bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sustainable responses in metastatic melanoma patients with/without brain metastases after immunotherapy induced CR.
Authors: Dimitriou Florentia , Ramelyte Egle , Allayous Clara , Gérard Camille L. , Kähler Katharina C. , Toussaint Frédéric , Schäfer Sarah , Hassel Jessica Cecile , Heinzerling Lucie , Hauschild Axel , Michielin Olivier , Lebbe Celeste , Braun Ralph P , Dummer Reinhard , Mangana Joanna 
Published: May 2019

e21042 Background: Immunotherapy (IT) has demonstrated an improved overall survival (OS) in advanced melanoma with 15% complete responses (CR) in treatment-naïve patients (pts) with brain metastases (met) in the anti-PD1/anti-CTLA4 combination. However, data on brain-met pts who discontinue treatment (EoT) after achieving a CR are lacking. Methods: Disease characteristics and clinical outcome were retrospectively collected from 6 centers on advanced melanoma pts treated with anti-PD1 or anti-PD1/anti-CTLA4. Pts were followed for at least 10 weeks (10.8 – 242). Off-treatment survival (OTS) was defined as time between last IT dose to disease progression or death. Results: Out of 890 pts, 62 achieved a CR; 40 pts stopped treatment due to CR, while 22 due to an adverse event (AE) (n = 19) or investigator decision (n = 3) with subsequent CR. 14 were treated with anti-PD1/anti-CTLA4 and 48 with anti-PD1. 24 had a BRAF mutation, of which 10 had previously received targeted therapy (TT). The median time to first CR was 31 weeks (6 – 138), median duration of response and OTS was 91.1 and 60.7 (10.6 – 242) weeks respectively. OTS was numerically longer for those pts with EoT after AE (85 weeks, 13-242) versus those with EoT due to CR (60 weeks, 11-130). Median OS was not reached. 6/62 (3%) progressed after EoT; 4 locoregionally while 2 were subsequently treated with IT. All pts were alive at last follow-up. 19 pts had brain mets. 8 were BRAF mutated. 10 were treatment naïve, 6 received previously anti-CTLA4, 1 chemotherapy and only 2 TT. Data on reasons for EoT and responses in brain mets are seen in the table. Conclusions: Early data suggest that OTS is numerically longer in patients with EoT due to AE with subsequent CR. EoT due to sustained CR is a feasible option also in brain mets. EoT due to AE with subsequent CR was a more frequent event in the combination treatment. [Table: see text]
Outcomes of melanoma soft parts/clear cell sarcoma (MSP/CCS) patients (pts) with immune and targeted therapies.
Authors: Jones Amy Little , Joon Aron , Haydu Lauren Elaine , Lazar Alexander J. , Tetzlaff Michael T. , Ravi Vinod , Davies Michael A. 
Published: May 2019

e21046 Background: Overall survival (OS) for pts with cutaneous melanoma has vastly improved with checkpoint inhibitors (CPI) and targeted therapy (TT), but less is known about outcomes of other rare tumors showing melanocytic differentiation. We examined outcomes for metastatic pts with MSP/CCS at MD Anderson (MDA) to characterize outcomes with contemporary therapies. Methods: Pts with MSP/CCS were identified in the MDA databases. Pts with < 2 visits to MDA or without molecular confirmation of dx were excluded. Log-rank testing was used to compare OS among distributions. Results: A total of 102 MSP/CCS pts were identified. Initial diagnosis was local disease 46%, regional metastases 34%, and systemic metastases 20%. Primary tumor site was lower extremity (LE) 48%, GI tract 29%, upper extremity (UE) 18%. 65 pts were diagnosed with metastatic disease (dz), including 32% with lung-only, 14% liver-only, and 51% with multiple metastatic sites. Median OS from diagnosis of distant metastatic dz was 22 mos (95% CI 16-34 mos). Primary tumor site (GI 46.4 vs. LE 19.1 vs. UE 14.7 mos; p = 0.018) and race (white 26.8 vs. black 6.5 mos, p = 0.019, HR 0.45) were significantly associated with OS from distant metastasis; sex, age, decade of diagnosis, size of primary, and prior treatment with neoadjuvant or adjuvant therapy were not. Treatments for metastatic dz included chemotherapy (n = 29), biochemotherapy (n = 11), biotherapy (n = 5), CPI (n = 11) and TT (n = 19). Median OS was 15.9 mos from start of CPI (range 10.7 to NR) and 16.9 mos from start of TT (range 7.8 to NR). Median OS from metastatic dz for pts not treated with CPI or TT was 17.1 mos (range 12.4 to 32.5), which was not significantly different versus CPI or TT. Duration of response was < 6 mos for 91% pts receiving CPI and 89% pts receiving TT. One pt had a durable response (41.8 mos) to anti-PD1 and one pt had a durable response (24.8 mos) to an AKT inhibitor. Conclusions: While rare responses to CPI and TT were observed, no significant difference was detected in OS compared to traditional therapies in pts with metastatic MSP/CCS. The development of more effective therapies remains an unmet need for this disease.
Mucosal melanoma of the female genital tract: Operation modalities.
Authors: Wang Xuan , Cui Chuanliang , Lian Bin , Zhou Li , Chi Zhihong , Si Lu , Sheng Xinan , Kong Yan , Mao Lili , Yan Xieqiao , Tang Bixia , Guo Jun 
Published: May 2019

e21060 Background: Primary melanomas originating from the female genital tract are rare and aggressive. There are still no established guidelines for its primary surgery , so we analyzed the effect of the surgical approach on its relapse free survival (RFS) and overall survival (OS ) based on a phase 3 randomized trial (NCT03435302). Methods: Mucosal melanoma patients with female genital tract primary which were stageⅠ-Ⅲ and completely resected were enrolled as part of the multicenter, randomized, controlled, phase 3 trial for the comparison of adjuvant chemotherapy (TMZ plus DDP 6 cycles) vs. High-dose interferon group (HDI, 1 year).The RFS and OS was compared between local and extensive excision group. Results: Seventy eight female genital tract primary melanoma patients were enrolled from Feb 2014 to Jun 2016, Surgical approach was chosen by the surgeon, 39.2% (29/74) took local excision and 60.8% (45/74) extensive excision. The average age was 52.3 years. Of all these patients 46.2% were vulvar primary, 53.8% vaginal, and 85.3%stage I/II, 14.7% stage III. Primary ulceration was found in 68.1% lesions, 7 cases harbored with BRAF mutation. 57.7% patients randomized to adjuvant chemotherapy and 42.3% in HDI group. All these factors showed no difference in local excision and extensive excision group. At a median follow-up of 31.2 months (range: 5.3-60.0m), 64.4% got metastases and 23.1% showed local recurrence. RFS (8.0m vs. 11.4m, p = 0.523) and local recurrence rate (13.8% vs.31.1%, p = 0.105 ) did not show significant difference between local excision group and extensive excision group. OS in whole cohort was 28.9 months, it also did not show significant difference between two groups(local 25.5m vs. extensive 40.1m, p = 0.653). In univariate analysis there was also no relation between surgical approach and OS in this cohort. Conclusions: Based on this trial, for resectable female genital tract primary mucosal melanoma, there was no difference of local control rate, RFS and OS between local excision and extensive excision group. Local excision might be adequate for the primary leision. Still more prospective data are needed for this subtype of melanoma. Clinical trial information: NCT03435302.
Experiences of general practitioners and medical specialists with incurable cancer patients with a protracted disease trajectory: A focus group study.
Authors: Buiting Hilde M. , Botman Femke , van der Velden Lilly-Ann , Brom Linda , van Heest Florien , de Mol Pieter , Bakker Ton 
Published: May 2019

e23010 Background: Advances in oncology have resulted in prolonged disease trajectories in patients with incurable cancer. In this disease-phase, patients are aware that cancer is incurable but they do not approach the last phase-of-life yet. We examined experiences and wishes of GPs and specialists concerning appropriate care-provision, delivered by GPs. Methods: We performed 6 focus groups in different regions in the Netherlands; 3 homogenous groups (N=15 GPs) and 3 heterogenous groups (N=23 GPs and medical specialists). Data were analysed with thematic content-analysis. Results: During the first focus-groups, the protracted disease phase was not acknowledged as a separate one; in the last focus-groups, however, this disease-phase received more attention. Physicians clearly distinghuished this trajectory from the palliative / terminal disease phase, partly because many patients did not experience severe physical problems. Most GPs preferred to be involved in the care of these patients as this would enable them to easily guide patients in their last phase-of-life. In these patients, GPs experienced difficulties in estimation of prognosis and advice of further treatment, partly because of insecurity of treatment side-effects of immunotherapy. Further, many physicians experienced difficulties in labeling this disease phase. ‘Stable’; ‘chronic’; and ‘Phase X’ were regularly mentioned. Medical specialists were more frequent involved with these patients but preferred to involve GPs as much as possible. They however also realised that this would become more difficult in future, given the growing group of patients in this disease phase. Conclusions: In the protracted disease phase, patients often do not experience severe physical symptoms. They often do not approach their patient for possible psycho-social problems. Apart from medical specialists, tools to easily communicate across specialties to optimise care need to be further explored.
Defining undertreatment and overtreatment in older patients with cancer: A scoping review of the literature.
Authors: DuMontier Clark , Loh Kah Poh , Bain Paul A , Silliman Rebecca A , Abel Gregory A. , Djulbegovic Benjamin , Driver Jane A. , Dale William 
Published: May 2019

e23020 Background: The terms “undertreatment” and “overtreatment” are often used to describe the management of older adults with cancer. The aim of this scoping review was to explore the explicit and implicit definitions associated with the use of these terms. Methods: We searched PubMed (NCBI), Embase (Elsevier), and CINAHL (EBSCO) for titles and abstracts that included the terms "undertreatment" or "overtreatment" (overtreat OR undertreat OR over treat OR under treat) of older adults with cancer. We included all types of articles, cancers, and treatments. We excluded studies that only included patients younger than 60 years old or studies without a defined focus on older adults. CD and KL independently reviewed a subset of included articles to assess for inter-reviewer reliability. Results: We identified 224 primary and secondary research articles that used the terms “undertreatment” (192), “overtreatment” (72), or both (45) regarding the management of older adults with cancer. Only 14 (6.3%) articles provided an explicit definition; for the remaining articles, we derived the implicit definitions from the terms’ surrounding context. There was substantial agreement between CD and KL in their interpretation of definitions of these terms (kappa 0.81). “Undertreatment” was commonly used to imply less than “standard” therapy (130 articles, 67.7%), or less than “standard” therapy that contributed to worse outcomes (62, 32.3%). Many articles did not account for the underrepresentation of older adults in trials leading to “standard” therapy, and 24 primary studies performed no or limited adjustment for geriatric domains (e.g., function) in their analyses that suggested worse survival in older adults treated with substandard therapy. “Overtreatment” was commonly used to imply cancer treatment in an older adult whose cancer would not have caused symptoms in his/her remaining lifetime (31, 43.1%), or aggressive treatment in whom the harms of treatment outweigh its benefits (41, 56.9%). Conclusions: Nearly all articles used the terms “undertreatment” and/or “overtreatment” without an explicit definition, and we identified variability and limitations in the meanings implied by these terms.
Genetic variability of tramadol pharmacokinetic genes and pain treatment outcome after breast cancer surgery.
Authors: Besic Nikola , Goricar Katja , Jeriha Jakob , Dolzan Vita , Strazisar Branka 
Published: May 2019

e23133 Background: Tramadol is a treatment of choice for pain management after axillary lymph node dissection in breast cancer patients. Tramadol is metabolized via CYP2D6 and UGT2B7, while ABCB1, ABCC2 and SLC22A1 are involved in transport of tramadol metabolites. Genetic variability of metabolizing enzymes or drug transporters may therefore affect efficacy and adverse effects of tramadol. The aim of this study was to evaluate the association of genetic variability in tramadol pharmacokinetics pathway on long-term outcome of tramadol pain treatment after breast cancer surgery. Methods: The study included 102 breast cancer patients treated with either 75 or 37.5 mg of tramadol for pain relief after breast cancer surgery including axillary lymph node dissection as part of a randomized clinical trial KCT 04/2015-DORETAonko/si at Institute of Oncology Ljubljana. All patients were genotyped for 14 polymorphisms in ABCB1, ABCC2, CYP2D6, SLC22A1 and UGT2B7 genes, as well as for CYP2D6 duplication and deletion. CYP2D6 phenotype was predicted from the genotype data and patients were categorized as poor (PM), intermediate, extensive or ultrarapid metabolizers. The association of genetic factors with pain one year after treatment was evaluated using logistic regression and Mann-Whitney test. Results: One year after treatment, 21 (20.8%) patients were still experiencing chronic and 25 (24.8%) neuropathic pain. CYP2D6 PMs were significantly more likely to experience chronic and neuropathic pain after tramadol treatment (OR = 5.96, 95% CI = 1.22-29.13, p = 0.027 and OR = 9.31, 95% CI = 1.65-50.59, p = 0.011, respectively), even after adjustment for tramadol dose (p = 0.032 and p = 0.016, respectively). PMs also had higher average pain intensity compared to others regardless of tramadol dose (p = 0.042). In patients receiving lower tramadol dose, ABCB1 rs1128503, rs2032582 and rs1045642 were associated with more chronic pain in the dominant model (p = 0.004, p = 0.004 and p = 0.047, respectively). Conclusions: Genetic variability in tramadol pharmacokinetics pathway may be associated with pain treatment outcome in breast cancer patients, therefore pharmacogenetic testing could enable more effective tramadol treatment. Clinical trial information: EudraCT 2015-000992-28.
HOME palliative care-Nepal: A cell-phone/website it system.
Authors: Paudel Bishnu D. 
Published: May 2019

e23134 Background: Worldwide, major clinical barriers to effective palliative care are the absence of: 1. Current data on symptom type and intensity; 2. Immediately accessible information on practical, affordable, and effective interventions; and 3. Self-sustaining systems to facilitate currently limited physician engagement in continuing palliative care. In Nepal, essentially all families have a cell phone, the majority of which are Android smart phones. 80% of the population lives in rural settings. Methods: Following a cross sectional study in 383 Nepalis with advanced cancers using a cell-phone “app” on the Android platform with a validated 15-item symptom questionnaire, in which all approached patients agreed and were able to complete the instrument in under 3 minutes, we assembled a Nepali/US development team of clinicians and computer scientists to create a tele-home palliative care system centered on use of this app. Results: We have developed an internet website (homepalliativecareNepal.net) with patient/family and physician information pages, a guest health professional site, and a password-protected physician site with organized patient demographic and medical summary data, and telephone-submitted app-symptom reports, local clinical practice guidelines, and an intervention menu of 30 written and mini-video items and links (the majority non-pharmacologic) including start-up drug prescriptions (5), which can be personalized and directly sent to the patient by phone. The system is managed by a local organization that also ensures regular physician/clinic visits by the patient, or by a family member with a patient phone check-in, at least every two weeks, with creation of documentation of provided services. Conclusions: Our adaptable, patient-centered, IT-tools-facilitated, and economical system offers significant potential for addressing the need to engage all types of health care practitioners in palliative care in different cultural settings.
A phase I study of LOXO-292, a highly selective RET inhibitor, in pediatric patients with RET-altered cancers.
Authors: DuBois Steven G. , Albert Catherine Michelle , Mascarenhas Leo , Laetsch Theodore Willis , van Tilburg Cornelis Martinus , Potter Samara L , Turpin Brian , Glade Bender Julia Lynne , Spunt Sheri L. , Hladun Raquel , Casanova Michela , Ziegler David Simon , Morgenstern Daniel A. , Eary Todd , Ibabekci Shannon , Qamoos Hope , Rothenberg Stephen M. , Cox Michael Craig , Balis Frank M. , Pappo Alberto S. 
Published: May 2019

TPS10066 Background: Genomic alterations in the RET kinase, including gene fusions and activating point mutations, are implicated in the pathogenesis of lung, thyroid, sarcoma and other cancers in both chidren and adults. Currently available multikinase inhibitors with anti-RET activity are non-selective and may be associated with less favorable toxicity profile. LOXO-292 is a novel, highly selective, ATP-competitive small molecule RET inhibitor. LOXO-292 has preclinical nanomolar potency against diverse RET alterations (e.g. fusions, activating mutations and anticipated acquired resistance mutations) and anti-tumor activity in the brain. LOXO-292 has demonstrated clinical activity in adult patients with RET-alterated solid tumors. Methods: LIBRETTO-121 (EudraCT 2019-000212-28) is an ongoing multicenter phase 1/2 dose escalation multicenter trial in patients 6 months-21 years of age with advanced, RET-altered solid and CNS tumors. Dose escalation follows a rolling 6 design starting at the equivalent of the adult recommended phase 2 dose. Enrollment began on 12 Feb 2019 and is ongoing. Key eligibility criteria include: solid or CNS tumor with a documented RET gene alteration refractory to standard therapy; age 6 months to 21 years of age; and adequate bone marrow, liver and kidney function. LOXO-292 is administered orally BID for continuous 28-day cycles. Both capsule and liquid suspension dosage forms are available. The primary objective of the phase 1 portion of the study is to determine safety and dose limiting toxicities. Key secondary objectives include characterization of pharmacokinetic properties, identification of the MTD and initial characterization of the anti-tumor activity of LOXO-292. Archival tissue will be used to further characterize molecular abnormalities. Clinical trial information: 2019-000212-28.
Phase 1/2 dose-escalation and expansion study investigating SAR439859 +/- palbociclib in postmenopausal women with estrogen receptor-positive (ER+)/HER2- metastatic breast cancer.
Authors: Bardia Aditya , Linden Hannah M. , Ulaner Gary A. , Chandarlapaty Sarat , Gosselin Alice , Celanovic Marina , Campone Mario 
Published: May 2019

TPS1105 Background: Endocrine therapy +/- cyclin-dependent kinase 4/6 inhibitors, such as palbociclib, is the standard of care for ER+/HER2- breast cancer. Tumors often become resistant to this combination but retain ER signaling dependence, allowing for sequential ER-directed therapy. Unlike other classes of endocrine therapy with one mode of action, selective ER degraders (SERDs) block signaling by both ER competitive antagonism and degradation, targeting resistance settings that other treatments cannot. SAR439859 is a potent, oral SERD with improved preclinical efficacy and pharmaceutical properties vs other SERDs. This study investigates SAR439859 +/- palbociclib in postmenopausal women with ER+/HER2- metastatic breast cancer. Methods: This prospective, open-label, non-randomized Phase 1/2 study (NCT03284957; TED14856) assesses SAR439859 single agent at dose levels increasing from 20 mg/day up to the maximum administered dose (Part A) followed by cohort expansion at the recommended dose (RD; Part B). The study will also assess two dose levels of SAR439859, in combination with palbociclib 125 mg/day (Days 1–21 in 28-day cycles; Part C) followed by cohort expansion (Part D). Postmenopausal women with ER+/HER2- metastatic breast cancer, who received ≥ 6 months of prior endocrine therapy, are eligible. Patients were permitted to have received ≤ 3 (Part A) or ≤ 1 (Parts B–D) prior chemotherapies for metastatic disease. Exclusion criteria include Eastern Cooperative Oncology Group performance status ≥ 2, concomitant illness (including those related to HIV or hepatitis and other cancers ≤ 3 years) and factors potentially affecting absorption of SAR439859 or palbociclib. Study endpoints include assessment of dose-limiting toxicities, determination of maximum tolerated dose and RD in dose escalation (Parts A and C), and objective response rate according to RECIST v1.1 in dose expansion (Parts B and D). 18FES-PET scan between Days 11–15 in Part A will assess ER availability. Safety, pharmacokinetics and response were evaluated for Parts A–D. Recruitment and screening are ongoing (Part A n = 16; B n = 18; C n = 2; D n = 0). Funding: Sanofi. Clinical trial information: NCT03284957.
NRG-BR002: A phase IIR/III trial of standard of care therapy with or without stereotactic body radiotherapy (SBRT) and/or surgical ablation for newly oligometastatic breast cancer (NCT02364557).
Authors: Chmura Steven J. , Winter Kathryn A. , Al-Hallaq Hania A , Borges Virginia F. , Jaskowiak Nora T. , Matuszak Martha , Milano Michael T. , Salama Joseph Kamel , Woodward Wendy A. , White Julia R. 
Published: May 2019

TPS1117 Background: This is a randomized Phase II/III trial to evaluate if stereotactic body radiotherapy (SBRT) and/or surgical resection (SR) of all metastatic sites in newly oligo-metastatic breast cancer who have received up to 12 months of first line systemic therapy without progression will significantly improve median progression free survival (PFS). If this aim is met the trial continues as a phase III to evaluate if SBRT/SR improves 5 year overall survival. Secondary aims include local control in the metastatic site, new distant metastatic rate, and technical quality. Translational primary endpoint is to determine whether < 5 CTCs is an independent prognostic marker for improved PFS and OS. Methods: Women with pathologically confirmed metastatic breast cancer to ≤ 4 sites who have been diagnosed within 365 days with metastatic disease and the primary tumor site disease is controlled. CNS metastases are ineligible. ER/PR and HER-2 neu status is required. Site radiation credentialing with a facility questionnaire and pre-treatment review of first case is required. Randomization is to standard systemic therapy with local radiotherapy/ surgery for palliation when necessary versus ablative therapy of all metastases with SBRT and/or SR. For the phase IIR portion to detect a signal for improved median PFS from 10.5 months to 19 months with 95% power and a 1-sided alpha of 0.15 and accounting for ineligible/lost patients, 128 patients will be required. For the Phase III, an additional 232 patients will be required to definitively determine if ablative therapy improves 5-year overall survival from 28% to 42.5% (HR=0.67), with 85% power and a one-sided type I error of 0.025. For the translational research assuming a two-sided probability of type I error of 0.05, the number of patients accrued in the Phase II-R and Phase III portions will provide sufficient power of at least 91% and 93% to detect whether < 5 CTC’s is prognostic for PFS and OS, respectively. Present accrual (1-31-2019): 105. Contact Information: Protocol: CTSU member web site https://www.ctsu.org . Enrollment: OPEN at https://open.ctsu.org . Support: This project is supported by NRG Oncology grants U10CA180868 and U10CA180822 from the National Cancer Institute (NCI). Translational science is supported by the Ludwig Foundation for Cancer Research. Clinical trial information: NCT02364557.