bluuebunny/crossref_metadata_2025_split huggingface dataset:
Economic burden of immunotherapy as second-line treatment of patients with advanced non-small-cell lung cancer at a Latin American oncology center.
Authors: Barron Feliciano Barron , Cabrera Luis Antonio , Cardona Zorrilla Andres Felipe , Arrieta Rodriguez Oscar Gerardo 
Published: May 2019

e18376 Background: Lung cancer is the leading cause of cancer-related mortality in México and worldwide. More than 80 percent of lung cancers are classified as non-small cell lung cancer (NSCLC). Immunotherapy has become integrated into the treatment of patients with specific genetic alterations, which has led to improvements in survival and quality of life. Pembrolizumab is a new drug approved in several countries for second-line therapy in non-small cell lung cancer (NSCLC) being programmed cell death ligand (PD-L1) positive. Methods: A retrospective study of medical records of 60 patients treated with immunotherapy as second-line treatment of advanced non-small-cell lung cancer was conducted at the National Institute of Cancerology (INCAN) in Mexico during 2016-2018. PD-L1 biomarker was not mandatory for receiving immunotherapy. The costs associated with the total costs of tretament were estimated as a mean value with confidence intervals of 95% confidence by costing the elements of treatment of the disease and adverse events as well the frequency of consultations, hospital stays, and monitoring obtained in the records. Costs are presented in US dollars. Results: The total mean monthly cost during immunotherapy was $1,649 (95% confidence interval [CI] = $1,484–$1,814), of which 93.8% represented immunotherapy costs, 5.4% drug application and monitoring, 0.8% adverse events treatment. We identified 30 potential patients per year candidates to receive immunotherapy as second line. From which the expected costs of treatment will be $49,476 [CI] = $44,528–$57,392), of which $41,766 are immunotherapy costs, application and monitoring represent $2,400 and the rest for adverse events. Conclusions: The therapeutic approach for the second-line treatment of patients with advanced non-small cell lung cancer (NSCLC) without actionable mutations has been revolutionized by the approval of new more efficacious drugs like pembrolizumab. Healthcare costs during immunotherapy treatment with pembrolizumab were largely attributed to anti-cancer therapy and less for adverse events. Pembrolizumab as second-line treatment of patients with advanced non-small-cell lung cancer, prolong overall survival, leading to fewer adverse events than chemotherapy.
Cost and time savings of subcutaneous trastuzumab (SC-T) in a public health system in Mexico.
Authors: Villarreal-Garza Cynthia , De la O-Maldonado Cristel , Díaz-Pérez Héctor , Mesa-Chavez Fernanda , García-García Marisol , Cardona-Huerta Servando , Peña-Curiel Omar 
Published: May 2019

e18387 Background: The subcutaneous presentation of trastuzumab has been recently incorporated into the treatment regimen of HER2-positive breast cancer (BC). Its use has been associated with cost savings and reduced chair time, being especially suitable for public health systems. Aim: To estimate the cost savings of the use of SC-T compared to intravenous trastuzumab (IV-T) according to patient weight, and calculate the infusion time of SC-T in a tertiary healthcare facility at TecSalud from Feb 2018 - Jan 2019. Methods: From a total of 2068 oncological treatments, 756 corresponded to SC-T, either alone or concomitantly with chemotherapy (CT). For cost estimation, we considered $1,103 USD per SC-T vial, $1,162 USD per IV-T vial and $2.6 USD per mg of IV-T, as per governmental rates. We compared the actual treatment cost of 600 mg fixed SC-T dose with the hypothetical cost of administering IV-T at a dose of 6 mg/kg, considering its price per vial and per mg. The total time of SC-T infusion was reported. Results: Median patient weight for the 756 reported SC-T treatments was 72 kg (45 - 127 kg). Of these, 561 consisted of SC-T alone; and 56% had adjuvant, 34% neoadjuvant and 10% palliative intent. The estimated cost of the 756 doses of SC-T was $833,500 USD. Considering patients’ weight, 46% of the infusion treatments would have required 2 IV-T vials, with a total of 1105 vials and an absolute cost of $1,282,374 USD. Likewise, if cost per mg of IV-T is examined, we would have used 338,744 mg of IV-T, with an estimated cost of $894,284 USD. Approximate savings of SC-T use would reach $448,874 USD per vial payment and $60,784 USD per mg payment. The median time of SC-T only infusion was of 3 minutes (1 - 20 minutes); and no adverse effects were documented during its administration. Conclusions: The SC-T fixed dose (irrespectively of patients’ weight) results in significant practical and financial advantages as weight-adjusted dosing is not required. This is specially relevant in countries like Mexico, where > 70% of BC patients are overweight/obese, requiring higher doses of IV-T and resulting in greater expenses. Thus, the use of SC-T not only offers greater convenience to patients, but also reduces overall healthcare costs compared to standard IV infusion.
Phase II trial of pembrolizumab (MK-3475) in metastatic cutaneous squamous cell carcinoma: An updated analysis.
Authors: Yushak Melinda Lynne , Lawson David H. , Goings Monica , Mckellar Marjorie , Maynard Necia , Woodruff Kristin Sieja , Gorgoglione Caroline , McBrien Stephanie , Delman Keith A. , Lowe Michael C. , Kudchadkar Ragini Reiney 
Published: May 2019

e21015 Background: Cutaneous squamous cell carcinomas (cSCC) are generally curable with surgery and/or radiation. Unfortunately, some patients develop locally advanced or metastatic disease, with an estimated 3900 to 8700 patients dying of cSCC in 2012. Aggressive disease is often associated with immunosuppression, and no treatment has shown an improvement in overall survival (OS). Recently the FDA has approved cemiplimab-rwlc which targets PD-1. This abstract provides an updated analysis and additional followup for patients treated with pembrolizumab which also targets PD-1. Methods: Clinical activity of pembrolizumab in cSCC patients was evaluated in patients who were not curable by surgery and/or radiation. Patients were treated with pembrolizumab 200mg IV every 3 weeks for up to 2 years. Tumor response was measured every 12 weeks using RECIST version 1.1. Response rate (RR) of pembrolizumab in metastatic cSCC was the primary objective. 6-month progression-free survival (PFS) and 1 year OS were secondary objectives. Results: 11 subjects have been enrolled thus far with a median age of 70.3 years. Two were female and all were Caucasian. ORR per RECIST criteria was 64% with 18% (2) having a complete response, 36% (4) a partial response, 36% (4) progressive disease (PD), and 9% (1) stable disease. The patient with stable disease had a clinical response and was eventually able to undergo surgery that rendered him without any evidence of disease. 6 month PFS for evaluable patients was 72%. Of those patients with a response, 50% had a durable response of 18 months or greater at the time of data cut-off. No subject deaths have occurred on study. Three grade 3 related-adverse events were noted (hepatitis and pneumonitis). Conclusions: Pembrolizumab is active in advanced cSCC. Responses appear durable and comparable to what has been seen in previous studies with the FDA-approved agent, cemiplimab. No new safety concerns were noted. Additional follow up is needed in order to establish an OS benefit. Clinical trial information: NCT02964559.
Clinical characteristics and treatments outcomes of patients with metastatic uveal melanoma (UM) in a Brazilian population: A retrospective unicentric study.
Authors: Campiolo Giovanna , De Barros E. Silva Milton Jose , Petaccia de Macedo Mariana , Rinck Jose Augusto 
Published: May 2019

e21018 Background: Uveal melanoma is the most common primary ocular tumor in adults and accounts for 5% of all melanoma diagnoses in the United States. Approximately fifty percent of patients with uveal melanoma develop metastatic disease. The most frequent site of metastasis from UM is the liver (89 to 95% of the cases) and liver failure is the leading cause of death. To date, no systemic therapy has shown benefits in terms of overall survival (OS) in UM. Methods: We retrospectively analyzed clinical characteristics and aspects of response to systemic and local therapy of a cohort of 58 patients with UM who were treated in our institution from January of 2000 to December of 2017. Survival curves were calculated by Kaplan-Meier method and log-rank test. Results: Median age was 55y. 64% of the patients were female and 48,3% of them were caucasian. With a median follow-up time of 23 months, the median OS was 28,4 months. The median time between primary treatment and systemic relapse was 3.7 years. In 90% of the cases the liver was the unique site of progression. 12% patients had liver metastasectomy as local treatment, with OS of 102,3 months vs. 24,5 months ( p= 0,04) for no local treatment. 12% of the patients with liver methastasis perfomed regional treatment with intra-arterial chemotherapy (IAC) and 17% with chemoembolization (CE). The progression free survival (PFS) for regional treatment was 2.9 months (0,9-27 m); 4,25 months (0,9-27 m) for IAC and 2,9 months (0,9-27 m) for CE. There was no significant benefit in OS for locorregional treatment. As first line treatment, 29% of patients had chemotherapy, 10% had ipilimumab and 3,4% had anti-PD1. The median PFS for first line treatment was 2,49 months; 2 months for chemotherapy, 3,8 months for ipilimumab and 14 months for anti-PD1. The median PFS for second line treatment was 2,8 months and for third line was 2,3 months. There was no consistent clinical impact in OS for systemic treatment. Conclusions: The current systemic treatments available for cutaneous melanoma have limited efficacy in UM, so far none have yet proven a survival benefit. Locorregional therapies are relevant for patients with unresectable hepatic metastases. Resection of liver lesions in highly selected cases has the potential to improve patient outcomes, but the survival advantage may partially reflect patient selection.
A real-world study of recombinant human endostatin continuous intravenous infusion combined with chemotherapy in the treatment of advanced mucosal melanoma.
Authors: Liu Xin , Cao Jun , Meng Yanchun , Zhang Xiaowei , Xu Yu , Wang Chunmeng , Chen Yong , Yang Huijuan , Kong Yunyi , Luo Zhiguo 
Published: May 2019

e21019 Background: There is no standard treatment for patients with advanced mucosal melanoma (AMM). Recombinant human endostatin (Endostar) combined with chemotherapy had been showed to improve the efficacy of advanced melanoma. This real world study was aimed to observe the efficacy and safety of endostar continuous intravenous infusion (Civ) combined with chemotherapy in patients with AMM. Methods: 23 patients with AMM treated with endostar plus dacarbazine or temozolomide plus cisplatin between April 2017 and December 2018 were collected. Endostar was given 105mg/m2 Civ168h (unlike the usual use of 7.5mg/m2/d d1-14) . 5 patients with local advanced disease received concurrent radiotherapy. Results: There were 11 males (48%) and 12 females (52%), with a median age of 58 years (30-72 years). Primary lesions were located in the nasal cavity and paranasal sinuses in 9 cases (39%), anorectum in 9 cases (39%), vagina in 3 cases (13%), esophagus in 1 case (4%), and choroid in 1 case (4%). There were 7 patients with local advanced disease and 16 patients with metastatic disease. 1 patient received prior anti-PD1 therapy, 1 patient received prior chemotherapy, the other 19 patients received no prior systemic therapy. A total of 21 patients underwent gene detection, there were 2 patients (10%) with BRAF mutation (one with V600E mutation, one with G606E mutation), 7 patients (33%) with NRAS mutation (3 with exon 2 mutation, 4 with exon 3 mutation), and 1 patient (5%) with KIT exon 11 mutation. Overall, 4 patients (13%) had CR, 4 patients (22%) had PR, 10 patients had SD (43%), and 5 patients (22%) had PD, resulting in a RR of 35% and a DCR of 78%. The 4 patients with CR were with localized disease and received concurrent radiotherapy. The RR were 44%, 33%, 33%, 0% and 0%, and the DCR were 100%, 67%, 67%, 0%, and 100% in patients with melanoma of the nasal cavity, anorectum, vagina, esophagus and choroid respectively. The median PFS was 7.5 months (95% CI: 1.0-14.0months). The median OS was 14.7 months (95% CI: 5.0-24.4months). Grade III/IV adverse events were leucopenia (13%), thrombocytopenia (13%), anemia (4%), nausea and vomiting (4%), elevated transaminase (4%), nasal hemorrhage (4%) and intestinal obstruction (4%). Conclusions: Endostar combined with chemotherapy is effective and safe in the treatment of AMM, especially for patients with melanoma of the nasal cavity and paranasal sinuses. For mucosal melanoma patients with local advanced disease, concurrent chemoradiotherapy may be a good choice. It deserves further study.
Staccato pulse interleukin-2 (IL-2) in metastatic melanoma (MM) previously treated with checkpoint inhibitors (CPI).
Authors: Quan Walter , Gutierrez Leah I , Quan Kyle , Quan Francine Marie 
Published: May 2019

e21022 Background: The CPI ipilimumab, nivolumab, and pembrolizumab have been adopted into common use for patients (pts) with MM. While their clinical activity is undeniable, a substantial fraction of pts treated with these agents experience disease progression. Additional approaches are therefore needed. Intravenous IL-2 given via daily single intravenous infusions (pulses) has been developed to mitigate toxicity while maintaining anticancer activity against MM. Staccato pulse IL-2 is based on three prior observations. Daily IL-2 schedules have previously been demonstrated to induce Lymphokine Activated Killer cell (LAK) activity [Mitchell, 1989]. LAK generated by IL-2 then subsequently exposed to more IL-2 display enhanced cytotoxicity in vitro [Hank, 1990]. Increased numbers of LAK are seen in pts with melanoma treated with daily IL-2 [Quan, 2011]. Methods: In this retrospective study, ten pts with MM were treated with IL-2 18 Million IU/M2 intravenously over 15-30 minutes on days 1-3 and 21.6 Million IU/M2 intravenously over 15-30 minutes on day 5 on an outpatient basis. Cycles were repeated every 3 weeks. Results: Characteristics: 8 females/ 2 males, median age-56 (range: 21-74), median ECOG-1 (0-1); common disease sites: lymph nodes (12), subcutaneous (6), lungs (5), soft tissue (4). Prior CPI: Ipilimumab (8); Pembrolizumab (5); Nivolumab (2). Common toxicities: nausea/emesis (8), myalgia/arthralgia (5), sinus/catarrhal symptoms (5), fatigue (5), and hypotension requiring intravenous fluids (5). No pts required hospitalization for toxicity related to therapy. Median number of cycles: 3 (2-8). Four pts have had partial responses (total response rate = 40%; 95% CI: 10-70%). The median duration of response exceeds 7.4+ months. One pt having had resolution of prior lung, lymph node, and peritoneal metastases (partial response of 24.5+ months) underwent surgical resection of the residual intraabdominal disease focus and is free of disease at 36.5+ months. Overall, responses have occurred in lung, lymph nodes, subcutaneous, bones, peritoneum, small bowel, and soft tissue sites. Conclusions: Staccato pulse intravenous IL-2 has activity in melanoma pts previously treated with CPI.
Real-world outcomes of advanced melanoma patients treated with pembrolizumab who have failed prior lines of therapy.
Authors: Ou Wanmei , Taymor Emilie , Diede Scott J. , Whitman Eric D. 
Published: May 2019

e21031 Background: Pembrolizumab (PEM), a humanized antibody targeting programmed death-1 receptor, has been approved by FDA for the treatment of patients (pts) with advanced melanoma (AM) in the US since 2014. Real-world (RW) data supports the clinical effectiveness of 1L use of PEM, but there is limited information of PEM later line use. The study examined the RW outcomes of pts treated with PEM who have failed prior lines of therapy in US oncology clinical practices. Methods: Flatiron Health longitudinal database was used to identify adult pts with AM who received ≥1 dose of PEM in second line (2L) or later (3L+) between September 4, 2014 and May 31, 2017. Pts were followed up to May 31, 2018. Pts in clinical trials were excluded. Pt demographic, treatment, and clinical characteristics were described. Time on treatment (ToT) and overall survival (OS) were analyzed using the Kaplan Meier (KM) method, with the first dose of PEM as the starting point. Results: Two hundred thirty-six pts were included in the analysis, of which there were 171 2L and 65 3L+. Overall, median age at PEM initiation was 66 years; most were male (66.1%) and Caucasian (95.4%). 41.1% of pts’ tumors were confirmed BRAF mutant; 49.6% of pts’ tumors were confirmed BRAF wildtype; the rest was not tested or indeterminate. When data were available, 26.2% had an elevated lactate dehydrogenase (> ULN), 24.6% had brain metastases, and 25.5% had an ECOG performance status of > 1. At the time of analysis, pts were followed for a median of 12.5 months (mo, range, 0.1-44.6). Overall median ToT was 4.4 mo (95% CI, 3.5-5.3), with 4.7 and 4.4 mo in 2L and 3L+, respectively. Overall median OS was 16.8 mo (95% CI, 12.2-25.9), with 16.8 and 18.9 mo for 2L and 3L+ respectively. 1-year and 2-year survival, using the KM method, was 58.0% (95% CI, 51.2-64.1; 2L, 57.4%; 3L+, 59.6%) and 44.7% (95% CI, 37.9-51.3; 2L, 44.3%; 3L+, 46.1%) respectively. Conclusions: The study reports RW use of PEM in a large cohort of pts with AM who have failed initial therapy in US oncology clinical practices, with a heterogeneous study population compared to clinical trials. The findings of OS based on RW use suggest PEM is an effective treatment option for patients in later lines of therapy.
Markers of melanoma progression in the blood serum structure.
Authors: Shikhlyarova Alla I. , Kit Oleg I. , Shatokhina Olga N. , Akhmedova Amira A. , Przhedetskiy Yury Valentinovich , Pozdnyakova Viktoria V. , Khokhlova Olga V. , Przhedetskaya Viktoria , Lysenko E. P. , Goncharova Anna S. , Zhadobina Anastasia I. , Zhukova Galina V. 
Published: May 2019

e21035 Background: Lack of prognostic markers of melanoma to assess its progression, metastasis (MTS), and treatment effectiveness, determines the feasibility of studying biophysical aspects of the transmission of events from cellular to extracellular environment. Receipt and circulation of pathological proteins of melanoma (M) in the blood carries important information, and its trap is the phase transition of biofluids into a solid state. The purpose of the study was to determine markers of melanoma at the supramolecular level in solid-state samples of the blood serum (BS). Methods: 240 samples of BS obtained prior to the surgery from 60 patients with M were studied. The preparations were prepared by the Shatokhina-Shabalin method by creating a closed "analytic cell": dehydration of a BS drop (10 mcL) under a cover glass at 20–240С, humidity 65–70%, for 72 hours. The folding of M proteins was assessed by a polarized light microscopy (Leica DM LS2 microscope, x400-640) using photo and video control and the Morphotest program. Results: The initial stages of M development were characterized by the early appearance of single combined melanoform crystals — anisotropic microspherolites (Mi) embedded in the center of a large anisomorphone (lAM). As M progressed, Mi aggregation with basic lAMs was enhanced. Anisotropy of Mi increased, revealing clear sectors filled with melanin. In the later stages of M growth, melanoform aggregations dominated with point, filamentous, and chained melanin structures. The manifestation of MTS was accompanied by the destruction of the aggregations and the filling of the analytic cell space with numerous Mi. Conclusions: Correspondence of crystallogenesis of M melanomorphic markers in BS in tumor progression allows using the studied supramolecular factors to predict the development of melanoma.
Prognostic differences and the effect of radiotherapy on survival in Merkel cell carcinoma: A retrospective analysis of a Swedish cohort.
Authors: Bjorn-Andtback Hannah , Masucci Giuseppe V. , Björnhagen-Säfwenberg Viveca , Lui Weng-onn , Villabona Lisa Elena Esther 
Published: May 2019

e21047 Background: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer. The pathogenesis is linked to the immune system and Merkel cell polyoma virus (MCPyV) is present in about 80% of MCC. Reports have shown that patients with a virus-negative MCC have a worse prognosis. Adjuvant radiotherapy given after surgery has previously been shown to give a survival benefit in retrospective data. Our aim is to analyze clinical variables and their prognostic impact in a Swedish cohort. Methods: All patients with confirmed diagnosis of MCC referred to Karolinska University Hospital in Sweden from 1989-2018 were included and retrospective data was collected. Results: 113 patients were included. Median age at operation was 75.4 years (range 19-99); 64 (57%) were female. Treatment included surgery with (n = 46) or without adjuvant radiotherapy (RT). 43% of female patients and 37% of male patients received RT. Median overall survival (OS) was 2,6 years (range 0,1-25,8), for female patients 3,4 years (range 0,1-25,8) and for male patients 1,8 years (range 0,1-19,0). Median OS in surgery group was 1,8 years (range 0,4-25,8). With adjuvant RT median OS improved with 1,7 years (p = 0,0001) to 3,5 years (range 0,2-22,1), for female patients 4,0 years (range 0,2-22,1) and for male patients 2,0 years (range 0,3-8,8). MCPyV status was available in 53 patients. 74% were MCPyV positive, 26% negative. MCPyV gave no difference in OS, however when gender was added in to multivariate analysis, female patients with virus negative disease had better outcome than virus negative males (p = 0.03). In virus positive MCC there was no difference in OS between female and male patients. Conclusions: Our data confirms the positive impact of adjuvant radiotherapy on survival and illustrates the difference in outcome between female and male patients, with women having a better outcome. In the MCPyV group the tendency is that men with virus negative MCC has the worst outcome. Our findings indicate that MCPyV positive and negative MCC act as two different diseases and it also raises questions if there is a difference in the disease itself or the immune response towards MCC between male and female patients.