bluuebunny/crossref_metadata_2025_split huggingface dataset:
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]