bluuebunny/crossref_metadata_2025_split huggingface dataset:
Duration of pemetrexed maintenance therapy with or without pembrolizumab is associated with risk of renal toxicity in patients with metastatic nonsquamous NSCLC.
Authors: Patil Tejas , Nie Yunan , Hu Junxiao , Schenk Erin Lynn , Pacheco Jose Maria , Purcell William T. , Bunn Paul A. , Camidge D. Ross 
Published: June 2021

e21205 Background: Use of maintenance pemetrexed with pembrolizumab is the standard of care among patients with metastatic nonsquamous NSCLC without EGFR or ALK alterations treated with the KEYNOTE-189 regimen. Whether the addition of pembrolizumab to pemetrexed maintenance alters the risk of renal toxicity is not well characterized. Methods: A single center retrospective study was performed. The frequency of acute kidney injury as well as the rates of discontinuation due to renal injury was assessed. Acute renal injury was defined as ≥ 0.3 increase in serum creatinine (sCr) above the upper limit of normal or a rise in sCr ≥ 1.5 times baseline per KDIGO criteria. A Fisher exact test was conducted to compare the rate of renal injury between the two groups. Logistic regression adjusting for performance status, prior lines of treatment, and number of maintenance cycles was performed. Results: We identified 114 patients who received either maintenance pemetrexed or pemetrexed + pembrolizumab. The median number of cycles for the maintenance pemetrexed and pemetrexed + pembrolizumab groups was 5 and 7 cycles respectively. Of these, 41% (47/114) patients developed acute renal injury during their treatment course. Renal injury was seen in 14.3% (5/35) patients who received single agent pemetrexed maintenance and 25% (3/12) who received maintenance pemetrexed + pembrolizumab with no significant difference in the rates of renal injury between both arms (p = 0.403). Among patients who developed acute renal injury, 9% (4/47) permanently discontinued maintenance due to nephrotoxicity. All patients who permanently discontinued therapy received maintenance pemetrexed alone. When adjusting for covariates, ECOG performance status and number of prior lines of therapy did not increase the risk of renal toxicity. Logistic regression analysis identified that the rate of renal injury was significantly associated with the number of maintenance cycles received (p-value = 0.017, OR = 1.14, 95% CI 1.03 - 1.29). The odds of developing renal injury were 1.14 times higher with each additional cycle of maintenance therapy received. Conclusions: Renal injury is common among patients treated with patients receiving maintenance therapy. The addition of pembrolizumab to maintenance pemetrexed did not significantly increase the rate of renal injury. The risk of renal injury appears to correlate with the total number of maintenance cycles received suggesting a cumulative risk of nephrotoxicity over time.
Combination of pembrolizumab (PEMBRO) plus temozolomide (TMZ) therapy in Chinese patients (pts) with advanced acral and mucosal melanoma.
Authors: Hu Tu , Sun Wei , Xu Yu , Luo Zhiguo , Chen Yong 
Published: June 2021

e21505 Background: Acral and mucosal melanoma are rare in Caucasians but have higher incidence in Asians and have poor prognosis. However, it has been reported that monotherapy seems to have limited efficacy in these population. Therefore, new treatments especially novel combination therapy are needed to further improve the outcome for these two subtypes. Here, we present the efficacy and safety of PEMBRO combined with TMZ in previously untreated pts with advanced acral and mucosal melanoma in China. Methods: The records of pts in Fudan University Shanghai Cancer Center with metastatic and unresectable acral and mucosal melanoma firstly treated with PEMBRO plus TMZ, PEMBRO alone or TMZ/DTIC based chemotherapy (CHEMO) were reviewed. Data regarding to best objective response rate (ORR), progression free survival (PFS) and toxicities were estimated. Response to treatment was assessed based on direct review of scan images and radiology reports according to the RECIST 1.1 criteria. Safety and tolerability were assessed per NCI-CTCAE v 4.0. Results: From May 2018 to February 2020, 49 pts were identified, including 28 (57.1%) with acral melanoma, 21 (42.9%) with mucosal melanoma. 32 (65.3%) pts had prior received adjuvant treatment, of which most (15, 30.6%) were interferon-α (IFN-α) or interleukin-2 (IL-2). Among these pts, PEMBRO alone was received by 18 (36.7%) pts with standard dosing of 2 mg/kg every 3 weeks. 20 (40.8%) pts received CHEMO at standard recommended dosing schedule, of which TMZ was given at 200 mg/m2 orally days 1–5, every 4 weeks. PEMBRO plus TMZ was given to 11 (22.4%) pts with the same dosing of each treatment alone. The ORR of PEMBRO plus TMZ (6/11, 54.5%) was significantly higher than PEMBRO alone (2/18, 11.1%; p = 0.011) or CHEMO(1/20, 5.0%; p = 0.002), however, the difference of ORR between PEMBRO alone and CHEMO was not statistically significant ( p = 0.485). The disease control rate of the three groups were 81.8%, 72.2% and 70.0% respectively (not significant). The median PFS of PEMBRO plus TMZ in the front-line therapy was 9.8 months (95% CI, 3.2 -16.4), as compared with 6.2 months (95% CI, 1.8 - 10.3) in PEMBRO alone and 4.2 months (95% CI, 2.8 - 5.6) in CHEMO ( p = 0.258). Grade 3 treatment-related adverse events (TRAEs) occurred in one acral melanoma patient (rash) in PEMBRO plus TMZ and two pts in CHEMO (one thrombocytopenia and one anemia, both were mucosal melanoma). No grade 3 TRAEs was reported in PEMBRO alone. There were no significant differences in grade 1/2 toxicity, with the common TRAEs including nausea, vomiting, fatigue, elevated transaminase and leukocytopenia. Conclusions: These results suggest that the combination of PEMBRO plus TMZ as first line therapy for advanced acral and mucosal melanoma could potentially be an effective strategy to enhance antitumor activity with a manageable toxicity profile. Need to be further evaluated in a large prospective study.
18F-FDG-PET/CT response assessment in patients with advanced melanoma treated with combination of low-dose ipilimumab and anti-PD1: A real-world experience.
Authors: Liz Caio Dabbous , Teixeira Marcos Rezende , Mendes Gomes Siqueira Luciana Beatriz , Rinck Jose A. , Lima Joao Paulo S. N. , Tavares Monique Celeste , Garcia Daniel , Oliveira Thiago Bueno , Cavicchioli Marcelo , Lima Eduardo , Duprat Joao , De Barros E. Silva Milton Jose 
Published: June 2021

e21533 Background: Combination therapy with anti-PD1 and low-dose ipilimumab has shown reduced rate of immune-related adverse effects compared with standard dose used in the Checkmates studies 067 and 204. However, the discussion whether low-dose ipilimumab may hamper the response rate in advanced melanoma is still open. Methods: We conducted a retrospective analysis of response evaluation based on 18F-FDG PET/CT for patients with advanced melanoma treated with combination of nivolumab 3mg/kg plus ipilimumab 1mg/kg for 4 cycles (N3+I1) followed by anti-PD1 maintenance therapy and compared the results to RECIST 1.1 response criteria in the same population. Results: Between December 2017 and August 2020, 45 patients with advanced melanoma treated with N3+I1 in first-line setting were identified. Unresectable stage III/stage IV were 2/43 patients, respectively. Among stage IV patients, 60.5% were M1c, 23.3% had elevated LDH and 28% had brain metastasis (3 or more brain lesions: 58%). At a median follow-up of 16.7 months, 11 patients (24.4%) had G3/G4 toxicity. During induction phase, three patients (6.6%) discontinued all drugs and 2 other patients (4.4%) interrupted only ipilimumab. Review of response evaluation by RECIST was possible in 36 patients and showed an objective response of 50%. Complete response (CR): 11% and partial response (PR): 39%. Eight percent presented progressive disease (PD). In 37 patients, review of response evaluation using 18F-FDG PET/CT was possible. Twenty-four patients (65%) achieved metabolic CR, 5 (13.5%) PD and 8 (21.5%) were classified as non-CR non-PD. Median progression-free survival (PFS) and overall survival(OS) were not reached. 12-month PFS and OS were: 72.5 and 89%, respectively. During the study follow-up, only 1 patient with metabolic complete response relapsed and 3 out of 8 with non-CR non-PD progressed. Conclusions: Using low-dose ipilimumab combination does not hamper the response rates and, possibly due to fewer protocol interruptions, these patients may achieve more complete responses as showed by 18F-FDG PET/CT evaluation.
Organic iodine-based preparation inhibits growth of B16/F10 melanoma in C57BL6 mice with thyroid disorders.
Authors: Kaplieva Irina V. , Frantsiyants Elena M. , Bandovkina Valeria A. , Surikova Ekaterina I. , Neskubina Irina V. , Trepitaki Lidia K. , Cheryarina Natalia D. , Nemashkalova Ludmila A. , Pozdnyakova Viktoria V. , Przhedetskiy Yuriy V. , Przhedetskaya Viktoria Yu. , Maksimova Natalia A. , Ilchenko Maria G. , Khokhlova Olga , Zakharova Natalia A. , Kit Oleg I. , Engibaryan Marina A. , Gvaramiya Astanda K. 
Published: June 2021

e21580 Background: The thyroid gland is the most important regulator of the body's response to stressful influences, including malignant growth. Iodine is a constituent of thyroid hormones, and it plays an important role in anti-tumor protection. The purpose of the study was to analyze the levels of thyroid hormones in the thyroid gland of male and female mice with B16/F10 melanoma, as well as the effect of an organic iodine-based preparation on the survival of animals with transplanted melanoma. Methods: Levels of total (T3, T4) and free (FT3, FT4) thyroid hormones were measured by RIA in the thyroid of male and female С57ВL/6 mice (n = 80) with transplantable B16/F10 melanoma. The effect of an organic iodine-based preparation on the dynamics of the melanoma growth was studied in the main group of animals (n = 42) receiving per os 1,3-diethylbenzimidazolium triiodide in a single dose of 0.4 mg/kg throughout the experiment; the control group (n = 20) received distilled water. The tumor volume and survival of mice were measured. Results: The lowT3/lowT4 syndrome developed in females with transplantable B16/F10 melanoma starting from week 2 of the experiment, diagnosed by decreasing levels of FТ3 and FТ4 by 3 times and lower and normal levels of T3 and T4. In males, melanoma growth caused the thyroid hypofunction expressed in a decrease in the levels of T3 and T4 by 2 times, and FT3 and FT4 by 1.5 times. The latent period prior to the tumor onset was 10-12 days in females and 5-7 days in males. The survival of females was 5-6 weeks, males – 3-4 weeks. The administration of the organic iodine-based preparation extended the latent period in females up to 14-18 days, in males up to 10-14 days; the survival of females increased by 1.8 times, males by 1.5 times. 9% of females in the main group showed complete tumor resorption without relapses throughout their lives. Conclusions: The growth of transplantable B16/F10 melanoma in male and female С57ВL/6 mice was accompanied by suppression of the thyroid function with the development of uncontrolled hypothyroidism in males and the lowT3/lowT4 syndrome in females, which correlates with the survival of animals.
Association of PTPN11 mutation with tumor mutation burden and survival in melanoma patients treated with immune checkpoint inhibitors.
Authors: Long De , Fan Dandan 
Published: June 2021

e21596 Background: Melanoma is a serious skin cancer. Immune checkpoint inhibitors (ICIs) have shown durable responses and have been approved by FDA. However, ICIs demonstrate antitumor effects only in a fraction of patients, and research exploring the association between gene mutation and clinical benefit is limited. Mutations of PTPN11 (Protein Tyrosine Phosphatase, Non-receptor type11) have been reported to be associated with higher response rate and prolonged survival in advanced Renal Cell Carcinoma, Glioblastoma. The association between PTPN11 mutation and the efficacy of ICIs for melanoma is unknown. Methods: Genomic and survival data of melanoma patients administrated with ICIs were retrieved from publicly accessible data (Melanoma.Allen2015.WES.110) and the association between PTPN11 mutation and progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier curves and log-rank tests. At the same time，the association between PTPN11 mutation with TMB was also analyzed in this public immunotherapy-treated cohort(Melanoma.Allen2015.WES.110), Wilcoxon test was used for the comparison of TMB. In addition, Genomic, immune cell infiltration data of 466 patients with Skin Cutaneous Melanoma (SKCM) was obtained from The Cancer Genome Atlas (TCGA). The correlation analysis between immune cell infiltration and PTPN11 mutation status was further analyzed by CIBERSORT. Statistical significance was set at p = 0.05. Results: 3.6% (4/110) patients in the clinical cohort harbored PTPN11 mutation. Survival analysis in the public cohort demonstrated that PTPN11 mutation resulted in significantly longer OS (33.6 vs 8.5 months; HR, 0.16; p = 0.037) and an increasing trend on PFS without significantly difference (9.1 vs 2.8 months; HR, 0.3; P = 0.078) in melanoma patients treated with ICIs. Moreover, PTPN11 mutation is associated with higher TMB in public cohort (p = 0.01). Furthermore, the correlation analysis between immune infiltration and PTPN11 mutation status in melanoma shows that M1 macrophages increased significantly (p = 0.0014), CD8 T cells, plasma B cells and activated NK cells also show an upward trend (p = 0.17, p = 0.17 and p = 0.19) while the resting NK cells decreased significantly (p = 0.016)in melanoma patients with PTPN11 mutation. Conclusions: This study shows that PTPN11 mutation may serve as a potential positive biomarker of ICIs in melanoma since it relatively correlated with higher TMB. In addition, the up regulation of M1 macrophages and the down regulation of resting NK cells may be a potential mechanism for the better efficacy of ICIs in patients with PTPN11 mutation.
Analysis of epigenomic signatures in cell-free DNA (cfDNA) from cancer patients and high-risk controls: A blinded test cohort of THUNDER-II study.
Authors: Gao Qiang , Li Bingsi , Xu Jiayue , Fang Shuai , Qiu Fujun , Su Jing , Wang Guoqiang , Cai Shangli , Zhao Heng , Zhang Wei , Li Ning , Wang Weilin , Qiao Gui-Bin , Liu Hao , Zhang Zhihong , Fan Jia 
Published: June 2021

e22518 Background: Early detection of cancer has the potential to provide a clinical benefit to patients, especially for those with hard-to-treat diseases like ovarian and pancreatic cancer. The THUNDER (the unintrusive detection of early-stage cancers) program was designed to develop and validate a multicancer detection blood test (ELSA-seq) through a series of prospective, observational case-control studies. The second sub-study of THUNDER program (THUNDER-II) includes a discovery, training/validation, and single-blind test (SBT) phase. This new analysis, comprising data from the SBT set of THUNDER-II, evaluated performance of ELSA-seq in an independent group of participants, including individuals at high risk of certain cancer types for the first time. Methods: In the SBT group reported here, all participants were recruited from sites that were not represented in training or validation. The cancer group focused on six deadly cancer types (lung, colorectal, liver, pancreatic, esophageal, and ovarian cancer), and the non-cancer controls were stratified to ‘healthy’ and ‘high-risk’ subgroups based on examination results of low-dose spiral chest CT scan (LDCT), abdominal ultrasound, and Hepatitis B serologic test (HBsAg). 10ml of blood from each participant was collected and methylation-sequencing libraries were prepared by ELSA-seq as described previously. The detection results were automatically reported by a locked computational pipeline to mimic a real-world test scenario (Burning Rock Biotech, China). All samples were delinked from the donors’ cancer status and experiments were performed by blinded personnel. Results: In general, the cancer and non-cancer groups were comparable with respect to age, sex, and tobacco/alcohol-consumption history. The assessment is still in progress, and we have studied 360 eligible participants including 202 cancer cases and 158 non-cancer controls (76 ‘healthy’; 82 ‘high-risk’). Overall, ELSA-seq achieved a specificity of 98.1% (95%CI: 94.1-99.5%) and a sensitivity of 74.8% (95%CI: 68.1-80.5%), consistent with the performance in training and validation1. Among six pre-specified cancer types, sensitivity was 53.0% (95%CI: 40.4-76.3%) in stage I, 73.3% (95%CI: 57.8-84.9%) in stage II, 90.4% (95%CI: 78.2-96.4%) in stage III, and 92.3% (95%CI: 78.0-98.0%) in stage IV. In terms of identifying the diseased organ(s), 80.8% (95%CI: 73.4-86.6%) of the predications matched the true TOO status. Conclusions: ELSA-seq demonstrated consistent results in sites that did not contribute to training, supporting that performance was not subject to sample-/site-dependent bias. It also showed a very low false positive rate in asymptomatic individuals with or without certain cancer-prone conditions, suggesting a potential applicability to broad populations.
The impact of live education on the competence and performance of oncology practitioners who care for patients with ovarian cancer.
Authors: Carranza Vanessa , Taylor Bryan Carson , Gitzinger Susan H. , Fowler Joan B. , Hall Jessica 
Published: June 2021

e23010 Background: About a third of ovarian cancer patients in the US have limited access to a gynecologic oncologist (GO) due to geographic disparities. A survey by The Society of Gynecologic Oncology (SGO) found that the majority of GOs found it was vital to coordinate local access to care, from diagnosis to survivorship, for patients living in areas of disparity. This allows rural/underserved patients broader access to novel therapies, as they increasingly become standard of care. It is critical for not only GOs to be current on the latest ovarian cancer data, but all clinicians who care for these patients. Methods: CEC Oncology developed two educational initiatives focused on PARP inhibitor therapy in ovarian cancer, which was targeted to all US healthcare professionals caring for ovarian cancer patients. Evaluations were collected from attendees attending an SGO Symposium and Ground Round (GR) series to assess impact on practice, increased competency, and intent to make a change in practice. Learning, knowledge, and competence was objectively assessed by analyzing pre-test, post-test, and follow-up survey data (sent 4-6 weeks post-activity). Chi-square analysis was conducted with a priori significance set at 0.05. Results: A total of 830 clinicians were educated, with SGO attendees primarily practicing in academic settings and GR attendees mostly from community practices. SGO attendees were asked case questions at baseline, immediately after the activity, and 4-6 weeks after the activity. Knowledge increased from pre- to post-test regarding current genetic testing recommendations (23% increase; P= .004) and appropriate selection of PARP inhibitor therapy (25% increase; P= .017). Knowledge was sustained at follow-up analysis. At follow-up, 90% of SGO and 84% of GR attendees made a change as a result of attending the activities. More attendees were able to incorporate germline multigene testing into practice, than originally intended; increase of 29% for SGO and 7% for GR audiences. All attendees experienced the barrier lack of patient education about the importance of genetic testing/counseling more than anticipated; increase of 7% for SGO and 13% for GR audiences. At follow-up, there was a 9% increase in GR attendees listing staying current with trial data and practice guidelines as a barrier. Conclusions: There were some notable differences seen in competence/performance among attendees of the two ovarian cancer educational initiatives. Differences may be attributed to practice setting (SGO primarily academic; GR primarily community.) Overall, GR attendees were more likely to face barriers, suggesting that community-based clinicians have fewer resources and experience more barriers to implementing best practices. Thus, it is vital to offer education for clinicians in community-based practices, particularly in areas that are considered ‘geographically disparate’.
Impact of the azoximer bromide concomitant therapy on outcomes in patients with soft tissue sarcoma.
Authors: Novik Aleksei Viktorovich , Shendaleva Natalya , Zozulya Anton , Nekhaeva Tatyana Leonidovna , Semenova Anna , Teletaeva Gulfiya Midhatovna , Latipova Dilorom Khamidovna , Semiglazova Tatiana , Protsenko Svetlana , Baldueva Irina Alexandrovna 
Published: June 2021

e23534 Background: Immunomodulators are used in the management of patients with soft tissue sarcoma, (STS). However, the precise mechanism behind their benefits in anticancer therapy effects have yet to be determined. We assessed the impact of the immunomodulator azoximer bromide (AB) as a prognostic factor for survival when used concomitant with standard therapy in patients with STS. Methods: We reviewed medical history and disease outcomes in STS patients attending the Petrov National Medical Research Centre of Oncology (St Petersburg, Russia). Data were collected per protocol on treatments and patient outcomes. A Cox proportional-hazards model for time-to-progression (TTP) was constructed in SPSS v19. Known prognostic factors (TNM stage and substage, sex, age, therapy by type, and by immunologic action, as well as treatment modality), setting and AB therapy extracted from patient records were included in the model. The model employed a ‘step-forward’ method with AB therapy identified as the ‘unknown’ variable. Results: Complete patient records were available on 243 clinic attendees (from 2010 to 2020), 25 had received treatment with AB. The median follow-up was 20.9 months. Patients received single- and multi-agent chemotherapy, vaccines, cytokines, radiation therapy and/or surgery in the adjuvant or metastatic setting. Significant factors in the TTP model were current therapy type (Hazards ratios: 0.59 for surgery, 0.533 per added method for complex therapy and HR 1.689 for single-agent chemotherapy), previous systemic chemotherapy (HR: 1.451) and AB therapy (HR 0.547). Conclusions: Use of AB with standard therapy in STS emerged as an independent favorable prognostic factor. Appropriately controlled, well-designed prospective trials are needed to investigate this finding further. [Table: see text]