bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term survival in newly-diagnosed ovarian cancer patients.
Authors: Szamreta Elizabeth A. , Li Yeran , Monberg Matthew J. , Othus Megan
Published: June 2022

e17543

Background: A proportion of women with ovarian cancer, even those with advanced-stage disease, will experience long-term survival post diagnosis. Mixture cure modeling provides insight into factors related to both short-term recurrence and death as well as long-term survival. The goals of this study were to estimate the long-term survival rate, and to evaluate associations between patient characteristics and the long-term survival rate and landmark 5- and 10- year survival, in a sample of newly-diagnosed ovarian cancer patients. Methods: The Tempus EMR dataset contains patients from academic & community oncology centers in the U.S. This study included adult women with a new primary diagnosis of ovarian, fallopian tube, or peritoneal cancer between 2000 and 2020. Women treated with a poly-ADP ribose polymerase inhibitor (PARPi), pembrolizumab, or nivolumab were excluded (n = 947; final sample size = 6,598). Mixture cure models were used to estimate the long-term survival rate (probability of living as long as an age- and gender-matched person without ovarian cancer), overall and stratified by patient demographic & clinical characteristics. Relative importance of variables associated with long-term survival was evaluated using logistic regression models with 5- and 10-year landmark outcomes. Results: Younger age, earlier stage, lower grade, favorable ECOG score, and platinum sensitivity were associated with better overall survival (OS). The long-term survival rate in our model was 25.0% (95% CI: 21.5-28.9). The long-term survival rate was higher for age < 65 vs. age 75+ [29.0% (24.8-33.6) vs. 10.5% (2.9-31.6)], early vs. advanced stage disease [62.0% (41.4-78.9) vs. 17.8% (14.1-22.2)], grade 1-2 vs. 3-4 [31.4% (12.1-60.3) vs. 20.4% (14.6-27.8)], ECOG 0-2 vs. 3-4 [26.1% (21.4-31.3) vs. 2.6% (0.05- 56.5)], and platinum sensitive vs. platinum resistant patients [47.5% (43.1-51.9) vs. 9.4% (7.0-12.5)]. Analyzing 5- and 10-year landmarks [n = 3,944 (59.8%), n = 3,107 (47.1%), respectively] in multivariable logistic regression models, platinum sensitivity had the strongest association, followed by cancer stage. Conclusions: Understanding differences in long-term survival based on patient characteristics is important for clinical decision-making and personalizing treatment. Overall, one quarter of ovarian cancer patients were long-term survivors; long-term survivors were more likely to be younger and have earlier stage disease, low grade disease, better performance status, or sensitivity to platinum-based therapy. These results also provide a baseline to evaluate long-term survival in patients on newer therapies such as PARPi when sufficient follow-up data are available.
Anlotinib plus letrozole in patients with platinum-resistant recurrent ovarian cancer: A prospective, single-arm, open-label, phase II study.
Authors: Wang Xipeng , Li Jiarui , Zhang Ping , Fang Xuhong , Wang Yizhi , Sun Huizhen
Published: June 2022

e17545

Background: Studies have suggested that estrogen regulates the malignant transformation of ovarian surface epithelial cells, stimulates the growth and migration of cancer cells. and promotes the VEGF expression in epithelial ovarian cancer. Anlotinib is a novel multi-target tyrosine kinase inhibitor, inhibiting tumor angiogenesis and proliferative signaling. In this study, we evaluate the activity of anlotinib combined with letrozole in patients with estrogen receptor positive, platinum-resistant recurrent ovarian carcinoma (NCT04720807). Methods: Patients who have previously received two or more chemotherapy treatments, with histopathologically confirmed high-grade serous ovarian cancer (including salpingo carcinoma and peritoneal carcinoma), estrogen receptor (ER) positive and ECOG 0-2 were considered eligible for enrollment. Anlotinib was taken orally (10mg mg qd, d1-14, 21 days per cycle), and letrozole was taken orally (2.5mg qd, d1-21, 21 days per cycle). The treatment was continued until disease progression, death, or intolerant toxicity. The primary endpoint was objective response rate (ORR) and the secondary endpoints included disease control rate (DCR), duration of remission (DOR) progression free survival (PFS), overall survival (OS) and safety. Results: Between September 2020 and November 2021, 13 patients with a median age of 62 years (range:53-72), FIGO histopathological stage IC (23.1%), IIIC (53.8%) and IV (23.1%) were enrolled. Twelve of these patients have been evaluated for efficacy. In the efficacy-evaluable population (n=12), the therapeutic evaluation showed that 2 and 7 patients achieved partial response and Stable disease respectively, yielding the ORR of 16.7% (2/12, 95% CI: 3.3 to 54.3). The DCR was 75% (9/12, 95% CI: 39.3 to 93.3). The median PFS was 6.25 months (95% CI: 2.3m to not reached) and the median OS was not reached. The most common adverse events (AEs) were grade 1 or 2, which included laryngitis (69.2%), hypertension (53.8%), stomatitis (38.5%), diarrhea (30.8%), hand-foot syndrome (23.1%), and hyperuricemia (23.1%). The grade 3 AEs were hypertension (38.5%), diarrhea (7.7%) and hyperuricemia (7.7%). No higher AEs or treatment-related death were observed. Conclusions: Conclusions Anlotinib plus letrozole showed a promising efficacy with a favorable toxicity profile for patients with platinum-resistant recurrent ovarian cancer. The trial is ongoing and more data will be provided in the future. Clinical trial information: NCT04720807.
Effects of five prescriptions in Synopsis of Golden Chamber on the malignant phenotype and expression of CA125, CEA, HE4 proteins in human ovarian cancer cells.
Authors: Si Fuchun , Si Gao
Published: June 2022

e17546

Background: Ovarian cancer(OC) is a common gynecological tumor with characteristics of low early diagnosis rate, late lack of effective treatment and high mortality. It is an important problem to find new effective treatment for ovarian cancer. Synopsis of the Golden Chamber is the miscellaneous diseases part of Treatise on Typhoid and Miscellaneous Diseases written by Zhang Zhongjing, a famous medical expert in Eastern Han Dynasty of China, and is also the earliest classical treatise on diagnosis and treatment of miscellaneous diseases, which records 205 prescriptions. This study aims to screen out formula with strong inhibitory effects on OC from 205 prescriptions of Synopsis of the Golden Chamber , and investigate the effects of screened prescriptions in Synopsis of the Golden Chamber on human ovarian cancer cell malignant phenotype and CA125, CEA and HE4 proteins expression. Methods: MTT method was applied to screen out the best effective prescription and determine the IC50 value of prescription on ovarian cancer ES-2 and OV-1063 cells. The effects of screened prescriptions on the proliferation, migration, invasion, cloning ability, cell cycle and CA125, CEA and HE4 proteins expression of ES-2 and OV-1063 cells were investigated by MTT assay, RTCA assay, soft agar assay, flow cytometry and western blot analysis. Results: Guizhi Fuling Pill, Dachaihu Decoction, Xuanfuhua Decoction, Baitouweng Decoction and Bentun Decoction were screened out, which all could obviously inhibit the proliferation of ES-2 and OV-1063 cells with dose-effect and time-dependent manner. The IC50 values of Guizhi Fuling Pill, Dachaihu Decoction, Xuanfuhua Decoction, Baitouweng Decoction and Bentun Decoction for ES-2 cell were 636.476, 315.859, 24.357, 9.519, 96.533μg/ml respectively; for OV-1063 were 403.119, 225.176, 12.977, 9.256, 115.86μg/ml respectively. The five prescriptions all significantly affected the cell morphology, proliferation, migration, invasion, cloning ability, cell cycle of ES-2 and OV-1063 cells. The five prescriptions all could decreased the protein expression levels of CA125 and CEA in ovarian cancer OV-1063 cells, while Guizhi Fuling Pill, Dachaihu Decoction, Xuanfuhua Decoction and Baitouweng Decoction decreased the expression of HE4 protein in OV-1063 cells. Conclusions: The five prescriptions in Synopsis of the Golden Chamber can inhibit the malignant phenotype of ovarian cancer, which may be related to the inhibition of CA125, CEA and HE4 proteins expression.
Characteristics of germline DNA damage response gene mutations in ovarian cancer in Southwest China.
Authors: Yin Rutie , Chen Jinghong , Li Qingli , Yan Xinyu , Wang Jie , Li Kemin , Song Liang , Zhong Lan , Ma Yu , Zhang Mengpei , Zeng Jing , Wang Danqing , Zhu Shida
Published: June 2022

e17606

Background: DNA damage response (DDR) pathway is responsible for repairing endogenous or exogenous DNA damage to maintain the stability of the cell genome. Germline mutations of DDR genes are potentially predictive and prognostic biomarkers for oncotherapy and may predispose carries to some malignancies. We aimed to profile the characteristics of germline DDR gene mutations in ovarian cancer treated in our center to provide highlight on regional disparity and susceptibility genes. Methods: We retrospectively and unselectively enrolled a cohort of patients diagnosed as advanced epithelial ovarian cancer from October 2016 to October 2020, who had complete clinicopathological data and signed informed consent for gene testing. In total, peripheral blood samples from 432 patients were collected in our center and evaluated on specific germline alterations. This study was approved by the Medical Ethics Committee of West China Second University Hospital, Sichuan University (Ethical Lot Number 20200076). Results: The most observed mutated genes were FANCD2 (47%), BRCA1 (27%), BRCA2 (27%), ERCC5 (18%) and RECQL4 (17%). The frequency of missense mutation was higher than other mutation types in most genes, except FANCD2, TSC2 and PHOX2B. Deleterious DDR gene mutations and deleterious homologous recombination repair gene mutations were detected in 346 patients (80.1%) and 240 patients (55.6%), respectively. The most observed genes with deleterious mutation were BRCA1 (18.5%), BRCA2 (12.5%), ERCC5 (6%), MLH1 (5.8%), PALB2 (3.7%) and ERCC4 (3.7%). The prevalence of BRCA2 deleterious mutations is higher than other studies (patients mainly from Eastern China), and so are the mismatch repair genes. Furthermore, we pointed out that deleterious mutations of FNACD2 and RECQL4 are potential ovarian cancer susceptibility genes and may predispose carriers to ovarian cancer. Conclusions: Our study presented here showed the germline DDR gene mutation spectrum of ovarian cancer patients in Southwest China, which is different from other regions of China in some genes. And we found germline FANCD2 and RECQL4 deleterious mutations were likely ovarian cancer susceptibility sites, which should draw more attention in patient management and genetic counseling.
Methylated DNA markers discriminate ovarian cancer from benign tissue in BRCA carriers.
Authors: Weng Jessica , Bakkum-Gamez Jamie Nadine , Slettedahl Seth , Mahoney Douglas W. , Cao Xiaoming , Foote Patrick H. , Burger Kelli , Berger Calise K. , O'Connell Maria , Arndt Jacquelyn R. , Doering Karen A. , Sherman Mark E. , Taylor William R. , Chen Longwen , Couch Fergus , Kisiel John B. , Samadder Jewel
Published: June 2022

e17610

Background: Methylated DNA markers (MDMs) associated with sporadic ovarian cancer (OC) are detected in plasma from patients with treatment naïve tumors, but not cancer-free controls. To assess potential benefits to patients at risk for hereditary OC, the aim of this study was to measure the performance of validated sporadic OC MDMs in OC and benign ovarian tissue (BOT), surgically obtained from germline BRCA1 or BRCA2 ( BRCA1/2) mutation carriers. Methods: BRCA1/2 carriers with OC and BRCA1/2 carriers who had undergone risk-reducing salpingo-oophorectomy (SO) were identified at a comprehensive cancer center. BRCA1/2 carriers in both OC and BOT groups were balanced on age and year of surgery with non- BRCA carriers with sporadic OC or benign indications for SO. OC and BOT formalin fixed paraffin embedded (FFPE) tissues were macrodissected following pathologist selection of representative sites; DNA was extracted, and bisulfite converted. 15 OC MDMs ( GDF6, IFFO1, MAX.chr1.147790358, MAX.chr6.10382190, MAX.chr11.14926602, C2CD4D, PDRM14, NCOR2, SKI, DSCR6, SIM2, PALLD, CDO1, GPRIN1, BCAT1) previously identified in sporadic OC were assayed by quantitative methylation specific PCR, normalized by β-actin, by blinded personnel. Areas under the receiver operating characteristic curve (AUC) were generated for each MDM to assess discrimination of OC from benign tissue and compared between BRCA1/2 and sporadic (non- BRCA) patients, using a z-test. Results: Among BRCA1/2 carriers, there were 48 OC ( BRCA-OC) and 48 BOT ( BRCA-BOT); among non- BRCA, we matched 48 OC (Sporadic-OC) and 48 BOT (non- BRCA-BOT). The median AUC for OC MDM discriminated between OC and BOT with AUCs in BRCA1/2 carriers was 0.87, (IQR, 0.83-0.93). Sporadic-OC vs non- BRCA-BOT median AUC was 0.88 (IQR, 0.83-0.92). AUCs were not significantly different for each MDM when stratified by BRCA or sporadic status. MDMs with an AUC of ≥0.9 in either group are shown (Table). Conclusions: OC MDMs identified and validated in sporadic OC are highly discriminant for OC from BOT in DNA extracted from tissues of people who carry a BRCA1/2 mutation. Testing the performance of these OC MDMs in plasma from BRCA1/2 carriers with and without OC may be of clinical value for high-risk patients and inform multi-cancer early detection testing strategies.[Table: see text]
Identifying targetable markers of resistance to dual TORC1/2 inhibition in endometrial cancer cell lines.
Authors: McGreal Katie , Crafton Sarah , David Jason , Stets Colin W. , Grosenbacher Nicholas , Chen James Lin , Hays John L.
Published: June 2022

e17633

Background: For patients with endometrial cancer, the PI3K/AKT/mTOR pathway is an attractive target due to dysregulation of the pathway secondary to commonly found genetic alterations. Previous trials of mTOR inhibitors in endometrial cancer have shown modest clinical activity and tolerability. Here we present a proteomics based approach to identify novel partners that will enhance the efficacy of dual TORC1/2 inhibition. Methods: Five endometrial cell lines (AN3CA, ECC, HEC1A, HEC1B, RL952) were treated with the TORC1/2 inhibitor TAK228 or vehicle for one hour and protein concentrations were analyzed by reverse phase protein arrays (RPPA). We examined baseline protein and changes in individual proteins after treatment with TAK228 to determine correlations with sensitivity to TAK228. Identified proteins were then targeted with single agent pharmacologic inhibition and cytotoxicity measured by XTT analysis. Target inhibition was validated using WB analysis. Cooperativity in cytotoxicity for relevant combinations was measured using the methods of Chou-Talalay. Other phenotypic endpoints including migration, cell cycle alterations by flow cytometry and cell growth using live cell imaging were also collected. Results: Based on proteomics analysis, altered phosphorylation of CHK1(S296), CHK2(T68) and increasing concentration of VEGFR2 were strongly correlated with TAK228 resistance. TAK228 (TORC1/2, IC50 4-20nM), AZD7762 (CHK1/2, IC50 15-160nM), LY2603618 (CHK1, IC50 260nM-7.5mM) and cediranib (VEGFR2, 800nM-1mM) all had significant cytotoxic effects as individual agents on multiple endometrial cell lines. AZD7762 in combination with TAK228 led to synergism in all cell lines tested (mean combination index, 0.2-0.8). Single agent AZD7762 increased the number of cells in S-Phase and decreased cellular migration. Addition of recombinant VEGF-A to cell culture enhanced resistance to TAK228 in a dose dependent manner as measured by cell growth assays using live cell imaging. Combination of cediranib and TAK228 also showed significant synergism in multiple cell lines. Conclusions: RPPA identified changes in phosphorylated CHK1/2 and total VEGFR2 as being correlated to resistance to dual TORC1/2 inhibition with TAK228 in multiple endometrial cancer cell lines. While single agent activity of TORC1/2, CHK1/2 and VEGFR2 inhibitors showed varying activity, combinations of TAK228 with either cediranib or AZD7762 showed significant synergism in multiple cell lines. Clinical examination of these combinations agents may prove useful in recurrent endometrial cancer.
Neutrophil-to-lymphocyte ratio as a predictor of survival in head and neck squamous cell carcinoma patients treated with cisplatin.
Authors: Kao Derek , Ferrandino Rocco , Roof Scott , Sigel Keith Magnus
Published: June 2022

e18004

Background: Neutrophil-to-lymphocyte ratio (NLR) is an easily attainable biomarker that is correlated with systemic inflammation and identifies increased risk of treatment complications and decreased survival in patients with cancer. Our objective was to investigate the use of NLR as an independent prognostic predictor of survival in patients with head and neck squamous cell carcinoma (HNSCC) treated with cisplatin chemotherapy. Methods: We conducted a retrospective study of 2,084 patients in the Veterans Health Affairs system with stages III–IVB head and neck squamous cell carcinoma diagnosed between 2000–2014 and treated with cisplatin-based chemoradiotherapy for curative intent. We calculated NLR values from laboratory values collected in the 30 days prior to initiation of chemoradiotherapy and dichotomized NLR using the Youden J-statistic (NLR = 3.64). We then compared outcomes using Cox proportional hazards methods, adjusting for sociodemographic characteristics (age, race, and sex), date of cancer diagnosis, smoking status, alcohol use, primary site of tumor, tumor characteristics (overall stage, T stage, and N stage), comorbidity score, eGFR, baseline neuropathy and hearing loss, BMI, and oncologic surgical procedures. Results: The cohort had a median age of 61. 99% of cases were male, 82% were white, 13% were black, and 4% were Hispanic. 36% of cases had an NLR > 3.64 prior to treatment initiation. Median overall survival was 32.6 months for the low-NLR group and 24.9 months for the high-NLR group. In unadjusted analyses, a high NLR was associated with an increased risk of all-cause death (hazard ratio [HR]: 1.21; 95% CI 1.08–1.34). In adjusted analyses, high NLR retained significance and predicted overall survival (HR: 1.15; 95% CI 1.02–1.30). We also performed a secondary analysis for death within six months of cancer diagnosis; high NLR was associated with > 50% increased risk of death after adjustment (HR: 1.56; 95% CI 1.04–2.33). Conclusions: In this large cohort of Veterans with advanced HNSCC undergoing chemoradiotherapy, NLR was an independent prognostic predictor of survival. NLR may be a useful clinical risk stratification tool prior to chemoradiotherapy initiation.
Real-world data of use of nivolumab in platinum refractory head and neck cancers.
Authors: Choudhary Jatin , Kumar Hemanth , Ravikrishna Madala , Patil Vijay Maruti , Prabhash Kumar
Published: June 2022

e18686

Background: Nivolumab is one of the approved agents for platinum refractory and second line treatment in head and neck cancers as per NCCN guidelines. However, accessibility of nivolumab in low- and middle-income countries is less than 1-3%.There is data suggesting that low doses of nivolumab can also be effective. Hence in this analysis we explore the outcomes and adverse events with low doses of nivolumab in the second line and beyond setting. Methods: The head and neck medical oncology unit of Tata memorial hospital maintains a prospective database of all patients undergoing immunotherapy. A query was raised in this database to identify head and neck cancer patients who were treated with low doses of nivolumab. We identified 42 patients. The baseline characteristics, compliance to nivolumab, the reason for administration of low dose and the outcomes (progression free survival, date of progression, date of death) were recorded. The dose of nivolumab used in this study was 40 mg flat dose every 2 weeks. Descriptive statistics were performed. Kaplan Meier estimates were used to see overall survival (OS) and progression free survival (PFS). Results: The median age of the patients was 55.8 (IQR: 25.8-82.8) Male to female ratio was 53:11. All patients were platinum refractory and had progressive disease within the last 6 months of the last dose of platinum. The ECOG performance status was 0- 1 in 56 (88.9%) in patients and 2 in 8 (11.1%) patients. Median number of immunotherapy cycles received was 2 (1-4). The response was seen in 15 (23.1%) patients. The median OS was 6.7months (3.4-8.8) and PFS was 2.3 months (0.6-4.02) The details regarding PD L-1 expression and effectiveness of nivolumab will be presented at the conference. Conclusions: Low doses of nivolumab can be an option which is efficacious in patients who do not have access to standard dose nivolumab. There is a need for testing this regimen in large randomized studies as full doses of nivolumab are not accessible to the vast majority of the patients in low- and middle-income countries.
Patient, caregiver, and physician preferences for treatment of relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).
Authors: Vukcevic Mirko , Yung Mallory , Khan Maliha , Schnell Frederick Mark
Published: June 2022

e18710

Background: Relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) patients ineligible for transplantation face complex, preference-sensitive treatment decisions. Shared decision making (SDM) can improve patient engagement and treatment satisfaction, despite limited data on patient preferences and values in treatment decision-making, particularly for 2nd and 3rd-lines. We conducted a primary qualitative research study to better understand R/R DLBCL treatment decision-making in patients, caregivers, and physicians. Methods: We conducted 1-hour semi-structured interviews with 14 adult R/R DLBCL patients, 8 paired caregivers, and 8 oncologists of R/R DLBCL patients to understand perceived patient and caregiver involvement in treatment-related decisions, 2nd and 3rd-line preferences and goals, treatment satisfaction, and current SDM practices. We used template analysis to code transcripts from 6 a priori codes. 2 interviewers double-coded 8 interviews to ensure interrater reliability > 75% and independently coded the remaining 22 interviews. Results: Patients said rapid-moving care and shock of diagnosis or failing treatment impeded individual and caregiver involvement in treatment decision-making, and thus relied on physician recommendations for 1st line treatment. All patients felt they followed a well-established standard of care, adding to low self-efficacy for SDM in 71% of patients and 38% of caregivers. Caregivers also perceived treatment decisions as directives. While physicians believe patients should have total control over their treatment decisions, they agreed on barriers for involving patients in decision-making (i.e., limited treatment options, established standard of care, lack of patient understanding). Patients found that cumulative treatment experience shaped preferences and considerations in 2nd and 3rd-line treatment; 43% perceived higher autonomy over decision-making and had clearer expectations. 10 patients (71%) said their oncologists shared educational materials around treatment options, but some wanted resources to address ancillary concerns (e.g., mental health, fertility). Patients found caregivers helpful in enhancing their understanding of treatment-related discussions, and all physicians encouraged caregiver inclusion in treatment planning. 71% of patients felt satisfied with their treatment experience, but 21% would have liked a more individualized approach. Conclusions: Results suggest while 2nd- and 3rd-line R/R DLBCL treatment options may be limited, patient preferences and goals can be incorporated into long-term treatment planning. Opportunities for improvement include developing tailored educational materials for caregivers to establish them as trusted messengers and physician tools to support integration of patients’ lived experiences into their clinical workflow.
Are patients with alcohol-related cancers (ARCs) more likely to quit drinking than the general population? Results of a national population-based survey.
Authors: Ishani Khalid , Chagpar Anees B.
Published: June 2022

e18716

Background: Alcohol is a known carcinogen, predisposing to a variety of cancers. While abstinence may reduce the risk of recurrence of these tumors, it is unclear whether patients diagnosed with an alcohol related cancer (ARC) are more likely to quit than the general population. Methods: We utilized the National Health Interview Survey (NHIS) dataset to compare the rate of quitting drinking between those with ARCs (mouth, pharynx, larynx, esophagus, liver, stomach, colon/rectum, breast, and pancreas) versus the general population. Results: In 2020, the NHIS surveyed 31,512 people, representing 251,697,992 in the population. Of these, 2.56% reported having been diagnosed with an ARC in the past. The proportion of people who had consumed alcohol at least once in their lives was similar between those with ARC and the general population (87.57% vs. 86.86%, p = 0.625); however, among those who had ever drunk, those with ARC were more likely to state they had not consumed any alcohol in the past 12 months (33.92% vs. 19.85%, p < 0.001). Patients diagnosed with an ARC were more likely to be white (75.43% vs. 63.34%), older than 65 (58.72% vs. 19.30%), with annual household income < $35,000 (32.56% vs. 22.92%) and a lower rate of private health insurance (48.12% vs. 62.08%), all p < 0.001. Controlling for these sociodemographic factors, among ever-drinkers, those with an ARC were still more likely to report having quit drinking (OR: 1.20; 95% CI: 1.00-1.44, p = 0.046). Of note, however, 5.95% of people with ARCs remained current heavy drinkers (similar to those without ARCs 5.98%, p = 0.977). Among people with ARCs, those who were older than 65 (69.31% vs. 59.10%, p < 0.001), with less than a high school education (20.63% vs. 6.02%, p = 0.001), public insurance (49.27% vs. 32.65%, p = 0.001), and annual household income < $35,000 (44.40% vs. 23.34%, p < 0.001) were less likely to continue to drink. On multivariate analysis, age (p < 0.001), education (p = 0.019) and income (p < 0.001) remained independent predictors of continuing to drink among ARC survivors. Conclusions: While patients with ARCs are more likely to have quit drinking than the general population, nearly two thirds of patients diagnosed with ARCs continue to consume alcohol, with nearly 6% being heavy drinkers. ARC survivors who continue to drink tend to be well-educated, affluent and well-insured; it may therefore behoove clinicians not to neglect educating this population on the merits of abstaining from alcohol after an ARC.
Economic impact of broad panel versus sequential single and narrow panel sequencing in lung cancer patients.
Authors: Hospodar Alexa , Byrd Brooke , Cullum Robert , Hastings Kevin , Teschner Taylor , Brown Trish , Reddy Shirisha , Belinson Suzanne , Schulin Joseff , Klien Ira , Hovanec Emma , Mergler Patrick , Avalos-Reyes Elisea , Johnson Kjel Andrew , Brito Rogelio A.
Published: June 2022

e18718

Background: Recent developments in next-generation sequencing (NGS) technology have revolutionized our understanding of cancer biology and clinical research by improving diagnoses and recognizing mutations for personalized therapies. Sequential single (SS) gene testing and narrow panel sequencing (NPS) are used to select targeted therapies and precision medicine strategies for lung cancer patients. While broad panel sequencing (BPS) can identify more mutations than SS and NPS, it is more expensive. This study aims to assess the long-term cost-effectiveness of BPS vs. SS and NPS in lung cancer patients. Methods: This study will evaluate lung cancer patients undergoing biomarker testing insured by a large commercial and Medicare health plan in the United States between January 1, 2021, and May 31, 2021. The SS and NPS group consists of patients with 50 or fewer genes sequenced; the BPS group consists of those with more than 50 genes sequenced. Our primary clinical endpoint for analysis is the total cost of care defined as the allowed costs paid for all medical and pharmacy claims six months from the first gene sequencing panel. Multivariable regression analysis will assess the influence of explanatory variables on costs. Analysis will be complete February 28, 2022.
Risk factors for cardiovascular events in patients treated with immunotherapy.
Authors: Garitaonaindia Yago , Blanco Mariola , Franco Fernando , Torrente Maria , Calvo Virginia , Collazo Ana , Gonzalez del Alba Aranzazu , Sanchez Juan Cristobal , Gutiérrez Lourdes , Royuela Ana , Nuñez Garcia Beatriz , Mendez Miriam , Hernández Roberto , Cantos Sanchez de Ibarguen Blanca , Martinez Cutillas Marta , Traseira Cristina , Aguado Ramon , Visedo Ceballos Guillermo , Provencio Mariano
Published: June 2022

e18736

Background: Immunotherapy (IO) is increasingly widespread in current clinical practice; however, little is known about its cardiovascular safety profile. The aim of this study is to identify clinical factors that are associated with increased risk of having a cardiac event (CE). Methods: we conducted a retrospective study in a single institution including patients treated with IO from 2014 to 2020. We analyzed their clinical characteristics and the CE developed during IO treatment and compared those who had a registered CE with those who had not. Results: 378 patients were analyzed. After a mean-follow up 15.9 months, we registered the following CE: ECG abnormalities 12.2%, congestive heart failure 3.4%, pulmonary embolism 1.9%, coronary syndrome 0.8%, myocarditis 0.5% and pericarditis 0.5%. The specific cardiac mortality was 0.8%. Results are shown in Table. Conclusions: In our study, elder age, history of ischemic heart disease or arrythmia, and reporting other immune-related adverse events (irAE), appear to be risk factors for developing a CE during IO treatment. Although most are well-known cardiovascular risk factors, the relationship between other irAEs and CE should be highlighted, and prospective studies are needed to delve into this hypothesis.[Table: see text]
Longitudinal trends of real-world evidence (RWE) reporting in oncology conferences: An 11-year ASCO Annual Meeting analysis.
Authors: Azad Farhan , Zhang Jiahua , Akhtar Othman Salim , George Anthony , Attwood Kristopher , Torka Pallawi
Published: June 2022

e18748

Background: Randomized-controlled trials are the gold-standard of clinical research. However, majority of patients with cancer (> 95%) are ineligible/unable to participate in these studies. Retrospective studies using real-world evidence (RWE) help fill the knowledge gap by reporting outcomes in under-represented populations such as patients with rare diseases, comorbidities or those at extremes of age. There is limited data on the pattern and quality of RWE reporting at oncology meetings or in the literature. In this study, we examine longitudinal trends in RWE reporting at ASCO annual meetings over an 11-year period. Methods: We used the search items “retrospective”, “real world” and “observational” to identify all retrospective observational studies reported between 2011 and 2021 at ASCO annual meetings. Population size, number of centers and topics represented were recorded. For studies selected as oral presentations, details about subsequent publication of the full manuscripts was also collected. The statistical significance of reporting trends was tested using the Cochran-Armitage trend test, and the Pearson chi-square test was used to study associations between categorical variables. Results: A total of 49,190 abstracts were reviewed and 6742 (13.7%) studies reporting RWE were identified. There was an increase in the relative frequency of studies reporting RWE, from 13.8% of all abstracts in 2011 to 16.2% in 2021, p < .0001. There was also an increase in the proportion of real-world studies with patient populations of ≥1000 over time (14.6% in 2011 to 19.9% in 2021, p= .0001), with fewer studies including ≤100 patients over the same period (41.4% to 32.3%, p= .0181). Overall, a majority of these studies (70.1%, 4785/6742) were accepted for publication only with a decrease in proportion of studies accepted as posters (43.9% in 2011 to 30.5% in 2021, p < .0001). There was no significant trend in proportion of studies accepted as oral presentations over the same period (.19% to 1.96%, p= .134). There was an association between number of institutions involved, population size and acceptance category (publication only vs poster or oral), p< .001). Only 27.2% of single-center studies were accepted for poster/oral presentation in comparison to 43.6% of studies involving multiple centers. Out of 54 studies that were accepted for oral presentations, 59.3% (32/54) involved ≥1000 patients ( p< .001); 28/54 were published in Pubmed-indexed journals (highest impact factor, 32.98). Conclusions: There has been a significant increase in the relative frequency of studies reporting RWE at the ASCO Annual Meetings. Involvement of multiple institutions and larger patient populations allow for collection of higher quality data, and are associated with increased acceptance as oral/poster presentations versus publication only, underscoring the importance of multi-center collaboration.
Patient preferences for treatment and outcomes in hormone-sensitive prostate cancer (HSPC).
Authors: George Daniel J. , Ganguli Arijit , Morgans Alicia K. , Tombal Bertrand F. , Hotte Sebastien J. , Suzuki Hiroyoshi , Bhadauria Hemant , Oh Mok , Scales Charles D. , Grover Kiran , Gonzalez Juan Marcos
Published: June 2022

e18757

Background: Treatment options for patients with HSPC have broadened, and data regarding patient preferences for therapies can aid in therapeutic decision-making. This study evaluated the impact of attributes associated with therapies for US patients with locally advanced prostate cancer (LAPC) or metastatic HSPC (mHSPC) from the perspective of patient preferences. Methods: An online discrete choice experiment (DCE) was developed for patients with LAPC or mHSPC. The DCE included 12 questions designed to systematically require tradeoffs between treatment attributes of efficacy (5-year overall survival [OS]), tolerability (fatigue, skin rash, neurotoxicity, and common chemotherapy-related toxicity), and convenience (administration factors [route, frequency, and setting], concomitant use of steroids, and monitoring requirements). Respondents could choose androgen deprivation therapy (ADT) alone or with hypothetical therapies that improved 5-year OS but had additional adverse events (AEs). Attribute-specific importance weights measuring their relative impact on treatment choices were estimated using a mixed-logit model, which also controlled for heterogeneity in preferences. Results: From September 3 to October 14, 2021, 82 respondents (mean age 61 years) completed the survey (LAPC, n = 40; mHSPC, n = 42), with 61 (74.4%) receiving ADT at the time of the survey. Respondents reported treatment efficacy (36% [95% confidence interval (CI) 22, 49]) as the most important aspect of treatment choice, followed by changes in chemotherapy-related toxicity (13% [95% CI 3, 22]) and the need for concomitant steroid use (12% [95% CI 5, 19]). Respondents considered monitoring requirements (8% [95% CI 5, 19]) to be more important than fatigue (5% [95% CI 2, 13]). Administration factors were comparable in importance to therapy AEs (Table). Respondents preferred, by at least 10 percentage points, adding therapies to ADT that could improve 5-year OS, at the detriment of additional AEs. Conclusions: After efficacy, convenience was considered to impact treatment choices at a rate comparable to tolerability issues, potentially influenced by perceived COVID-19 exposure risks. Patients with LAPC and mHSPC prioritize efficacy despite the detriment of additional AEs.[Table: see text]
Reduced blood product utilization via implementation of an anemia clinic and consult service in a large health system hospital.
Authors: Bowers Reid Christian , Korman Sandra Tomany , Thompson Michael A. , Sana Sherjeel , Pant Manish Krishna , Sanchez Federico Augusto
Published: June 2022

e18799

Background: An Anemia Clinic program was started Sept. 2016 as part of system wide implementation of Patient Blood Management (PBM) initiated in 2015. Methods: The Anemia Clinic accepted referrals for non-cancer anemia, predominantly preoperative cardiovascular surgery (CVS) Pts. Hgb thresholds were < 13 g/dL in men and < 12 g/dL in women. Non-anemia cytopenias triggered Hematology referral. All Pts were screened for iron, B12, folate, and reticulocyte count. Nutrient deficiencies were supplemented. Pts with CKD or chronic disease were considered for erythropoiesis stimulating agents. Results: PBM implementation resulted in a drop in packed red blood cell (PRBC) usage (Table). Of CVS Pts pre-operatively anemic in 2021, 169 were referred to the Anemia Clinic and 352 were not. The percentage of Pts who received PRBCs after Anemia Clinic referral was statistically different from those who were not referred (67.5% vs. 52.8% chi-square p = 0.002). Of preoperatively anemic Pts who were transfused in 2021, an average of 2.67 PRBCs were used in the referred group vs. an average of 2.36 PRBCs in those in the not referred group (negative binomial p = 0.18). Length of stay (LOS) which was a median 10d ( P25= 7d, P75 =18d) in the referred group vs a median 10d ( P25= 6d, P75 =16.5d) in the non-referred group was not statistically different between groups (Smirnov p = 0.36). LOS analyses of observed-to-expected (O/E) ratios used the Premier Healthcare Providers Alliance Database (PHD) which contains data on approximately 45% of US hospital discharges. For 2021 through Nov. the referred group had an O/E = 0.93 (observed LOS μgeo = 10.88 days, expected LOS μgeo = 11.67 days, N = 154). The not referred group had an O/E = 1.04 (observed LOS μgeo = 10.56 days, expected LOS μgeo = 10.18 days, N = 305). Conclusions: PBM decreased PRBC use through systematization of best practices during the initial year, and that decrease has persisted for six years. Subsequent addition of Anemia Clinic services did not decrease PRBC use further. A trend toward shorter LOS for patients referred to Anemia Clinic did not continue this year, but the difference in LOS from the not referred group was not statistically significant and observed LOS for the referred group was lower than expected LOS. Our methods improved nutrient deficiency identification which may improve both later health outcomes not detected here and access to treatment for hematologic malignancies.[Table: see text]
Real-world progression-free and overall survival for patients with advanced ovarian cancer utilizing PARP inhibitor second-line maintenance therapy vs active surveillance.
Authors: Reid Robert Lawrence , Shi Junxin , Monnette Alisha , Wallace Katrine L
Published: June 2022

e18812

Background: Ovarian cancer (OC) is the fifth leading cause of cancer death among women. Poly(ADP-ribose) polymerase inhibitors (PARPis) are recommended following response to second-line (2L) chemotherapy as 2L maintenance treatment by the National Comprehensive Cancer Network for OC patients (pts), based on results from clinical trials demonstrating their ability to extend progression-free survival (PFS), the time between chemotherapy and relapse, in this patient population. We present recent estimates of real-world PFS and overall survival (OS) for pts on 2L PARPi maintenance therapy vs active surveillance. Methods: From the iKnowMed electronic health record database and a review of patient charts within the US Oncology Network, which includes 1200 physicians operating in over 470 sites of care in the US, adult females were included if they were diagnosed with advanced OC, had received a 2L platinum-containing regimen for advanced OC, and had ≥2 visits within the database between 1 Jan 2016 and 1 Dec 2020. Among these, a subset of charts were reviewed to confirm eligibility and to assess PFS. Patients were followed longitudinally until 31 March 2021, the last pt record, or date of death, whichever occurred earliest. Kaplan-Meier survival methods and log-rank tests were used to estimate and compare the OS as well as PFS of the groups to 24 months. Results: A total of 1154 pts met study inclusion criteria for advanced OC and either a PARPi or active surveillance for the 2L maintenance period. Of these, 142 patient charts were further manually reviewed to assess real-world PFS: 84 received a PARPi, and 58 received active surveillance. Median age at the start of 2L maintenance was 65.7 years and was not significantly different between groups. There was a significant difference in the distribution of the ECOG PS category between groups (ECOG PS 0: 22.6% vs 1.7%, ECOG PS 1: 39.3% vs 50.0%, for PARPi vs active surveillance, respectively; P< 0.0001). Median follow-up time from discontinuation of 2L platinum chemotherapy until the end of observation was significantly longer in the active surveillance group (41.5 vs 23.5 months; P< 0.0001). PFS probability from the beginning of 2L maintenance was higher in the PARPi group vs active surveillance (24% vs 10% at 24 months; P= 0.0003). OS probability was also significantly higher in the PARPi group vs active surveillance (78% vs 55% at 24 months; P= 0.0272). Conclusions: This study of PARPi therapy vs active surveillance confirms the efficacy benefits that have been demonstrated in randomized clinical trials of PARPis vs placebo, and it provides further evidence of the real-world effectiveness of PARPi maintenance therapy to improve survival in a population with advanced OC.
Acute promyelocytic leukemia: A single institution's experience.
Authors: Bennett Joseph , Lin Tara L. , Venkatesh Priyanka , Male Heather Jean , Byrd Kenneth
Published: June 2022

e19001

Background: Acute Promyelocytic Leukemia (APL) is highly curable but carries high risk of early morbidity and mortality, including hemostatic abnormalities, differentiation syndrome and infection. Induction regimens include all-trans-retinoic acid (ATRA) to promote promyelocyte differentiation and arsenic trioxide (ATO), with chemotherapy added for high-risk patients. Our objective was to characterize clinical characteristics and complications during APL induction. Methods: Electronic medical records were screened for ATRA, ATO, or idarubicin from 2011-2021. APL induction hospitalization records were reviewed for: demographics, white blood cell (WBC) and platelet count at presentation, fibrinogen at presentation, time to ATRA administration, time to complete remission (CR), infection, thrombohemorrhagic complications, ATO related QT interval prolongation, incidence of and time to differentiation syndrome. Results: 56 patients (pts) (median age 50) were analyzed. Mean time from initial presentation at our institution to ATRA administration was 1.5 days (range 0-6 days). Findings upon arrival: median WBC 1.7 K/UL (range 0.3-134.9), median platelets 32 K/UL (range 7-373), hypofibrinogenemia in 39.2% (N = 22) (median 161 MG/DL, range 35-473). 80.3% had documented thrombohemorrhagic complications during induction hospitalization: DIC (N = 24), venous thromboembolism (N = 12), gastrointestinal bleed (N = 6), oral mucosal bleeding (N = 5), vaginal bleeding (N = 3), gross hematuria (N = 3), intracranial hemorrhage (N = 3), epistaxis (N = 2), intraocular hemorrhage (N = 1), cerebral vascular accident (CVA) (N = 1). 21% (N = 12) developed differentiation syndrome with mean time of onset of 8.8 days (range 1-23 days). 55% (N = 31) had clinically significant infections most commonly neutropenic fever (N = 13), bacterial pneumonia (N = 10), skin (N = 5) and bacteremia (N = 5). 48 pts were given ATO during induction and 31% (N = 15) developed QT interval prolongation with no arrhythmias in the cohort. Among 8 pts who did not receive ATO, one died prior to therapy initiation and 7 were treated prior to ATO as standard of care. Among evaluable patients (N = 51): 98% (N = 50) achieved complete remission (CR) or complete remission with incomplete count recovery (CRi). Median time to CR was 35 days (range 27-50). 6 pts did not achieve CR or had unknown status: 1 patient died during induction (CVA) and 5 had post-induction bone marrow evaluations at outside facilities. Conclusions: Thrombohemorrhagic complications, infection and differentiation syndrome are critical to be mindful of during the early phase of treatment in APL. Our data adds to the landscape of knowledge regarding the incidence and timeline of complications. Although we observed prolonged QTc in pts on ATO, there were no arrhythmias detected and all pts were able to quickly resume therapy.
Treatment outcomes for newly diagnosed, untreated TP53-mutated acute myeloid leukemia: A systematic review and meta-analysis.
Authors: Daver Naval Guastad , Iqbal Shahed , Renard Camille , Chan Rebecca J. , Hasegawa Ken , Hu Hao , Tse Preston , Yan Jiajun , Zoratti Michael J. , Xie Feng , Ramsingh Giridharan
Published: June 2022

e19020

Background: TP53 mutations are present in 10%–15% of patients with acute myeloid leukemia (AML) and are associated with resistance to therapy and poor outcomes. Currently available frontline therapies for TP53-mutated ( TP53m) AML include intensive chemotherapy (IC), hypomethylating agents (HMA), and venetoclax combined with HMA (VEN+HMA). This systematic review and meta-analysis evaluated outcomes associated with IC, HMA, and VEN+HMA in newly diagnosed, untreated TP53m AML. Methods: EMBASE and MEDLINE were searched May 20, 2021 to identify studies of interest. Single-arm data on complete remission (CR), CR with incomplete hematologic recovery (CRi), median overall survival (mOS), event-free survival (EFS), and duration of response (DoR) were extracted and pooled for each treatment. Response rates were pooled using random-effects models; the median of medians method was used for time-related outcomes. Results: Of 3006 abstracts identified, 17 publications describing 12 studies met the inclusion criteria: 6 were randomized clinical trials (RCTs), 2 were single-arm trials, and 4 were retrospective studies. Outcomes are displayed in the Table. CR rate was highest with IC at 43% (95% CI, 30%, 56%), followed by VEN+HMA, 33% (22%, 47%), and HMA alone 21% (7%, 49%). Rates of CR/CRi were 49% (37%, 60%) for VEN+HMA, 46% (39%, 53%) for IC, and 13% (2%, 48%) for HMA alone. mOS was similarly low across the 3 treatments: IC, 6.5 months (N=155; 5.1, 8.5); VEN+HMA, 6.2 (N=73; 5.2, 7.2); HMA, 6.1 (N=34; 4.9, 7.2). Conclusions: CR, CR/CRi, and mOS were low across all treatments for patients with newly diagnosed, untreated TP53m AML. Addition of venetoclax to HMA showed a trend toward improved response vs HMA alone but not for mOS. There is a significant unmet need for more effective treatment for this very difficult-to-treat population. [Table: see text]