bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase 1b study of unesbulin (PTC596) plus dacarbazine for the treatment of patients with locally recurrent, unresectable, or metastatic relapsed/refractory leiomyosarcoma.
Authors: Van Tine Brian Andrew , Ingham Matthew , Attia Steven , Meyer Christian Frederick , Baird John , D'Silva Dhiren , O'Keefe Kylie , Maliakal Pius , Wahba Mona M. , Weetall Marla , Schwartz Gary K.
Published: June 2022

11507

Background: Leiomyosarcoma (LMS) is one of the most common subtypes of soft tissue sarcoma and is associated with high risk of relapse and a poor prognosis for advanced disease. In preclinical LMS models, unesbulin, a microtubule polymerization inhibitor, potentiated the activity of dacarbazine (DTIC) (Jernigan F, et al. Mol Cancer Ther. 2021;20:1846–1857). Here, we report preliminary safety and efficacy results from a Phase 1b dose escalation study evaluating the combination of unesbulin with DTIC in patients with advanced LMS (NCT03761095). Methods: In this single-arm, open-label, Phase 1b clinical trial, patients with advanced LMS received unesbulin orally at 200, 300, or 400 mg twice weekly (BIW) in combination with intravenous DTIC at 1,000 mg/m2 once every 21 days. The primary objectives were to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of unesbulin in combination with DTIC and to characterize the safety profile of the combination. The time-to-event continual reassessment model (TITE-CRM) was used for dose finding. An expansion cohort with up to 12 additional patients is currently being enrolled. Results: As of the data cutoff on January 6, 2022, 29 LMS patients have been treated. Median prior lines of therapy were 3 (range 1–6). Of 27 evaluable patients, 12 had non-uterine and 15 had uterine LMS. The MTD/RP2D of unesbulin was determined to be 300 mg BIW with DTIC 1,000 mg/m2 every 21 days using the TITE-CRM. At the RP2D, the most common treatment-related adverse events included fatigue, diarrhea, neutropenia, and thrombocytopenia. In the intent-to-treat population, the overall response rate (ORR) was 17.2% (5/29) and the disease control rate (DCR) (DCR = complete response + partial response + stable disease at 12 weeks) was 58.6%. At the 300 mg dose level, the ORR was 19% (4/21) and the DCR was 57.1%. Patients received a median of four cycles (range 1–12). The study is ongoing, with patients continuing to receive treatment. Conclusions: Unesbulin 300 mg BIW in combination with DTIC 1,000 mg/m2 every 21 days was well tolerated and demonstrated promising efficacy in a heavily pre-treated patient population with advanced LMS; these results support further investigation. Updated clinical results will be presented as the data mature. A randomized, placebo-controlled, Phase 2/3 trial is planned. Clinical trial information: NCT03761095.
Spine high-grade osteosarcoma in the era of radiotherapy with high-energy charged particles: A single institution retrospective analysis.
Authors: Evangelisti Gisberto , Falzetti Luigi , Palmerini Emanuela , Cianchetti Marco , Schwab Joseph H. , Boriani Stefano , Ibrahim Toni , Gasbarrini Alessandro
Published: June 2022

11532

Background: Limited are data on high-grade osteosarcoma occurring in the spine. Wide resection is recommended, but it is a difficult and high morbidity procedure in the spine. High-energy particle therapy has been recently used. The goal of this study was to examine treatment and outcome of patients with osteosarcoma in the mobile spine. Methods: Spine high grade osteosarcoma patients who underwent surgery at the Rizzoli Institute between 2009 and 2020 were identified. Treatment, outcome, and prognostic factors in patients treated in a single institution were examined. Results: Characteristics of the 20 patients (8 female; 12 male) included: median age, 39.7 years (range, 14-71 years), 5 (25%) with tumors in the cervical spine, 6 (30%) with tumors in the thoracic spine, and 9 with tumors in the lumbar spine (45%); 14 (70%) patients with localized disease and 6 (30%) with metastatic disease at the time of presentation. Nineteen patients (95%) underwent chemotherapy, the majority were treated with MAP (methotrexate, doxorubicin, cisplatin) regimen. In 12 patients undergoing preoperative chemotherapy (n = 11) or chemotherapy and radiotherapy (n = 1), the median tumor % necrosis was 20 (IQR 20 - 40), with none achieving a good histologic response (> 90%). All patients underwent surgery. Adequate surgical margins were achieved in 5 patients (25%). In patients with positive margins, radiotherapy was administered to 8 (40%) patients. Four patients with positive margins after resection received photon neoadjuvant or adjuvant therapy. Four patients received high-energy particles as adjuvant therapy after planned gross total excision. The median overall survival rate was 10.5 months (IQR 5.8 - 15.0) for patients with metastatic disease and 25.5 months (IQR 8.3 - 46.0) for patients with localized disease (P =.0501). Patients treated with planned intralesional gross total resection followed by adjuvant high-energy particle therapy had a significant higher disease-specific survival than patients with positive margins after resection with or without additional conventional radiotherapy (P =.023). Conclusions: Metastatic disease, is a poor prognostic factor for high grade osteosarcoma of the spine. Post-operative high-energy particle therapy improved overall survival in patients undergoing a planned gross total resection compared to intralesional resection in this series. Chemotherapy induced necrosis was low underscoring the need of more aggressive multidisciplinary approaches for these patients.
Regorafenib third-lined therapy in advanced GISTs: A single center analysis based on different genotypes.
Authors: Chen Sile , Xia Yanzhe , Yang Shaohua , Qian Yan , Zhai Ertao , Huang Shaoqing , Shi Yihang , He Yulong , Cai Shirong , Zhang Xinhua
Published: June 2022

11537

Background: The relationship between primary and secondary mutational status and efficacy of regorafenib in third-line therapy on GISTs is yet clear. Methods: From Jun 2017 to Dec 2021, a total of 62 patients with advanced GIST refractory to imatinib and/or sunitinib were enrolled in this study from the First Affiliated Hospital, Sun Yat-sen University. Results: Primary mutational was most common in KIT exon 11(40/62, 64.5%), followed by exon 9 (19.4%), exon 17 (4.8%). Six cases (9.7%) belonged to SDH deficiency and one case (1.6%) was NF1-associated GISTs. Before receiving treatment of regorafenib, specimens obtaining for secondary mutations were as follows: 39 cases from surgery，12 from core-needle biopsy; ctDNA alone was performed in 9 cases and 2 patients refused to secondary mutational test. Excluding 6 patients with SDH deficiency, 14 patients (25.8%) had mutations in exon 11+13, 15 (27.7%) in exon 11+17, 7 (13.0%) in exon 9+17, 4 (7.4%) in exon 11+13+17. Exon 11 + 18, exon 11 + 13 + 18, exon 11 + 13 + 17 + 18, exon 9 + 16, exon 11 + 17 + 18 and NF-1 were found in 1 case, respectively (1.9%). Eight (14.7%) patients with primary KIT mutation were not detected any secondary mutation（2nd-not-detected）. There was no complete response, 4 of partial response (4/54, 7.4%), 27 of stable disease (50.0%). Progression disease was seen in 23 patients (42.6%) and 8 were not applicable (no assessable lesion) to imaging response assessment due to R0/1 surgery before using regorafenib. The median follow-up time was 19.0 months. The median progression-free survival (mPFS) was 5.4 months (0.2-29.1 months) and the median overall survival (mOS) was 20.3 months (0.2-37.0 months). For primary mutation analysis, it was found that SDH-deficient patients had longer mPFS (29.1 months) than those with mutations in exon 9 or exon 11 (5.4 and 4.8 months, respectively; P= 0.013). In terms of secondary mutations, patients with activation loop mutations (exon 17+18) showed both longer mPFS (7.3 months vs 1.9 months, P= 0.001) and longer mOS (20.3 months vs 7.7 months, P= 0.059) than those patients with non-activation loop mutations. Not any specific or new adverse reaction was found in all patients. By Cox-regression analysis, response to regorafenib and mutational status were independent predictors of PFS，response to regorafenib was also an independent predictor of OS. Conclusions: Regorafenib seems to have better treatment efficacy in GIST patients with SDH deficiency compared to those with primary KIT mutations, and better with secondary mutations in activation loop than those with non-activation loop mutations. It is necessary to carry out clinical research for later-line treatment choice based on different genotypes for imatinib-resistant GISTs.
Interruption of imatinib in advanced gastrointestinal stromal tumor after prolonged imatinib maintenance in the absence of gross tumor lesions.
Authors: Kang Yoon-Koo , Kim Hyung-Don , Kim Hyun Jin , Park Young Soo , Beck Moyeol , Ryu Min-Hee
Published: June 2022

11539

Background: Although current guidelines recommend indefinite imatinib treatment in advanced gastrointestinal stromal tumor (GIST) patients, prolonged imatinib treatment is often challenging. Imatinib-refractory progression-free survival (PFS) and overall survival were reportedly not different between those who interrupted imatinib and those did not. Methods: Clinical outcomes of 77 consecutive patients with recurrent or metastatic GIST who interrupted imatinib treatment after maintaining around 5 years of imatinib treatment in the absence of gross tumor lesions were retrospectively analyzed. Association between clinical factors and progression-free survival (PFS) following imatinib interruption was analyzed. Results: Median time from the absence of gross tumor lesions to imatinib interruption was 61.5 months (range 41.4–122.7 months). Since imatinib interruption, median PFS was 19.6 months, and the PFS rate at 60 months was 26.3%. Among patients who had progressive disease following interruption, imatinib re-introduction led to 88.6% objective response rate and 100% disease control rate, with the median imatinib-refractory PFS since re-introduction of 112.4 months. Complete removal of initial gross tumor lesion(s) (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.12–0.81, P = 0.016) and complete removal of residual gross tumor lesion(s) (HR 0.45, 95% CI 0.21–0.94, P = 0.033) by local treatment (vs. no local treatment or residual lesions after local treatment) were independently associated with favorable PFS. Conclusions: Interruption of imatinib may be considered with close surveillance in selected patients who maintained years of imatinib treatment in the absence of gross tumor lesions, especially for those who had complete removal of gross tumor lesions by local treatment.
Excess of blood TNFa-R as a sign of recurrence of G1 soft tissue sarcomas in older men and G3 soft tissue sarcomas in older women.
Authors: Kaplieva Irina V. , Sagatelyan Susan A. , Frantsiyants Elena M. , Vashchenko Larisa N. , Goroshinskaya Irina A. , Ausheva Tatiana V. , Chernogorov Pavel V. , Pogorelova Yulia A. , Sheiko Elena A. , Nemashkalova Ludmila A. , Gusareva Marina A. , Serdyukova Elizaveta V. , Bykadorova Oksana V. , Atmachidi Dmitriy P. , Maslov Andrey A. , Kit Oleg I.
Published: June 2022

11556

Background: Tumor necrosis factor alpha (TNFa) and its receptor (TNFa-R) play an important role in tumor genesis. However, their involvement in the recurrence of sarcomas is poorly studied. The purpose of this study was to analyze levels of TNFa and TNFa-R in the blood of patients with recurrent soft tissue sarcomas. Methods: The study included 64 male and female patients, mean age 63.4±5.2 years. Main groups included patients with recurrent G1 and G3 soft tissue sarcomas T2bN0M0; comparison groups included patients with primary G1 and G3 soft tissue sarcomas T2bN0M0. 95% of tumors were liposarcomas, with solitary rhabdamyosarcomas, myxofibrosarcomas, epithelioid and undifferentiated sarcomas. All recurrent patients had previously underwent surgical and radiation treatment for primary sarcomas and their relapses (up to 2 episodes), with the last surgery more than 1 year ago. Control groups (n = 10 each) included healthy donors of similar age. Levels of TNFa and TNFa-R were measured in the blood serum by ELISA before the treatment. Results: No significant differences were found between TNFa levels in patients with primary and recurrent soft tissue sarcomas and in donors. Levels of TNFa-R in men with primary G3 sarcomas were 1.5 times (p < 0.05) higher compared with donors, 1.7 times (p < 0.05) higher than in men with primary G1 sarcomas, and 1.3 times (p < 0.05) higher than in women with primary G3 sarcomas. TNFa-R increased by 1.7 times (p < 0.05) in all men with recurrent sarcomas regardless of the tumor grade, compared with the levels in healthy men; however, in G1 it was 1.9 times (p < 0.05) higher than in men with primary G1 sarcomas, while in G3 it did not differ significantly from the levels in men with primary G3 sarcomas. TNFa-R in women increased only in recurrent G3 sarcomas by 2.5 times compared to healthy women. No differences were observed in TNFa-R levels between men and women with recurrent G3 sarcomas. Conclusions: An excess of TNFa-R in the blood is characteristic for the recurrent soft tissue sarcomas G1 in older men and G3 in older women. At the same time, high grade tumors in men are accompanied by an increase in TNFa-R in the blood in both primary and recurrent sarcomas.
Synergistic activity of PARP inhibitors (PARPi) in combination with standard chemotherapy (CTx) in leiomyosarcoma.
Authors: Vornicova Olga , Babichev Yael , Al-awar Rima , Marcellus Richard , Abdul Razak Albiruni Ryan , Gladdy Rebecca Anne
Published: June 2022

11560

Background: Leiomyosarcomas (LMS) are genetically heterogeneous tumors that arise from smooth muscle. Currently, the mainstay of systemic treatment for patients with advanced/metastatic disease is doxorubicin (Dox) based CTx. Several genomic analyses of LMS reveal defects in homologous recombination (HR) DNA repair pathway in about half of patients, consistent with a druggable “BRCAness” phenotype. Thus, we sought to determine which combinations of standard CTx and PARPi might be synergistic promising therapeutic strategies for LMS. Methods: Dox, Docetaxel (Doc), Temozolomide (Tmz) were evaluated in combination with PARPi (Olaparib [Ola], Niraparib [Nira] and Talazoparib [Tala]) at 12 different drug concentrations. Four LMS cell lines of different origins (gynecological - GY, abdominal - A, extremity - E) were tested in a high throughput manner. All drug concentrations were chosen according to EC50. Cells were incubated with each combination for 7 days. Viability was assessed by ATPlite Luminescence Assay System.Evaluation of drug combination effect was performed using a Bliss synergy score. This system quantifies the degree of synergy as multiplicative effect of single drugs as if they acted independently. With a synergy score of -5 to 5, the interaction between two drugs is considered as additive; <-5 antagonistic and > 5 synergistic, and therefore a promising combination. Results: Anticancer activity, ranging from additive to synergistic was seen with all combinations. Results were consistent among all cell lines, independent of site of cell line origin (Table) Most synergistic combination in the majority of LMS cell lines were Dox or Tmz when combined with Tala, reaching up to 15 % and 27% above Bliss respectively. In contrast, Doc showed only additive effect with all analyzed PARPi. Conclusions: The data suggest that the combination of Dox or Tmz with PARPi may represent promising treatment options for LMS patients. Recent clinical studies support this notion in uterine LMS. Importantly these results suggest that such approach may be extended to all sites of LMS. Pre-clinical studies are underway to identify the most promising combinations for future clinical trial design. [Table: see text]
Five-year results of a phase 2 trial using ipilimumab (I), nivolumab (N), and trabectedin (T) for previously untreated advanced soft tissue sarcoma (NCT03138161).
Authors: Gordon Erlinda Maria , Chawla Sant P. , Chua-Alcala Victoria S. , Kim Ted T. , Adnan Noufil , Sekhon Simranjit , Angel Nicole , Fernando Mitchel , Brigham Don Arlen , Quon Doris V. , Moradkhani Ania , Wong Steve
Published: June 2022

11573

Background: Understanding the bifunctional role that the immune system plays in tumor eradication vs growth promotion is critical in the design and timing of tumoricidal and immunologic therapies for sarcomas. Hypothesis: Immune checkpoint inhibitors that promote sustained T cell activation would be most effective when given as first line therapy, together with a tumoricidal agent. Methods: Eligible patients for this Phase 2 study are males or females ≥ 18 years of age with locally advanced unresectable or metastatic soft tissue sarcoma, previously untreated, with measurable disease by RECIST v1.1. Treatment protocol: (I) mg/kg i.v. q 12 wks, (N) 3 mg/kg i.v. q 2 wks, (T) 1.2 mg/m2 CIV q 3 wks. Treatment Outcome Parameters: (1) Best objective response rate by RECIST v1.1, (2) Progression-free survival (PFS), (3) Overall survival (OS), and (4) Incidence of treatment-related adverse events. Results: Ninety-nine patients were enrolled. Efficacy analysis (n = 88): There were 8CR (1 surgical CR), 11PR, 58SD, 11PD. Overall response rate was 21.6%, Disease Control Rate, 87.5%. The median PFS was 7 (range:1-44) months, median OS, 14 (range: 1-46) months. Grade 3 TRAEs include fatigue (n = 8), adrenal insufficiency (n = 1), dehydration (n = 1), hyponatremia (n = 2), increased AST (n = 8), increased ALT (n = 24), increased ALP (n = 2), port site infection (n = 2), psoriasis exacerbation (n = 1), anemia (n = 9), thrombocytopenia (n = 2), and neutropenia (n = 5). Grade 4 TRAES include anemia (n = 1), neutropenia (n = 1), thrombocytopenia (n = 2), increased AST (n = 2), increased ALT (n = 2), and increased CPK (n = 2). Grade 5 TRAES include rhabdomyolysis (n = 1). There was no incidence of alopecia nor cardiac toxicity reported. Conclusions: Taken together, these data indicate that first-line combinatorial therapy with Ipilimumab, Nivolumab, and Trabectedin (1) may be more effective than standard first line therapy (doxorubicin/ifosfamide/mesna), and (2) is safer than standard first line therapy for advanced soft tissue sarcoma. Clinical trial information: NCT03138161.
Efficacy and safety of eribulin in the treatment of advanced adult soft tissue sarcoma (STS): First real-world data in Chinese population.
Authors: Guo Xi , Zhou Yuhong , Zhuang Rongyuan , You Yang , Zhang Chenlu , Wang Zhiming
Published: June 2022

11577

Background: Eribulin has shown efficacy in STS, especially for the L-type sarcomas, including liposarcoma (LPS) and leiomyosarcoma (LMS). We investigated the efficacy and safety of eribulin in the treatment of advanced adult STS in Chinese population. Methods: The study retrospectively analyzed data from patients diagnosed as advanced STS and received eribulin monotherapy or combination regimens in the Department of Oncology, Zhongshan Hospital affiliated to Fudan University from January 2020 to February 2021. Primary endpoint was objective response rate (ORR) by RECIST v1.1. Secondary endpoints included disease control rate (DCR), progress-free survival (PFS) and treatment-related adverse events (TRAE) by CTCAE v5.0. Results: A total of 40 patients who received at least two doses of eribulin and underwent at least one post-baseline response assessment were included in analysis. The mean age was 48 years. 82.5% (33/40) had L-type sarcomas, and 17.5% (7/40) had non-L-type sarcomas. Overall, 25% (10/40) of patients received eribulin alone; and 75% (30/40) received combination regimens. Drugs used with eribulin included gemcitabine, tyrosine kinase inhibitors (TKIs), anti-PD-1 antibodies, or TKIs plus anti-PD-1 antibodies. For the 40 patients, the ORR was 27.5% (11/40) and the DCR was 60% (24/40). The ORR for myxoid liposarcoma was especially encouraging: 54.5% (6/11) and the DCR was 72.7% (8/11). 10 patients received the combined therapy of anti-PD-1 antibodies, TKIs, and eribulin and showed a likely better ORR of 30% (3/10) and DCR of 70% (7/10). After a median follow-up time of 12.57 months (IQR, 8.43-16.30), the median PFS was 4.13 months (95% CI, 2.17-8.40). 10 out of 33 (30.3%) patients with L-type sarcomas had achieved PR and the median PFS was 4.45 months, 1 out of 7 (14.3%) patients with non-L-type sarcomas had achieved PR and the median PFS is 2.67 months. Common TRAEs were bone marrow suppression (42.5%), hypertriglyceridemia (25%), fatigue (10%), hypertension (7.5%). No treatment-related death happened. Logistic regression analysis of the multiple factors influencing ORR revealed no difference between taxane-treated and taxane-naïve patient groups. Conclusions: This study presents the first real-world data on the use of eribulin in STS in Chinese population. Eribulin monotherapy or combination therapy were likely more effective in this population, as well-tolerated as with Study 309, especially in treating liposarcoma. Eribulin used in combination with TKI and anti-PD-1 antibody showed potential efficacy in STSs. Further clinical exploration of front-line eribulin monotherapy and combination strategies in this setting is warranted.
The emerging fifth epidemiologic subtype of Kaposi sarcoma in HIV-negative men who have sex with men at a tertiary care center in NYC from 2000 to 2021.
Authors: Morales Ayana E , Benson Gabrielle , Glavan Stephanie , Giuliano Rosemary , Dickson Mark Andrew
Published: June 2022

11579

Background: Kaposi sarcoma (KS) is a vascular tumor caused by human herpesvirus 8, also known as Kaposi sarcoma herpesvirus. There are 4 widely accepted distinct epidemiologic subtypes of KS: classic, endemic, iatrogenic, and epidemic (HIV-associated) forms. An emerging 5th subtype is increasingly recognized: non-epidemic KS in men who have sex with men (MSM) who are HIV-negative and have no other known causes for immunodeficiency. Objectives: To characterize a cohort of non-epidemic KS seen at the Sarcoma Medical Oncology or Dermatology Clinics at Memorial Sloan Kettering Cancer Center in New York City from 2000 to 2021 to identify risk factors, presentation, treatment course, and prognosis of these patients. Methods: Following IRB approval, a retrospective observational study was performed. Eligible patients were identified through the Electronic Health Records (EHR). The patients were characterized based on age at presentation, sex, gender identity, comorbidities, coinfections, and treatments and outcomes amongst other factors. Study data were collected and managed using REDCap electronic data capture tools. Results: Seventy-two patients were identified. The median age at time of diagnosis was 58 (range: 32-83). At initial diagnosis, 46% (33/72) of patients underwent observation, 50% (36/72) received localized treatment (i.e. excision, cryotherapy or topical therapy), and 4% (3/72) received systemic treatment with chemotherapy. The median duration of follow-up was 22 months. In follow-up, 43% (31/72) of patients had progression of disease requiring recurrent treatment: 24% (17/72) received localized treatment while 18% (13/72) received chemotherapy. Patients who received chemotherapy, predominantly pegylated liposomal doxorubicin, received treatment for a median duration of 13 months (range: 2-72 months). By the end of the follow-up period, 7 patients had died, of which 2 deaths were attributed to KS. During follow up, 10% (7/72) of patients were diagnosed with a lymphoproliferative disorder. Conclusions: This study is the largest yet, to our knowledge, to characterize the non-epidemic KS subtype in HIV-negative MSM. It is important to recognize this KS subtype to identify these individuals, who despite not having HIV are at increased risk for KS. Accurate recognition of this subtype may also allay patient concerns regarding overall prognosis, given that the majority of these patients present with indolent disease and have favorable outcomes compared to the epidemic variant of KS. Additional research is needed to understand the potential increased risk of lymphoproliferative disorders.
Preliminary findings of implementing the G8 screening tool in an academic cancer center.
Authors: Wen Kuang-Yi , Swartz Kristine , Zhan Tingting , Lombardo Joseph , Cappelli Louis , Lopez Ana Maria , Chapman Andrew E.
Published: June 2022

12010

Background: Older patients often experience more toxicity from cancer treatments due to their functional age and co-morbidities. The G8 is a geriatric screening tool designed to identify patients who are appropriate for a comprehensive geriatric assessment (CGA) which will inform and optimize oncology therapeutic decision making, reduce toxicities and improve outcomes. Using a nurse-led assessment approach, we have implemented an EMR embedded G8 tool across our cancer center since June 2020. We aim to describe the characteristics of those patients who scored abnormal (≤ 14) on the G8. Methods: The demographic and clinical characteristics were collected from the EMR for those who were ≥ 65 and have completed the G8 screening tool from June 2020 to Jan 2022. Summary statistics such as means, standard deviations and proportions were reported. Comparisons of various endpoints between dichotomized (≤ 14 vs. > 14) G8 scores were performed using pairwise two-sample t-test, pairwise proportion test, Fisher’s exact test and/or Pearson’s chi-squared test. Selected stakeholders were elicited for their perspectives on the implementation process. Results: 544 patients age ≥ 65 completed G8 screening with a mean score of 13.4 (± 2.3). The mean age was 75.2 (± 7.0), and 55.7% were females and 78.3% were non-Hispanic White. The most frequent cancer type was breast cancer (21.3%), followed by lung/respiratory cancer (18.2%), and GI cancer (15.8%). The percentage of patients appropriate for a CGA (based on an abnormal G8 score) was 59% (n = 332), of which only 10% (n = 31) were referred. A spearman correlation of 0.4 (p < 0.001) between G8 scores and age was obtained. A statistically significant association between ECOG and G8 groups was found, but not for any comorbidities. The prevalence of current/former smoking and extreme polypharmacy (> 10) is significantly higher in the G8 abnormal group. Implementation process evaluation found new patients with cancer overwhelmed with information, a lack of patient education and provider engagement, and an unstandardized referral process to CGA, were barriers for CGA referral. Conclusions: The G8 is an effective tool identifying patients appropriate for a CGA. An EMR embedded G8 steadily improved the G8 utilization uptake but not referral for CGA at our institution. To further improve awareness, utilization and referral, we are redesigning a hybrid workflow integrating patient-mediated MyChart implementation and nurse navigator engagement. EPIC enhancements are being designed to inform the oncologist of the patient’s G8 score, CGA referral status and the final CGA report.
Association of parental cancer and minor child’s unmet economic needs in food, housing, and transportation.
Authors: Zheng Zhiyuan , Jemal Ahmedin , Zhao Jingxuan , Han Xuesong , Fan Qinjin , Yabroff K. Robin
Published: June 2022

12014

Background: A cancer diagnosis is associated with substantial economic burden among cancer survivors and their families. Some families make sacrifices that adversely affect food, housing, and transportation to offset high out-of-pocket medical expenses. Cancer survivors with minor children may be particularly vulnerable to financial hardship, even years after diagnosis. However, little is known about the extent to which parental cancer affects minor children’s food insecurity, unmet housing needs, and delayed medical care due to transportation barriers. Methods: The 2013 to 2018 National Health Interview Survey was used to identify minor children (ages 5-17 years) living in families with a parental cancer history (n = 812, representing 860,488 children) and children without a parental cancer history (n = 22,129, representing about 24.5 million children). Multivariable logistic regressions were used to compare family-level food insecurity, parent’s worry about ability to pay monthly bills and housing costs, and delayed medical care for the child because of no transportation between minor children with and without a parental cancer history. All analyses adjusted for child-, parent-, and family-related characteristics, including child’s age group, sex, and race/ethnicity; parent’s age group, sex, race/ethnicity, health insurance coverage, number of comorbid conditions, and obesity status; family’s structure (married/cohabiting parents versus single parent families), highest educational attainment in the family, and family income as a percentage of the federal poverty level. Results: About 3.4% of minor children were living in families with a parental cancer history. In adjusted analyses and compared to children whose parents did not report a history of cancer, children of cancer survivors were more likely to live in families that experience shortages in basic economic needs, such as food bought did not last 26.0% (95% confidence intervals[CI]: 22.3%-29.7%) vs 16.7% (95CI: 16.1%-17.3%), inability to afford balanced meals 16.9% (95CI: 13.8%-20.0%) vs 13.3% (95CI: 12.8%-13.8%), worry about paying monthly bills 44.8% (95CI: 40.6%-48.9%) vs 37.9% (95CI: 37.1%-38.7%), and worry about housing costs 35.7% (95CI: 31.9%-39.5%) vs 30.7% (95CI: 30.0%-31.5%). Moreover, children with a parental cancer history were more likely to experience delayed medical care due to lack of transportation than children without a parental cancer history 3.6% (95CI: 2.2%-4.9%) vs 1.6% (95CI: 1.4%-1.9%), all p <.05. Conclusions: Parental cancer is associated with greater likelihood of food insecurity, worse housing and other living conditions, and transportation barriers to medical care for minor children. Efforts to identify minor children with a parental cancer history and develop strategies to attenuate their unmet economic needs are warranted.
Psychological mobile app for patients with acute myeloid leukemia (AML): A randomized clinical trial.
Authors: El-Jawahri Areej , Luskin Marlise Rachael , Greer Joseph A. , Lavoie Mitchell W. , Vaughn Dagny , Yang Daniel , Boateng Kofi , Newcomb Richard , Fathi Amir Tahmasb , Hobbs Gabriela , Brunner Andrew Mark , Abel Gregory A. , Stone Richard M. , DeAngelo Daniel J. , Wadleigh Martha , Temel Jennifer S.
Published: June 2022

12018

Background: Patients with AML experience substantial decline in their quality of life (QOL) and mood during their hospitalization for intensive chemotherapy. Yet, few interventions have been developed to enhance patient-reported outcomes during treatment. Methods: We conducted a randomized trial of a psychological mobile app (DREAMLAND) for patients with a new diagnosis of AML receiving intensive chemotherapy at Massachusetts General Hospital and Dana-Farber Cancer Institute. Patients were randomly assigned to DREAMLAND or usual care. DREAMLAND was tailored to the AML trajectory and included four required modules focused on 1) supportive psychotherapy to help patients deal with the initial shock of diagnosis; 2) psychoeducation to manage illness expectations; 3) psychosocial skill-building to promote effective coping; and 4) self-care. The primary endpoint was feasibility defined as at least 60% of eligible patients enrolling, and 60% of those enrolled completing at least 60% of the required modules. We assessed patient QOL (Functional-Assessment-of-Cancer-Therapy-Leukemia), psychological distress (Hospital-Anxiety-and-Depression-Scale [HADS] and Patient-Health-Questionnaire-9 [PHQ-9]), symptom burden (Edmonton-Symptom-Assessment-Scale), and self-efficacy (Cancer Self-Efficacy Scale) at baseline and day +20 post chemotherapy. We used ANCOVA to assess the effect of DREAMLAND on outcomes. Results: We enrolled 66.7% (60/90) of eligible patients and 62.1% completed ≥ 75% of intervention modules. At day +20 after intensive chemotherapy, patients randomized to DREAMLAND reported improved QOL (132.06 vs. 110.72, P = 0.001), lower anxiety (3.54 vs. 5.64, P = 0.010) and depression (HADS: 4.76 vs. 6.29, P = 0.121; PHQ-9: 4.62 vs. 8.35, P < 0.001) symptoms, and improved symptom burden (24.89 vs. 40.60, P = 0.007) and self-efficacy (151.84 vs. 135.43, P = 0.004) compared to the usual care group. Conclusions: A psychological mobile app for patients newly diagnosed with AML is feasible to integrate during hospitalization for intensive chemotherapy and may improve QOL, mood, symptom burden, and self-efficacy. Clinical trial information: NCT03372291.
Influence of decision support persons on breast cancer treatment decisions among Latinas.
Authors: Morales Krystal A , Abrahamse Paul , Veenstra Christine M , Hawley Sarah T. , Jagsi Reshma , Wallner Lauren P.
Published: June 2022

12025

Background: Prior studies suggest that decision support persons (DSPs) involvement in breast cancer promotes greater deliberation and decision quality. Despite having the highest level of involvement, Latinx DSPs report the lowest satisfaction with their involvement. The reasons for this remain unknown. We examined the treatment decision-making experiences of Latinx DSPs, their influence on treatment deliberation, subjective decision quality (SDQ), and treatment received. Methods: Women with newly diagnosed early-stage breast cancer as reported to the Surveillance, Epidemiology, and End Results (SEER) registries of Georgia and Los Angeles County in 2014-2015 were surveyed. Participants identified the DSPs who played a key role in treatment decisions, who were also surveyed. We examined: (1) bivariate associations of DSP characteristics (e.g type, age, race/ethnicity, education, acculturation level) with DSP-reported level of engagement (informed about decisions, involvement (extent and satisfaction), and aware of patient preferences), (2) DSP engagement with patient-reported SDQ and treatment deliberation using multivariable linear regression with standardized scales (3), and treatment received by DSPs preferred treatment. Results: 2502 patients (68%) and 1203 eligible DSPs (70%) responded, resulting in 1,173 dyads, 292 where the patient identified as Latina, and 881 as non-Latina. Among Latina dyads, 78%, 17%, and 5% DSPs identified as Latinx, White, and Asian/Black/Other, respectively. Latinx DSPs within Latina/Latinx dyads were younger, had lower educational attainment and acculturation when compared to other dyads. The proportion of married/partnered status was not different across dyads, but the key DSP for the Latina-Latinx dyads was more often a daughter (37%), over a husband/partner (21%), compared to the other dyads. Latinx DSPs reported being more informed (adjusted mean 4.26, p = 0.058) compared to the other dyads, and being more informed was positively associated with higher patient SDQ (adjusted mean difference 0.176, p = 0.034), despite no difference in treatment deliberation. Overall, Latinx DSP had a higher preference for mastectomy, especially with reconstruction when compared to non-Latinx (40% vs 28%). Overall, 27% of Latinas (vs 13% non-Latina) underwent lumpectomy despite their DSP’s preference for mastectomy. Conclusions: These findings reveal that the key DSP for many married Latinas is often a daughter over spouse/partner. Our results suggest that including daughter/DSPs in treatment decisions and tailoring strategies to meet their information needs may positively impact Latina SDQ. Potential areas of improvement include surgical options preferences, where notable discrepancy was seen between Latinas and non-Latinas. Awareness of these differences can minimize treatment regret, improve decision quality, and ultimately outcomes in Latinas.
Prognostic impact of systemic anti-cancer therapy on patients with advanced cancer at end of life: Analysis of a multicenter prospective cohort study using propensity score methods.
Authors: Hiramoto Shuji , Oya Kiyofumi , Tokutani Rie , Kirishima Toshihiko , Maeda Isseki , Tetsuo Hori , Amano Koji , Yamauchi Toshihiro , Hiratsuka Yusuke
Published: June 2022

12029

Background: Prognosis is said to worsen when systemic anti-cancer therapy (SACT) is administered until a patient’s end of life (EOL) and professional palliative care is delayed. However, the prognostic impact of SACT at EOL is unclear. Methods: In this pre-planned secondary analysis of a multicenter, prospective East Asian cross-cultural collaborative cohort study, consecutive patients with advanced cancer admitted to palliative care units between January and December 2017 were divided into four groups: patients who had and had not received SACT (SACT vs. non-SACT) and patients whose last administration of SACT was before or within 1 month of study enrolment (non-1M SACT vs. 1M SACT). The primary endpoint was difference in survival time from a palliative performance scale (PPS) of < 20 to death between the SACT and non-SACT groups, and the 1M SACT and non-1M SACT groups. The analysis was adjusted for age; sex; primary cancer site; metastatic site; comorbidity (Charlson comorbidity index); and history of radiotherapy, smoking, and psychiatric disorders. Weighting for inverse probability of treatment was applied. A secondary endpoint was to identify EOL symptom and care factors prognostic for survival time using a Cox proportional hazards model. Results: The 1396 study patients (712 men, 684 women; median age: 73 years) came from 21 institutions throughout Japan. Primary tumor sites were upper gastrointestinal (471 patients), lower gastrointestinal (193 patients), lung (241 patients), breast (93 patients), urologic (101 patients), gynecologic (82 patients), head and neck (56 patients), central nervous system (25 patients), and hematologic (39 patients). Metastatic sites were liver (554 patients), lung (522 patients), bone (373 patients), and brain (199 patients). The SACT, non-SACT, 1M SACT, and non-1M SACT groups consisted of 853, 539, 126, and 1270 patients, respectively. Survival time was significantly shorter in the SACT group (6.83 days, p = 0.03) than in the non-SACT group (9.01 days). No significant difference between the 1M SACT group (7.57 days) and the non-1M SACT group (7.36 days) was evident. Prognostic factors were use of opioids (HR 1.289), antipsychotics (HR 0.787), and anxiolytics (HR 0.867); infusion of more than 1 L daily (HR 0.727); and apnea (HR 0.874), dyspnea (HR 1.874), nausea (HR 0.612), fatigue (HR 1.284), and ascites (HR 1.236). Conclusions: Prognosis was shorter for patients with a history of SACT than for those without a history of SACT at EOL. However, SACT at EOL was not a prognostic factor. This information is useful in advance care planning for selecting and explaining treatment at EOL to patients and their families.
Predictive factors of toxicity of immune checkpoint inhibitors (ICI) in older patients with lung cancer: The ToxImmune study.
Authors: Helissey Carole , Difoum Francoise , Vanquaethem Hélène , Vuagnat Perrine , Picchi Hugo , Le Roy Audrey , Schernberg Antoine
Published: June 2022

12048

Background: Immunotherapy (Im) improved the survival of patients with lung cancer. It may be responsible for adverse events impacting these patients' quality of life. We have few data on the tolerance of older cancer patients (OP) to immunotherapy. The Toximmune study aims to describe the safety of older lung cancer patients to Im and identify clinical, biological and radiological markers that can help to predict immune-related adverse events for OP. Methods: All patients aged 60 years and older who had received at least one dose of ICI between June 2015 and December 2020 and diagnosed with lung cancer were included. We collected patients' baseline demographic characteristics, biological blood markers and imaging by PET-scanner. All adverse events (AEs) and immune-related AEs (irAEs) were recorded (CTCAE V.5.0). Results: 49 patients were included, median age was 71 (range 61-97). The incidence of grade 2 and grade 3-4 was 34% and 6% respectively. The main irAEs reported were: asthenia in 51% patients after 13.5 months median delay (grade ≥2 in 22%),musculoskeletal disorders in 45% after 21 months median delay (grade ≥2 in 10%), pneumonitis in 37% after 21 months median delay (grade ≥2 in 10%), and colitis in 35% after 21 months median delay (grade ≥2 in 6%). Female sex, primitive tumor SUV max < 5, number of metastases ≥ 3, prior systemic therapy > 1, PLR < 250 were significantly associated with a risk of toxicity in univariate analysis (p < 0.05) We developed the ToxImmune score (0, 1, or ≥2) to predict the risk of having a grade ≥2 adverse event by adding the following risk factors: Primitive Tumor SUV < 5 = 1, Number of metastases ≥3 = 1, And L1 = 0 vs > L1 = 1. The incidence of grade ≥2 adverse events was 31%, 35% and 86% with ToxImmune scores 0, 1 and 2 respectively (p = 0.032). Median overall survival times (OS) & progression-free survival (PFS) were 21.8 & 21 months, 15.1 & 6.6 months, and 9.8 & 2.1 months for ToxImmune scores 0, 1 and ≥ 2 respectively (p = 0.06 & p = 0.001). There was significant association between the ToxImmune score and the risk of "progressive disease" at the first assessment of the disease: 16% for score = 0, 48% for score = 1, and 71% for score = 2, (p = 0.01). Conclusions: The quality of life is our goal for OP care. The ToxImmune score, which is based on objective clinical parameters, identifies OP with a significant higher risk of severe adverse events. Also, this score was significantly associated with patients’ PFS risk of developing rapid tumor progression. It could be used in clinical practice to personalize toxicity surveillance in OP treated for lung cancer with immunotherapy. This score will be validated in larger prospective cohorts.
SNP-SNP interactions and a 4-locus model for prediction the risk of anthracycline-mediated cardiotoxicity in patients with breast cancer.
Authors: Gvaldin Dmitry Yu. , Timoshkina Natalya N. , Vashchenko Larisa N. , Ausheva Tatiana V. , Dashkova Irina R. , Ryadinskaya Ludmila A. , Kechedzhieva Emma E. , Vladimirova Liubov Yu
Published: June 2022

12076

Background: Numerous pharmacogenetic studies have identified genetic polymorphisms (SNPs) associated with an increased risk of anthracycline-mediated cardiotoxicity (AMC). The purpose was to search for SNP-SNP interactions associated with the risk of cardiotoxic manifestations caused by anthracycline therapy in breast cancer patients. Methods: The study included 256 Caucasian patients (median age - 55 years) with a diagnosis of breast cancer with normal cardiovascular system parameters at baseline, who were treated with anthracyclines in 2019-2020. For SNP genotyping of c.4544G > A rs8187710 (ABCC2), c.1744C > T rs11549465 ( HIF1A), g.22125504G > C rs1333049 ( CDKN2A/ B) and c.214T > C rs4673 ( CYBA). DNA was extracted from blood by using DNA-sorb-B (AmpliSens, Russia). HRM-PCR was performed on a CFX96 amplifier (Bio-Rad, USA). The presence of polymorphism was confirmed by the Sanger method on a Genetic Analyzer 3500 (ABI, USA). Results: During the follow-up period 21 (8.2%) patients developed signs of subacute (changes developed within several weeks after the last course of therapy) or early chronic anthracycline mediated cardiotoxicity (changes developed within a year after completion of anthracycline therapy). Using the multifactorial dimension reduction method. We obtained a 4-locus model of SNP-SNP interactions c.4544G > A rs8187710 ( ABCC2) x g.22125504G > C rs1333049 ( CDKN2A/B) x c.214T > C rs4673 ( CYBA) x g.23708527G > A rs28714259 which has high prognostic properties. The specificity of the test based on the 4-locus model was 68%, the sensitivity was 100%, and the overall accuracy was 71%. The results of the analysis of SNP-SNP interactions indicate the greatest contribution of rs4673 and rs28714259 to the predisposition to AMC. The first ones yet into antagonistic interactions with rs28714259, rs1333049 and rs11549465, the second with rs8187710, rs11549465 and rs4673. On the contrary rs11549465 and rs1333049 contribute to a synergistic effect. Conclusions: The 4-locus model discovered in this study can form the basis of prognostic tests that predict early the risks of developing AMC in cancer patients, which in the future allow to personalize and select the most optimal treatment regimen.
CT scan versus bioelectrical impedance spectrometry sarcopenia assessment to predict chemotherapy toxicity in early breast cancer.
Authors: Aleixo Gabriel , Valente Stephanie A. , Wei Wei , Chen Po-Hao , Moore Halle C. F.
Published: June 2022

12078

Background: There is growing literature on the impact of the progressive loss of skeletal muscle known as sarcopenia in women with early breast cancer (EBC). Imaging techniques such as Computed Tomography (CT) scans are the most studied methods to detect sarcopenia in patients with cancer; however, most patients with EBC do not require routine CT scans. Bioelectrical impedance spectrometry (BIS) is a method that does not expose patients to radiation and provides measurements to assess sarcopenia instantaneously. The extent to which BIS-assessed sarcopenia correlates with CT-assessed sarcopenia is uncertain. It is also unclear whether sarcopenia detected with either method can be associated with chemotherapy tolerance To address these questions, we evaluated the correlation between CT and BIS sarcopenia and associations of sarcopenia by each method with chemotherapy related outcomes in patients with EBC. Methods: This retrospective study identified patients with EBC who received chemotherapy (ACT, TC, TH, THP), underwent BIS analyses (ImpediMed) at any point between diagnosis and treatment completion and also received a CT abdomen including L3 level. Axial CT L3 segments were analyzed using Slice-O-Matic software. CT L3, and BIS generated the Skeletal Muscle (SM). Skeletal Muscle Index (SMI) was then calculated to assess for sarcopenia: BIS SMI= (SM in kg)/ (patient height, m2) and CT L3 SMI (SM cm2/ height m2). Patients were divided into normal SMI, and sarcopenia (if BIS was used SMI <6.75 kg/m2 and if CT SMI <40 cm2/m2). Patient medical records were reviewed for patient characteristics, grade 3 and 4 toxicity, including neuropathy symptoms, chemotherapy dose reductions, early treatment discontinuation or need for hospitalization during chemotherapy treatment. Spearman's rank coefficient was used to assess the correlation between CT SMI and BIS SMI. Multivariable logistic regression was used to associate sarcopenia with outcomes, controlling for age and BMI. Results: 361 patients received chemotherapy, underwent BIS; of those 171 had L3 CT scans. The correlation between L3 CT SMI and BIS SMI was r= 0.64 p<0.0001. In the multivariable model, sarcopenia assessed by L3 CT scan was associated with chemotherapy dose reduction (CI 0.04-0.60 p=0.01) and neuropathy (CI 0.10-0.95 P=0.04) but not with grade 3 or 4 chemotherapy toxicity (CI 0.13-1.09 p=0.07), early treatment discontinuation (p=0.3) or hospitalization (p=0.60). Sarcopenia assessed by BIS was associated with grade 3 or 4 chemotherapy toxicity (CI 0.2-0.83 p=0.01), neuropathy (CI 0.1-0.51 p=0.0003), early treatment discontinuation (OR 0.26 CI 0.11-0.80 p=0.001), and hospitalization (CI 0.12-0.68 p=0.004). Conclusions: There is a strong correlation between L3 CT scan and BIS screened sarcopenia in patients with EBC. Sarcopenia detected with either CT L3 or BIS is associated with worse chemotherapy tolerance.