bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness of Olaparib plus Bevacizumab versus Bevacizumab in the maintenance of patients with HRD+ advanced ovarian cancer after response to first-line platinum-based chemotherapy in Spain.
Authors: Perez-Fidalgo Jose Alejandro , Cercos Lleti Ana Cristina , Manso Luis , Casado Herraez Antonio , Ventayol Bosch Pedro , Garí Carla , Padres Martí Miriam , Cedillo Gomez Sergio
Published: June 2022

e17591

Background: Olaparib, a poly (ADP-ribose) polymerase inhibitor (PARPi), monotherapy as first-line maintenance treatment has shown to be cost-effective in ovarian cancer (OC) patients with BRCA mutations in Spain. Regardless of BRCA status, patients with homologous recombination deficiency positive (HRD+) also benefit from PARPi following first-line platinum-based therapy. PAOLA-1 trial confirmed that adding Olaparib to bevacizumab (BEV) significantly increased progression-free survival (PFS) in OC patients. The aim of this study was to assess the cost-effectiveness of Olaparib plus BEV versus BEV monotherapy for the maintenance treatment of HRD+ advanced OC patients after response to first-line platinum-based therapy plus BEV from Spanish National Health System perspective. Methods: A lifetime partitioned survival model with monthly cycles and four health states (PFS, first progression, second progression, and death) was developed. Long-term survival defined as 60 months was included in the mixed survival model as a landmark to extrapolate PFS from the PAOLA-1 trial. Weibull distribution was selected as the most accurate survival model for PFS extrapolation. Time to second progression, and overall survival (OS) were extrapolated using parametric survival models. Mortality was obtained from the OS and adjusted by Spanish mortality rates. Health state utilities and adverse event (AE) frequencies were obtained from PAOLA-1. An expert panel validated data and assumptions. Direct costs including drug acquisition and administration, follow-up, subsequent therapies, AE, and end-of-life were obtained from local sources. A 3% annual discount rate was applied to costs and outcomes. The incremental cost-effectiveness ratio (ICER) was calculated as cost per quality-adjusted life-years (QALYs) gained. One-way and probabilistic sensitivity analyses (PSA) were performed to assess the robustness of the model. Results: Base-case analysis of Olaparib plus BEV compared with BEV showed an ICER of €24,371 per QALY gained. Discount rates applied to outcomes and the cost of Olaparib generated the most significant changes in the ICER. PSA demonstrated that Olaparib plus BEV had a 49.5% and 90.3% probability of being cost-effective versus BEV at a willingness-to-pay of €25,000 and €60,000 per QALY gained, respectively. Conclusions: Olaparib plus BEV is a cost-effective maintenance therapy compared with BEV for patients with HRD+ advanced OC in Spain.[Table: see text]
Partner and localizer of BRCA2 (PALB2) pathogenic variants and ovarian cancer: A systematic review and meta-analysis.
Authors: Narayan Priyanka , Ahsan Muhammad Danyal , Beaumont Shanice , Lin Jenny , Perez Luiza , Bull Leslie , Wolfe Isabel , Hickner Andy , Chapman-Davis Eloise , Cantillo Evelyn , Holcomb Kevin , Sharaf Ravi , Frey Melissa Kristen
Published: June 2022

e17597

Background: Approximately 20% of ovarian cancers are due to an underlying germline pathogenic variant. While several genes have been well-established in the development of hereditary ovarian cancer (e.g. BRCA1/2, RAD51C, RAD51D, BRIP1, mismatch repair genes), there are other genes for which the cancer risk is less certain and management recommendations remain controversial, including partner and localizer of BRCA 2 (PALB2). We sought to evaluate the association between PALB2 germline pathogenic mutations and ovarian cancer in the first meta-analysis on this topic. Methods: We conducted a systematic review and meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO no.: CRD42021281325). We searched key electronic databases to identify studies evaluating multigene panel testing in patients with ovarian cancer. Eligible trials were subjected to meta-analysis. Results: Thirty-seven studies met inclusion criteria. We found 55,137 cases of ovarian cancer with information available on germline PALB2 pathogenic variant status. Reported histological subtypes included serous adenocarcinoma (74.8%), endometroid (6.5%), clear cell (2.1%), mucinous (3.1%), and other (13.5%). Most ovarian cancers were stages III (73.5%) and IV (22.3%), followed by II (6.0%), and I (4.1%). Among ovarian cancer cases with PALB2 sequencing data available, 0.4% demonstrated a germline pathogenic variant in the PALB2 gene and the pooled odds ratio (OR) for having a PALB2 mutation was 2.31 (95% CI 0.89- 5.98). Among 94 patients with a germline PALB2 pathogenic variant, the pooled odds ratio (OR) for developing ovarian cancer was 2.85 (95% CI 1.58-5.15) relative to 33,855 patients without PALB2 mutations. Conclusions: Our meta-analysis demonstrates that the pooled OR for developing ovarian cancer with an underlying PALB2 germline pathogenic variant was 2.85 (95% CI 1.58-5.15). While this risk is lower than many of the well-established hereditary ovarian cancer genes, it does exceed the baseline population risk of 1-2%. Whether this meets the threshold to consider risk-reducing salpingo-oophorectomy is up for debate. Large population-based studies and evaluation of the combination of PALB2 mutations and cancer family history are needed to improve management recommendations for patients harboring pathogenic mutations in this gene.
Anatomic distribution of local recurrence of nasopharyngeal carcinoma in the Era of IMRT: Suggestion of modification of clinical target volume delineation.
Authors: Ou Xiaomin , Wang Jiazhou , Yan Wenbin , Lu Xueguan , Ying Hongmei , He Xiayun , Hu Chaosu
Published: June 2022

e18060

Background: Target volume delineation in nasopharyngeal carcinoma (NPC) remains a challenge because of the narrow therapeutic margin. There are no-well established guidelines for clinical target volume (CTV) delineation with long-term follow-up. Current consensus continues to rely heavily on bony structure and experience from conventional two and three- dimensional radiation. The aim of our study, is to clarify different anatomic distribution of local recurrence of NPC based on various T stages and spread patterns, provide a high-risk map of local recurrence of NPC, and thus provide suggestion for modification of CTV delineation based on T stages and spread patterns. Methods: We retrospectively enrolled 869 patients with newly diagnosed nonmetastatic NPC treated with definitive IMRT in our institution. With a median follow-up of 54.4 months, 72 patients developed local failure. All the cases of local failure were reviewed and those of local residual disease were excluded. After that, 52 cases with tracaeble primary radiotherapy plans and MR imaging of local recurrence were included in this study. Gross tumor volume of local recurrence (GTVr) and normal structures were delineated in each recurrent patient on primary CT of radiotherapy. The overlap of normal structures with GTVr were analyzed, as well as the stepwise patterns of tumor spread in NPC, based on different T stages and relapsed risk (≥5%, ≥10%, ≥20%, etc). Results: The anatomic distributions of local recurrence of various primary T stages were compared between early and late stages of NPC. Of note, these structures were significantly highly involved in T3/4 cases, compared with T1/2 cases, including lateral pterygoid muscle, inferior orbital fissure，posterior ethmoid sinus，cavernous sinus as well as hypoglossal canal. As for tumor spread patterns of local relapse, most cases relapsed in the nasopharynx and retropharyngeal lymph node (38.5%), followed by anterior-lateral tumor extension (via nasal cavity-pterygoid process-pterygopalatine fossa, 17.31%), posterior tumor extension (via prevertebral muscle-clivus, 13.46%), anterior-superior extension (via nasal cavity-ethmoid sinus-sphenoidal sinus,13.46%), superior extension(via foramen lacerum-cavernous sinus, 11.54%), etc. Finally, we depicted a map of high-risk area based on different T stages and relapsed risk (≥5%, ≥10%, ≥20%). Conclusions: Comprehensive analysis of local recurrence distributions and tumor spread patterns in real-world IMRT provides important reference for modification of CTV delineation for primary NPC. Certain structures such as cavernous sinus and lateral pterygoid muscle are not routinely recommended in the delineation of high-risk CTV for T1-2 disease. Future individualized delineations should be based on relapsed risk and tumor spread patterns.
Effect of plasma fibrinogen on the curative effect and prognosis of locally advanced oropharyngeal cancer after induction chemotherapy.
Authors: JIN feng Li yuan-yuan Wu wei-li
Published: June 2022

e18062

Background: To investigate the effect of plasma fibrinogen on the curative effect and prognosis of locally advanced oropharyngeal cancer after induction chemotherapy. Methods: Data from 52 patients with locally advanced oropharyngeal cancer who received sequential chemoradiotherapy with induction chemotherapy were retrospectively analyzed. Univariate and multivariate analyses were performed based on logistic regression models to identify clinicopathological factors associated with the efficacy of induction chemotherapy. Cox regression model was used to determine the correlation between clinical or pathological parameters and overall survival (OS) and progression-free survival (PFS). Kaplan-meier test and log-rank test were used for survival analysis. Results: ROC curve was used to determine the optimal threshold of response after induction chemotherapy. Patients were divided into low Fib group and high Fib group (Fib≤4.01g/L and ＞4.01g/L).The proportion of stage IVb and P16 negative in the high Fib group was higher than that in the low Fib group (55.6% vs 29.4%, P= 0.027; 72.2% vs 47.1%, P = 0.082) .Regarding overall response, 42(80.8%)patients responded to IC and 10(19.2%)patients did not respond.The proportion of stage IVb and p16 negative in the non-responding group was higher than that in the responding group (80% vs 28.6%, χ2= 9.026, P= 0.003; 90% vs 47.6%, χ2= 5.881, P= 0.015).In logistic regression model, high Fib level was significantly correlated with no response to induction chemotherapy (OR = 6.946, 95% CI 1.015̃47.516, P = 0.048). Multivariate analysis showed that total stage, P16 status and plasma Fib level before treatment were independent influencing factors of OS and PFS. The 3-year OS and PFS in pre-treatment high Fib group was significantly lower than that of the low Fib group ( P< 0.001, P = 0.005) .Responding to induction chemotherapy was independent influencing factors of PFS. The 3-year OS and PFS in the responding group was significantly higher than that in the non-responding group (65.2% vs 12.7%, P< 0.001; 64.5% vs 12.2%, P= 0.015). Conclusions: Responding to induction chemotherapy was independent influencing factors of PFS.High plasma Fib(Fib＞4.01g/L) was significantly associated with no response to locally advanced oropharyngeal cancer after induction chemotherapy. In addition, patients with pre-treatment high Fib level had significantly lower OS and PFS than those with low Fib level.
Gender distribution of speakers and moderators at the Russian cancer congresses in 2016-2021.
Authors: Abdullaeva Sheyda , Shamrikova Valentina , Gushchin Vadim , Shilo Polina
Published: June 2022

e18516

Background: Gender equity in world medicine has recently received widespread attention. There is evidence that men and women may practice medicine differently, and better women representation in the oncology workforce and leadership may improve patient outcomes. Nevertheless, women continue to be under-represented in the big academic events, also in oncology. Methods: A retrospective analysis of the programs of major annual Russian oncological congresses: Russian Oncology Congress and White Nights was carried out. The gender of speakers and moderators was collected from 2016 to 2021. Participation of the same person in several sessions or in different roles in one session was considered as a separate case. Data are presented by descriptive statistics, and differences between groups were assessed using the Сhi-square test. P-values below 0.05 were considered statistically significant. Results: The data of 1350 sessions, 796 moderators and 1756 speakers were available for analysis. For the analyzed period of time (2016-2021), the total percentage of female speakers was 42.2% (n = 3120), the percentage of female moderators was 34.8% (n = 1196). There were more male speakers than female speakers in surgical sessions (87.9% and 12.1% p < 0.001). There were more male moderators than women in surgical sessions (92.4% and 7.6% p < 0.001). There were more male speakers than female speakers in chemotherapy sessions (55.2% and 44.8% p < 0.001). There were more male moderators than women in chemotherapy sessions (58.9% and 41.1% p < 0.001). Conclusions: The gender inequality in oncology is more pronounced in the leadership positions in male-dominated specialties such as surgical oncology. Better women representation in the oncology leadership may be an effective strategy to improve oncology care in Russia
Variations in Ewing sarcoma and rhabdomyosarcoma patient outcomes based on treatment center volume.
Authors: Yeo Sarah , Xu Ying Hui , Yu Min Lee Ursula Joan , Simmons Christine E. , Smrke Alannah , Wang Ying
Published: June 2022

e18530

Background: Due to their rarity and requirement for multi-modality care, evidence suggests (and guidelines recommend) patients (pts) with Ewing Sarcoma (ES) and rhabdomyosarcoma (RMS) treated at high volume centres (HVC) with multidisciplinary tumour board discussions (MTDs) have improved outcomes. However, access to care at HVC is challenging for pts who live remotely, such as many pts in British Columbia (BC), Canada. Our study explores the difference in outcomes of patients with ES and RMS based on location of diagnosis and treatment in BC. Methods: A multi-center retrospective chart review of adults diagnosed with ES and RMS Jan 1st 2000 to Dec 31st 2020 was performed for pts undergoing curative intent therapy at one of six provincial cancer centers. All pts underwent expert pathology review. Descriptive statistics were performed. Fisher’s exact and chi-squared tests were used to evaluate associations. Cox proportional hazards model was used to assess for predictors of better survival outcomes by treatment centre. HVCs was defined as those that saw ≥15 patients. Results: 77 patients were included in this analysis; 46 (60%) and 31 (40%) were treated at HVC and LVC respectively. By HVC and LVC respectively, mean age was 36 and 35, 14 (45%) and 20 (43%) were female, 23 (74%) and 26 (57%) had ES, and 11 (35%) and nine (20%) had localized disease. Pts treated at HVCs were more likely to: receive curative intent radiation (p = 0.006), be presented at MTDs (p = 0.042), and less likely to experience disease progression on fist line therapy (p = 0.04) (Table). Time from biopsy to start of chemotherapy (chemo) was 13 days sooner at HVCs vs LVCs (34 vs 47 days, p = 0.12). Initial chemo regimen (p = 0.25) and surgical treatment (p = 0.75) were not significantly different between HVCs vs LVCs. Age, ECOG, stage, and Charlson Comorbidities Index (CCI) were all significant contributors to overall survival (OS). There was no statistically significant difference in OS by treatment center (HR 0.68, 95% CI 0.36 – 1.29). Conclusions: Variations in care exist for both treatment and outcomes amongst ES and RMS pts treated at HVC vs LVC in BC. Pts treated at HVCs were more likely to be presented at MTDs, to receive curative intent radiation, and less likely to experience disease progression. This may reflect differences in access to resources, sarcoma-specific clinician specialists, and familiarity with upfront aggressive treatment protocols. This study can be used to better inform decisions regarding triaging and centralization of curable ES and RMS patients.[Table: see text]
Medical oncologists' perspectives of end-of-life care communication with racial/ethnic minority and limited English proficiency patients.
Authors: Garcia-Jimenez Maria De Lourdes , Glaspy John A. , Anand Sidharth , Walling Anne M.
Published: June 2022

e18585

Background: Racial/ethnic minority (REM) and limited English proficiency (LEP) patients with cancer receive more intensive treatment at the end-of-life (EOL) compared to non-Hispanic whites. Various factors at the health system, patient, and provider level contribute to this disparity. While some data exists on the role of provider communication, little is known about medical oncologists' knowledge and attitudes regarding EOL care communication with REM and LEP patients with cancer. Methods: We conducted a cross-sectional, anonymous, pilot survey of medical oncology attendings and fellows at one academic center. Over 3 months, 57 individuals were invited to participate. The survey addressed 6 domains about EOL care communication with REM and LEP patients (role of language, barriers, facilitators, provider beliefs, provider communication skills, and cultural competency training). Questions used Likert scales and were modified from previously validated items when possible. Results: Of 35 individual respondents (61% response rate) 21 (60%) were male, 14 (40%) were female, and 29 (83%) were attendings. Average participant age was 42 years (range 31-60 years) and average years in practice was 9 (range 2-25 years). Twenty-three (66%) self-identified as non-Hispanic white, 11 (31%) as Asian, and 1 (3%) as other. Thirty-three (94%) reported their primary language as English and 23 (66%) reported speaking a second language. A majority (77%) strongly agreed discussing EOL care is part of an oncologist’s job and 69% strongly agreed patients with cancer, regardless of race/ethnicity or English language ability, should be engaged in EOL care discussions. Among several facilitators identified, two most highly rated as “Very Important” were eliciting patient belief systems about their disease (71%) and about death/dying (69%). However, only 14% strongly agreed they ask patients their beliefs about death/dying, and a minority strongly agreed they feel comfortable having EOL care discussions with REM (34%) and LEP (29%) patients. Importantly, 77% rated themselves at 6 or 7 (on a scale from 0 to 10, with 10 being the best) in how well they currently communicate about EOL care with REM and LEP patients, 74% reported wanting to be at 8 or 9 in 6 months, and 89% completely or somewhat agreed with wanting help to improve. Conclusions: Our results suggest there is conceptual understanding among academic medical oncologists of the need to engage all patients in EOL care discussions and elicit patient belief systems on the topic. Though there is lack of comfort in having EOL care discussions with REM and LEP patients, and infrequent inquiry about patient belief systems, there is also motivation to improve communication skills in this area. Interventions that foster medical oncologists' comfort and skills in cross-cultural, language non-congruent communication about EOL care are needed.
Association between control group therapy and magnitude of clinical benefit of cancer drugs.
Authors: Molto Consolacion , Tibau Ariadna , Bujosa Aida , Tapia Jose Carlos , Mittal Abhenil , Tamimi Faris , Amir Eitan
Published: June 2022

e18604

Background: Oncology societies have developed tools to quantify the magnitude of clinical benefit. These include the American Society of Clinical Oncology Value Framework (ASCO-VF) version 2, the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) version 1.1, the National Comprehensive Cancer Network (NCCN) Evidence Blocks and the ASCO Cancer Research Committee criteria (ASCO-CRC). Associations between the characteristics of approved drugs and magnitude of clinical benefit have been explored in depth. Here, we assess the association between characteristics of control group therapy and magnitude of clinical benefit. Methods: We searched Drugs@FDA to identify new solid tumor cancer drugs approved based on randomized trials (RCTs) between January 2012 and December 2021. Substantial clinical benefit was defined as: overall survival gain ≥ 2.5 months and progression-free survival gain ≥ 3 months for the ASCO-CRC (palliative setting only); ASCO-VF threshold score ≥45 (palliative and curative setting); NCCN Evidence Blocks threshold score ≥16 (palliative and curative setting); and grade A or B for trials of curative intent and 4 or 5 for those of non-curative intent using ESMO-MCBS. Associations between characteristics of control group therapy (e.g. type of active therapy, use of matched placebo and overlap between experimental and control therapy) and substantial clinical benefit scores were explored using logistic regression. Results: We identified 174 RCTs supporting the approval of 76 drugs for 164 indications. Of these, 47% (82/174) were placebo-controlled trials among which 42% (34/82) comprised active treatment with a matched placebo. Substantial clinical benefit was observed in 45%, 46%, 72% and 73% using the ESMO-MCBS, ASCO-VF, NCCN Evidence Blocks and ASCO-CRC, respectively. These low proportions resulted in an inability to fit multivariable models adequately. RCTs with a control group comprising of active treatment with a matched placebo were associated with significantly lower odds of substantial benefit with ESMO-MCBS (OR 0.27, P = .003) and ASCO-VF (OR 0.30, P = .008) but not with NCCN Evidence Blocks (OR 0.74, P = .55) or ASCO-CRC criteria (OR 1.36, P = .54). Similar results were observed when excluding trials in the curative setting. There was a non-significant association with higher odds of substantial benefit with ESMO-MCBS with trials in which the control group was chemotherapy (OR 1.97, P = .07). For ASCO-CRC a non-significant association in the opposite direction was observed (OR 0.40, P = .06). Conclusions: Clinical benefit scales can be sensitive to the type of control group therapy. RCTs with an active treatment and matched placebo in the control group were less likely to be scored as providing substantial clinical benefit using the ESMO-MCBS and the ASCO-VF scales. Control group therapy did not influence NCCN Evidence Blocks or ASCO-CRC scores.
Improving advanced directive completion rates on an inpatient oncology unit using internal medicine resident participation: A quality improvement study.
Authors: Bloom Matthew Doran , Pan Kelsey , De Leo Edward , Altshuler Ellery
Published: June 2022

e18636

Background: A written advanced directive (AD) allows patients to indicate their preferences for medical care should they ever lose the ability to make their wishes known. This may take the form of a living will or designation of a healthcare surrogate. AD completion rates remain poor on inpatient oncology units, with only 20-40% of patients having an AD. This is despite the fact nearly all cancer patients (95%) believe discussing ADs is an important issue. It has recently been shown that nearly 87% of cancer patients would support a policy in which admitting physicians offered to have a conversation regarding ADs. The goal of our project was to increase the percentage of patients with documented ADs on our inpatient oncology unit from 30% to 50% using the participation of internal medicine residents. Our secondary objective was to initially assess resident knowledge, confidence and skills with AD discussions. Methods: We carried out a prospective QI project in which we first calculated the percentage of consecutive patients on our inpatient oncology unit with documented ADs. After providing educational materials and delivering AD forms to the resident workroom to increase accessibility, we again calculated the percentage of consecutive patients with documented ADs. We also initially surveyed residents about their knowledge, comfort levels, and barriers to having AD discussions with patients. Results: Pre-intervention, 15 out of 50 (30%) consecutive patients on our inpatient oncology unit had documented ADs. Post-intervention, 13 of 27 (48%) consecutive patients in our oncology unit had documented ADs. Most residents felt their knowledge of ADs was average (46.88%, n = 15) or good (28.13%. n = 9). When asked about comfort in filling out ADs with patients, most responded as average (28.13%, n = 9) or poor (28.13%, n = 9). The main barrier to completing ADs was lack of time (25%, n = 20) followed by lack of knowledge (25%, n = 8) and not feeling the responsibility (12.5%, n = 4). Most residents were interested (65.53%, n = 21) or maybe interested (28.13%, n = 9) in further teaching on ADs. Conclusions: Our study showed that AD completion rates on an inpatient oncology unit can be improved using the participation of internal medicine residents. This was done through a standardized approach of housestaff offering to discuss ADs on admission after they had received short small group teaching sessions on AD discussions. Furthermore, we identified that most internal medicine residents had average or poor comfort in initiating advanced care discussions, but were interested in obtaining further knowledge to help discuss ADs with patients.
A randomized, open-label, crossover study assessing the pharmacokinetic and pharmacodynamic bioequivalence of pegfilgrastim-cbqv via on-body injector vs prefilled syringe.
Authors: Tang Hong , Civoli Francesca , Tatarewicz Suzanna , Miyasaki Lisa , O'Kelly Hillary , Young Alasdair , Finck Barbara
Published: June 2022

e18637

Background: Pegfilgrastim-cbqv, a pegfilgrastim biosimilar, is administered 24-72 h after myelosuppressive chemotherapy to prevent febrile neutropenia. Pegfilgrastim delivery via an on-body injector (OBI) applied on the day of chemotherapy eliminates the need for a second healthcare visit. This study evaluated the pharmacokinetic (PK), pharmacodynamic (PD) bioequivalence (BE), and the safety of pegfilgrastim-cbqv administered via OBI vs prefilled syringe. Methods: In this open-label, 2-period crossover study, healthy adult male participants were randomized 1:1 to 2 treatment sequences to receive a 6-mg subcutaneous (SC) injection of pegfilgrastim-cbqv via OBI or prefilled syringe in period 1 and an injection via the other method in period 2 (after a 6- to 8-wk washout). Primary endpoints (PK) were area under the concentration-time curve from time 0 to infinity (AUC0-inf), the AUC from time 0 to the last quantifiable concentration (AUC0-last), and the maximum plasma concentration (Cmax). Secondary endpoints (PD) were area under the absolute neutrophil count (ANC)-time curve from time 0 to the last quantifiable ANC (ANC AUC0-last) and maximum ANC (ANCmax). PK/PD BE was established if the 90% CI for the geometric mean ratios (GMRs) fell within 80-125%. Safety and immunogenicity were also assessed. Results: The 90% CIs of the GMRs for PK and PD endpoints in healthy participants fell within the predetermined range (Table). Treatment-emergent adverse events (TEAEs) occurred in 87.8% (OBI) vs 75.8% (prefilled syringe) of participants. Most TEAEs were musculoskeletal effects and mild in severity. The most common injection siterelated TEAE was erythema (OBI 34.1%; prefilled syringe 2.5%). The injection site erythema reactions were mild in severity and self-limiting. The incidence of treatment-emergent antidrug antibodies (ADAs) in period 1 was similar with OBI (40.0%) vs prefilled syringe (36.6%); ADA titers were low, transient, and primarily directed to the polyethylene glycol (PEG) moiety of pegfilgrastim-cbqv. The ADAs had no apparent impact on PK, PD, or safety. Neutralizing antibodies were not detected in any participant. Conclusions: This study demonstrated PK and PD BE of pegfilgrastim-cbqv administered via OBI vs prefilled syringe in healthy adult males. OBI and prefilled syringe administration had similar safety and immunogenicity profiles. No unexpected safety signals were identified.[Table: see text]
Impact of weekend effect on neutropenic fever admissions associated with malignancy.
Authors: Kannayiram Sandhya Shri , Mariappan Aathi Lakshmi , Desai Palak
Published: June 2022

e18658

Background: The impact of the “weekend effect” (increased mortality rate during Saturday and/or Sunday admissions) on hospitalizations for various medical emergencies has been studied with results often showing adverse patient outcomes. Febrile neutropenia in cancer patients is an acute oncological emergency with significant mortality and morbidity. Here, we attempt to explore if the day of admission impacts outcomes and healthcare utilization in cancer patients admitted for neutropenic fever. Methods: We performed a retrospective analysis using the National Inpatient Sample (NIS) database from 2019, and identified all adult admissions with cancer (hematological and solid cancers) and a concomitant primary or secondary diagnosis of Febrile Neutropenia using ICD 10 codes. These patients were divided based on the day of admission (group 1: weekday vs. group 2: weekend). The groups were compared for demographic differences, inpatient mortality, length of stay (LOS), and hospital charges (TCHG). Secondary outcomes studied were complications like sepsis, septic shock (SS), and mechanical ventilation (MV). Statistics were performed using the t-test, chi-square test, multivariate logistic analysis. Results: A total of 136,895 cancer patients were admitted with febrile neutropenia, and of those, 28,559 patients were admitted during the weekend. Both groups had similar demographics (p = > 0.05) with a mean age of 61 years, more males (52% vs. 51%), admitted in large-sized and urban teaching hospitals, and a majority had Medicare insurance (48% vs. 50%). 4.6% of weekday and 4.7 % of the weekend admissions died during hospitalization. Weekend admissions were likely to have a slightly lower mortality, although not statistically significant(aOR = 0.96,95% CI = 0.81-1.1, p = 0.72). The mean LOS was 9 days for group 1 and 8 days for group 2 (p < 0.001*). TCHG was lower for the weekend by $ 15,770 per admission (p < 0.001*). The rates and odds of having sepsis, SS, MV were similar between both groups (p > 0.05). In addition, increasing age, Hispanic race, and comorbid chronic kidney disease, diabetes, congestive heart failure, acute kidney injury, acute respiratory failure resulted in higher mortality, LOS, and all complications (p = < 0.001*) regardless of the day of the admission. Conclusions: The mortality rate and other outcomes in neutropenic fever did not statistically change between weekday and weekend admissions. Interestingly, the healthcare resource utilization (LOS and TCHG) was higher on weekdays. It is encouraging to note that the “weekend effect” has not impacted the in-hospital outcomes. However, patients admitted with febrile neutropenia have a high mortality rate and increased risk of serious complications. Therefore, utmost vigilance and close follow-up are necessary when treating these patients. *p = < 0.05 was considered significant; aOR = Adjusted Odds Ratio.
A retrospective analysis of the concordance of diagnosis predicted by cancer type ID test with pathological or clinical diagnosis with incorporation of treatment response data.
Authors: Xu Yiqing , Kulkarni Ajinkya , Eze-Raphael Chinenye , Toom Sudhamshi
Published: June 2022

e18684

Background: Carcinoma of unknown primary site (CUP) is a clinical conundrum, where there is metastatic cancer in multiple organs, but the original site of the cancer cannot be determined either by clinical information, or by pathological specification. In most scenarios, clinical and pathological information may narrow down to 2 or 3 most likely primaries; while in some cases, the pathological diagnosis and the clinical picture may not be in concordance. Cancer type ID test, using a panel of 92 genes detectable by RT-PCR test, and bio-informative algorithm, may provide independent information on the cancer of origin. Incorporating this result, as well as the treatment information, one may be able to get closer to the true site of origin for CUP cases. Methods: Patients who have had a Cancer type ID test (ID test) performed and had received systemic treatment were eligible for this study. We analyzed the concordance of ID result of major probability (> 90% probability) with pathology diagnosis, the concordance of ID result of minor probability (6% probability or “cannot exclude with < 5% probability” with pathology diagnosis, and the concordance of ID result of major probability with final clinical diagnosis (incorporating treatment response data, tumor next gene sequencing data, and genetic test data). We also divided cases into groups of differentiation between 2-3 possible primaries, or true CUPs (as shown in the table below). Results: 26 patients were identified. There were 9 males and 17 females. The median age was 65 years old (ranger 37-92). The final clinical diagnoses were GI (upper and lower intestinal) (n = 6), pancreatic (n = 3), cervical (n = 2), lung adeno (n = 2), lung carcinoid (n = 1), sarcoma (n = 1), GYN (n = 2), Head neck (n = 1) and breast (n = 1). 7 cases remained as CUP. Conclusions: Cancer type ID test, with a combination of 90% probability, the 6% probability as well as the “cannot exclude with a less than 5% probability”, may reach 92% concordance with pathological diagnosis. It has the highest prediction in differentiation of 2-3 primaries, especially when one primary involves pancreas. However, the concordance between the clinical diagnosis and the diagnosis rendered by the ID test major prediction is not optimal, and will need further improvement.[Table: see text]
Evaluating the impact of performance status criteria on minority eligibility for oncology clinical trials.
Authors: Bhandari Sudip , Mann Jeremy , Chawla Jitesh , Jain Prerna , Knight Margot , Lagor Charles , Mueller Judith , Raska Paola , Southwick Steve , Whyte Warren
Published: June 2022

e18701

Background: Restrictive criteria contribute to low enrollment in clinical trials. These criteria can also amplify health disparities by reducing the racial and ethnic diversity of the cohort. Many studies show that minority patients exhibit worse Eastern Cooperative Oncology Group (ECOG) performance status than white patients. Based on clinical trial data, some researchers have hypothesized that relaxing the ECOG criterion in clinical trial criteria could improve the diversity of the cohort. However, little research exists to measure ECOG’s impact on minority eligibility. Using Real-World Data (RWD), we evaluate whether relaxing the ECOG criterion monotonically increases the racial diversity of the cohort in oncology clinical trials. Methods: We used ConcertAI’s database of US oncology Electronic Medical Record (EMR) data, which includes clinical data from CancerLinQ Discovery™. We conducted sensitivity analyses for the inclusion criteria of 16 different clinical trials across multiple cancer indications. For each trial, we created five cohorts based on five different ECOG score upper limits. For example, the first cohort only included patients who had an ECOG of 0, the second cohort included patients with an ECOG of 0 or 1, etc. We then recorded the percentage of non-white patients for the resulting cohorts. We ran simple linear regressions to measure whether the change in the percentage of non-white patients was statistically significant. Results: Relaxation in ECOG status led to no uniform change in the racial diversity of patients across the 16 trials. The limited changes we did observe were not statistically significant. Conclusions: Our findings suggest that improving diversity will require more than just relaxing ECOG restrictions, and a multi-faceted approach may be needed. Future research exploring the relationship between ECOG and diversity should control for potential confounders like age, gender, and comorbidities using multivariable models. Such research needs to also account for patients with unknown race and ECOG, which represented large parts of our study population. Such research could elucidate whether the phenomenon observed in the general population—that minority patients tend to have worse performance status than whites—holds true in the sub-population of oncology patients.[Table: see text]
Impact of COVID-19 on risk of venous thromboembolism (VTE) in cancer patients: A single institution analysis.
Authors: Ananthula Aneesha , Thomas Katharine , Tran Dat , Nguyen Anh , McQueen Amaker Katie Lauren McLemore , Thrash Brandon T , Gibson William , Germain Monique , Mani Shyam , Chapple Andrew G , Subbiah Suki
Published: June 2022

e18732

Background: Cancer is known to increase the risk of VTE when compared to the non-cancer population. Additionally, SARS-CoV-2 infection has been associated with hypercoagulability and VTE. A study by Patell et al noted similar cumulative incidence of thrombotic events (arterial and venous) in patients hospitalized with COVID-19 with active cancer than those without cancer (14.2% vs 18.2%). Data from the COVID-19 and Cancer Consortium (CCC19) Registry reported incidence of VTE of 7.6% in cancer patients within 90 days of hospitalization for COVID-19. However, it is unknown whether patients with cancer are at significantly higher risk for VTE in the setting of COVID-19 compared to cancer patients without COVID-19. Our study objectives were to: 1) determine the overall incidence of VTE in patients with cancer with and without COVID-19, regardless of hospitalization status; 2) assess the relative risk of VTE due to COVID-19 in cancer patients; 3) examine risk for VTE in cancer patients with COVID-19 based on certain demographic characteristics and comorbidities. Methods: An institutional retrospective cohort analysis was performed from March 1, 2020 through July 31, 2021. 228 patients with COVID-19 and cancer were identified and compared to matched controls without COVID-19 (n = 448) during the same study period based on age, gender, and BMI. Results: Incidence of VTE in cancer patients with COVID-19 was significantly higher than in cancer patients without COVID-19 (11% vs 3.1%) [RR 3.45, 95% CI 1.85-6.67]. There was no significantly increased risk of VTE in cancer patients with COVID-19 based on the following characteristics: non-White race, male gender, diabetes mellitus, hypertension, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and end-stage renal disease receiving dialysis. However, patients with any history of smoking (including current smokers) had increased risk of VTE compared to never-smokers (RR 2.2756, 95% CI 1.0498-4.9326). Conclusions: COVID-19 further increases the risk of VTE in cancer patients, a population with an independent risk factor for VTE at baseline. Whether the increased risk is additive or synergistic is currently unknown. Demographic factors and comorbidities that have been associated with increased severity of COVID-19 in other studies do not appear to significantly increase risk of VTE in cancer patients with COVID-19, with the exception of smoking status (either current or past). Given the impact on morbidity and mortality, further analyses, including with larger datasets, are warranted.
Measuring the great objective: Have we transferred the increase in overall survival in stage IV non-small cell lung cancer from clinical trials to clinical practice?
Authors: Sanchez Juan Cristobal , Nuñez García Beatriz , Blanco Mariola , Calvo Virginia , Cantos Sanchez de Ibarguren Blanca , Mendez Miriam , Aguado Ramon , Ramos-Vegue Arturo Jose , Royuela Ana , Provencio-Pulla Mariano
Published: June 2022

e18734

Background: In the last five years, different immunotherapy (IO) clinical trials have improved overall survival (OS) for stage IV non-small cell lung cancer (NSCLC) without driver mutation. However, it is necessary to check whether outcomes of clinical trials are reproduced in the general population, the true objective of any scientific advance. Methods: We conducted a retrospective observational study selecting all patients with stage IV NSCLC without driver mutation treated in the Medical Oncology Department at Puerta de Hierro University Hospital between 2016 and 2019. Data cut off was June 30, 2021. Our goal was to evaluate treatment changes for NSCLC in clinical practice in our institution with OS in the real-world as the main outcome, in addition to assessing quality of care. Results: Between 2016 and 2019, 317 patients with stage IV NSCLC were diagnosed, 260 without driver mutation and 189 of them received systemic treatment. We observed a higher proportion of stage IVB patients in 2018 and 2019 compared to 2016 and 2017. A progressive greater use of IO was observed, except for a small decrease in 2019 compared to 2018. At the date of analysis, 77.8% of patients had died. With a median follow-up of 40.8 months, we observed a gradual increase in OS, with medians of 12.3, 13.6, and 18.9 months for patients diagnosed in 2016, 2017, and 2018, respectively, with a decrease to 10.4 months for patients diagnosed in 2019. Survival rates over time show the same trend. IO (any line) was significantly associated with a reduced risk of death: HR 0.35 (95% CI: 0.23 - 0.58) in multivariate analysis. The deterioration of the results of the patients diagnosed in 2019 is manifested in the median survival and in the survival rates at different points from 6 months onwards, which should correspond to the excess mortality in the year 2020 in our studied population. Conclusions: Our study shows that IO reduced risk of death: HR 0.35 (95% CI: 0.23 - 0.58) in stage IV NSCLC, observing an increase in overall survival from a median of 12.3 to 18.9 months for patients diagnosed in 2016 and 2018, suggesting that the progressive use of IO for NSCLC in the years 2016, 2017 and 2018 has transferred the benefit observed in clinical trials to the general population. The deterioration of outcomes for patients diagnosed in 2019, with a median OS of 10.4 months and decreased survival at 6, 12 and 18 months, could suggest the negative impact and excess mortality in the pandemic year 2020.[Table: see text]
Ramifications and healthcare costs of Clostridioides difficile infections in hospitalized patients with solid tumors.
Authors: Tarar Zahid , Au Pak Ho , Nwabara Kelechi , Franco Diana , Egwom Peter , Gvazava Nanuli , Saleh Mohammad , Ghous Ghulam
Published: June 2022

e18801

Background: Clostridioides difficile infection (CDI) is notorious for its perilous effect on frail patients, but its assault is even more so threatening on cancer patients as they are more prone to CDI due to damage to intestinal mucosa by chemotherapy agents and weak immune system, hence higher risk of getting affected from hospital-acquired infections. Here we analyze National inpatient sample database (NIS) of hospitalized patients with solid tumors to find out aftermath of CDI in this particular patient population. Methods: We used NIS database from year 2019 and recruited all patients admitted with C. diff colitis with underline solid tumors with or without metastatic disease. We used international classification of disease,10th revision (ICD-10) codes to identify these patients. Our outcomes of interest were all cause inpatient mortality, acute kidney injury (AKI), sepsis, ICU admission, pressor use and hospital resource utilization including mean length of stay (LOS) and mean total charges. Using STATA 17, we performed the multivariate regression analysis. Results: A total of 15,161 (1.41%) hospitalizations due to principal diagnosis of C. diff Colitis were recorded in solid tumor patients in year 2019. Patients with history of solid tumors who were admitted with C. diff colitis had higher adjusted odds of all-cause in-hospital mortality (AOR 1.23, 95% CI1.08-1.41, P 0.002) compared to patients without underline solid tumor. These patients also had higher odds of sepsis (AOR 2.22, 95% CI 1.89-2.59, P < 0.001), AKI (AOR 1.91, 95% CI 1.73-2.10, P < 0.001), ICU admission (AOR 1.66, 95% CI 1.39-1.97, P < 0.001) and pressors use (AOR 1.82, 95% CI 1.38-2.40, P < 0.001). Patients with underline solid tumors who developed C. diff colitis had increased mean LOS (AOR 3.88, 95% CI 3.41-4.34, P < 0.001). These patients also incurred more hospital charges (Co-efficient 33836$, 95% CI 25907$-41766$, p < 0.001). [Table]. Conclusions: Patients with solid tumors admitted with CDI have an increased risk of sepsis, AKI, ICU admission and in-hospital mortality. They also have a significantly longer duration of hospital stay; hence higher cost of care. There is a dire need for awareness regarding strict contact precautions, hand hygiene, effective environmental cleaning, minimizing antibiotics use/adherence to antibiotic stewardship programs, using prophylactic vancomycin where indicated, avoidance of unnecessary hospital visits utilizing telehealth, etc. and aggressive management of CDI in patients admitted to hospital with solid tumors.[Table: see text]
Dissection of the expressed actionable fusions’ repertoire in solid tumors tested serially in the clinical setting across 14 cancer types.
Authors: Lopez-Diaz Fernando J. , Schell Rachel , Duong Chaugiang , Rivera Steven , Funari Vincent Anthony
Published: June 2022

e18804

Background: More frequently, select gene fusions have been tested in clinical practice as more approvals of very effective therapies targeting oncogenic chimeric fusion proteins. Large studies based on DNA-based NGS testing alongside clinical trials have established the prevalence of clinically actionable gene fusions such as NTRK1/2/3. However, much less is known about the broader repertoire and prevalence of bonafide expressed gene fusions. Methods: 6009 tumors across 14 cancer types were tested in our clinical laboratory between January and October 2021. Enrichment was performed using a custom hybridization-based capture after RNA to cDNA conversion with custom designed probes targeting > 1104 different genes and enriched for 2230 specific RNA fusions to maximize sensitivity and breadth before sequencing ̃50 million 150x150 reads/sample on a NovaSeq 6000. Data was deidentified and aggregated according an approved IRB. Statistical significance was calculated by Fisher’s exact test. Results: We found that 37% of tumors tested carry > 1 expressed chimeric transcript and that 7.2% of tumors (n = 431) express a gene fusion involving one of 19 actionable gene families/pathways targeted by an approved therapy. The most frequent involved FGFR1/2/3/4 (15%), ALK (14%), NTRK1/2/3 (12%), BRAF, ERBB2, RET and MET (6% each), RAS/RAF/MAPK and CDK4/6 pathway (5%). These fusions imply intra- and inter-chromosomal translocations on all chromosomes, especially on chromosomes 1, 3, 6, 7, 11, 12 and 17. NTRK1/2/3 fusions prevalence (0.9%) is significantly higher (p = 1.1e-10) than the 0.3% reported on a recent study from a large dataset (296K samples) based on DNA-sequencing testing (1). Moreover, we found that 32% of the NTRK partners were unique vs. 10% (p = 6.5e-08) from the Westphalen et al. study (1). 14 of 25 unique NTRK partners have not been described on large datasets (1) and only 3 have been reported on the literature as NTRK partners. Among them, we identified the hypoxia-induced neovascularization gene HIF1A, as a novel in frame 3’ fusion partner of NTRK3 [t(15;14)(15q25.3; 14q23.1). Finally, NTRK fusions were detected across 14 cancer types with higher frequency on brain tumors (17%), followed by lung cancers, colorectal and head and neck cancer (13% each) and sarcomas (12%). Conclusions: Gene fusions involving common actionable genes showed a high prevalence in the clinical setting. This study confirms that the number and breadth of gene fusions can present with common actionable information in > 7% of clinical cases. We report here 14 new unique NTRK partners. Despite a 50 times smaller dataset, 3-fold more actionable expressed NTRK fusions involving novel partners were detected with a targeted RNA based hybridization approach in lieu of DNA based testing supporting the benefit of this strategy. Overexpression and translation can be confirmed only by this approach.