bluuebunny/crossref_metadata_2025 huggingface dataset:
Anlotinib plus pemetrexed as a further treatment for patients with platinum-resistant ovarian cancer: A single-arm, open-label, phase II study.
Authors: Chen Jueming , Wei Wei , Zheng Lie , Li Han , Feng Yanling , Wan Ting , Qiu Jiaqi , Jiang Xingyu , Xiong Ying , Zheng Min , Li Jundong , Huang He , Song Libing , Liu Jihong , Zhang Yanna
Published: June 2021

5533

Background: Non-platinum chemotherapy is widely used in platinum-resistant recurrent ovarian cancer treatment but with limited efficacy. Combing chemotherapy with angiogenic inhibitors is a new therapeutic choice. Anlotinib is a novel tyrosine kinase inhibitor targeting multiple receptors involved in tumor proliferation, vasculature, and tumor microenvironment. The study aimed to further assess the efficacy and safety of anlotinib combined with pemetrexed in platinum-resistant ovarian cancer. Methods: Patients who had received at least two different chemotherapy regimens (including the first line platinum-based regimen), with histologically proven recurrent platinum-resistant or platinum-refractory epithelial ovarian cancer (including salpingocarcinoma and peritoneal carcinoma), ECOG 0-2, were considered eligible for enrollment to receive six 21-days cycles of anlotinib (12 mg QD from day 1 to 14; 21 days per cycle) orally plus pemetrexed intravenously (0.5 g/m2 on day 1; 21 days per cycle). Subsequent maintenance treatment was anlotinib monotherapy (12 mg QD from day 1 to 14; 21 days per cycle) till disease progression or intolerant toxicity. The primary endpoint was objective response rate (ORR), and the secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and safety. Results: As of Jan 2021, 27 patients were enrolled. The median number of chemotherapy was 4 (range, 2-10) and 51.9% (14/27) of patients had ever received antiangiogenic therapy. The ORR was 36.4% (partial response (PR) in 8 patients; 95% CI, 17.2-59.3). The DCR was 100.0% (PR in 8 patients and stable disease (SD) in 14 patients; 95% CI, 73.5-100). The median time of the first response was 1.6 months (range, 1.3-4.4). The median PFS was 9.3 months (95% CI, NE-NE). Furthermore, the ORR of patients with and without prior antiangiogenic therapy was 16.7% (95%CI, 2.1-48.4) and 60.0% (95%CI, 26.2-87.8) respectively (P = 0.074). Any grades of adverse events (AEs) were observed in 92.6% (25/27) of patients, containing allergic eruption (33.3%), hand-foot syndrome (29.6%), hypertension (25.9%), and fatigue (25.9%). The grade 3-4 adverse events were only observed in 5 patients, including 1 with grade 3 proteinuria, 1 with grade 3 ascites, 1 with grade 3 fatigue, 1 with grade 3 edema limbs and 1 with grade 4 anemia. Conclusions: The treatment of anlotinib plus pemetrexed showed a promising antitumor activity with tolerable toxicity for patients in platinum-resistant and refractory ovarian cancer. Clinical trial information: ChiCTR2000029654.
Efficacy of niraparib maintenance therapy in Chinese women with platinum-sensitive recurrent ovarian cancer with and without secondary cytoreductive surgery: Results from the NORA trial.
Authors: Wu Lingying , Wu Xiaohua , Zhu Jianqing , Yin Rutie , Yang Jiaxin , Liu Jihong , Wang Jing , Liu Ziling , Gao Yunong , Wang Danbo , Lou Ge , Yang Hongying , Zhou Qi , Kong Beihua , Huang Yi , Chen Lipai , Li Guiling , An Ruifang , Tan Tao , Dong Juan
Published: June 2021

5534

Background: NORA is the first, phase III, randomized controlled trial (RCT) that demonstrated individualized starting dose regimen of niraparib, which significantly improved PFS in Chinese patients with platinum-sensitive recurrent ovarian cancer (PSROC). This sub-group analysis evaluated the efficacy of niraparib maintenance therapy with and without secondary cytoreductive surgery (SCS) in PSROC. Methods: The NORA phase III RCT included adult (≥18 years) Chinese women with PSROC who were randomized in a 2:1 ratio to receive oral niraparib (n = 177) or matched placebo (n = 88). This retrospective subgroup analysis was based on the progression-free survival (PFS) of niraparib maintenance therapy in these two groups of patients with PSROC, patients with SCS, and patients without SCS. The PFS was assessed by blinded independent central review. The Kaplan-Meier (KM) estimator and log-rank test were performed to calculate the median PFS time. Results: Of the 265 evaluable patients, 69 (26.0%) patients received the SCS (niraparib, n = 48; placebo, n = 21), and 196 (74.0%) patients were without SCS (niraparib, n = 129; placebo, n = 67). Among patients with and without SCS, baseline characteristics for BRCA mutation were 26.1% vs 41.8%, complete response to last platinum-based chemotherapy were 68.1% vs 43.9%, time (6-12 months) to progression after penultimate therapy were 23.2% vs 34.7%, respectively. Treatment with niraparib led to a significant reduction of risk to disease progression compared with placebo in patients with SCS (Hazard ratio [95% CI]: 0.32 [0.13–0.78]; P = 0.0102) and without SCS (0.34 [0.23–0.50]; P< 0.001). Moreover, in the subgroups of patients who received SCS, niraparib maintenance therapy had a significantly longer PFS compared with placebo (Median [95% CI]: not reached [18.33 – not estimable] vs 5.75 months [3.68 – not estimable]; P = 0.0102). This trend was also similar in the subgroup of patients who did not receive SCS (Median [95% CI]: 10.28 months [7.49 – 18.37] vs 4.90 months [3.71 – 5.52]; P < 0.0001). Conclusions: The results from this retrospective sub-group analysis revealed that niraparib maintenance therapy provided significant clinical efficacy in patients with PSROC, irrespective of SCS. Clinical trial information: NCT03705156.
Patient care and clinical trials in gynecological oncology: Implications of the COVID-19 pandemic.
Authors: Nasser Sara , Fotopoulou Christina , Guktekin Murat , Dimitrova Desislava , Morice Philippe , Sehouli Jalid
Published: June 2021

5564

Background: This is a prospective international Survey to evaluate the impact of the COVID-19 Pandemic on the management of patients with gynecological malignancies from the multidisciplinary physicians' perspective, with particular focus on clincial infrastructures, and trial participation. Methods: The anonymous online survey consisted of 53 COVID-related questions. It was sent to all healthcare professionals in gynaecological oncology centres across Europe and the Pan-Arabian region from April 2020 to October 2020. All healthcare professionals treating women with gynecological cancers were able to participate in the survey. Results: A total of 243 answers were collected from 30 different countries. The majority (73%) of participants were gynecological oncologists from university hospitals(71%) with at least an Intensive care unit with cardiopulmonary support available at their institutions. Most institutions continued to perform elective surgeries only for oncological cases (98%). Patients had to wait on average 2 weeks longer for their surgery appointments compared to previous years(range 0-12 weeks). Cases that were prioritised for surgical intervention across all tumors (Ovarian, Endometrium, Cervical) were early stage disease (74%), primary situation (61%), and good ECOG status (63%). The radicality of surgery did not change in the majority of cases (78%) across all tumor types. During the pandemic, only 38% of clinicians stated they would start a new clinical trial. 45% stated the pandemic has negatively impacted the financial structure and support for clinical trials. 79% do not routinely screen patients included in trials for SARS CoV2. Overall, approx. 20% of clinicians did not feel well informed regarding clinical pathways for COVID-19 patients throughout the pandemic. The majority preferred regular updates and training via Webinars (75%), followed by tumorboards and interdisciplinary conferences (45%). 30% of clinicians stated that they are currently experiencing difficulties in providing adequate medical care due to staff shortage. Conclusions: Despite well-established guidelines for patient care and performing clinical trials in gynecological oncology, the COVID-19 pandemic has impacted clinical research, and financial structures. Longer waiting times for operative interventions, less support for clinical trials and concerns regarding provision of adequate medical care and triaging patients are very real. This survey underlines the necessity for building robust emergency algorithms tailored to gynecological oncology patients in the future.
HER2 in uterine serous carcinoma: Testing platforms and implications for targeted therapy.
Authors: Klc Tenley , Wu Sharon , Wilhite Annelise M. , Jones Nathaniel L. , Powell Matthew A. , Olawaiye Alexander , Simpkins Fiona , Girda Eugenia , Brown Jubilee , Puechl Allison , Ali-Fehmi Rouba , Winer Ira Seth , Herzog Thomas J , Korn Wolfgang Michael , Erickson Britt Kristina
Published: June 2021

5580

Background: HER2 is an emerging prognostic and therapeutic target in uterine serous carcinoma (USC). Testing algorithms and platforms in breast and gastric cancers are well studied and validated, but optimal HER2 testing in uterine cancer is not yet established. We aimed to assess the concordance of chromogenic in situ hybridization (CISH), immunohistochemistry (IHC), and next generation sequencing (NGS) platforms to aid in the development of USC specific testing guidelines. We also evaluated the rate of downstream mutations that may affect response to HER2 directed therapy. Methods: A total of 2,192 USC tumors were analyzed using NGS (NextSeq, 592 Genes and WES, NovaSEQ), a subset of 1,423 tumors were also tested by IHC and CISH (Caris Life Sciences, Phoenix, AZ). HER2 positivity through IHC (4B5, Ventana) and CISH (INFORM DUAL HER2 ISH Assay, Ventana) was determined based on 2007 and 2018 ASCO/CAP HER2 breast cancer guidelines. PD-L1 expression was tested by IHC using SP142 (Spring Biosciences) (positive cut-off >1%). Microsatellite instability (MSI) was tested by fragment analysis (FA), IHC and NGS. Tumor mutational burden (TMB) was measured by totaling somatic mutations per tumor (TMB-high cut-off > 10 mutations per Mb). Statistical significance was determined using chi-square. Results: Rates of HER2 positivity were comparable using the 2018 and 2007 breast cancer guidelines (19.5% vs 17.5%; p=0.25). Based on 2018 guidelines, the concordance between IHC and CISH was 98.9%. Specifically, 229/1423 patients (16%) were IHC+/CISH+, 5 patients (0.4%) were IHC+/CISH- and 11 patients (0.8%) were IHC-/CISH+ (Table). Common pathway alterations in HER2+ USC include TP53, RTK RAS, PI3K, NOTCH, chromatin remodeling and cell cycle genes. Single gene alterations in HER2+ tumors that may implicate HER2 therapy resistance (based on pathway analyses in other tumor types) included PI3K (36%), KRAS (2.6%), and PTEN (2.1%). HER2+ tumors had low immunotherapy biomarker profiles (0.3% MSI-H, 0.8% TMB, 17.1% PD-L1). Conclusions: High concordance rates were observed between CISH and IHC. Ultimately these testing platforms need to be validated by response to HER2 targeted therapies in order to develop USC specific HER2 testing guidelines.[Table: see text]
Potential impact of HPV vaccine on incidence of high-grade vulvar, vaginal, and anal precancers among females and males aged 15 to 39 years, United States 2000 to 2017.
Authors: Saraiya Mona , Senkomago Virginia
Published: June 2021

5594

Background: Since introduction of HPV vaccine, cervical precancers have decreased, but the vaccine’s impact on non-cervical anogenital precancers is unknown. These precancers are identified opportunistically and are not routinely collected in most cancer registries. Methods: We examined high-grade vulvar (VIN3), vaginal (VAIN3), and anal (AIN3) precancers among persons aged 15-39 years using 2000-2017 data from select cancer registries covering 27.8% of the U.S. population. Incidence trends were evaluated with Joinpoint regression. Results: VIN3 rates declined 21% per year post-HPV vaccination introduction among women. VAIN3 rates declined 19.1% per year among women aged 15-29 years, also post-HPV vaccination introduction. Compared to the pre-vaccination period when AIN3 rates were increasing, AIN3 rates were stable among women aged 15-29 years and among men aged 30-39 years. Conclusions: Decreases in rates of VIN3 and VAIN3 after HPV vaccine introduction among younger age groups were similar to declines observed in cervical precancers, suggesting HPV vaccine impact.
Impact of different sequencing strategies of talazoparib and carboplatin combination upon efficacy and toxicity in BRCA-wild type and BRCA-mutant triple-negative breast cancer models.
Authors: Beniey Michele , Cotte Alexia , Hubert Audrey , Bechir Nelly , Haque Takrima , Tran-Thanh Danh , Hassan Saima Noor
Published: June 2021

586

Background: PARP inhibitors (PARPi) such as talazoparib and olaparib, have demonstrated an improvement in progression-free survival (PFS) amongst metastatic HER2-negative breast cancer patients with germline mutations in BRCA1/2 (BRCA-MUT). Clinical trials have evaluated PARPi in combination with carboplatin, but with mixed results. Earlier trials studied the combination of carboplatin and a low-dose PARPi of low potency, veliparib. The concomitant combination of carboplatin and talazoparib, a higher-potency PARPi, was also evaluated in solid tumors, using a heavily pre-treated population. Here, we perform a comparative evaluation of different sequencing strategies of talazoparib and carboplatin to determine efficacy and toxicity in BRCA-MUT and BRCA wild-type (WT) TNBC models. Methods: We used three orthotopic xenograft models in NSG (NOD scid gamma) mice, with 7-14 mice in each treatment group: MDAMB231 (BRCA-WT), HCC1806 (BRCA-WT), and MX1 (BRCA-MUT). We treated mice with carboplatin (C) (35 mg/kg intraperitoneally) in combination with talazoparib (T) (0.33 mg/kg oral gavage) using 2 dosing strategies: a) concomitant administration of C + T; and b) T first, followed by C three days later, each compared to vehicle control. We evaluated primary tumor inhibition and hematologic toxicity. Kruskal-Wallis test and Dunn’s multiple comparison test was used to assess statistical significance. Results: Using the MDAMB231 xenograft, we found the T-first approach led to a 66.7% (P < 0.0001), and the concomitant approach resulted in a 51.4% decrease in primary tumor volume, (P = 0.08), in comparison to control. In HCC1806, the T-first approach resulted in a 62.0% decrease in tumor volume (P < 0.0001), whereas the concomitant combination showed a 54.4% decrease (P = 0.002). In MX1, the T-first and concomitant approaches resulted in 72.7% (P < 0.0001) and 81.4% (P < 0.0001) decrease in tumor volume, respectively. With regards to neutrophil counts, T-first approach decreased neutrophils by 66.2% and 43.0% in MDAMB231 and HCC1806 xenografts respectively, similar to the trend with concomitant T + C: 61.4% and 38.0%. In the MX1 cohort, the T-first approach resulted in a 66.2% decrease in neutrophils (P = 0.001), and the concomitant approach led to a 77.5% decrease in neutrophils (P = 0.006). Conclusions: Our results demonstrate that the talazoparib-first approach is effective in two BRCA-WT models with no statistically significant neutropenia. While the concomitant combination approach demonstrated greater tumor inhibition in the BRCA-MUT model, this was also associated with significant neutropenia. This is suggestive that sequencing of talazoparib and carboplatin may have differential effect in BRCA-WT and BRCA-MUT tumors and may play an important role in improving efficacy in BRCA-WT tumors.
The association of skeletal muscle mass and cisplatin pharmacokinetics in head and neck cancer patients: The prospective PLATISMA study.
Authors: Molenaar-Kuijsten Laura , Chargi Najiba , Devriese Lot , de Bree Remco , Huitema Alwin
Published: June 2021

6021

Background: Locally advanced head and neck squamous cell carcinoma (HNSCC) is commonly treated with cisplatin-based chemoradiotherapy (CRT). Cisplatin is associated with severe toxicity, which negatively affects survival. In recent years, a relationship between low skeletal muscle mass (SMM) and toxicity has been described. This increased toxicity may be related to an altered cisplatin distribution and binding in the fat-free body mass, of which SMM is the largest contributor. This study aims to investigate the association between cisplatin pharmacokinetics and SMM in HNSCC patients. Methods: We performed a prospective observational study in HNSCC patients treated with CRT with cisplatin. Patients received standard-of-care chemotherapy with three cycles of cisplatin, at a dose level of 100 mg/m2 per cycle. Quantitative data on body size descriptors including SMM, measured on computed tomography scans, and cisplatin pharmacokinetics (total and ultrafilterable plasma concentration) were collected, as well as data on toxicity. Results: 45 evaluable patients were included in the study. A large proportion of the study population had a low SMM (46.7%). The majority of patients (57.8%) experienced cisplatin dose limiting toxicities. Pharmacokinetic analysis showed a significant relationship between cisplatin pharmacokinetics and the body size descriptors SMM, weight, fat-free mass, and body surface area ( p< 0.005). In a simulation, patients with a low SMM were predicted to reach higher bound cisplatin concentrations. The higher concentration of bound cisplatin could be seen as a reflection of the smaller volume of distribution, and could thereby explain the increased toxicity in patients with a low SMM. Conclusions: We found an association between cisplatin pharmacokinetics and SMM. Patients with a low SMM were predicted to reach higher bound cisplatin concentrations, which could be an explanation for the increased toxicity in this patient group. Clinical trial information: Trial NL7469 (NTR7711).
Mathematical predication models to optimize post-treatment surveillance in HPV-associated oropharyngeal cancer.
Authors: Nair Vivek , Auger Samuel , Kochanny Sara , Howard Frederick , Ginat Daniel , Pasternak-Wise Olga , Juloori Aditya , Izumchenko Evgeny , Agrawal Nishant , Rosenberg Ari , Vokes Everett E. , Skandari Reza , Pearson Alexander T.
Published: June 2021

6027

Background: In this study we develop post-treatment imaging surveillance schedules for locally advanced oropharyngeal carcinoma (OPC) specific to the unique recurrence patterns of tumor stage and HPV status, using mathematical models. Current post-treatment imaging surveillance recommendations for OPC are not evidence based. The exception is the use of a positron emission tomography (PET) scan at 3 months post-treatment, after which practice across institutions diverge. An optimized and personalized surveillance schedule for OPC patients can minimize costs and diagnostic delays. Methods: A Markov multi-state model defining local and distant recurrences was trained using 2159 patients from the National Cancer Database. Patients from 2010-2015 treated at an academic or major cancer center with curative radiotherapy were included. Tumors must have been stage III to IVB (AJCC 7th edition) with known p16/HPV status. Model performance was then successfully externally validated using the 2016 International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) study. Optimized radiographic surveillance schedules were created using this model, assuming a PET at month 3 and including 0 to 6 additional computed tomography (CT) scans of the neck and chest. Optimization was done for minimization of latency, defined as time between disease recurrence and radiographic discovery. Results: Model-selected schedules varied significantly from commonly utilized-surveillance schedules (such as imaging every 3 months within the first year from treatment) and showed lower mean diagnostic latency for every stage and HPV status (shown in Table). In the lowest risk cohort (Stage III HPV+), the optimized schedule had a sensitivity of 65% and latency of 3.1 months. In the highest risk group (Stage IVB HPV-), the optimized schedule had a sensitivity of 76% and latency of 1.9 months. Conclusions: Mathematical model optimization for HPV status and stage is feasible and produces non-intuitive results. These results could be used to inform surveillance if payors reimburse for fewer total scans. Across all cohorts, each added CT scan increases surveillance sensitivity and decreases latency. Incorporation of physical exam and direct visualization results into the model are still needed. Future steps include cost effectiveness research and prospective clinical trials.[Table: see text]
Quantitative immunofluorescence and mRNA analysis of immune-related biomarker groups in matched paired tumor samples from OPHELIA window study in head and neck squamous cell carcinoma (HNSCC).
Authors: Psyrri Amanda , Moutafi Myrto , Koliou Georgia-Angeliki , Papaxoinis George , Gavrielatou Niki , Economopoulou Panagiota , Kotsantis Ioannis , Gkotzamanidou Maria , Anastasiou Maria , Pectasides Dimitrios G. , Fernandez Aileen , Yaghoobi Vesal , Shafi Saba , Vathiotis Ioannis , Nwe Aung Thazin , Gkolfinopoulos Stavros , Foukas Periklis , Fountzilas George , Rimm David L.
Published: June 2021

6064

Background: Preclinical models suggest that PARP inhibitor-induced DNA damage can promote immune priming through a range of mechanisms including STING pathway activation. PARP inhibition also leads to adaptive upregulation of PD-L1 expression in preclinical models. To understand the distinct effects that different forms of DDR defects may have on tumor immunogenicity we decided to integrate genomic profiling with gene expression profiling and immunohistochemistry (IHC)/fluorescent assessments of PD-L1 expression, CD8 T-cell infiltration, and broad immune infiltrate, in order to define the overlap between DDR and immune-related biomarker groups and to build a deeper understanding of how DNA damage interfaces with antitumor immunity. Methods: 39 patients were enrolled in OPHELIA phase II trial in which pts were randomized 3:3:3:1 to Cisplatin (C) 60 mg/m2 on d1 followed by Olaparib (O) 75mg d 1-5 (Arm A), O 300 mg bid for 21-28 days (Arm B), no treatment (ARM C) or D 1500 mg on d1 followed by O 600 mg daily for 21-28 days (Arm D). PD-L1, STING, Ki67 and γ-H2AX were assessed using quantitative immunofluorescence (QIF). The GeneXpert (GX) closed system real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used for quantitative assessment of CD274 (PD-L1), PDCD1LG2 (PD-L2), CD8A, and IRF1 multiplex mRNA panel in pre- and post-treatment samples. Results: Ki67 was decreased in 23 out of 29 (79.3%) available samples when assessed by QIF; 13 / 23 had a decrease of at least 25%. Δγ-H2AX did not differ among treatment groups. A significant increase was observed in PD-L1 and PD-L2 mRNA levels after treatment with D-O (p = 0.023 and p = 0.016, respectively). An increase trend in posttreatment CD8A mRNA was observed in 23 out of 29 cases in the three treatment arms (p = 0.21, ARM A; p = 0.082, ARM B; p = 0.16, ARM D). IRF1 mRNA and STING protein levels were not upregulated after olaparib- based treatment in the available paired treatment samples. Conclusions: This window study demonstrated a significant upregulation of PD-L1 mRNA, corresponding to our previous data of increased Combined Positive Score (CPS) in the D-O arm post-treatment. Our findings suggest that addition of D to O leads to PD-L1 upregulation. Dual blockade of PARP and PD-1 can boost immune response and antitumor activity in HNSCC. Clinical trial information: NCT02882308.
The SINTART 1 study: A phase II trial of induction chemotherapy (IC), surgery, photon-, proton-and carbon ion-based radiotherapy (RT) integration in locally advanced operable sinonasal epithelial tumors patients (pts).
Authors: Resteghini Carlo , Castelnuovo Paolo , Nicolai Piero , Orlandi Ester , Bossi Paolo , Vischioni Barbara , Schreiber Alberto , Iacovelli Nicola Alessandro , Battaglia Paolo , Mattavelli Davide , Facchinetti Nadia , Gambazza Simone , Calareso Giuseppina , Ravanelli Marco , Facco Carla , Tartaro Tiziana , Sponghini Andrea Pietro , Pagella Fabio , Mariani Luigi , Licitra Lisa F.
Published: June 2021

6066

Background: Sinonasal epithelial tumors are rare diseases with several histotypes and poor prognosis. Multimodal approach including surgery is widely used, although no standard therapy has been established in prospective trials. This study assessed activity and safety of an innovative integration of multimodality treatment - IC, surgery and RT - modulated by histology, molecular profile and response to IC. Methods: Pts with untreated, operable squamous cell carcinoma (SCC), p53 wild type intestinal type adenocarcinoma (ITAC), sinonasal undifferentiated and neuroendocrine carcinoma (SNUC, SNEC) were enrolled in a single-arm, phase II, multicenter clinical trial from 2014 to 2018. Pts was treated with up to 5 IC cycles, whose regimen was selected according to histotype, followed either by curative radio-chemotherapy (CRT) (pts with ≥80% reduction of initial tumor volume (TV)) or surgery and adjuvant (C)RT. Photon and/or proton/carbon ion-based RT was employed according to disease site and stage. Primary endpoint was 5 years PFS, secondary endpoints were OS, IC ORR per RECIST 1.1 and safety. Results: Out of 39 enrolled pts, 35 pts were evaluable for primary endpoint. Two pts were only considered for safety analyses because definitive diagnosis on surgical specimen did not meet the study entry criteria; other two pts were screening failure due to inoperable disease. Five-year PFS was 38% (95% CI, 21 – 69), with a median PFS of 26 months. Five-year OS was 46% (95% CI, 28 – 75), with a median OS of 36 months. Responses to IC are reported in table. Globally, 15 pts avoided surgery. Overall treatment safety was in line with multimodality intensive head and neck cancer treatments (5% of pts with G3-4 adverse event during IC). One sudden cardiac death was recorded. At a median follow up of 27 months, 5 G3-4 RT related late adverse events have been recorded (1 G3 neurotoxicity, 2 G3 hearing impairment, 2 G3 xerostomia). Three-year PFS - OS for pts achieving PR/CR vs SD/PD to IC were 49.8% - 56.7% vs 43.2% - 53%, respectively. Conclusions: Treatment of advanced SNC with histology-driven IC followed by locoregional therapy tailored to response to IC was safe and showed survival rate similar to surgery containing case series. In the first prospective study, a surgery sparing multimodal approach proved feasible and effective in IC responsive pts. Clinical trial information: NCT02099175. [Table: see text]
Association of state Medicaid income eligibility limits and long-term survival after cancer diagnosis in the United States.
Authors: Zhao Jingxuan , Han Xuesong , Nogueira Leticia , Jemal Ahmedin , Yabroff Robin Robin
Published: June 2021

6512

Background: Income eligibility limits for Medicaid, the health insurance programs for low-income populations in the United States, vary substantially by state for the non-elderly population. This study examined associations between state Medicaid income eligibility limits and long-term survival among newly diagnosed cancer patients. Methods: 1,426,657 adults aged 18-64 years newly diagnosed with 17 common cancers between 2010 to 2013 were identified from the National Cancer Database. States’ Medicaid income eligibility limits were categorized as < = 50%, 51%-137%, and > = 138% of Federal Poverty Level (FPL). Survival time was measured from diagnosis date through December 31, 2017, for up to 8 years of follow-up. Multivariable Cox proportional hazard models with age as time scale were used to assess associations of eligibility limits and stage-specific survival, controlling for age group, sex, race/ethnicity, metropolitan statistical area, number of health conditions other than cancer, year of diagnosis, facility type, and the random effect of state of residence. Results: Among newly diagnosed cancer patients aged 18-64 years, 22.0%, 43.5%, and 34.5% resided in states with Medicaid income eligibility limits ≤50%, 51%-137%, and ≥138% FPL, respectively. Compared to patients living in states with Medicaid income eligibility limits ≥138% FPL, patients living in states with Medicaid income eligibility limits ≤50% and 51-137% FPL were more likely to have worse survival for most cancers in both early and late stage. The highest hazard ratios (HRs) were observed among patients living in states eligibility limits ≤50% FPL (p trend < 0.05). For example, for early stage female breast cancer patients, the HRs were 1.31 (95% confidence interval [95% CI]: 1.18 – 1.46) and 1.17 (95% CI: 1.06 – 1.30) for patients living in states with Medicaid income eligibility limits ≤50% and 51%-137% compared to those living in states with Medicaid income eligibility limits ≥138% FPL. Conclusions: Lower Medicaid income eligibility limits were associated with worse long-term survival within stage, with variation below the Medicaid eligibility threshold as part of the Affordable Care Act. States that have not expanded Medicaid income eligibility limits should expand them to help improve survival among cancer patients.
National Cancer Institute (NCI) implementation of the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (Friends) broadening clinical trials eligibility criteria.
Authors: Denicoff Andrea M. , Ivy S. Percy , Worthington Katherine H. , Zhao Jinxiu , Seibel Nita , Mishkin Grace E. , Mooney Margaret M. , Little Richard F.
Published: June 2021

6518

Background: The 2017 ASCO/Friends eligibility criteria guidelines recommend inclusiveness to promote generalizable trial results and clear rationale for necessary exclusion. These guidelines focused on brain metastases, minimum age for enrollment, HIV infection, and organ dysfunction and prior and concurrent malignancies. In September 2018, the NCI Cancer Therapy Evaluation Program (CTEP) implemented modernized protocol template language to operationalize these criteria. We evaluated utilization of the new language among CTEP-sponsored treatment trials. Methods: We evaluated protocols first approved by CTEP between 11/01/2018 and 4/30/2020. The most recent approved protocol version was evaluated for consistency with the new template language for brain metastases, HIV infection, prior or concurrent malignancies, minimum age, and cardiac, liver and kidney function. If a particular criterion was not relevant for a trial, it was not included in the analysis. We did not score age in pediatric or adult-specific trials (e.g. prostate). Results: 122 trials (71% early and 29% late phase) were identified and included in the analysis. Compliance with the new criteria language ranged from a high of 87.7% for liver function to a low of 11.5% for “new or progressive brain metastases” (table). Modernized criteria language was lacking in nearly 46% of trials in the use of concurrent or prior malignancy criteria and 31% of trials for the cardiac criteria. Of the 87 trials for non-localized disease or non-brain tumor trials, 64.4% did not address brain metastases, leaving it to investigator discretion. Thus, 75.9% of trials could theoretically enroll patients with brain metastases. Only 6 trials were considered relevant for patients < 18 years old; 50% were consistent with the age criterion (not shown in table). Conclusions: Implementing ASCO/Friends eligibility criteria requires focused reviews during protocol development to ensure compliance. CTEP is using these findings to continue to improve its protocol review processes to broaden eligibility in clinical trials. Maximizing opportunities for diverse populations to participate in trials is a priority for the National Cancer Institute and CTEP will continue efforts to achieve this goal.[Table: see text]
Social determinants of health, genetic ancestry, and mortality in ECOG-ACRIN E5103.
Authors: Obeng-Gyasi Samilia , O'Neill Anne M. , Miller Kathy , Schneider Bryan P. , Partridge Ann H. , Timsina Lava R , Sledge George W. , Wagner Lynne I. , Carlos Ruth
Published: June 2021

6527

Background: Social determinants of health (SDH) and genetic ancestry have been independently implicated in breast cancer presentation, treatment and mortality. However, little is known about the relationship between SDH and genetic ancestry on clinical trial outcomes. The objective of this study is to assess the association between SDH, genetic ancestry and clinical outcomes in patients enrolled in an adjuvant breast cancer clinical trial. Methods: ECOG-ACRIN (EA) 5103 randomized patients to receive AC + taxane + bevacizumab or placebo. SDH were operationalized as insurance status at trial registration (individual SES) and neighborhood socioeconomic status (nSES). Insurance categories included: (1) Private, 2) Medicare including private/Medicare, military, 3) Medicaid including Medicaid/Medicare, uninsured, 4) self-pay). The nSES index was calculated using zip codes linked to county level data on occupation, income, poverty, wealth, education and crowding. Genome-wide single-nucleotide polymorphism arrays were used to define African ancestry (AA), European ancestry (EA) and other (OA). Multivariable regression and Cox-Proportional Hazard models (odds ratios (OR) and hazard ratios (HR) with corresponding 95% confidence intervals (CI)) were used to assess associations with chemotherapy completion and overall mortality. Estimates were adjusted for the following clinical covariates: age, tumor size, nodal status, hormone receptor status, and primary surgery at randomization. Results: The study cohort included 2453 EA (79.2%), 381 AA (12.2%) and 265 OA (8.6%). Medicaid patients (OR 0.76(0.59-0.99); ref private) and those with AA (OR 0.62(0.49-0.78); ref EA) were less likely to complete chemotherapy. Regarding overall mortality, Medicaid insurance (HR 1.42(1.05-1.92) was associated with a higher mortality than private insurance. Conversely, there was no significant difference in mortality by ancestry (AA HR 1.27 (0.97-1.66); OA HR 0.90 (0.63-1.29): ref EA). Neighborhood socioeconomic status did not appear to be associated with chemotherapy completion or mortality. Conclusions: SDH reflective of individual SES, such as insurance, appear to be stronger drivers of trial completion and mortality compared to nSES among patients enrolled in E5103. Moreover, study results suggest an interplay between ancestry and individual proxies for SDH in trial completion. Nevertheless, the relationship between ancestry and lower rates of chemotherapy completion do not appear to translate into higher mortality rates among patients of AA.
Racial differences in geriatric assessment (GA) impairments, health-related quality of life (HRQOL), and body composition in older adults with gastrointestinal (GI) malignancies: Results from the Cancer and Aging Resilience Evaluation (CARE) registry.
Authors: Williams Grant Richard , Dai Chen , Foster Carson , Al-Obaidi Mustafa , Harmon Christian , Nyrop Kirsten A. , Gbolahan Olumide B. , Bhatia Smita , Giri Smith
Published: June 2021

6537

Background: Despite recent cancer advances, racial disparities in outcomes persist. Our objective was to examine racial differences in GA impairments, HRQOL, and body composition metrics as a novel way to understand outcome disparities in older adults with GI malignancies. Methods: The CARE registry at the University of Alabama at Birmingham (UAB) is an ongoing prospective cohort study that consecutively enrolls older adults (≥60y) with GI malignancies. The CARE registry utilizes a patient-reported GA that measures a broad range of aging-related health issues. HRQOL is measured using PROMIS Global-10. Computed-Tomography (CT) images are procured to measure skeletal muscle index (SMI) and skeletal muscle density (SMD) from the L3 cross-section. For this study, we examined the adjusted odds ratio (aOR) for racial differences in GA impairments, HRQOL, sarcopenia (defined as men BMI < 25, SMI ≤43 cm2/m2; men BMI ≥25, SMI < 53 cm2/m2; women SMI < 41 cm2/m2), and myosteatosis (defined as BMI < 25, < 41 Hounsfield Units [HU]; BMI ≥25, < 33 HU), adjusting for age, sex, education, cancer type, cancer stage, and comorbidity. Results: We included 448 patients with GI malignancies, with self-reported race as White or Black, a completed GA and available CT imaging +/- 60 days of GA completion. Mean age at enrollment was 70±7.2y, 58% were male and 25% were Black. Primary cancer diagnoses included colorectal cancer (33%), pancreatic cancer (25%), and other GI malignancies (52%). Black participants had lower education (high school or < 54% vs. 38%, p< 0.01) and were less likely to be married (55% vs 71%, p< 0.01). Black participants reported more limitations in activities of daily living (aOR = 2.0 (95% confidence level [CI] 1.01-3.9, p= 0.03) and frailty (aOR = 1.9, 95% CI 1.1-3.3, p= 0.02). Similarly, Black participants reported lower HRQOL (physical: β coefficient, -2.7; p= 0.03; mental: β coefficient, -2.4; p= 0.03). Conversely, Black participants were less likely to have sarcopenia (aOR = 0.5, 95% CI 0.3-0.9, p= 0.02) and myosteatosis (aOR = 0.12, 95% CI 0.02-0.8, p= 0.02). Conclusions: Differences in frailty, HRQOL, and body composition between Black and White participants present the first step towards understanding disparities in cancer outcomes amongst older adults.
Mediators of racial disparity in the use of prostate MRI.
Authors: Leapman Michael S. , Dinan Michaela Ann , Pasha Saamir , Washington Samuel L. , Ma Xiaomei , Gross Cary Philip
Published: June 2021

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Background: Evidence of racial disparity in the use of prostate MRI presents new obstacles to closing recognized gaps in treatment and outcome for black men with prostate cancer. To anticipate strategies for improving equity in cancer care, we examined mediators of racial disparity in the use of prostate MRI surrounding the diagnosis of prostate cancer. Methods: We conducted a multiple mediation analysis among patients with localized prostate cancer in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between January 2008 and December 2015. We assessed claims for prostate MRI within the six-month period preceding or following diagnosis. We first identified candidate clinical and sociodemographic meditators based on their association with both race and prostate MRI, including the Index of Concentrations at the Extremes (ICE), a measure of racialized residential segregation calculated at the zip code or census tract level. We used non-linear Multiple Additive Regression Trees (MART) models to estimate the direct and indirect relative effects of mediators. Results: We identified 71,597 eligible patients. Black patients with prostate cancer were less likely (5.3%) to receive a prostate MRI when compared with white patients (7.0%; unadjusted odds ratio 0.75, 95% CI 0.67-0.84, p < 0.001). 33.1% (95% CI 20.6-44.9) of the racial disparity in prostate MRI use was attributable to variation in SEER region, 22.5% (95% CI 13.0-30.2) to residence in a high poverty area, 17.2% to residential segregation (ICE group 17.2%, 95% CI 8.1-27.9%), and 13.2% to dual eligibility for Medicaid (95% CI 8.6-20.2%). Clinical and pathologic factors were not significant mediators. After accounting for the mediators, the direct effects of race accounted for 6.2% of the observed disparity in prostate MRI use. Conclusions: Sociodemographic factors including geographic region, and area-level measures of income and residential segregation explain the majority of the observed racial disparity in the use of prostate MRI among older Americans with prostate cancer. The findings underscore that measurable structural factors can be readily identified that underlie racial disparity in access to emerging diagnostic tools for patients with cancer.
Comprehensive or specialty-specific cancer care in the United States: A story of continuing underperformance.
Authors: Aquina Christopher Thomas , Becerra Adan Z. , Ejaz Aslam , Monson John R.T. , Fleming Fergal J.
Published: June 2021

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Background: “Textbook oncologic outcome” (TOO) is a composite measure representing the “ideal” outcome for patients undergoing cancer surgery and is associated with improved survival. Using TOO as the primary outcome, we asked whether hospitals are high-performing across multiple cancer types. Methods: Patients undergoing potentially curative breast, colon, rectal, lung, or pancreatic cancer resection were identified within the National Cancer Database (2010-2016). Organ-specific TOO was defined as: adequate lymph node yield, R0 resection, non-length of stay outlier, no hospital readmission, no 90-day postoperative mortality, and receipt of guideline-concordant chemotherapy and/or radiation. Mixed-effects analyses estimated the risk-adjusted TOO rate for each hospital stratified by cancer type. Results: Among 1,094,550 cancer resections (breast = 690,442; colon = 213,918; lung = 121,771; rectum = 40,315; pancreas = 28,104), 434 hospitals performed ≥10 resections for each cancer type. Only 11 hospitals (2.5%) ranked in the top quartile for adjusted TOO rate for all five cancer types. Of the 323 hospitals (74.4%) that ranked in the top quartile for one cancer type, 149 hospitals (46.1%) also ranked in the bottom quartile for another cancer type. There was a weak correlation between hospital rankings across cancer types with the strongest correlations between colon and rectal cancer (R2= 0.148) and lung and pancreatic cancer (R2= 0.098). Conclusions: Most U.S. hospitals do not provide high-quality care across cancer types with respect to TOO. Perhaps this knowledge should be used to guide referral for oncology care.
Associations between patient knowledge of others' experiences and treatment choice in men with localized prostate cancer.
Authors: Katz Aaron J. , Cao Ying , Shen Xinglei , Usinger Deborah , Walden Sarah , Chen Ronald C.
Published: June 2021

6578

Background: Men with localized prostate cancer must select from multiple treatment options, without one clear best choice. Consequently, personal factors, such as knowing other prostate cancer patients who have undergone treatment, may influence patient decision-making. However, associations between knowledge about others’ experiences and treatment decision-making among localized prostate cancer patients has not been well characterized. We used data from a population-based cohort of localized prostate cancer patients to examine whether patient-reported knowledge of others’ experiences is associated with treatment choice. Methods: The North Carolina Prostate Cancer Comparative Effectiveness & Survivorship Study (NC ProCESS) is a population-based cohort of localized prostate cancer patients enrolled from 2011-2013 throughout the state of North Carolina in collaboration with the North Carolina Central Cancer Registry. All patients were enrolled prior to treatment and followed prospectively. Patient decision-making factors including knowledge of others’ experiences with prostate cancer treatment options were collected through patient report. Patient treatment choice was determined through medical record abstraction and cancer registry data. Results: Among 1,202 patients, 17% reported knowing someone who pursued active surveillance (AS) while 28%, 46%, and 59% reported knowing someone who received brachytherapy, external beam radiation (EBRT), or radical prostatectomy (RP), respectively; 26% underwent AS, 9% brachytherapy, 21% EBRT, and 39% RP as their initial treatment. In unadjusted analyses, patients with knowledge of others’ experiences with brachytherapy, EBRT or RP had more than twice the odds of receiving that treatment compared to patients who did not. Knowledge of others’ experience with AS was not associated with choice to undergo AS. Multivariable analysis adjusting for age, race, risk group, and patient-reported goals of care showed knowledge of others’ experiences with brachytherapy (OR 4.60, 95% confidence interval [CI] 2.76 to 7.68), EBRT (OR 2.38, 95% CI 1.69 to 3.34), or RP (OR 4.02, 95% CI 2.84 to 5.70) was significantly associated with odds of receiving that treatment. The odds of receiving a particular treatment option were further increased among patients who reported knowing someone who had a “good” experience with the treatment in question. Conclusions: This is the first population-based study to directly demonstrate the impact of a patient’s knowledge of others’ experiences on treatment choice in prostate cancer. These data provide a new consideration to clinicians in their counseling of patients with newly diagnosed prostate cancer, and also impacts research into the informed decision-making process for this disease.
Provision of subspecialized expert oncology (SEO) opinions using Navya Cancer Data Model (NCDM), a technology-based platform: Prospective study to facilitate access to care.
Authors: Traina Tiffany A. , Kantoff Philip W. , Matasar Matthew J. , Dunn Lara , Friedman Claire Frances , Voss Martin H , Seidman Andrew David , Cahlon Oren , Zauderer Marjorie Glass , Manship Cole , Kauff Emily , Srivastava Gitika , Ramarajan Naresh , Abou-Alfa Ghassan K.
Published: June 2021

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Background: Outcomes for patients (pts) with cancer may vary widely based on accessibility and quality of care. Subspecialized expert care is associated with improved outcomes yet access to this scarce resource is limited. Providing SEO opinions in legacy ways is time-consuming and difficult to scale. We hypothesized that summarizing comprehensive pt records could enhance efficiency of a remote opinion process. In this prospective pilot, oncologists (MDs) at Memorial Sloan Kettering (MSK) tested the NCDM, a clinically-validated, semi-automated system which abstracts pertinent data elements from medical records into a structured summary to support SEO decision making for remote opinions. Methods: From July to December 2020, 12 MSK MDs provided remote opinions to consecutive pts from an international second opinion service who were specifically seeking MSK expertise. NCDM summaries, with relevant DICOM imaging, were provided to MDs via web and mobile app. MDs answered a brief survey about their experience after each opinion. Time spent to read and respond to an NCDM summary was tracked electronically. Pt feedback was collected by prospective phone follow up. Results: N = 101 remote opinions. Cancer type (N): breast (24), gastrointestinal (15), heme malignancy (14), prostate (12), renal (8), gynecologic (7), head & neck (11), lung (9) and skin (1). 92% MD response rate. Pt characteristics: median age (60 years, range 17-83); stage of disease (early stage 41%, advanced 59%); 86% of pts had received prior treatment. MDs survey responses: median time to complete record review and render opinion = 4.8 min (IQR 2.7 – 7.9 min); NCDM provided adequate information needed to make a decision in this case = 95.7% (89/93); Decision making was easy in this case with data presented in the NCDM format = 96.8% (90/93). Pt survey responses (71/88): 92% shared recommendation with local MD; 87% received the recommended treatment; 99% stated they would recommend a NCDM enabled remote opinion service to others. Conclusions: NCDM summaries enabled subspecialized MSK cancer experts to provide oncology remote opinions with ease. Patients reported high satisfaction with the experience. Technology assisted abstraction and case summary can facilitate access to subspecialized expert opinions at a global scale.