bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Development and validation of targeted treatments for the rare tumor syndrome infantile myofibromatosis.
Authors: Chen Ying , Das Srirupa , Pandya Deep , Billaud Jean-Noel , Reva Anna , Roth Annabel , Dottino Peter Remsen , Hakonarson Hakon , Martignetti John
Published: May 2020

e22519

Background: Infantile myofibromatosis (IMF; MIM 228550) is an autosomal dominant disorder characterized by fibroblastic tumors of skin, muscles, viscera and bones. Tumor growth may begin during fetal development, where it may lead to early death, and/or can be present throughout adult life. We originally demonstrated that mutations in the platelet-derived growth factor receptor beta gene (PDGFRb) result in IMF. Currently, beyond surgical removal and chemotherapy, there is no effective treatment. Using an integrated genomic, bioinformatic and functional approach based on analysis of patient-derived IMF cells and mouse models, encapsulating multiple IMF-causing PDGFRb mutations, we sought to identify potentially druggable targets and validate them in preclinical models. Methods: Patient samples were genetically characterized by whole exome (WES) and RNA sequencing. Patient-derived cell lines from tumor and adjacent normal tissue (PDCL) were generated from a patient with a novel F864L mutation. This IMF-causing mutation along with two others, R561C and P660T, were stably expressed in BAF3 cells for functional characterization. PDCL-F864L were used to generate an orthotopic mouse IMF model. Results: WES of paired patient tumor, PDCL and germline samples confirmed a novel germline PDGFRb mutation (c.2590T > C, Phe864Leu). Using PDCL, the F864L mutation was shown to result in constitutive PDGFRb activation. Based on these findings, the tyrosine kinase inhibitors Imatinib and Sunitinib were chosen as candidate therapies. As predicted, they markedly inhibited cell proliferation and blocked PDGFRb activation and downstream signaling molecules AKT and ERK. Similar results were obtained in F864L, R561C and P660T mutant expressing BAF3 (natively PDGFRb null) cells when compared to WT PDGFRb expressing controls. Having established these findings using cultured cells, the effects of Imatinib and Sunitinib were next tested on an orthotopic mouse model. Given to IMF tumor mice as a single drug, both drugs markedly and sustainably decreased tumor size compared to control mice. Conclusions: Our findings demonstrate that IMF-associated PDGFRb mutations are gain-of-function mutations. Using patient-derived IMF models, Imatinib and Sunitinib effectively target these GOF mutations through PDGFRb signaling pathway inhibition. These findings provide preclinical data for targeted treatment of this rare cancer.
Primary care utilization and barriers among pediatric cancer and bone marrow transplant survivors.
Authors: Lipak Keagan , Gerhardt Cynthia , Olshefski Randal S. , Bajwa Rajinder , Skeens Micah
Published: May 2020

e22523

Background: The Institute of Medicine (IOM) report on childhood cancer survivorship specified the need to create and evaluate standards and alternative models of care delivery, including collaborative practices between oncologists and primary care physicians (PCP).1 We aimed to examine the utilization of primary care physicians by childhood cancer and bone marrow transplant (BMT) survivors, as well as identify barriers to non-oncology follow-up care. Methods: Survivors and caregivers were recruited from a cancer and bone marrow transplant survivorship clinic at a large Midwestern pediatric hospital. Participants completed a demographic survey and an 8-item semi-structured interview in clinic or online. Results: A total of 472 participants (211 survivors, 259 caregivers, 2 left unanswered) completed the survey (Survivors Mage= 26.11, SD= 7.32). Most participants were Caucasian (89%) and female (58%). Only 57 (12.3%) survivors received a BMT. There were no significant differences in PCP utilization between BMT survivors and those who did not receive a BMT, t(448) = -.519, p = .604. In addition, there were no significant group differences in PCP utilization between oncological and hematologic survivors, t(387) = 1.144, p = .253. Most survivors (87%) had a PCP, but 43% sought care for ill visits only. Survivors most commonly chose their PCP through referral from family or friends (45%), with only 4% obtaining a recommendation from their oncology provider. Top reasons for not having a PCP included being unsure who to see (52%), lack of insurance (20%), and not perceiving a need for a PCP (18%). In a logistic regression, greater annual family income ( β= .209, p< .001) and having health insurance ( β= .161, p< .01) were predictive of having a PCP. The frequency of PCP visits was also positively correlated with annual family income ( r= .13, p= .014). Conclusions: While most survivors had a PCP, higher income and insurance coverage were important predictors of having a PCP. There is a clear need for education and formal transition programs to primary care, as survivors and their family identified the need for guidance in choosing a PCP. Stronger partnerships between oncology and primary care providers may improve surveillance and outcomes for these survivors. 1. Blaauwbrock R, Zwart, N., Bouma, M., Meyboom-de Jung, B., Kamps, W., & A. Postma. The willingness of general practitioners to be involved in the follow up of adult survivors of childhood cancer. Journal of Cancer Survivors. 2007;1:292-297.
Longitudinal evaluation of alanine aminotransferase after treatment for childhood cancer. A report from the St. Jude Lifetime Cohort Study.
Authors: Green Daniel M. , Wang Mingjuan , Krasin Matthew J. , Srivastava Deokumar , Relling Mary V. , Howell Carrie R. , Ness Kirsten K. , Kaste Sue C. , Greene William , Jay Dennis W. , Davidoff Andrew M. , Pui Ching-Hon , Jeha Sima , Bishop Michael William , Furman Wayne Lee , Robison Leslie L. , Hudson Melissa M.
Published: May 2020

e22525

Background: Many childhood cancer survivors have been exposed to hepatotoxic agents. We assessed longitudinal hepatic injury, using alanine aminotransferase (ALT) elevation, and associated factors in a large cohort of long-term survivors. Methods: We evaluated SJLIFE participants ( > 10 years post-diagnosis, age ≥18 years) who had two or more determinations of ALT (T1 baseline, T2 last evaluation). Elevated ALT was defined as ALT > Upper Limit of Normal (ULN, 30 IU/mL for males and 19 IU/mL for females). Elastic net was used to perform model selection for elevated ALT at T2. Modified Poisson regression was used to identify risk factors for elevated ALT at T2. Results: Serial ALT assessments were available for 1941 survivors (49.6% female, 82.2% non-Hispanic white [NHW]). Their median age at diagnosis and T1 were 7.6 years (interquartile range [IQR] = 3.4-13.5) and 31.7 years (IQR = 26.1-38.1), respectively. Elapsed time from diagnosis to T1, and T1 to T2, were 23.3 years (IQR = 17.8-29.6) and 5.2 years (IQR = 4.4-5.7). ALT was normal at T1 and T2 in 45.7%, and persistently (25.9%) or newly (11.7%) abnormal in 37.6%. Compared to those with normal ALT at T1, those with elevated ALT at T2 were more likely to have NHW race/ethnicity, treatment with busulfan, increasing volume of the liver exposed to 10 Gray (Gy) or more (V10), body mass index (BMI) > 25 kg/m2, hepatitis C, metabolic syndrome, or treatment with atorvastatin, rosuvastatin or simvastatin at T2. History of hematopoietic stem cell transplantation (HSCT), but not busulfan, were additional risk factors included in the models for V15 and V20 (Table). Conclusions: Demographic, treatment, lifestyle, and non-oncologic interventions increase the risk for ALT elevation in survivors. These results may guide future treatment designs and lifestyle interventions. [Table: see text]
Prevalence of childhood growth hormone deficiency in survivors of pediatric intracranial germ cell tumors.
Authors: Lone Diana , Sadak Karim Thomas , Miller Bradley S , Roesler Michelle , Poynter Jenny N
Published: May 2020

e22526

Background: Survival rates for childhood cancer continue to rise, and there are now greater than 420,000 survivors in the United States. However, high cure rates come at the cost of short and long-term treatment-related toxicities. Endocrine disorders are among the most common late effects and are associated with poor health outcomes and lower quality of life. Survivors of pediatric intracranial germ cell tumors (iGCTs) are at high risk for endocrine disorders, particularly for growth hormone deficiency (GHD), due to their exposures to cranial radiation, chemotherapy, and brain surgery. To date, no long-term follow-up studies have explored the late effects experienced by survivors of iGCTs. Methods: Study participants were enrolled in the Germ Cell Tumor Epidemiology Study, which is a case-parent triad study conducted using the resources of the Children’s Oncology Group’s Childhood Cancer Research Network. Eligibility criteria included diagnosis with a germ cell tumor in any location at age 0-19 years in the years 2008-2015. The study population included 233 cases with a diagnosis of iGCT. We are currently following the cohort to evaluate outcomes and late effects of treatment, including medical record review to extract data on treatment characteristics and hormone deficiencies. This interim analysis includes chart review for 57 iGCT cases. Results: Of the 57 cases reviewed, there was a male predominance (73.7%) with the highest prevalence in non-Hispanic whites (80.4%). Cases of iGCTs can be subdivided into two main histologic subtypes, germinomas (36 cases) and non-germinomatous GCTs (NGGCT, 21 cases). The median age at diagnosis was 14.6 years for the germinomas and 10.5 years for NGGCTs. Data on growth hormone deficiency (GHD) was available for 42 of the 57 cases with a median follow-up of 7.4 years. Twenty-eight of the 42 cases (66.7%) had GHD; 19 in the germinoma group and 9 in the NGGCT group (p = 0.47). 17 of those with GHD were males (p = 0.10). There was no significant difference in prevalence of GHD by age of tumor diagnosis (p = 0.20). Conclusions: Survivors of iGCTs are at high risk for growth hormone deficiency. Identifying specific risk factors for developing GHD amongst these survivors can enhance the current guidelines for screening and management.
lncRNA, PVT-1, controls tumorigenesis and cancer stem-like phenotypes in osteosarcoma through PI3K/TSC2.
Authors: Tsang Susan , Rainusso Nino Carlo , Yustein Jason Todd
Published: May 2020

e23512

Background: Osteosarcoma is the most common pediatric bone cancer and a key genetic characteristic of this particular malignancy is its complex karyotype. Specifically it has been reported that 40% of osteosarcoma patients’ present with 8q24 amplification. The presence of this specific amplification has been previously associated with a high rate of relapse and poor prognosis for osteosarcoma patients. Within this amplicon resides, a long non-coding RNA gene, PVT-1. Prior studies indicates that PVT-1 has pro-oncogenic properties however the function of PVT-1 in osteosarcoma is not well characterized. Methods: To understand PVT-1 copy number, Fluorescent In Situ Hybridization was performed on both osteosarcoma cell lines and osteosarcoma patient-derived xenografts. In addition the PVT-1 RNA level is elevated in a majority of osteosarcoma samples compared to normal bone. To test PVT-1 pro-oncogenic role in osteosarcoma, several functional assays were performed. Results: Our studies demonstrated that overexpression of PVT-1 in osteosarcoma cell lines promotes multiple tumorigenic behaviors including enhanced proliferation, migration, invasion and chemotherapeutic resistance to cisplatin. PVT-1’s ability to mediate metastasis and contribute to chemotherapeutic sensitivity is a shared phenotype of cancer stem cells. Based on this observation, we hypothesize targeting PVT-1 will reduce cancer stem-cell properties. Osteosarcoma lines with increased levels of PVT-1 exhibited higher expression of cancer stem cell genes: Nanog, SOX2, c-Myc, and Oct4 at both the transcriptomic and proteomic level. In Vitro and In Vivo self-renewal capacity studies showed enhanced osteosarcoma cell self-renewal in the PVT-1 overexpression cohort. Additional molecular studies were performed in order to gain additional insights into potential mechanism of action for PVT-1 including Reverse Phase Protein Array. Initial analysis suggest a role for PVT-1 in regulating the PI3K-AKT-TSC2 pathway. Conclusions: This suggests a potential oncogenic pathway in which PVT-1 enhances cancer stem cell phenotypes. On-going investigations are addressing potential PI3K/TSC2 pathway inhibitors, BEZ-2335 and LY3023414, which could be utilized to regulate PVT-1 mediated tumorigenic roles and cancer stem-like properties.
Zinc finger E-box-binding homeobox 1 (ZEB1): A novel predictor for the prognosis in gastrointestinal tumors.
Authors: Yang Shenglan , Min Jiang
Published: May 2020

e23515

Background: The gastrointestinal stromal tumors (GISTs) are the most common soft tissue sarcoma arising anywhere along gastrointestinal tract. The advanced and metastatic GISTs are the leading cause in GISTs inducing death. GISTs are the most commonly resulted from KIT or PDGFRA activation mutation. Currently adjuvant therapy with imatinib also targets the KIT and PDGFRA signals, which significantly increases the relapse-free survival and overall survival. However, KIT and PDGFRA mutation are not completely responsible for the progression of disease, especially metastasis of GISTs. So, there could be other molecular mechanism in GISTs progression. ZEB1 (zinc finger E-box-binding homeobox 1), as a member in zinc finger and homeodomain transcriptional factor family, plays a key role in metastasis of some epithelial carcinomas, such as colorectal cancer, breast cancer and NSCLC. We present that ZEB1, as a vital molecular in epithelial-mesenchymal transition, could be a promising marker in predicting the prognosis in GISTs. Methods: Immunohistochemistry staining for paraffin-embedding slices from 157 patients firstly diagnosed as GIST is applied for detecting the ZEB1 expression. Clinical, pathological, molecular and survival time were analyzed. All performances were approved by the Medical Ethics Committee in the First Affiliated Hospital of Chongqing Medical University. Results: In 157 patients, metastasis was found in 87 patients. In 87 patients with metastasis, high expression of ZEB1 almost exhibited (80 high/96 VS 7 non or low/96), while non or low expression was frequently detected in patients without metastasis (50 non or low/70 VS 20 high/70) (p < 0.0001). There was no significant difference between high and non/low expression patients in gender (48% VS 46% for male rate; 52% VS 54% for female rate), age (53 vs 54 years for median age), primary location (esophagus 2% VS 1.8%; stomach 57% VS 52.6%; duodenum and small intestine 31% VS 31.6%; colorectum and anus 10% VS 14.0%), tumor size (0.5-24cm, median 9.7cm VS 1-25.5cm, median 10.1cm), mitotic index (55.0% VS 58.6% for > 5/50HPF; 45.0% VS 41.4% for ≤5/50HPF), and risk stratification (low/intermediate risk 60.7% VS 63%; high risk 39.3% VS 37%). In addition, the 5-year OS rate was considerably lower in patients with ZEB1 high expression than those with ZEB1 none or low expression at baseline (37% vs 86%; p = 0.011). Conclusions: High expression of ZEB1 facilitates metastasis and indicates the poor prognosis in GISTs. ZEB1 could be a novel predictor for GIST’s prognosis.
Radiomic features for patients with primary soft tissue sarcomas: A prognostic study.
Authors: Pasquali Sandro , Bologna Marco , Infante Gabriele , Vigorito Raffaella , Messina Antonella , Morosi Carlo , Miceli Rosalba , Greco Gabriella , Casale Alessandra , Corino Valentina , Barretta Francesco , Mainardi Luca , Palassini Elena , Sanfilippo Roberta , Stacchiotti Silvia , Casali Paolo Giovanni , Callegaro Dario , Gronchi Alessandro
Published: May 2020

e23532

Background: Prognosis of extremity soft tissue sarcomas (ESTS) and retroperitoneal sarcomas (RPS) is currently estimated on clinical-pathological features, as those incorporated in the Sarculator nomogram. This study investigated the added value of end-point specific radiomic signatures (RS) in patients with primary ESTS and RPS. Methods: We retrospectively analysed data from patients with a ESTS (N = 100) or a RPS (N = 116) who underwent surgery (Jan2011-Dec2015) at one sarcoma reference institute and had magnetic resonance imaging (MRI) or computed tomography (CT) scan, respectively. Radiomic features were extracted from DICOM files of MRI and CT scan for ESTS and RPS, respectively. The study end-points were incidence of distant metastases (DM) and overall survival (OS) for ESTS and disease-free survival (DFS) and OS for RPS. A RS was established for each end-point. Models discriminative ability was measured using the Harrell c-index (C). Results: ESTS histology was undifferentiated pleomorphic sarcoma, myxofibrosarcoma, myxoid liposarcoma, dedifferentiated/pleomorphic liposarcoma, and others in 28, 21, 18, 9, and 24 patients, respectively. At a median follow-up of 61 months, the 5-yr DM-free rate and OS were 73.6% (95%CI 64.2-82.2%) and 73.4% (95%CI 64.5-83.6), respectively. A prognostic model based on the Sarculator and a DM-RS achieved higher C (0.86, 95%CI 0.77-0.93) than the Sarculator alone (0.83, 95%CI 0.71-0.94). For OS, the RS was not able to increase the Sarculator discriminative ability (Sarculator and OS-RS: C = 0.73, 95%CI 0.62-0.82; Sarculator alone: C = 0.72, 95%CI 0.62-0.81). RPS histology was well differentiated liposarcoma, dedifferentiated liposarcoma, leiomyosarcoma, and other in 22 (19%), 60 (52%), 22 (19%), and 12 (10%) patients, respectively. At a median follow-up of 58 months, 5-yr DFS and OS were 46.7% (95%CI, 37.8-57.6%) and 68% (95% CI 59.9-79.0%), respectively. RS extracted from CT scan without contrast enhancement slightly improve the discriminative ability of the Sarculator for DFS (Sarculator and DFS-RS: C = 0.65, 95%CI 0.57-0-72; Sarculator alone: C = 0.63, 95%CI 0.55-0.70) but not for OS (0.70, 95%CI 0.60-0.80 and 0.69, 95%CI 0.59-0.79, respectively). Conclusions: RS did not improve the discriminative ability of the Sarculator for OS. The added value for RS in relapse prediction (DM incidence for ESTS and DFS for RPS) deserves further investigations.
Phase II trial using haploidentical hematopoietic cell transplantation (HCT) followed by donor natural killer (NK) cell infusion and sirolimus maintenance for patients with high-risk solid tumors.
Authors: Thakar Monica S. , Browning Meghen , Hari Parameswaran , Charlson John A. , Margolis David A. , Logan Brent , Schloemer Nathan , Kelly Michael E. , Newman Amy , Johnson Bryon , Keever-Taylor Carolyn Anne , Malarkannan Subramaniam
Published: May 2020

e23551

Background: Patients with relapsed solid tumors have dismal predicted OS < 10-20% at 5 years with conventional salvage therapies. We hypothesized that a multi-faceted immunotherapy approach to optimize graft-versus-tumor (GVT) effects, in combination with a mammalian target of rapamycin (mTOR) inhibitor maintenance strategy, would enhance early disease-control rates (DCR), leading to improved progression-free survival (PFS) and OS for this high-risk population. Methods: Treatment consisted of HLA-haploidentical marrow (n = 12) or peripheral blood stem cell (n = 3) transplantation to optimize GVT effects, preceded by reduced-intensity conditioning (fludarabine, cyclophosphamide, and 3 Gy total body irradiation) to promote engraftment of these mismatched stem cells. Haplo-NK cells were given to boost this GVT effect. They were purified from non-mobilized donor mononuclear cells by CD3 depletion followed by CD56 selection using the Miltenyi CliniMACS system and were infused fresh on day +7 after HCT. Postgrafting immunosuppression included sirolimus maintenance, which continued until 6 months post-HCT. Results: Fifteen patients with relapsed Ewing sarcoma (EWS) (n = 9), rhabdomyosarcoma (n = 4), osteosarcoma (n = 1), and medulloblastoma (n = 1) having stable or undetectable gross disease were enrolled on this Phase II trial. Median age at HCT was 19 (4.5-37) years old and median performance status was 80%. Four patients underwent prior autologous transplants. Patients received a median NK dose of 6.5 (3.7-11.4) x 106/kg. NK cell products had a median log T cell depletion of 5.94 (5.18-6.75), median NK recovery of 62% (48-71%), and median NK purity of 92% (74%-97%). All donor NK infusions were well-tolerated without cytokine release syndrome. All patients engrafted, and all had sustained full donor chimerism ( > 95% CD3). Two patients developed grade II acute graft-versus-host disease (GVHD), and 2 patients developed chronic GVHD. No patients died from transplant-related causes. With a median follow-up of 1.3 years (range, 70 days – 5 years), 6-month DCR is 72%. 1- and 2-year OS for the entire cohort is estimated at 64% and 40%, respectively, while PFS is 29% and 22%, respectively. For patients with EWS,1- and 2- year -OS is estimated at 75% and 45%, and PFS is 38% and 25%, respectively. Conclusions: This dual immunotherapy approach followed by mTOR inhibition maintenance was well-tolerated, with better than expected OS for this high-risk set of diseases. Clinical trial information: NCT02100891 .
Prognostic and predictive factors for the outcomes of clear cell sarcoma (CCS) multidisciplinary treatment: The role of lymph node involvement.
Authors: Teterycz Pawel , Czarnecka Anna Malgorzata , Szmajdzinska Aleksandra , Kalejta Magdalena , Spalek Mateusz , Rosinska Magdalena , Poleszczuk Jan , Switaj Tomasz , Zdzienicki Marcin , Falkowski Slawomir , Rutkowski Piotr
Published: May 2020

e23554

Background: CCS is a rare aggressive sarcoma with melanocytic differentiation and specific genetic background of EWSR1/ATF1 or EWSR1/CREB1 translocations. It typically localizes in the tendons, fascia, and aponeuroses. The role of lymph node dissection (LND) remains to be elucidated in this sarcoma, although it was indicated to have a high rate of clinically occult regional lymph node (LN) metastases. Methods: 23 consecutive patients (pts) (15 women and 8 men) were referred, diagnosed and underwent multidisciplinary treatment in our Institute between 07/2000 and 12/2019. Kaplan-Meier estimator was used in survival analysis and univariate Cox proportional hazard model was used to investigate prognostic and predictive factors. Cases for whom local relapsed were not noted or those not known to be dead were censored at last visit. OS was compared for nodal involvement, including both: clinically detected and treated with therapeutic LND and microscopic metastases evaluated in sentinel LN biopsy (SLNB). Local relapse and radiotherapy were analyzed. Results: The median age at diagnosis was 32y (range:20-72). The median tumor size was 3.5cm (2-15cm). 15 pts underwent surgery of the primary tumor and 8 - resection of local relapse after non-complete resection outside the reference center. In 11 cases SNLB was performed, while in 7 – therapeutic LND. SLNB was positive in 2 (18%) cases and was followed by completion LND. For pts treated due to primary tumor, R0 resection was achieved in 12 cases and R1 in 3. After median follow-up of 65.6 months (m) (95% confidence interval, CI 55.3–NR) 11 (48%) pts are alive. Median OS was 59m (95%CI: 39-NR). Clinically detectable LN were correlated with shorter DFS (HR: 6.6, 95%CI: 1.5-28.8, p = 0.01). The number of involved LN also correlated with DFS (HR 1.7 per 1 LN; 95%CI:1.1-2.6, p = 0.009). No such correlations were found for OS. 5-year LRFS rate was 72.5% (95%CI: 53.8-97.7). 15 pts underwent neoadjuvant radiotherapy and for these pts 5-year LRFS rate was 75.0% (95%CI: 50.3-100). There was no statistical difference for LRFS if radiation therapy was not applied, which may be due to the number of pts. Conclusions: CCS is a highly aggressive sarcoma with poor prognosis. High quality surgery remains the gold standard for these pts, with the increasing role of SLNB and LND. Multimodal treatment should be considered in all cases. There is unmet need for new therapies for advanced CCS pts.
Prevalence of delay to seeking medical attention in patients with synovial sarcoma and association with inferior outcomes.
Authors: Seto Tiffany , Song Meena , Russell Elisabeth , Sam Danny , Pan Minggui
Published: May 2020

e23556

Background: Synovial sarcoma is an aggressive soft tissue sarcoma that predominantly affects young patients with high rate of relapse and mortality. Systemic study of patients’ presenting symptoms and possible delay of seeking medical attention is lacking. Methods: We retrospectively reviewed the electronic records of all patients diagnosed with synovial sarcoma from 2005 to 2016 within Kaiser Permanente Northern California to identify the pattern of presenting symptoms and its correlation with outcomes. Results: Of the 77 patients with synovial sarcoma, 64 had early stage disease and 13 had metastatic disease at diagnosis, with median age at diagnosis of 47 years. Anatomically, 48 patients had primary disease at the extremity, 12 trunk, and 17 visceral. Median duration of follow up is 40 months. The median time from symptom to first medical appointment (TTM) is 3 months (range 0.1 to 180 months). Nine out of 13 patients who presented with metastatic disease were visceral primary. For the 60 patients with an extremity/trunk primary, patients who presented with pain without a palpable mass had a median duration of TTM of 12 months, compared to the TTM of 3 months for patients who presented with a palpable mass. The relapse rate (RR) and disease-free survival (DFS) for patients with an extremity/trunk primary who presented with pain but without a palpable mass were significantly worse when compared to patients who presented with a palpable mass (RR 50% vs. 26.5%, and DFS 27 vs. 42.5 months, p < 0.005). TTM was inversely correlated with DFS for the 64 cases with early stage disease and for the 60 cases with extremity/trunk primary (p < 0.00000001). Of the 11 patients with a foot primary, a similar pattern of TTM and DFS was also observed. Conclusions: Patients with synovial sarcoma who presented with pain but without a palpable mass had longer TTM, worse DFS and higher RR compared to patients who presented with a palpable mass. Longer TTM was associated with worse DFS.
Utility of immune checkpoint inhibitors (ICI) in 3 patients (pts) with sarcomas of antigen presenting cells (follicular dendritic cell sarcoma [FDCS], histiocytic sarcoma [HS]).
Authors: Lee Mee-young , Bernabe Ramirez Carolina , Ramirez Daniel C. , Maki Robert G.
Published: May 2020

e23574

Background: FDCS and HS are rare tumors arising from sustentacular cells of the lymph node, rather than lymphocytes. Surgical resection is often employed in case of localized disease, but for unresectable disease, anthracycline-based therapy is commonly used. PD-L1 staining is reportedly positive in 50-80% of FDCS. As a result, we treated 3 patients (pts) with ICI ipilimumab and nivolumab (Ipi/Nivo), and demonstrated the activity of these agents in these rare cancers. Methods: Two FDCS pts and one HS pt, all with B symptoms at the start of treatment, received Ipi/Nivo in the approved dose/schedule (Table). The HS patient was HIV(+) with undetectable viral load on treatment. One FDCS patient received radiation therapy to an active site of disease during immunotherapy. We reimaged patients every 2 months for the first 6 months, then less frequently. PDL-1 IHC and mutation data were available in all cases. Results: Mutation burden varied from low to intermediate; mutations in kinase genes were also observed. Case 1 (FDCS) demonstrated RECIST 1.1 complete response, but also received radiation, and Case 2 (FDCS) had RECIST partial response. Both continue on treatment 9 months after initiation. Case 3 (HS) demonstrated a minor response to treatment, then disease worsened after 4 months, and he subsequently received radiation to the residual site of disease. All patients showed resolution of B symptoms on ICI. Conclusions: We treated these pts with ICI based on their role as antigen presenting cells, as well as their high PD-L1 expression. We speculate that FDCS and related tumors such as HS represent extreme examples of cancers that have evidence of tertiary lymphoid structures, increasingly recognized as important in ICI responsiveness. Prospective clinical trials of ICI in these diagnoses will help us understand the basis of immune responses to ICI in other cancers. [Table: see text]
Evaluation of patient and healthcare provider (HCP) knowledge, attitudes, and behavior for safety and use of pexidartinib.
Authors: Salas Maribel , Julian Michele , Drogaris Leonidas , Islam Zahidul , Henderson Mackenzie , Stemhagen Annette , O'Donnell Natalie , Tu Nora
Published: May 2020

e23580

Background: Pexidartinib, a kinase inhibitor, is approved for treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Due to risk of serious and potentially fatal liver injury, pexidartinib is available via a Risk Evaluation and Mitigation Strategy (REMS) Program. A requirement of the REMS is to conduct a qualitative evaluation of stakeholder Knowledge, Attitudes, and Behavior (KAB) of risks via surveys. The objective of the qualitative evaluation is to review key risk message questions with respect to understanding, relevance, clarity and provide recommendations on alternative language, phrasing, and structure. Methods: Anonymized, one-on-one 45–60-min phone interviews with patients and HCPs were conducted by UBC. Patients ≥18 y, diagnosed with TGCT (prioritized) or metastasis/sarcoma of the connective tissue, with different levels of education and fluent reading/speaking English were included. To participate, HCPs were required to treat patients with TGCT (prioritized) or metastasis/sarcoma of the connective tissue, treat patients ≥75% of their time, and clearly read/speak English. Participants were required to complete an Interview Release Form (IRF) and confirm access to a computer/tablet. Participants had little/no familiarity with pexidartinib materials. All interviews followed a standard process, used a pre-scripted guide on general instructions, confidentiality, safety event reporting, rapport building and assessment of health literacy (patients only). Feedback regarding understanding, relevance, and clarity were used to recommend potential alternate language/phrasing. To receive compensation participants were required to execute/return the IRF. Results: Twelve patients were interviewed, majority 67% had TGCT; mean age 52 y; 58% female; 42% reported some college/associates degree. 12 HCPs were interviewed, 67% treated patients with TGCT; 100% male; mean years practicing 22; all spent 75% or more time seeing patients; primary specialty Orthopedics. Areas of confusion/misunderstanding were reported, and questions were then revised. Patient findings: complexity and wordiness; HCP findings: repetition/difficulty reading, and some terminology was not self-explanatory. Conclusions: Feedback from HCPs and patients was received to improve the key risk messages of the KAB. Qualitative research is recommended to improve comprehension and data quality collected.
Analysis of hospice duration and metrics in cancer patients in rural Appalachia.
Authors: Manthri Sukesh , Mansurov Alay , Brooks Bill , Singal Sakshi , Jaishankar Devapiran
Published: May 2020

e24006

Background: Several factors influence the duration of hospice care/average length of stay (ALOS) for cancer patients choosing hospice, including patient and family acceptance of hospice, availability of services, demographics, provider preferences, advances in treatment options, and type of cancer. Cancer diagnoses account for 30.1 % of Medicare hospice beneficiaries. Based on the national hospice and palliative care organization (NHPCO) summary released in 2019 the median length of stay on hospice for cancer patients is 19 days. The purpose of this study is to analyze the length of stay on hospice, and other metrics in a rural Appalachian community given the paucity of published data. Methods: A retrospective chart review (IRB approved) of all adult patients enrolled in three different hospice agencies (total 106) over two years (2016 and 2017) in a rural community in Southern Appalachia. We looked at the interval from metastatic diagnosis to hospice admission, interval from last oncological treatment to hospice admission and length of stay on hospice. Results: Medianinterval from metastatic diagnosis to hospice admission was 143 days (range 6-2948 days). The median interval from the last oncological treatment to hospice admission was 35 days (interquartile range 15-83 days). The median length of stay on hospice was 24 days (interquartile range 7.5 to 52.5 days). ALOS for patients with prostate, colorectal, breast and lung cancer were 77.33, 103.8 (skewed by a single patient-741 days, minus outlier-33 days), 38.9, 31.70 days, respectively. Conclusions: Few studies in the past have focused on the length of stay on hospice and even fewer have analyzed metrics as noted in our study. The median duration of hospice care in this community (24 days) was modestly better than the national data (19 days). This study provides unique data on median interval from the last treatment to hospice admission (35 days) is longer than the time on hospice (24 days). We infer socio cultural barriers to hospice acceptance in the Appalachian community and a need for education. It may be invaluable to assess if similar barriers to acceptance of hospice are a factor in other communities and would be worthy of further study and research.
Patient factors associated with changes in functional status during systemic cancer therapy in older adults: A systematic review.
Authors: Lam Vivian , Loh Kah Poh , Webber Katey R , Padam Simran , Sedrak Mina S. , Musinipally Vivek , Grogan Madison , Presley Carolyn J , Grandi Janice , Sanapala Chandrika , Digiovanni Grace , Castillo Daniel , Walter Louise Christie , Wong Melisa L.
Published: May 2020

e24022

Background: Maintaining function and preventing functional decline during cancer treatment is critically important to older adults. This systematic review characterized and identified patient factors associated with functional change during systemic cancer therapy in older adults. Methods: Following PRISMA guidelines, we searched PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials for articles examining changes in function during systemic cancer treatment published in English through 1/11/19. Studies were eligible if they included adults age >65 and analyzed associations between patient factors and change in function. At least two independent investigators reviewed each article with discrepancies resolved by consensus. Major findings were summarized; no meta-analysis was planned a priori given the heterogeneity in studies. Results: We screened 15,244 titles/abstracts and 519 full texts. The final analysis included 69 studies, which enrolled > 11,000 patients with cancer. Most studies enrolled adults of all ages; 20% included only adults age >65 and 13% only adults age >70. A quarter of studies enrolled patients with lung cancer while 22% included all solid tumors and hematologic malignancies. The majority of studies evaluated function during chemotherapy (96%) with 9% including targeted therapy and 4% immunotherapy. Function was primarily measured with patient-reported outcomes (93% of studies). Reporting of functional change was heterogeneous with many reporting change scores or means at multiple time points. Among studies that reported the percentage of patients who developed functional decline, results ranged widely from 6% to 90%. Functional improvement occurred among 2% to 57% of patients. The most common patient factors associated with functional decline during systemic cancer therapy were older age (n = 8 studies), fatigue (n = 8), worse baseline performance status (n = 8) and physical activity (n = 5), and anemia (n = 5). Only 10 studies examined factors associated with functional recovery, identifying 12 unique patient factors. Conclusions: Among older adults with cancer, functional changes during systemic cancer therapy are common. Interventions to target modifiable patient factors associated with functional decline are needed to help patients maintain or improve function during treatment. Additionally, evaluating both functional decline and improvement is necessary to better characterize functional trajectories during systemic cancer therapy.