bluuebunny/crossref_metadata_2025 huggingface dataset:
Delivery of cancer survivorship education to community health care professionals.
Authors: Pariser Ashley , Brita Javin , Harrigan Maura , Capozza Scott , Khairallah Angela , Sanft Tara B.
Published: May 2020

11032

Background: Cancer survivorship care is an integral part of oncology care. Although oncologists overwhelmingly demonstrate a desire to be a part of their cancer survivors’ care and management, only 60% of oncologists feel comfortable promoting healthy lifestyle behaviors, screening and prevention care. There is currently no standard of care for survivorship care education and data evaluating current educational models is limited. Methods: Project ECHO (Extension for Community Healthcare Outcomes) utilizes telehealth to promote long-distance learning and sharing of best practices. We utilized the Project ECHO model to deliver a survivorship curriculum in 6 hourly, biweekly sessions from October 2019 to December 2019. The curriculum was aligned with the 4 central tenets of survivorship care and was developed based on a needs assessment. Recruited participants included registered nurses (RN), registered dietitians (RD), advanced practice providers (APP), radiation oncologists and medical oncologists. Participants were enrolled in either a local ECHO curriculum or a national ECHO curriculum. Local Connecticut participants were invited to participate in semi-structured interviews to evaluate their experience. Results: Eight participants including 3 MDs, 1 APP, 1 SW and 3 RNs from 3 community oncology clinics in suburban Connecticut enrolled in the local ECHO curriculum. Twenty-eight participants including 17 RDs, 2 MDs, and 3 APPs from 13 hospital and community practices enrolled in the national ECHO curriculum. Four participants (50%) agreed to participate in semi-structured interviews. Motivations to participate included ease of participation and interest in survivorship. Participants described a positive experience, citing a well-structured curriculum and sense of community as highlights. Two participants described the sessions as empowering, leading to more discussions and engagement with survivors. All participants described an increased awareness of resources available for cancer survivors. Areas for improvement included greater assistance with technology and session time management. Concomitant patient care was the most cited barrier to participation. Conclusions: This pilot study is the first to demonstrate the feasibility of the Project ECHO model for delivering cancer survivorship education to community oncology providers. Further research evaluating the correlation between improved provider knowledge and survivorship care outcomes is needed.
Three versus one year of adjuvant imatinib for high-risk gastrointestinal stromal tumor (GIST): Survival analysis of a randomized trial after 10 years of follow-up.
Authors: Joensuu Heikki , Eriksson Mikael , Sundby Hall Kirsten , Reichardt Annette , Hermes Barbara , Schuette Jochen , Cameron Silke , Hohenberger Peter , Jost Philipp , Al-Batran Salah-Eddin , Lindner Lars H , Bauer Sebastian , Wardelmann Eva , Nilsson Bengt E. , Kallio Raija S. , Jaakkola Panu , Junnila Jouni , Alvegard Thor , Reichardt Peter
Published: May 2020

11503

Background: Adjuvant imatinib improves recurrence-free survival (RFS) when administered after surgery to selected patients with operable gastrointestinal stromal tumor (GIST). It is uncertain whether overall survival (OS) improves, since imatinib improved OS in only one of the 3 large randomized trials conducted, and in this trial (the Scandinavian Sarcoma Group XVIII/German trial; SSGXVIII/AIO; NCT00116935) the statistical significance for OS remained borderline. The objective of the present analysis was to evaluate long-term OS of patients who participated in the SSGXVIII/AIO trial. Methods: SSGXVIII/AIO is an open-label, randomized (1:1), multicenter phase 3 trial. Four hundred patients who underwent macroscopically complete surgery for GIST with a high estimated risk for recurrence according to the modified National Institutes of Health Consensus Criteria were accrued between February 2004 and September 2008. Imatinib was scheduled to be administered 400 mg/day orally for either 12 months or 36 months after surgery. The patients were scheduled to be followed up for 10 years after study entry. Imaging of the abdomen was carried out periodically. The primary end point was RFS; the secondary objectives included OS and treatment safety. Results: The median follow-up time was 119 months. In the Intention-To-Treat Population 194 RFS events and 96 OS events were recorded. In the 36-month group, 5-year and 10-year RFS was 71.4% and 52.5%, and in the 12-month group, 53.0% and 41.8%, respectively (HR 0.66, 95% CI 0.49-0.87; P = .003). In the 36-month group, the 5-year and 10-year OS rates were 92.0% and 79.0%, and in the 12-month group, 85.5% and 65.3%, respectively (HR 0.55, 95% CI 0.37-0.83; P = .004). In the Efficacy Population, from which 15 patients who did not have GIST in central pathology review and 24 patients who had intra-abdominal metastases removed at surgery were excluded, 10-year OS was 81.6% in the 36-month group and 66.8% in the 12-month group (HR, 0.50, 95% CI 0.32-0.80; P = .003). No new safety signals were detected. Conclusions: About 50% of deaths can be avoided during the first decade of follow-up after surgery with 3-year imatinib treatment as compared to 1-year treatment. Clinical trial information: NCT00116935 .
A phase II multi-arm study of durvalumab and tremelimumab for advanced or metastatic sarcomas.
Authors: Somaiah Neeta , Conley Anthony Paul , Lin Heather Y. , Amini Behrang , Sabir Sharjeel H , Araujo Dejka M. , Benjamin Robert S. , Livingston J Andrew , Patel Shreyaskumar , Ratan Ravin , Ravi Vinod , Zarzour Maria Alejandra , Wang Wei-Lien , Tate Taylor , Roland Christina Lynn , Daw Najat C. , Futreal Andrew , Lazar Alexander J. , Wistuba Ignacio Ivan , Hwu Patrick
Published: May 2020

11509

Background: The combination of durvalumab (D), (anti- PD-L1) and tremelimumab (T), (anti-CTLA-4), was evaluated to determine activity in specific sarcoma subtypes (NCT02815995). We report final results of the clinical efficacy, safety and correlatives. Methods: Pts ≥12 yrs, with advanced/metastatic sarcoma, were enrolled based on subtype: LPS, LMS, angiosarcoma (AS), UPS, synovial sarcoma, osteosarcoma, ASPS, chordoma, and other sarcomas. Pts received D 1500mg and T 75mg every 4 wks for 4 cycles followed by D alone every 4 wks for up to 12 months (mo) unless the patients experienced unacceptable toxicity or disease progression. Re-treatment was allowed if progression occurred after stopping therapy within the next 12 mo. The primary end-point was PFS at 12 wks (RECIST). Secondary objectives included safety, response rates (irRC and RECIST) and survival. Biopsies were collected at baseline and at 6 wks for flow, PD-L1, multiplex IHC staining and sequencing. Results: Baseline characteristics of the 57 pts who received treatment are listed in the Table. Median OS for all pts was 20.8 mo (95% CI: 11.7, NR), the 12-mo survival was 63% (95% CI: 52%, 78%) and the 24-mo survival was 45% (95%CI: 33%, 61%). The mPFS for all pts was 4.5 mo (95% CI: 2.8, 6.9). The PFS at 12 wks for all pts was 51% (95%CI: 37%, 63%), PFS at 12 mo was 28% (95% CI: 18%, 43%), and PFS at 24 mo was 25% (95% CI: 16%, 41%). The 12 wk PFS was lowest for the LPS cohort (6 pts) at 16% (95% CI: 1%, 52%), and highest for the ASPS cohort (10 pts) at 90% (95% CI: 47%, 99%). PRs by irRC were observed in ASPS (5/10), chordoma, (1/5), UPS (1/5), and cutaneous AS (1/1), and 14 pts completed 12 mo of therapy. 14 pts (24.6%) experienced grade ≥3 related AEs (colitis, nausea, cardiac dysfunction, thyroiditis, pneumonitis, hepatitis, myositis, anemia and fatigue). Clinical benefit correlated with tumors with an inflamed phenotype; based on higher than median density of 3 major categories of tumor infiltrating lymphocytes (TIL): CD3+, CD3+CD8+, CD3+CD8+GZB+, seen in the 36 paired biopsies. Conclusions: In addition to histology (ASPS, cutaneous AS, UPS, chordoma), a higher TIL immune score can help predict clinical benefit. Clinical trial information: NCT02815995 . [Table: see text]
Association of immune-related adverse events (irAEs) with improved clinical outcome in sarcoma patients treated with immune checkpoint blockade (ICB).
Authors: Rosenbaum Evan , Seier Kenneth , Kelly Ciara Marie , Kiesler Hannah , Martindale Moriah , Nicholls Cory , Chi Ping , Dickson Mark Andrew , Gounder Mrinal M. , Keohan Mary Louise , Movva Sujana , Nacev Benjamin , Hwang Sinchun , Qin Li-Xuan , D'Angelo Sandra P. , Tap William D.
Published: May 2020

11510

Background: IrAEs are associated with improved clinical outcomes after treatment with ICB in select epithelial malignancies. We hypothesized that sarcoma patients (pts) treated with ICB who developed an irAE would have improved outcomes compared to pts who had no irAE. Methods: Adverse events (AEs) from 3 sarcoma-specific ICB trials (nivolumab plus NKTR-214, pembrolizumab plus epacadostat, and pembrolizumab plus T-VEC) were reviewed. AEs probably or definitely related to ICB were classified as immune- or non-immune-related by the principal investigator. Endpoints of interest included best overall response (BOR) by RECIST 1.1 (complete response [CR]/partial response [PR]), durable clinical benefit (DCB; CR/PR/stable disease [SD] ≥ 16 weeks), and progression-free survival (PFS). Outcomes were stratified by the presence or absence of ≥ 1 irAE of any grade and by grade 1-2, grade 3-4, or no irAE (three-category comparison). Results: A total of 124 pts received ICB on these studies. Median pt age was 56 (range: 13-90); 53% were male; all but one pt had a performance status of ≤ 1. BOR was PR in 12 pts, SD in 41, and PD in 69. 2 pts were not evaluable. 40 pts (32%) had ≥ 1 irAE of any grade, 6 of whom had a grade 3-4 irAE. The most common irAEs (≥ 5% of pts) were rash (15%), arthralgia (11%), myalgia (9%), pruritis (8%), and hypothyroidism (6%). The proportion of pts with a CR/PR was higher in pts with than without an irAE (18% vs. 6%, respectively; P = 0.058). A significantly higher proportion of pts with an irAE had DCB compared to those without (53% and 29%, respectively; P = 0.017). The median PFS of pts with an irAE was 16.6 months compared to 10.6 in those without (P = 0.013). The proportion of pts with a grade 3-4 irAE and a CR/PR was highest (33%) compared to pts with grade 1-2 (15%) or no irAE (6%) (P = 0.048). More pts with grade 3-4 irAE achieved DCB (67%) than grade 1-2 (50%) or no irAE (29%) (P = 0.027). Median PFS was 22.6, 15, and 10.6 weeks in the grade 3-4, grade 1-2, and no irAE groups, respectively (P = 0.047). Conclusions: Approximately one-third of advanced sarcoma pts with ICB-based immunotherapy developed an irAE. As reported previously in select carcinomas, sarcoma pts with irAEs were more likely to have clinical benefit than those without irAEs. Further research is needed to understand the mechanism behind this association and to validate these findings prospectively.
Survivin-responsive conditionally replicating adenovirus for patients with advanced sarcoma demonstrated potent and long-term efficacy and high safety in a phase I clinical trial.
Authors: Nagano Satoshi , Futagawa Toshitaka , Sumi Eriko , Ijichi Nobuhiro , Yamaguchi Munekazu , Nakajo Masanori , Hashiguchi Teruto , Takeda Yasuo , Yoshiura Takashi , Shimizu Akira , Takatani Muneo , Komiya Setsuro , Kosai Ken-ichiro
Published: May 2020

11512

Background: Whereas one of oncolytic viruses (OVs), inducing selective tumor killing and systemic anti-tumor immunity, was approved by FDA in 2015, the best OV that more safely and efficiently treats intractable cancers has not been successfully developed. By our platform technology to efficiently construct next-generation OVs, i.e., “conditionally replicating adenoviruses (CRAs) that target and/or treat tumor cells with multiple factors” (m-CRAs), we identified that among candidates, survivin-responsive m-CRAs (Surv.m-CRAs) exhibited the most potent antitumor efficacy and cancer selectivity ( i.e., safety) in preclinical studies ( Cancer Res, 2005 et al.). Here we present the data of First-In-Human phase I clinical trial of Surv.m-CRA-1 for musculoskeletal tumors (MST). Methods: This single-arm, open label study included 9 patients with unresectable and advanced MST. Patients underwent a single intratumoral injection of either 1×10^10 viral particle (vp) (low), 1×10^11 vp (mid) or 1×10^12 vp (high). The primary endpoints were safety and tolerability. The secondary endpoints included the local control of treated tumor at one month, defined by RECIST and Choi criteria, analysis of dissemination of Surv.m-CRA-1, serum cytokine and adenoviral antibody. Long-term follow-up was done in some patients. Results: Four patients (44.4%) had grade 3 or higher adverse events, including lymphopenia, leukocytopenia and mildly elevated liver transaminase in 2, 1 and 1 patient, respectively. Virus excretions, including second peak of viremia from viral replication in tumor, were observed in 1, 2 and 3 patients of low, mid and high dose, respectively. Out of 9 patients, 5 PR, 3 SD and 1 PD by Choi, and 8 SD and 1 PD by RECIST were observed. During follow-up, another 1 and 2 patients became PR by Choi and RECIST, respectively. Of note, long-term PR (over 2 years) after a single injection of Surv.m-CRA-1 was achieved in two chordoma cases in low dose. Conclusions: Surv.m-CRA-1 was well tolerated and showed antitumor activity for prolonged periods against advanced MST. We about to start Phase I/II study of multiple injections of Surv.m-CRA-1 for advanced solid tumors in two-arms for musculoskeletal tumors and pancreatic cancer. Clinical trial information: R000026464 .
Genomic analysis of advanced malignant soft tissue tumors to suggest effect of genome-wide loss-of-heterozygosity of germline mutations/variants on anti-PD-1 immunotherapy response and survival of the patients.
Authors: Takahashi Katsuhito , Miyaji Yasutomo , Higuchi Hajime , Komohara Yoshihiro , Doi Koichi , Sano Hiroko , Aida Shinsuke , Yashima Jun , Yamamoto Hiromasa , Suzawa Ken , Takahashi Yuko , Toyooka Shinichi , Saito Ayumi , Oyama Yu , Narahara Hiroyuki , Yotsumoto Junko , Ono Yasuo , Teraoka Satoshi
Published: May 2020

11531

Background: Malignant soft tissue tumor is a rare cancer with few therapeutic options. Although recent genomic characterization of soft tissue sarcoma revealed massive CNA and an excess of polygenic burden of pathological germline variants, their clinical and therapeutic significance remains to be understood. Methods: We recruited 155 patients with malignant soft tissue tumors (135 female and 20 male, mean age 51, 100 LMS, 19 LPS, 4 ESS, 3 UPS, 3 AS, 3 MPT, 3 GIST and others) of confirmed metastasis/recurrence. Whole exome sequencing was performed as reported in 2018ASCO. The MSI status was analyzed by PCR. Tumor immune microenvironment was assessed by immunohistochemistry. Results: Of the 595 COSMIC genes, heterozygous germline mutations/variants of the genome-wide 0-44 genes (av. 9.7/tumor) showed somatic loss-of-heterozygosity (LOH) with allele frequency of more than 70%. Patients with less than 33% LOH (n=53) in the total of somatic and LOH mutations showed improved 5-year survival rate compared with those (n=102) with more LOH (71% vs 52%, p=0.037). LMS (n=100) had higher value of LOH mutations than other tumors (n=55)(av. 55.5 vs 31.2%, p<0.001). Two patients with bone metastasis, one from liver undifferentiated sarcoma (case 1) and the other from uterine LMS (case 2) were identified as MSI-High and resultant higher TMB of 6.48 and 6.60/Mb, respectively than 1.47/Mb in av. Tumors from both cases had de novo mutations of MMR deficiency as EXO I (A153V) and WRN (S1120F) in case 1 and MSH2 (G674D) in case 2. Case 1 with pleural dissemination was treated with 5 cycles of Pembrolizumab (200mg/body, d1 q3weeks) but was progressive disease, while case 2 had no evaluable lesion after surgical removal of bone metastasis. Number of CD8+ T-cell infiltration (TIL), one of the best parameter with response to PD-1 blockade, was much higher in case 2 than in case 1 (av. 907 vs 290/mm2). Case 2 had no LOH mutations while case 1 had 37% LOH with more total mutations in tumor (16.1 vs 85.9/Mb). Higher values of LOH (av. 67 vs 19%) were clearly correlated with decreased density of CD8+TIL in tumor tissues (av. 9.6 vs 429/mm2, n=5, p=0.018). Conclusions: Our results, for the first time, suggest that in malignant soft tissue tumors, accumulation of genome-wide LOH of germline mutations/variants, from which self-antigens could be generated, may influence tumor immune microenvironment, and thus influence immunotherapy response and survival of the patients.
Long-term results of selective internal radioembolization (SIRT) to control progressive liver metastases of gastro-intestinal stromal tumors (GIST) beyond treatment with tyrosine kinase inhibitors (TKI).
Authors: Hohenberger Peter , Rathmann Nils , Buesing Karen , Menge Franka , Diehl Steffen
Published: May 2020

11538

Background: Liver and peritoneum are the main area of metastatic spread in GIST. Liver resection does not play a role for hepatic metastases in comparison to f.e. colorectal cancer. If hepatic metastases are the only or major area of tumor progression and are resistant to available TKIs due to a missing mutation in KIT/PDGFRA/SDH ( ‘wildtype’) or after treatment with 1st/2nd/3rd/4th line therapy, interventional radioembolization with yttrium-90 (90Y) microspheres are promising treatment options, as radiation doses as high as 200Gy can be applied locally. We analyzed the long-term results of SIRT with respect to hepatic-progression-free survival (HEP-PFS) in a consecutive cohort of patients.. Methods: From 1/2008 to 1/2018, 25 pts (12f, 13m) with biopsy proven liver metastases of GIST which were the only (n = 13) or the dominant site of progression (n = 12) were treated by SIRT. Median age at GIST diagnosis had been 51.8 yrs and when receiving SIRT was 57.6yrs (range, 18–75yrs). The mutational status was ‘wildtype’ (n = 7, 2 NF-1), exon 11 (n = 7), exon 11+2nd mutation (n = 6), exon 9 (n = 3), exon 9+2ndmut (n = 1), and, exon 13 (n = 1). All patients except of two had prior TKI therapy: 1 line n = 3, 2 lines n = 11, 3-4 lines n = 9. Follow-up after SIRT was done via dynamic MRI and contrast-enhanced (CE)-CT, the median follow-up is 30.6 mos (range, 12-100mos) and all patients were followed until death. Results: The median hepatic-progression free survival (HEP-PFS) after SIRT was 17 months (range, 5-53+, 95%CI 11.8-22.1 mos). Of the patients with concomitant extrahepatic disease, the extraHEP-PFS was median 10 months. Twelve patients received next-line TKI therapy for progressive extrahepatic disease, whereas six patients required this for progressive liver metastases. When comparing the results according to the mutational status, patients with a ‘wildtype’ tumor showed a better median HEP-PFS of 19 mos (range, 12-53+, 95%CI 16.7-21.2 mos.) in comparison to KIT exon 9/11/13 mutated patients with only 14 months (range, 4-34 mos., 95%CI 6.5-21.4 mos), p < 0.11 (Wilcoxon). Conclusions: 90Y radioembolization (SIRT) offers a safe and effective treatment for patients with liver metastases of GISTs being the dominant site of tumor progression and with no drug treatment options available. In patients known to have no mutation in KIT/PDGFRA (wt, also NF-1 associated) it looks whether the results might be even more promising and SIRT could be used in early treatment lines.
Which patients with pre-treated locally advanced or metastatic sarcoma benefit most from trabectedin treatment: First results of a retrospective study of the German Interdisciplinary Sarcoma Group (GISG-14 - ReTraSarc).
Authors: Pink Daniel , Richter Adrian , Andreou Dimosthenis , Richter Stephan , Flörcken Anne , Deinzer Christoph , Kasper Bernd , Egerer Gerlinde , Ivanyi Philipp , Tuchscherer Armin , Kessler Torsten , Schuler Markus , Schmidt Christian , Bahr Jeannette , Ittermann Till , Reichardt Peter
Published: May 2020

11554

Background: Despite the growing amount of published data regarding the outcomes of sarcoma patients treated with trabectedin, still some questions remain unanswered. The aim of the ReTraSarc trial (NCT03284320) was to evaluate the efficacy and safety of trabectedin in a large German population. Methods: Patients treated between 2007-2018 were retrospectively analyzed. All patients had histologically confirmed soft tissue (STS; n = 478) or bone (BS; n = 31) sarcoma; either metastatic (n = 468) or locally advanced (n = 41) disease, and had received at least one cycle of trabectedin. Based on follow-up data (until October 2019), progression-free survival (PFS) and overall survival (OS) after initiation of trabectedin treatment were estimated according to the Kaplan-Meier method. Results: A total of 509 patents were analyzed. Patients had a mean age of 54 years for STS and 30 years for BS-patients, and 25.4% of them aged > 65 years. Overall, 71.4% of patients had a good performance status (ECOG 0/1), and 37.7% received two prior lines, 28.3% three and 34% received > 3 prior lines of systemic treatment. Patients received a median of 3 cycles (IQR: 2-6 cycles) of trabectedin. Trabectedin resulted in an objective response rate (ORR) of 10% with a 37.4% of disease control rate (DCR). The median PFS and OS were 2.5 months (IQR: 1.4-6.1 months) and 8.2 months (IQR: 3-21 months), respectively. Significantly more patients with liposarcoma (22.1%; 95% CI: 15.2-32.2) were free from progression at 12 months after treatment as compared with patients with leiomyosarcoma (8.5%; 95% CI: 4.8-14.9). More analyses of effectiveness and safety are in progress (e.g. stratified per sarcoma subtypes or therapeutic line) and will be presented. Conclusions: The results of this real-life study, with a large number of patients and long-term follow-up, allow us to better analyze PFS and OS in sarcoma patients treated with trabectedin, given in different treatment lines and after dose modifications and/or cycle delays. Additionally, the results of this study enable us to evaluate the real-life impact of rechallenge with trabectedin in a further therapy line. Clinical trial information: NCT03284320 .
Multicenter, open-label phase II study of daily oral regorafenib for chemotherapy-refractory, metastatic and locally advanced angiosarcoma.
Authors: Agulnik Mark , Robinson Steven Ian , Okuno Scott H. , Siontis Brittany , Attia Steven , Kocherginsky Masha , Milhem Mohammed M. , Monga Varun , Chawla Sant P. , Oppelt Peter John , Hirbe Angela C. , Van Tine Brian Andrew
Published: May 2020

11561

Background: Angiosarcoma has a particularly poor prognosis with 5-year overall survival rates of approximately 30-40%. Treatment of locally advanced and metastatic angiosarcoma is inadequate. Data strongly suggest concurrent, potent inhibition of VEGFR and Tie2 represents an attractive therapeutic strategy in angiosarcoma. Regorafenib displays potent VEGFR and Tie2 receptor inhibition and also possesses activity against additional potential targets in angiosarcoma including PDGFRs, RAF, KIT and FGFR, amongst others. Methods: A multicenter phase II study of regorafenib in patients with locally advanced or metastatic angiosarcoma was conducted through the Midwest Sarcoma Trials Partnership. Adequate performance status, organ function, measurable disease (RECIST 1.1) and 1-4 prior therapies were required. Regorafenib 160 mg PO daily was given in 28-day cycles (21 days on, 7 days off) until disease progression (PD) or unacceptable toxicity. The primary endpoint was progression-free survival (PFS), assessed at 16 weeks. Secondary endpoints include overall response rate (ORR), clinical benefit rate (CBR), OS, and safety and tolerability. A Simon 2-stage design was used. Results: After final enrollment of the second stage, a total of 31 pts were enrolled at 6 sites, 23 are evaluable for response. Median age was 65 (range 30-91); 50% were female, 67.7% had metastatic disease. PFS at 4 months is 52.2% with a median PFS and OS of 3.55 and 11.4 months. 1 confirmed CR and 2 PR, 12 SD and 8 PD were observed. ORR and CBR are 14.29 and 65.2%, respectively. No uncommon grade 3-4 adverse events were observed. 6 pts were non-evaluable due to refusal of further therapy and 2 patients progressed prior to first evaluation. Conclusions: Regorafenib was well tolerated in this study of pretreated patients with angiosarcomas and met its primary endpoint with a median PFS > 45% at 4 months. Treatment was feasible and did not reveal any previously unreported toxicities. Efficacy outcomes were complicated by early withdrawals of patients. RECIST responses were encouraging and regorafenib has a clinically meaningful 4-month PFS. Clinical trial information: NCT02048722 .
Efficacy, safety, and immune priming effect of tazemetostat in patients with epithelioid sarcoma.
Authors: Gounder Mrinal M. , Stacchiotti Silvia , Schoffski Patrick , Cote Gregory Michael , Villalobos Victor Manuel , Jahan Thierry Marie , Chen Tom Wei-Wu , Ratan Ravin , Gupta Abha A. , Dileo Palma , Agulnik Mark , Italiano Antoine , Attia Steven , Mir Olivier , Pressey Joseph Gerald , Sierra Laura , Lingaraj Trupti , Yang Jay , Agarwal Shefali , Jones Robin L.
Published: May 2020

11564

Background: Epithelioid sarcoma (ES) is a rare, aggressive soft tissue sarcoma characterized by loss of inhibitor of integrase 1 (INI1), allowing enhancer of zeste homologue 2 (EZH2) to repress cell differentiation and promote tumorigenesis. Tazemetostat (TAZ) is a selective inhibitor of EZH2 approved by the FDA for treatment of patients (pts) aged ≥16 years with metastatic or locally advanced ES ineligible for complete resection. Methods: This open-label, multicenter, multi-cohort phase 2 study (NCT02601950) evaluated safety and efficacy of TAZ in pts with INI1-negative tumors. ES pts were enrolled in Cohorts 5 and 6; pts in Cohort 6 underwent mandatory pre-dose (at screening) and post-dose biopsies (at Day 1 of cycle 2). Herein, we report the interim efficacy and safety data from Cohort 6. Results: As of July 31 2019, 44 pts were enrolled into Cohort 6 and treated with TAZ 800 mg BID. The objective response rate (ORR) was 11.4%; 4 pts (9.1%) had a partial response and 1 pt (2.3%) had a complete response (Table). Another 17 pts (38.6%) had stable disease (SD). 18 pts had progressive disease; 13 of these pts remained on study beyond progression. Progression-free survival (PFS) and overall survival (OS) at 56 weeks were 19.4% and 59.4%, respectively. In a pooled posthoc analysis of 106 ES pts from Cohorts 5 (n = 62), and 6, ORR was 13.2%. Grade 3–4 adverse events (AEs) were reported in 16 pts (36.4%), most commonly anemia (6.8%; n = 3) and tumor pain (6.8%; n = 3). 3 pts (6.8%) experienced grade 3–4 treatment-related AEs. One pt discontinued study drug and there were no treatment-emergent dose reductions or treatment-related deaths. These safety data from Cohort 6 are consistent with previously reported data from Cohort 5. 19 paired biopsies were included for translational endpoint analyses. Preliminary RNA seq and pathway analyses are currently ongoing and updated data, including additional biomarker data will be presented. Conclusions: Consistent with previously reported data from the completed Cohort 5, TAZ demonstrated clinically meaningful, durable, single agent activity in ES pts. Efficacy data from Cohort 6 continue to mature with 8 patients still on treatment. TAZ was well tolerated with a low incidence of treatment related AEs. Clinical trial information: NCT02601950 . [Table: see text]
Effect of early integration of specialized palliative care into standard oncologic treatment on the quality of life of patients with advanced head and neck cancers: A phase III randomized controlled trial.
Authors: Singhai Pankaj , Patil Vijay Maruti , Muckaden Mary Ann , Deodhar Jayita , Salins Naveen , Noronha Vanita , Joshi Amit , Menon Nandini Sharrel , Khake Ashwini , Dhumal Sachin Babanrao , Prabhash Kumar
Published: May 2020

12013

Background: Early palliative care is an important aspect of palliative treatment but has never been evaluated in head and neck cancer. Hence we performed this study. Methods: This was an open-label phase 3 randomised study which enrolled adult patients with squamous cell carcinoma of the head and neck region which warranted palliative systemic therapy. They were 1:1 allocated to either systemic therapy with (EPC arm) or without the addition of early palliative care service (STD arm). Patients were administered the Edmonton Symptom Assessment Scale (ESAS-r) and FACIT HN questionnaire at baseline and 4 weekly thereafter for 12 weeks. The primary endpoint was change in the quality of life (QOL) measured using FACIT HN 12 weeks after randomization. The secondary endpoints were changed in symptom burden at 12 weeks in ESAS-r and overall survival. A repeated-measures analysis of covariance (ANCOVA) was performed to examine the effects of arm and stratum on change in QOL (or symptom score), after controlling for baseline score. Results: Ninety patients were randomised in each arm between 1st June 2016 to 14th August 2017. The compliance with the questionnaires was 100% at baseline. In EPC arm the 70 patients were alive at 3 months and 67 (95.7%) completed the FACIT HN and 64 (91.4%) completed ESAS-r questionnaires. While in the STD arm out of 69 alive the corresponding figures were 61(88.4%) and 59 (85.5%) respectively. There was no statistical difference in change in QOL scores and ΔESAS-r at 12 weeks between the 2 arms (Table). The median overall survival was similar between the 2 arms. (Hazard ratio for death-1.006 (95%CI 0.7347-1.346)). Conclusion: In this phase 3 study, integration of early palliative care in head and neck cancer patients did not result in improvement in the quality of life scores, symptom scores or overall survival. Clinical trial information: CTRI/2016/03/006693 . [Table: see text]
Prevalence and temporal trends of prescription drug use in cancer survivors: A population study, 2001 to 2016.
Authors: Liu Elisa , Kurz Sylvia Christine , Ahn Jiyoung , Sulman Erik P.
Published: May 2020

12023

Background: The burden of prescription drug use is higher in cancer survivors than the general population. We examined the prevalence and temporal trends of prescription drug use among cancer survivors, with an emphasis on central nervous system (CNS) active medications used to manage long-term cancer sequelae. Methods: Adult respondents with (n=3207) and without (n=40,440) a prior cancer diagnosis from 8 cycles (2001-2016) of the National Health and Nutritional Examinational Survey (NHANES) were evaluated for prescription drug usage. Cross-sectional analyses and temporal trends across cycles were evaluated and weighted to represent the US adult population. Results: Cancer survivors report higher rates of prescription drug usage (85.1% vs 54.3%, p<0.001, and 75.8%, p<0.001) and polypharmacy (27.8% vs 10.7%, p<0.001, and 22.7%, p<0.001) than both unadjusted and age-adjusted controls. Younger survivors report greater usage of CNS (36.8% vs 13.1%, p<0.001), psychotherapeutic (18.4% vs 7.7%, p<0.001), hormonal agents (19.1% vs 10.1%, p=0.003), and gastrointestinal (10.7% vs 4.7%, p=0.02) than controls, while differences are attenuated in older cohorts. Among broad drug categories, the usage of cardiovascular (p-trend<0.001), metabolic (p-trend<0.001), and immunologic agents (p-trend=0.01) has increased. Among CNS active subclasses, the usage of anticonvulsants (p-trend<0.001), anxiolytics (p-trend =0.02), narcotics (p-trend=0.02) and GABA analogs (p-trend<0.001) has increased. When comparing respondents with and without a history of cancer, the increased usage of anti-depressant prescription medications (18.3% vs 1.5% p<0.001), including SSRIs (11.2% vs 1.0%, p<0.001), SSNRIs (3.5% vs 0.3%, p<0.001), tricyclics (2.8% vs 0.1%, p<0.001), among cancer survivors was disproportionate compared to the increased proportion of positive depression screens (9.2% vs 7.0%, p=0.006). Conclusions: Cancer survivors report higher prescription drug use for both chronic conditions and late effects of cancer. The usage of CNS active medications, many of which are used on and off label for their pain management properties, has increased. The higher rates of pharmaceutical use may result in unanticipated long-term toxicities and financial burdens.
The adoption of immune checkpoint inhibitors and patterns of care at the end of life.
Authors: Riaz Fauzia , Gan Geliang , Li Fangyong , Davidoff Amy J. , Adelson Kerin B. , Presley Carolyn J , Adamson Blythe J.S. , Shaw Pooja , Parikh Ravi Bharat , Mamtani Ronac , Gross Cary Philip
Published: May 2020

12027

Background: As immune checkpoint inhibitors (ICIs) have transformed the care of patients with cancer, it is unclear whether treatment at end of life (EOL) has changed. Because aggressive therapy at EOL is associated with increased costs and patient distress, we explored the association between the FDA approvals of ICIs and treatment patterns at EOL. Methods: We conducted a retrospective, observational study using patient-level data from the Flatiron health EHR-derived de-identified database. Patients had advanced melanoma, non-small cell lung cancer (NSCLC) (cancer types with an ICI indication) or microsatellite stable (MSS) colon cancer (a cancer type without an ICI indication) and died between 2013 and 2017. We calculated annual proportions of decedents who received systemic cancer therapy in the final 30 days of life and used logistic regression to model the association between the post-ICI Federal Drug Administration (FDA) approval time period and use of systemic therapy at EOL, adjusting for patient characteristics. We also assessed the use of chemotherapy or targeted/biologic therapies at EOL, before and after FDA approval of ICIs using Pearson Chi Square test. Results: There was an increase in use of EOL systemic cancer therapy in the post-ICI approval period for both melanoma (33.9% to 43.2%, p-value < 0.001) and NSCLC (37.4% to 40.3%, p-value < 0.001). In contrast, the control group of decedents with MSS colon cancer demonstrated no significant increase in use of systemic therapy at EOL. After controlling for patient characteristics, there was a significantly higher odds of receiving systemic treatment at EOL in the post-ICI time period compared to the pre-ICI time period in melanoma (OR 1.42, 95% CI 1.09-1.86, p-value < 0.001) and NSCLC (OR 1.13, 95% CI 1.06-1.20, p value < 0.001), with no significant difference in receipt of systemic therapy in patients with MSS colon cancer. After FDA approval of ICIs, patients with NSCLC and melanoma had a decrease in the use of chemotherapy, with a concomitant increase in use of ICIs at EOL. Decedents with MSS colon cancer did not have a statistically significant change in use of chemotherapy or targeted/biologic therapies during the study period. Conclusions: The adoption of ICIs was associated with a substantive increase in the use of systemic therapy at EOL in melanoma, and a smaller yet significant increase in NSCLC.
Abbreviated geriatric assessment (GA) in new oncology patients and its association with early death.
Authors: Maranzano Michael , Neerukonda Anu Radha , Wallace James Alfred , Dale William , Polite Blase N. , Chow Selina Lai-ming
Published: May 2020

12035

Background: The ASCO 2018 Geriatric Oncology Guidelines support the broad application of GA to risk-stratify patients age ≥65 undergoing cancer-directed therapy. Despite this, GA has not been widely adopted due largely to perceived time and resource constraints. We administered an abbreviated GA by medical assistants (MAs) in an outpatient oncology clinic to explore its feasibility and correlation with adverse events. Methods: This is a single-institution, retrospective study of adults establishing oncology care at an academic medical center from 11/2016-4/2017. MAs completed an abbreviated GA of well-validated tests. Cognitive function was screened by the Mini-Cog (score < 4) and physical function by the Five Times Sit-to-Stand Test (FTSST ≥ 15 seconds). Patient-reported Outcomes (PRO) screened for malnutrition by the Malnutrition Screening Test (MST ≥ 2), for vulnerability by Vulnerable Elders Survey (VES-13 ≥ 3) and for depression by Patient Health Questionnaire-4 (PHQ-4 > 2). The first result within 3 months of the initial visit was used for analysis. ED visits, inpatient admissions and early death, defined as within the first 6 months from the initial visit, were collected from the electronic medical record. GA results and baseline characteristics were modeled for these events using univariate logistic regression. Multivariable regression was performed when univariate regression revealed at least 2 factors with p< 0.1. Results: New patients 65+ years (n=304, median age 72) established care in our practice during this six-month period. Nearly all patients (n=285, 94%) completed at least one GA test. Fewer patients completed the Mini-Cog and FTSST (60% completed) compared to the PRO screenings (83-90% completed). Those with any positive GA screening test were nearly 3 times as likely to die within 6 months of their initial outpatient visit compared with those with no deficits (OR 2.95, 95% CI 1.11-9.30). Those with FTSST ≥ 15 sec or unable to complete were more likely to have an ED visit within 6 months (OR 2.40, 95%CI 1.04-5.46).No other individual screening test had a statistically significant association with adverse events. Conclusions: An abbreviated version of GA completed by MAs can be incorporated into new oncology patient visits for all older adults, and those with any abnormalities on screening tests had a higher likelihood of early death. [Table: see text]
Communication about comorbidities among 527 older patients with advanced cancer and their oncologists and caregivers: A multisite cluster-randomized controlled trial.
Authors: Kleckner Amber , Gilmore Nikesha , Belcher Elizabeth , Magnuson Allison , Dunne Richard Francis , Kleckner Ian , Xu Huiwen , Culakova Eva , Wells Megan , Vogelzang Nicholas J. , Dib Elie G. , Targia Valerie , Peppone Luke Joseph , Mustian Karen Michelle , Mohile Supriya Gupta
Published: May 2020

12040

Background: Older patients with advanced cancer often have comorbidities that increase the risk of toxicity from neoplastic therapy but are not always considered in treatment planning. We assessed the utility of a geriatric assessment (GA) intervention to increase the number and quality of discussions about comorbidities among oncologists, older patients, and caregivers. Methods: This multi-site trial enrolled patients who were ≥70 years, had advanced solid tumors or lymphoma, had ≥1 GA impairment, and who were considering or receiving cancer treatment. All patients received the GA and completed an Older Americans Resources and Services Comorbidity survey, which evaluated 15 conditions and interference with activities (clinical impairment = ≥3 comorbidities or ≥1 highly interfering). Oncology practices were randomized to intervention (GA with a summary with management recommendations provided to oncologists) or usual care (GA only). The clinic visit after GA was audio-recorded, transcribed, and coded for GA topics including comorbidity. Generalized linear mixed models adjusting for site (random effect) were used to assess the effect of the intervention. Results: Patients (n=527 evaluable, 76.6±5.2 years, 49% female) and oncologists (n=131, 63 in intervention) were enrolled from 31 sites. In total, 94.5% of patients had ≥1 comorbidity with an average of 3.2±1.9; 64% were clinically impaired by comorbidity (p=0.76 between arms). The intervention arm had twice the number of conversations about comorbidities (1.02 vs. 0.52 conversations per patient, difference 0.50, 95% CI 0.18-0.81, p=0.004) and conversations were more likely to be initiated by the oncologist (p<0.001, Table). Moreover, among patients who had conversations about comorbidities, more patients in the intervention arm had discussions specifically addressing comorbidities (e.g., cancer treatment modification, communication with the primary care physician; 24.3% vs. 7.5%, p=0.003). Conclusions: Providing oncologists with a GA summary and recommendations encouraged them to engage in more discussions about their patients’ comorbidities with the goal of addressing interactions between comorbidities, cancer, and its treatments. Funds: PCORI CD4634, NCI UG1CA189961 Clinical trial information: NCT02107443 . [Table: see text]
Gait speed and recommended treatment intensity among older adults with blood cancers.
Authors: Hantel Andrew , Odejide Oreofe O , Luskin Marlise Rachel , Sperling Adam Samuel , Hshieh Tammy , DuMontier Clark , Chen Richard , Soiffer Robert , Driver Jane A. , Abel Gregory A.
Published: May 2020

12041

Background: Gait speed identifies frailty and predicts survival among older adults with hematologic malignancies (Liu, Blood, 2019). It is not known if gait speed correlates with the intensity of oncologists’ recommended treatment in this population. Methods: From 2/2015-11/2019, patients ≥75 years presenting for an initial hematologic malignancy consultation at the Dana-Farber Cancer Institute were approached for a screening frailty assessment including a 4-meter gait speed test, reported as <0.4, 0.4-0.6, 0.6-0.8, or >0.8 meters/second (m/s). Faster gait speed is associated with less frailty and predicts better survival. Gait speed was not reported to the oncologist. Treatment recommendations were categorized into standard, reduced, or no therapy based on NCCN guidelines, as applicable. Gait/treatment intensity “mismatches” were characterized as patients with lowest quartile gait speed recommended standard intensity and highest quartile not recommended standard intensity. Multivariable regression was performed to assess if gait speed predicted treatment intensity (controlling for age, sex, ECOG performance status [PS], and disease type). Results: Of 786 patients enrolled, 408 required active treatment where NCCN guidelines vary by fitness. Mismatches were seen in 26.7% of patients (Table: column percentages with 95% CI, mismatches starred): 10 (21.3%) with lowest quartile gait speed recommended standard intensity and 99 (55.0%) with highest quartile recommended reduced or no therapy. In multivariable analysis, PS was predictive of no therapy as compared to standard intensity (all p<0.02) and age was predictive of reduced as compared to standard intensity (p<0.01); gait speed was not reliably predictive in either case. Conclusions: In this large cohort of older adults with hematologic malignancies, gait/treatment intensity mismatches occurred in over one-quarter of patients. Oncologists’ recommendations were predicted by age and PS but not gait speed. Given that gait speed is a strong predictor of survival in this population, oncologists should integrate it to minimize over- and under-treatment when making treatment recommendations. [Table: see text]
External validation of two predictive scores of chemotherapy toxicities among older patients with solid cancer, from ELCAPA prospective cohort.
Authors: Frelaut Maxime , Caillet Philippe , Culine Stephane , Paillaud Elena , Tournigand Christophe , Canoui-Poitrine Florence
Published: May 2020

12050

Background: Severe chemotherapy toxicities are frequent among older patients, and may have a major impact on mortality, comorbidities, and quality of life. Two scores were developed to predict severe toxicities: Chemotherapy Risk Assessment Scale for High-age patients (CRASH) score, and Cancer and Aging Research Group Study (CARG) score. The main objective of the present study was to evaluate the predictive value of both scores on an external cohort. Secondary objective was to identify individual predictive factors of severe chemotherapy toxicities. Methods: The Elderly Cancer Patients (ELCAPA) survey consists in a prospective cohort including patients aged 70 years or older referred for a geriatric assessment (GA) before anticancer treatment, such as chemotherapy for solid cancer. CARG and CRASH score were retrospectively collected. Main endpoint was grade 3/4/5 toxicities for CARG-score, hematologic grade 4/5 and non-hematologic grade 3/4/5 toxicities for CRASH-score. Calibration and discrimination (Area Under ROC Curve, AUC) were evaluated. Results: From July 2010 to March 2017, 248 patients were included. Among them, 150 (61%) experienced severe toxicity as defined in CARG study, and 126 (51%) as defined in CRASH study. There was no increased risk of toxicity in intermediate and high risk groups of CARG-score compared to low risk group (OR = 0.3, IC95% [0.1 – 1.4], p= 0.1; and OR = 0.4, IC95%[0.1 – 1.7], p= 0.2 respectively, AUC-ROC = 0.55). Similarly, there was no more risk of severe toxicities in intermediate low, intermediate high, and high risk groups compared to low risk groups of CRASH combined score (respectively OR = 1, IC95% [0.3 – 3.6], p= 0.99; OR = 1, IC95% [0.3 – 3.4], p= 0.9; OR = 1.5, IC95% [0.3 – 8.1], p= 0.67; AUC-ROC = 0.52). A multivariate predictive model including cancer type, performance status (PS 0 vs. PS 1-2), number of severe comorbidities (Cumulative Illness Rating Scale for Geriatrics, CIRS-G, ≥1 grade 3 or 4 comorbidity), body mass index (BMI > 25 kg/m² protective vs. normal BMI), and Chemotox score (1 vs. 0) had an AUC of 0.78. Conclusions: Neither CARG nor CRASH score was predictive of severe chemotherapy toxicities in the ELCAPA cohort. There is a need to identify new predictors of chemotherapy toxicity in older patients with solid cancers.