bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world economic burden of rapid disease progression (RDP) in patients (pts) with advanced/metastatic non-small cell lung cancer (aNSCLC).
Authors: Byfield Stacey DaCosta , Molife Cliff , Batus Marta , Winfree Katherine B. , White John C , Cui Zhanglin Lin , Lal Lincy S. , Stefaniak Victoria Jennifer , Bonomi Philip D.
Published: March 2020

e20716

Background: RDP on initial therapy imposes significant clinical burden among pts with aNSCLC. This retrospective claims study provides estimates of the economic burden associated with RDP during subsequent therapy following RDP v non-RDP on platinum-based (Pt) therapy. Methods: Adult Medicare Advantage or commercially insured aNSCLC pts receiving a subsequent line of therapy (LOT) from 03/2015 to 08/2017 after initial Pt therapy were identified in the Optum Research Database and assigned to unmatched RDP & non-RDP cohorts based on Pt treatment duration (≤ 12 and > 12 weeks, respectively) as a surrogate. All-cause healthcare costs were inflation adjusted to 2017 US$ and computed as per patient per month (PPPM) during the subsequent LOT. Total costs were the sum of medical (inpatient, ambulatory, ER, and other costs) and outpatient pharmacy costs. Results: Patient characteristics were similar between RDP (n = 751) and non-RDP (n = 1,304) cohorts, with mean age of 68 years for the total study sample (n = 2,055). Overall, nivolumab was the most common subsequent regimen post Pt; 40% of the total study sample. While duration of subsequent LOTs was shorter for RDP pts (Kaplan-Meier median, 167 v 192 days and log rank test P = 0.03), mean systemic therapy drug costs were similar ($10,516 v $9,642, P = 0.14) during the LOT and PPPM total costs for RDP pts were $4,103 higher than those for non-RDP pts, driven by higher PPPM costs for inpatient stays and ambulatory visits (Table). Conclusions: This study sheds light on the significant economic burden of aNSCLC that rapidly progresses, and may inform management strategies to improve outcomes and lower downstream costs for RDP pts. Future research should continue to explore unmet needs for RDP pts, including underlying cost drivers, to provide context for the rapidly changing aNSCLC treatment landscape.[Table: see text]
Sedation practices in pediatric ALL patients.
Authors: Nugent Bethany D. , Davis Peter J. , Noll Robert , Tersak Jean M.
Published: March 2020

e21500

Background: The 5-year survival rate for pediatric acute lymphoblastic leukemia (ALL) is greater than 90%. A common late effect of pediatric ALL is neurocognitive deficits, such as lower IQ. In recent years, the use of sedation during lumbar punctures (LPs) for treatment of pediatric ALL is becoming increasingly widespread. These patients are exposed to repeated doses of sedatives. Among the most common Children’s Oncology Group (COG) ALL protocols, approximately 30 LPs are performed over a period of 2-3 years. Studies in animals (both rodents and primates) have revealed that common sedation drugs cause harm to the developing brain and can negatively affect behavior, learning, and memory. Gaps in knowledge exist regarding their use in children, particularly with repeated exposures. For children with ALL, little is known about sedation practices such as how commonly sedation is used; what medications are most common; and who administers the medications. The purpose of this study is to summarize sedation practices at COG institutions for LPs related to treatment of pediatric ALL. Methods: All Responsible Investigators (RIs) of the Cancer Control Committee (a subcommittee of COG) were invited to complete an internet-based survey about sedation practices for ALL patients at their institution. Results: Surveys were sent out to 103 RIs with a 62.1% response rate ( N = 64). A combined 2018 new patients with ALL were seen each year ( M = 31.5, range = 3-110); of these patients, 95.7% received sedation for LPs. While there was considerable variability across institutions in medications used (general anesthesia, Propofol with opioid and/or Versed, Versed and opioid, other), the most common was Propofol alone ( n = 36, 56.3%). Anesthesiologists administered sedation at the majority of institutions ( n = 36, 56.3%) while trained sedationists, oncologists, and nurses administered sedation at other institutions. Conclusions: A substantial number of pediatric patients with ALL receive sedation for LPs. However, there is much variation in the types of medications administered and who is administering these medications. Better understanding of sedation practices in children with ALL may inform future research to investigate which methods of sedation are safest, with a particular emphasis on its long-term effects.
High concentration of plasma cell free DNA alerted progressive and recurrent disease in children with high risk neuroblastoma.
Authors: Su Yan , Wang Lijun , Jiang Chiyi , Yue Zhixia , Hongjun Fan , Hong Huimin , Duan Chao , Jin Mei , Zhang Dawei , Qiu Lihua , Cheng Xianfeng , Xu Zhong , Ma Xiaoli
Published: March 2020

e21506

Background: Neuroblastoma (NB) happens most frequently among babies and it is also the third-most common cancer in children after leukemia and brain tumor. The unexpected occurrence of NB progression and relapse accounts for the low survival free event rates, therefore finding an effective biomarker to predict the progressive and recurrent events is urgent. Methods: A total of 116 NB patients with high risk (HR-NB) from Beijing Children’s Hospital between February 1, 2015 and December 31, 2017 were recruited. All patients received the regular multiple-disciplinary treatments and then followed the evaluation for therapeutic response according to the standards of Response Evaluation Criteria in Solid Tumors (RECIST). Blood samples were collected to quantify cell-free DNA levels at important time points including one week before or the beginning of maintenance stage, every or every three month after the beginning of maintenance stage, diagnosis of progression and recurrence. Results: Results showed that 36 HR-NB patients developed progressive disease (PD) and recurrent disease. More intriguingly, cfDNA concentration was extremely higher in NB patients with progression and recurrence than those with events free (29.34 ng/ml VS 10.32 ng/ml), and increasing cfDNA levels happened at least 0.55 months before the progression and recurrence was confirmed. By analyzing the area under the receiver operator characteristic (ROC) curve (AUC), it showed that the area of cfDNA level was 0.67 at 12.93 ng/ml with 62.5% sensitivity and 71.3% specificity. Conclusions: Taken together, it was suggested increasing cfDNA concentration in plasma may benefit to warn the incurrence of progression and recurrence in NB patients in clinic, which will help clinicians win much more valuable time to save patients’ lives.
Mortality and survival rates in children and adolescents enrolled in early phase trials with a dose-finding/dose-confirmation component: An innovative therapies for children with cancer (ITCC) study.
Authors: Carceller Fernando , Bautista Francisco , Castañeda Alicia , Surun Aurore , Wasti Ajla , Revon-Riviere Gabriel , Cortes Marta , Bergamaschi Luca , Juan Ribelles Antonio , Millen Gerard , Campbell Hewson Quentin , Amoroso Loredana , Van der Lugt Jasper , Fagioli Franca , Zwaan Michel , Marshall Lynley V , Vassal Gilles , Pearson Andrew DJ , Geoerger Birgit , Moreno Lucas
Published: March 2020

e21509

Background: Participation of children with advanced solid cancers in phase I trials raises ethical and logistic dilemmas. Life-expectancy beyond 8-12 weeks is a common inclusion criterion, but it can be difficult to gauge. This multicentric European study assessed the mortality and survival rates in pediatric phase I trials. Methods: Retrospective study of patients aged < 18 years with solid tumors enrolled in phase I trials in ITCC centres between 2015-2017. Outcome variables were described and prognostic factors analysed. Results: 256 patients across 12 centres in 5 countries were eligible. Median age 11.8 years (range, 0.5-17.9). Female:Male ratio 1:1.9. Tumor location: central nervous system (CNS) 66% vs extra-CNS 34%. Main diagnoses: 22% soft tissue sarcomas, 13% high grade gliomas, 11% osteosarcomas. Most frequent therapy: single targeted agent (63%). Ten cases (4%) were not evaluable for response and 128 (50%) had progressive disease at first evaluation. Best responses were complete in 12 cases (5%), partial in 29 (11%) and stable disease in 77 (30%). Median follow-up 7 months (range, 0.5-42.4). Median Time On Study (TOS) 2.1 months (range, 0.2-38.1). The 30 and 90-day mortality on trial were 3% (8/256) and 21% (54/256), respectively. The 90-day survival (95%CI) for patients with CNS vs extra-CNS tumors was 88% (78-93) vs 76% (68-82), respectively. One-year Overall Survival (95%CI) for the whole sample was 40% (33-46). No toxic deaths on trial were reported. Twenty-five cases (10%) survived ≥365 days on trial. Median TOS 21.5 months (range, 12.3-38.1). Compared to patients who died within 365 days from Cycle1-Day1, those on trial ≥365 days had lower rates of metastatic disease (74% vs 28%, respectively, p < 0.001), higher objective response rates (13% vs 44%, respectively, p < 0.001) and higher disease stabilization (27% vs 56%, respectively, p < 0.001). Conclusions: Currently few patients die within the first cycle of treatment. However a fifth of all patients died within 3 months from trial initiation. Patients with CNS tumors have comparable survival rates to those with extra-CNS and should not be excluded from phase I trials solely because of their diagnosis. The survival rates beyond one year remain modest.
The evaluation of long term follow-up (LTFU) of children with osteosarcoma: The first report from a center in a developing country.
Authors: Tacyildiz Nurdan , Unal Emel Cabi , Dincaslan Handan , cakmak Tokuc Mine , Oktay Tanyildiz Gulsah , Kartal Omer , Yildiz Yusuf , Basarir Kerem , Yavuz Gulsan
Published: March 2020

e21512

Background: The increased survival rate of childhood cancers resulted in long term side effects (LTSE). The aim was to investigate LTSE in our osteosarcoma survivors and compare the quality of life (QOL criteria with their own siblings as a developing country experience with no National LTFU guideline yet . Methods: At Ankara University Department of Pediatric Oncology 54 osteosarcoma pts have been followed between 2003- 2019 . Rate of heart, kidney disease, hearing difficulty, neurological problems, Life style parameters like; smoking, alcohol consumption, marital status, parenthood, education, the use of health care services and pain status of the 39 survivors were compared with their siblings (n = 77). Amputated and non-amputated groups were compared for QOL. Information obtained retrospectively from the patient charts, and phone calls. Kaplan-Meier, Chi-square, independent sample t-test were used. Results: The age and gender ratios were similar in the groups. The 16-year overall survival rate (OSR) was 72.4%. Patients with the poor risk criteria were in the Euramos MAP + IE regimen with 71.4% OSR ; 94.1%, in the low risk patients in Euramos MAP (p = 0.023) and 50.0% in the previous HDMTX regimens (p = 0.012). The rates of kidney (p = 0.045), heart disease (p < 0.001), neurological problems (p = 0.045), use of health care services (p < 0.001), limitations of physical function (p < 0.001) and pain (p = 0.002) were significantly higher in the survivors than siblings. The physical functions were normal in 76 siblings (98.7%) and in 14 of the survivors (35.9%) (p < 0.001). Being married (p = 0.001), having parenthood (p < 0.001), educated (p = 0.014) and employed (p < 0.001) were significantly higher in the siblings than in the survivors. The rates of hearing problems, smoking, alcohol consumption and psychiatric problems were similar in both groups. Secondary malignancy (1 leukemia, 1 bone tumor) was detected in two survivors while no cancer was found in the control group. The OS was 55.6% and 75.6% respectively in patients with amputation and with no amputation with no significant difference in the QOL (p = 0.424). Conclusions: Heart, neurological and kidney disease, physical dysfunction, and pain rates were significantly higher in survivors of osteosarcoma than their siblings in almost 2 decades. The social status (marriage, parenthood, education) of the survivors was also found to be markedly affected negatively. As we planned, development of risk-based LTFU guidelines are required to increase QOL during LTFU of these patients in our country.
Tumor molecular profiling in advanced pediatric brain tumors.
Authors: Basu Gargi D. , Natarajan Thanemozhi G , Szelinger Szabolcs , Bair Candyce M , White Tracey , LoBello Janine R , Garinger Nathan , Kurdoglu Ahmet , Royce Thomas
Published: March 2020

e21516

Background: With the advent of high-throughput molecular profiling, clinical outcome in pediatric cancers has greatly improved due to our greater understanding of genetic origin of pediatric cancer, and availability of biomarker specific treatment options. However, pediatric brain tumors continue to be challenging in terms of therapy. The goal of this study was to evaluate the utility of integrative clinical sequencing in pediatric patients with brain tumors. Methods: Targeted exome sequencing of 562 genes in paired tumor-normal DNA was performed on 14 patients and tumor DNA and RNA was sequenced on additional 4 patients. Sequence analysis identified SNVs, indels, copy number events, fusions, alternate transcripts, breakpoints, TMB and MSI status. Clinically, actionable alterations were identified which could be targeted by FDA approved agents or clinical trials. Results: A total of 18 patients (1-17 y.o.) with low grade (n = 5) and high grade (n = 13) brain tumors were profiled. The cohort consisted of a spectrum of GBMs (45%), medulloblastomas (10%) astrocytomas (22%), and other brain tumors (23%). At least one targetable, driver alteration was identified in 83% of all patients, and 92% of high-grade patients had at least one targetable driver event. Targetable mutations were identified in histone and chromatin modifier genes like H3F3A in 3/18 cases (17%), SETD2, ARID1A, PBRM1 in 2/18 cases (11%), activation of PI3K/AKT/mTOR pathway genes in 6/18 cases (33%), DNA repair genes NBN, ATRX and BRCA2 in 3/18 cases (17%); BRAF V600E in 3 high-grade and a KIAA1549/BRAF fusion in a low-grade tumor, activation of cell cycle in 2/18 cases (11%), activation of FGFR pathway with FGFR1/TACC1 fusion and activating mutation in 2/18 cases (11%), activation of PDGFRA in 2/18 samples (11%), TP53 mutations in 4/18 cases (22%). A breakpoint translocation concurrent with LOH of PTCH1 locus was noted in a medulloblastoma patient. High TMB or MSI instability was not observed. Conclusions: Our results underline the importance of clinical sequencing in identifying targetable markers in high- risk brain tumors. Although limited by small sample size, our study highlights the need for ongoing clinical trials to integrate the genomic discoveries leading to better clinical outcomes.
Serum biomarkers for detection of cardiomyopathy in survivors of childhood cancer: A report from the St. Jude Lifetime Cohort.
Authors: Dixon Stephanie , Howell Carrie R. , Lu Lu , Ness Kirsten K. , Plana Juan , Joshi Vijaya , Luepker Russell V , Durand Jean-Bernard , Ky Bonnie , Lenihan Daniel John , Green Daniel M. , Partin, MS Robyn , Santucci Aimee , Howell Rebecca M. , Srivastava Deokumar , Hudson Melissa M. , Robison Leslie L. , Armstrong Gregory T.
Published: March 2020

e21526

Background: Childhood cancer survivors are at increased risk for cardiovascular morbidity and mortality. Little is known about the utility of cardiac biomarkers (NT-proBNP, cardiac troponin-T [TnT]) for long-term surveillance. Methods: Cross-sectional analyses of 1213 survivors ≥18 years of age and ≥10 years from cancer diagnosis (786 exposed to cardiotoxic therapy [174 radiation therapy (RT) alone, 366 anthracycline alone, 246 both] and 427 unexposed). TnT > 0.01 ng/ml and NT-proBNP levels > 97.5th percentile age- and sex-specific cutoffs were considered abnormal. Three-dimensional left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), diastolic function and cardiomyopathy (CM) according to the CTCAE v4.03 were evaluated. Generalized linear models estimated risk ratios (RR) and 95% confidence intervals (CI). Results: Among survivors (median 8.7 [range 0.0-23.6] years at diagnosis; 35.5 [range 19.1-62.2] years at evaluation), NT-proBNP and TnT were abnormal in 22.5% and 0.4%, respectively. A dose-dependent increased risk for abnormal NT-proBNP was seen with exposure to chest RT (referent no RT, 1- < 20 Gy RR 1.62 [CI 1.07-2.46], 20- < 30 Gy RR 1.68 [1.23-2.30], ≥30 Gy RR 3.66 [2.89-4.64]; p for trend < 0.0001) and anthracycline (referent no anthracycline, 1-200mg/m2 RR 1.39 [1.01-1.91], 201-350mg/m2 RR 2.28 [1.74-2.99], > 350mg/m2 RR 2.99 [2.27-3.95]; p for trend < 0.0001). Survivors with CM at the time of evaluation had abnormal NT-proBNP (grade 2 CM RR 1.46, CI 1.08-1.99; grade 3-4 CM 2.66, 2.02-2.39). However, among exposed survivors previously undiagnosed with clinical CM, NT-proBNP had poor sensitivity and moderate specificity in identifying those with new onset of abnormal LVEF ( < 53%), GLS or diastolic dysfunction: sensitivity (29%, 30%, 33%), specificity (75%, 77%, 76%). Also, 132 (20.2%) had abnormal NT-proBNP with normal LVEF (≥53%). Conclusions: Abnormal NT-proBNP levels were prevalent and associated with prior cardiotoxic therapy and established CM but were not sensitive for detection of new onset CM. Longitudinal follow-up is needed to determine whether abnormal NT-proBNP in the large number of survivors without CM is predictive of future CM.
A pilot study of sleep-related breathing disorders and hypersomnia in adult survivors of childhood Hodgkin lymphoma treated with thoracic radiation.
Authors: Mandrell Belinda Neal , Lewis William , Ogg Susan , Wise Merrill , Mulrooney Daniel A. , Robison Leslie L. , Hudson Melissa M. , Krull Kevin R.
Published: March 2020

e21527

Background: Survivors of childhood Hodgkin lymphoma (HL) often report fatigue and daytime sleepiness. The presence of sleep disorders, such as obstructive sleep apnea (OSA), could further increase cardiovascular and cerebrovascular morbidity and mortality in these patients. The purpose of this pilot study was to assess for the presence of sleep-related breathing disorders and hypersomnia in adult survivors of childhood HL treated with thoracic radiation. Methods: Survivors, ≥18 years of age and ≥10 years from diagnosis, were randomly selected from the St. Jude Lifetime Cohort (SJLIFE) study and assessed with nocturnal polysomnography (PSG) and the multiple sleep latency test (MSLT). Enrollment was stratified by body mass index (BMI) to include an equal number of normal weight and overweight/obese survivors. Survivors with a history of neurotoxicity related to cancer therapies, and neurological, genetic, or neurodevelopmental conditions associated with neurocognitive impairment were excluded. Results: Thirty adult survivors of childhood HL (60% male; 73% white; mean age 35.8 years [range,19.9-52.8]; BMI 28.6 [range, 18.2-43.5]) enrolled, and 14 (47%) met PSG criteria for mild or moderate OSA (OSA; apnea-hypopnea index 5-30). Of those with OSA, 11 had concurrent hypersomnia using the MSLT criteria and 3 of these 11 met diagnostic criteria for narcolepsy. Twelve (40%) had hypersomnia without OSA and 3 of these 12 met diagnostic criteria for narcolepsy. Within the cohort, 86% had objective evidence of OSA and/or hypersomnia/narcolepsy. Conclusions: Findings suggest adult survivors of childhood HL may be at increased risk for OSA, which when concurrent with treatment-related cardiopulmonary and cerebrovascular risk may further increase morbidity and mortality. Future studies are warranted to compare the prevalence of OSA in this population with a matched community control group and examine whether and how the mechanism for OSA might differ from that in the general population.
Ultrasound versus physical exam to screen for secondary thyroid cancer among high-risk childhood cancer survivors.
Authors: Hess Jennifer , Walsh Alexandra Maria , Newbern Dorothee , Schafernak Kristian , Vern-Gross Tamara , Foote Janet
Published: March 2020

e21528

Background: Thyroid cancer is a common secondary malignancy among childhood cancer survivors who have received radiation to the head, neck and/or upper thorax. The optimal strategy for surveillance for thyroid carcinoma in childhood cancer survivors remains controversial. Current Children’s Oncology Group recommendations are limited to physical exam. The objective of this study was to determine the sensitivity and specificity of thyroid ultrasound versus neck exam by a pediatric endocrinologist in the diagnoses of thyroid cancer in a cohort of high-risk childhood cancer survivors. Methods: Medical records of childhood cancer survivors who received radiotherapy to the head, neck and/or upper thorax were reviewed. These patients were seen in a comprehensive childhood cancer survivorship clinic from 01/01/2010 to 12/31/2017. Patient populations included oncology, bone marrow transplant and brain tumor patients. Results: 226 patients received radiation to the head, neck and/or upper thorax. Of those, 129 patients were male (57%). Sixteen (7.1%) of patients developed a secondary thyroid malignancy including 4 patients previously treated for an oncological malignancy, 9 patients treated with bone marrow transplantation, and 3 patients with a CNS malignancy. Median radiation dose was 1800 cGy (range 400-5940 cGy). Time to thyroid carcinoma diagnosis occurred at a median of 12 years (range 4-19 years) from treatment with radiation. Screening ultrasounds were obtained in 146 (65%) patients while 226 (100%) had a physical exam. Two cases were identified by abnormalities on physical exam. The sensitivity of US was 100% (CI 80.6-100) compared to a sensitivity of 12.5% (CI 3.5-36) using physical exam (P < 0.0001). Screening ultrasound had a specificity of 73% (CI 65.1-80.1) while physical exam yielded a specificity of 100% (CI 98.2-100). Conclusions: Regular screening with ultrasounds provide the greatest sensitivity for detection of secondary thyroid carcinomas after head, neck and upper thorax radiation in childhood cancer survivors. If screening ultrasounds were not routinely utilized in our clinic, 14 of the 16 patients (87.5%) would have had a delay in their diagnosis of a secondary thyroid malignancy. Screening ultrasounds may lead to earlier detection of thyroid carcinomas, with the potential to decrease the need for aggressive surgery, radioiodine therapy and, ultimately, to decrease recurrence risk.
Peripheral-blood stem cell transplantation in pediatric recipients in Peru: Experience of a reference center.
Authors: Maradiegue Essy , Sulca-Huamani Oliver Guillermo , Quincho-Lopez Alvaro Jesus , Meza Kelly Jasmin , Vasquez Liliana , Garcia Juan Luis , Chavez Sharon , Ugaz Cecilia , Montoya Jacqueline , Ordoñez Katy , Diaz Coronado Rosdali Yesenia , Zapata Arturo , Morales Roxana , Reaño Romulo , Hernandez Broncano Eddy
Published: March 2020

e21530

Background: Stem cell transplantation (SCT) is a curative treatment for children with refractory/relapsed malignancies. However, data on pediatric transplantation in developing countries like Peru is still needed. The aim of this study was to describe and assess the survival and complications of children with neoplastic disease who have received peripheral-blood stem cell transplantation (PBSCT) at a reference center in Peru. Methods: A retrospective longitudinal study was performed by reviewing medical histories of 20 children (≤14 years) with neoplastic disease who underwent related allo- or auto-PBSCT from October 2014 to December 2017 of INEN (Instituto Nacional de Enfermedades Neoplásicas). In the cases of ALL > 3 years, radiotherapy was not part of the conditioning regimen. The Kaplan-Meier method was used to determine the overall survival (OS) and event-free survival (EFS). Data were analyzed using Stata/MP 14.0. Results: We found 13 males and 7 females with a median age of 9.5 years (1-14), of whom 18 received allo-SCT and 2 auto-SCT. Diagnosis: 14 ALL(66.6%), 1 AML(4.7%), 1 NHL(4.7%), 2 biphenotypic leukemia(9.5%), 1 juvenile chronic myelomonocytic leukemia(4.7%) and 1 germ cell tumor(4.7%) who performed two auto-transplants. Complete remission (CR) was achieved before transplantation in 19 cases: 8(38%) 1CR; 8(38%) 2CR and 3(14.2%) 3CR. A median of 7.14x106CD34+/kg (3.97-13.05) (auto- vs allo-; 6.35 vs 7.27) were collected and median time to myeloid engrafment: 11 days. At a median follow-up of 12 months (1-39) the 2-year OS and EFS were 75.7% (95% confidence interval [CI], 38-92%) and 51.6% (95% CI, 22-74%) respectively. Considering only ALL > 3 years, OS and EFS were 51.9% and 45.1%, respectively. Acute graft-versus-host disease (GVHD), chronic GVHD, transplantation-related mortality (TRM) and relapse were 27.7%, 11.1%, 4.7%, and 33.3%, respectively. Conclusions: We are encouraged by this first experience in our country. OS and EFS are comparable with results at the international level. However, survival of children with ALL > 3 years who did not receive radiotherapy is less than international standards. Studies with a higher number of cases and longer follow-up time are needed to reach definitive conclusions.
Current practices and attitudes in menstrual management in adolescents with cancer: A national survey of pediatric oncology providers.
Authors: Close Allison , Jones Kelley , Landowski Allison , Switzer Galen E , Miller Elizabeth , Friehling Erika
Published: March 2020

e21533

Background: Adolescents and young adult (AYA) females with cancer are at risk of heavy menstrual bleeding (HMB) due to thrombocytopenia, coagulopathy, and/or disruption of the hypothalamic-pituitary-gonadal axis. Options for temporary menstrual suppression (MS) include combined oral contraceptives (OCPs), progestin-only therapy, GnRH agonists, and intrauterine devices. Currently, little is known about current practices to help prevent and treat HMB in AYA women with cancer. Methods: We conducted a national cross-sectional internet-based survey of providers from 100 pediatric oncology centers. Institutions were randomly selected to allow for even representation by program size and geography. Face and content validity were assessed prior to distribution. Descriptive statistics were used to analyze respondent characteristics, attitudes, and practices for managing menstrual suppression. Chi-squared test or Fischer’s Exact test (for small cell sizes across groups) were used for analysis of categorical data. Kruskal-Wallis one-way ANOVA tests were used to compare means. Results: The majority of respondents (94%) have recommended preventative MS. MS in pediatric oncology patients is most often managed by oncology (61%) versus gynecology (22%) or adolescent medicine (12%). Greater than 50% of respondents agreed that patients with the following types of cancer should receive preventative MS: sarcomas, acute leukemias, lymphomas, and germ cell tumors. GnRH agonists were the most preferred method of MS (52%). Most respondents agreed that it is important to consider MS (94%), and that a formal guideline about initiation of MS would be helpful (95%). Less than half (46%) of participants felt comfortable personally managing MS. Conclusions: The vast majority of pediatric oncologists have used preventative MS, most commonly GnRH agonists, and feel that it is important to consider in the majority of AYA cancers. Although pediatric oncologists are most often managing MS, they do not feel comfortable doing so and desire guidelines to help with management.
Parental insights into phase I pediatric oncology clinical trials: Findings from a phenomenological study.
Authors: Crane Stacey , Croop James , Lee Jill Lunsford , Walski Jamie , Haase Joan
Published: March 2020

e21534

Background: Phase I clinical trials (P1Ts) are an essential step in the validation of novel therapies to treat childhood cancer. Children with cancer participate in P1Ts when no known curative therapy remains for their cancer. It is important to understand the experiences of children with advanced cancer and their families in P1Ts to ensure that participation supports the participants well-being. Methods: An empirical phenomenology study, using an adapted Colaizzi method, was conducted of 11 parents lived experiences of their childs participation in pediatric oncology P1Ts. Parents were recruited from two pediatric academic medical centers in the Midwest United States and from national childhood cancer groups not affiliated with either medical center. Parents participated in individual interviews (mean length 59.1 minutes), with one broad data-generating question. Demographics and the childs clinical trial records provided additional context for understanding the experiences. This presentation describes the study themes identified that were specifically related to pediatric oncology P1T processes and logistics. Results: Parents experiences during the P1Ts were primarily positive. However, data analysis revealed five aspects of P1T participation that were problematic for parents to varying degrees. These aspects were: (1) Learning About Clinical Trials, (2) Being Referred to Another Institution, (3) Undergoing Research-Only Procedures, (4) Complying with the Trial Requirements, and (5) Taking Oral Medications. Conclusions: While overall experiences during P1T participation were positive, improvements can be made that could potentially enhance participants experiences. In particular, enhancing the education provided to participants during on-trial processes and minimizing the logistical burdens associated with P1T requirements may help to address problematic aspects of P1Ts.
Efficacy and safety of anlotinib in advanced soft tissue sarcoma: results from one of multi-centers in a phase IIB trial (ALTER0203).
Authors: Tang Lina , Wang Yonggang , Zhang Jianjun , Yu Wenxi , Huang Yujing , Yao Yang
Published: March 2020

e22518

Background: There is no standard therapy for soft tissue sarcoma (STS) patients progressing after first-line chemotherapy. Anlotinib significantly prolonged PFS in advanced STS patients in the earlier results of ALTER0203. In view of regional differences, we further analysis results from Affiliated Sixth People’s Hospital, Shanghai Jiaotong University, one center in this IIB trial. Methods: Patients aged from 18 to 70 with advanced STS, progressing after anthracycline-based chemotherapy (not adapted to alveolar soft part sarcoma (ASPS) and clear cell sarcoma (CSC)), angiogenesis inhibitor naive, at least one measurable lesion according to RECIST 1.1, were eligible. Patients were randomised in a 2:1 ratio to receive anlotinib (12 mg per day 2 weeks on and 1 week off) or placebo. Primary endpoint was progression free survival (PFS). Secondary endpoints were overall response rate (ORR), disease control rate (DCR). Results: This center of ALTER0203 enrolled 48 eligible patients who received either anlotinib (n = 32) or placebo (n = 16). Leiomyosarcoma (LMS) (13/48), ASPS (12/48), synovial sarcoma (SS) (11/48) were major subtypes. The median PFS was 1.57 months (95% CI: 1.19-1.95) for placebo versus 6.27 months (95% CI: 1.89-10.65) for anlotinib ( P= 0.009). ORR was 0% (0/16) for placebo versus 18.75% (6/32) for anlotinib ( P= 0.16); DCR was 18.75% (3/16) for placebo versus 56.25% (18/32) for anlotinib ( P= 0.02). The most common adverse events (AEs) were hypertension, elevated TSH, hypertriglyceridaemia (HTG). The most common Grade ≥3 AEs were menstrual disorder, hypertension, gamma glutamyl transferase (GGT) elevation and lipase elevation. Conclusions: The efficacy and safety of anlotinib is further confirmed in advanced STS patients regarding regional differences. Clinical trial information: NCT02449343. [Table: see text]
The phase Ib result of the safety and efficacy of lenvatinib (lenv) plus eribulin (eri) in advanced adipocytic sarcoma (LPS) and leiomyosarcoma (LMS): LEADER study (NCT03526679).
Authors: Chen Tom Wei-Wu , Hong Ruey-Long , Yen Chueh-Chuan , Chen San-Chi , Guo Jhe-Cyuan , Hsu Meng-Chi , Kung Ting-Fang
Published: March 2020

e22524

Background: Eri, although approved for advanced LPS, has limited activity in terms of tumor shrinkage. Anti-angiogenic agents have shown to increase tumor response in certain cancer types. This study aims to understand the safety, optimal dose, and efficacy of the combination of lenv, a multi-kinase anti-angiogenic inhibitor, and eri in LMS and LPS. Methods: Advanced LMS and LPS with no more than 2 lines of systemic chemotherapy were eligible. The starting dose was lenv 18mg/day daily and eri 1.1mg/m2 D1, D8 in a 21-day cycle. The primary endpoint of the phase Ib part was to assess the dose-limiting toxicity (DLT) in the first 21 days and to determine the recommended phase II dose (RP2D). A rule-based (≤ 33% DLT in first 6 pts) design was implemented in the phase Ib part. Results: From 2018 Jul 24 to 2019 Jan 8, a total of 6 pts (4 LMS, 1 dedifferentiated LPS, 1 myxoid LPS) were enrolled. The median age was 56 (range 30-70), female: male 3:3. Only 1 pt had a DLT, which was < 75% of the planned dosage. Within all (27) cycles, common grade (gr) 3 or higher adverse events (AE) included hypertension (HTN, n = 4), hand-foot syndrome (HFS, n = 3), and neutropenia (n = 4). However, 4 pts had late-onset gr3 or multiple coexisting gr2 AEs that necessitated dose reduction(s) (dr) for lenv (7 dr) or eri (2 dr) after the DLT assessment period (see table). The median time to 14 mg/day, 10mg/day of lenv, and eri 0.7mg/m2 was 22, 28 (after starting lenv 14mg/day), and 69 days, respectively. In terms of preliminary anti-tumor activity, 5 (83%) pts had target lesion shrinkage and 2 (33%) reached PR (1 confirmed) as best response according to RECIST 1.1. Conclusions: Late-onset AEs after cycle 1 leading to dose reduction was notable for lenv + eri and the RP2D was thus determined at a lower starting dose of lenv 14mg/day and eri 1.1mg/m2. The preliminary tumor response was also promising. Efficacy and safety of lenv + eri for LMS and LPS will continue to be explored in phase II study. Clinical trial information: NCT03526679. [Table: see text]
Outcomes of advanced angiosarcoma and hemangioendothelioma on propranolol based regimens from sarcoma medical oncology clinic in North India.
Authors: G Naresh , Rastogi Sameer , Barwad Adarsh , Dhamija Ekta , van Houdt Winan J. , Steeghs Neeltje , Panday Rambha , Aggarwal Aditi , Garg Rakesh
Published: March 2020

e22539

Background: Angiosarcoma is an extremely rare subtype of soft tissue sarcoma with a dismal prognosis. The response rate with current standard treatment is low and new approaches are needed. Propranolol is a well-known, generic ß-blocker that has recently been approved for the treatment of a benign vascular tumor, hemangioma, with high response rates. Several preclinical studies and case reports suggest that propranolol could also be repurposed to treat malignant vascular tumors like angiosarcoma. Methods: All patients with advanced or unresectable angiosarcoma and hemangioendothelioma that were treated in the Sarcoma medical oncology clinic in North India from January 2016 to August 2018 were included. Patients were treated with 40 mg BID propranolol with or without chemotherapy or targeted agents. Results: Eight patients with angiosarcoma or hemangioendothelioma were treated with propranolol in combination with pazopanib, methotrexate and vinblastine or methotrexate monotherapy. The median follow up period was 15 months, response rates were 14%. Median PFS was not reached, but the 10 months PFS was 60%. Median OS was not reached, but the 10 months OS was 80%. Conclusions: Treatment of angiosarcoma or hemangioendothelioma patients with propranolol in combination with chemotherapy or targeted therapy shows promising results in terms of survival albeit with relatively low response rates .To determine the exact place of propranolol in the treatment of angiosarcoma, more patients need to be treated, the efficacy of propranolol as monotherapy needs to be evaluated and the role of β-adrenergic receptor as a predictive biomarker needs to be clarified further. Additionally, different combination partners should be tested to determine the optimal backbone for the combination therapy with propranolol.
Desmoid tumor (DT) management in dedicated sarcoma medical oncology clinic in a developing country: Lessons learnt.
Authors: Rastogi Sameer , Aggarwal Aditi , Dhamija Ekta , Barwad Adarsh , Panday Rambha , Khan Shah Alam , Sampat kumar Venkat , Shishak Sorun , Kumar C Santosh , Deo Svs , Manasa Parisa , Kapoor Rashi , Kumar Pankaj
Published: March 2020

e22541

Background: There is lack of data about desmoid tumors from India except case reports. It is not known how these patients are dealt with outside tertiary care centres who lack expertise. Methods: We retrospectively analysed all patients of DT from a prospectively maintained database who were referred to AIIMS Sarcoma Medical Oncology Clinic from January 2016 till 2019. Results: There were total of 56 patients with male: female ratio of 3:4. Median age was 26 (3-57) years. Extremity was most common site (57%) and median tumour size was 12 (range 3-20) cm. One patient (1.8%) had FAP and 1 (1.8%) had multifocal disease. A total of 27 patients received first treatment outside our institute and was primary surgery in all (100%). However, of the remaining 29 patients who primarily presented to us, surgery was done only in 3 (10%) because of patients choice and pelvic location. Five patients were kept under observation and all are doing well. Tamoxifen with celecoxib was most common first line therapy in 80% (40/50) with other options being sorafenib (6/50) and chemotherapy (4/50). Chemotherapy was used in abdomen (3/4) and head neck (1/4) primary patients. Menstrual irregularities including amenorrhoea was most common toxicity in 33% (13/40) with tamoxifen combination and a cause of concern in this cohort of young females leading to discontinuation of therapy inspite of SD in 54% (7/13) patients. Second line therapy was started in 20 patients with sorafenib being most common (13/20), others being chemotherapy (4/20), tamoxifen combination (2/20) and imatinib (1/20). Of all 19 patients on sorafenib, 10 (53%) experienced Hand Foot Syndrome. None discontinued sorafenib due to HFS. After median follow up of 15 months, median progression free survival (PFS) with first line was 29 months (11-46) and with second line it was not reached. There have been three deaths till date (5.3%), all were non-extremity primaries. Conclusions: In Indian setup, majority of patients presenting outside tertiary care centre undergo surgery as the first line therapy without any inclusion of medical therapy. This might be attributed to lack of awareness about medical therapy and natural trajectory of disease. Tamoxifen though was a commonly used option, led to toxicity which is of concern in young Indian patients leading to discontinuation. Sorafenib is well tolerable except HFS but longer follow up is needed for efficacy analysis.
Molecular characterization and management of secondary resistance to serial TRK inhibitors.
Authors: Nathenson Michael , Hemming Matthew Louis , Malik Karan , Lin Jia-Ren , Santagata Sandro , Du Ziming , Marino-Enriquez Adrian , Hagan Timothy J , Chipashvili Otari , Thornton Katherine Anne , Raut Chandrajit P. , Childs Barrett H. , Bertagnolli Monica M. , Sicinska Ewa , Ku Nora , Demetri George D.
Published: March 2020

e22547

Background: TRK inhibitor drugs such as the highly selective larotrectinib (Laro), have proven highly effective in malignancies harboring fusions of NTRK1, 2, or 3. Resistance in patients (pts) with progressive disease (PD) after response to initial TRK inhibitor therapy has been attributed to secondary mutations in the solvent front or gatekeeper domains of the NTRK fusion gene. LOXO-195 (L195) is a 2nd generation TRK inhibitor that overcomes these mutations. Mechanisms of resistance to L195 have not yet been well characterized. Methods: We analyzed molecular mechanisms of resistance in one adult pt with undifferentiated pleomorphic sarcoma (UPS) who had serial responses and PD on Laro and L195. Targeted DNA sequencing, RNA sequencing and multicolor cyclic immunofluorescence (CyCIF) were performed on pre- and post-PD specimens on both drugs. Results: The patient was enrolled on the phase 2 clinical trial of Laro (NCT02576431) with TPM3-NTRK1 fusion UPS. Multifocal PD and resistance to Laro developed after major objective response RECIST -74.9%, of 10 months (mo); the resistant tumor harbored both the initial TPM3-NTRK1 fusion but also evolved a new solvent front mutation in NTRK1 [c.1783G > A (p.G595R)]. A single pt protocol (NCT03206931) was designed to treat with L195. After an initial response to L195, PD limited to 2 sites developed; both sites were resected at 5 and 10 mo. The pt continues on L195 with systemic disease control 20 mo after initiation (in total 30 mo since Laro initiation). Analysis of tumor samples pre- and post-PD on L195 identified the emergence of a KRAS G12V mutation, with associated activation of the KRAS signaling pathway and a significant infiltration by inflammatory cells. A cell line and pt-derived xenografts (PDX), all harboring the initial TPM3-NTRK1 fusion, were generated from this pt. Conclusions: Resection of oligoclonal PD and continuation of L195 post-PD can be an effective treatment strategy. Oncogenic activation of the KRAS pathway is a possible mechanism of resistance to L195. Our studies indicate that the tumor microenvironment of TRK-fusion sarcomas resistant to TRK inhibitors may increase inflammatory cell infiltrates, which may provide clues for future combination therapy.
Clinical features and prognosis of patients with liposarcoma: Single-center experience.
Authors: Demir Metin , Guven Deniz Can , Aktas Burak Yasin , Güner Gürkan , Aktepe Oktay Halit , Taban Hakan , Kilickap Saadettin , Kars Ayse , Turker Alev , Yalcin Suayib , Dizdar Omer
Published: March 2020

e22557

Background: Liposarcomas constitute 15% of all soft tissue sarcomas.They consist of four subtypes;well-differentiated,dedifferentiated,myxoid and pleomorphic.In this trial we assessed demographic and clinical features of patients with liposarcoma who were treated in our hospital.Methods: Patients who were diagnosed with liposarcoma in Hacettepe University Medical Oncology Department between 2005and2015(n = 119) were included. Patients’ data were collected from hospital registration system.Survival analyses were performed with Kaplan Meier analyses.Results: At the time of diagnosis, the vast majority of patients had localized and/or node positive disease(n = 98),8 patients had metastatic disease.Further analyses hold for only early stage disease:Median age was 52(min:18-max:81).105 patients(94.6%) had upfront surgery.26(23.4%) and 30 patients(27%) received perioperative chemotherapy(CT) and radiotherapy(RT),respectively.The most commonly used CT agents were ifosfamide, anthracyclines, etoposide,taxanes and gemcitabine.At a median follow-up of 45months, relapses were observed in 34 patients(30.6%) and 35 patients(31.5%) died.Median overall survival(OS) was 113.1 months and median relapse free survival (RFS) was 23.8 months.Perioperative CT and RT were not associated with improved RFS and OS.Among patients with early stage disease; median RFS of patients with well-differentiated, dedifferentiated, myxoid and pleomorphic subtypes were 31.8,34.3,28 and 5.2months,respectively(p = 0.013).Well-differentiated group had significantly higher RFS than those with pleomorphic liposarcomas(p = 0.003).The mostly used CT drugs in recurrent setting were ifosfamide+doxorubicine(42.9%) and ifosfamide+etoposide(21.4%).Conclusions: Liposarcoma prognosis varies significantly with histological subtype and the efficacy of systemic chemotherapy is limited both in early stage and advanced disease.[Table: see text]
Patient perceptions of treatment benefit in advanced cancer.
Authors: Patell Rushad , Einstein David Johnson , Halleck Jennifer , Buss Mary K.
Published: March 2020

e23163

Background: Informed consent assumes accurate perceptions of potential benefits and risks of treatment, yet many patients receiving palliative cancer therapies misperceive the likelihood of cure. Our study aims to further explore patient perceptions of benefits and risks of palliative treatments and to examine this in the era of novel therapeutics. Methods: We surveyed patients with advanced solid cancers and their oncologists regarding benefits/risks of palliative therapies. We serially assessed patients’ perceptions of likelihood of tumor response, survival benefit, symptom palliation and side effects, as well as information-seeking behavior pre-treatment and decisional regret at the end of treatment. We also compared patients’ perceptions of benefits/risks to that of their oncologists. Results: Across four disease groups, 52 patients have enrolled (target accrual: 120). Median age is 64 years (range 20-84), 58% are male, and 60% had prior treatment. Treatments included chemotherapy (42%), targeted therapy (31%), and immunotherapy (27%). Misperceptions (patient-assessed likelihood minus oncologist-assessed likelihood) at the beginning of treatment across different domains are shown in the table. Conclusions: Compared with their oncologists, patients overestimate not only curability but also chance of tumor response, symptom palliation, and survival benefit, yet they accurately perceive chance of toxicity. Thus, efforts at improving communication should focus on the chances of treatment benefit and multiple types of benefits rather than treatment risks. In future analyses after full accrual, we will assess differences between domains, internal consistency of misperceptions, change in misperceptions over time on treatment, decisional regret at end of treatment, and association of misperceptions with information-seeking behavior and sources of education. [Table: see text]
Utilizing the patient-reported outcomes measurement information system (PROMIS) to assess quality of life among breast cancer patients at an academic center.
Authors: Matthys Madeline B. , Dempsey Andre , Melisko Michelle E. , Basu Amrita , Dreher Nickolas , van 't Veer Laura , Esserman Laura
Published: March 2020

e23171

Background: NCI PROMIS assesses physical, mental and social health across multiple health conditions. Despite interest in using PROMIS in oncology trials and clinical care, reference values in cancer are not well established. Methods: Electronic intake questionnaires assessing self-reported history and 8 PROMIS domains (depression, anxiety, fatigue, sleep-related impairment (SRI), sleep disturbance, cognitive function, applied cognition and physical function) are sent to all new patients (pts). 2886 pts with self-reported breast cancer completed the questionnaire/consented to research. PROMIS T-Scores were calculated using the Health Measures system. Results: For all domains except depression, cognitive function and applied cognition, pts had clinically meaningful ( > 3 point diff.) worse mean PROMIS scores than US means (50). Compared to stage 0-III, stage IV pts had worse scores for all assessed domains (p < 0.05). Among Stage IV pts < 49, QoL was significantly worse in 7/8 domains (see table). Across all age groups, there were significant differences in mean PROMIS scores for Stage IV pts in anxiety, depression, cognitive function and applied cognition (p < 0.05). Conclusions: PROMIS scores among pts indicate impaired QoL in multiple domains. These scores provide insight into the physical, mental and social health of our pts and can serve as robust estimates for breast cancer trials and clinical care. [Table: see text]