bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of response to checkpoint inhibition in ovarian cancer.
Authors: Buras Andrea Leigh , Martin Alexandra , Zhou Jun Min , Boulware David C , Conejo-Garcia Jose , Wenham Robert Michael
Published: June 2021

e17538

Background: Despite evidence that ovarian cancer (OC) is an immunogenic disease, single-agent checkpoint inhibitors have shown limited response. A clinical trial was conducted evaluating dose-dense paclitaxel and pembrolizumab in platinum-resistant OC. Our aim was to evaluate for biomarkers of response to this combination. Methods: Immunohistochemistry was performed to identify PD–L1 and tumor infiltrating lymphocytes (TIL) in pretreatment formalin fixed paraffin embedded tissue. We performed flow cytometry on matched blood to identify presence of immunosuppressive myeloid-derived suppressor cells (MDSCs) in circulation. We performed T-cell receptor (TCR) sequencing on tumor and matched blood to evaluate whether an oligoclonal or polyclonal immune response would be associated with outcomes. On selected patients we assessed peripheral T-cell responses to treatment using an interferon-ɣ enzyme-linked immunospot (IFN-ɣ ELISpot) assay between excellent and poor responders. Cox proportional hazards model was used to estimate hazards ratios (HR) for response in relation to each biomarker. Kaplan-Meier analysis and log-rank test were used to evaluate associations between progression free survival (PFS), overall survival (OS) and each biomarker. Results: Analysis was limited to 34 patients with tumor available and one RECIST response evaluation. Odds of response trended higher (OR = 4.1) in patients with PD-L1 (+) than patients with PD-L1 (-) tumors (p = 0.061). When restricting analysis to best response of CR/PR versus PD, the odds was 13.0 (p = 0.041). Patients with PD-L1(+) tumors had a HR for progression 0.56 (0.26-1.22; p = 0.144). Presence of TILs was classified as 0-3 (0-1 low, 2-3 high). High TIL presence was not associated with response, but was associated with improved OS and trend toward improved PFS; HR 0.29 (0.09-0.90, p = 0.022) and HR 0.47 (0.21-1.05, p = 0.06). Pre- and post-treatment levels of MDSCs were not associated with response or survival, though a trend was noted; a one unit increase in pretreatment MDSCs leads to 5% decrease in the odds of being responder. Immunoseq analysis of TCR repertoire pre- and post-treatment suggested that in increase in productive clonality was associated with increased odds of being a responder; this was not statistically significant. Notably, IFN-ɣ ELISpot assay demonstrated a significant T-cell response against neoantigens post-treatment in patients who had a partial response and long overall survival. Post treatment T-cell response showed a significantly mixed response to neoantigens in the patient analyzed who had progressive disease. Conclusions: Finding biomarkers predicting benefit from checkpoint inhibitors has been challenging. Though inconclusive, these data suggest biomarkers that may be associated with this combination. T-cell response to neoantigens in patients with response to treatment suggests neoantigens as a potential target for therapeutic direction.
Efficacy and safety of weekly paclitaxel in elderly patients with heavily pretreated platinum-resistant ovarian carcinoma.
Authors: Sanchez-Bayona Rodrigo , Tolosa Pablo , Sanchez de Torre Ana , Castelo Alicia , Bernal-Hertfelder Elsa , Lema Laura , Ciruelos Eva M. , Manso Luis
Published: June 2021

e17552

Background: In platinum-resistant ovarian cancer treatment, single-agent paclitaxel can be used alone or in combination with bevacizumab. We aimed to assess the efficacy and safety profile of a weekly paclitaxel (WP) scheme in heavily pretreated platinum-resistant high-grade serous ovarian carcinoma. Methods: We retrospectively analyzed 30 adult patients with platinum-resistant high-grade serous ovarian carcinoma treated with WP at our institution between 2015 and 2020. Patients with platinum-resistant ovarian, fallopian tube or primary carcinoma of the peritoneum who had received at least 3 doses of WP (80 mg/m2) alone or in combination with bevacizumab until disease progression or unacceptable toxicity were included in the analysis. Progression-free survival was assessed according to the Response Evaluation Criteria in Solid Tumors version 1.1. Information about toxicity was gathered from medical reports and lab tests. Kaplan-Meier curves and Log-rank test were performed for survival estimates. Results: In our sample, the median age was 68 years (IQR: 60-75) and the median number of previous lines of systemic treatment was 3 (range 1-5). 40% of patients received WP in combination with bevacizumab. The disease control rate was 60.7% (42.9% partial response and 17.8% stable disease). In the overall analysis, the median progression-free survival (mPFS) was 5.0 months (95% CI: 2.0-7.1 months). The presence of ascites significantly shortened the mPFS compared to patients without it (1.1 vs 5.1 months, p < 0.001). Even though the addition of bevacizumab to WP improved the mPFS, the difference was not statistically significant compared to WP alone (7.1 vs 4.06 months, p=0.30). Peripheral neuropathy was the most common adverse event (78% all grades, 18% grade 3). No grade 3 hematologic toxicity was registered. Treatment was discontinued in 6 patients (20%) – 4 due to peripheral neuropathy and two because of toxicoderma. Conclusions: In our sample, WP was an active and safe regimen in heavily pretreated platinum-resistant ovarian carcinoma. WP was well tolerated in elderly patients. The presence of ascites was associated to a shorter PFS in patients treated with WP compared to ascites-free patients.
Functional status of patients suffering from ovarian cancer: A cross-sectional study.
Authors: Iglesias Campos Marcos , Pajares Bella , Roldán Jiménez Cristina , Bermejo-Perez Maria-Jose , Alba Emilio , Cuesta Vargas Antonio
Published: June 2021

e17556

Background: Physical activity displays multiple benefits in oncology patients, with the strongest evidence related to breast cancer. But there is little information about patient with ovarian cancer, even less in those who are metastatic. The main objective of this study was to assess and describe the performance´s in patients suffering from ovarian cancer in terms of function and cancer-related fatigue (CRF). Methods: Patients willing to join therapeutic exercise program (TEP) were at the Medical Oncology Unit of the Hospital Virgen de la Victoria, Malaga. A physiotherapist carried out an interview and a baseline assessment. The following outcomes were recorded: number of repetitions (n) performed in 30 seconds sit-to-stand test (30-STS), handgrip strength (Kg), cancer related fatigue (CRF) measured by Piper Fatigue Scale (0-10), upper and lower limb function measured by Upper Limb Functional Index (ULFI) and Lower Upper Limb Functional Index (LLFI), respectively (%). Results: Patients recruited had a diagnosed of an advanced ovarian cancer receiving or not active treatment. All participants had a good performance status (PS) and signed informed consent. 8 women were included, with a mean age of 52.66 (9.53) years and a mean BMI of 27.22 (4.56) kg/m2. Women performed 22 (4.24) repetitions of 30-STS test. Handgrip strength was 22 (2.7) Kg and CRF 5.43 (2.91) points. Patients reported 64.81% (34.65) and 66.83% (37.91) in ULFI and LLFI questionnaires, respectively. Conclusions: At the light of these preliminary results, ovarian cancer patients present a good level of function measured by 30-STS and a good grip strength. However, they report a moderate level of CRF and affected upper and lower limbs function. In additions, patients measured had function enough to participate in a therapeutic exercise program. Given the heterogeneity of the sample and its low number of participants, future studies with a wider sample should be carried out.
Prevalence and variety of HPV types in dependence on gender and age.
Authors: Zykova Tatiana A. , Nikitina Vera P. , Zhenilo Oksana E. , Verenikina Ekaterina V. , Ivanova Viktoria A. , Menshenina Anna P. , Shevchenko Alexey N. , Khomutenko Irina A. , Filatova Elena V. , Shevyakova Elena A. , Velikorodnaya Lilia A.
Published: June 2021

e17575

Background: Analysis of the typical structure of age, sex and territorial patterns of HPV spread is of interest, since it allows assessing the potential impact of modern immunoprophylaxis. The purpose of the study was to analyze the prevalence and variety of HPV types in dependence on gender and age. Methods: The study included 424 patients (334 women and 90 men) under 45 years of age (228 women and 46 men) and over 46 years old (106 and 44, respectively). Vaginal and cervical swabs were examined in women and urethral swabs in men. DNA extraction was performed by Real-time PCR. Results: HPV DNAs were found in 150(35.4%) patients, including 115(34.4%) women and 35(38.9%) men (p > 0.05). HPV was less frequently detected in older women, and more frequently in older men. Thus, HPV DNAs were found in 85(37.3%) women < 45 years and in 30(28.3%, p = 0.068) women >46 years; in men – 14(30.9%) and 21(47.7%, p = 0.071), respectively. Some HPV types were more frequent in younger patients, compared to older ones: in 26(26.3%) and in 5(9.8%), p = 0.068) of HPV-positive patients, respectively. The most common HPV types were 16(46.7%), 52(16.0%), 56(12.7%), 31(10.7%); HPV16 dominated both in females - 50(50.4%) and males - 12(34.6%). After HPV16, most frequent types in women were: 31-12(11.3%) and 52-13(11.3%), 18-12(10.4%) and 56-119(, 6%); in men - 52-11(31.4%), 56-8(22.9%), 45-4(11.4%) and 18-3(8.6%) types. The total share of two HPV types with the greatest oncogenic potential (types 16 and 18) was 85(56.7%) of all HPV-positive patients, and in women it was higher than in men: 70(60.9) vs. 15(42.9%, p = 0.046), respectively. Conclusions: Simultaneous infection with several HPV types was statistically significantly more often detected in younger patients compared with the older age group among men. HPV16 was the most common type both in men and women; however, the rates of other HPV types differed. Cumulative frequency of types 16 and 18 was statistically significantly higher in women, compared to men.
MVX-ONCO-1 in advanced refractory cancers: Safety, feasibility, and preliminary efficacy results from all HNSCC patients treated in two ongoing clinical trials.
Authors: Fernandez Eugenio , Vernet Remi , Charrier Emily , Migliorini Denis , Joerger Markus , Belkouch Marie-Claude , Urwyler Muriel , Von Rohr Olivier , Saingier Valentin , Ancrenaz Virginie , Grandjean Nicole , Lavalliere Emmanuel , Lafferma Elisabeth , Rubin Olivier , Villard Jean , Grogg Julien , Mach Nicolas
Published: June 2021

e18005

Background: MVX-ONCO-1 is an active, personalized cancer immunotherapy combining irradiated autologous tumor cells and encapsulated, genetically engineered allogeneic cells producing GM-CSF. The immunostimulant cytokine is released locally in a sustained manner over one week at the immunization site. All cancer types are potential candidates and more than 40 patients have been treated in two clinical trials. Here we report the data on all HNSCC patients treated, as of 31st January 2021. Methods: Eleven (11) patients with locally advanced/metastatic HNSCC relapsing after at least one line of systemic therapy were enrolled in 2 open-label, single-arm clinical trials (NCT02193503 and NCT02999646) evaluating the safety, feasibility and efficacy of MVX-ONCO-1. All patients were treated with at least 5 administrations of MVX-ONCO-1 over 8 weeks (W1,2,3,4,6,8). Each administration consists of the subcutaneous implantation in healthy skin of 2 capsules containing each 8x105 cells, producing > 20ng/24h of GM-CSF, and an injection of 4x106 irradiated autologous tumor cells between the 2 capsules. Results: Eleven (11) patients are evaluable for safety and feasibility. Ten patients (91%) with at least 6 months, respectively 9 patients (82%) with 12 months follow-up are evaluable for efficacy analysis. Eight patients (80%) failed both Cisplatin based chemotherapy and anti-PD1 therapies prior to enrolment. The most common treatment-related adverse event (AE) was local hematoma at implantation site in 3 patients (27%). None experienced > grade 2 treatment-related AE. Overall Survival is 70% (7/10pts) at 6 months, and 56% (5/9pts) at 12 months. Eight patients (80%) presented some degree of disease control with 4SDs, 2PRs and 2CRs. Both CRs are longstanding, with both patients not any longer on anticancer therapy for 24 and 6 months respectively. While 1 PR was observed on MVX-ONCO-1, 1PR and 1CR were observed on subsequent Nivolumab therapy (both CPS0), and 1 CR was observed after carboplatin-cetuximab. Two patients had progressive disease as best overall response. Conclusions: Treatment with MVX-ONCO-1 is feasible, safe and well tolerated. Preliminary efficacy data shows an encouraging rate of tumor control including prolonged CR in patients subsequently treated with nivolumab or chemotherapy. Efficacy of the concurrent use of anti-PD-1 and MVX-ONCO will be assessed in a planned clinical trial. Clinical trial information: NCT02999646.
A multiparameter model for prediction of pathological nodal status in clinically early stage oral cancer using machine learning.
Authors: Mallick Indranil , Saha Saheli , Chatterjee Sanjoy , Roy Paromita
Published: June 2021

e18025

Background: The current approach to neck treatment in clinical T1-2 oral cancers is to offer elective nodal dissection to all patients, despite the fact that the majority of patients are pathologically node negative. This is due to the poor predictive ability of clinico-radiological assessment and subsequently poorer survival in those in whom neck dissection is omitted based on this. A robust prediction model for pathological nodal status may allow individualized decisions for neck dissection. Our aim was to develop a multiparameter prediction model to identify pathological node-negative status using machine learning. Methods: We identified 497 patients with cT1-2 oral cancer from a single institutional database from 2011-2018 who underwent primary resection and neck dissection. We compared the sensitivity, positive predictive value and accuracy of prediction of pathologically negative neck from clinico-radiological staging alone vs. a model created from multiple parameters including clinical features (clinico-radiological nodal status, ages, sex, subsite of primary lesion) and pathological features of the resected primary tumor (maximum dimension, depth of invasion, lymphovascular invasion, perineural invasion, grade and margins of resection). The multiparameter model was built from a training dataset of the first 400 patients using an ensemble of logistic regression, random forests and support vector machines. A cohort of 97 patients was used for independent validation. Results: In this cohort 232 (47%) were clinico-radiologically node negative, while 307(62%) were pathologically node negative. The sensitivity, positive predictive value and accuracy of the clinico-radiologically assigned nodal status was 56%, 74% and 61%, while that of the multiparameter machine learning model was 87%, 89% and 89% respectively. The area under curve (AUC) of the clinico-radiological prediction was 0.62 whereas that of the multiparameter predictive model was 0.91. In the validation dataset, 58/62 pathologically node negative patients were predicted correctly by the model. The accuracy of the model on the external validation dataset was 82%. Conclusions: The performance of the multiparameter predictive model was considerably superior to clinico-radiological neck staging for prediction of pathological node negative neck. This could be validated on an independent dataset. This could be considered for prospective clinical evaluation of individualized neck dissection.
A potential survival impact of blood immune cells in patients with locoregionally advanced nasopharyngeal carcinoma treated with concurrent chemoradiotherapy.
Authors: Yang Li , Xu Zhiyuan , Lee Victor Ho-Fun , Lee Anne W. M.
Published: June 2021

e18027

Background: To exam the changes of blood immune cells during concurrent chemoradiotherapy (CCRT) and explore their effects on survival in patients with locoregionally advanced nasopharyngeal carcinoma. Methods: Study population included stage III-IVA (TNM-8th edition) locoregionally advanced nasopharyngeal carcinoma (NPC) patients treated with induction chemotherapy followed by CCRT from January 2015 to October 2019. Patients 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 or 40mg/m2 weekly for a total of 6 weeks 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. All had complete blood counts with differentials at baseline and before each chemotherapy. The primary endpoint was progression-free survival (PFS). “Immune cells” of our interest included lymphocytes, neutrophils and platelets. Results: A total of 139 patients were eligible and recruited. The median follow-up was 34 months (range 4-72). All immune cells decreased significantly during CCRT; the rate of grade 3/4 lymphopenia, neutropenia and thrombocytopenia during CCRT were 96.4%, 25.2% and 9.4%, respectively. The median (interquartile range, IQR) time to nadir from the start of CCRT were 40 (32-44), 26 (20-42) and 30 (15-39) days for lymphocytes, neutrophils and platelets, respectively. The median PFS was not reached and estimated 2-year PFS was 90.2%. Patients with lymphocyte nadir ≤ 0.2×109/L had better PFS compared with those with lymphocyte nadir > 0.2×109/L（2-yr PFS 95.5% vs. 87.5%, P=0.048). Patients with platelet nadir < 100×109/L had better PFS compared with those with platelet nadir ≥ 100×109/L(2-yr PFS 96.9% vs. 84.2%, P=0.011). Neutrophil nadir was not associated with PFS in univariate analysis. Multivariate analysis including prognostic variables in univariate analysis showed that platelet nadir (< 100 × 109/L vs ≥ 100 × 109/L, hazard ratio [HR] 0.279, 95% confidence interval [CI] 0.091-0.857, P=0.026), stage (III vs IVA, HR 0.321, 95% CI 0.115-0.901, P=0.031) and cumulative concurrent cisplatin dose (< 180mg/m2 vs ≥ 180mg/m2, HR 3.422, 95% CI 1.366-8.577, P=0.009) were prognostic of PFS by adjusting lymphocyte nadir and baseline hemoglobin. Conclusions: Blood immune cells decreased during CCRT and thrombocytopenia was prognostic of PFS in patients with LANPC. Longer follow-up is warranted to identify prognostic factors of overall survival.
EGFR blockade leads to singular oncogene-addiction in ETV6-NTRK3 transformed human epithelial cells and hypersensitization to entrectinib.
Authors: Kannan Nagarajan , Kalthur Guruprasad , Aalam Musheer , Viringipurampeer Ishaq , Emperumal Chitra Priya , Beer Philip A , Sadanandam Anguraj , Garcia Joaquin J. , Janus Jeffrey R.
Published: June 2021

e18055

Background: Entrectinib, a TRK kinase inhibitor, has been approved for the treatment of tissue agnostic rare tumors positive for TRK fusions. A very low frequency molecular subset of TRK fusion tumors dubbed as secretory carcinoma (SC) are characterized by organ-agnostic epithelial origin, ETV6-NTRK3 (EN) fusion and distinguishable secretory-type tumor cells. These tumors have been frequently miscategorized as acinic cell carcinoma or adenocarcinoma. A previous mouse study identified EGF dependent epithelial progenitors as putative cell-of-origin for SC. Methods: To test the role of EGFR signaling in EN mediated transformation and therapy resistance, we expressed EN, kinase-dead EN-K380M, and drug-resistant EN-G623R in human epithelial MCF10A cells with EGF-dependent primitive function and investigated their ability to grow in the presence and absence of EGF and/or entrectinib. To understand the significance of findings based on our model, we analyzed a total of 22 ‘rare’ patients from Mayo Clinic Tissue Registry and analyzed TCGA PanCan datasets. Results: We report herein that EGF signaling is essential for normal growth but dispensable during EN driven transformation. Our findings suggest that levels equivalent to circulating EGF (0.5-1ng/ml) is sufficient to drive 100% resistance to entrectinib in vitro. Three different strategies to blockade EGF/EGFR axis including depletion of EGF in culture system, genetic depletion of EGFR using shRNA as well as cetuximab antibody-based EGFR neutralization potentiated oncogene-addiction and hypersensitivity to entrectinib in our models. As predicted, models with G623R mutation in EN was refractory to entrectinib under all experimental conditions. Further omics analysis of TCGA PanCan suggested that EN and EGFR mutations are mutually exclusive and entrectinib-resistant G623R mutation were uncommon. Interestingly, nearly all EN tumors from Mayo Clinic Tissue Registry immunostained weakly or strongly for EGFR and showed perfect concordance with pEGFR suggesting pathway activation. Conclusions: Together, these findings raise an important question whether blockade of ‘wildtype’ EGFR signaling could improve medical intervention in SC patients presenting with wildtype EGFR and no drug-resistant mutation in entrectinib, by improving oncogene-addiction and attendant hypersensitization of transformed cells to entrectinib.
Pediatric cancer communication in Guatemala.
Authors: Graetz Dylan E. , Rivas Silvia Elena , Wang Huiqi , Vedaraju Yuvanesh , Devidas Meenakshi , Fuentes Ana Lucia , Caceres-Serrano Annie , Antillon-Klussmann Federico , Metzger Monika , Rodriguez-Galindo Carlos , Mack Jennifer W.
Published: June 2021

e18508

Background: Effective diagnostic communication is a cornerstone of cancer care. While > 90% of children with cancer live in low- and middle-income countries, little is known about patients’ and families’ communication priorities and experiences. We examined parent priorities for communication and the quality of information-exchange and decision-making during diagnostic communication in Guatemala. Methods: This study was conducted at Unidad Nacional de Oncologia Pediatrica. A cross-sectional survey was verbally administered in Spanish to 100 parents of children with cancer within 8 weeks of diagnosis. The survey included items utilized in pediatric communication studies from high-income countries and novel questions developed specifically for the study population. Results: Guatemalan parents prioritized communication functions including information exchange (99%), fostering healing relationships (98%), decision-making (97%), enabling self-management (96%) and managing uncertainty (94%) over functions such as responding to emotions (66%) and cultural awareness (48%). Almost all Guatemalan parents (96%) wanted as many details as possible about their child’s cancer. However, only 67% reported that they were always given the information they needed without asking for it, and most said they sometimes (56%) or always (18%) had questions they wanted to discuss with the doctor but did not. Half of parents (54%) correctly identified their child’s diagnosis, primary site, extent of disease (localized versus metastatic), length of proposed treatment, and treatment intent (curative versus palliative). Parents of children diagnosed with leukemia were more likely to understand all pieces of information than those whose children had solid tumors (p < 0.001). Most parents (76%) preferred to share in decision-making with oncologists. Two-thirds of parents (65%) held their preferred role in decision-making, with fathers more likely to hold their preferred role than mothers (p = 0.02). Reflecting on decisions they had made, 94% of parents strongly agreed they had made the right decisions. However, 17% of parents endorsed feeling that their choices had caused their children harm. Conclusions: Similar to findings from the United States, parents in Guatemala prioritize many aspects of diagnostic communication, especially information exchange, development of healing relationships, and decision-making. Nonetheless, many parents report challenges in information exchange and decision-making, suggesting a need for interventions to support communication processes.
Healthcare access disparity among U.S. cancer population and evaluation of social determinants of health using NHANES data for 2013-18.
Authors: Wahab Ahsan , Rafae Abdul , Mushtaq Kamran , Masood Adeel , Ehsan Hamid , Khakwani Maria , Khan Aqsa , Khakwani Muhammad Shahzeb Khan , Haider Mobeen Zaka , Mushtaq Muhammad Umair
Published: June 2021

e18527

Background: Ethnic minorities in US have poorer outcomes due to poor socioeconomic determinants. We evaluated association between ethnicity and insurance status among US adults with cancer who participated in National Health and Nutrition Examination survey for 2013-18. Methods: This was a cross-sectional study involving participants with history of cancer; participants with missing insurance/ethnicity information were excluded. Outcome of interest was insurance coverage in minorities vs Whites. The comparison of baseline characteristics (Table) stratified by insurance (Yes vs No) was made using Chi-square and t-tests incorporating survey procedures in SAS v. 9.4. Logistic regression was used for adjusted and unadjusted odds ratio (OR). Results: Among 29,400 participants, 1,684 had cancer. After excluding 81 participants with missing data, 1,603 were included; 5.2% were uninsured. Table summarizes characteristics of participants stratified by insurance. The uninsured individuals were 14 years younger, predominantly females, Hispanics and non-US born, and were less educated compared to the insured. Unadjusted OR of no insurance vs insurance was 4.23 (95%CI: 2.40-7.47) for Hispanics, 1.23 (95%CI: 0.64- 2.38) for Blacks and 1.50 for others (95%CI: 0.48-4.74) when compared to Whites. After adjusting for age, sex, education, US born status and routine place for medical care, OR for Hispanics, Blacks and others were 1.31 (95%CI: 0.73-2.36), 1.00 (95%CI: 0.46-2.18) and 0.86 (95%CI: 0.26-2.78), respectively. Conclusions: Poor socioeconomic indicators among US cancer population may leave them being uninsured; thereby making them vulnerable to poor outcomes in particular in the ethnic minorities including Hispanics. [Table: see text]
Change in facility-level share of Medicaid patients with cancer following implementation of the affordable care act.
Authors: Buck Matthew , Demkowicz Patrick C , Nie James , Marks Victoria A. , Salazar Michelle C. , Kenney Patrick Aloysius , Boffa Daniel J. , Leapman Michael S.
Published: June 2021

e18543

Background: Although Medicaid expansions associated with the Affordable Care Act (ACA) significantly increased insurance coverage for Americans with cancer, there is evidence that some facilities limit the number of Medicaid patients they treat due to lower reimbursement. We aimed to assess facility-level changes in the proportion of patients with Medicaid who were diagnosed with cancer in relation to Medicaid expansions associated with the ACA. Methods: We identified adult patients with the 19 most commonly diagnosed cancers using the National Cancer Database who were diagnosed with cancer from 2010 through 2017. We clustered Commission on Cancer (CoC) accredited institutions and included those diagnosing at least 10 patients in each year. The primary study endpoint was the change in the proportion of Medicaid-insured individuals relative to the implementation of the ACA (pre- and post-Jan 1, 2014). We used adjusted difference-in-differences (DID) estimation and multivariable logistic regression to examine patient and facility-level factors associated with changes in the proportion of Medicaid insured individuals. Results: We identified 1,064 eligible facilities in the study period. There were considerable changes in the share of Medicaid insured patients at the facility-level (range -20.0% to +44.7%, IQR -0.64% to +5.63%). There were significantly larger changes in facilities located in Medicaid expansion states (11.5 to 16.5% percentage points) versus non-expansion states (9.2 to 8.9% percentage points) with adjusted DID +5.79% (p < 0.001). Despite overall increases, 14.6% of facilities in expansion states experienced reductions in their share of Medicaid insured patients. Facility factors associated with decreasing share of Medicaid patients were non-expansion status (OR: 6.25, 95% CI 3.89 – 9.98, p < 0.001) and higher baseline Medicaid population (OR: 2.93, 95% CI 2.00 – 4.35, p < 0.001). There was also significant regional variation with larger decreases in the West South Central (OR: 5.86, 95% CI 2.30 – 15.74, p < 0.001) and West North Central (OR: 2.46, 95% CI 1.07 – 5.87, p = 0.037) regions. Conclusions: Although state expansions associated with the ACA led to increases in the share of Medicaid-insured patients diagnosed with cancer at CoC facilities, there was considerable variation in changes at the facility-level. These findings highlight that improved insurance coverage may not be sufficient to improve access to care, and facility-level policies may remain a source of access disparity.
Concrete case: An opportunity to improve cervical cancer prevention—Primary and secondary prevention of cervical cancer in patients with cervical cancer and their families.
Authors: Telles O Lima Jurema , Azevedo Carla Rameri Alexandre Silva De , Lima Candice Lima , Katz Leticia , Sales Mozart j t , Pinto Rodrigo alves , Andrade Gabriela Arruda de , Keller Fernanda Araújo , Santos Paula Marina Carneiro , Soares Igor Gouveia , Moura Beatriz Vieira , Coutinho Ana Luísa Lopes Marques , Mello Maria Julia Gonçalves
Published: June 2021

e18571

Background: cervical cancer (CC) reveals regional and social inequalities and should be understood not only as an oncological indicator, but essentially as an indicator of social vulnerability and health care needs.CC is the second most incident and the most deadly among women from the Northeast’S Brazil and the third most incident in Brazil Although the HPV vaccine coverage and the Pap smear test are available through the Brazilian public health system, the coverage of the target population is low. objective: Verify the conditions of access/use of the health system by women with cervical cancer (CC) and their families. Methods: Cross-sectional study involving cancer patients admitted to IMIP between 2016 and 2019. The variable data were related to the sociodemographic profile, preventive examination, Human Papillomavirus (HPV) and the influence of the diagnosis of CC on the search for preventive and screening measures by women's family members. Results: Out of the 285 participants,between 9-21 years old and 101 between 25-69 years old. Of the patients studied,55,8% lives urban area. It has a higher performance of biopsies in the public sector (59,5%). The sociodemographic analysis highlights the non-white race (78,2%) and only 6,8% with complete high school. The knowledge about performing the Pap smear reached 88,9% and the disinformation about the HPV reached 44,4%.the school was the largest source of information about the HPV vaccine (30,6%). Related to the influence of cancer, 62,2% said that young family members underwent HPV vaccination and 82,2% related their diagnosis to search for preventive in family members over 25 years old. a much higher percentage than vaccination coverage and preventive exam in the study region report that the diagnosis of cancer influenced the decision to vaccinate (42%) and update the pap test (69%). about 30% of patients had never taken the pap test. the early start (15 - 19y) of the pap test was not significant for the periodic performance of the pap test. 46% reported the lack of information about the importance of the exam as a reason for not performing it and 34% reported fear. conclusion :Strengthening educational activities and offering vaccines against HPV and Pap smears in the diagnosis of a case of cervical cancer can be an opportunity to expand the coverage of preventive measures more effectively among people close to the patient and her community, which cannot be missed. The school was an important source of information about the HPV vaccine and should be directly involved in this fight.Reducing an inequality cycle.
Non-fatal self-injury after a diagnosis of cancer: A population-based study.
Authors: Noel Christopher , Eskander Antoine , Sutradhar Rinku , Mahar Alyson , Vigod Simone , Isenberg-Grzeda Elie , Bolton James , Deleemans Julie , Chan Wing , Zuk Victoria , Haas Barbara , Mason Stephanie , Coburn Natalie G. , Hallet Julie ,   Enhanced Supportive Psycho-oncology Canadian Care (ESPOC) Group
Published: June 2021

e18577

Background: Psychological distress is a key construct of patient-centred cancer care. While an increased risk of suicide for cancer patients has been reported, more frequent consequences of distress after a cancer diagnosis, such as non-fatal self-injury (NFSI), remain largely unknown. We examined the risk for NFSI after a cancer diagnosis. Methods: Using linked administrative databases we identified adults diagnosed with cancer between 2007-2019. Cumulative incidence of NFSI, defined as emergency department presentation of self-injury, was computed accounting for the competing-risk of death from all causes. Factors associated with NFSI were assessed using multivariable Fine and Gray models. Results: Of 806,910 included patients, 2,482 had NFSI and 182 died by suicide. 5-year cumulative incidence of NFSI was 0.27% [95%CI 0.25-0.28%]. After adjusting for key confounders, prior severe psychiatric illness whether requiring inpatient care (sub-distribution hazard ratio (sHR) 12.6, [95% CI 10.5-15.2]) or outpatient care (sHR 7.5, 95% CI 6.48-8.84), and prior self-injury (sHR 6.6 [95% CI 5.5-8.0]) were associated with increased risk of NFSI. Young adults (age 18-39) had the highest NFSI rates, relative to individuals >70 (sHR 5.4, [95% CI 4.5-6.5]). The magnitude of association between prior severe psychiatric illness and NFSI was greatest for young adults (interaction term p < 0.01). Certain cancer subsites were also at increased risk, including head and neck (sHR1.52, [95%CI 1.19-1.93]). Conclusions: Patients with cancer have higher incidence of NFSI than suicide after diagnosis. Younger age, prior severe psychiatric illness, and prior self-injury were independently associated with NFSI. These exposures act synergistically, placing young adults with a prior mental health history at greatest risk for NFSI events. Those factors should be used to identify at-risk patients for psycho-social assessment and intervention.
Patient-reported outcomes predicting non-fatal self-injury after a cancer diagnosis: A population-based case-control study.
Authors: Hallet Julie , Sutradhar Rinku , Isenberg-Grzeda Elie , Noel Christopher , Mahar Alyson , Vigod Simone , Bolton James , Deleemans Julie , Chan Wing , Zuk Victoria , Coburn Natalie G. , Eskander Antoine
Published: June 2021

e18583

Background: Psychological distress is key in cancer care. Non-fatal self-injury (NFSI) represents a patient-centred, objectively measured manifestation of the greatest level of distress occurring in 3 out of 1,000 patients after a new cancer diagnosis. How to identify patients at high risk for NFSI remains unknown. We examined the relationships between routinely collected patient-reported outcomes measures and the risk of subsequent NFSI following a cancer diagnosis. Methods: We conducted a population-based case-control study of patients with a new cancer diagnosis (2007-2019) reporting a Edmonton Symptom Assessment (ESAS) score within 36 months of diagnosis. Cases were patients with NFSI within 36 months of diagnosis and controls those without NFSI (assigned a dummy index date corresponding to the case’s NFSI). Cases and controls were matched 1:4 on time from cancer diagnosis, ESAS record in 180 days prior index, age, sex, cancer site, and history of self-injury. Multivariable conditional logistic regression assessed the association between moderate-to-severe ESAS symptoms and total ESAS (t-ESAS) score with NFSI within 180 days. Results: Of 408,858 patients reporting >1 ESAS within 36 months of cancer diagnosis, 748 patients had a NFSI, including 425 patients with an ESAS score within 180 days preceding the NFSI event. Of those 406 cases were matched to 1,624 controls without NFSI. Cases reported a higher proportion of moderate-to-severe symptoms and higher t-ESAS than controls prior to the event (p < 0.01 for all). After adjusting for psychiatric illness history and cancer therapy received, reporting of moderate-to-severe anxiety (odds ratio – OR 1.61, 95%CI 1.14-2.27), depression (OR 1.66, 95%CI 1.2-2.31), and shortness of breath (OR 1.65, 955CI 1.18-2.31) were independently associated with higher risk of NFSI within 180 days. Each 10-point increase in t-ESAS (score 0-90) was independently associated with increased risk of NFSI within 180 days (OR 1.51; 95%CI 1.40-1.63). Conclusions: Reporting moderate-to-severe anxiety, depression, and shortness of breath, and increasing t-ESAS after cancer diagnosis are associated with higher odds of NFSI in the following 180 days. These data support the prospective identification of patients at high risk for NFSI via routine ESAS screening to improve supportive care. Patients with at-risk ESAS scores should receive tailored assessment, management, and longitudinal follow-up.
Bone modifying agents and skeletal related events in patients with metastatic non-small cell lung cancer treated with immune checkpoint inhibitors.
Authors: Das Parthib , Zhao Songzhu , Wei Lai , Miah Abdul , Li Mingjia , Lopez Gabrielle , Patel Sandip H. , Johns Andrew , Grogan Madison , Bertino Erin Marie , He Kai , Shields Peter G. , Carbone David Paul , Otterson Gregory Alan , Presley Carolyn J , Owen Dwight Hall
Published: June 2021

e18593

Background: Bone metastases and skeletal related events (SREs) are a common cause of morbidity among patients with metastatic non-small cell lung cancer (mNSCLC). SREs include pathologic bone fractures, spinal cord compression, orthopedic surgery/stabilization, and palliative radiation to bone. Bone modifying agents (BMA) such as bisphosphonates and RANK ligand inhibitors are often used for mNSCLC patients with bone metastases to reduce the incidence of SRE. Data on the associations between BMA use and overall survival (OS) and the development of SRE among patients with mNSCLC treated with immune checkpoint inhibitors (ICI) is limited. Methods: We conducted a retrospective study of patients with mNSCLC treated with first line pembrolizumab or pembrolizumab plus chemotherapy at The Ohio State University from 2017-2020. The associations between SRE and categorical variables were studied using Fisher’s exact test and with continuous variables using the Kruskal-Wallis test. The association between BMA and risk of osseous progression was studied using Fisher’s exact test. The association between BMA and OS was examined using a Cox proportional hazard model. Median OS was estimated using the Kaplan-Meier method with 95% CI. OS was calculated from date of ICI initiation to death from any cause or last follow up. Results: We identified a cohort of 228 patients: 107 (47%) treated with pembrolizumab and 121 (53%) treated with pembrolizumab plus chemotherapy; 48 (21%) had squamous histology and 179 (79%) had nonsquamous histology (1 had NSCLC histology not specified); median age 62.6 years; median OS was 26.8 months (95% CI: 17.2 – 34.5 months). A total of 95/228 (42%) patients had bone metastases at time of ICI initiation; 45/95 (42%) had treatment with BMA and 50/95 (58%) were not treated with BMA. Among patients with bone metastases at time of ICI, 45 (42%) developed SRE after ICI initiation and BMA use was not associated with risk of SRE (p = 1). BMA use was not significantly associated with risk of osseous progression (p = 0.21). For patients with baseline bone metastases prior to ICI, the use of BMA was not associated with OS (p = 0.24); the type of BMA used (bisphosphonate vs RANK ligand inhibitor) was also not associated with OS (p = 0.13). Conclusions: In patients with metastatic NSCLC treated with first line pembrolizumab alone or with chemotherapy, bone modifying agents were not associated with OS, decreased risk of osseous progression, or development of SRE in patients with baseline bone metastases prior to ICI initiation. The type of BMA used was also not associated with survival. Further studies evaluating the utility and impact of BMA use in this patient population are needed.
A cross-sectional analysis of muscle density and physical function in head and neck cancer patients.
Authors: Shaver Amy L. , Ray Andrew , Platek Mary Elizabeth , Singh Anurag K. , Erickson Kayleigh , Wendel Elizabeth , Wilding Gregory , Ochs-Balcom Heather , Noyes Katia
Published: June 2021

e18597

Background: Head and neck cancer (HNC) is a debilitating disease that affects tens of thousands each year and both the disease and its treatment can cause long-term morbidity. HNC patients with greater physical function at baseline may better withstand both disease and treatment, therefore we hypothesized that baseline physical function is associated with baseline skeletal muscle density (SMD). Methods: A cross-sectional study of existing medical records was conducted. SMD was classified using pre-treatment PET-CT scans and interpreted using Sliceomatic software, and pre-treatment physical function assessed in three ways: hand grip strength, timed up and go, and short physical performance battery. Linear regression models were utilized to assess the association between SMD and each measure of physical function, with adjustment for muscle mass, sex and cancer stage in the hand grip strength model and adjustment for muscle mass and age in both the timed up and go, and short physical performance battery models. Results: The sample of 90 HNC patients, was mostly white, male, former smokers with an average BMI of 28 kg/m2. In adjusted models that included men only, we observed that for every Hounsfield unit increase in SMD there was a 0.08 increase in SPPB score (p=0.005), a 0.31 kg increase in hand grip strength (p=0.04), and a 0.13 second decrease in timed up and go (p=0.0007). In adjusted models that included women only, we observed that for every Hounsfield unit increase in SMD there was a 0.03 decrease in SPPB score (p=0.75), a 0.12 kg increase in hand grip strength (p=0.65), and a 0.01 second increase in timed up and go (p=0.84). Conclusions: Baseline physical function is associated with higher baseline physical SMD. Larger studies involving a more women are needed to replicate these findings and to further examine the potential role of effect modification by both sex and muscle mass.
Priority levels in cancer patients admitted to medical intensive care at a safety net hospital.
Authors: Epistola Raisa , Shodiya Michael Olufemi , Epistola Jordan , Chang Dong , Yeh James Jen-Chi
Published: June 2021

e18599

Background: Admissions of cancer patients to intensive care units (ICU) are increasing with improved mortality. While ICU care can be lifesaving, its higher cost does not always result in reduced mortality. Moreover, timely goals of care (GOC) discussions correlate with less ICU use in those with certain cancers. We investigate if hospital mortality and disposition outcomes for cancer patients correlate to triage by ICU providers. Methods: This subgroup analysis of a prospective cohort of 808 patients admitted to the ICU from 1 July 2015- 15 June 2016 at an academic safety net hospital included 106 patients diagnosed with cancer. Medical records were reviewed by ICU physicians, who assigned priority ranks using Society of Critical Care Medicine guidelines: 1: critically ill, needing treatment/monitoring not provided outside of ICU, 2: not critically ill, but requiring close monitoring/potentially immediate intervention, 3: critically ill patients with reduced likelihood of recovery, 4: not appropriate for ICU, equivalent outcomes achieved with non-ICU care. We did a chart review for factors like prior therapy and documentation of GOC discussions. Statistical tests were conducted to examine if priority levels correlate with disposition, mortality, and length of stay (LOS). Results: χ2-tests revealed priority rank correlated with disposition after hospitalization (p<.05) with group 3 having the highest proportion of deaths and lowest proportion of discharges home. It revealed that mortality rate differed by group (p<.05) with logistic regression showing that priority 3 predicted increased mortality (p<.05). ANCOVA indicated ICU LOS differed by priority group (p<.05), with priority 3 averaging the longest LOS. While priority 3 had the most in-hospital GOC discussions, relatively few were documented pre-hospitalization. Conclusions: Overall, our patients were accurately triaged, with worse mortality and discharge outcomes among priority 3 and a dearth of pre-hospitalization GOC documentation for all groups. Our data show the importance of triaging patients and having early, frequent GOC discussions to minimize ICU admission given increasing demand and costs. GOC discussions are associated with less aggressive medical care near death and better patient quality of life. Thus, holding these talks with our sickest patients prior to potential ICU admission is an area to improve cost-effective high quality care.[Table: see text]
The effect of neoadjuvant chemotherapy on quality of life for patients with muscle invasive bladder cancer (MIBC) undergoing cystectomy.
Authors: Sossenheimer Christina , Cizik Amy , Lenherr Sara , O Neil Brock , Dechet Christopher B. , Sanchez Alejandro , Tward Jonathan David
Published: June 2021

e18614

Background: To examine the relationship between neoadjuvant chemotherapy (NAC) clinical risk factors, and patient reported quality of life in patients with MIBC undergoing cystectomy. Methods: cT2-T4, N0, M0 MIBC patients who underwent radical cystectomy were identified from a prospectively maintained institutional outcomes database. PROMIS-Ca surveys (physical function (PF), pain interference, fatigue, depression, and anxiety domains) were administered at consultation and follow-up as part of routine clinical care. Patients were stratified as receiving NAC vs. none and surveys were anchored to date of cystectomy. Non-parametric kernel regressions with variance-covariance matrix bootstrapping were used to estimate the mean effect of covariates on each domain T-score with 95% confidence intervals. Covariates were: body mass index, smoking history, age, Charlson comorbidity score, pT and pN stage, urinary diversion-type, and survey time relative to the cystectomy date. T-score changes over time were modeled by including univariable parameters with a P<=0.1 in a multivariable model (MVA) for each domain and predicting the marginal means at date of cystectomy, 6 and 12 months postop. Results: The median age was 68 (IQR 60-73) years. NAC was received by 69/134 patients (40 Gem/Cis, 24 MVAC, 5 unknown). On univariate analyses NAC significantly reduces PF (mean change in t-score, 95%CI; -2.4, -3.7 to -0.8, p=0.001), trends toward more pain (0.94, -0.20 to 1.78, p=0.074), but does not influence fatigue, depression or anxiety. Other covariates with p<0.05 reducing PF were BMI (-0.31, -0.53 to -0.03), pT4 vs pT1-2 (-0.31, -0.53 to -0.03), Charlson 1 vs 0 (-0.31, -0.53 to -0.03), age (-0.31, -0.53 to -0.03), and days from surgery (-0.31, -0.53 to -0.03). Table shows how t-scores predicted from the MVA change over time. Conclusions: MIBC patients have mild to moderate impairment in physical function, fatigue, and pain before and after cystectomy, suggesting a need for increased focus on rehabilitation and wellness programs. Although the univariable analysis implies there may be differences in PF and Pain for those receiving NAC vs none, future studies with increased power are needed to properly adjust for the interplay of other significant covariates.[Table: see text]