bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of IBI110 (anti-LAG-3 mAb) in combination with sintilimab (anti-PD-1 mAb) in first-line advanced squamous non-small cell lung cancer (sqNSCLC): Initial results from a phase Ib study.
Authors: Zhou Caicun , Xiong Anwen , Li Wei , Wang Lei , Wu Fengying , Yu Jia , Mao Chenyu , Qian Jiong , Zheng Yulong , Jiang Haiping , Gao Yuan , Xiao Cheng , Wang Wenxiang , Zhuang Wu , Yang Jun , Sun Jiya , Wang Hongli , Liu Ying , Xu Nong 
Published: June 2022

e21145 Background: Although PD-1/L1 inhibitors have shown efficacy in advanced/metastatic sqNSCLC, many patients do not respond to this treatment. More effective combination therapies are needed. The efficacy and safety of IBI110 in combination with sintilimab as first-line therapy for advanced sqNSCLC was evaluated in a phase Ib study. Here, we report the initial results. Methods: Eligible patients with previously untreated, unresectable, locally advanced or metastatic NSCLC were enrolled in cohort D. Patients received IBI110 200mg IV Q3W and sintilimab 200mg IV Q3W until disease progression, unacceptable toxicity or death, in combination with chemo regimen (paclitaxel 175 mg/m2 plus carboplatin) IV Q3W for 4 cycles. The primary objective was to evaluate the safety, tolerability and efficacy of the combination therapy. Results: Totally, 20 patients were enrolled (median age: 63 [range: 52-74]; male: n = 19; ECOG 1: n = 16). As of data cutoff date, Jan 20, 2022, median follow up was 3.3 months (range: 2.6-7.0). The median exposure of combination therapy was 15.1 weeks (range: 6-52). The objective response rate was 80% (16/20, 9 patients with ≥2 efficacy assessments were confirmed PR and 7 needed further confirmation). The median progression-free survival and overall survival were not reached. The most common treatment-related adverse events (TRAEs) included white blood cell count decreased (50%), alopecia (50%), anaemia (45%), asthenia (40%), neutrophil count decreased (35%), rash (35%), and hyperglycaemia (30%); most common TRAEs ≥ grade 3 were neutrophil count decreased (30%), and white blood cell count decreased (20%). Immune-related AEs occurred in 11 patients (55%) and most were grade 1-2. The biomarker analysis including LAG-3 and PD-L1 expression in tumor specimen was ongoing. Conclusions: IBI110 in combination with sintilimab in first-line advanced sqNSCLC showed promising anti-tumor activity with acceptable safety. The study is still ongoing. Clinical trial information: NCT04085185.
Literature on target therapy of malignant melanoma.
Authors: Esmaeil Pour Mohammad Ali , Mohebtash Mahsa , Amin Ali , Khayyat Azadeh , Khalili-Toosi Amir-Reza , Guo Mengni , Mousavi Seyedreza , Liu Jieying 
Published: June 2022

e21506 Background: Malignant melanoma (MM) of mucosal membranes (excluding anus and head and neck) is a rare but aggressive disease with poor outcome. There is little information available on the mechanism of development, risk factors and management of this tumor, mainly due to the low number of cases. Methods: We performed a literature review on MMM (between 1970-2020) with a focus on nonsurgical management and outcome. Results: We identified 9-papers discussing 1500-MM cases. Formerly, for the management of MMM, Dacarbazine, Interferon b, DAV-Feron, Carboplatin, Imatinib, and Paclitaxel were administered. More recently, novel immunotherapeutic and chemotherapeutic medications such as Immune Checkpoint Inhibitors (ICPI) and anti-VEGF agents have been administered in these patients. In 502 patients of metastatic MMM, adding ipilimumab to dacarbazine increased OS from 9.1-to-11.2 months with one year survival increasing from 36.3%-to-47.3 %. For nivolumab & ipilimumab combination therapy in 361 patients with MMM and CMM, MPSF in nivolumab monotherapy was 3-months and 6.2-months (for MMM and CMM, respectively); but in nivo-ipili combination, MPFS was 5.9-months and 11.7-months (for MMM and CMM, respectively). A benefit of bevacizumab addition to platinum-based chemotherapy in patients showing advanced disease on ICPI is unknown; however, combination-therapy may be reasonable if no access to ICPI or autoimmune diseases. Conclusions: MMM patients could benefit from combination of nivolumab to ipilimumab more than monotherapy with either medication alone.[Table: see text]
Characteristics of cytokine profiles of peripheral blood in patients with melanoma receiving checkpoint inhibitor therapy with disease progression.
Authors: Teplyakova Maria A. , Vladimirova Liubov Yu , Popova Irina L. , Lyanova Aza A. , Abramova Natalia A. , Storozhakova Anna E. , Ryadinskaya Ludmila A. , Tikhanovskaya Natalia M. , Udalenkova Irina A. , Kalabanova Elena A. , Kabanov Sergey N. , Sagakyants Aleksandr B. , Zlatnik Elena Yu , Shulgina Oksana G. , Zolotareva Ekaterina I. , Ulianova Elena P. , Pozdnyakova Viktoria V. , Przhedetskiy Yuriy V. 
Published: June 2022

e21509 Background: The limited range of patients clinically responding to checkpoint inhibitor therapy (CIT) is of interest and requires studying the immunological mechanisms underlying this phenomenon. It also remains to be decided or better clarified which biomarkers should be considered when selecting patients for immunotherapy. The purpose of this study was to evaluate some parameters of the cytokine profiles of peripheral blood in melanoma patients receiving CIT with the disease progression. Methods: The study included 11 patients aged 47-82 years with advanced melanoma. CIT (nivolumab 3 mg/kg once every 14 days or 240 mg once every 14 days) continued until the appearance of reliable signs of the disease progression (in combination with symptomatic deterioration of the patient's condition). The levels of cytokines (TNF-α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IFN-γ) in the blood serum of patients were determined by ELISA before treatment, after 4 and after 8 injections. The results were expressed as specific content (units/mg). Results: All patients developed disease progression after immunotherapy. CIT was accompanied by different changes most pronounce after the 8th CIT cycle. Levels of IL-1β, IFN-γ, IL-10 and α-TNF exceeded the values before CIT by 118%, 131%, 84% and 20%, respectively (5.2 [4.37; 6.1] versus 2.0 [0.44;4], p≤0.041, 3.9 [3.7;4.5] vs. 1.7 [0.5;3.5], p≤0.021, 6.5 [5.8 ;8.2] vs. 3.5 [3.2;5.4], p≤0.04; 4.1 [3.9;4.9] vs. 3.4 [3.2;3.9] pg/ml, p≤0.047). Levels of IL-6, on the contrary, decreased by the 8th CIT cycle by 32%: 5.1 [3.5; 6.1] versus 7.5 [6.2; 22.3] pg/ml, p≤ 0.045. Levels of IL-2 and IL-8 did not change. Conclusions: The revealed significant increase in levels of IL-1β, IFN-γ, IL-10 and α-TNF, as well as the IL-6 decrease, may indicate certain features of the cytokine profile of melanoma patients during the treatment, which may affect the imbalance of regulatory molecules and contribute to the disease progression.
Survival outcomes following immune checkpoint inhibitor therapy of advanced cutaneous melanoma by age and tumor infiltrating lymphocytes in the primary cutaneous site.
Authors: Kane Mallory , Holmes Aaron N. , Kerr Phil , Hegde Upendra P. 
Published: June 2022

e21514 Background: Tumor infiltrating lymphocytes (TILs) in the tumor microenvironment generate anti-tumor immunity and are associated with response to immune checkpoint inhibitor (ICI) therapy of melanoma. However, likelihood of response to ICI therapy depends upon intensity of TILs, proportion of effector and regulatory T cells and age. Methods: In a research study approved by the Institutional Review Board of University of Connecticut, we retrospectively analyzed outcome of patients diagnosed with cutaneous melanoma between 2009 and 2019 and developed unresectable stage III or stage IV disease requiring ICI treatment. Patients were stratified by age (< 75 and > 75 years old) and TILs at the primary cutaneous melanoma site categorized as brisk (present throughout vertical phase), non-brisk (present in one of more foci of vertical phase) or absent. Patient’s age at the time of metastases, as well as 12-month and 24-month overall survival (OS) following ICI treatment was recorded. Results: A total of 93 patients were screened, and 68 were included for analysis of survival outcome. Patients had to receive at least one dose of ICI treatment at UConn Health and had available data on TILs of primary cutaneous melanoma. In patients over 75 years of age, those with brisk TILs had an increased 24-month survival compared to those with non-brisk or absent TILs (100% vs. 45%, p = 0.04). In patients < 75 years of age, the 24 month survival was similar in those with brisk and non-brisk or absent TILs (67% vs. 69%, p = .91). There was no significant difference in overall survival between patients < 75 or > 75 years with brisk TILs (67% vs. 100%, p = .19). Additionally, in patients with non-brisk or absent TILs, there was a not quite significant difference in survival between those > 75 vs < 75 years (45% vs. 69%, p = .09). Conclusions: Our findings suggest that intensity of TILs in primary cutaneous melanoma is predictive of outcome following ICI treatment of advanced melanoma in patients over 75 years of age. These findings support possible interaction between qualitative differences of TILs and patient age. Our findings may help identify older melanoma patients who may benefit from ICI treatment.
Survival outcomes of pulmonary metastasectomy in advanced melanoma patients: An inverse probability weighted analysis.
Authors: Syaj Sebawe , Akhdar Marah , Alser Osaid , Elshami Mohamedraed , Hamouri Shadi 
Published: June 2022

e21518 Background: Pulmonary metastasectomy (PM) is a commonly performed procedure for certain patients with lung metastasis. We aimed to estimate the effect of PM on the survival outcomes of advanced melanoma patients with lung metastasis. Methods: We queried the Surveillance, Epidemiology, and End Results (SEER) database for all adult patients with advanced melanoma (AYA site recode) with lung metastasis (Stage M1b according to AJCC 7th edition) who were diagnosed from 2010 to 2015. Patients with known liver, brain, or bone metastasis were excluded. Our primary outcomes were overall survival (OS) and cancer-specific survival (CSS) in months. We used Kaplan-Meier plots to compare survival outcomes between treatment groups. We adjusted for potential confounders including age, sex, marital status, primary tumor surgery, chemotherapy, and radiotherapy in a multivariate analysis. We carried out an inverse probability (IP)-weighted Cox regression in an attempt to eliminate the effect of nonrandomization when estimating the treatment effect of PM on OS and CSS. Results: We included 520 patients; 98 (18.8%) underwent PM and 422 (81.2%) did not. The sample median age was 71 (IQR: 61-80). T0 stage was prevalent in 179 (34.4%) and N0-1 in 302 (58.1%). Primary surgical resection was performed for 217 (41.7%) patients, 136 (26.2%) patients had undergone chemotherapy, and radiotherapy was administered in 64 (12.3%) patients. Patients who underwent PM had a higher median OS than patients who did not (43.0 months, 95% CI: 25.0-not reached vs. 13 months, 95% CI: 11-16). The median CSS in PM group patients was not reached (95% CI: 43.0-not reached), while it was 16 months (95% CI: 13-21) in non-PM patients. After multivariate adjustment, older age, being single, and not undergoing primary surgical resection, were all significant independent prognostic factors for worse OS and CSS. In contrast, sex and receipt of chemotherapy and/or radiotherapy did not affect either OS or CSS. PM group patients had a significant survival advantage than non-PM patients, in terms of OS and CSS (HR = 0.50, 95% CI: 0.37-0.67 and HR = 0.45, 95% CI: 0.32-0.63, respectively). On the IP-weighted Cox analysis, the survival benefits of PM were still significantly favorable for OS (IP-weighted HR = 0.42, 95% CI: 0.30-0.59) and CSS (IP-weighted HR = 0.38, 95% CI: 0.26-0.57). Conclusions: PM in a multimodality treatment setting resulted in a marked survival advantage for patients with advanced melanoma who had lung metastasis only. The management of such patients should be delicately individualized to optimize their survival outcomes.
Safety and effectiveness of avelumab in patients with curatively unresectable merkel cell carcinoma (MCC) in a real-world setting: A post-marketing surveillance in Japan.
Authors: Uhara Hisashi , Kiyohara Yoshio , Sato Masashi , Endo Shehla , Song Bingbing , Sato Yoshinori , Tanaka Yutaro , Kambe Anzu , Yamazaki Naoya 
Published: June 2022

e21528 Background: Avelumab is an anti–PD-L1 monoclonal antibody that was approved in Japan for the treatment of patients with curatively unresectable MCC in Sept 2017. Because the number of Japanese patients with MCC participating in the global Phase II JAVELIN Merkel 200 study was limited (3 patients), Japan was mandated to conduct an all-case surveillance as a post-marketing surveillance (PMS) study. In the all-case surveillance, safety and efficacy information is accumulated with respect to a defined period of time or a defined number of post-approval prescription cases and is provided as real-world data. This report summarizes the results of the final analysis of this MCC PMS. Methods: This PMS is a multicenter, non-comparative, prospective, observational study. Since Nov 2017 (following approval in Japan), all patients with MCC who received at least one dose of avelumab in Japan were enrolled, and case report forms (CRF) were collected for all patients who started treatment through Oct 2019. Results: As of Sept 22, 2021, 152 patients from 86 sites were enrolled, and CRFs were collected from 77 patients. Of the 75 patients (53 sites) who met the analysis adequacy criteria, 48% were female, and the median age at the start of avelumab treatment was 77.0 years (42-95 years). Of the treatment lines in which avelumab was administered, 93.3% (70/75) were prescribed as first-line therapy. The incidence of adverse reactions was 61.3% (46/75), and 9.3% (7/75) discontinued treatment due to adverse reactions. Grade 3 and 4 adverse reactions occurred in 12.0% (9/75) and 4.0% (3/75), respectively; no grade 5 adverse reactions were reported. Infusion reactions were reported in 28.0% (21/75). The objective response rate (proportion of patients whose best response was assessed by the investigator as a complete or partial response) up to 1 year after the start of avelumab treatment was 45.3% (95% CI: 33.8, 57.3). The 1-year overall survival rate was 59.6% (95% CI: 47.0, 70.1). Conclusions: This study report is the first real-world evidence collected and analyzed from actual clinical use of avelumab in patients with curatively unresectable MCC in the East Asia region. Despite the different baseline patient characteristics, avelumab therapy in clinical practice had a manageable safety profile with no new safety concerns and has shown similar efficacy to that observed in the JAVELIN Merkel 200 trial.
Predictors of complication after groin dissection: A contemporary experience.
Authors: Jamjoum Ghader , Araji Thea , Nguyen Diana , Meguerditchian Ari N. 
Published: June 2022

e21531 Background: Inguinal lymphadenectomy (ILND) has historically been associated with significant morbidity. The advent of sentinel node biopsy and selective dissection protocols have significantly decreased the frequency with which ILND is performed, reserving it for complex, recurrent disease. The study objective is to obtain contemporary morbidity rates for this complex procedure and to identify potentially preventable risk factors. Methods: Retrospective review of medical charts for all superficial, deep, and combination groin dissections performed for melanoma, sarcoma, and other rare cancers at a single, high-volume academic center between 01/2007 and 12/2020. Data points collected: patient, disease, surgery characteristics, and cancer outcomes. Outcome of interest: any complication within 30 days of surgery. Complications: wound infection, wound necrosis/disruption, seroma, drainage procedure, hematoma, lymphedema, and other. Multivariate logistic regression performed using SAS Enterprise 9.4. Results: : 139 cases were identified; type of dissection was 89, 12, and 38 for superficial, deep, and combined respectively. Melanoma accounted for 84.9% of cases, sarcoma for 8.6%. 56.1% of patients had an adverse postoperative event within 30 days. The majority of patients did not have a history of smoking, diabetes, cardiovascular disease, hypothyroidism, or radiation therapy. 61.2% were recurrent cancer cases with 56.8%, 19.4%, and 23.7% being clinically evident, radiological-only, and sentinel node positive disease respectively. Type and frequency of complications is reported in Table. Increasing age (OR: 1.04, 95CI: 1.01-1.07, P < 0.01) and number of positive lymph nodes harvested (OR: 1.22, 95CI: 1.00-1.50, P = 0.05) were associated with more complications. Deep dissection showed lower likelihood of complications than those with superficial (OR: 0.15, 95CI: 0.03-0.84, P < 0.05). Conclusions: A number of risk factors for complications were identified opening up opportunities for preventative intervention such as prehabilitation, use of frailty score, and neo-adjuvant therapy. Deep vein thrombosis, abscess, general deterioration, neuropathic pain, numbness. Frequency by occurrence, not patient. [Table: see text]
Attacking effect of diabetes mellitus and chronic neurogenic pain on malignant process:Are mitochondria of the heart damaged?
Authors: Neskubina Irina V. , Frantsiyants Elena M. , Kaplieva Irina V. , Cheryarina Natalia D. , Surikova Ekaterina I. , Shikhlyarova Alla I. , Bandovkina Valeria A. , Pogorelova Yulia A. , Nemashkalova Ludmila A. , Trepitaki Lidia K. , Kachesova Polina S. , Kotieva Inga Movlievna , Morozova Maria I. , Przhedetskiy Yuriy V. , Zhukova Galina V. , Goroshinskaya Irina A. , Kit Oleg I. 
Published: June 2022

e21557 Background: Mitochondrial dysfunction is one of the mechanisms for the development of heart disease that requires close study. Diabetic cardiomyopathy is the leading cause of death in such patients due to the development of heart failure. Chronic pain may be associated with higher prevalence of cardiovascular disease, and little is known about its potential biological consequences. The purpose of this study was to analyze parameters of free radical oxidation and mitochondrial respiration in heart cells in experimental animals with malignant tumors growing in presence of diabetes mellitus (DM) and chronic neurogenic pain. Methods: The study included outbred female rats (n = 32) weighing 180-220 g and C57BL/6 female mice (n = 84) weighing 21-22 g. Experimental groups of rats were: intact animals (n = 8), controls (n = 8) with DM, comparison group (n = 8) with subcutaneously inoculated Guerin’s carcinoma, and main group (n = 8) with Guerin’s carcinoma subcutaneously inoculated after 1 week of persistent hypothyroidism. Experimental groups of mice were: intact animals (n = 21), controls (n = 21) with a model of chronic neurogenic pain (CNP) created by bilateral sciatic nerve ligation, comparison group (n = 21) with subcutaneously inoculated melanoma (B16/F10), and main group (n = 21) with melanoma subcutaneously inoculated 3 weeks after the CNP model was created (CNP+B16/F10). Heart mitochondria were isolated by differential centrifugation. Levels of cytochrome C (ng/g of protein), 8-hydroxy-2'-deoxyguanosine (8-OHdG) (ng/g of protein), and malondialdehyde (MDA) (nM/g of protein) were measured in mitochondrial samples by ELISA. Statistical analysis was performed using the Statistica 10.0 program. Results: DM in rats upregulated 8-OHdG by 6.3 times and MDA by 1.9 times (p < 0.05) and downregulated cytochrome C by 1.5 times (p < 0.05) in heart cell mitochondria, compared to intact values. DM+Guerin’s carcinoma in rats increased 8-OHdG by 14.0 times and MDA by 1.7 times (p < 0.05) and decreased cytochrome C by 1.5 times (p < 0.05), compared to intact values. CNP in mice did not affect the studied parameters in mitochondria of the heart. CNP+B16/F10 in mice increased 8-OHdG by 7.1 times and MDA by 1.6 times (p < 0.05) and decreased cytochrome C by 1.6 times (p < 0.05) in heart cell mitochondria. Conclusions: Comorbidity (diabetes mellitus, chronic neurogenic pain) together with malignant pathology aggravates mitochondrial dysfunction of heart cells which results in DNA damage and destabilization of the respiratory chain mediated by free radical oxidation processes.
Prognostic factors for recurrence and mortality in patients with localized malignant melanoma: Analysis of the Epidemiological Registry of Malignant Melanoma in Colombia REMMEC ACHO.
Authors: Ospina Serrano Aylen Vanessa , Contreras Fernando , Triana Ivan , Ortiz Diaz Juan David , Ramos Pedro , Vargas Claudia , Arango Natalia , Idrobo Henry , Munevar Isabel , Yepes Andres , Mantilla William , Jimenez Paola , Rivas Tafurt Giovanna Patricia , Lema-Medina Mauricio , Alcala Marcela , Gomez Diego , Chinchia Isabel , Barrero Angela , Sanchez-Vanegas Guillermo 
Published: June 2022

e21572 Background: Malignant melanoma is the skin cancer with the highest mortality rate. In early stages, it may have a better prognosis and some possibility of cure. In Colombia, given the increase in cases, a national registry of the disease has been initiated with the aim of characterizing the population and establishing the prognostic factors in the local context. Methods: Cohort study based on data from the Epidemiological Registry of Malignant Melanoma in Colombia (REMMEC). For this first phase,data from January 2011 to December 2021 were analyzed. Patients were older than 18 years, with confirmed diagnosis of localized melanoma. Mortality and recurrence incidence rates were calculated using the Kaplan-Meier method, overall survival was estimated at 5 years of follow-up for each stage. Finally, a prognostic model was made for the mortality outcome, using the Cox proportional hazards method. Results: 759 patients were included, the mean age was 66 years (SD: 15.6), 57% women (n = 431), 29% phototype I or II (n = 219), and the most frequent histological subtype was acral lentiginous (n = 211; 36%). In relation to the stage, 13.9% with stage 0 (n = 106), 24.2% in stage I (n = 184), 30% in stage II (n = 228), and 31.7% in stage III (n = 241). ECOG-3-4 in 1.05% (n = 8). Regarding the health regimen, the subsidized patients were 199 (26%), and the contributive 560 (73.8%), of which 35 and 30.6% had stage III, respectively. 92% of all patients underwent local surgery (n = 699) and 30% (n = 226) local lymphadenectomy. The median follow-up time was 36 months (IQR: 17-72). The mortality incidence rate was 3.6 cases per 100 person-years (95% CI: 2.9-4.3), and the recurrence rate was 6.8 cases per 100 person-years (95% CI: 5.9 -7.8). Overall survival at five years for patients in stage 0 and I was 97% (95% CI: 89-99), for stage II it was 80% (95% CI: 72.6-86.6); for stage III 65% (95% CI: 57-72). 22.4% (n = 170) received adjuvant treatment . 26.2% (n = 199) had metastatic recurrence. The prognostic factors for mortality are presented in Table. Conclusions: In the Colombian context, in patients with localized melanoma, ECOG 3 or 4, stage III at the time of diagnosis, receiving radiotherapy, the presence of ulceration, chronic sun exposure, and the subsidized health regimen are poor prognostic factors.[Table: see text]