bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular profiling and clinical characteristic of malignant melanoma in younger patients.
Authors: Chantharasamee Jomjit , Wong Karlton , Chmielowski Bartosz 
Published: May 2020

e22087 Background: Combination of clinical and molecular data has not yet been well established in adolescent and younger adult patients with melanoma Methods: We performed a retrospective analysis of the molecular profiles and clinical outcome of patients diagnosed at the age younger than 40 treated at UCLA during 2010 to 2019. Patient’s molecular profile, characteristics, and treatment outcome were described using descriptive statistic. Kaplan-Meier curve was used for disease-free survival (DFS) and overall survival (OS). Results: 150 patients with a median age of 29 year (12-39) were analyzed. 101 (67.3%) patients had cutaneous melanoma, 49 (32.7%) had localized uveal melanoma. Of those 101, 23.8% had pre-existing benign or congenital nevus. 70/101 (69.3%) was stage I-II, 26/101 (25.7%) stage III and 5/101 (4.9%) stage IV. Of those 37 patients with molecularly characterized tissue, 23 (62%) had BRAF mutation including 17 V600E, 4 V600 unknown codon, 2 G469A, 2 NRAS and 1 NF-1 mutation. 11/37 were BRAF negative. 79.6% of patients who were not tested were stage I. For patients with stage III, 16/26 (61%) received adjuvant immunotherapy, none of adjuvant targeted therapy. At 35.1 months follow-up time, 27/96 (28%) localized cutaneous melanoma experienced relapse. 1-year DFS was 73% in adjuvant vs. 90% in no adjuvant immunotherapy group. Among 49 uveal melanoma patients, the median age was 27 years old. 23/49 (49%) had a T1 tumor, 18/49 (36.7%) T2, 6/49(12.2%) T3, 1/49(2%) T4. At 45 months follow-up time, three (6.1%) patients developed metastasis. 5-year DFS and OS was 90% and 100%, respectively. 45 patients had tissue for gene expression profiling and/or FISH testing. 15/45 (33%) had class IA, 13/45 (28%) had class IB, and 8/45 (17.7%) had class 2. 24 samples were analyzed by FISH: 14 with disomy 3, 5 with complex disomy 3 with gain of chromosome 6 or 8, and 5 with monosomy 3. Conclusions: Similarly to general population, most of younger patients with melanoma are diagnosed with stage I disease. Among patients with stage III melanoma treated with adjuvant immunotherapy 1-year DFS was comparable to the general population. Patients with stage III who did not receive adjuvant therapy had an excellent DFS which confirms that the decision on selecting patients for treatment was appropriate. The prognosis of younger patients with uveal melanoma was much better than predicted by molecular testing, and much better than expected regardless of gene expression profile or cytogenetic testing.
Rate of complete and durable responses of intralesional therapy with talimogene laherparepvec for stage IIIB-IVM1a melanoma and association with tumor load.
Authors: Stahlie Emma H.A. , Franke Viola , Zuur Charlotte L. , Klop Willem M.C. , Van Der Hiel Bernies , Van De Wiel Bart A. , Wouters Michel W.J.M. , Schrage Yvonne , van Houdt Winan J. , Van Akkooi Alexander Christopher Jonathan 
Published: May 2020

e22089 Background: Talimogene laherparepvec (T-VEC) is a genetically modified herpes simplex type 1 virus, which is used as an oncolytic immunotherapy in stage IIIB-IVM1a melanoma patients. It is known to be an effective therapy for injectable cutaneous, subcutaneous and nodal melanoma lesions, as approved by the European Medicines Agency (EMA). Combination therapy is not yet approved by EMA pending the results of the phase 3 Masterkey-265 trial. The objective of the current study was to identify prognostic factors for achieving a complete response (CR) that can be used to select patients for treatment with T-VEC monotherapy. Methods: Patients with stage IIIB-IVM1a melanoma, treated with T-VEC at the Netherlands Cancer Institute between 2016-12 and 2019-05 with a follow-up time > 6 months, were included. Data was collected on baseline characteristics, responses and adverse events (AEs). Durable response rate (DRR) was defined as the percent of patients with a CR or partial response (PR) maintained continuously > 6 months. Univariable analyses were conducted and a prediction model was developed to identify prognostic factors associated with complete response. Results: For this study, a total of 71 patients were included with a median follow-up of 16.1 months. The median age was 70 years (range: 35-90). As best response, 47 patients (66%) had a CR and 10 patients (14%) had a PR, resulting in an overall response rate of 80%. Twenty-one patients (30%) stopped treatment because of progressive disease and sixteen patients (23%) developed a recurrence during follow-up after achieving a PR or CR. Median duration of CR was 11 months. The durable response rate was 42%. Grade 1-2 AEs occurred in almost every patient. Tumor size, type of metastases, previous treatment with systemic therapy and stage (8Th AJCC) were independent prognostic factors for achieving a CR and for progression-free survival. Achieving a CR was associated with a reduced risk of death. The prediction model includes tumor size, type of metastases (only cutaneous vs. subcutaneous (+/- cutaneous) vs. nodal (+/- cutaneous/subcutaneous)) and number of lesions as predictors. Conclusions: This study shows that intralesional T-VEC monotherapy for stage IIIB-IVM1a melanoma is able to achieve high complete and durable response rates. The prediction model shows that use of T-VEC in patients with less tumor burden is associated with better outcomes, suggesting T-VEC should perhaps be used earlier in the course of the disease.
Unknown primary tumor high-risk melanoma as a unique patient population with distinct prognosis in the adjuvant setting: An ECOG-ACRIN E1609 study analysis.
Authors: Tarhini Ahmad A. , Lee Sandra J. , Hodi F. Stephen , Cohen Gary Irvin , Rao Uma , Sondak Vernon K. , Kirkwood John M. 
Published: May 2020

e22090 Background: E1609 enrolled 1670 adult patients (pts) with resected AJCC7 stages IIIB, IIIC, M1a, M1b melanoma and compared adjuvant ipilimumab at 3 or 10 mg/kg (ipi3 and ipi10) to high dose interferon-alfa (HDI). With over 5 years of follow up, the risk of relapse and death by primary tumor status and by stage group is expected to inform the design of future adjuvant trials and ultimately, clinical practice. Methods: Unknown primary melanoma status was defined as initial presentation with cutaneous, nodal or lung metastasis that was completely resected without a history of known primary melanoma. We evaluated the pt distribution by the initial site of metastasis. Further, we evaluated the risk of relapse and death by primary tumor status and by stage group. Five-year relapse-free survival (RFS) and overall survival (OS) rates and 95% CIs were estimated by Kaplan-Meier method. Stratified (by stage) log-rank test was used to compare RFS and OS by primary tumor status. Two-sided p-values were derived. Results: Unknown primary melanoma represented 12.8% of the total study population including 11.7% on the ipi arms and 14.7% on HDI. Site of metastasis at initial presentation among unknown primary cases included cutaneous and nodal (97%) and lung (3%). Among the overall study population, M1a stage group included the highest proportion of pts with unknown primary (42.2%). Stratifying by stage, RFS (p = 0.001) and OS (p = 0.009) were significantly better for pts with unknown primary compared to known primary. Including only ipi3 and ipi10 pts, RFS (p = 0.005) and OS (p = 0.023) were consistently significantly better in favor of unknown primary. Five-year RFS and OS rates by primary tumor status and stage group among pts treated with ipi (ipi3 and ipi10) are summarized in Table. Conclusions: Unknown primary status represents a unique population among high-risk melanoma pts treated with ipi with improved RFS and OS outcomes that support their separate assessment in future immunotherapy adjuvant trials. In-depth analyses of the tumor biology and host immunology are ongoing. Outcome analyses by the overall study stage groups and the HDI arm will be reported at the meeting. Clinical trial information: NCT01274338. [Table: see text]
Influence of chronic neuropathic pain on VEGFA in tumors of mice with genetically determined inhibition of tumor growth.
Authors: Frantsiyants Elena M. , Kaplieva Irina V. , Surikova Ekaterina I. , Neskubina Irina V. , Bandovkina Valeria A. , Trepitaki Lidia K. , Cheryarina Natalia D. , Nemashkalova Ludmila A. , Lesovaya Natalia S. , Pozdnyakova Viktoria V. , Przhedetskiy Yuriy V. , Khokhlova Olga V. , Przhedetskaya Viktoria Yu. , Zakharova Natalia A. , Kit Oleg I. , Ushakova Natalya D. 
Published: May 2020

e22103 Background: Chronic neuropathic pain (CNP) demonstrates the ability to stimulate tumor growth and neoangiogenesis. Our purpose was to study VEGFA levels in the growth of B16/F10 melanoma with CNP in mice with genetically determined inhibition of tumor growth. Methods: Females of С57ВL/6 mice (normal genome (uPA+), n = 26) and C57BL/6-Plautm1.1BugThisPlauGFDhu/GFDhu mice (urokinase gene knockout (uPA–), n = 16) received subcutaneous transplantation of B16/F10 melanoma 2 weeks after bilateral sciatic nerve ligation (CNP model). After 3 weeks of carcinogenesis in CNP, tumor volumes were measured and levels of VEGFA were studied in tumors by ELISA. Results: Tumor volumes in (uPA+) females with CNP in week 3 of carcinogenesis were similar to that in (uPA+) females without CNP and were on average 2.6 cm3 (2.5 and 2.8 cm3 respectively). Tumor volumes in (uPA–) females were 0.04 cm3, i.e. 70 times lower (p < 0.001) than in (uPA+) females without CNP. Tumor volumes in (uPA–) females with CNP were 144 times higher (p < 0.001) than in (uPA–) females without CNP and were 5.76 cm3. VEGFA levels in tumors of (uPA+) females with CNP were 11.1 times higher (p < 0.001) than in (uPA+) females without CNP. VEGFA in tumors of (uPA–) females with CNP was 5.2 times higher (p < 0.001) than in (uPA–) females without CNP. Conclusions: The CNP state showed higher VEGFA concentrations in tumor tissues of female mice with normal genome and uPA-deficient females (with genetically determined inhibition of tumor growth) which may cause a larger tumor volume in (uPA–) female mice.
Tanning bed exposure in association with multiple primary melanoma.
Authors: Karapetyan Lilit , Yang Xi , Wang Hong , Karunamurthy Arivarasan , Sander Cindy , Moyer Ashley , Wilson Melissa , Kirkwood John M. 
Published: May 2020

e22107 Background: Patients with primary cutaneous melanoma are at increased risk of subsequent new primary melanoma. Indoor tanning is a risk factor for melanoma. The primary objective of this study was to determine the association between indoor tanning and multiple primary melanoma (MPM). The secondary objective was to compare clinical and pathological characteristics of primary and secondary malignant melanoma. Methods: This retrospective case-control study of MPM and gender-matched controls with single primary melanoma retrieved at 2:1 ratio from the University of Pittsburgh Cancer Institute Melanoma Center Biological Sample and Nevus Bank from January 1996 through October 2019. Logistic regression models were used to examine the association between MPM and risk factors. Results: In total, 330 patients (39.1% men; median [SD] age, 51 [15] years) were enrolled, including 110 with single and 220 with MPM. Median time between diagnosis of first and second primary melanoma was 13 months. 22.7% of patients with MPM had 3 or more primary melanomas. Compared with patients who had a single primary melanoma, patients with multiple melanomas were younger at diagnosis of first melanoma (median age 46 vs 52, p = 0.006), more likely to be discovered at Stage 0 and 1 (68% vs 49%, p < 0.0001), and to have had indoor tanning exposure (34% vs 10%, p < 0.0001), family history of melanoma (18% vs 8%, p = 0.0045), atypical moles (37% vs 13%, p < 0.0001), dysplastic nevi (21% vs 5%, p < 0.0001), and Breslow thickness of less than 1 mm (61% vs 33%, p < 0.0001). Compared with the patient’s first melanoma, subsequent melanomas were more likely to be thinner (0.6mm vs 1.2mm, p = 0.0007) or in situ (24% vs 13%, p = 0.0004). The estimated probability of locus that was the same for first and second primary melanomas was 34% with (95% CI 25%, 44%). The most common location for second primary melanoma was upper extremity (34%). In univariate analysis, lifetime tanning bed exposure of > 10 sessions was associated with an increased risk of second primary melanoma OR 4.60 [95% CI, 2.52-8.42, p < 0.0001]. In multivariate analysis after adjusting for age, family history of melanoma, presence of atypical and dysplastic nevi, recreational sun exposure, indoor tanning remained significantly associated with MPM (OR 4.32 [95% CI, 1.54-12.15, p = 0.0026]). Conclusions: Indoor tanning for > 10 sessions is associated with increased risk of second primary melanoma. Subsequent melanomas are more likely to be thin or in situ, and to occur in different anatomic locations.
Acral lentiginous melanoma: Population-based analysis of incidence and survival in United States from 1993 to 2013.
Authors: Thumallapally Nishitha , Meshref Ahmed , Mousa Mohammed 
Published: May 2020

e22108 Background: Acral Lentiginous melanoma (ALM) is a rare form of cutaneous melanoma with aggressive nature. This study investigates the incidence and survival patterns in patients diagnosed with ALM in USA from 1993-2013 using data from the Surveillance, Epidemiology, and End Results (SEER) Registry. Methods: The 18 cancer registries of SEER program were used to identify patients diagnosed with ALM according to international classification of diseases for oncology (ICDO-3) codes. Age adjusted incidence rates in addition to 5 and 10-year relative survival rates were calculated. Results: 2189 patients were included in this retrospective study.The age-adjusted incidence rate of ALM was 2.11 per million person-years.Hispanic whites had highest incidence rates of ALM among all racial subgroups ( 2.58, p = 0.005). Incidence of ALM was higher between 2003-2013 compared to 1993-2003 (2.3 vs 1.9).Median age at diagnosis was 61.68 years. 53.9 % were female. Our study population was dominated by Non-Hispanic Whites (69.2%) followed by Hispanic Whites (13.5%), Blacks (8.2%), Asians or Pacific Islanders (7.3%) and other races (1.8%). stage III was the most frequent (24.7%) followed by stage I (20.9%). In terms of tumor thickness, 43.2 % presented with T3 thickness at the time of diagnosis. The ALM 5 - and 10-year survival rates were highest in age < 40, females, T1, non ulcerated, lymph node negative lesions ( p < 0.05). Among racial subgroups, non Hispanic whites had highest survival rates (83 vs 74 % ). Asian/Pacific Islanders (75.1%vs 49.8%) had lowest survival rates followed Hispanic whites ( 76.4 % vs 63.9 ) and Blacks (74.7 vs 71.5 %) ( p = 0.19). Conclusions: ALM is rare subtype of cutaneous melanoma with increased incidence in people of color. Patients present with increased tumor thickness and advanced stage at the time of diagnosis. Poor survival rates are seen among Asian/Pacific Islanders and Hispanic whites.
Feasibility of evidence-based treatment of childhood acute myeloid leukemia in a Sub-Sahara Africa center.
Authors: Nzamu Irene , Ssenyondwa Joseph , Naitala Ronald , Akullo Anne , Ankunda Siyadora , Kashaigili Heronima , Omeddo Deborah , Nakiddu Nana , Namazzi Ruth , Munube Deogratias , Kasirye Phillip , Bakulumpagi Deogratias , Naturinda Ernest , Lubega Joseph , Wasswa Peter 
Published: May 2020

e22508 Background: The proportion of Acute Myeloid Leukemia (AML) among childhood leukemias is putatively higher in Sub-Sahara Africa (SSA) compared to Western experiences. However, the treatment of childhood AML is challenging in SSA settings because of inadequate facilities for supportive care to deliver intensive AML regimens and, hence, high treatment-related mortality (TRM). Many pediatric oncology centers in SSA treat childhood AML with a palliative intent, with or without chemotherapy. At the Mulago National Referral Hospital (MNRH)/Global HOPE Center in Uganda, we treat AML with a curative intent. We distinguish Acute Promyelocytic Leukemia (APL) and AML with Down Syndrome (AML-DS) from other subtypes of AML. We treat APL with Children’s Oncology Group (COG) AAML1331 and AML-DS and other AML with modified reduced intensity regimens. We hereby share our experience of anti-cancer and supportive treatment, TRM, remission rates, and short-term overall survival (OS). Methods: We performed a retrospective cohort analysis of children diagnosed with AML between March 2019 and February 2020. The diagnosis of AML was established by bone marrow or peripheral blood morphology and immunophenotyping by flow cytometry according to WHO criteria. All cases of APL were confirmed by cytogenetics for t(15;17). Children without DS or APL received 2 cycles of Cytarabine 100mg/m2 12 hourly Days 1-10, Daunorubicin 50mg/m2 Days 1,3,5 and a single triple intrathecal chemotherapy for induction and 2 cycles of high dose Cytarabine 3000mg/m2 for consolidation. Supportive care comprised warm saline oral rinses, antiseptic baths, antimicrobial prophylaxis with cotrimoxazole, ciprofloxacin and itraconazole, and blood product support. Results: Of the 74 children diagnosed with leukemia 23 (31%) were AML; 4/23 (17%) of AML were APL and 3/23 (13%) were AML-DS. The mean age at diagnosis of AML was 6.1 (SD 4.3) years and 16/23 (70%) were males. For the 4 cases of APL, TRM 1/4 (25%) due to differentiation syndrome, remission rate 2/4 (50%), 1-year OS 75%; 95% CI 32.5-100. For the 3 cases of AML-DS, TRM 1/3 due to severe sepsis with respiratory failure, remission rate 1/3, and 1 was referred to another treatment center. For the other AML, TRM 2/16 (12.5%) due to severe sepsis, remission rate 9/16 (56%) and 1-year OS 78.6%; 95% CI 57.1-100. Conclusions: It is feasible to treat, manage TRM, and achieve remission in childhood AML in the SSA setting. Although there were several TRMs, a remission rate of 56% in the non-APL non-AML-DS is a promising outcome.
Innovations in retinoblastoma treatment and reflection to enucleation rate of 362 eyes of 262 CASES: Twenty years retrospective assessment at Ankara University.
Authors: Unal Emel Cabi , Tosun Hande , Tacyildiz Nurdan , Dincaslan Handan , Gunduz Kaan , Yavuz Kivilcim , Tanyildiz Gulsah , Yavuz Gulsan 
Published: May 2020

e22509 Background: Enucleation used as the first-line tx option for RB, dx in advanced stages. Methods: To evaluate the enucleation rates of RB cases in 20 years period, to emphasize the recent developments in the tx of RB that contribute to the improvement of tx outcomes. Results: 262 patients, with the dx of RB between June 1998 &December 2018 in Ankara University Departmant of Pediatric Oncology were evaluated retrospectively. The M / F ratio was 1.2, mean age at dx 19.39 mos; 22.7 mos for unilateral &14.1 mos for bilateral dx. 61.8% of the patients had unilateral, 38.2% bilateral RB. 362 eyes were evaluated, 12.5% of the patients had a family history of RB bilateral dx was more frequent. The initial findings were leucocori in 58%& strabismus in 27.9%, similar to the literature. According to ICRB, 6% of the patients were diagnosed in Group A, 22% in Group B, 19% in Group C, 22% in Group D and 31% in Group E. Patients with bilateral dx were diagnosed at an earlier stage. Enucleation, in 50.5% of 362 eyes analyzed. There was no enucleated eye in Group A. In group B,10.1% of the eyes were enucleated, as of recurrence. 32.3% of eyes in Group C, 60.7% of eyes in Group D and 92.9% of eyes in Group E were enucleated. Enucleation was performed in 25.4% of the eyes within the first month after dx as of the advanced stage. 33.7% of of the eyes who did not have enucleation at the time of dx required enucleation at FU. The most common causes of enucleation were tumor recurrence, total retinal detachment & vitreous hemorrhage. The tx methods other than enucleation are systemic CT, RT & local treatments; cryotherapy, thermotherapy, episcleral brachytherapy, intravitreal CT & intraarterial CT. Systemic CT applied to 77% of the patients.CT protocol were VEC and ICE.RT was applied to 17% of the patients. After 2012, radiotherapy was used only in 2 patients with systemic involvement. Cryotherapy was performed in 48.3% of the eyes, thermotherapy in 38.6%, episcleral brachytherapy in 3.8% of the eyes included.Intraarterial CT to be used after 2004 was applied to 16.6% of eyes dx & intravitreal CT was used after 2009 was applied to13.2% of eyes. Enucleation was avoided in 84.6% of eyes in which these two tx modalities were applied together. Enucleation rates of 56.3% &61.2% between 1998-2004 and 2004-2009, respectively; with active use of intraarterial and intravitreal CT, decreased to 40.2% between 2009-2018. Conclusions: It was observed that enucleation rates &RT gradually decreased with using systemic CT and local treatment methods.
Percutaneous cryoablation in pediatric solid tumors: A case series.
Authors: Hentea Cristiana , Kaufman Olaf , Rokes Christopher Alan , Woods-Swafford Wendy 
Published: May 2020

e22516 Background: Percutaneous cryoablation is an effective treatment of focal tumors. With a low complication rate it is a useful adjuvant therapy option to chemotherapy and radiation. To date there is no literature on the use of cryoablation in pediatric solid tumors. Methods: We conducted a retrospective analysis of pediatric solid tumor patients who received percutaneous cryoablation for local control of relapsed disease over the past 10 years within our institution. The following information was extracted from EMR: age, diagnosis, number of ablated lesions and tissue involved (lung, liver, bone), complications following procedure, and rate of local relapse. Results: A total of 40 metastatic lesions were treated by percutaneous cryoablation in 7 patients (ages 5-22yo, median 15yo) with a wide range of solid tumor diagnoses (Ewing sarcoma, Wilms tumor, Osteosarcoma, Germ cell tumor). Lesions represented sites of relapse or metastasis, refractory to several lines of therapy. Sites of cryoablated tumor included lung (33%), bone (32%), chest wall (10%) among others. Each patient had 2-5 separate cryoablation procedures (total 22 procedures) over the course of their therapy. 54% of instances patients were monitored overnight for pain control, with no major complications. One patient required ICU-level care due to pulmonary hemorrhage following lung cryoablation in setting of thrombocytopenia. No infectious complications. Three patients progressed and died within two years following first cryoablation intervention (diagnoses of Ewings and Wilms). Of the remaining four patients, control at the ablation site was achieved with median follow-up of 17 months (range 8-43). Conclusions: Percutaneous cryoablation is a safe and durable approach for local control of solid tumors in children. We present the first pediatric case series detailing response to percutaneous cryoablation.