bluuebunny/crossref_metadata_2025 huggingface dataset:
Local hormonal status of tumor and adjacent tissues in patients with melanoma depending on their gender.
Authors: Bandovkina Valeria A. , Frantsiyants Elena M. , Rozenko Ludmila Ya. , Pozdnyakova Viktoria V. , Ilchenko Maria G. , Agarkova Elena I. , Maksimova Natalia A. , Przhedetskiy Yuriy V. , Kit Oleg I.
Published: May 2020

e22084

Background: Gender is an important independent prognostic factor for cutaneous melanoma incidence, and survival in women is better. The purpose of the study was to determine the content of sex steroids and prolactin in tumor, perifocal and resection line tissues in male and female patients with melanoma. Methods: The study included 13 men and 22 women with cutaneous melanoma (M) pT1-2N0M0. Levels of free testosterone (fT), estradiol (E2), estrone (E1), progesterone and prolactin were measured by ELISA in M, perifocal (P) and resection line (RL) tissues after surgical treatment. The average age of patients was in men 54±3.56 years (median age 53, 32-81), in women 65±2.67 years (median age 63, 39-82). Skin tissues obtained from 20 non-cancer patients after plastic surgery served as the control. Results: In M of women, levels of fT, E2 and E1 were elevated on average by 1.3 times, while in men fT was decreased by 1.7 times, and estrogens were increased – E2 by 1.7 and E1 by 3.7 times, compared to the corresponding control levels. In women, fT in P tissues was increased by 1.6 times, while parameters in RL were similar to control values. In men, fT in P and RL tissues was decreased by 3.8 and 2.3 times respectively, and E2 was increased by 1.6 and 1.3 times respectively. E1 in P tissues was decreased by 1.7 times, in RL – similar to control levels. Conclusions: M in patients of both genders has an altered hormonal profile characterized by hyperestrogenia, with the prevalence of E1 and androgen deficiency in men. The expansion of the “tumor field” due to changes in the hormonal profile of P and even RL tissues was established only in male patients with the same morphological prevalence of the process, which may be one of the reasons for the more aggressive tumor course.
Relationship of chronic neurogenic pain and fibrinolysis in the blood of patients with melanoma.
Authors: Rozenko Ludmila Ya. , Frantsiyants Elena M. , Bandovkina Valeria A. , Pogorelova Yulia A. , Cheryarina Natalia D. , Gusareva Marina A. , Kit Oleg I.
Published: May 2020

e22085

Background: The plasminogen regulation system is critical in triggering proteolysis to cleave the extracellular matrix and basement membrane. The “uPA-uPAR” system is involved in extravascular fibrinolysis and is responsible for the formation of plasmin associated with invasion and metastasis. The purpose of the study was to analyze levels of factors of the plasminogen regulation system in the blood of patients with cutaneous melanoma (M) and chronic neurogenic pain (CNP). Methods: Blood levels of PAP, uPA, uPAR and PAI-1 were measured by ELISA in patients with Т3-4NxM0 melanoma: 21 women with CNP (pelvic pain - 7, osteochondrosis – 14), mean age 67.2±2.7 years; 17 men with CNP (osteochondrosis), mean age 65.6±3.1 years. The control group included patients with melanoma similar in age, gender and disease stages without CNP. Results: Blood levels of PAP in women with M+CNP were twice higher than in patients with M without CNP, the levels in men with M+CNP did not change; uPA content increased in both women and men with M without CNP by 1.4 and 1.5 times, uPA activity was elevated only in women by 2.4 times, in men it was reduced by 2 times; uPAR was increased by 1.5 times in women and men compared to the values in both female and male patients with M without CNP. PAI-1 content in women and men with M+CNP was similar to control values, and its activity was increased in women by 1.5 times and decreased in men by 2.5 times. Conclusions: The study gives significant additional information on the effect of CNP on relationships in the plasminogen activation system in a combination of cutaneous melanoma and CNB showing marked gender differences. The results should be taken into account in the special treatment of patients with melanoma.
AMBLor: A prognostic and stratifying biomarker for adjuvant immunotherapy of AJCC stage II melanomas.
Authors: Labus Marie , Ellis Robert , Ewen Tom , Podlipnik Sebastian , Greenwood Alison , McConnell Ashleigh , Long Anna , Ness Tom , Jones Claire , Stefanos Niki , Sloan Philip , Husain Akhtar , Barrett Paul , Puig Susana , McArthur Grant A. , Lovat Penny
Published: May 2020

e22094

Background: The success of adjuvant therapy for patients with AJCC stage III melanomas coupled with the increased risk of mortality for patients with AJCC stage IIB compared to IIIA tumours has paved the way to adjuvant immunotherapy trials for patients with sentinel lymph node (SLNB) –ve AJCC stage II disease. However, the lack of biomarkers able to appropriately stratify high-risk tumour subsets limits patient recruitment. We have recently identified the combined immunohistochemical (IHC) expression of AMBRA1 and Loricrin (AMBLor) in the epidermis overlying non-ulcerated AJCC stage I melanomas as a robust prognostic biomarker and valuable pre SLNB test. Methods: Retrospective analysis of AMBLor was performed in three geographically distinct cohorts of AJCC stage II melanomas using a clinically validated automated IHC assay and semi quantitative binary scoring analysis to define high vs low risk subgroups. Results: Data revealed loss of AMBLor overlying non-ulcerated high risk AJCC stage IIA or B tumours correlated with a significant reduction in disease free survival (DFS) at 12 years to 55% compared to 89% for patients with AMBLor low risk tumours (P = 0.015; HR 4.83, 95% CI: 2.29-10.14). Sub-cohort multivariate analysis of 80 non ulcerated stage IIB tumours also revealed reduced DFS at 12 years to 68% in AMBLor high-risk compared to 83% in AMBLor low-risk tumour subsets, with an assay sensitivity of 97% and a negative predictive value of 90%. Furthermore, sub-cohort analysis of SLNB –ve AJCC stage IIA or B tumours additionally identified 5 genuinely low risk cases in which DFS at 10 years was 100% compared to only 36% in 37 patients in which AMBLor was lost. Conclusions: Collectively these data indicate AMBLor as a novel prognostic biomarker for patients with non-ulcerated AJCC stage II melanomas as well as companion/stratifying biomarker for adjuvant immunotherapy, the use of which will increase clinician confidence for patient recruitment as well as reduce patient morbidity.
Adjuvant therapy in non-metastatic melanoma result from a Brazilian cohort.
Authors: Silva Sinara Figueiredo , Tavares Monique Celeste , De Barros E Silva Milton Jos , Rinck José Augusto , Lima Joao Paulo SN , Garcia Daniel , Calsavara Vinicius Fernando
Published: May 2020

e22095

Background: The PD-1–blocking antibodies, combination of target therapy and anti-CTLA4 have shown a favorable safety profile with better efficacy than high-dose interferon in the adjuvant setting. However, in Brazil only a minority of patients in private institutions have access to new therapies in adjuvants. Here, we describe the evolution of patients with non metastatic melanoma who received anti-PD1 or target therapy adjuvant or only followed. Methods: This is an observational, descriptive, retrospective cohort, which included patients diagnosed with cutaneous, mucous or acral melanoma (operated stage III or stage IVa) submitted or not they undergoing adjuvant chemotherapy between January 2013 and December 2019 at AC, São Paulo, Brazil. Results: We evaluated 82 patients with a median age of 54 years, 62.2% of the patients were male, the majority, 81.1%, white. In 29.3% had primary ulceration and presence of satellites was observed in 18.3% and the average Breslow value of the cases was 3,3mm. We found that 18.3% of patients were classified as stage IIIA, 4.9% IIIB, 22% IIIC, 8.5% IIID and 9.8% stage IV operated. The 44.6% of patients completed 1 year of adjuvant treatment. Related to the presence of ulceration, we observed a progression-free survival of 36.3 months for cases with ulceration versus 47.1 months for cases with absent ulceration, ( p= 0.449). Patients with satellite presence had a progression-free survival of 29.9 months versus 49.1 months for cases of missing satellite, ( p= 0.118). Patients who underwent lymph node dissection had a progression-free survival of 50.3 versus 36.4 months, those who did not undergo ( p= 0.201). Patients who completed 1 year of adjuvant therapy achieved a recurrence-free survival of 66.1 versus 27.9 months who did not complete, ( p= 0.003). Considering the tumor staging, patients classified T1a-T2a had a progression-free survival of 59.8 months, T2b-T3b of 42 months and those grouped as T4a, T4b, of 29.9 months, ( p = 0.021). The median progression-free survival was 44 months, 40.6 months for patients who received adjuvant treatment versus 27.2 months for those who did not ( p = 0.271) with a reduced risk of progression in the order of 33% for patients who received adjuvant. Conclusions: The presence of ulceration, satellites and advanced T staging were associated with a worse outcome with a greater chance of recurrence. Emptying of the lymph node chain, receiving adjuvant treatment and completing 1 year of adjuvant treatment were directly associated with improved survival
Preoperative treatment for marginally resectable metastatic melanoma: A single center experience in China.
Authors: Xu Yu , Shen Xuxia , Sun Wei , Kong Yunyi , Chen Yong , Yan Wangjun
Published: May 2020

e22096

Background: Large randomized trials have proved that targeted therapy (TT) and immunotherapy (IT) can improve RFS for resectable Stage III melanoma. However, there is still a risk around 15%~25% of relapse within 1 year, especially worse for Stage IIID disease. Several neoadjuvant trials have shown a potentiality of long-term relapse-free after a pathologic complete response, especially for immunotherapy. We conducted a prospective study to investigate the impact of preoperative treatment on the anti-tumor efficacy and disease-free survival for Chinese melanoma. Methods: Stage IIID patients with matted nodes were recruited. For BRAF V600E-muted patients, Vemurafenib (V) was given for one months ahead of the surgery. For BRAF-wide-type patients, anti-PD1 antibody, Pembrolizumab(P) or Toripalimab (T) was given one dose per 3 weeks until response or intention-to-progression was observed. Pathologic assessment followed the principles for neoadjuvant therapy established by INMC. Results: Totally seven patients have been recruited. Detail information was listed in Table. Clinical ORR was 71%, however with no pCR observed. One patient in Vemurafenib group occurred brain mets within 1 month after surgery. All four patients in anti-PD1 group were relapse-free so far after median follow-up of 11 months. Conclusions: Preoperative BRAF targeted and anti-PD1 immunotherapy might guarantee a positive impact on anti-tumor response and local disease control for marginally resectable melanoma. However, the pathological criteria for neoadjuvant treatment might not be suitable to evaluate the matted or bulky specimen after preoperative treatment. [Table: see text]
Three times of intratumor injection of the sustained released by ROS with penicillin-combined chemotherapy drugs for the long of survival period of the tumor-bearing mouse.
Authors: Chen Dong , Fu Qiang , Zhang Jian , Han Yan , Li Bian , Zheng Guoqin , Zhao Ming , Yu Baofa ,   Shandong Baofa Cancer Therapeutics, Inc.
Published: May 2020

e22098

Background: To study the effect of sustained release by ROS with hapten for three intratumoral injections of chemical drugs on the survival of tumor-bearing mice. Methods: Mice bearing solid tumors of H22 liver cancer were randomly divided into groups with the longest tumor diameter of about 4-7 mm. They were administered intratumorally the next day, with a second interval of 7 days and an interval of 14 days (the 15th day of the experiment). During the period of administration and observation, the death of mice was observed daily, and the time of death was recorded to calculate the life extension rate. Results: The weight of mice in group Ⅲ and group Ⅳ was lower than that in control group, suggesting that chemotherapeutic drugs caused damage of mice and did not significantly increase body weight. Tumor size: Tumor volume experimental groups were different from the Control group, showing a significant anti-tumor effect; but there was no difference compared with Dox Control. Survival The survival rate of each group of mice is closely related to the tumor progression and drug treatment. The survival rate of each group after 45 days of treatment is significantly higher than that of the Control group. The average survival time of group Ⅳ, group Ⅰ and group Ⅱ was longer than that of control group with significant difference. Conclusions: After intratumoral injection 3 times, the survival time of mice is been prolonged.
Effect of urokinase gene knockout and chronic neurogenic pain on melanoma growth in the experiment.
Authors: Kaplieva Irina V. , Frantsiyants Elena M. , Surikova Ekaterina I. , Neskubina Irina V. , Bandovkina Valeria A. , Trepitaki Lidia K. , Lesovaya Natalia S. , Cheryarina Natalia D. , Nemashkalova Ludmila A. , Pozdnyakova Viktoria V. , Przhedetskiy Yuriy V. , Zakharova Natalia A. , Khokhlova Olga V. , Przhedetskaya Viktoria Yu. , Kit Oleg I.
Published: May 2020

e22099

Background: Studies have shown that the axis of the urokinase-type plasminogen activator (uPA–uPAR) has a pleiotropic effect in different stages of cancer. The purpose of the study was to reveal characteristics of the B16/F10 melanoma development in mice with the uPA gene knockout with and without chronic neurogenic pain (CNP). Methods: The study included male and female С57ВL/6 mice (n = 102) and C57BL/6-Plautm1.1BugThisPlauGFDhu/GFDhu mice with the uPA gene knockout (n = 48). B16/F10 melanoma was transplanted subcutaneously to the animals in the main groups 2 weeks after bilateral sciatic nerve ligation (CNP model). Mice with the standard melanoma transplantation were the controls. Results: The survival of uPA gene-knockout mice with melanoma was similar to that in controls and was 1.5 times (p < 0.05) longer in females than in males; the melanoma onset in these mice was observed a week earlier; the dynamics of tumor growth showed a pronounced gender dependence: in females, the tumor practically did not grow, and its volume before the death did not exceed 1.0 cm3, while in males the tumor was characterized by an active growth with two peaks of the volume increase (weeks 2 and 4); melanoma metastasized weakly - single metastases to the lungs (in females) or no metastases but with hemorrhages in the lungs and heart (in males). CNP reduced the survival of uPA gene-knockout females, similar to mice with the normal genome, but did not affect the survival of males; primary tumors in uPA gene-knockout mice emerged a few days later than in the control, but grew more intensively, with gender differences smoothed out; increased metastasis was demonstrated by the initiation of metastatic lesions of the lungs and liver in males, while hemorrhages in the lungs maintained, and by an increased number of metastases in the lungs with the appearance of lung hemorrhages in females. Conclusions: The uPA gene knockout differently changes the course of B16/F10 melanoma in male and female mice. CNP enhances the tumor growth, erasing gender differences, and activates metastasis of melanoma.
Management of pyrexia in metastatic melanoma patients: A real-world clinical experience survey study.
Authors: Satija Ambika , Pickard A. Simon , Ionescu-Ittu Raluca , Laliberté François , Ling You-Li , Nakasato Antonio Reis , Kang Barinder , Duh Mei Sheng , Patel Jeetvan
Published: May 2020

e22102

Background: Patients with BRAF+ metastatic melanoma (MM) have more options for treatment, including targeted therapy and immunotherapy. However, the risk of toxicities may contribute to lower treatment rates and duration. Pyrexia is a reversible adverse event commonly associated with BRAF/MEK inhibitors. However, little is known about the features, management strategies, as well as variations in pyrexia management in clinical practice. Methods: The study was conducted over two phases. Phase 1 was a qualitative study conducted with expert nurses to develop a pyrexia management questionnaire. The questionnaire was further enhanced through a pre-test with nurses to improve reliability and internal validity of the responses captured for this study. During Phase 2, a cross-sectional web-based questionnaire was administered to oncology registered nurses, nurse practitioners and physician assistants. All respondents were required to have managed pyrexia in patients with MM receiving dabrafenib+trametinib (D+T). Results: Respondents (N = 201, 57.2% academic center and 42.8% community based), on average, had 12.5 years of experience and >50% had managed more than 10 patients with BRAF-MEK inhibitor in the past 12 months. Almost all respondents (97.5%) discussed pyrexia with patients at D+T initiation. At the onset of the first episode of pyrexia in a patient, most respondents either try to keep patients on the starting dose (34.9% for D, 42.8% for T) or withhold the medication only temporarily (52.4% for D and 47.8% for T), even with a fever of 104°F. Mean time to treatment reinitiation was 1.5 days and, in more than half of the instances (52.3% for D and 51.4% for T), respondents would ask the patients to reinitiate at the starting dose. Respondents also asked patients to initiate antipyretics (87.5%) or corticosteroids (34.5%) to manage pyrexia symptoms. Even at pyrexia recurrence, respondents generally preferred keeping patients on treatment, with only 4.2% recommending permanent discontinuation. In general, respondents were very comfortable in managing pyrexia-related symptoms in their patients (mean score 7.8, 1 = very uncomfortable, 10 = very comfortable). Conclusions: In clinical practice, respondents were very comfortable in managing pyrexia. They tried to keep patients on D+T as long as possible. Experienced oncology nurses, nurse practitioners and physician assistants are able to manage pyrexia symptoms and keep patients on treatment for a longer duration to help obtain maximum clinical benefit.
Levels of mRNA of iLBP family genes and retinoic acid receptors in embryonal tumors in children.
Authors: Popovyan Olga P. , Kit Oleg I. , Potemkin Dmitrii S. , Timoshkina Natalya N. , Kuznetsov Sergei A.
Published: May 2020

e22517

Background: Neuro- and nephroblastoma are the most common pediatric solid tumors. Their varying clinical behavior determines challenging prognosis and choice of treatment tactics. Along with many clinical parameters, the genetic characteristics of tumor cells appear promising. Methods: The study included patients diagnosed with neuroblastoma (n = 10) and nephroblastoma (n = 10) (median age from 2 months to 8 years; 10 boys and 10 girls). Total RNA was extracted from paired tumor/normal samples using the miRNeasy Mini Kit (Qiagen, USA) and cDNA libraries obtained with the Reverta-L kit. Expression of the CRABP1, CRABP2, FABP4, FABP5, RAR, RXRA, RXRB, and PPARD genes was evaluated by RT-PCR on the CFX96 amplifier (Bio-Rad, USA). GAPDH and B2M were reference loci. Relative expression (Exp) was calculated by the 2-ΔCt method. Results: The qPCR-RT showed a significant increase in the transcriptional activity in both tumors, compared to normal tissues, for the FABP4, FABP5, and RXRA loci (p < 0.01). Interestingly, we observed multidirectional changes in mRNA levels in neuroblastomas and nephroblastomas for the CRABP1, RAR, and PPARD loci. Unlike solid tumors of adult patients, the expression activity of the CRABP1 gene either did not differ from the conditional norm (in nephroblastoma), or significantly dropped to 70% (in neuroblastoma). In contrast to adult solid tumors, the CRABP1 gene expression activity in children was normal (in nephroblastoma) or decreased significantly up to 70% (in neuroblastoma). Conclusions: The pilot study revealed differentiating aberrant expression of genes encoding the family of retinoic acid transporters and receptors in pediatric neuroblastomas and nephroblastomas. This may be essential for choosing the optimal treatment volume and establishing a prognosis and resistance to chemotherapy in patients with these tumors.
Image-guided core needle biopsy for relapsed and refractory neuroblastoma: A focus on sample adequacy for genetic sequencing.
Authors: Samoyedny Andrew , States Lisa , Alai Emma , Srinivasan Abhay , Maris John M. , Mosse Yael P. , Cahill Anne Marie
Published: May 2020

e22521

Background: Relapsed and refractory neuroblastoma (NBL) is a prime target for novel therapies targeting specific mutations. The genomic landscape of NBL can change between time of initial diagnosis and relapse, necessitating subsequent biopsy and next generation sequencing (NGS) to detect mutations within the relapsed neoplasm. Tissue of insufficient quality and quantity leads to specimen failure during NGS. Thus the goal of this study is to review core needle biopsy for relapsed and refractory NBL in a pediatric interventional radiology department and explore factors that enhance biopsy adequacy. Methods: Retrospective review of clinical records and images for 66 patients (36M, 30F) with median age 8.7 years (range 0.9 – 49.3 y) who underwent 95 biopsies (55 bone, 40 soft tissue) over a 12-year period. Results: Biopsy yield for neuroblastic tissue from 123I mIBG-avid masses was 89.7% overall, 84.9% in bone, and 91.6% in soft tissue. 87/95 masses were mIBG-avid; 2 non-avid masses were NBL-positive (but also 18F-FDG avid). 48/59 samples sent for NGS were adequate for analysis (81.4%); bone and soft tissue biopsies did not differ in adequacy (77.1% vs 87.5%, p = 0.32). Tumor cell percent (TC%) for adequate samples was 49.9% vs 11.1% for NGS failures (p = 0.0003). Number of needle passes performed in bone and soft tissue lesions was positively correlated with NGS adequacy (Bone: r2= 0.68, Soft: r2= 0.33). In bone and soft tissue, adequate biopsies tended towards higher mean needle passes than inadequate ones (Bone: 5.1 vs 3.4, p = 0.0582) (Soft: 10.5 vs 4.7, p = 0.0428). Total needle volume passed into a soft tissue mass (calculated as inner needle cylindrical volume * # of passes) was higher in the “adequate” vs “inadequate” group (0.20 cm3 vs 0.05 cm3, p = 0.0004). Lesion mIBG avidity was quantified with a ratio of lesion:liver SUV; this mIBG SUV ratio was positively correlated with TC% (R2 = 0.55, N = 14). Using a linear regression line, a TC% of 50% (the mean value for samples adequate for NGS) corresponded to an SUV ratio of 2.89. The rate of minor complications (requiring only nominal therapy) was 7/95 (7.4%). The rate of major complications (requiring longer hospital stay) was 1/95 (1.5%). Conclusions: Image-guided core needle biopsy for relapsed and refractory NBL has a moderately high yield for procuring tumor samples adequate for NGS with a low rate of major complications. Adequate bone and soft tissue biopsies averaged >5 and >10 needle passes, respectively. An approximate lesion:liver mIBG SUV ratio of >3 may maximize specimen quality for NGS.
“Being healthy and living life as if I never had cancer”: The meaning of “living well” from adolescents with cancer.
Authors: Schreiner Katherine , Grossoehme Daniel H. , Baker Justin N. , Needle Jennifer , Friebert Sarah , Lyon Maureen E
Published: May 2020

e22532

Background: Extensive resources are devoted to discovering novel cancer treatments. Meanwhile, patient priorities and experiences must also be addressed. Specifically, among adolescents with cancer, patients’ definitions of “living well” may elucidate treatment preferences, guide care teams and families, and influence future behavioral interventions. The objective was to develop an empirical definition of “living well” for adolescents with cancer to enhance shared decision-making. Methods: Video recordings were analyzed from the Next Steps: Respecting Choices interviews with n = 30 adolescents ages 14-21 years with cancer and their families, a subsample of N = 126 adolescent/family dyads participating in a randomized clinical trial, FAmily CEntered (FACE) Advance Care Planning. Interviews were transcribed, verified and anonymized. A phenomenological analytic method was used to identify psychological meaning in participants’ statements. Results: Adolescents with cancer conceptualize living well as meaning maintaining physical, mental and emotional health, while engaging in purposeful, typical, adolescent-appropriate activities with people important to the adolescents. This has four components: living mindfully; living an identity as a healthy adolescent; spending time with friends and family; and living a purposeful life without depression. Living well means most often enjoying these activities while spending time with family and friends. An exemplary quotation is, “...being able to have a life where everything is going good, and being able to live healthy...gets rid of some of your worries not only for yourself but for your friends and family...less worries means a less stressful life...” Conclusions: By determining what “living well” means to adolescents with cancer, care teams and families can more easily understand patients’ priorities. A firm grasp on patients’ definitions of “living well” could relieve significant burden from families and increase families’ willingness to honor adolescent treatment preferences. Findings may guide future psychosocial interventions. Clinical trial information: NCT01670461.
Implementation of psychosocial support project in a pediatric oncology camping program.
Authors: Mozzilli Simone Lehwess , Salvetti Marina , Manhaes Maria Fernanda , Szylit Regina , Freitas Mariana , Garcia Fernanda Rafaela
Published: May 2020

e22534

Background: The oncological treatment can generate psychosocial distress for patients and their families. The Beaba Camping aims to educate and empower patients and caregivers through Technology Information and Gamification. In August 2019, in the third edition of the project, a pilot of Psychosocial Support Program was implemented to provide an integrative care to 71 children and adolescents under cancer treatment and 68 caregivers. Methods: Five psychologists, specialized in paediatric psycho oncology and palliative care, were selected to structure the Psychosocial Support Program and conduct interventions during three days of the camping. Based on evidences and experiences, the psychologists divided the interventions in: 1. Individually - children and adolescents. 2. Group - caregivers: 2.1. Belonging: identification and recognition of peers. Identification of psychological distress and similar fears; 2.2. Psychological Group Intervention: creation of groups to facilitate the intervention and bonding; 2.3. Feeling of the Day: expression of which emotion was the most prevalent each day of camping; 2.4. A Word of Support: exchange supportive statements among the peers. Results: 20 children/adolescents and 19 caregivers were attended individually, with demands variating from: Anxiety and sadness; Fear of future and prognosis; Social isolation and adaptation. 68 adults participated in groups that brought discussions involving: Biggest fears and difficult moments of the treatment; Relationship with their children and adolescents; Coping strategies and spirituality. Conclusions: The Psychosocial Support is an important and essential part of the cancer treatment. The Camping with Psychosocial Support Program may enable the demystification of the role of the psychologist, the link between professionals and patients and their caregivers, the binding among peers and the education about how the psychosocial support can be helpful to everyone involved in the treatment. For future improvements, more psychologists will participate in order to attend a larger number of participants and to perform more group interventions, including with children and adolescents.
Risk factors associated to infectious complications in children with febrile neutropenia induced by chemotherapy: A cohort study.
Authors: Díaz Ramírez Karla , Ortiz Morales Daniel , Zapata Tarres Marta
Published: May 2020

e22535

Background: Children cancer is the second cause of mortality, most of deaths are related to infectious complications due to immunosuppression provoked by chemotherapy. Febrile neutropenia is one of the most common issues in oncological patients and it’s considered an emergency. Studies have tried risk predicting models implementation, although they still need to be validated, updated and reproducible in different scenarios. The aim of this study was the early identification of conditioning factors to severe infectious complications in patients with febrile neutropenia that would allow taking decisions for diagnosis and treatment. Methods: We present a prospective cohort study that estimated the risk associated to clinical and paraclinical factors and the development of infectious complications in pediatric patients with febrile neutropenia induced by chemotherapy on their admission of an emergency room (ER). The clinical features analyzed were: age, type of cancer, chemotherapy regime, time between chemotherapy administration and ER admission, use of colony-stimulating factors, presence of central venous catheter, highest temperature registered, tachycardia, polypnea, hypoxemia and hypotension. The paraclinical features included were leucocyte, neutrophil and monocyte count, and C-reactive protein levels. Results: From 186 febrile neutropenia events, 101 cases reported infectious complications (54%). Clinical infection was the most frequent issue (38%). On the multivariate analysis we found that the features independently associated to infectious complication were tachycardia (OR1.07, CI95% 1.70-6.99) and highest temperature level reported in the ER (OR1.07, CI95% 1.00-1.13). Conclusions: Febrile neutropenia is the most common complication in pediatric oncological patients and it is related to life-threatening infections and high mortality rate. Risk prediction during the initial assessment in the ER is important to stratify patients and offer target therapy to decrease complications and prolonged hospitalization.
Functional and oncologic outcomes after excision of proximal femur primary bone tumors using a cost-effective indigenous prosthesis.
Authors: Gulia Ashish , Harsha Sri , Gupta Srinath , Puri Ajay
Published: May 2020

e23500

Background: Proximal femur endoprosthetic replacement(PFER) has become aprimary treatment option for aggressive benign and malignant tumors of proximal femur allowing early return to weight bearing and improvement in functional status. We present our experience in these cases with respect to oncological outcomes, functional outcomes and implant survival. Methods: All cases were retrieved from our prospectively maintained surgical database. 98 patients(35 males and 63 females) with a mean age of 29 years(10– 69 years)were operated between August 2006 and September 2017. Median followup was 49 months(1 - 160 months).The diagnosis included osteosarcoma(18), Ewing’s sarcoma(38), chondrosarcoma(32), and GCT(8) synovial sarcoma (2) .They were evaluated by Musculoskeletal Tumor Society score, recurrence free survival, patient survival, and implant survival. Results: Mean resection length is 18.5cm (8 – 35cm). 8 patients underwent revision surgery,7 for mechanical (3 for aseptic loosening, 4 for dislocations and for implant failures), 1 for non mechanicalcause (infection) and 2 patients underwent amputation for local recurrence. One patient had dislocation recently for whom revision is adbvised. At last follow-up, out of 98 cases 6 were lost to follow up, 32 patients had died(28 due to disease and 4 due to other causes) and 60 are alive. There were 3 only local recurrences(3 alive-1 external hemipelvectomy, 1 excision, 1 definitive chemo radiation), 9 had both local and distant recurrence (1 alive – hip disarticulation for local, definitive cheomoradiation for distant recurrence), and 26 had distant recurrences(6 alive - 3 pulmonary metastetectomy,1 nodal metastasis, 1 lung metastasis and 1 bone metastasis treated with definitive cheomoradiation) . The 5year OS, LRFS,DRFS were 68.3,85.7,61.5% respectively. The mean Musculoskeletal Tumor Society score was 26(22 – 28). The implant survival was 87.4% at 5 years. Conclusions: The use of a PFER in the treatment of primary tumours of bone is oncologically safe and gives consistent and predictable results with low rates of complication. We found that low cost indigenous prosthesis (one fourth the cost of imported prosthesis) fare equivalent to existing imported prosthesis. This can immensely helpful in offering limb salvage in resource constraint settings.
The outcome of vincristine, dactinomycin D, ifosfamide and doxorubicin (VAIA) as first-line therapy for adult-patients with metastatic ewing sarcoma; a single-center experience.
Authors: Atallah Jean Paul , Elshenawy Mahmoud Abdelsatar , Badran Ahmed ali , Alata Maaz Kamal , Gad Ahmed , Alharbi Abdulrahaman H. , Alquaydheb Hisham N. , Alshamsan Bader I
Published: May 2020

e23501

Background: Ewing sarcoma family of tumors (ESFT) is a rare malignancy among adults. Most studies from western countries have reported improvement in outcomes following multi-agent chemotherapy. We report our experience in the management of this disease among Arab ethnicity. The aim of this study is to assess the outcome of VAIA combination as a first-line treatment in Adult-patients with metastatic Ewing sarcoma. Methods: Patients who were newly diagnosed as metastatic Ewing sarcoma between 03/1997 and 11/2016 at King Faisal Specialist Hospital and Research Center, who received VAIA as first-line therapy were eligible. The patient's characteristics were summarized using Medians with interquartile ranges (IQR) and frequencies for continuous and categorical variables, respectively. Variables including age, sex, primary tumor size, site (skeletal vs extraskeletal) and extent of metastasis in correlation with progression and overall survival were analyzed using the Kaplan–Meier method and Cox proportional hazards regression. Results: Thirty-nine patients were identified. Male (26, 66.7%), Female (13, 33.3%). Skeletal (27, 69.2%), Extraskeletal (12, 30.8%). The median longest diameter of the primary tumor 9.75 (IQR 8-15). The most common metastatic sites were Lungs (22, 56.4%) & Bone (10, 25.6%), however, the least common sites were Bone Marrow (3, 7.7%) and liver (2, 5.1%). The median number of VAIA cycles was 10 cycles (IQR 5-14). Objective response rate (ORR) was noticed in 20 patients (51.2%) (Complete Remission (7, 17.9%), Partial Remission (13, 33.3%). One patient had stable disease and 12 (30.8%) patients had progressive disease. The assessment was not feasible in 3 (7.7%) patients. With a median follow up duration of 18 months (1-44).20 patients died (62.5%). The median PFS and OS was 10,18 months respectively with 3,5 years overall survival rate of;35.7%,26.9% respectively. Univariate analysis correlation among different variables were insignificant. Conclusions: VAIA chemotherapy combination showed poor outcomes among our patients in comparison to literature further improvement is needed in this aggressive malignancy in our region.
The treatment results in patients with Ewing Sarcoma: The Polish Sarcoma Group Experience.
Authors: Lugowska Iwona , Jagodzinska-Mucha Paulina , Raciborska Anna , Bilska Katarzyna , Kosela-Paterczyk Hanna , Kozak Katarzyna , Dawidowska Anna , Poleszczuk Jan , Rutkowski Piotr
Published: May 2020

e23503

Background: Ewing Sarcoma is a rare type of aggressive tumor that occurs in bones or in the soft tissue around the bones. The multidisciplinary approach chemotherapy (CHT), radiotherapy (RTH) and surgery (S) is the standard of care. The aim of our study was to analyze prognostic factors and treatment results in patients with Ewing Sarcoma. Methods: 504 patient with Ewing sarcoma treated between 1998 and 2019, F:M 1:1.34, with metastases at presentation was 195 patients (39%), axial localization was in 277 patients (55%). All patient were treated with multimodal treatment based on chemotherapy, radiotherapy and surgery. Kaplan-Meier estimator, log rank test and multivariate Cox model were used for statistical analysis. Results: Five year overall survival (5y-OS) was 54% (CI:49-60%), prognostic factors were: gender (5y-OS for females and males equal to 63% and 48%, respectively), age (5y-OS stratified patients between < 10y; 10-15y; 15-25 and 25+ was 65%, 70%, 41% and 55%;p < 0.001), metastases (5y-OS in group with M1 was 31% and in M0 - 70%; p < 0.001), type of local treatment (5y-OS in group CHT/S/RTH was 61%, CHT/S 59%, only RTH 50% and palliative treatment without local treatment equals 12%; p < 0.001). Multivariate Cox analysis revealed death hazard dependence on gender (male vs. female; HR = 1.80; p < 0.01), metastatic status (M1 vs. M0; HR = 2.91; p < 0.001), bone/bone marrow involvement (present vs. absent; HR = 2.10; p < 0.01) and chemotherapy regime (other vs. VIDE/VAI; HR = 0.69; p = 0.049). Conclusions: The treatment results in Ewing sarcoma are significantly better in children than in adults, which can be related to the more intensive chemotherapy regiments applied. The treatment should be provided in referral centers and based on up-to-dated guideline.
Updated 5-year local control (LC), metastasis-free survival (MFS), and overall survival (OS) data from a phase I study of nilotinib plus radiation (RT) in high-risk chordoma.
Authors: Cote Gregory Michael , DeLaney Thomas F. , Miao Ruoyu , Schwab Joseph H. , Raskin Kevin , Lozano Calderón Santiago , Mullen John Thomas , Haynes Alex Bernard , Hornicek Francis J. , Chen Yen-Lin , Choy Edwin
Published: May 2020

e23505

Background: Chordomas are malignant tumors arising from remnant notochordal tissue. Despite improved local control with preoperative/postoperative RT, progression-free survival and OS remain poor in patients (pts) with high-risk features. Chordoma has been identified to express and activate platelet-derived growth factor receptor signaling. We conducted a phase 1 trial to identify the maximum tolerated dose (MTD), safety, and feasibility of nilotinib with RT as either preoperative or definitive treatment for patients with high-risk chordoma. Enclosed is an updated report on LC, MFS, and OS. Methods: We recruited 23 pts with nonmetastatic chordoma to the phase I and dose expansion arms of the study. High-risk was defined as the presence of any of the following: local recurrence after surgery, previous intralesional resection, unplanned incomplete resection, unresectable/marginally resectable disease, or declining surgery due to excessive morbidity. Pts were treated with nilotinib and concurrent RT to 50.4 Gy relative biological effectiveness (RBE) followed by surgery and postoperative RT to a cumulative dose up to 70.2 Gy RBE or definitively up to 77.4 Gy RBE without surgery. On completion of RT, pts were eligible to continue nilotinib until disease progression. Results: The dose escalation arm of the study identified nilotinib 200 mg daily as the maximum tolerated dose (MTD). Eighteen evaluable pts were treated with nilotinib plus RT at the MTD. The objective best response rate was 6% (1 of 18 pts). The 4 and 5-year LC rates were 94.3% (95% CI 83.2-100) and 70.7% (95% CI 20.8-100), respectively. The MFS rate was 74.3 at 4 and 5 years (95% CI 51.8-96.7). The 4 and 5-year OS rates were 70.2% (95% CI 44.4-95.9) and 54.6% (95% CI 20.5-88.6). Conclusions: In updated data from a cohort of high-risk chordoma pts nilotinib 200 mg/d with RT +/- surgery, with long-term follow-up, local control and distant metastasis free survival remains favorable. Clinical trial information: NCT01407198 . [Table: see text]
Mesenchymal chondrosarcoma: An Australian multi-centre cohort study.
Authors: Strach Madeleine Cornelia , Grimison Peter S. , Boyle Richard , Stalley Paul , Connolly Elizabeth Anne , Bhadri Vivek
Published: May 2020

e23509

Background: Mesenchymal chondrosarcoma (MCS) is a rare sarcoma that has a more aggressive course than conventional chondrosarcoma. Treatment is often multimodal with combinations of surgery, chemotherapy and radiotherapy. This study gives opportunity to evaluate prognostic factors and treatments in an Australian setting. Methods: We performed a retrospective study on patients with MCS registered on the ACCORD prospective sarcoma database from 6 Australian sarcoma centres since 2009. We collected data including baseline demographics, clinicopathological variables, treatment characteristics and survival status. We assessed outcomes of overall survival (OS), progression-free survival (PFS) and proportions of metastatic and localised patients receiving surgery, chemotherapy and/or radiotherapy. Results: We identified 20 patients diagnosed with MCS between Jan 2001 and Dec 2019. Median age was 35 years (range 20-69 years). Two (10%) had metastatic disease at diagnosis and 7 (35%) developed metastases on follow up. Median follow-up was 20 months (0.4 – 210 months). 17 (85%) patients underwent surgical resection (17 of primary, 8 of recurrence/metastasis), 10 (50%) received chemotherapy (95% anthracycline; 1 preoperative, 9 palliative), 12 (60%) received radiotherapy (7 to primary, 9 to recurrence/metastasis), and 13 (65%) received multimodality therapy. All six patients who received surgery alone remained alive at follow-up with no metastatic disease. Table shows survival estimates for the study population. There was no difference in median OS in patients who received all therapies compared to those who did not (8.4 v 7.5 years; p = 0.53). Median PFS was not prolonged in those who received all therapies compared to those who did not (37 vs 43 months, p = 0.4). Conclusions: This study demonstrates contemporary Australian treatment patterns of MCS. Understanding treatment patterns and outcomes helps promote standardisation of treatment and design of prospective trials for novel therapeutic strategies. Future analysis of prospective patients for patient and treatment factors influencing survival is planned. [Table: see text]
Neoadjuvant therapy for localized gastrointestinal stromal tumors (GISTs): A propensity score weighted analysis.
Authors: Marqueen Kathryn E. , Moshier Erin , Buckstein Michael , Ang Celina
Published: May 2020

e23516

Background: Retrospective and single-arm prospective studies have reported clinical benefit associated with receipt of neoadjuvant imatinib for GISTs. In the absence of randomized phase III data, the impact of neoadjuvant systemic therapy (NAT) on survival, in comparison to upfront resection, remains unknown. Methods: We identified N = 14,402 patients with complete clinical, demographic, treatment and pathologic data within the National Cancer Database (2004-2016) who underwent resection of localized GIST of the stomach, esophagus, small bowel, and colorectum, with or without ≥3 months of NAT. Inverse probability of treatment weighting (IPTW) was used to adjust for covariable imbalance among treatment groups, with the propensity score estimated by logistic regression. The effect of NAT on overall survival was estimated with a weighted time-dependent Cox proportional hazards model. A weighted logistic regression was used to estimate the effect of NAT on 90-day postoperative mortality and R0 resection. Results: 759 (5.3%) patients received NAT followed by resection, compared to 13,643 (94.7%) who underwent upfront resection. Median length of NAT was 6.3 months. 53% of NAT patients were male vs. 49% of UR patients, 68% vs. 66% had primary gastric GIST, and 73% vs 49% were high risk. Patients receiving NAT had larger tumors (p < 0.001) and higher mitotic index (p = 0.003). There was a significant survival benefit associated with receipt of NAT (table). 90-day postoperative mortality rate was 3/759 (0.4%) among NAT patients vs. 307/13,643 (2.3%) UR patients. Receipt of NAT was significantly associated with lower odds of 90-day postoperative mortality (table). Of the 13,562 patients with information on margin status, the R0 resection rate was 635/716 (88.7%) for the neoadjuvant group vs. 11,823/12,846 (92%), with no significant difference between treatment groups (table). Conclusions: After adjustment for imbalance in prognostic and demographic factors, this analysis demonstrates that receipt of NAT for localized GIST is associated with a modest overall survival benefit. Although NAT patients had higher risk features, NAT was associated with a lower risk of 90-day postoperative mortality, with no difference in likelihood of achieving an R0 resection. [Table: see text]
High frequency of c-KIT genetic variants in exons 9, 11, 13 and 17 and PDGFRA in exon 18 in gastric GIST tumors.
Authors: Omelchuk Ekaterina P. , Gvaldin Dmitry Yu. , Timoshkina Natalya N. , Vladimirova Liubov Yu , Gevorkyan Yuriy A. , Soldatkina Natalya V. , Kharagezov Dmitry A. , Dashkov Andrey V. , Kaymakchi Dmitry O. , Poluektov Sergey I. , Kolesnikov Vladimir E. , Dontsov Vladimir A. , Tolmakh Roman E. , Ilchenko Sergei A. , Stateshny Oleg N. , Petrov Dmitry S. , Grechkin Fedor N. , Oganyan Nairi B. , Kolesnikov Valeriy V. , Mirzoyan Ellada
Published: May 2020

e23525

Background: Gastrointestinal stromal tumors (GIST) are rare malignant mesenchymal neoplasms of the gastrointestinal tract, the diagnosis and treatment of which is associated with the presence of mutations in the c-KIT and PDGFRA genes. Purpose of this study was molecular genetic genotyping of GIST according to clinically significant exons of the c-KIT and PDGFRA genes. Methods: The study included patients with an immunohistochemically confirmed diagnosis of GIST who underwent treatment in the RRIO, Rostov-on-Don, for the period 2018-2019 (n = 20, median age 63.5 years, men/women–10 people each, gastric tumors). DNA was isolated from FFPE tissue using the GeneJET FFPE DNA Purification Kit, USA. The presence of mutations in exons 9, 11, 13 and 17 of c-KIT and exon 18 of PDGFRA was detected by Sanger sequencing. Results: Activating mutations in exon c-KIT were detected in 10 ps, including one substitution p.V560E and 4 deletions – p.V559_E561del, p.M552_V555delMYEV, p.W557_V559 > F and p.W557_V559 > C. These mutations cause sensitivity to imatinib. Pathogenic mutations were detected in PDGFRA exon 18: an activating deletion p.I843_D846delIMHD (2 ps) and a substitution p.D842Y, which determines imatinib resistance (2 ps). Thus, 20% of GIST cases are promising for obtaining avapritinib, the first FDA approved drug in 2020 for patients with GIST with a mutation in PDGFRA exon 18. In addition, neutral genetic variants were revealed: in 17 exon c-KIT in 16 patients, benign rs1008658, in PDGFRA 18 exon – rs3830355 (3 ps) and silent mutation p.V824V (3 ps). Conclusions: Genotyping of c-KIT and PDGFRA identified 12 types of clinically significant mutations and, in 80% of cases, the carriage of benign polymorphisms and / or SNPs of unknown clinical significance. As a result, 70% of patients from the South of Russia with GIST may be sensitive to treatment with imatinib and/or avapritinib.