bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated, IHC/FISH-free, H&E histopathology image-based HER2 amplification, tumor infiltrating lymphocyte (TIL) and tumor heterogeneity profiling in breast cancer.
Authors: Mukhopadhyay Satabhisa , Dasgupta Tathagata , Orsi Nicolas M , Cummings Michele , Berwick Angelene
Published: June 2021

593

Background: Digital pathology has fostered the development of automated diagnostic solutions. However, current technologies in breast cancer remain unable to determine HER2 amplification status, which is established by immunohistochemistry (IHC) and/or fluorescent in situ hybridization (FISH). These ancillary tests carry a significant cost, prolong diagnostic time and fail to capture HER2 tumor heterogeneity and tumor infiltrating lymphocyte (TIL) burden, both of which determine the effectiveness anti-HER2 targeted therapy. Methods: This study describes the real-life clinical context development and validation of a patented novel, universal, automated, white-box, scanning platform agnostic solution that determines HER2 amplification status, prognostically significant TIL levels and tumor heterogeneity index (HI) from hematoxylin and eosin (H&E) stained malignant breast biopsy whole slide images (WSIs) alone. Unlike conventional artificial intelligence-based approaches, the underlying proprietary algorithm’s prediction criteria are explainable and are based on deterministic, hard-coded observational relationships of scale constructed from image morphological features mapped to observables representing underlying tumor-related perturbations in biological pathways/mitotic checkpoints.This includes G1/S deregulation signatures reflecting oncogenic HER2-neu. Results: Blinded validation of HER2 status prediction (n = 197 WSIs; 118 independent cases/patients) showed excellent diagnostic performance (κ = 0.85) relative to existing standard-of-care methodologies. This was independent of WSI file format, background histology, tumor subtype/grade or hormone receptor status. The device also displayed good accuracy (92%) in determining TIL profiles, and its combined HER2-TIL and HER2-HI prediction scales both exhibited a significant association with progression-free survival (CoxPH hazard ratio: 1.856; 95% CI: 1.002-3.438; p = 0.049 and CoxPH hazard ratio: 3.45; 95% CI: 0.95-12.55; p = 0.060). Conclusions: This technology opens up the future possibility of bypassing existing ancillary HER2 profiling investigations, thus potentially reducing laboratory workloads/healthcare costs while accelerating diagnostic turnaround times for patient benefit. In the interim, if used as an adjunct tool, this device could provide an objective HER2 testing reference scale while the robustness of its prediction of patient response to anti-HER2 targeted therapy is fully explored.
Phase II trial of soluble EphB4-albumin in combination with PD-1 antibody (pembrolizumab) in relapsed/refractory head neck squamous cell carcinoma.
Authors: Jackovich Alexandra , Gitlitz Barbara J. , Tiu-lim Justin Wayne Wong , Duddalwar Vinay , King Kevin George , El-Khoueiry Anthony B. , Thomas Jacob Stephen , Tsao-Wei Denice , Quinn David I. , Gill Parkash S. , Nieva Jorge J.
Published: June 2021

6016

Background: EphB4 receptor tyrosine kinase and its ligand EphrinB2 are highly induced in head neck squamous cell carcinoma (HN SCC) tumor cells and vessels, particularly in HPV negative tumors. Each are predictors for poor survival with worse prognosis when both are induced. EphB4 provides tumor cell survival and EphrinB2 inhibits immune cell invasion. Soluble EphB4-Alb blocks bidirectional signaling, enhances immune cell recruitment alone and when combined with PD-1 antibody. Methods: A phase II trial of sEphB4-Alb combined with pembrolizumab accrued HN SCC patients after failure of one or more prior regimens. IHC positivity for p16 was used as a surrogate for HPV infection. Treatment regimen was sEphB4-Alb 10 mg/kg weekly IV infusion with pembrolizumab 200 mg IV infusion every three weeks. Study endpoints were toxicity, overall response rates (ORR) and overall survival (OS). Response to therapy was based on RECIST 1.1 criteria. Patient tumor samples were collected at baseline with a 2nd biopsy at week 8 on therapy, for tissue analysis of PD-L1, EphrinB2 and other biomarkers. Results: Twenty-four patients were accrued to the phase II trial combination of sEphB4-Alb and pembrolizumab. Age, sex, prior treatment, HPV status, and response data are summarized in the table below. The most common toxicity was hypertension with 8 patients experiencing grade 3 HTN. No grade 4 or above toxicities were observed. Among HPV negative cases, partial and complete responses were observed in 6 of 14 patients (43%) with complete response (CR) observed in 3 of 6 responders. Additionally, rapid response was observed in 3 of 14 HPV negative patients. Response was associated with increase in immune markers on 2nd biopsy. Median overall and progression-free survival in all patients was 12.6 months and 8.6 months, respectively. Conclusions: 1. sEphB4-Alb was well tolerated in combination with PD-1 antibody. 2. sEphB4-Alb was associated with increased immune response to tumor, when combined with PD-1 antibody. 3. sEphB4-Alb appears to have substantial activity (including complete remission) when combined with PD-1 antibody in relapsed/refractory HPV negative HN SCC. Clinical trial information: NCT03049618. [Table: see text]
Long-term follow-up of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in advanced squamous cell carcinoma of the head and neck (SCCHN).
Authors: Cho Byoung Chul , Daste Amaury , Ravaud Alain , Salas Sébastien , Isambert Nicolas , McClay Edward Francis , Awada Ahmad , Borel Christian , Helwig Christoph , Rolfe P. Alexander , Ojalvo Laureen S. , Gulley James L. , Penel Nicolas
Published: June 2021

6020

Background: Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. A previous report of an expansion cohort from a phase 1 study (NCT02517398) suggested that bintrafusp alfa had a manageable safety profile and early signs of clinical activity in patients with heavily pretreated, advanced SCCHN after a median follow-up of 86.4 weeks. Here we report long-term efficacy and safety for this cohort. Methods: Patients with advanced SCCHN that progressed/recurred after platinum therapy in the recurrent/metastatic setting, or < 6 months after platinum therapy in the locally advanced setting, received bintrafusp alfa 1200 mg every 2 weeks until confirmed progressive disease, unacceptable toxicity, or trial withdrawal. The primary endpoint was confirmed best overall response assessed per RECIST 1.1 assessed by independent review committee (IRC); safety was a secondary endpoint. Results: As of May 15, 2020, 32 patients had received bintrafusp alfa for a median of 2.8 months (range, 0.5-29.9 months), no patient remained on treatment, and median follow-up to data cutoff was 41.7 months (range, 39.8-43.5 months). The objective response rate (ORR; 13%) was unchanged since the previous report; median duration of response (DOR) was increased at 21.4 months (95% CI, 5.5 months to not reached [NR]). While the clinical activity of bintrafusp alfa may be improved in patients with HPV-positive tumors (Table), outcomes were generally similar between PD-L1 subgroups (≥1% vs < 1% tumor cells). The overall safety profile was consistent with the previous report for this cohort, without grade 4 nor 5 treatment-related adverse events (TRAEs); no new TRAEs of grade 3 or that led to discontinuation of bintrafusp alfa were reported. Conclusions: With a median follow-up of over 3 years in patients with heavily pretreated advanced SCCHN, bintrafusp alfa showed sustained clinical activity and 3-year OS of 24.0%, which compares favorably to historical data. Clinical activity appeared to be greater in patients with HPV-positive tumors than those with HPV-negative tumors. The safety profile was manageable and consistent with earlier analysis. Further investigation of bintrafusp alfa in SCCHN and other HPV-associated cancers is ongoing. Clinical trial information: NCT02517398. [Table: see text]
Maintenance intervention to improve survival in patients with metastatic nasopharyngeal carcinoma who benefit from first-line treatment: A prospective multicenter randomized controlled clinical study.
Authors: Lu Ying , Huang Haixin , Yang Hui , Hu Xiaohua , Feng Xianbing , Huang Changjie
Published: June 2021

6035

Background: The role of drug maintenance intervention in improving survival outcomes remains controversial.To investigate the safety and effect of Tegafur(S1) maintenance intervention in patients with metastatic nasopharyngeal carcinoma who benefit from the first-line treatment in a multicenter randomized controlled study, and to identify the related biological prognostic factors and guide the individualized treatment choice. Methods: Patients with metastatic nasopharyngeal carcinoma in the Fourth Affiliated Hospital of Guangxi Medical University and other cancer centers who met the inclusion criteria were randomly divided into maintenance therapy group: S1 maintenance therapy until disease progression or intolerance; Observation group: follow-up to disease progression. PFS, overall survival (OS) and adverse reactions of S1 maintenance therapy were compared between the two groups. The correlation between EBV-DNA, human serum amyloid A (SAA) and prognosis was evaluated. Results: Follow-up was conducted to May 2020, with a median follow-up of 19.8 months (6.1-51.3 months), 183 cases were evaluable (88 cases in S1 maintenance treatment group, 95 cases in observation group). Compared with the observation group, the S1 maintenance treatment group significantly increased patients' median PFS (16.2 months vs. 8.7 months, P < 0.001) and median OS (32.1 months vs. 18.2 months, P < 0.001). Reduced the risk of poor prognosis for PFS and OS (PFS: HR 0.305, 95%CI 0.211-0.441, < 0.001; OS: HR 0.363, 95%CI 0.238-0.553, P < 0.001). In the maintenance treatment group, the median S1 treatment lasted for 14 courses (4-58 courses), and the main adverse reactions were grade 1 skin pigmentation, oral mucositis, hand-foot syndrome, nausea, etc. No grade 4 toxic reaction occurred, and it was well tolerated. Compared with observation patients with negative EBV-DNA, observation patients with positive EBV-DNA had a higher risk of poor prognosis for PFS (HR 1.764, 95%CI 1.078-2.887, P = 0.024). The risk of poor prognosis in patients with positive EBV-NDA was significantly reduced by 61.1% ( < 0.001) for PFS and 65.5% (P = 0.001) for OS (P = 0.001). Compared with the observation group with stable SAA expression, S1 maintenance therapy significantly improved the prognosis of patients. Patients with continuous decline in SAA had a 61.9% lower risk of poor prognosis in PFS (P < 0.001) and a 60.2% lower risk of poor prognosis in OS (P = 0.007). Conclusions: For patients with metastatic nasopharyngeal carcinoma who benefit from first-line treatment, maintenance therapy of S1 can significantly improve the survival prognosis and is well tolerated. Patients with positive EBV-DNA and continuous decline in SAA may benefit more from maintenance intervention. Clinical trial information: ChiCTR-IOR-16007939.
Update and external validation of a multivariable prediction model for tube feeding dependency for at least four weeks during chemoradiotherapy for head and neck cancer.
Authors: Willemsen Anna C. H. , Kok Annemieke , Baijens Laura W.J. , De Boer J. P. , de Bree Remco , Devriese Lot , Driessen Chantal M.L. , Van Herpen Carla M.L.- , Hoebers F. J.P. , Kaanders Johannes H.A.M. , Karsten Rebecca T. , Van Kuijk Sander , Lalisang Roy Iqbal , Navran Arash , Pereboom Susanne R. , Schols Annemie M.W.J. , Terhaard Chris H.J. , Hoeben Ann
Published: June 2021

6040

Background: Patients who receive chemoradiation or bioradiation (CRT/BRT) for locally advanced head and neck squamous cell carcinoma (LAHNSCC) often experience high toxicity rates, which may interfere with oral intake, leading to (temporary) tube feeding (TF) dependency. International guidelines recommend gastrostomy insertion when the expected use of TF exceeds four weeks. In this study we aimed to update and externally validate a prediction model to identify patients in need for TF for at least four weeks, meeting the international criteria for prophylactic gastrostomy insertion. Methods: This retrospective multicenter cohort study was performed in four tertiary referral head and neck cancer centers in the Netherlands. The prediction model was developed using data from the University Medical Center Utrecht and the Netherlands Cancer Institute. The model was externally validated in patients from the Maastricht University Medical Center and Radboud University Medical Center. The primary endpoint was TF, initiated during or within 30 days after completion of CRT/BRT, and administered for at least four weeks. Potential predictors were retrieved from patient medical records and radiotherapy dose-volume parameters were calculated. Results: The developmental and validation cohort included 409 and 334 patients respectively. Multivariable analysis showed significant predictive value (p < 0.05) for adjusted diet at start of CRT/BRT, percentage weight change prior to treatment initiation, WHO performance status, tumor-site, nodal stage, mean radiation dose to the contralateral parotid gland, and mean radiation dose to the oral cavity. The area under the receiver operating characteristics curve for the updated model was 0.73 and after external validation 0.64. Positive and negative predictive value at 90% cut off were 80.0% and 48.2% respectively. Conclusions: This externally validated prediction model to estimate TF-dependency for at least four weeks in LAHNSCC patients performs well. This model, which will be presented, can be used in clinical practice to guide personalized decision making on prophylactic gastrostomy insertion.
Cisplatin and capecitabine induction chemotherapy in nasopharyngeal carcinoma.
Authors: Xu Zhiyuan , Yang Li , Lee Victor Ho-Fun , Lee Anne W. M.
Published: June 2021

6065

Background: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is now one of the standard treatment for locally advanced nasopharyngeal carcinoma (LANPC). Cisplatin/fluorouracil is one of the recommended IC regimens. Capecitabine is an oral fluoropyrimidine prodrug with higher concentrations of fluorouracil attained in the tumor cells after enzymatic conversions. We conducted this study to evaluate the feasibility, efficacy and safety of cisplatin and capecitabine (PX) IC followed by CCRT in LANPC. Methods: Newly diagnosed patients with LANPC (stage III-IVB according to 7th edition of AJCC/UICC system [TNM-7] and stage III-IVA according to 8th edition [TNM-8) were prospectively recruited from January 2015 to October 2019. They received induction PX (cisplatin: 80mg/m2 on day 1 + capecitabine: 1000mg/m2 twice daily from day 1 to 14 every 3 weeks for 3 cycles) followed by CCRT (cisplatin: 100mg/m2 every 3 weeks for a total of 2-3 cycles concurrent with intensity-modulated radiation therapy [IMRT]). IMRT with doses of 70Gy, 63Gy and 56Gy were delivered to 3 levels of planning target volumes (PTV) (high, intermediate and low risk) respectively and simultaneously in 35 fractions/7 weeks. Tumor response by MRI and CT was evaluated after completion of IC and 16 weeks after completion of CCRT according to RECIST v1.1. All adverse events were graded with NCI CTCAE v4.03. Results: One hundred and forty-five patients were recruited. The stage distributions according to TNM-8 were 82(56.6%) and 63(43.3%) for stage III and IVA, respectively. One hundred and thirty-seven patients completed 3 cycles of induction PX and 122 patients completed IMRT with 2 to 3 cycles of concurrent cisplatin. The median (interquartile range, IQR) tumor regression rates after 2-3 cycles of PX at the nasopharynx (NP) and the neck region (NK) were 51.2% (37.3%-66.5%) and 71.8% (56.7%-81.1%), respectively. At 16 weeks after CCRT, only one patient had residual disease. After a median follow-up of 33 months, 20 treatment failures and 8 deaths were observed. The estimated 2-year progression-free survival (PFS) and overall survival (OS) were 89.8% and 97.2%. The rates of grade 3/4 leukopenia, neutropenia, anemia, nausea/vomiting and electrolyte disturbance during IC were 6.2%, 15.9%, 6.9%, 4.1% and 9.0%, respectively. The corresponding rates were 45.1%, 24.6%, 27.5%, 2.8% and 11.3% during CCRT. Only 1 (0.7%) grade 3/4 hand-foot syndrome and 3 (2.1%) grade 3/4 diarrhea during IC were observed. The rates of grade 3/4 mucositis and dermatitis were 31.0% and 12.7%, respectively. There were no treatment-related deaths. Conclusions: Induction PX followed by CCRT was effective and well tolerated in patients with LANPC. Clinical trial information: NCT03427359.
Comparative assessment of the eighth and seventh AJCC staging edition prognostic performance of patients with p16 positive oropharynx cancer.
Authors: Lazar Neto Felippe , Sousa Luana Guimarães , Johnson Faye M. , Lee J. Jack , Frank Steven J. , Moreno Amy Catherine , Dahlstrom Kristina , Ferrarotto Renata
Published: June 2021

6067

Background: The American Joint Committee on Cancer (AJCC) TNM staging system defines the anatomical extent of disease and serves as a guide for treatment and prognosis. The favorable prognosis of p16+ oropharyngeal squamous cell carcinoma (OPSCC) compared to p16 negative counterpart led to major updates in the AJCC 8th edition. Its prognostic performance, however, warrants further validation. Methods: We included patients diagnosed with p16+ OPSCC enrolled in a prospective registry ( Stiefel) at The University of Texas MD Anderson Cancer Center between March 2015 and December 2018. Patients’ stage at diagnosis was classified according to the AJCC 7th (AJCC-7) and 8th (AJCC-8) editions. Overall survival (OS) and progression-free survival (PFS) was defined as time from diagnosis to death or to progression or death, respectively. The Kaplan-Meier method was used to calculate 1- and 3-year survival probabilities. Differences between groups were compared using the log-rank test. Prognostic discriminative performance of each staging system was evaluated using Harrel’s C-statistic. Survival differences between heavy (> 10 pack-years [PY]) vs. light/never smokers (≤ 10 PY) by AJCC-8 staging groups was assessed with the log-rank test. Results: Of 463 patients, the median follow-up was 34.7 months (2.3-169.74). Nearly 90% (N=413) of patients were down-staged from AJCC-7 to AJCC-8 with 69% of patients with IVA disease based on AJCC-7 (N=319) re-staged as stage I (N=196 [42%]), II (N=79 [17%]) or III (44 [10%]) according to AJCC-8. Over 60% (N=279) of patients were staged as I with AJCC-8. Compared to AJCC-7, AJCC-8 had improved prognostic ability (C-statistic, 0.58 for AJCC-7 vs. 0.63 for AJCC-8) and provided better discriminative survival probabilities at 1 and 3-year follow-up (Table). Similar results were observed for PFS. Smoking status did not impact OS when stratified by AJCC-8 staging groups: I, p=0.347; II, p=0.310; and III, p=0.532 for > 10 vs. ≤ 10 PY. Conclusions: Our cohort validates that the AJCC-8 provides better prognostic discriminative performance when compared to AJCC-7, however, a disproportionate number of patients were classified as stage I. Smoking was not associated with survival within each staging group.[Table: see text]
The efficacy and safety of anlotinib in neoadjuvant treatment in locally advanced thyroid cancer: A single-arm phase II clinical trial.
Authors: Huang Naisi , Sun Guohua , Wang Yulong , Chen Jiaying , Guan Qing , Lu Zhongwu , Xiang Jun , Wei Wenjun , Ma Ben , Ji Qinghai , Wang Yu
Published: June 2021

6069

Background: Surgery is the primary treatment for locally advanced thyroid cancer (TC). For some locally advanced TC, R0/R1 resection could not be achieved at initial diagnosis and neoadjuvant treatment would be an option. However, there is still little evidence regarding neoadjuvant treatment in locally advanced TC. Methods: This single-arm, phase 2 study investigated the efficacy and safety of Anlotinib (12mg orally daily, for two weeks on/on week off) for 2-6 cycles in patients with locally advanced TC in the neoadjuvant setting. Operable patients received surgery after neoadjuvant treatment. The primary endpoint was objective response rate (ORR). Results: A total of 13 patients were included and received an average of 3.5 cycles (range: 3-6 cycles) of Anlotinib treatment. 12 cases were papillary thyroid cancer, and 1 was follicular thyroid cancer. The ORR of Anlotinib was 76.9% with 10 partial response (PR), 2 stable disease (SD), and 1 progressive disease (PD). 8 PR and 1 SD patients received surgery after neoadjuvant treatment, of whom 8 had R0/1 resections and 1 had R2 resection. 2 PR patients refused to have surgery and the rest 2 patients were not operable. The R0/1 resection rate for intent to treat population was 61.5% and for per-protocol population was 72.7%. The maximum reduction in sum of tumor diameter was an average of 34.8% (range: 30.9%-45.5%) for PR patients. Most adverse events were grade 1 or 2. Common adverse events of all grade were hypertension (76.9%), hypertriglyceridemia (69.2%), proteinuria (53.8%), TSH increase (53.8%), cholesterol elevation (53.8%) and hand-foot syndrome (38.5%). The majority of adverse events discontinued after the neoadjuvant treatment stopped. Conclusions: Anlotinib demonstrated antitumor activity in the neoadjuvant treatment in locally advanced TC and the majority of patients achieved R0/1 resection. Adverse events were consistent with the known Anlotinib adverse event profile. These results suggest that Anlotinib neoadjuvant treatment represents a new option for locally advanced TC. Clinical trial information: NCT04309136.
Phase Ib, international, dose-escalation study to evaluate the safety, pharmacokinetics (PK) and efficacy of ST-617 for the attenuation of oral mucositis (OM) in patients receiving chemoradiation (CRT) for head and neck (H&N) cancer.
Authors: Osei-Fofie Daniel , Wetter Julie , Landers Greg A. , Kraus Peter Alfred , Sukumaran Shawgi , Mun Hui , Stein Brian N. , Bray Victoria Jane , Framroze Bomi , Gelfand Jeffrey , Song Paul Y. , Lategan Andries , Dimitriu Mikaela , Sonis Stephen T.
Published: June 2021

6075

Background: OM is a common, painful, and costly toxicity associated with cytotoxic regimens used to treat H&N cancers, which may result in radiotherapy treatment interruptions to negatively impact tumor control. There are currently no approved interventions to successfully prevent or delay OM onset among patients being treated with radiation therapy, with or without concomitant chemotherapy (CRT). Oxidative stress is a critical event in OM’s pathogenesis. Through its effect on Nrf2, ST-617 has marked anti-oxidative activity/properties. Supportive Therapeutics is developing ST-617, a dithioethione, for the attenuation of OM onset, duration and severity. The objective of this trial was to assess the safety, tolerability, PK, PD and efficacy of ST-617 in patients at high risk of severe OM (SOM). Methods: A dose escalation trial in which ST-617 administered as an oral suspension, 1-2 hours before the administration of daily RT fractions was performed at 9 study sites in South Africa and Australia. Eighteen patients with diagnoses of oral or oropharyngeal CA were enrolled (up to 6 pts/dose). Patients received concomitant cisplatin either weekly or tri-weekly. ST-617 was administered 3 days prior to CRT, and then continuing daily until the end of treatment. Safety outcomes, using CTCAE criteria (v 4.03) were used. Dose escalation occurred in the absence of toxicity. OM occurrence and severity were assessed by trained and validated evaluators using WHO, NCI-CTC and RTOG criteria; scores were centrally assigned. The primary efficacy endpoints included the incidence and duration of SOM (WHO grades 3 or 4) vs historical controls. PD tracking measured total ROS/RNS, GSH/GSSG, regulation in plasma and buccal epithelial cells. Results: 17 pts completed the 50, 100 and 150mg/day with no safety issues. No early dose limiting toxicity (DLT) or serious Adverse Event linked to ST-617 were observed. AEs observed were mainly nausea which is usually associated with CRT as expected. The 100 mg/day dose has been well tolerated with no grade 4 OM. No CRT dose interruptions or delays due to OM has been observed. Total ROS/RNS levels in plasma and buccal samples show significant decrease with increased ST-617 dosing from 50 to 100 mg/day. Conclusions: ST-617 administration was safe at all doses tested. The course and severity of patients treated with ST-617 compared favorably with historical controls. Mechanistic correlation between ROS/RNS levels was seen. A randomized, controlled, double blind trial is planned with the recommended dose of 100mg/day. Clinical trial information: 20180138.
A pooled analysis of response to selective RET inhibitors among patients with medullary thyroid cancer with M918T versus non-M918T RET mutations.
Authors: Kim Janice , Bradford Diana , Chatterjee Somak , Mishra-Kalyani Pallavi Shruti , Shen Yuan-Li , Beaver Julia A. , Singh Harpreet
Published: June 2021

6078

Background: Medullary thyroid cancer (MTC) accounts for 1 to 2% of thyroid cancers in the United States; RET alterations occur in >95% of hereditary and 50% of sporadic forms. Up to 80% of patients with sporadic MTC have somatic M918T RET mutations, which is associated with poor prognosis (1). The tyrosine kinase inhibitors (TKIs) cabozantinib and vandetanib are approved to treat patients with MTC regardless of RET status; however, retrospective analyses have suggested that there may be greater benefit in patients with M918T mutations (1,2). Newly approved therapies selpercatinib and pralsetinib, developed for patients with RET mutations, have demonstrated higher response rates than previous first line therapies. In this analysis, we examine the differences in overall response rate (ORR) between patients with MTC with RET M918T non- RET M918T mutations. Methods: An analysis of ORR in patients with MTC with RET M918T mutations with non-M918T mutations was conducted using the efficacy populations used to support the approvals of pralsetinib and selpercatinib using the following groups: Patients who received prior cabozantinib or vandetanib (referred to as “previously treated”). Patients with no prior cabozantinib or vandetanib (“TKI naïve”). All patients regardless of prior therapy. Results: Exploratory analysis of ORR of pooled population of Selpercatinib and Pralsetinib in patients with MTC with RET M918T mutations and non-M918T mutations. 1 Prior vandetanib or cabozantinib. 2 No prior vandetanib or cabozantinib. Two groups of patients were analyzed ( RET M918T mutation and RET non-M918T mutation), with subgroups with respect to prior treatment. Among all patients regardless of prior therapy, the ORR was similar between M918T non-M918T groups. Among previously treated patients, the ORR was lower in the M918T group vs. the non-M918T group, while in the TKI naïve group the ORR was higher in the M918T groups vs the non-M918T group although the 95% CIs overlap in both comparisons. Conclusions: There were no major differences in ORR among mutational subtypes in patients with MTC treated with RET inhibitors, regardless of prior therapy. ORR was similar between patients with M918T and non-M918T mutations. Additional experience in ongoing clinical studies may provide additional data regarding responses across specific mutation types. References: 1.Sherman SI et al “Correlative analyses of RET and RAS mutations in a phase 3 trial of cabozantinib...” Cancer. 2016;122(24):3856-3864. 2.Wells SA Jr et al “Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer...” J Clin Oncol. 2012;30(2):134-41.[Table: see text]
Racial and ethnic disparities among patients with breast cancer and COVID-19.
Authors: Nagaraj Gayathri , Accordino Melissa Kate , French Benjamin , Kuderer Nicole M. , Lyman Gary H. , Stover Daniel G. , Blinder Victoria Susana , Schmidt Andrew Lachlan , Shatsky Rebecca Arielle , Grover Punita , Puc Matthew , Hwang Clara , Wulff-Burchfield Elizabeth Marie , Lewis Mark Andrew , Menendez Alvaro G. , Bilen Mehmet Asim , Warner Jeremy Lyle , Lustberg Maryam B. , Shah Dimpy P
Published: June 2021

6500

Background: Racial/ethnic minorities have disproportionately increased risk of contracting COVID-19 and experiencing severe illness; they also have worse breast cancer (BC) outcomes. COVID-19 outcomes among racial/ethnic minorities with BC are currently unknown. We sought to compare clinicopathologic characteristics and COVID-19 outcomes stratified by race/ethnicity. Methods: The COVID-19 and Cancer Consortium registry (NCT04354701) was used to identify patients with invasive BC and laboratory-confirmed SARS-CoV-2 diagnosed in the U.S. between 2020-03-06 and 2021-02-04. The primary analysis was restricted to women who self-identified as non-Hispanic White (NHW), non-Hispanic Black (NHB), or Hispanic (H). Demographic, cancer characteristics, and COVID-19 outcomes were evaluated. COVID-19 outcomes included: hospital admission, intensive care unit (ICU) admission, mechanical ventilation, death within 30 days of COVID-19 diagnosis and death from any cause during follow-up. Descriptive statistics were used to compare clinicopathologic characteristics and Fisher exact tests were used to compare COVID-19 outcomes across the 3 racial/ethnic groups. Results: A total of 1133 patients were identified of which 1111 (98%) were women; of which 575 (52%) NHW, 243 (22%) NHB, 183 (16%) H, and 110 (10%) other/unknown. Baseline characteristics differed among racial/ethnic groups. H were younger (median age: NHW 63y; NHB 62y; H 54y) and more likely to be never smokers (NHW 62%; NHB 62%; H 78%). NHB had higher rates of obesity (NHW 40%; NHB 54%; H 46%), diabetes (NHW 16 %; NHB 32%; H 20%) and combined moderate and severe baseline COVID-19 at presentation (NHW 28%; NHB 42%; H 28%). Cancer characteristics are as shown (Table). Significant differences were observed in outcomes across racial/ethnic groups including higher rates of hospital admission (NHW 34%; NHB 49%; H 34%; P <0.001), mechanical ventilation (NHW 3%; NHB 9%; H 5%; P=0.002), 30-day mortality (NHW 6%; NHB 9%; H 4%; P=0.043) and total mortality (NHW 8%; NHB 12%; H 5%; P=0.05) among NHB compared to NHW and H. Conclusions: This is the largest study to show significant differences in COVID-19 outcomes by racial/ethnic groups of women with BC. The adverse outcomes in NHB could be due to higher moderate to severe COVID-19 at presentation and preexisting co-morbidities. H did not have worse outcomes despite having more active disease and recent anti-cancer therapy, including with cytotoxic chemotherapy – potentially due to younger age and nonsmoking status.[Table: see text]
Mortality risk for patients undergoing cancer treatment who acquire SARS-CoV-2: ASCO registry.
Authors: Mileham Kathryn Finch , Bruinooge Suanna Steeby , Aggarwal Charu , Patrick Alicia L. , Davis Christiana , Mesenhowski Daniel , Spira Alexander I. , Clayton Eric J. , Waterhouse David Michael , Moore Sue , Jazieh Abdul-Rahman , Chen Ronald C. , Kaltenbaugh Melinda , Williams Jen Hanley , Schilsky Richard L. , Garrett-Mayer Liz
Published: June 2021

6509

Background: The ASCO Registry was created to analyze the impact of COVID-19 (COVID) on treatment (Tx) and outcomes of patients (pts) with cancer. Methods: The Registry includes pts with 1) a confirmed COVID diagnosis (Dx) and 2) clinically evident cancer receiving Tx/supportive care or resected cancer on adjuvant Tx <12 mos since surgery. Practices report data on cancer Dx and Tx at COVID Dx, COVID symptoms, comorbidities, cancer/COVID Tx, and survival. Kaplan-Meier estimation provided 30- and 90-day mortality rate estimates for pts with COVID Dx before or since 6/1/20 within pt subgroups with 95% confidence intervals (CI). Data submission cutoff for all practices was 10/24/20, except one that was 11/16/20. Results: This analysis reports on 453 pts with COVID Dx 3/5/20 to 10/22/20 who were on anticancer drug Tx for regional (9%) or metastatic (53%) solid tumors or hematologic cancers (38%) at COVID Dx. 38 practices entered data: health system-owned 51% of pts, privately-owned 25%, academic 24%. 53% of pts have ≥30 days follow-up or died ≤30 days from COVID Dx. Median age is 64 years; 53% of pts are female; 28% of pts are asymptomatic at COVID Dx. Multiple myeloma was most frequent cancer (17%). All-cause mortality rates (30 and 90 days) increased with pts’ age at COVID Dx [Table]. No mortality difference was seen based on sex, race, or comorbidities (hypertension, diabetes, pulmonary disease). Pts with COVID Dx before June 1 had worse survival than pts diagnosed on/after June 1. Pts with B-cell malignancies had higher mortality rates than pts with solid tumors. Conclusions: Severity of COVID illness and mortality were greater for patients with COVID Dx pre-June 1 than on/after June 1. Differences on/after June 1 may be attributed to improvements in COVID management, higher COVID testing rates, and more asymptomatic pts diagnosed. Variations in COVID-19 pt populations over time due to these changes should be considered when analyzing and interpreting pandemic data. Cancer pts with advanced age and B-cell cancers are at greatest risk of death but mortality rates for all groups (except those admitted to ICU) improved after 6/1/2020.[Table: see text]
Impact of Medicaid expansion on two-year mortality among stage IV breast cancer (BC) patients according to race.
Authors: Malinowski Catalina , Lei Xiudong , Zhao Hui , Giordano Sharon H. , Chavez Mac Gregor Mariana
Published: June 2021

6525

Background: Inadequate access to healthcare services is associated with worse outcomes. Disparities in access to cancer care are more frequently seen among racial/ethnic minorities, uninsured patients, and those with low socioeconomic status. A provision in the Affordable Care Act called for expansion of Medicaid eligibility in order to cover more low-income Americans. In this study, we evaluate the impact of Medicaid expansion in 2-year mortality among metastatic BC patients according to race. Methods: Women (aged 40-64) diagnosed with metastatic BC (stage IV de novo) between 01/01/2010 and 12/31/2015 and residing in states that underwent Medicaid expansion in 01/2014 were identified in the National Cancer Database. For comparison purposes, 2010-2013 was considered the pre-expansion period and 2014-2015 the post-expansion period. We calculated 2-year mortality difference-in-difference (DID) estimates between White and non-White patients using multivariable linear regression models. Results are presented as adjusted differences (in % points) between groups in the pre- and post-expansion periods and as adjusted DID with 95%CI. Covariates included age, comorbidity, BC subtype, insurance type, transfer of care, distance to hospital, region, residence area, education, income quartile, facility type and facility volume. In addition, overall survival (OS) was evaluated in pre- and post-expansion periods via Kaplan-Meier method and Cox proportional hazards models; results are presented as 2-year OS estimates, hazard ratios (HRs), and 95% CIs. Results: Among 7,675 patients included, 4,942 were diagnosed in the pre- and 2,733 in the post-expansion period. We observed a reduction in 2-year mortality rates in both groups according to Medicaid expansion. Among Whites 2-year mortality decreased from 42.5% to 38.7% and among non-Whites from 45.4% to 36.4%, resulting in an adjusted DID of -5.2% (95%CI -9.8 to -0.6, p = 0.027). A greater reduction in 2-year mortality was observed among non-Whites in a sub-analysis of patients who resided in the poorest quartile (n = 1372), with an adjusted DID of -14.6% (95%CI -24.8 to -4.4, p = 0.005). In the multivariable Cox model, during the pre-expansion period there was an increased risk of death for non-Whites compared to Whites (HR 1.14, 95% CI 1.03 to 1.26, P = 0.04), however no differences were seen in the post-expansion period between the two groups (HR 0.93, 95% CI 0.80 to 1.07, P = 0.31). Conclusions: Medicaid expansion reduced racial disparities by decreasing the 2-year mortality of non-White patients with metastatic breast cancer and reducing the gap when compared to Whites. These results highlight the positive impact of policies aimed at improving equity and increasing access to health care.
Financial toxicity, symptom burden, illness perceptions, and communication confidence in cancer clinical trial participants.
Authors: Perni Subha , Gorton Emily , Park Elyse R , Chabner Bruce Allan , Moy Beverly , Nipp Ryan David
Published: June 2021

6526

Background: Cancer clinical trial (CCT) participants are at high risk for experiencing adverse effects from financial toxicity, yet this remains understudied in the CCT population. We sought to describe associations among patient-reported financial toxicity (financial burden [FB] and trial cost concerns), physical and psychological symptoms, illness perceptions, and communication confidence in CCT participants. Methods: From 7/2015-7/2017, we prospectively enrolled CCT participants who expressed interest in financial assistance and a group of patients matched by age, sex, cancer type, specific trial, and trial phase. We assessed FB (burdened by costs of cancer care), trial cost concerns (worried about affording medical costs of a CCT), physical (Edmonton Symptom Assessment Scale [ESAS]) and psychological (Patient Health Questionnaire-4 [PHQ-4]) symptoms, illness perceptions (Brief Illness Perception Questionnaire [BIPQ]), and communication confidence (Perceived Efficacy in Patient-Physician Interactions [PEPPI]). We used regression models to explore sociodemographic associations with FB and trial cost concerns, and to examine associations of FB and trial cost concerns with patients’ symptom burden, illness perceptions, and communication confidence, adjusting for age, sex, race, performance status, marital status, and metastatic status. Results: Of 198 patients enrolled, 112 (56.6%) reported FB and 82 (41.4%) had trial cost concerns. Patients with FB were younger (OR 0.96, 95% CI 0.94-0.98) and had lower incomes ( < $100,000, OR 4.61, 95% CI 2.35-9.01). Patients reporting trial cost concerns also had lower incomes ( < $100,000, OR 2.78, 95% CI 1.45-5.29). On adjusted analyses, patients with FB had higher ESAS total (OR 1.03, 95% CI 1.02-1.05), ESAS physical (OR 1.04, 95% CI 1.02-1.07), PHQ-4 depression (OR 1.54, 95% CI 1.22-1.94), and PHQ-4 anxiety (OR 1.30, 95% CI 1.08-1.55) scores, as well as more negative illness perceptions (OR 1.04, 95% CI 1.01-1.07), but no significant difference in communication confidence (OR 0.98, 95% CI 0.93-1.05). Patients reporting trial cost concerns had higher ESAS total (OR 1.03, 95% CI 1.01-1.05), ESAS physical (OR 1.04, 95% CI 1.01-1.06), PHQ-4 depression (OR 1.35, 95% CI 1.10-1.65), and PHQ-4 anxiety (OR 1.27, 95% CI 1.07-1.51) scores, as well as more negative illness perceptions (OR 1.06, 95% CI 1.03-1.10), and lower communication confidence (OR 0.93, 95% CI 0.87-0.99). Conclusions: In this study of CCT participants, younger patients with lower incomes were most vulnerable to financial toxicity. Financial toxicity was associated with greater symptom burden, more negative illness perceptions, and lower communication confidence, which underscores the importance of addressing these issues when seeking to alleviate the adverse effects of financial toxicity in CCT participants.
Disparities in cancer prevalence in African Americans: A United States population study 2021.
Authors: Kassem Ahmad Nader , Alkrekshi Akram , Arroyo Suarez Raul
Published: June 2021

6531

Background: African-Americans (AA) have the highest incidence and death rates from cancer and the shortest survival of all racial groups in the USA, as reiterated by the American Cancer Society’s Cancer Facts and Figures for AA from 2019. We studied cancer prevalence in AA compared to Caucasians, focusing on patients with above-normal Body Mass Index (BMI). Methods: Data was collected from Explorys, IBM, a national database including over 73 million patients. Patients were divided based on age (18-64 and ≥ 65 years; for female cancers 18-49 and ≥ 50 years), race (Caucasians and AA), and BMI (18.5 - < 25 and ≥ 25.0 kg/m2). The odds ratio (OR) and 95% confidence interval (CI) for multiple cancer rates in AA compared to Caucasians were calculated with P values <0.001 considered significant. Results: N: Normal BMI EW: Excess weight (Females) C: Caucasian S: Significant NS: Non-significant. Conclusions: Our results show a significantly lower than expected prevalence of screenable cancers in AA compared to Caucasians, diverging widely from established incidence rates. The difference was more remarkable in pre-Medicare age (< 65 years) and excess weight patients. These disparities are concerning for a compromised healthcare access contributing to underdiagnosis of cancer or shorter survival among AA in the US.[Table: see text]
Accessibility of Telehealth services for cancer care at cancer hospital in the United States.
Authors: Marks Victoria A. , Hsiang Walter R. , Nie James , Umer Waez , Haleem Afash , Galal Bayan , Pak Irene , Kim Dana , Kenney Patrick Aloysius , Leapman Michael S.
Published: June 2021

6535

Background: The COVID-19 pandemic has dramatically accelerated the availability of telehealth services for patients with cancer. However, little national cross-sectional data is available to inform potential gaps in access. We aimed to characterize overall access to and trends in telehealth availability for new cancer care patients at hospitals across the United States. Methods: We performed a cross sectional secret-shopper study to evaluate the availability of telehealth services for new patients for three major cancer types—colorectal, breast, and skin cancer—at Commission on Cancer accredited hospitals during the period of April to November 2020. American Hospital Association and Center for Medicare and Medicaid Service databases were queried to determine hospital characteristics. We described hospital variation in access to telehealth services using descriptive statistics. Univariable and multivariable logistic regression were used to identify factors associated with telehealth availability. Results: Of 334 successfully contacted facilities, 248 (74%) offered new patient telehealth services for at least one cancer type. However, access differed by cancer site: telehealth availability for new patients with skin, colorectal, and breast cancer was 47%, 42%, and 38%, respectively. Of the facilities sampled, 47% offered telehealth for one cancer type, 40% for two cancer types, and 14% for all three cancer types. Rates of any telehealth access among the cancer types ranged from 61% at Community Cancer Programs to 100% at NCI Designated Programs. In multivariable logistic regression, facility type was significantly associated with telehealth access while factors such as bed size, ownership, and volume were not significantly associated. Conclusions: Although access to telehealth services for patients with cancer has increased, overall gaps in access remain. Within facility differences in telehealth access imply opportunities to better align services within institutions, though further investigation is warranted as these offerings mature.[Table: see text]
COVID-19 and exacerbation of screening mammography inequities.
Authors: Wang Gary X. , Chen Jarvis , Lamb Leslie , Testa Christian , Waterman Pamela , Lehman Constance Dobbins , Krieger Nancy
Published: June 2021

6543

Background: After state-mandated cessation of screening mammography (SM) in Spring 2020 due to COVID-19, centers were urged to resume screening, particularly of patients at increased risk. As our tertiary-care medical center’s screening program provides SM at four sites across our metropolitan area, we examined whether sites that historically served more patients from more disadvantaged areas returned slower to pre-COVID volumes. Methods: Patient records were linked by ZIP code of residence to ZIP Code Tabulation Area (ZCTA)-level area-based social metrics (ABSMs) from the 2014-2018 American Community Survey. We compared baseline pre-COVID (May-October, 2015-2019) SM population ABSMs between our four imaging sites for: % persons below poverty (≥ vs < 10%), % persons of color (POC) (quintiles: top 2 vs bottom 3), index of racialized economic segregation (quintiles: bottom 2 [more POC low-income households] vs top 3 [more white non-Hispanic (WNH) high-income households]); and race/ethnicity (% WNH vs POC). We modeled weekly SM volumes per screening day by site using Poisson regression and tested for weekly differences at each site, COVID-era (May-October 2020) vs pre-COVID; and tested for monthly differences in SM population composition by logistic regression modeling. Results: There were 89,082 pre-COVID and 16,220 COVID-era SM exams. At pre-COVID baselines the four sites differed in population composition by ABSMs and race/ethnicity (all chi-square P values <.001) (Table). The two sites that served more disadvantaged populations (A, B) returned slower to pre-COVID volumes (site-specific weekly screening volume no longer different [ P >.05] vs pre-COVID) (Table). As a result, compositions of the aggregate SM population across all sites showed a smaller proportion of patients from the most disadvantaged ZCTAs by ABSMs (all P values <.001) before returning to pre-COVID compositions three months after SM resumption. Conclusions: SM was slower to return to pre-COVID volumes at imaging sites that historically served lower-income communities of color. As a result, our COVID-era SM population skewed away from patients in disadvantaged ZCTAs. Our findings highlight the need to monitor for emergent disparities in the pandemic era. Future work will focus on understanding causes of inequitable SM engagement across our imaging sites to mitigate care disparities for our most vulnerable patients.[Table: see text]