bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical significance of next generation sequencing (NGS) in Chinese patients with relapsed/refractory Wilm’s tumor.
Authors: Wang Juan , Chai Huizi , Zhao Lele , Yang Xueyu , Xiao Mingzhe , Qi Chuang
Published: June 2022

e22014

Background: Medical advances have been greatly improved in the five-year survival rate for Wilms’ tumor, but the survival is still dismal for relapsed/refractory (R/R) patients. In the present study, we aimed to investigate the genomic profiling and the incidence of germline cancer susceptibility mutationsof Chinese patients with R/R WT. Methods: Next-generation sequencing (NGS) of tumor specimens with matched blood samples obtained from R/R pediatric WT in Sun Yat-Sen University Cancer Center were used in a CAP-certified laboratory (Simcere Diagnostic Co, Ltd). Clinical information including age, gender and tumor histology were collected. Somatic and germline mutations including single nucleotide variants (SNV), insertion-deletion variants (Indels), copy number variations (CNVs) and fusion, as well as tumor mutational burden (TMB) were analyzed. Results: Nineteen patients with R/R WT were enrolled in this study, including 10 males and 9 females, with a median age of 4 years old (range, 0-14). All of the pathology was identified as favorable histology WT (FHWT). Somatic mutations were detected in 84.21% (16/19) of patients, and CNVs accounted for the majority of the total somatic aberrations, followed by SNVs. The most common somatic mutations were identified in the following genes, CTNNB1 , ERBB2, MCL1 , CDK2 and MDM4. Of the top 3 frequently mutated genes, the mutation frequency and their most common mutation type were CTNNB1, 26%, in-frame deletion, missense mutation; ERBB2 21%, missense mutation, amplification; MCL1 21%, amplification. It is worth noting that MCL1 mutation has never been reported in Chinese R/R WT patients before, which may be a potential valuable mechanism. Germline mutations were detected in 89.47% (17/19) of patients, and CNVs accounted for the majority of the total germline aberrations, followed by SNVs. The most common germline mutations were identified in the following genes, MCL1, RET, ALK, EPCAM, and FANCA. Of the top frequently mutated genes frequency and most common mutation type were MCL1 21%, amplification; RET 21% missense mutation, multiple mutations. There are also some suspected clinically pathogenic germline mutation of genes CDK4 , ERBB2, and MDM4 . All the mutation type were amplification. Notable cancer driver mutations were also characterized, such as the amplifications of ERBB2 / MET/EGFR / FGFR1, and the point mutations of CHEK2/FBXW7/NF1. The median TMB was 1.47 (range, 0-7.8). Conclusions: Overall, clinical and new results were detected in 14 (73.68%) in Chinese R/R WT patients. We discovered some driver genes mutations which potentially sensitive to the corresponding targeted drugs in Chinese R/R WT patients. Large sample size was needed to provide a better understanding of molecular features in R/R WT patients to achieve precision medicine.
Bone mineral density (BMD) deficits in adult survivors of childhood cancer: Attributable risks and long-term consequences.
Authors: Goodenough Chelsea Goodliffe , Baedke Jessica L , Li Nan , Brinkman Tara M. , Wilson Carmen Louise , Delaney Angela M. , Inaba Hiroto , Clark Karen L , Armstrong Gregory T. , Talleur Aimee C. , Pui Ching-Hon , Green Daniel M. , Merchant Thomas E. , Srivastava Deo Kumar , Yasui Yutaka , Hudson Melissa M. , Robison Leslie L. , Kaste Sue C. , Ness Kirsten K. , Chemaitilly Wassim
Published: June 2022

e22021

Background: Survivors of childhood cancer are at risk for BMD deficits. Contributions of treatment, physical and lifestyle factors to overall risk are unknown as are long-term consequences of moderate and severe deficits. Methods: BMD deficits were evaluated in 3919 five-year childhood cancer survivors in the St. Jude Lifetime Cohort (median age 31.7 [range 18.0-69.9] years, 52.6% male, 80.4% non-Hispanic White) using lumbar quantitative computed tomography and classified by age- and sex-specific Z-scores as moderate (<-1SD) or severe deficit (<-2SD). Multivariable logistic regression estimated odds ratios (OR), risk factor attributable fractions (AF), and associations between BMD deficits and long-term outcomes (social/functional outcomes, fracture, mortality). Results: BMD deficits were moderate in 21.7% (95% CI 20.4%-23.0%) and severe in 6.9% (95% CI 6.1%-7.7%) of survivors. Risk factors for moderate deficit included age 5-9 years at diagnosis (OR 1.63, 95% CI 1.31-2.03), >20Gy cranial radiotherapy (OR 1.75, 95% CI 1.41-2.18), >3240 mg/m2 glucocorticoids (OR 1.34, 95% CI 1.09-1.66), and smoking (OR 1.55, 95% CI 1.27-1.90). AF were 7.2%, 0.7%, 5.9%, and 6.1% respectively; 80.1% of risk was unexplained. Risk factors for severe deficits included age 5-9 years at diagnosis (OR 1.95, 95% CI 1.36-2.80), BMI<18.5 kg/m2 (OR 3.95, 95% CI 2.28-6.85), >20Gy cranial radiotherapy (OR 5.22, 95% CI 3.74-7.30), testicular/pelvic radiation (OR 1.70, 95% CI 1.19-2.44), smoking (OR 1.71, 95% CI 1.21-2.43), and physical inactivity (OR 1.91, 95% CI 1.10-3.33). AFs were 10.9%, 7.0%, 2.9%, 11.5%, 6.7%, and 3.2% respectively; 57.8% of risk was unexplained. Those with deficits were less likely to live independently, to be employed, and more likely to require assistance with personal care needs (Table). Fracture risk was greatest among those with any BMD deficit, and mortality risk was greatest among those with severe deficits. Conclusions: Deficits in BMD among childhood cancer survivors are related not only to treatment, but also to modifiable health behaviors. In this population, children exposed to radiation or glucocorticoids are at greatest risk for poor bone quality and should be counselled to optimize health behaviors.[Table: see text]
Prevalence of HPV and cytological abnormalities in young women in Almaty, Kazakhstan.
Authors: Bolatbekova Raikhan , Kaidarova Dilyara , Dushimova Zaure , Shatkovskaya Oxana , Zhylkaydarova Alma , Kukubassov Yerlan , Sadykova Tolkyn , Satanova Alima , Bertleuov Orynbassar , Kaldybekov Dauren
Published: June 2022

e22503

Background: Cervical cancer (CC) is the second most common type of cancer for women worldwide. 99% of cases of CC are associated with high-risk human papillomaviruses (HPV HR). Unfortunately, data on the epidemiology of HPV in Kazakhstan are limited, especially in young kazakhstani women. This study was provided to determine the prevalence of HPV HR and the cytological abnormalities in young Kazakhstani women, which will allow strengthening control in the existing CC screening in this age. Methods: 101 women aged 18-30 years were invited to this cross-sectional study. Women were mentally healthy and did not have a positive human papillomaviruses (HPV) history. Cervical samples for HPV were analyzed with using of Cobas 4800 HPV test. Cytological examination of smears with using the Bethesda terminology system and HPV test were conducted at Kazakh Institute of Oncology and Radiology. Results: The mean age of the study group was 21.0±2.8 years (range 18-30 years). Prevalence of HPV was 11,8% (12 cases). HPV 16 and 18 were the most common type in analyzed cases (5,9%). Cytological abnormalities occurred in 19,8% (20 cases). The Mann-Whitney test of the frequency of cytological abnormalities showed that the ASCUS and LSIL was significantly more found in the group up to 25 years. The HSIL was more common in a group of women 25 years and older and accounted for 1.9 % out of 2 cases (p < 0.05). Conclusions: The results of this study confirm the need for HPV vaccination of adolescent girls and improvement of the existing screening through the inclusion of women to screening from 25 years of age. Changing of CC screening through implementation of HPV screening with cytological triage of HPV - positive of women can reduce the burden of CC in young age in KazakhstanPrevalence of high risk HPV and cytological abnormalities in young women in Almaty, Kazakhstan.
Lethality of lung cancer in southeast of Brazil: Real-world data.
Authors: Aleixo Sabina B. , Parmanhane Narelle , Pulido Jose Zago
Published: June 2022

e22515

Background: Lung Cancer (LC) is one of the most common neoplasm of all malignant tumors, with an increasing lethality and incidence, corresponding to 13.5% of all types of cancer. The world estimate for 2020 was 19 million cases of cancer worldwide, with 10 million deaths of which lung cancer represented 18% of the deaths. It is estimated that in Brazil, according to INCA (National Cancer Center of Brazil) that in the year 2022 there will be 30,200 new cases, the second most common among men and the fourth among women. Unfortunately most cases are diagnosed in late stages and have low survival. Methods: Retrospective study of data from SisRHC (brazilian cancer registry system) of patients diagnosed with LC, treated at the reference cancer center Hospital Evangélico de Cachoeiro de Itapemirim/ES, from January 1, 2010 to December 31, 2019. Results: A total of 440 patients were included and their main characteristics at diagnoses was advanced stages (73.2% III/IV) and only 58 % where able to receive first line treatment: chemotherapy concomitantly with radiotherapy (22,3%), isolated chemotherapy (21.4%) and isolated radiotherapy (14.6%). After first line treatment outcome status was death (49.4%) and disease progression (12.3%). Median survival was 10.3 months. Conclusions: Despite the limitations of the retrospective study these data are important for understanding the pattern of disease in a developing country where acess to health is limited. Unfortunately the barrier of 12 months survival common in developed nations is still not a brazilian reality. Public policies are necessary for improvement
The future landscape of cancer incidence and mortality until 2036 in the Russian Federation.
Authors: Tsimafeyeu Ilya , Rahib Lola
Published: June 2022

e22518

Background: Understanding the future of the burden of cancer is important to plan for future research funding, allocations of resources and other efforts. In 2019, the most incident solid tumors in Russia were colorectal, breast, lung, prostate, and gastric cancers; most deaths were lung, colorectal, gastric, breast, and pancreas cancers. We project cancer incidences and death to the year 2036 utilizing population growth estimates and observed current rates and trends in Russia. Methods: Average annual percent change (AAPC) adjusted estimations of cancer incidences and death to 2036 were calculated for the 10 most incident and deadly cancers for male and female individuals. We combined the most recent sex and cancer-specific delay-adjusted incidence rates from the Herzen Russian Cancer Statistics (official Russian cancer statistics) and GLOBOCAN database with existing Federal State Statistics Service (Rosstat) demographic population growth projections by sex to calculate estimated incidences and death to 2036. Calculations assume that the annual percent change in the incidence and death rates observed will remain constant through 2036. Results: We project that by 2036 the incidence will increase by 19.5% and the most incident cancers in Russia will be different than the current rankings. Excluding non-melanoma skin cancer, breast is projected to be the most incident cancer with 99,700 diagnoses (currently second most incident; 73,918 diagnoses in 2019), colorectal is projected to be second with 95,200 diagnoses (currently first, 77,062 diagnoses in 2019). Lung (60,113 diagnoses in 2019) and prostate (45,763 diagnosis in 2019) will drop from fourth and third place to third and fourth place with 85,400 and 53,100 diagnoses in 2036 respectively. Despite the increase in incidence, cancer deaths will decline by 18% by 2036. Lung and colorectal cancer are projected to continue to be the top 2 leading causes of cancer related death with 35,800 deaths in 2036 due to lung cancer and 32,100 deaths due to colorectal cancer. Pancreas cancer is projected to surpass breast and gastric cancer to become the 3rd leading cause of cancer related deaths in 2036 (21,800 deaths in 2036). Breast cancer is projected to move from the fourth leading cause of cancer related deaths to fifth and gastric cancer will no longer be one of the top 5 causes of cancer deaths. Conclusions: We present projections on cancer incidence and deaths to 2036 in Russia. We show a shift in the rankings of the top 5 most common cancers and most markedly we show that pancreas cancer will be the third leading (currently fifth) cause of cancer related deaths by 2036. These projections can guide future research focus and planning.
Effects of anxiety and depression on the quality of life of male cancer patients undergoing genetic investigation for hereditary cancer predisposition syndromes.
Authors: Barbosa Oliveira Francisca Fernanda , Silva Paulo Goberlânio de Barros , Bitencourt Flávio da Silveira , Sant'Ana Rosane Oliveira , Silva-Fernandes Isabelle Joyce de Lima , Bezerra Maria Júlia Barbosa , Luciano Maria Claudia dos Santos , Picanço-Albuquerque Clarissa Gondim , Souza Thuany Pinto Rocha de , Lima Marcos Venício Alves
Published: June 2022

e22529

Background: Genetic tests have been increasingly requested to identify families at risk of hereditary cancer. In a family with a known mutation, the offspring of a carrier, whether male or female, have a 50% risk of inheriting the mutation. Most studies on the psychological implications associated with genetic testing have focused on women and few studies have focused on the male population. Methods: A total of 56 men with a personal history of cancer underwent screening for mutations in a panel of 31 genes associated with hereditary cancer. Assessment of quality of life (QoL) and levels of anxiety and depression was performed after patients received the genetic test result. For this, the HADS and WHOQOL-BREF scales were used. Wilcoxon, X², and Spearman correlation tests were used (SPSS v20.0 for Windows). Results: Of the 56 participants, 28.6% had a pathogenic mutation, 32.1% had a Variant of Undetermined Significance (VUS), and 39.3% had no mutation. The presence of the mutation was not associated with QoL (p = 0.967) or anxiety (p = 0.436) or depression (p = 0.945). Mean QoL was 77.95±7.38 (range = 50.00-95.20), mean anxiety was 5.14±2.62 (range = 1-14) and mean depression scores were 4.14±2.55 (range = 0-14). QoL was inversely correlated with levels of anxiety (p < 0.001, r = -0.496) and depression (p < 0.001, r = -0.494), parameters that were directly correlated (p = 0.037, r = 0.279). Most patients had QoL > 80 (n = 38, 67.9%), and only 16 (28.6%) and 13 (23.2%) men had HAD scores > 5. Conclusions: The result of carrying a mutation did not influence the quality of life and anxiety or depression levels in the male population evaluated. However, it was observed that levels of anxiety and depression can compromise the quality of life. The data from the present study reinforce the importance of considering the psychological aspects in the process of genetic investigation for hereditary cancer. In addition, it suggests that educational levels must be investigated to assess whether the low levels of anxiety and depression observed are associated with a low level of understanding of the clinical significance of carrying a pathogenic mutation.
The impact of virtual live education on the competence and knowledge of gynecologists caring for ovarian cancer patients.
Authors: Carranza Vanessa , Taylor Bryan Carson , Gitzinger Susan H. , Fowler Joan B. , Hall Jessica
Published: June 2022

e23003

Background: About 35% of ovarian cancer patients in the US have geographic-related disparities in their access to gynecologic oncologists. This disparity becomes more apparent as advances in the treatment of ovarian cancer continues to improve, particularly in regard to maintenance therapy (e.g., PARP inhibitors). Thus, it is critical for gynecologists who are most likely to see these patients over the span of their lives, have an intimate understanding of the management of these patients. Methods: CEC Oncology developed an educational initiative presented at four American College of Obstetricians and Gynecologists District Meetings, targeting obstetricians, gynecologists, and other health professionals. Education focused on PARP inhibitors in ovarian cancer, identification of those eligible for genetic testing and counseling, and strategies to improve patient outcomes. Evaluations were collected from attendees attending the District Meetings to assess impact on practice, increased competency, and intent to make a change in practice. This was objectively assessed by analyzing pre-test, post-test, and follow-up survey data (sent 4-6 weeks post-activity). Chi-square analysis was conducted with a priori significance set at 0.05. Results: A total of 183 clinicians were educated, practicing in academic settings (44%), community hospital settings (24%), private practice (25%), and government (7%). Attendees were asked case questions at baseline, immediately after the activity, and 4-6 weeks after the activity to assess knowledge about the DNA damage response pathway, genetic testing guidelines, and management of therapy toxicities. Knowledge increased from pre- to post-test and from pre-test to follow-up for all topics, with the greatest increase in the management of adverse events (41% increase from pre- to post-test; 50% increase from pre-test to follow-up; P< 0.01). Additionally, there was a 22% and 24% increase in confidence in identifying patients eligible for germline genetic testing and in recognizing toxicities with PARP inhibitors from pre-test to six-week follow-up, respectively. 60% of participants stated that there was a lack of patient education regarding the importance of genetic testing and counseling. At follow-up, 100% stated that they had educated patients on genetic testing and counseling, highlighting the value of educating gynecologists on this topic. Conclusions: Attendees of this educational initiative were eager to take back the knowledge learned to their clinical practices. While there was a measurable increase in knowledge with regard to different ovarian cancer related topics, educational gaps remain. Collectively, this particular audience stated that they care for > 1,000 ovarian cancer patients, elucidating the need for OB/GYNs to feel more comfortable regarding PARP inhibitor toxicities, as they become more prevalent in practice.
Two oncologists, three opinions? Second opinions in oncology: Noise, bias, and disagreement.
Authors: Gil Deza Ernesto , Gil Deza Lourdes , Abal Mariana , Garcia Gerardi Carlos , Martin Reinas Gaston , Tognelli Flavio A , Dragosky Marta , Smolje Leonel , Marin Ordoñez Alba , Brandon Maximiliano , Montiel Monica , Gonzalez Cesar , Jaunarena María del Huerto , Rivarola Edgardo G. J. , Morgenfeld Eduardo L. , Gercovich Daniela ,   ECOE USAL 2021 Team
Published: June 2022

e23009

Background: Systematic reviews show that second opinion consultations in Oncology are frequent (1 – 35%) and differ from initial recommendations by up to 50% (BMJ Open 2021;11:e044033). This study evaluates the variability of second opinions of Oncology Fellows in a Virtual Observational Standard Clinical Examination (V-OSCE 2021) (J Clin Oncol 39, 2021, suppl 15; abstr 11005). Methods: One of the stations of the V-OSCE 2021 included a simulated patient’s relative requesting a second opinion. The patient was a 62-year-old male with advanced lung adenocarcinoma (Mts in lymph nodes, bone and liver) PDL1 3%. All other markers (EGFR, ALK, ROS1 and Her2) were negative. The tumor progressed at first line with standard chemoimmunotherapy (Carboplatin + Pemetrexed + Pembrolizumab). At the time of consultation, the patient had PS2, depression, hepatic progression without evidence of CNS lesions and all laboratory results were normal. Docetaxel had been recommended as a second line of treatment. The case was sent to each Fellow before the examination, and the evaluation consisted of ten standardized prognostic and therapeutic questions. Results: A total of 16 Oncology Fellows were evaluated. Sex Female/Male (11/5) Age: Mean 33 years (r= 30-35). We analyzed the answers to ten standardized questions (Table). Conclusions: A) The Oncology Fellows agreed on only two out of ten answers to the standardized questions (incurability and mental health referral); and in the remaining eight, disagreement is evident. B) Within the first seven questions, all Fellows differed among themselves in at least one answer. C) These findings coincide with our daily practice: It is highly likely that if a patient gets a second opinion, they will get divergent and even contradictory answers about their case. D) Are these findings a product of differing knowledge or physicians’ noises and biases? Further research could address how medical education and professional development can help with reflecting upon these issues.[Table: see text]
Adaptive expertise for medical oncology fellows: How to foster evidence-based medicine mastery.
Authors: Agarwal Parul , Regan Linda , Donehower Ross C. , Marrone Kristen
Published: June 2022

e23015

Background: Adaptive expertise (AE) describes a physician’s ability to effectively apply pre-existing knowledge to unfamiliar clinical situations. This skill relies on understanding not just “how” solutions work, but instead developing a framework of “why” a specific decision is correct for a particular situation. Acquiring this skillset enables one to rely on foundational knowledge, while simultaneously reaching for novel information in order to make the best clinical decision. Given the expansion of primary literature and evolving treatment options in oncology, development of AE is critical for fellows to provide high level patient care. There is limited research focused on oncology trainee development of AE and evidence-based medicine (EBM) mastery. Methods: We designed an observational cohort study of ten first-year medical oncology fellows at Johns Hopkins during the 2021-2022 academic year (IRB00293232). Fellows were required to attend a case-based, faculty moderated EBM peer-teaching curriculum. A validated, ten question Likert scale AE questionnaire (Carbonell instrument) was administered to each fellow at baseline. Data collection from weekly questionnaires measuring efficiency and innovation in case preparation and presentation is ongoing. These data will be quantitatively summarized and correlated with the baseline AE instrument to evaluate change and development of AE over the academic year. Results: Ten learners have participated in the curriculum as of February 2022. All questions in the baseline AE instrument had a 100% response rate. Selected results are presented in Table.While all participants “strongly agree” that knowledge in their discipline keeps on developing, only 50% “strongly agree” that they are able to apply knowledge in new and unfamiliar situations with a degree of success, highlighting the need for a curriculum focused on AE for trainees. Conclusions: AE utilizing EBM in medical oncology is an essential skill for trainees to acquire. Next steps will include moderated focus groups at the 6 month and 10-month time point, followed by analysis of the weekly questionnaires, which will allow for formal assessment of this curriculum. Future directions will include expansion to include other institutions and adaption for different learner levels.[Table: see text]
A multicenter evaluation of treatment patterns and outcomes for Adamantinoma-like Ewing sarcoma.
Authors: Dorand Rodney Dixon , Wang Daniel Ying , Keedy Vicki Leigh , Davis Elizabeth J.
Published: June 2022

e23500

Background: Sarcomas are a rare and heterogenous group of malignancies comprised of > 150 histologic subtypes. Adamantinoma-like Ewing sarcoma (ALES) is a rare, small round blue cell tumor that represents a variant of Ewing sarcoma (EWS). First described 20 years ago, ALES harbors a EWS subset defining EWS-related translocation; however, ALES has a complex epithelial differentiation component defining it as a distinct clinical entity. Most ALES cases arise in the head and neck, but it has also been reported in the extremities and thorax. Given the rarity of ALES, there is a paucity of literature to guide treatment and describe outcomes. Methods: We performed a retrospective review (January 1, 2010-January 1, 2022) at two sarcoma centers in the United States and identified 4 cases of ALES. Tumor and patient characteristics were described, and patient outcomes were assessed. Results: Four patients were identified. 3 (75%) were male. Median age at diagnosis was 37 years (range 23-57). Primary site of ALES was head and neck (50%) and thorax (50%). Median tumor size was 4 cm (2.7-5.5 cm). All patients underwent resection of their primary tumor, and two (50%)received adjuvant radiation therapy. All pts received/are receiving adjuvant chemotherapy. 75% of patients were treated with Vincristine, Doxorubicin, and Cyclophosphane (VDC) alternating with Ifosfamide & Etoposide (IE) for 12-14 cycles. One patient received 4 cycles of adjuvant carboplatin and etoposide and radiation after an initial diagnosis of basaloid carcinoma but recurred 47 months later and diagnosed at ALES at that time. That patient underwent re-resection followed by adjuvant chemotherapy with Vincristine, Doxorubicin, and Ifosfamide (VAI). Median follow-up from initial diagnosis was 25 months (3-39 months). All patients are alive with no evidence of disease. Conclusions: Similar to treatment of EWS, a multidisciplinary strategy is paramount. VDC/IE is a reasonable treatment strategy. Further multicenter collaboration is essential to define clinical characterization of this rare sarcoma subtype and to guide treatment particularly in the relapsed or refractory setting.[Table: see text]
Treatment facility: Effects on stage IV osteosarcoma survival.
Authors: Furtmann Amanda , Eaton Vincent , Silberstein Peter T. , Tupper Connor
Published: June 2022

e23501

Background: Osteosarcoma is a malignant, bone-forming tumor that makes up approximately 20% of bone cancers. Osteosarcoma has an overall 5-year survival of 68%, so to see significant changes in survival, this study looks only at Stage IV osteosarcoma. Osteosarcoma is most commonly treated with a combination of chemotherapy and surgery, but no studies have been conducted to investigate the facility type at which treatment is received and its effect on survival outcomes. The goal of this study is to investigate the survival of patients with stage IV osteosarcoma based on treatment facility type. Methods: There were 1,634 patients with stage IV osteosarcoma identified in the National Cancer Database (NCDB), with 657 including data on facility type. SPSS version 27 was used to generate both descriptive statistics regarding demographics and Kaplan-Meier curves to determine the impact treatment facility type has on overall survival. Results: Stage IV osteosarcoma was more common in males (59.5%) and white race (77%) with 55.4% receiving treatment at academic centers, 22.5% at comprehensive community programs, 16.9% at integrated cancer programs, and 5.2% at community cancer programs. Patients on Medicare also demonstrated a decreased overall survival when compared to all other insurance types (p < 0.001). In stage IV osteosarcoma patients, there were statistically significant differences in survival outcomes when comparing each facility type to each other (with p values all < 0.05), except for the comparison between comprehensive community cancer programs and integrated network cancer programs. Patients who received treatment at academic/research programs demonstrated the best overall survival with a median of 7.29 months when compared to community center programs, comprehensive community cancer programs, and integrated network programs (with p values of < 0.001, 0.046, and 0.03, respectively). Patients treated at academic research programs were more likely to be white males with private insurance or Medicare. Conclusions: Patients treated at academic centers for stage IV osteosarcoma had better survival outcomes compared to those treated at nonacademic facilities. These patients were more likely to be white, insured individuals. African Americans and Medicare patients were associated with increased risk of mortality from stage IV osteosarcoma. Future studies can be done with multivariate analyses to determine other variables that may affect outcomes in this patient population.[Table: see text]
Pazopanib in metastatic soft tissue sarcoma (STS): Results of a multi-institutional observational study.
Authors: Bilici Ahmet , Koca Sinan , Karaagac Mustafa , Eraslan Emrah , Ocak Birol , Goktas Aydin Sabin , Sezgin Goksu Sema , Paydas Semra , Derin Sumeyye , Ergun Yakup , Yekegunduz Emre , Erol Cihan , Tataroglu Ozyukseler Deniz , Demiray Atike Gokcen , Karaca Mustafa , Guc Zeynep Gulsum , Menekse Serkan , Yesil Cinkir Havva , Gumusay Ozge , Sakin Abdullah ,   Turkish Oncology Group
Published: June 2022

e23542

Background: Soft tissue sarcomas (STS) are a heterogenous group of tumors which have limited therapeutic options and poor prognosis in advanced/metastatic settings. Herein, we present the clinical outcomes of metastatic STS patients treated with pazopanib (PAZ) in real-life. Methods: We retrospectively collected data about adult patients treated with PAZ for metastatic STS in Turkey. We described the clinical characteristics and tumor responses, and estimated the progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method. The Cox proportional hazards regression model (HR, 95%CI) was used for evaluation of prognostic factors for PFS. Results: 507 patients (median age: 52 [range: 18-87]; 56.8% female) were included in the analysis. Extremities were the most common primary tumor sites (n:202; 39.8%) followed by abdomen (n:116; 22.9%) and pelvic cavity (n:102;20.1%) where 98% of STSs arose in uterus (n:100). The leading histologic subtypes were leiomyosarcoma (n:192; 37.9%), synovial sarcoma (n:58; 11.4%) and undifferentiated pleomorphic sarcoma (n:48; 9.5%). Of the reported tumor grades (n = 350), 61.4% (n:215) were grade 3. The most common metastatic sites were lungs (52.7%) and liver (20.3%). Doxorubicin plus ifosfamide (45.9%) was the preferred front-line regimen and PAZ was the treatment of choice in second (59.8%) and third-line (61.8%) settings. The median follow-up under PAZ treatment was 5.03 (0.10-84.67) months. Objective response and disease control rates were 31.4% and 42.2%, respectively. Overall, 183 (36.1%) patients were alive at last follow up, 123 of which (67.2%) did not show progression. The median PFS and OS for the study group and the most commonly observed types of STS are shown in Table. Favorable prognostic factors for PFS were low-intermediate tumor grade (HR[95% CI] for grade I and 2 vs 3:1.371[1.016-1.849]; p = 0.039) and ECOG (Eastern Cooperative Oncology Group) score (HR[95% CI] for ECOG score < 2 vs ≥2: 2.698[1.923-3.787]; p = 0.0001). Weakness/asthenia (10.8%), impaired liver function tests (4.7%) and diarrhea (3.6%) were the most common adverse events, no grade 4 or 5 events were observed. Conclusions: This large scale real-life study confirms that PAZ, with its positive impact on clinical outcomes and acceptable tolerability and safety profile is a valuable treatment option for metastatic STS.[Table: see text]
Characteristics and outcomes of soft tissue sarcoma in Saudi Arabia.
Authors: Alshamsan Bader , Alrifai Omar , Atayeb Mohammad , AlAboud Mohammed , Alshomrani Aiman , Alsadoun Nouf , Bin Khidhr Rashed , Pant Rajeev , Shaheen Mahmood , Atallah Jean Paul
Published: June 2022

e23544

Background: Soft tissue sarcomas (STS) are a rare heterogeneous group of neoplasms that count for less than one percent of all solid cancers in adults. There is limited data from Saudi Arabia (SA). We aimed to describe the disease characteristics and clinical outcome of STS from a specialized referral center in STS management in SA. Methods: All adult patients treated at King Faisal Specialist Hospital and Research Center between January 2010 and December 2019 were reviewed. Continuous variables are described in median and interquartile range, and categorical variables are described in frequency and compared by the Chi-square test. Survival analysis was estimated by the Kaplan-Meier method and compared by the Log-Rank test. Results: Two hundred fourteen patients diagnosed with soft tissue sarcoma were eligible for the study. The median age at diagnosis was 38 years old (IQR: 26-50.5), and males were (56.1%). The most common histology subtypes were synovial sarcoma (19.6%), liposarcoma (13.5%), undifferentiated pleomorphic sarcoma (11.6%), leiomyosarcoma (9.8%). The most common presentation was painless swelling (49.1%), and the median duration of symptoms was 8 (IQR: 4–13) months. The majority (131 patients, 61.2%) were localized diseases, and the most common primary site was the lower limb (62.1%). The median tumor size was 10 (IQR: 6.8-15) cm, and the tumors were deep to fascia in 144 (67.3%) patients. Eighty-three patients (38.8%) presented with de novo metastasis, and lung (81.9%) was the most common site. The local therapy was as follows; surgery (45.3%), radiation (7.5%), both (41.6%), and none (5.6%). Eighty-five patients received chemotherapy as follows; anthracycline (51%), ifosfamide (28%), and both (23.5%). Seventy-nine patients (36.9%) achieved complete response, 56 (26.2%) developed distant metastasis, and 11 (5.1%) local relapse. Thirty-one patients received salvage chemotherapy, and 30 patients received second-line chemotherapy. The best response of first-line chemotherapy in metastatic patients was CR (3%), PR (14%), SD (8%), and PD (63%). The median follow-up was 37 (IQR: 12-76.75) months. The median OS for the localized disease was not reached, and three years OS was 88.2%. There was a statistical difference in OS between extremities vs. trunk (90.9% vs. 66.7%), (p = 0.01), histological subtypes (p = 0.006), nodal involvement (p < 0.001), T stage (p = 0.03), and complete response 96.9 vs. 68.5% (p < 0.001). The median OS for metastatic disease was 26 (95% CI: 16–35.5) months. The median OS for patients who underwent surgery, radiation, both or none were 26, 23, 31, and 9 months, respectively (p = 0.004). Conclusions: STS in SA is diagnosed at a younger age, with a longer median time for diagnosis and a more advanced stage. Histological subtypes and the advantage of local disease control and metastasectomy are consistent with other figures.
Outcomes in pleomorphic liposarcoma of the extremity and trunk: Is multimodality therapy indicated?
Authors: Tseng William W. , Barretta Francesco , Radaelli Stefano , Colombo Chiara , Callegaro Dario , Barisella Marta , Morosi Carlo , Sanfilippo Roberta , Fabbroni Chiara , Stacchiotti Silvia , Fiore Marco , Gronchi Alessandro
Published: June 2022

e23545

Background: In comparison to the more common histologic subtypes of liposarcoma (e.g., well differentiated/dedifferentiated; myxoid round cell), pleomorphic liposarcoma (PLPS) is poorly understood but generally regarded as more aggressive, with a high risk of distant metastasis. In this study, we sought to 1) assess outcomes after surgery for primary, non-metastatic PLPS and 2) explore indications for multimodality therapy (e.g., perioperative chemotherapy, radiation therapy) in this ultra-rare malignancy. Methods: Clinicopathologic data were retrospectively collected for eligible adult patients treated from 2002-2019 at our sarcoma referral center. Descriptive data was summarized and Kaplan-Meier plots were constructed for overall survival (OS) and crude cumulative incidences (CCI) of disease-specific death (DSD), local recurrence (LR) and distant metastasis (DM). Univariable models were performed to assess the association of specific variables of interest (e.g., tumor size) on outcome. Results: In total, 51 PLPS patients were included in this study. Mean tumor size was 9.7 cm. Tumors originated mostly in the extremity (67%), were deep in location (73%), and high grade (FNCLCC 3/3, 78%). All patients underwent complete (R0/R1) resection. Chemotherapy was given in 33% of patients and radiation therapy in 69%. With a median follow-up of 62 months, OS was 76% at 5 years. CCI of DSD, LR and DM at 5 years was 16%, 2% and 26%. Greater tumor size was observed to be strongly associated with worse OS (p = 0.002) and DSD (p = 0.006). Survival did not seem to be affected by pre-referral inadequate excision once patients (n = 18) underwent re-excision at our center. A separate subgroup of patients (n = 14) was identified with smaller (mean: 5.4 cm), superficial, lower grade tumors who underwent surgery alone without any DSD. Conclusions: In primary, non-metastatic PLPS, adequate surgery combined with perioperative chemotherapy and radiation therapy, when appropriate, is associated with favorable outcomes. Subgroups with potentially better clinical outcomes likely exist suggesting heterogeneity within PLPS. Multidisciplinary collaborative efforts across sarcoma centers are needed to better characterize these subgroups and determine the optimal strategies for management.
Compartment-specific clinical outcomes in patients with soft tissue sarcomas of the thigh.
Authors: Morinaga Sei , Yamamoto Norio , Hayashi Katsuhiro , Takeuchi Akihiko , Miwa Shinji , Igarashi Kentaro , Yonezawa Hirotaka , Asano Yohei , Saito Shiro , Tsuchiya Hiroyuki
Published: June 2022

e23549

Background: Approximately one-third of all soft tissue sarcomas develop in the thigh, and the risk factors for developing a complication after soft tissue sarcoma resection include the tumour’s location in the lower extremity. This study analysed the relationship between various factors, particularly tumour location and clinical outcome, in patients with primary soft tissue sarcoma of the thigh. Methods: Patients who underwent wide excision of soft tissue sarcomas of the thigh without metastasis at the time of the initial visit between January 2006 and March 2018 were included in the study. Seventy-four patients were included in this retrospective study. The relationships between variables and prognosis were statistically analysed. Results: The mean patient age was 58.7 years (10–86 years), the mean follow-up period was 75 months (24–173 months). A total of 37 tumours were predominantly located in the anterior compartment of the thigh, 17 in the medial compartment, and 20 in the posterior compartment. Multivariate analysis of the patient clinical data demonstrated that seromas developed more often in the medial compartment tumours and postoperative complications excluding seroma occurred more frequently in patients with two or more muscles resected or stage III tumours. A low Musculoskeletal Tumor Society score was associated with a long operative time (more than 120 min), anterior compartment tumours, and more than two muscle resections. In addition, soft tissue sarcomas in the medial compartment and stage III sarcomas were associated with a low 5-year metastasis-free survival. Conclusions: Soft tissue sarcomas in the medial compartment were associated with postoperative seroma and metastasis, whereas sarcomas in the anterior compartment correlated with low postoperative function. Surgeons should be aware of compartment-specific clinical outcomes in patients with soft tissue sarcomas of the thigh.[Table: see text]
A phase II study of anlotinib in the first-line treatment of locally advanced or metastatic soft-tissue sarcoma: Updated results.
Authors: Li Tao , Ye Zhaoming , Wei Yongzhong , Wang Shoufeng , Liu Yunxia , Chen Jia
Published: June 2022

e23559

Background: Standard treatment for patients with unresectable locally advanced or metastatic soft-tissue sarcoma is chemotherapy based on anthracyclines, while the tolerance of chemotherapy is limited. Anlotinib had demonstrated promising efficacy and favorable tolerance in the first-line treatment of these patients in the previously report ( 2021 ASCO). We updated the latest long-term efficacy and safety data. Methods: This multicenter, open-label, single-arm, phase II clinical trial (NCT03792542) was done at 7 hospitals in China. Patients diagnosed with locally advanced or metastatic soft-tissue sarcoma who had evaluable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 were eligible for inclusion. Additional inclusion criteria were 1) 18-70 years old, 2) ECOG PS 0-2, 3) chemotherapy intolerance judged by investigators, 4) chemotherapy and anti-angiogenesis treatment naïve. All patients received 12mg anlotinib once daily for 14 days every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Safety assessment was done in patients who received at least one dose of anlotinib. Results: 39 patients (24 males and 15 females) were enrolled between April 2019 to October 2021with a median follow-up 13.4 months (IQR 6.55-19.40), and the median age is 58 (range 23-69) years old. Pathological types included liposarcoma (n = 11), fibrosarcoma (n = 8), undifferentiated pleomorphic sarcoma (n = 5), leiomyosarcoma (n = 4), synovial sarcoma (n = 4), malignant peripheral nerve sheath tumor (n = 4), and others (n = 3). At the data cutoff date on December 27, 2021, the median PFS and median overall survival (OS) were 7.1 months [95%CI 5.42-8.77], 24.3 months [95%CI 14.9-33.7], respectively. The PFS at 6 months was 60.0%, and the OS at 12 months was 76.6%. 37 patients were eligible for the evaluation of tumor response.1 achieved confirmed partial response (PR) and the objective response rate (ORR) was 2.7% (1/37). 30 had stale disease (SD) and the disease control rate (DCR) was 83.8% (31/37). The incidence of adverse events of grade 3 was 33.3%, with a higher incidence of hypertension (12.8%), proteinuria (7.7%) and fatigue (5.1%). Conclusions: Anlotinib has shown encouraging anti-tumor activity and well tolerance in the first-line treatment of locally advanced or metastatic soft-tissue sarcoma who were not suitable for chemotherapy. Clinical trial information: NCT03792542.
Clinical benefit of imatinib in patients with relapsed tenosynovial giant cell tumor/pigmented villonodular synovitis (TGCT/PVNS).
Authors: Yu Jeanette Cu , Sidhu Manpreet Kaur , Fang Andrew , Morse Lee Jae , Pan Minggui
Published: June 2022

e23561

Background: TGCT/PVNS is an uncommon benign but locally aggressive tumor that affects joints and can lead to significant morbidity. It is characterized in most cases by a t(1;2) translocation that leads to overexpression of colony-stimulating factor 1 (CSF-1) and the accumulation of inflammatory cells that express CSF-1 receptor (CSF-1R) in the affected joints. Imatinib inhibits the tyrosine kinase activity of CSF-1R. Methods: We retrospectively reviewed patients with TGCT/PVNS who received treatment with imatinib within Kaiser Permanente Northern California. Results: Nine patients with relapsed TGCT/PVNS were treated with imatinib from 2019 to 2022. Median age was 43 years. 6 patients were female. The imatinib dose was 400 mg daily. All patients had been treated with surgery previously and relapsed, and further surgery was considered not to be beneficial. All patients presented with persistent joint pain that affected joint mobility and walking. After imatinib therapy was initiated, 7 patients (78%) reported significant improvement in their symptoms, while 2 patients (22%) reported no significant changes. Improvement in symptoms occurred soon after starting therapy, ranging from 3 days to 5 weeks. 8 patients (89%) had stable disease by RECIST criteria based on MRI, and 1 patient was not evaluable. 5 patients are still receiving imatinib currently. The longest treatment duration is 27 months. 4 patients required a dose reduction secondary to toxicity, and 3 patients discontinued therapy (2 patients with G3/4 hepatotoxicity and 1 patient self-discontinued treatment). 2 patients who discontinued imatinib continue to experience resolution of joint pain and other symptoms 10 and 24 months later respectively. Conclusions: Our study shows that treatment with imatinib can result in rapid and lasting symptomatic improvement in patients with relapsed TGCT/PVNS, even after treatment discontinuation. This suggests that imatinib can be an effective and safe treatment option for patients with relapsed TGCT/PVNS refractory or not amenable to further surgery.
Evaluation of formulation-associated ifosfamide neurotoxicity.
Authors: Abernathy Karin , McCabe Colleen , Perciavalle Matthew , Cortez Manuel , Miller Ryan , Yelvington Bradley , Keedy Vicki Leigh , Davis Elizabeth J.
Published: June 2022

e23562

Background: Ifosfamide, an alkylating agent used commonly in both hematologic and solid tumor malignancies, carries a notable risk for neurotoxicity/encephalopathy. Ifosfamide is available as both a reconstituted powder formulation and a solution for injection. Literature has shown that there may be higher rates of ifosfamide neurotoxicity/encephalopathy (INT/E) with the solution compared to the reconstituted powder. The primary objective of this study was to compare the rates of neurotoxicity/encephalopathy in association with the two available pharmaceutical formulations of ifosfamide. Methods: We performed a retrospective study of adult patients receiving at least one dose of either available pharmaceutical formulation of ifosfamide. The primary outcome was the incidence of formulation-associated INT/E. Secondary outcomes included additional risk factors for development of INT/E. Results: Of 218 patients evaluated, 212 were included in the study with 56 patients receiving the reconstituted powder formulation and 156 patients receiving the solution for injection formulation of ifosfamide. Baseline characteristics were similar between the two groups, including dose of ifosfamide received, use of INT/E prophylaxis, and renal and hepatic function. INT/E occurred in 4 patients (7.1%) receiving the reconstituted powder formulation vs 32 patients (20.5%) receiving the solution for injection (p = 0.022) Evaluation and analysis of additional risk factors for development of INT/E are ongoing, including the impact of baseline demographics, ifosfamide dosing, renal and hepatic function, and concomitant medications. Conclusions: In this study, hematology/oncology patients who were treated with ifosfamide had significantly lower rates of INT/E with the reconstituted powder formulation compared to the solution for injection. Further analysis regarding additional risk factors for INT/E development is ongoing.[Table: see text]