overall HRQoL and better social, emotional, and functional well-being in this cross-sectional study of patients with ovarian cancer. The NCI Framework for PCC in Cancer Care posits that PCC promotes HRQoL by strengthening the therapeutic alliance, enhancing social support, and improving patient knowledge. Although PCC is theorized to promote patient self-management, PCC was not significantly associated with physical well-being in this sample. Future research should (a) identify mediators of the associations between PCC and HRQoL; (b) examine inter-individual variability in characteristics that may compromise HRQoL; (c) and examine associations between PCC and HRQoL over time.
The association between the coronavirus disease 2019 (COVID-19) pandemic and quality of life and depression symptoms in patients with advanced lung cancer.
Authors: Heuer Lauren , Post Kathryn Elizabeth , Gallagher Emily R. , Trotter Chardria , Elyze Madeleine , Vyas Charu , Plotke Rachel , Greer Joseph A. , Temel Jennifer S. , El-Jawahri Areej
Published: June 2021

12122

Background: It is unclear whether patients with cancer experience greater distress as a result of the COVID-19 pandemic. Thus, we assessed the relationship of the COVID-19 pandemic with quality of life (QOL) and depression symptoms in patients newly diagnosed with advanced lung cancer. Methods: We conducted a cross-sectional study of patients with advanced lung cancer enrolled in two multisite randomized supportive care trials. We enrolled adult patients within 12 weeks of diagnosis of advanced lung cancer and an Eastern Cooperative Oncology Group (ECOG) Performance Status from 0 to 3 across 23 institutions in the United States. At the time of enrollment, participants completed the Functional Assessment of Cancer Therapy-Lung (FACT-L), which includes four wellbeing subscales (i.e., physical, social, emotional, and functional) as well as lung cancer symptoms, and the Patient Health Questionnaire-9 (PHQ-9) to assess their QOL and depression symptoms, respectively. We compared QOL and depression symptoms between participants enrolled prior to COVID-19 (i.e., those enrolled in the following time periods: March 2018 to January 2019 and March 2019 to January 2020) and during the COVID-19 pandemic (March 2020 to January 2021). We used linear regression models adjusting for age, race, gender, and time since diagnosis of advanced cancer to examine the relationship between the period of enrollment and patients’ QOL and depression symptoms. Results: A total of 860 patients were included in this analysis (665 participants enrolled prior to COVID-19 and 195 participants during COVID-19). The two cohorts did not differ significantly with respect to baseline demographic factors [Mean age 65.4 (SD = 11.4), 51.9% female]. In multivariate regression models, enrollment during COVID-19 was not associated with physical (B = -0.16, SE = 0.52, P = 0.763), social (B = -0.48, SE = 0.39, P = 0.217), emotional (B = -0.16, SE = 0.41, P = 0.693), functional (B = -0.83, SE = 0.55, P = 0.128) wellbeing, or lung cancer symptoms (B = -0.11, SE = 0.44, P = 0.806). Enrollment during COVID-19 was not associated with overall QOL (FACT-L: B = -1.32, SE = 1.69, P = 0.436) or depression symptoms (PHQ-9: B = -0.02, SE = 0.45, P = 0.973). Conclusions: Despite the prevailing belief that COVID-19 has negatively impacted QOL and distress in patients with cancer, we found no differences in QOL or depression symptoms in patients newly diagnosed with advanced lung cancer during the COVID-19 pandemic compared to those diagnosed prior to the pandemic. These findings suggest that factors other than the COVID-19 pandemic, such as patients’ experience with their cancer, contribute to their QOL and depression symptoms.
The surgical oncology clinical trial landscape: A cross-sectional analysis of ClinicalTrials.gov from 2008-2020.
Authors: Perera Nirosha D. , Turner Brandon E. , Shen Jolie Z. , Wong Bonnie O. , Litt Henry K. , Stavins MaKenna A. , Bellomo Tiffany R. , Saleki Massoud , Bell Alexander , Ionescu Ruxandra , Shyu Margaret , Wang Max M. , Tao Jacqueline , Sarsour Nadeen , O'Keefe Ryan M , Takasugi Jordan M. , Steinberg Jecca R. , King Roderick , Mahipal Amit , Wren Sherry M.
Published: June 2021

1561

Background: Surgical interventions are studied less often than medical or radiation interventions in oncology clinical trials. We characterized surgical oncology trials registered on ClinicalTrials.gov, analyzed funding sources and identified features associated with early discontinuation and results reporting. Methods: We employed a cross-sectional study design with descriptive, logistic regression, cox regression, time series and survival analyses. We downloaded all 270,172 studies registered on the Aggregate Analysis of the ClinicalTrials.gov database from October 1, 2008 to March 9, 2020. After excluding non-interventional trials, applying cancer/oncology specific Medical Subject Heading terms to the remaining trials and excluding phase 1 trials, 27,915 trials were identified for manual review. Primary exposure variables were trial focus: neoplasia site and treatment modality (surgical interventions included investigations of outcomes from surgical resection or intra-operative/peri-operative changes), and funding: industry, U.S. government, academic. Results: 26,815 trials were found to have true oncology content; 1,661 (6.2%) involved surgical oncology, representing 311,789 patients. Funding sources were: 82.7% by academic institutions, 10.9% by industry, and 6.2% by U.S. government. The most studied neoplasia sites were colorectal (17.4% of trials), breast (10.7%), gastric (10.5%), hepatic (8.6%), lung (7.5%), brain/CNS (6.7%) and cervical (6.6%). U.S. government funded surgical oncology trials had the lowest risk of early discontinuation (adjusted HR 0.50, 95% CI: 0.26-0.99, p<0.047) and the highest odds of results reporting (adjusted OR 1.08, 95% CI: 0.55-2.11, p=0.83) (Table 1). Conclusions: There is a paucity of surgical oncology clinical trials compared to other treatment modalities, especially in context of surgery’s role in overall cancer care. From 2008-2020 only 6.2% of trials focused on surgical oncology, and U.S. government funded trials displayed the lowest hazard of early discontinuation and highest odds of results reporting. Stakeholders should look to government funded trials as models of improvement, but must increase representation and results dissemination of surgical oncology trials to guide treatment recommendations. Surgical oncology trial features and associated early discontinuation/results reporting. [Table: see text]
The TIME Trial Network to facilitate rapid clinical trial activation, patient screening, and enrollment in molecularly targeted trials.
Authors: OLeary Stephanie , Shulman Megan , Ritt Kevin , Degele Meghan , Protomastro Ewelina , Clauson Jennifer , Franzen Amy , Anderson Ian Churchill , Barve Minal A. , Oubre David N. , Priego Victor , Saverimuthu Angela , Senecal Francis Mark , Vaddepally Raju Kumar , Blackwell Kimberly L. , Cooney Matthew M.
Published: June 2021

1563

Background: Clinical trials that require patients to have specific actionable mutations based on next generation sequencing (NGS) present unique problems, such as recruiting patients with rare mutations, low enrollment rates, and distance between patients and trial sites. Such barriers can slow the pace of trial enrollment and delay the development of new therapeutic options. Methods: Tempus Labs has partnered with experienced research sites and pharmaceutical companies with molecularly targeted clinical trials to create the TIME Trial Network. The study portfolio includes pharmaceutical sponsored phase I-III clinical trials across solid tumors and hematological malignancies, targeting actionable mutations. This network was established to ensure rapid just-in-time (JIT) activation of trials by streamlining start-up activities (i.e., execution of CTAs and study budgets/financial exhibits, regulatory paperwork, SIV planning and conduct, drug and study supply shipments, submission to the central IRB, and sponsor-specific requirements). Rapid activation begins upon receipt of an activation form from a site partner. “Site Activated” describes a site that has fulfilled all regulatory, documentation, contracting requirements, and has sponsor approval to screen and enroll patients. Results: In Q4 2020, JIT activations were completed for 6 unique interventional clinical trials across 10 sites in 8 US states in the TIME Trial Network. On average, sites were activated in 9.4 business days. Patients enrolled had rare NGS mutations and were from geographically diverse locations. In one urgent case, trial activation, patient consent, screening, and treatment were achieved in 5 business days. In total, 91.7% of patients consented to trial. The average timeline from activation to consent was 4.5 days (range 0 - 24 days), with half of patients consenting within 1 business day. 45.5% of patients who consented to trial received the study drug within 1 day of consent; 2 patients dosed on day of consent. Conclusions: Over a 3-month period, on average, TIME Trial sites were activated in 9.4 days (compared to the 20+ week industry-wide average), and patient consent was completed in 4.5 days. Rapid JIT activations through the TIME program provide significant improvements in trial enrollment timelines and increase access to therapies nationwide. JIT activations may be especially useful for rural, underserved communities, as sites can enroll diverse patient populations and help address the equity gap in clinical trials across ethnic groups.[Table: see text]
Implementing virtual mind-body programming to support cancer patients during COVID-19.
Authors: Mao Jun J. J. , Hung Kin Wai (Tony) , Emard Nicholas , Polubriaginof Fernanda C. G. , Lynch Kathleen , Atkinson Thomas Michael , Trevino Kelly Marie , Jensen Claus
Published: June 2021

1585

Background: Despite growing evidence of mind-body therapies for physical and psychological health among patients with cancer, their access remains limited. The COVID-19 pandemic has further disrupted the delivery of necessary cancer and supportive care; thus, the need to support patients with cancer is unprecedented. To expand the reach and access of mind-body therapies, we developed, implemented, and evaluated a novel virtual mind-body program for patients with cancer. Methods: We rapidly developed a 7-day a week virtual mind-body program, Integrative Medicine at Home (IM@Home), for patients with cancer (ages ≥18 years) and deployed it on April 1st, 2020. IM@Home included mind-body group therapy classes in fitness, meditation, yoga, dance, tai chi, and music delivered using Zoom video conferencing. Classes ranged from 30-45 minutes and were led by an integrative medicine clinician. Patients had the option to register for a 1-month, 3-month, or 6-month membership to gain unlimited access to all virtual mind-body classes. Multi-method evaluation was conducted using the RE-AIM conceptual framework to guide surveys and qualitative interviews. Surveys were analyzed using descriptive statistics and interviews were analyzed using grounded theory. Results: Between April 2020 and January 2021, IM@Home registered over 32,000 class participants, with a weekly average attendance of 700-800 participants. In a 4-month post-deployment survey (n = 131), nearly all participants were satisfied with IM@Home (93.9%) and would recommend the program to friends and family (95.4%). A majority of participants also found IM@Home to be simple to use (87.0%) and said the program had a variety of classes that interested them (93.1%). Three-quarters of participants (74.8%) were taking 3 to 7 classes a week (range: 1 to 15 classes), among which the most popular classes were fitness (88.7%), chair yoga (37.1%), and tai chi (33.1%). Most participants preferred a 3-month membership (51.6%), followed by a 6-month membership (19.5%). In qualitative interviews (n = 30), participants reported IM@Home helped them to: 1) maintain structured routines and stay motivated to exercise; 2) cope with COVID-19-related and cancer-related stressors; and 3) connect with their fellow cancer patient community and foster social relationships during a time of isolation. Conclusions: Virtual mind-body programming, through IM@Home, reached many patients with cancer to address their physical and psychological challenges during COVID-19. As patients with cancer experience high physical and psychological symptom burden following diagnosis, future clinical trials are needed to evaluate the specific effects of IM@Home when integrated into active treatment and survivorship care.
ALK inhibitors for treatment of adult-onset neuroblastoma.
Authors: Stiefel Jessica , Kushner Brian H. , Basu Ellen M. , Roberts Stephen S. , Modak Shakeel
Published: June 2021

2001

Background: Neuroblastoma (NB), a rare malignancy of the sympathetic nervous system, is a tumor of early childhood with > 90% of cases diagnosed before 5 years of age. Adult-onset NB (AON) is extremely rare and differs significantly from childhood disease. AON, while more indolent, is usually metastatic at diagnosis, generally chemotherapy-resistant, and almost invariably lethal. Additionally, standard therapies for NB such as dose-intensive chemotherapy and anti-GD2 antibody are poorly tolerated by adults. Prior studies have shown AON is enriched for genomic aberrations especially ALK (Suzuki et al 2018). Although ALK inhibitors (ALKi) are effective for therapy of lymphoma and non-small cell lung cancer, their use in AON has not previously been reported. Methods: Retrospective review of patients > 18 years old at diagnosis seen at Memorial Sloan Kettering Cancer Center (MSKCC) was performed after IRB approval. Response to ALKi was evaluated using International Neuroblastoma Response Criteria; objective responses were also noted. Progression-free (PFS) and overall survival (OS) was calculated using Kaplan-Meier methods. Results: Since 1979, 52 patients with AON were seen at MSKCC. Of 23 patients evaluated, 14 (61%), harbored somatic ALK mutations. Seven were treated with FDA-approved ALKi. One patient initially diagnosed at 12 years of age was treated with ALKi following a relapse 15 years later. Overall, all ALKi were well-tolerated; reported adverse events included grade 1-2 nausea and vomiting (n = 6), and neurologic symptoms including hallucinations, drowsiness, and dizziness (n = 1 patient each) which resolved after stopping ALKi. Four patients received > 1 ALKi either due to progressive disease or intolerance. Most patients responded to the first ALKi with objective though partial response (n = 5) while one had progressive disease (PD). Median time to progression for initial ALKi was 15.5 months (10-45). One patient with no evaluable disease after four prior relapses was treated with alectinib for 36 months without PD. Of the patients treated with a second ALKi (n = 4), 1 had CR and 2 had PR after not having progressed previously, while the other had stable disease. Median OS from beginning treatment with first ALKi was 46.5 (17-74) months. Conclusions: AON is a rare disease which is a therapeutic challenge. Enrichment of ALK mutations permits consideration of targeted therapy. ALKi were well tolerated, often associated with significant responses, and treatment with serial ALKi led to ongoing benefit. Given this, ALKi should be considered for treatment in future AON cases.
Targeted agents recommended by the CNS TAP tool compared to those selected by a tumor board in a molecularly-driven clinical trial in children and young adults with DIPG.
Authors: Roberts Holly , Ravi Karthik , Kline Cassie , Mueller Sabine , Koschmann Carl Johannes , Marini Bernard , Franson Andrea
Published: June 2021

2048

Background: Genetic sequencing of diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG) biopsy specimens has revealed genomic heterogeneity, fueling an interest in individualized, targeted treatment options. The Pacific Pediatric Neuro-Oncology Consortium recently completed a feasibility study PNOC003: Molecular Profiling for Individualized Treatment Plan for DIPG (NCT02274987), in which a multidisciplinary tumor board recommended targeted agents based on the molecular and genetic profiling of each patient’s tumor. Separately, our group developed a numeric scoring tool of targeted anticancer agents, the Central Nervous System Targeted Agent Prediction (CNS TAP) tool, which combines pre-clinical, clinical, and CNS penetration data with patient-specific genomic information to generate a numeric score for each agent to objectively evaluate these targeted therapies for use in patients with CNS tumors. We hypothesized that highly-scored agents within the CNS-TAP tool would overlap, at least in part, with the agents recommended by the molecular tumor board in PNOC003. Methods: For each study participant (n=28), a retrospective analysis was completed, utilizing the genomic report to identify actionable genetic alterations and to input patient-specific data into CNS TAP to identify the highest scoring agents. We compared high-scoring agents within the CNS TAP tool with recommendations from the PNOC003 tumor board for each of the enrolled 28 patients. Results: Overall, 93% (26/28) of patients had at least one agent recommended by both the tumor board and CNS TAP. Additionally, 39% (37/95) of all agents recommended by the tumor board were also selected by CNS TAP, with additional analysis ongoing. Conclusions: There was significant overlap between the highest-scoring and selected agents via CNS TAP compared with those chose by the molecular tumor board. Through this work, we also identified factors that likely contributed to the discordance in choice of targeted therapies. Without clinician input, the CNS TAP tool is unable to account for drug-drug interactions, includes only designated anticancer agents, and cannot easily be updated in real time, requiring extensive manual literature review for each included agent. However, CNS TAP provides an objective evaluation of targeted therapies, in contrast to inherently subjective recommendations of a tumor board. Given the discordance identified between these methods and the strengths of each, a prospective study incorporating both CNS TAP and a molecular tumor board for targeted therapy selection in patients with high grade glioma is warranted.